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1.  Recent advances in understanding Golgi biogenesis 
The Golgi complex is a central processing station for proteins traversing the secretory pathway, yet we are still learning how this compartment is constructed and how cargo moves through it. Recent experiments suggest a key role for Ras-like Rab GTPases and provide important new ideas for how the Golgi may function.
PMCID: PMC2897732  PMID: 20625450
2.  Recent advances in polyubiquitin chain recognition 
F1000 biology reports  2010;2(20):1-5.
Polyubiquitin chains are regulatory signals for a wide array of biological processes. Recent structural studies reveal novel modes of polyubiquitin chain recognition and implicate the diverse repertoire of interactions in providing the specificity of polyubiquitin recognition.
PMCID: PMC2847284  PMID: 20357899
3.  Recent advances in pancreas development: from embryonic pathways to programming renewable sources of beta cells 
F1000 biology reports  2010;2(17):1-4.
In recent years, there has been significant progress in understanding the detailed mechanisms of pancreas development. These studies have in turn influenced research aimed at producing pancreatic islet cells from stem cells. Here, we review recent progress in both of these areas.
PMCID: PMC2863342  PMID: 20445833
4.  RNA pseudoknots: folding and finding 
RNA pseudoknots are important for function. Three-dimensional structural information is available, insights into factors affecting pseudoknot stability are being reported, and computer programs are available for predicting pseudoknots.
PMCID: PMC2873773  PMID: 20495679
5.  Understanding lipid rafts and other related membrane domains 
Evidence in support of the classical lipid raft hypothesis has remained elusive. Data suggests that transmembrane proteins and the actin-containing cortical cytoskeleton can organize lipids into short-lived nanoscale assemblies that can be assembled into larger domains under certain conditions. This supports an evolving view in which interactions between lipids, cholesterol, and proteins create and maintain lateral heterogeneity in the cell membrane.
PMCID: PMC2894464  PMID: 20606718
6.  Mechanisms of growth cone repulsion 
Research conducted in the last century suggested that chemoattractants guide cells or their processes to appropriate locations during development. Today, we know that many of the molecules involved in cellular guidance can act as chemorepellents that prevent migration into inappropriate territories. Here, we review some of the early seminal experiments and our current understanding of the underlying molecular mechanisms.
PMCID: PMC2919842  PMID: 20711492
7.  CRISPR-Cas: an adaptive immunity system in prokaryotes 
Most of the archaea and numerous bacteria possess an elaborate system of adaptive immunity to mobile genetic elements known as the CRISPR (clustered regularly interspaced short palindromic repeats)-associated system (CRISPR-Cas), which consists of arrays of short repeats interspersed with unique DNA spacers and adjacent operons encompassing CRISPR-associated (cas) genes with predicted and, in some cases, experimentally validated nuclease, helicase, and polymerase activities. The system functions by integrating fragments of alien DNA between the repeats and employing their transcripts to degrade the DNA of the respective invading elements via an RNA interference-like mechanism. The CRISPR-Cas system is a case of apparent Lamarckian inheritance.
PMCID: PMC2884157  PMID: 20556198
8.  HIV vaccination: turning the spotlight on effector memory T cells as mucosal gatekeepers 
F1000 biology reports  2009;1(89):nihpa161827.
The accumulating failures in HIV vaccine development demonstrate that the immunization approaches used so far are insufficient to reproduce the naturally occurring immunity that controls the virus in long-term non-progressors, HIV controllers, and continuously exposed sex workers. They also underscore the desperate need for new approaches in the design of more effective vaccination protocols. Recent findings might have brought us closer to that goal by providing proof of concept for a novel preventative HIV vaccine by establishing CD8 effector memory T cells within the mucosal sites of transmission.
PMCID: PMC2799925  PMID: 20046812
9.  Telomeric RNAs as a novel player in telomeric integrity 
Telomeres protect linear chromosome ends from being recognized and processed as double-strand breaks by DNA repair activities. This protective function of telomeres is essential for chromosome stability. Until recently, telomeres have been considered to be transcriptionally silent. This notion was overturned in a series of recent papers that describe the existence of telomeric repeat-containing RNAs (TERRAs) in vertebrates and yeast. Here, we summarize recent developments in this field of telomere research, in particular the possible mechanisms that control TERRA expression.
