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Subcellular localization critically influences protein function , and cells control protein localization to regulate biological processes . We have developed and applied Dynamic Organellar Maps , a proteomic method that allows global mapping of protein translocation events . We initially used maps statically to generat...
The interior of every cell is highly organised , and contains many compartments , called organelles , that are dedicated to specific roles . Proteins are the tools and machines of the cell , and each organelle has its own set of proteins that it requires to work correctly . Each cell contains ten or more organelles , a...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods", "Acknowledgments" ]
[ "computational", "and", "systems", "biology", "cell", "biology", "tools", "and", "resources" ]
2016
Global, quantitative and dynamic mapping of protein subcellular localization
During their final maturation in the cytoplasm , pre-60S ribosomal particles are converted to translation-competent large ribosomal subunits . Here , we present the mechanism of peptidyltransferase centre ( PTC ) completion that explains how integration of the last ribosomal proteins is coupled to release of the nuclea...
Biological machines called ribosomes make proteins in the cells of our body . Mammalian cells build roughly 7 , 500 new ribosomes every minute , each one containing 80 proteins and four RNA molecules . Problems that prevent ribosomes from assembling correctly have been linked to cancers such as leukemia , and a class o...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "structural", "biology", "and", "molecular", "biophysics" ]
2019
Mechanism of completion of peptidyltransferase centre assembly in eukaryotes
Variation in the risk and severity of many autoimmune diseases , malignancies and infections is strongly associated with polymorphisms at the HLA class I loci . These genetic associations provide a powerful opportunity for understanding the etiology of human disease . HLA class I associations are often interpreted in t...
When considering someone’s risk of disease , every person is different but some similarities can be found when looking across populations . Some people are more likely to develop a certain disease , while others are protected in some way . Part of this variation is explained by the individual’s genes , while their life...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "computational", "and", "systems", "biology", "immunology", "and", "inflammation" ]
2020
Identifying the immune interactions underlying HLA class I disease associations
The Arabidopsis mutant wrky33 is highly susceptible to Botrytis cinerea . We identified >1680 Botrytis-induced WRKY33 binding sites associated with 1576 Arabidopsis genes . Transcriptional profiling defined 318 functional direct target genes at 14 hr post inoculation . Comparative analyses revealed that WRKY33 possesse...
Crop yields can be badly affected by diseases caused by some fungi and other microbes . One fungus called Botrytis cinerea is able to infect many different species of crop plants—including tomatoes and grapes—and can cause severe damage both before and after harvest . This fungus belongs to a group of microbes that kil...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "plant", "biology" ]
2015
Negative regulation of ABA signaling by WRKY33 is critical for Arabidopsis immunity towards Botrytis cinerea 2100
Host–parasite interactions are often embedded within complex host communities and can be influenced by a variety of environmental factors , such as seasonal variations in climate or abiotic conditions in water and soil , which confounds our understanding of the main drivers of many multi-host pathogens . Here , we take...
Mycobacterium ulcerans is a slow-growing bacterium that causes a rare tropical disease in humans called Buruli ulcer . The infection affects the skin and underlying tissues , initially causing small painless lesions that can develop into large open sores or ulcers that are responsible for significant handicap in rural ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "ecology", "epidemiology", "and", "global", "health" ]
2015
Mycobacterium ulcerans dynamics in aquatic ecosystems are driven by a complex interplay of abiotic and biotic factors
Serotonin's function in the brain is unclear . One challenge in testing the numerous hypotheses about serotonin's function has been observing the activity of identified serotonergic neurons in animals engaged in behavioral tasks . We recorded the activity of dorsal raphe neurons while mice experienced a task in which r...
Rewards and punishments can both encourage animals to change their immediate behavior and influence their mood over a longer term , particularly when given repeatedly . A region of the brain that increases its activity in response to rewards and punishments also contains many neurons that communicate with each other by...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2015
Serotonergic neurons signal reward and punishment on multiple timescales
CDK9 is the kinase subunit of positive transcription elongation factor b ( P-TEFb ) that enables RNA polymerase ( Pol ) II's transition from promoter-proximal pausing to productive elongation . Although considerable interest exists in CDK9 as a therapeutic target , little progress has been made due to lack of highly se...
Cancers are often caused by mutations in genes that allow cells to proliferate uncontrollably . One gene that is frequently mutated in many cancers encodes a protein called MYC . The activity of this gene is normally tightly controlled , but the mutations found in human cancer cells mean that this gene is constantly sw...
[ "Abstract", "Introduction", "Results", "Discussion" ]
[ "chromosomes", "and", "gene", "expression", "biochemistry", "and", "chemical", "biology" ]
2015
Compensatory induction of MYC expression by sustained CDK9 inhibition via a BRD4-dependent mechanism
The nuclear pore complex ( NPC ) is the principal gateway between nucleus and cytoplasm that enables exchange of macromolecular cargo . Composed of multiple copies of ~30 different nucleoporins ( Nups ) , the NPC acts as a selective portal , interacting with factors which individually license passage of specific cargo ...
Transposons are genetic sequences , which , when active , can move around the genome and insert themselves into new locations . This can potentially disrupt the information required for cells to work properly: in reproductive organs , for example , transposon activity can lead to infertility . Many organisms therefore ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "chromosomes", "and", "gene", "expression", "cell", "biology" ]
2021
Channel nuclear pore complex subunits are required for transposon silencing in Drosophila
Centrioles are cylindrical cell organelles with a ninefold symmetric peripheral microtubule array that is essential to template cilia and flagella . They are built around a central cartwheel assembly that is organized through homo-oligomerization of the centriolar protein SAS-6 , but whether SAS-6 self-assembly can dic...
Many cells have tiny hair-like structures called cilia on their surface that are important for communicating with other cells and for detecting changes in the cell’s surroundings . Some cilia also beat to move fluids across the cell surface—for example , to move mucus out of the lungs—or act as flagella that undergo ra...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]
2014
Structure of the SAS-6 cartwheel hub from Leishmania major
Deep sequencing analyses have shown that a large fraction of genomes is transcribed , but the significance of this transcription is much debated . Here , we characterize the phylogenetic turnover of poly-adenylated transcripts in a comprehensive sampling of taxa of the mouse ( genus Mus ) , spanning a phylogenetic dist...
Traditionally , the genome – the sum total of DNA within a cell – was thought to be divided into genes and ‘non-coding’ regions . Genes are copied , or “transcribed” , into molecules called RNA that perform essential tasks in the cell . The roles of the non-coding regions were often less clear , although it has since b...
[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]
[ "genetics", "and", "genomics" ]
2016
Fast turnover of genome transcription across evolutionary time exposes entire non-coding DNA to de novo gene emergence
To better understand how organisms make decisions on the basis of temporally varying multi-sensory input , we identified computations made by Drosophila larvae responding to visual and optogenetically induced fictive olfactory stimuli . We modeled the larva's navigational decision to initiate turns as the output of a L...
Living organisms can sense cues from their surroundings and respond in appropriate ways . For example , animals will often move towards the smell of food or away from potential threats , such as predators . However , it is not fully understood how an animal's nervous system is set up to allow sensory information to con...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2015
Computations underlying Drosophila photo-taxis, odor-taxis, and multi-sensory integration
Despite their fundamental importance for body size regulation , the mechanisms that stop growth are poorly understood . In Drosophila melanogaster , growth ceases in response to a peak of the molting hormone ecdysone that coincides with a nutrition-dependent checkpoint , critical weight . Previous studies indicate that...
The development of many of an animal's traits and characteristics are sensitive to the conditions of its environment . The conditions experienced early on in life , in particular , can alter how an animal grows and develops . The availability of food during development , for example , affects the final body size of man...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology" ]
2014
Nutritional control of body size through FoxO-Ultraspiracle mediated ecdysone biosynthesis
We use the myotendinous junction of Drosophila flight muscles to explore why many integrin associated proteins ( IAPs ) are needed and how their function is coordinated . These muscles revealed new functions for IAPs not required for viability: Focal Adhesion Kinase ( FAK ) , RSU1 , tensin and vinculin . Genetic intera...
