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issn:1757-594
1.  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.
doi:10.3410/B1-95
PMCID: PMC2884157  PMID: 20556198
2.  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.
doi:10.3410/B1-89
PMCID: PMC2799925  PMID: 20046812
3.  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.
doi:10.3410/B1-90
PMCID: PMC2849317  PMID: 20376293
4.  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.
doi:10.3410/B1-83
PMCID: PMC2788957  PMID: 20161436
5.  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.
doi:10.3410/B1-81
PMCID: PMC2779035  PMID: 20161371
6.  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.
doi:10.3410/B1-72
PMCID: PMC2847299  PMID: 20357902
7.  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.
doi:10.3410/B1-69
PMCID: PMC2832337  PMID: 20209018
8.  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.
doi:10.3410/B1-85
PMCID: PMC2886298  PMID: 20563314
9.  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.
doi:10.3410/B1-66
PMCID: PMC2873777  PMID: 20495680
10.  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.
doi:10.3410/B1-64
PMCID: PMC2832315  PMID: 20209017
11.  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
12.  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.
doi:10.3410/B1-62
PMCID: PMC2818080  PMID: 20150950
13.  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.
doi:10.3410/B1-98
PMCID: PMC2873783  PMID: 20495683
14.  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.
doi:10.3410/B1-22
PMCID: PMC2773505  PMID: 20160888
15.  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.
doi:10.3410/B1-98
PMCID: PMC2873783  PMID: 20495683
16.  Putative functions of caspase-2 
Caspase-2 is the most evolutionarily conserved of caspase family members, yet its physiological function has remained unclear and is a matter of considerable debate. Newly published data now suggest that caspase-2 is required for cell cycle regulation, repair of damaged DNA, and in suppressing Myc-induced lymphomagenesis. Additionally, loss of Casp2 in mice leads to features of premature ageing. These findings suggest that caspase-2 has non-apoptotic functions in addition to its context-dependent roles in cell death.
doi:10.3410/B1-96
PMCID: PMC2948275  PMID: 20948596
17.  Natural killer T cell recognition of lipid antigens 
Natural killer T cells recognize lipid antigens in the context of CD1 molecules. Recent publications show that this mode of recognition differs substantially from that of classic T-cell receptor peptide-major histocompatibility complex interaction.
doi:10.3410/B1-97
PMCID: PMC2948285  PMID: 20948595
18.  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.
doi:10.3410/B1-95
PMCID: PMC2884157  PMID: 20556198
19.  Aberrant mRNA transcripts and nonsense-mediated decay 
Nobody's perfect, and even the cell turns out a certain fraction of erroneous mRNA transcripts. One of the key quality control mechanisms put in place to recognize and eliminate these transcripts before they can be translated into faulty proteins is nonsense-mediated decay. Proteins involved in nonsense-mediated decay are highly conserved across species from plants to humans, and recent studies in Arabidopsis thaliana reveal both intriguing similarities and differences in the mechanisms employed to carry it out.
doi:10.3410/B1-93
PMCID: PMC2948277  PMID: 20948598
20.  Insulators: linking genome architecture to gene regulation 
Insulator elements have long been associated with a proposed domain boundary function, ensuring appropriate associations between regulatory elements and transcription units through the physical organisation of the genome into looped domains. Recent experiments in Drosophila have, however, highlighted a more direct involvement of insulators in transcriptional regulation.
doi:10.3410/B1-92
PMCID: PMC2948281  PMID: 20948599
21.  Prediction of function in protein superfamilies 
Assignment of function for enzymes encoded in sequenced genomes is a challenging task. Predictions of enzyme function can be made using clues from superfamily assignment, structure, genome context, phylogenetic conservation, and virtual screening to identify potential ligands. Ultimately, confident assignment of function requires experimental verification as well as an understanding of the physiological role of an enzyme in the context of the metabolic network.
doi:10.3410/B1-91
PMCID: PMC2948282  PMID: 20948600
22.  Current themes and recent advances in modelling species occurrences 
Recent years have seen a huge expansion in the range of methods and approaches that are being used to predict species occurrences. This expansion has been accompanied by many improvements in statistical methods, including more accurate ways of comparing models, better null models, methods to cope with autocorrelation, and greater awareness of the importance of scale and prevalence. However, the field still suffers from problems with incorporating temporal variation, overfitted models and poor out-of-sample prediction, confusion between explanation and prediction, simplistic assumptions, and a focus on pattern over process. The greatest advances in recent years have come from integrative studies that have linked species occurrence models with other themes and topics in ecology, such as island biogeography, climate change, disease geography, and invasive species.
doi:10.3410/B1-94
PMCID: PMC2948293  PMID: 20948597
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.
doi:10.3410/B1-41
PMCID: PMC2786071  PMID: 19960095
24.  HIV vaccination: turning the spotlight on effector memory T cells as mucosal gatekeepers 
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.
doi:10.3410/B1-89
PMCID: PMC2799925  PMID: 20046812
25.  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.
doi:10.3410/B1-90
PMCID: PMC2849317  PMID: 20376293

Results 1-25 (113)