PMCID: PMC2849317  PMID: 20376293
10.  An old dog learns new tricks: novel functions of the exocyst complex in polarized epithelia in animals 
F1000 biology reports  2009;1(83):nihpa159599.
The role of the exocyst complex has been studied mainly in the context of basolateral sorting of cargos in polarized cells. Recent developments indicate an extended yet specific function of the exocyst in the outgrowth of the primary cilium from the apical membrane, thereby highlighting a role for the exocyst in ensuring membrane trafficking to important signaling stations in the cell, the tight junctions, and the cilia.
PMCID: PMC2788957  PMID: 20161436
11.  Transcranial magnetic stimulation studies of visuospatial attentional control 
F1000 biology reports  2009;1(81):nihpa156411.
Transcranial magnetic stimulation (TMS) is an established technique in cognitive neuroscience which is used to interrupt processing in the brain, creating a brief ‘virtual lesion’. Here, we review recent studies that have employed TMS to gain insight into the roles of frontal and parietal cortex in visuospatial attention control.
PMCID: PMC2779035  PMID: 20161371
12.  Conformational changes in receptor tyrosine kinase signaling: an ErbB garden of delights 
F1000 biology reports  2009;1(72):1-4.
The ErbB family of receptor tyrosine kinases plays important roles in cell proliferation, differentiation, and apoptosis. Recent structural studies of these receptors have demonstrated dramatic conformational effects that are critical to their ligand binding and activation, and have shown that these receptors provide levels of control beyond the classic dimerization/activation mechanism. These results indicate that this class of receptors has evolved subtle regulatory mechanisms via genetic and protein structural changes to influence their effects on cell behaviors.
PMCID: PMC2847299  PMID: 20357902
13.  Diversity of protein structures and difficulties in fold recognition: the curious case of protein G 
We examine the ability of current state-of-the-art methods in protein structure prediction to discriminate topologically distant folds encoded by highly similar (>90% sequence identity) designed proteins in blind protein structure prediction experiments. We detail the corresponding prognosis for the protein fold recognition field and highlight the features of the methodologies that successfully deciphered this folding riddle.
PMCID: PMC2832337  PMID: 20209018
14.  The evolving story of orexin biology: the hits keep coming 
In the span of just 11 years since their discovery, the study of the orexins (hypocretins) has not only provided insight into the biology of sleep/wakefulness, but also demonstrated the importance of the development of new pharmacologic tools and genetic models with which to understand basic physiologic mechanisms and provide potential strategies for the treatment of human pathologies. Highlights from recently published novel approaches and findings are reviewed here.
PMCID: PMC2886298  PMID: 20563314
15.  Setting the absolute threshold of vision 
The performance of sensory systems in many cases is limited by the physical nature of the stimulus. For vision, the quantal nature of light limits detection by dark-adapted observers; only now are we beginning to be aware of the subtleties in the biophysical mechanisms underlying this exquisite sensitivity.
PMCID: PMC2873777  PMID: 20495680
16.  Do apicomplexan parasite-encoded proteins act as both ligands and receptors during host cell invasion? 
Apicomplexan parasites are responsible for a wide range of diseases in animals, including humans, in whom Plasmodium species cause the devastating disease malaria. Several recent discoveries now indicate that these intracellular parasites may use a conserved mechanism to infect their host cells by using parasite-encoded proteins as both parasite ligands and receptors anchored to the host cells.
PMCID: PMC2832315  PMID: 20209017
17.  Vesicle coating and uncoating: controlling the formation of large COPII-coated carriers 
F1000 biology reports  2009;1:65-.
The basic mechanisms underlying the formation of coated vesicles are now defined in considerable detail. This article highlights recent developments in our understanding of the problem of exporting large macromolecular cargo such as procollagen from the endoplasmic reticulum and discusses the implications that this has for cell and tissue organisation and human disease.
PMCID: PMC2854804  PMID: 20401317
18.  Cryptococcus gattii outbreak expands into the Northwestern United States with fatal consequences 
In the past decade, the primary fungal pathogen Cryptococcus gattii has evolved and adapted to the temperate climate of the Pacific Northwest region of North America. This pathogen is now endemic and an increasingly common cause of life-threatening pulmonary and central nervous system infections that are difficult to manage and, in some cases, fatal to humans and other mammals throughout the region. A series of recent reports provide evidence that evolutionary, climatic, and anthropogenic factors may be causing the expansion of the Vancouver Island outbreak genotype into the United States, with the concomitant emergence of a unique genotype in the state of Oregon. Ongoing studies address the molecular epidemiology, roles of mating and genetic exchange, and geographic origins of this unprecedented outbreak of fungal infection of considerable public health magnitude.