Our body consists of many different types of cells that build our tissues and organs . To do so , cells need to be able to stick together . One family of proteins called integrins helps to keep cells connected . They sit across cell membranes and anchor cells to the networks of protein fibres outside cells that link an...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology", "cell", "biology" ]
2018
Novel functions for integrin-associated proteins revealed by analysis of myofibril attachment in Drosophila
Homotypic or entotic cell-in-cell invasion is an integrin-independent process observed in carcinoma cells exposed during conditions of low adhesion such as in exudates of malignant disease . Although active cell-in-cell invasion depends on RhoA and actin , the precise mechanism as well as the underlying actin structure...
Entosis is the invasion of one cell by another and can be observed in aggressive cancers . Although the invading cell is usually killed , the surviving cell is sometimes left with the wrong number of chromosomes . This suggests that entosis may help cancer to progress because cells with an abnormal number of chromosome...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "cell", "biology" ]
2014
G-protein-coupled receptor signaling and polarized actin dynamics drive cell-in-cell invasion
MAF1 represses Pol III-mediated transcription by interfering with TFIIIB and Pol III . Herein , we found that MAF1 knockdown induced CDKN1A transcription and chromatin looping concurrently with Pol III recruitment . Simultaneous knockdown of MAF1 with Pol III or BRF1 ( subunit of TFIIIB ) diminished the activation and ...
An organism's genetic material is made of segments of DNA called genes , which contain instructions to make proteins . First , copies of the DNA are made using another molecule called ribonucleic acid ( RNA ) in a process known as transcription . Then the RNA is used as a template to make a protein . During transcripti...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]
2015
MAF1 represses CDKN1A through a Pol III-dependent mechanism
Animal–animal recognition within , and across species , is essential for predator avoidance and social interactions . Despite its essential role in orchestrating responses to animal cues , basic principles of information processing by the vomeronasal system are still unknown . The medial amygdala ( MeA ) occupies a cen...
Many animals emit and detect chemicals known as pheromones to communicate with other members of their own species . Animals also rely on chemical signals from other species to warn them , for example , that a predator is nearby . Many of these chemical signals—which are present in sweat , tears , urine , and saliva—are...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2014
Sex-specific processing of social cues in the medial amygdala
Kainate receptors ( KARs ) are a subfamily of glutamate receptors mediating excitatory synaptic transmission and Neto proteins are recently identified auxiliary subunits for KARs . However , the roles of Neto proteins in the synaptic trafficking of KAR GluK1 are poorly understood . Here , using the hippocampal CA1 pyra...
Information is transmitted in the brain by cells called neurons . To communicate with neighboring cells , neurons release chemicals called neurotransmitters across a structure called a synapse that forms a junction between the cells . The neurotransmitters bind to receptors on the surface of the receiving neuron , and ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2015
Neto auxiliary proteins control both the trafficking and biophysical properties of the kainate receptor GluK1
Coupling of endoplasmic reticulum ( ER ) stress to dimerisation-dependent activation of the UPR transducer IRE1 is incompletely understood . Whilst the luminal co-chaperone ERdj4 promotes a complex between the Hsp70 BiP and IRE1’s stress-sensing luminal domain ( IRE1LD ) that favours the latter’s monomeric inactive sta...
Cells produce many protein molecules . These are made of chains of building blocks called amino acids that then fold into three-dimensional shapes . Specialist proteins known as chaperones assist this folding process . For example , the chaperone BiP helps other proteins fold in a compartment within the cell called the...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology" ]
2019
Unstructured regions in IRE1α specify BiP-mediated destabilisation of the luminal domain dimer and repression of the UPR
A significant body of research in cognitive neuroscience is aimed at understanding how object concepts are represented in the human brain . However , it remains unknown whether and where the visual and abstract conceptual features that define an object concept are integrated . We addressed this issue by comparing the n...
Our ability to interact with the world depends in large part on our understanding of objects . But objects that look similar , such as a hairdryer and a gun , may do different things , while objects that look different , such as tape and glue , may have similar roles . The fact that we can effortlessly distinguish betw...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2018
Integrative and distinctive coding of visual and conceptual object features in the ventral visual stream
Kinase inhibitors are effective cancer therapies , but tumors frequently develop resistance . Current strategies to circumvent resistance target the same or parallel pathways . We report here that targeting a completely different process , autophagy , can overcome multiple BRAF inhibitor resistance mechanisms in brain ...
Cancers of the brain and spine are the second most common kind of tumor in children , after cancers of the blood and bone marrow . Yet brain and spine tumors kill more children than any other cancer , in part because many become resistant to treatment . Like in other cancers , cells in brain and spine tumors often use ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology", "cancer", "biology" ]
2017
Autophagy inhibition overcomes multiple mechanisms of resistance to BRAF inhibition in brain tumors
The segmentation gene network in insects can produce equivalent phenotypic outputs despite differences in upstream regulatory inputs between species . We investigate the mechanistic basis of this phenomenon through a systems-level analysis of the gap gene network in the scuttle fly Megaselia abdita ( Phoridae ) . It co...
Similar biological phenomena can result from different processes occurring in different organisms . For example , the early stages of how an insect develops from an egg can vary substantially between different species . Nonetheless , all insects have a body plan that develops in segments . The same outcome occurring as...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "developmental", "biology", "evolutionary", "biology" ]
2015
Quantitative system drift compensates for altered maternal inputs to the gap gene network of the scuttle fly Megaselia abdita
Constraint-based modelling ( CBM ) is a powerful tool for the analysis of evolutionary trajectories . Evolution , especially evolution in the distant past , is not easily accessible to laboratory experimentation . Modelling can provide a window into evolutionary processes by allowing the examination of selective pressu...
Virtually all plants use energy from sunlight to convert carbon dioxide and water into oxygen and sugars via a process called photosynthesis . This process has many steps that each rely on different enzymes to drive specific chemical reactions . Most plants use a pathway of enzymes that is referred to as C3 photosynthe...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "plant", "biology", "computational", "and", "systems", "biology" ]
2019
Evolution of C4 photosynthesis predicted by constraint-based modelling
Stressful experiences potently activate kappa opioid receptors ( κORs ) . κORs in the ventral tegmental area regulate multiple aspects of dopaminergic and non-dopaminergic cell function . Here we show that at GABAergic synapses on rat VTA dopamine neurons , a single exposure to a brief cold-water swim stress induces pr...
People who are recovering from drug addiction are more vulnerable to cravings and relapse when under stress . This ability of stress to boost drug relapse can also be shown in animals previously exposed to addictive drugs . Rats can learn to press a lever to administer themselves a dose of cocaine and , during withdraw...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2017
Constitutive activation of kappa opioid receptors at ventral tegmental area inhibitory synapses following acute stress
The increase in activity of the two-pore potassium-leak channel Kcnk5b maintains allometric juvenile growth of adult zebrafish appendages . However , it remains unknown how this channel maintains allometric growth and how its bioelectric activity is regulated to scale these anatomical structures . We show the activatio...
Organs , limbs , fins and tails are made of multiple tissues whose growth is controlled by specific signals and genetic programmes . All these different cell populations must work together during development or regeneration to form a complete structure that is the right size in relation to the rest of the body . Growin...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology" ]
2021
A calcineurin-mediated scaling mechanism that controls a K+-leak channel to regulate morphogen and growth factor transcription
Tumor-associated macrophage ( TAM ) significantly contributes to cancer progression . Human cancer is enhanced by PPARγ loss-of-function mutations , but inhibited by PPARγ agonists such as TZD diabetes drugs including rosiglitazone . However , it remains enigmatic whether and how macrophage contributes to PPARγ tumor-s...
The immune system can both contribute to cancer progression and restrain the growth of tumors . Some immune cells – called macrophages – create an inflammatory environment around a tumor , which can support the spread of the cancer cells . Independent observations and experiments have shown that a protein called PPARγ ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cancer", "biology" ]
2016
Macrophage PPARγ inhibits Gpr132 to mediate the anti-tumor effects of rosiglitazone
While axon fasciculation plays a key role in the development of neural networks , very little is known about its dynamics and the underlying biophysical mechanisms . In a model system composed of neurons grown ex vivo from explants of embryonic mouse olfactory epithelia , we observed that axons dynamically interact wit...