PMCID: PMC2818080  PMID: 20150950
19.  RecA-independent single-stranded DNA oligonucleotide-mediated mutagenesis 
F1000 biology reports  2010;2(1):56.
The expression of Beta, the single-stranded annealing protein (SSAP) of bacteriophage λ in Escherichia coli promotes high levels of oligonucleotide (oligo)-mediated mutagenesis and offers a quick way to create single or multiple base pair insertions, deletions, or substitutions in the bacterial chromosome. High rates of mutagenesis can be obtained by the use of mismatch repair (MMR)-resistant mismatches or MMR-deficient hosts, which allow for the isolation of unselected mutations. It has recently become clear that many bacteria can be mutagenized with oligos in the absence of any SSAP expression, albeit at a much lower frequency. Studies have shown that inactivation or inhibition of single-stranded DNA (ssDNA) exonucleases in vivo increases the rate of SSAP-independent oligo-mediated mutagenesis. These results suggest that λ Beta, in addition to its role in annealing the oligo to ssDNA regions of the replication fork, promotes high rates of oligo-mediated mutagenesis by protecting the oligo from destruction by host ssDNA exonucleases.
PMCID: PMC2920528  PMID: 20711416
20.  Transport vesicle uncoating: it’s later than you think 
Transport vesicle coat proteins play active roles in vesicle cargo sorting as well as membrane deformation and fission during vesicle biogenesis. For years, it was assumed that this was the extent of the coats’ function and that the coats depolymerized immediately after vesicle budding, leaving the exposed fusion machinery free to find, dock, and fuse with the proper target membrane. Recently, however, it has become increasingly clear that the coat remains on transport vesicles during their post-budding life and in fact helps properly pair up the vesicle with its intended target membrane. These data have brought up urgent questions about exactly when vesicles do uncoat and how uncoating is regulated. Here, we summarize the latest round of evidence for post-budding roles for coats, including a few hints about how the uncoating process may be coupled to docking and fusion. We also speculate about the possibility of post-fusion functions for residual coats.
PMCID: PMC2919759  PMID: 20706600
21.  Brd4 engagement from chromatin targeting to transcriptional regulation: selective contact with acetylated histone H3 and H4 
Bromodomain-containing protein 4 (Brd4) contains two tandem bromodomains (BD1 and BD2) that bind preferentially to acetylated lysine residues found in histones and nonhistone proteins. This molecular recognition allows Brd4 to associate with acetylated chromatin throughout the cell cycle and regulates transcription at targeted loci. Recruitment of positive transcription elongation factor b, and possibly the general initiation cofactor Mediator as well, plays an important role in Brd4-regulated transcription. Selective contacts with acetyl-lysines in nucleosomal histones and chromatin-binding factors likely provide a molecular switch modulating the steps from chromatin targeting to transcriptional regulation, thus further expanding the ‘acetylation code’ for combinatorial regulation in eukaryotes.
PMCID: PMC2873783  PMID: 20495683
22.  Latest advances in innate antiviral defence 
F1000 biology reports  2009;1(22):nihpa103883.
Recent identification of key components in the pattern recognition receptor pathway of retinoic acid-inducible gene-1-like receptors, coupled with characterisation of a new cytoplasmic DNA-sensing molecule, have led to a greater understanding of the role viral nucleic acids play in activating innate immunity. This activation of type I interferon is essential for both limiting viral infection and stimulating activation of the adaptive immune response.
PMCID: PMC2773505  PMID: 20160888
23.  Osmolyte solutions and protein folding 
F1000 biology reports  2009;1(41):1-3.
In this brief review we discuss the evolution of recent thought regarding the role and mechanism of osmolytes with respect to protein stability. Osmolytes are naturally occurring intracellular compounds that change the protein folding landscape. Contributions from experiments are considered in the context of current theory and simulation results.
PMCID: PMC2786071  PMID: 19960095

Results 1-23 (23)