As an animal develops , neurons within the nervous system connect with one another to form complex networks . Each neuron has a long cable-like protrusion known as an axon that establishes connections with other neurons . The axon has a structure called the growth cone at its tip , which navigates toward its target in ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology" ]
2017
Axon tension regulates fasciculation/defasciculation through the control of axon shaft zippering
HIV-1 assembles at the plasma membrane ( PM ) of infected cells . PM association of the main structural protein Gag depends on its myristoylated MA domain and PM PI ( 4 , 5 ) P2 . Using a novel chemical biology tool that allows rapidly tunable manipulation of PI ( 4 , 5 ) P2 levels in living cells , we show that deplet...
Viruses are parasites that must infect the living cell of a host in order to grow and replicate . To do so , the virus attaches to the host’s cell and transfers its genetic material to the inside . The virus then hijacks the cell and forces it to build proteins and more genetic material that will assemble into new copi...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology", "microbiology", "and", "infectious", "disease" ]
2017
Synchronized HIV assembly by tunable PIP2 changes reveals PIP2 requirement for stable Gag anchoring
Cell-based studies showed that several Mdm2-binding ribosomal proteins , upon overexpression , stabilize and activate p53 . In contrast , here we show in a mouse knockout study that Mdm2-binding ribosomal protein S27-like ( Rps27l ) , upon disruption , activates p53 . Germline inactivation of Rps27l triggers ribosomal ...
There are over a hundred different types of cancer that can affect humans; but , in general , all cancers are caused by mutations that cause cells to grow and divide abnormally . ‘Tumor suppressor genes’ are genes that normally protect a cell from genetic changes that can lead a cell towards becoming cancerous . About ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology", "cell", "biology" ]
2014
Ribosomal protein S27-like is a physiological regulator of p53 that suppresses genomic instability and tumorigenesis
The neural control of social behaviors in rodents requires the encoding of pheromonal cues by the vomeronasal system . Here we show that the typical preference of male mice for females is eliminated in mutants lacking oxytocin , a neuropeptide modulating social behaviors in many species . Ablation of the oxytocin recep...
Oxytocin is a hormone that promotes milk production , contractions during childbirth , and many social interactions in humans and other creatures . It has also been implicated in conditions like autism or schizophrenia , which show altered social interactions . Oxytocin is made and released by cells in the brain called...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2017
Oxytocin signaling in the medial amygdala is required for sex discrimination of social cues
Cholesterol is a major structural component of the plasma membrane ( PM ) . The majority of PM cholesterol forms complexes with other PM lipids , making it inaccessible for intracellular transport . Transition of PM cholesterol between accessible and inaccessible pools maintains cellular homeostasis , but how cells mon...
The human body contains trillions of cells . At the outer edge of each cell is the plasma membrane , which protects the cell from the external environment . This membrane is mostly made of fatty molecules known as lipids and about half of these lipids are specifically cholesterol . Human cells can either take up choles...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]
2019
Movement of accessible plasma membrane cholesterol by the GRAMD1 lipid transfer protein complex
Long-term adult stem cells sustain tissue regeneration throughout the lifetime of an organism . They were hypothesized to originate from embryonic progenitor cells that acquire long-term self-renewal ability and multipotency at the end of organogenesis . The process through which this is achieved often remains unclear ...
Many tissues and organs in an adult’s body – including bone marrow , skin and intestines – contain a small number of cells called adult stem cells . These cells usually stay dormant within these tissues ( at a site called a ‘niche’ ) until they are required to repair damaged or lost cells . At this point , adult stem c...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "stem", "cells", "and", "regenerative", "medicine" ]
2015
Embryonic attenuated Wnt/β-catenin signaling defines niche location and long-term stem cell fate in hair follicle
Protein kinases are potentially attractive therapeutic targets for neglected parasitic diseases , including African trypanosomiasis caused by the protozoan , Trypanosoma brucei . How to prioritize T . brucei kinases and quantify their intracellular engagement by small-molecule inhibitors remain unsolved problems . Here...
Human African trypanosomiasis—commonly known as sleeping sickness—is a debilitating and potentially fatal tropical disease that is widespread in sub-Saharan Africa . It is caused by the single-celled parasite Trypanosoma brucei , which is transmitted to humans by the bite of the tsetse fly . The infection takes its nam...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]
2013
Hypothemycin, a fungal natural product, identifies therapeutic targets in Trypanosoma brucei
Using serial block-face scanning electron microscopy , we report on the internal 3D structures of the brown planthopper , Nilaparvata lugens ( Hemiptera: Delphacidae ) at nanometer resolution for the first time . Within the reconstructed organs and tissues , we found many novel and fascinating internal structures in th...
Since the 19th century , scientists have been investigating how the organs of insects are shaped and arranged . However , classic microscopy methods have struggled to image these small , delicate structures . Understanding how the organs of insects are configured could help to identify new methods for controlling pests...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology" ]
2021
Three-dimensional reconstruction of a whole insect reveals its phloem sap-sucking mechanism at nano-resolution
How neurons become sensitive to the direction of visual motion represents a classic example of neural computation . Two alternative mechanisms have been discussed in the literature so far: preferred direction enhancement , by which responses are amplified when stimuli move along the preferred direction of the cell , an...
The brain extracts information from signals delivered from the eyes and other sensory organs in order to direct behavior . Understanding how the interactions and wiring of a multitude of individual nerve cells process and transmit this critical information to the brain is a fundamental goal in the field of neuroscience...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2016
Complementary mechanisms create direction selectivity in the fly
Proteasomes are essential for protein homeostasis in eukaryotes . To preserve cellular function , transcription of proteasome subunit genes is induced in response to proteasome dysfunction caused by pathogen attacks or proteasome inhibitor drugs . In Caenorhabditis elegans , this response requires SKN-1 , a transcripti...
Proteins perform many important roles in cells , but these molecules can become toxic if they are damaged or are no longer needed . A molecular machine called the proteasome destroys ‘unwanted’ proteins in animal and other eukaryotic cells . If the proteasome stops working properly , unwanted proteins start to accumula...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology", "cell", "biology" ]
2016
Proteasome dysfunction triggers activation of SKN-1A/Nrf1 by the aspartic protease DDI-1
It was studied if early suPAR-guided anakinra treatment can prevent severe respiratory failure ( SRF ) of COVID-19 . A total of 130 patients with suPAR ≥6 ng/ml were assigned to subcutaneous anakinra 100 mg once daily for 10 days . Primary outcome was SRF incidence by day 14 defined as any respiratory ratio below 150 m...
People infected with the SARS-CoV-2 virus , which causes COVID-19 , can develop severe respiratory failure and require a ventilator to keep breathing , but this does not happen to every infected individual . Measuring a blood protein called suPAR ( soluble urokinase plasminogen activator receptor ) may help identify pa...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "medicine", "immunology", "and", "inflammation" ]
2021
An open label trial of anakinra to prevent respiratory failure in COVID-19
Methanogenic archaea use a [NiFe]-hydrogenase , Frh , for oxidation/reduction of F420 , an important hydride carrier in the methanogenesis pathway from H2 and CO2 . Frh accounts for about 1% of the cytoplasmic protein and forms a huge complex consisting of FrhABG heterotrimers with each a [NiFe] center , four Fe-S clus...
Many microbes grow by producing methane gas from carbon dioxide and hydrogen gas , and enzymes known as hydrogenases play important roles in this metabolic process . The production of methane in these microbes depends on a nickel–iron hydrogenase called Frh adding electrons to a coenzyme called F420 . This hydrogenase ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "structural", "biology", "and", "molecular", "biophysics" ]
2013
De novo modeling of the F420-reducing [NiFe]-hydrogenase from a methanogenic archaeon by cryo-electron microscopy
Among coupled exchangers , CLCs uniquely catalyze the exchange of oppositely charged ions ( Cl– for H+ ) . Transport-cycle models to describe and explain this unusual mechanism have been proposed based on known CLC structures . While the proposed models harmonize with many experimental findings , gaps and inconsistenci...
Cells are shielded from harmful molecules and other threats by a thin , flexible layer called the membrane . However , this barrier also prevents chloride , sodium , protons and other ions from moving in or out of the cell . Channels and transporters are two types of membrane proteins that form passageways for these ch...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "structural", "biology", "and", "molecular", "biophysics" ]
2020
A CLC-ec1 mutant reveals global conformational change and suggests a unifying mechanism for the CLC Cl–/H+ transport cycle
Stem cell properties change over time to match the changing growth and regeneration demands of tissues . We showed previously that adult forebrain stem cell function declines during aging because of increased expression of let-7 microRNAs , evolutionarily conserved heterochronic genes that reduce HMGA2 expression . Her...
Stem cells are found throughout the body , and play key roles in promoting tissue growth during fetal development , and in maintaining tissues in the adult . When stem cells divide , they can either give rise to more stem cells , or they can generate specialized cells required for tissue function . However , the proper...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "stem", "cells", "and", "regenerative", "medicine" ]
2013
A network of heterochronic genes including Imp1 regulates temporal changes in stem cell properties
Many developmental processes break left–right ( LR ) symmetry with a consistent handedness . LR asymmetry emerges early in development , and in many species the primary determinant of this asymmetry has been linked to the cytoskeleton . However , the nature of the underlying chirally asymmetric cytoskeletal processes h...
Most living things have left and right sides that are not identical . A well-known example of this ‘left–right asymmetry’ is the position of the human heart within the human body . While the human heart is always on the left , in other situations it is possible for either the left side or the right side to be preferred...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "physics", "of", "living", "systems" ]
2014
Active torque generation by the actomyosin cell cortex drives left–right symmetry breaking
Although Rad51 is the key protein in homologous recombination ( HR ) , a major DNA double-strand break repair pathway , several auxiliary factors interact with Rad51 to promote productive HR . We present an interdisciplinary characterization of the interaction between Rad51 and Swi5-Sfr1 , a conserved auxiliary factor ...
The DNA within cells contains the instructions necessary for life and it must be carefully maintained . DNA is constantly being damaged by radiation and other factors so cells have evolved an arsenal of mechanisms that repair this damage . An enzyme called Rad51 drives one such DNA repair process known as homologous re...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "chromosomes", "and", "gene", "expression", "biochemistry", "and", "chemical", "biology" ]
2020
Cooperative interactions facilitate stimulation of Rad51 by the Swi5-Sfr1 auxiliary factor complex
Munc13–1 acts as a master regulator of neurotransmitter release , mediating docking-priming of synaptic vesicles and diverse presynaptic plasticity processes . It is unclear how the functions of the multiple domains of Munc13–1 are coordinated . The crystal structure of a Munc13–1 fragment including its C1 , C2B and MU...
The human brain contains billions of cells called neurons that communicate with each other using molecules called neurotransmitters . An electrical signal in one neuron triggers the release of neurotransmitters from the cell , which then activate or inhibit electrical signals in neighboring neurons . Inside the cell , ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "structural", "biology", "and", "molecular", "biophysics", "neuroscience" ]
2017
Mechanistic insights into neurotransmitter release and presynaptic plasticity from the crystal structure of Munc13-1 C1C2BMUN
Recent epidemiological and laboratory-based studies suggest that the anti-diabetic drug metformin prevents cancer progression . How metformin diminishes tumor growth is not fully understood . In this study , we report that in human cancer cells , metformin inhibits mitochondrial complex I ( NADH dehydrogenase ) activit...
Metformin is widely used to reduce the high blood sugar levels caused by diabetes . Recently , several studies have suggested that patients taking metformin who also develop cancer have tumors that grow more slowly than average . As clinical trials have already started to investigate if metformin is an effective anti-c...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cancer", "biology" ]
2014
Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis
Neuropeptides released from dense-core vesicles ( DCVs ) modulate neuronal activity , but the molecules driving DCV secretion in mammalian neurons are largely unknown . We studied the role of calcium-activator protein for secretion ( CAPS ) proteins in neuronal DCV secretion at single vesicle resolution . Endogenous CA...
Our ability to think and act is due to the remarkable capacity of the brain to process complex information . This involves nerve cells ( or neurons ) communicating with each other in a rapid and precise manner by releasing synaptic vesicles containing neurotransmitters across the gaps—called synapses—between neurons . ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2015
CAPS-1 promotes fusion competence of stationary dense-core vesicles in presynaptic terminals of mammalian neurons
Innate immune cellular effectors are actively consumed during systemic inflammation , but the systemic traffic and the mechanisms that support their replenishment remain unknown . Here , we demonstrate that acute systemic inflammation induces the emergent activation of a previously unrecognized system of rapid migratio...
When the body becomes infected with disease-causing pathogens , such as bacteria , the immune system activates various mechanisms which help to fight off the infection . One of the immune system’s first lines of defense is to launch an inflammatory response that helps remove the pathogen and recruit other immune cells ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "medicine", "immunology", "and", "inflammation" ]
2021
Inflammation rapidly recruits mammalian GMP and MDP from bone marrow into regional lymphatics
The thermodynamics of protein folding in bulk solution have been thoroughly investigated for decades . By contrast , measurements of protein substrate stability inside the GroEL/ES chaperonin cage have not been reported . Such measurements require stable encapsulation , that is no escape of the substrate into bulk solu...
All cells contain molecules known as proteins that perform many essential roles . Proteins are made of chains of building blocks called amino acids that fold to form the proteins’ three-dimensional structures . Many proteins fold spontaneously into their well-defined and correct structures . However , some proteins fol...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]
2020
Measuring protein stability in the GroEL chaperonin cage reveals massive destabilization
Although numerous extracellular phosphoproteins have been identified , the protein kinases within the secretory pathway have only recently been discovered , and their regulation is virtually unexplored . Fam20C is the physiological Golgi casein kinase , which phosphorylates many secreted proteins and is critical for pr...
Some proteins must be modified in order to work effectively . One common modification is to add a phosphate group to the protein , which is performed by enzymes called protein kinases . Although most of the protein kinases work on proteins inside the cell , it was discovered recently that a small group of kinases work ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology" ]
2015
A secretory kinase complex regulates extracellular protein phosphorylation
Bone morphogenetic protein ( BMP ) signaling has emerged as an important regulator of sensory neuron development . Using a three-generation forward genetic screen in mice we have identified Megf8 as a novel modifier of BMP4 signaling in trigeminal ganglion ( TG ) neurons . Loss of Megf8 disrupts axon guidance in the pe...
The peripheral nervous system relays information between the brain and spinal cord ( the central nervous system ) and the rest of the body . During development , neurons of the peripheral nervous system must extend processes ( axons ) long distances to reach the cells that they will eventually form connections with . S...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology", "neuroscience" ]
2013
MEGF8 is a modifier of BMP signaling in trigeminal sensory neurons
Many organisms , including species from all kingdoms of life , can survive desiccation by entering a state with no detectable metabolism . To survive , C . elegans dauer larvae and stationary phase S . cerevisiae require elevated amounts of the disaccharide trehalose . We found that dauer larvae and stationary phase ye...
Many organisms can survive losing all the water from their body in periods of severe drought by suspending their life . This ability is called anhydrobiosis ( from the Greek for ‘life without water’ ) . When the desiccated organisms encounter water again , they resume life as normal . Two organisms commonly used in res...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]
2016
The glyoxylate shunt is essential for desiccation tolerance in C. elegans and budding yeast
The Maternal Embryonic Leucine Zipper Kinase ( MELK ) has been reported to be a genetic dependency in several cancer types . MELK RNAi and small-molecule inhibitors of MELK block the proliferation of various cancer cell lines , and MELK knockdown has been described as particularly effective against the highly-aggressiv...
Like a person who is dependent on coffee to be productive , cancer cells are dependent on the products of certain genes in order to dominate their environment and grow . Cancer cells will stop growing and die when the activity of these gene products is blocked . These genes are known as cancer dependencies or “addictio...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "short", "report", "cancer", "biology" ]
2017
CRISPR/Cas9 mutagenesis invalidates a putative cancer dependency targeted in on-going clinical trials
The eukaryotic cell membrane is connected to a dense actin rich cortex . We present FCS and STED experiments showing that dense membrane bound actin networks have severe influence on lipid phase separation . A minimal actin cortex was bound to a supported lipid bilayer via biotinylated lipid streptavidin complexes ( pi...
All cells are surrounded by a lipid membrane that protects the cell , controls the movement of molecules into and out of the cell , and passes messages about environmental conditions to the cell . This membrane is made of two layers of molecules called lipids , with various proteins embedded in it . There are many diff...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "structural", "biology", "and", "molecular", "biophysics" ]
2014
A lipid bound actin meshwork organizes liquid phase separation in model membranes
The cellular messenger cAMP regulates multiple cellular functions , including signaling in cilia and flagella . The cAMP dynamics in these subcellular compartments are ill-defined . We introduce a novel FRET-based cAMP biosensor with nanomolar sensitivity that is out of reach for other sensors . To measure cAMP dynamic...
Cells can change the way they grow , move or develop in response to information from their environment . This information is first detected at the surface of the cell and then the information is relayed around the interior of the cell by signaling molecules known as “second messengers” . A molecule called cAMP is a wel...
[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]
[ "cell", "biology", "tools", "and", "resources" ]
2016
A novel biosensor to study cAMP dynamics in cilia and flagella
Decision bias is traditionally conceptualized as an internal reference against which sensory evidence is compared . Instead , we show that individuals implement decision bias by shifting the rate of sensory evidence accumulation toward a decision bound . Participants performed a target detection task while we recorded ...
How do you decide whether to buy a new car ? One factor to consider is how well the economy is doing . During an economic boom , you might happily commit to buying a new vehicle that goes on sale , but prefer to sit on your savings during a financial crisis , despite how good the offer may be . Adjusting how you make d...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2019
Humans strategically shift decision bias by flexibly adjusting sensory evidence accumulation
Sedimentary rocks host a vast reservoir of organic carbon , such as 2-methylhopane biomarkers , whose evolutionary significance we poorly understand . Our ability to interpret this molecular fossil record is constrained by ignorance of the function of their molecular antecedents . To gain insight into the meaning of 2-...
The cell membrane that separates the inside of a cell from its outside environment is not a fixed structure . A cell can change the amount and type of different molecules in its membrane , which can alter the rigidity and permeability of the membrane and allow the cell to adapt to changing conditions . The cell membran...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "evolutionary", "biology", "structural", "biology", "and", "molecular", "biophysics" ]
2015
Methylation at the C-2 position of hopanoids increases rigidity in native bacterial membranes
The collapse of iconic , keystone populations of sockeye ( Oncorhynchus nerka ) and Chinook ( Oncorhynchus tshawytscha ) salmon in the Northeast Pacific is of great concern . It is thought that infectious disease may contribute to declines , but little is known about viruses endemic to Pacific salmon . Metatranscriptom...
Keystone species are animals and plants that play a pivotal role in supporting the ecosystems they live in , making their conservation a high priority . Chinook and sockeye salmon are two such species . These fish play a central role in the coastal ecosystems of the Northeast Pacific , where they have supported Indigen...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "ecology", "short", "report", "microbiology", "and", "infectious", "disease" ]
2019
Endangered wild salmon infected by newly discovered viruses
The role of the cellular microenvironment in enabling metazoan tissue genesis remains obscure . Ctenophora has recently emerged as one of the earliest-branching extant animal phyla , providing a unique opportunity to explore the evolutionary role of the cellular microenvironment in tissue genesis . Here , we characteri...
The emergence of the diversity of multicellular animals involved cells joining together to form tissues and organs . The ‘glue’ that enabled the cells to work together is made of rope-like molecules called collagen , which assemble into scaffolds . These smart scaffolds tether proteins forming basement membranes that c...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology", "evolutionary", "biology" ]
2017
Collagen IV and basement membrane at the evolutionary dawn of metazoan tissues
Ubiquitylation ( ubi ) by the E3-ligases Mindbomb1 ( Mib1 ) and Neuralized ( Neur ) is required for activation of the DSL ligands Delta ( Dl ) and Serrate ( Ser ) to activate Notch signalling . These ligases transfer ubiquitin to lysines of the ligands' intracellular domains ( ICDs ) , which sends them into an Epsin-de...
Cells use chemical signals to communicate , setting off chains of reactions known as signalling pathways . One key signalling pathway , thought to be required for the development of all animals , is called Notch . In fruit flies , signal proteins known as Delta and Serrate activate the Notch pathway by binding to recep...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology" ]
2017
Ubiquitylation-independent activation of Notch signalling by Delta
A parental cancer diagnosis is psychologically straining for the whole family . We investigated whether a parental cancer diagnosis is associated with a higher-than-expected risk of injury among children by using a Swedish nationwide register-based cohort study . Compared to children without parental cancer , children ...
A diagnosis of cancer can be devastating for both a person and his or her family . Over the past 40 years , the number of individuals in Sweden diagnosed with cancer has more than doubled leaving growing numbers of families coping with the aftermath . Many individuals diagnosed with cancer have young children . Parents...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "epidemiology", "and", "global", "health" ]
2015
Childhood injury after a parental cancer diagnosis
Proteasome inhibition elicits an evolutionarily conserved response wherein proteasome subunit mRNAs are upregulated , resulting in recovery ( i . e . , ‘bounce-back’ ) of proteasome activity . We previously demonstrated that the transcription factor Nrf1/NFE2L1 mediates this homeostatic response in mammalian cells . We...
Cells exposed to high temperatures , infections and other forms of stress often produce oxygen ions and peroxide molecules that can cause damage to proteins and DNA . Cells therefore rely on molecular machines called proteasomes to eliminate damaged proteins , before they cause too much harm . Two related transcription...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology" ]
2014
p97-dependent retrotranslocation and proteolytic processing govern formation of active Nrf1 upon proteasome inhibition
The circuit mechanisms behind shared neural variability ( noise correlation ) and its dependence on neural state are poorly understood . Visual attention is well-suited to constrain cortical models of response variability because attention both increases firing rates and their stimulus sensitivity , as well as decrease...
The world around us is complex and our brains need to navigate this complexity . We must focus on relevant inputs from our senses – such as the bus we need to catch – while ignoring distractions – such as the eye-catching displays in the shop windows we pass on the same street . Selective attention is a tool that enabl...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods", "and", "materials" ]
[ "neuroscience" ]
2017
Attentional modulation of neuronal variability in circuit models of cortex
Fusion of mitochondrial outer membranes is crucial for proper organelle function and involves large GTPases called mitofusins . The discrete steps that allow mitochondria to attach to one another and merge their outer membranes are unknown . By combining an in vitro mitochondrial fusion assay with electron cryo-tomogra...
Yeast and other eukaryotic cells contain distinct compartments that have specific roles . For example , compartments called mitochondria – which are surrounded by two layers of membrane – provide the energy needed for many cell processes . The organization of the network of mitochondria in a cell has a large effect on ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology", "structural", "biology", "and", "molecular", "biophysics" ]
2016
A mitofusin-dependent docking ring complex triggers mitochondrial fusion in vitro
The budding yeast centromere contains Cse4 , a specialized histone H3 variant . Fluorescence pulse-chase analysis of an internally tagged Cse4 reveals that it is replaced with newly synthesized molecules in S phase , remaining stably associated with centromeres thereafter . In contrast , C-terminally-tagged Cse4 is fun...
When cells multiply , it is essential for each new cell to get a copy of the organism's genetic blueprint . If an error occurs during cell division , and one of the daughter cells ends up with too many or too few copies of a chromosome , the cell can die or malfunction . Errors during cell division can , for example , ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "chromosomes", "and", "gene", "expression", "cell", "biology" ]
2014
Imaging the fate of histone Cse4 reveals de novo replacement in S phase and subsequent stable residence at centromeres
The tuberculosis ( TB ) epidemic is fueled by a parallel Human Immunodeficiency Virus ( HIV ) epidemic , but it remains unclear to what extent the HIV epidemic has been a driver for drug resistance in Mycobacterium tuberculosis ( Mtb ) . Here we assess the impact of HIV co-infection on the emergence of resistance and t...
Tuberculosis is an infectious disease caused by a bacterium called Mycobacterium tuberculosis that causes more deaths worldwide than any other infection . Individuals who are infected with the Human Immunodeficiency Virus ( HIV ) , which weakens the immune system , are particularly vulnerable to tuberculosis . However ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "microbiology", "and", "infectious", "disease" ]
2016
Impact of HIV co-infection on the evolution and transmission of multidrug-resistant tuberculosis
There is growing recognition that co-morbidity and co-occurrence of disease traits are often determined by shared genetic and molecular mechanisms . In most cases , however , the specific mechanisms that lead to such trait–trait relationships are yet unknown . Here we present an analysis of a broad spectrum of behavior...
Many individuals who have diabetes also have other diseases that affect the heart and blood vessels . It is not uncommon for human diseases to occur together like this; and understanding the relationships between diseases and other traits can make it easier to diagnose conditions . Furthermore , it can also help resear...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "computational", "and", "systems", "biology" ]
2015
Linking traits based on their shared molecular mechanisms
Hebbian plasticity is thought to require glutamate signalling . We show this is not the case for hippocampal presynaptic long-term potentiation ( LTPpre ) , which is expressed as an increase in transmitter release probability ( Pr ) . We find that LTPpre can be induced by pairing pre- and postsynaptic spiking in the ab...
Neurons communicate with one another at junctions called synapses . One neuron at the synapse releases a chemical substance called a neurotransmitter , which binds to and activates the other neuron . The release of neurotransmitter thus enables the electrical activity of one cell to influence the electrical activity of...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2017
Glutamate is required for depression but not potentiation of long-term presynaptic function
It is well established that inducible transcription is essential for the consolidation of salient experiences into long-term memory . However , whether inducible transcription relays information about the identity and affective attributes of the experience being encoded , has not been explored . To this end , we analyz...
Can we tell what important event a mouse – or even a person – has recently experienced ? The current experience of an individual can be inferred from brain imaging experiments . However , along with changing brain activity , such an experience also switches on gene activity throughout the brain . This enables neurons t...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2018
Salient experiences are represented by unique transcriptional signatures in the mouse brain
During development , proliferation must be tightly controlled for organs to reach their appropriate size . While the Hippo signaling pathway plays a major role in organ growth control , how it senses and responds to increased cell density is still unclear . In this study , we use the zebrafish lateral line primordium (...
How do organs and tissues know when to stop growing ? A cell communication pathway known as Hippo signaling plays a central role as it can tell cells to stop dividing . It is activated when cells in developing tissues come into contact with each other and causes a protein called Yap1 to be modified , which prevents it ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology" ]
2015
Amotl2a interacts with the Hippo effector Yap1 and the Wnt/β-catenin effector Lef1 to control tissue size in zebrafish
The knirps ( kni ) locus encodes transcription factors required for induction of the L2 wing vein in Drosophila . Here , we employ diverse CRISPR/Cas9 genome editing tools to generate a series of targeted lesions within the endogenous cis-regulatory module ( CRM ) required for kni expression in the L2 vein primordium ....
Gregor Mendel was an Austrian monk and botanist whose work with pea plants in the 19th century founded the field of genetics . Though he was not aware of genes at the time , Mendel essentially worked out that pea plants had two copies of each gene , and that each copy had a 50% chance of being passed on to any one offs...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology", "tools", "and", "resources", "genetics", "and", "genomics" ]
2017
CRISPR/Cas9 and active genetics-based trans-species replacement of the endogenous Drosophila kni-L2 CRM reveals unexpected complexity
The entorhinal cortex ( EC ) is the primary site of interactions between the neocortex and hippocampus . Studies in rodents and nonhuman primates suggest that EC can be divided into subregions that connect differentially with perirhinal cortex ( PRC ) vs parahippocampal cortex ( PHC ) and with hippocampal subfields alo...
In the early 1950s , an American named Henry Molaison underwent an experimental type of brain surgery to treat his severe epilepsy . The surgeon removed a region of the brain known as the temporal lobe from both sides of his brain . After the surgery , Molaison's epilepsy was greatly improved , but he was also left wit...
[ "Abstract", "Introduction", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2015
Functional subregions of the human entorhinal cortex
Strict L-chiral rejection through Gly-cisPro motif during chiral proofreading underlies the inability of D-aminoacyl-tRNA deacylase ( DTD ) to discriminate between D-amino acids and achiral glycine . The consequent Gly-tRNAGly ‘misediting paradox’ is resolved by EF-Tu in the cell . Here , we show that DTD’s active site...
Proteins are made up of many different building blocks called amino acids , which are linked together in chains . The exact order of amino acids in a protein chain is important for the protein to work properly . When a cell makes proteins , molecules known as transfer ribonucleic acids ( or tRNAs for short ) bind to sp...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]
2017
Role of D-aminoacyl-tRNA deacylase beyond chiral proofreading as a cellular defense against glycine mischarging by AlaRS
GPCRs are increasingly recognized to initiate signaling via heterotrimeric G proteins as they move through the endocytic network , but little is known about how relevant G protein effectors are localized . Here we report selective trafficking of adenylyl cyclase type 9 ( AC9 ) from the plasma membrane to endosomes whil...
Cells sense changes in their chemical environment using proteins called receptors . These proteins often sit on the cell surface , detecting molecules outside the cell and relaying messages across the membrane to the cell interior . The largest family of receptors is formed of ‘G protein-coupled receptors’ ( or GPCRs f...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology" ]
2020
G protein-regulated endocytic trafficking of adenylyl cyclase type 9
Segmentation and tracking of cells in long-term time-lapse experiments has emerged as a powerful method to understand how tissue shape changes emerge from the complex choreography of constituent cells . However , methods to store and interrogate the large datasets produced by these experiments are not widely available ...
Cells interact , divide , rearrange and change shape to build an organ during development . Modern microscopy and computer technology can follow each individual cell of an entire organ in a living organism . However , to understand how the complex choreography of cells leads to well-shaped organs , researchers need too...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "computational", "and", "systems", "biology", "cell", "biology", "tools", "and", "resources" ]
2016
TissueMiner: A multiscale analysis toolkit to quantify how cellular processes create tissue dynamics
Phenotypic screens allow the identification of small molecules with promising anticancer activity , but the difficulty in characterizing the mechanism of action of these compounds in human cells often undermines their value as drug leads . Here , we used a loss-of-function genetic screen in human haploid KBM7 cells to ...
Many of the medications that are available to treat cancer are either collected from natural sources or inspired by molecules existing in nature . While it is often challenging to understand how these natural compounds selectively kill cancer cells , characterizing these mechanisms is essential if researchers are to de...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology", "cancer", "biology" ]
2016
The anticancer natural product ophiobolin A induces cytotoxicity by covalent modification of phosphatidylethanolamine
Two classes of riboswitches related to the ykkC guanidine-I riboswitch bind phosphoribosyl pyrophosphate ( PRPP ) and guanosine tetraphosphate ( ppGpp ) . Here we report the co-crystal structure of the PRPP aptamer and its ligand . We also report the structure of the G96A point mutant that prefers ppGpp over PRPP with ...
DNA’s iconic double helix has made it possibly the most widely recognized biological molecule . The closely related RNA , however , is less well known but just as vital . In contrast with DNA’s typical rigid structure , RNA is more flexible and can fold into a wide range of shapes; this allows RNA molecules to have man...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "structural", "biology", "and", "molecular", "biophysics" ]
2018
Structures of two aptamers with differing ligand specificity reveal ruggedness in the functional landscape of RNA
During the development , tight regulation of the expansion of neural progenitor cells ( NPCs ) and their differentiation into neurons is crucial for normal cortical formation and function . In this study , we demonstrate that microRNA ( miR ) -128 regulates the proliferation and differentiation of NPCs by repressing pe...
The neurons that transmit information around the brain develop from cells called neural progenitor cells . These cells can either divide to form more progenitor cells or to become specific types of neurons . If these carefully regulated processes go wrong – for example , if progenitors fail to stop dividing in order to...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology", "neuroscience" ]
2016
MiRNA-128 regulates the proliferation and neurogenesis of neural precursors by targeting PCM1 in the developing cortex
Studies of the genetic basis and evolution of complex social behavior emphasize either conserved or novel genes . To begin to reconcile these perspectives , we studied how the evolutionary conservation of genes associated with social behavior depends on regulatory context , and whether genes associated with social beha...
Animal species vary widely in their degree of social behavior . Some species live solitarily , and others , such as ants and humans , form large societies . Many researchers have tried to understand the genetic changes underlying the evolution of social behavior . Some researchers suggest that it involves recycling exi...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "evolutionary", "biology" ]
2015
Genes associated with ant social behavior show distinct transcriptional and evolutionary patterns
Aging stem cells lose the capacity to properly respond to injury and regenerate their residing tissues . Here , we utilized the ability of Drosophila melanogaster germline stem cells ( GSCs ) to survive exposure to low doses of ionizing radiation ( IR ) as a model of adult stem cell injury and identified a regeneration...
Stem cells are unspecialized cells that have the unique ability to replace dead cells and repair damaged tissues . To give rise to new cells , stem cells need to divide . This process , known as the cell cycle , includes several stages and is regulated by many different genes . For example , in many organisms , a gene ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "stem", "cells", "and", "regenerative", "medicine", "cell", "biology" ]
2017
Loss of foxo rescues stem cell aging in Drosophila germ line
Persistent reservoirs remain the major obstacles to achieve an HIV-1 cure . Prolonged early antiretroviral therapy ( ART ) may reduce the extent of reservoirs and allow for virological control after ART discontinuation . We compared HIV-1 reservoirs in a cross-sectional study using polymerase chain reaction-based techn...
Many people with HIV infections are able to live relatively normal lives thanks to major advances in drug therapies . A cure , however , remains elusive . One reason for this is that the virus can hide in certain types of human cells , where it is protected from the immune system and the effects of “antiretroviral” dru...
[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]
[ "microbiology", "and", "infectious", "disease" ]
2015
Impact of a decade of successful antiretroviral therapy initiated at HIV-1 seroconversion on blood and rectal reservoirs
Endogenous retroviral sequences provide a molecular fossil record of ancient infections whose analysis might illuminate mechanisms of viral extinction . A close relative of gammaretroviruses , HERV-T , circulated in primates for ~25 million years ( MY ) before apparent extinction within the past ~8 MY . Construction of...
Over millions of years , viruses and the animals that they infect have been locked in a battle for survival , where each has needed to evolve ways to counteract the effects of the other . While the evolution of ancient animals can be studied by looking at the fossilized remains of their extinct relatives , studying how...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "evolutionary", "biology", "microbiology", "and", "infectious", "disease" ]
2017
Co-option of an endogenous retrovirus envelope for host defense in hominid ancestors
Huntington disease ( HD ) is a neurological disorder caused by polyglutamine expansions in mutated Huntingtin ( mHtt ) proteins , rendering them prone to form inclusion bodies ( IB ) . We report that in yeast , such IB formation is a factor-dependent process subjected to age-related decline . A genome-wide , high-conte...
Huntington’s disease is a neurological disease that is caused by mutations in the gene that encodes a protein called Htt . Individuals with this mutation gradually lose neurons as they age , resulting in declines in muscle coordination and mental abilities . The mutant Htt proteins tend to form clumps inside cells , bu...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "short", "report", "cell", "biology" ]
2016
Spatial sequestration and detoxification of Huntingtin by the ribosome quality control complex
Double-stranded DNA ( dsDNA ) binding and cleavage by Cas9 is a hallmark of type II CRISPR-Cas bacterial adaptive immunity . All known Cas9 enzymes are thought to recognize DNA exclusively as a natural substrate , providing protection against DNA phage and plasmids . Here , we show that Cas9 enzymes from both subtypes ...
Similar to humans , bacteria use an immune system known as the CRISPR-Cas system to protect themselves against invading pathogens such as viruses . CRISPRs are specialized stretches of DNA that guide Cas9 to the right location , while Cas9 proteins act like scissors that can cut foreign DNA . When a virus infects a bac...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology" ]
2018
RNA-dependent RNA targeting by CRISPR-Cas9
Recent technological advances now allow for the collection of vast data sets detailing the intricate neural connectivity patterns of various organisms . Oh et al . ( 2014 ) recently published the most complete description of the mouse mesoscale connectome acquired to date . Here we give an in-depth characterization of ...
Within the brain , neurons organize themselves into extensive networks . The physical connections between neurons determine which groups of neurons are able to communicate with one another . Recently , researchers mapped out the neural circuits within the entire brain of an adult mouse . The resulting wiring diagram , ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "computational", "and", "systems", "biology", "neuroscience" ]
2016
A simple generative model of the mouse mesoscale connectome
Hemodynamic forces regulate vascular functions . Disturbed flow ( DF ) occurs in arterial bifurcations and curvatures , activates endothelial cells ( ECs ) , and results in vascular inflammation and ultimately atherosclerosis . However , how DF alters EC metabolism , and whether resulting metabolic changes induce EC ac...
Atherosclerosis is the build-up of fatty material inside the blood vessels , and is one of the leading causes of heart disease and stroke . The blood vessels affected are typically inflamed for many years before the condition develops , and the condition often occurs at sites where blood vessels branch or turn . The ce...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology" ]
2017
HIF-1α is required for disturbed flow-induced metabolic reprogramming in human and porcine vascular endothelium
The ability to recognize small organic molecules and chemical modifications of host molecules is an essential capability of the adaptive immune system , which until now was thought to be mediated mainly by B cell antigen receptors . Here we report that small molecules , such as cyanine 3 ( Cy3 ) , a synthetic fluoresce...
Our immune system responds to invading microbes—such as viruses and bacteria—and tries to eliminate the threat via two distinct but connected systems: the innate and the adaptive immune systems . Cells of the innate immune system patrol our organs and tissues in an effort to identify and eliminate threats with a quick ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "immunology", "and", "inflammation" ]
2014
Gamma delta T cells recognize haptens and mount a hapten-specific response
Phagocytic immune cells kill pathogens in the phagolysosomal compartment with a cocktail of antimicrobial agents . Chief among them are reactive species produced in the so-called oxidative burst . Here , we show that bacteria exposed to a neutrophil-like cell line experience a rapid and massive oxidation of cytosolic t...
A group of cells of the immune system defends the body against infections by wrapping themselves around bacteria , and effectively ‘eating’ them . During this process , called phagocytosis , the cell also douses the bacterium with a deadly cocktail of chemicals , including an antiseptic – hydrogen peroxide – and bleach...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "microbiology", "and", "infectious", "disease" ]
2018
Neutrophil-generated HOCl leads to non-specific thiol oxidation in phagocytized bacteria
Misfolded proteins in the lumen of the endoplasmic reticulum ( ER ) are retrotranslocated into the cytosol and polyubiquitinated before being degraded by the proteasome . The multi-spanning ubiquitin ligase Hrd1 forms the retrotranslocation channel and associates with three other membrane proteins ( Hrd3 , Usa1 , Der1 ...
Just like factories make mistakes when producing products , cells make mistakes when producing proteins . In cells , a compartment called the endoplasmic reticulum is where about one third of all proteins are produced , and where new proteins undergo quality control . Damaged or misfolded proteins are removed by a proc...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]
2019
Cycles of autoubiquitination and deubiquitination regulate the ERAD ubiquitin ligase Hrd1
Tumor suppressor p53 is the most frequently mutated gene in tumors . Many mutant p53 ( mutp53 ) proteins promote tumorigenesis through the gain-of-function ( GOF ) mechanism . Mutp53 proteins often accumulate to high levels in tumors , which is critical for mutp53 GOF . Its underlying mechanism is poorly understood . H...
Cancer can develop if cells in the body acquire mutations that enable them to grow rapidly to form a mass called a tumor . The gene that encodes a protein called p53 is the most commonly mutated gene in human tumors . Most of these mutations result in the production of mutant p53 proteins that are similar in size to th...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology", "cancer", "biology" ]
2015
BAG2 promotes tumorigenesis through enhancing mutant p53 protein levels and function
Formation of the three embryonic germ layers is a fundamental developmental process that initiates differentiation . How the zebrafish pluripotency factor Pou5f3 ( homologous to mammalian Oct4 ) drives lineage commitment is unclear . Here , we introduce fluorescence lifetime imaging microscopy and fluorescence correlat...
As an animal embryo develops , cells divide and establish three distinct layers called the ectoderm , mesoderm and endoderm . Proteins called transcription factors control this process by regulating the activity of particular genes . Two or more transcription factors may interact to modulate each other’s activity . Zeb...
[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]
[ "developmental", "biology", "structural", "biology", "and", "molecular", "biophysics" ]
2016
Quantitative imaging reveals real-time Pou5f3–Nanog complexes driving dorsoventral mesendoderm patterning in zebrafish
A fundamental question of biology is what determines organ size . Despite demonstrations that factors within organs determine their sizes , intrinsic size control mechanisms remain elusive . Here we show that Drosophila wing size is regulated by JNK signaling during development . JNK is active in a stripe along the cen...
A key challenge in biology is to understand what determines size . As an animal grows , signals are produced that control the size of its organs . Many of the signaling pathways that regulate size during normal animal development also contribute to the formation of tumors . Therefore , it is important to find out exact...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "developmental", "biology" ]
2016
Localized JNK signaling regulates organ size during development
Pain is the most prominent symptom of osteoarthritis ( OA ) progression . However , the relationship between pain and OA progression remains largely unknown . Here we report osteoblast secret prostaglandin E2 ( PGE2 ) during aberrant subchondral bone remodeling induces pain and OA progression in mice . Specific deletio...
Many people will suffer from joint pain as they age , particularly in their knees . The most common cause of this pain is osteoarthritis , a disease that affects a tissue inside joints called cartilage . In a healthy knee , cartilage acts as a shock absorber . It cushions the ends of bones and enables them to move smoo...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "medicine", "neuroscience" ]
2020
Aberrant subchondral osteoblastic metabolism modifies NaV1.8 for osteoarthritis
PRDM9 binding localizes almost all meiotic recombination sites in humans and mice . However , most PRDM9-bound loci do not become recombination hotspots . To explore factors that affect binding and subsequent recombination outcomes , we mapped human PRDM9 binding sites in a transfected human cell line and measured PRDM...
Human cells have two copies of each chromosome: one from the mother , and one from the father . When cells divide to form sex cells , such as sperm or egg cells , the maternal and paternal chromosomes line up next to each other and swap some of their DNA . This process , known as genetic recombination , creates differe...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "chromosomes", "and", "gene", "expression", "genetics", "and", "genomics" ]
2017
A map of human PRDM9 binding provides evidence for novel behaviors of PRDM9 and other zinc-finger proteins in meiosis
Vulnerability to noise-induced tinnitus is associated with increased spontaneous firing rate in dorsal cochlear nucleus principal neurons , fusiform cells . This hyperactivity is caused , at least in part , by decreased Kv7 . 2/3 ( KCNQ2/3 ) potassium currents . However , the biophysical mechanisms underlying resilienc...
Tinnitus is often described as ‘ringing in the ears’ . Though the phantom sounds , which are heard in the absence of any genuine external noise , can take a variety of forms including buzzing , whistling , or humming . While training the brain to pay less attention to these internally generated sounds can sometimes red...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2015
Noise-induced plasticity of KCNQ2/3 and HCN channels underlies vulnerability and resilience to tinnitus
Evolutionary adaptation is a major source of antibiotic resistance in bacterial pathogens . Evolution-informed therapy aims to constrain resistance by accounting for bacterial evolvability . Sequential treatments with antibiotics that target different bacterial processes were previously shown to limit adaptation throug...
Overuse of antibiotic drugs is leading to the appearance of antibiotic-resistant bacteria; this is , bacteria with mutations that allow them to survive treatment with specific antibiotics . This has made some bacterial infections difficult or impossible to treat . Learning more about how bacteria evolve resistance to a...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "evolutionary", "biology" ]
2021
High potency of sequential therapy with only β-lactam antibiotics
Upon fertilization , the highly specialised sperm and oocyte genomes are remodelled to confer totipotency . The mechanisms of the dramatic reprogramming events that occur have remained unknown , and presumed roles of histone modifying enzymes are just starting to be elucidated . Here , we explore the function of the oo...
During fertilization , an egg cell and a sperm cell combine to make a cell called a zygote that then divides many times to form an embryo . Many of the characteristics of the embryo are determined by the genes it inherits from its parents . However , not all of these genes should be “expressed” to produce their product...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "chromosomes", "and", "gene", "expression", "developmental", "biology" ]
2016
Maternal LSD1/KDM1A is an essential regulator of chromatin and transcription landscapes during zygotic genome activation
Mutations in the genes for PINK1 and parkin cause Parkinson’s disease . PINK1 and parkin cooperate in the selective autophagic degradation of damaged mitochondria ( mitophagy ) in cultured cells . However , evidence for their role in mitophagy in vivo is still scarce . Here , we generated a Drosophila model expressing ...
Parkinson’s disease is a brain disorder where certain nerve cells slowly die , and the symptoms gradually worsen over time . While the risk of developing the condition increases with age , in certain patients the illness is caused by defects in two proteins , PINK1 and parkin . PINK1 and parkin help to manage mitochond...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "short", "report", "cell", "biology" ]
2018
Deficiency of parkin and PINK1 impairs age-dependent mitophagy in Drosophila
Gamma synchronization increases during movement and scales with kinematic parameters . Here , disease-specific characteristics of this synchronization and the dopamine-dependence of its scaling in Parkinson’s disease are investigated . In 16 patients undergoing deep brain stimulation surgery , movements of different ve...
Parkinson’s disease is a disorder of the nervous system that affects more than 1% of people over the age of 60 . Symptoms include uncontrollable shaking or tremor , and difficulty with large or fast movements . These symptoms occur when neurons that produce the chemical dopamine die . The loss of dopamine disrupts the ...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods", "and", "materials" ]
[ "medicine", "neuroscience" ]
2018
Dopamine-dependent scaling of subthalamic gamma bursts with movement velocity in patients with Parkinson’s disease
Earlier reports showed that hyperplasia of sympathoadrenal cell precursors during embryogenesis in Nf1-deficient mice is independent of Nf1’s role in down-modulating RAS-MAPK signaling . We demonstrate in zebrafish that nf1 loss leads to aberrant activation of RAS signaling in MYCN-induced neuroblastomas that arise in ...
Neuroblastoma is one of the most common childhood cancers and is responsible for about 15% of childhood deaths due to cancer . The neuroblastoma tumors arise in cells that develop into and form part of the body’s nervous system . Many researchers have studied the genetics of this disease and have recognised common patt...
[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]
[ "cancer", "biology" ]
2016
Synergy between loss of NF1 and overexpression of MYCN in neuroblastoma is mediated by the GAP-related domain
Migraine is the sixth most prevalent disease worldwide but the mechanisms that underlie migraine chronicity are poorly understood . Cytoskeletal flexibility is fundamental to neuronal-plasticity and is dependent on dynamic microtubules . Histone-deacetylase-6 ( HDAC6 ) decreases microtubule dynamics by deacetylating it...
Migraines are a common brain disorder that affects 14% of the world’s population . For many people the main symptom of a migraine is a painful headache , often on one side of the head . Other symptoms include increased sensitivity to light or sound , disturbed vision , and feeling sick . These sensory disturbances are ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2021
Neuronal complexity is attenuated in preclinical models of migraine and restored by HDAC6 inhibition
Changes in chromosome number impair fitness by disrupting the balance of gene expression . Here we analyze mechanisms to compensate for changes in gene dose that accompanied the evolution of sex chromosomes from autosomes . Using single-copy transgenes integrated throughout the Caenorhabditis elegans genome , we show t...
DNA inside cells is packaged into structures called chromosomes , each of which contains numerous genes . Many organisms , including humans , have two copies of most chromosomes in their cells . If the process of cell division goes awry , cells can end up with too many or too few copies of their chromosomes , which can...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "chromosomes", "and", "gene", "expression" ]
2016
Chromosome-wide mechanisms to decouple gene expression from gene dose during sex-chromosome evolution
Recent breakthroughs in 3-dimensional ( 3D ) organoid cultures for many organ systems have led to new physiologically complex in vitro models to study human development and disease . Here , we report the step-wise differentiation of human pluripotent stem cells ( hPSCs ) ( embryonic and induced ) into lung organoids . ...
Cell behavior has traditionally been studied in the lab in two-dimensional situations , where cells are grown in thin layers on cell-culture dishes . However , most cells in the body exist in a three-dimensional environment as part of complex tissues and organs , and so researchers have been attempting to re-create the...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "stem", "cells", "and", "regenerative", "medicine" ]
2015
In vitro generation of human pluripotent stem cell derived lung organoids