Telomeres are DNA-protein complexes that cap and protect the ends of linear chromosomes. In almost all species, telomeric DNA has a G/C strand bias, and the short tandem repeats of the G-rich strand ...have the capacity to form into secondary structures in vitro, such as four-stranded G-quadruplexes. This has long prompted speculation that G-quadruplexes play a positive role in telomere biology, resulting in selection for G-rich tandem telomere repeats during evolution. There is some evidence that G-quadruplexes at telomeres may play a protective capping role, at least in yeast, and that they may positively affect telomere maintenance by either the enzyme telomerase or by recombination-based mechanisms. On the other hand, G-quadruplex formation in telomeric DNA, as elsewhere in the genome, can form an impediment to DNA replication and a source of genome instability. This review summarizes recent evidence for the in vivo existence of G-quadruplexes at telomeres, with a focus on human telomeres, and highlights some of the many unanswered questions regarding the location, form, and functions of these structures.
In the rodent vibrissal system, active sensation and sensorimotor integration are mediated in part by connections between barrel cortex and vibrissal motor cortex. Little is known about how these ...structures interact at the level of neurons. We used Channelrhodopsin-2 (ChR2) expression, combined with anterograde and retrograde labeling, to map connections between barrel cortex and pyramidal neurons in mouse motor cortex. Barrel cortex axons preferentially targeted upper layer (L2/3, L5A) neurons in motor cortex; input to neurons projecting back to barrel cortex was particularly strong. Barrel cortex input to deeper layers (L5B, L6) of motor cortex, including neurons projecting to the brainstem, was weak, despite pronounced geometric overlap of dendrites with axons from barrel cortex. Neurons in different layers received barrel cortex input within stereotyped dendritic domains. The cortico-cortical neurons in superficial layers of motor cortex thus couple motor and sensory signals and might mediate sensorimotor integration and motor learning.
► Barrel cortex targets superficial pyramidal neurons in the motor cortex (vM1) ► vM1 cells projecting to the barrel cortex receive strong input from the barrel cortex ► vM1 cells projecting out of the cortex receive little input from the barrel cortex ► Cortico-cortical neurons in the motor cortex mediate sensorimotor integration
Water oxidation is a key chemical transformation for the conversion of solar energy into chemical fuels. Our review focuses on recent work on robust earth-abundant heterogeneous catalysts for the ...oxygen-evolving reaction (OER). We point out that improvements in the performance of OER catalysts will depend critically on the success of work aimed at understanding reaction barriers based on atomic-level mechanisms. We highlight the challenge of obtaining acid-stable OER catalysts, with proposals for elements that could be employed to reach this goal. We suggest that future advances in solar fuels science will be accelerated by the development of new methods for materials synthesis and characterization, along with in-depth investigations of redox mechanisms at catalytic surfaces.
Since the discovery of ocular dominance plasticity, neuroscientists have understood that changes in visual experience during a discrete developmental time, the critical period, trigger robust changes ...in the visual cortex. State-of-the-art tools used to probe connectivity with cell-type-specific resolution have expanded the understanding of circuit changes underlying experience-dependent plasticity. Here, we review the visual circuitry of the mouse, describing projections from retina to thalamus, between thalamus and cortex, and within cortex. We discuss how visual circuit development leads to precise connectivity and identify synaptic loci, which can be altered by activity or experience. Plasticity extends to visual features beyond ocular dominance, involving subcortical and cortical regions, and connections between cortical inhibitory interneurons. Experience-dependent plasticity contributes to the alignment of networks spanning retina to thalamus to cortex. Disruption of this plasticity may underlie aberrant sensory processing in some neurodevelopmental disorders.
Hooks and Chen review how circuits in the mouse visual system mature and respond to changes in visual experience during development. Circuit plasticity is essential for normal sensory development, and disruption of this process may underlie some neurodevelopmental disorders.
G-quadruplexes are four-stranded guanine-rich structures that have been demonstrated to occur across the genome in humans and other organisms. They provide regulatory functions during transcription, ...translation and immunoglobulin gene rearrangement, but there is also a large amount of evidence that they can present a potent barrier to the DNA replication machinery. This mini-review will summarize recent advances in understanding the many strategies nature has evolved to overcome G-quadruplex-mediated replication blockage, including removal of the structure by helicases or nucleases, or circumventing the deleterious effects on the genome through homologous recombination, alternative end-joining or synthesis re-priming. Paradoxically, G-quadruplexes have also recently been demonstrated to provide a positive role in stimulating the initiation of DNA replication. These recent studies have not only illuminated the many roles and consequences of G-quadruplexes, but have also provided fundamental insights into the general mechanisms of DNA replication and its links with genetic and epigenetic stability.
Sphingosine‐1‐phosphate (S1P) is a signalling lipid that regulates many cellular processes in mammals. One well‐studied role of S1P signalling is to modulate T‐cell trafficking, which has a major ...impact on adaptive immunity. Compounds that target S1P signalling pathways are of interest for immune system modulation. Recent studies suggest that S1P signalling regulates many more cell types and processes than previously appreciated. This review will summarise current understanding of S1P signalling, focusing on recent novel findings in the roles of S1P receptors in innate immunity.
Developing energy storage devices to be utilized within a rapidly advancing energy market requires a multipronged approach whereby material synthesis and engineering fundamentals combine to enable ...technological advances. These devices should be able to store a large amount of energy in a small, lightweight package, and should be able to distribute that energy quickly for high rate applications. Pseudocapacitors made from conducting polymers, which store charge via rapid reduction and oxidation reactions, are a particularly promising candidate. This perspective explores conductivity and charge storage mechanisms in conducting polymers and describes how synthetic strategies can affect these properties. We further develop chemical correlations that have been shown to enhance the performance of pseudocapacitive electrochemical capacitors fabricated from conducting polymers. Important device engineering strategies for improving the lifetime and applicability of pseudocapacitors are also discussed.
Chromatin is a complex of DNA, RNA, histones and non-histone proteins and provides the platform on which the transcriptional machinery operates in eukaryotes. The structure and configuration of ...chromatin are manipulated by families of enzymes, some catalysing the dynamic addition and removal of chemical ligands to selected protein amino acids and some directly altering or displacing the basic structural units. The activities of many of these enzymes are sensitive to environmental and metabolic agents and can thereby serve as sensors through which environmental agents can alter gene expression. Such changes can, in turn, precipitate either local or cell-wide changes as the initial effect spreads through multiple interactive networks. This review discusses the increasingly well-understood mechanisms through which these enzymes alter chromatin function. In some cases at least, it seems that the effects on gene expression may persist even after the removal of the inducing agent, and can be passed on, through mitosis, to subsequent cell generations, constituting a heritable, epigenetic change. If such changes occur in germ cells or their precursors, then they may be passed on to subsequent generations. Mechanisms are now known to exist through which an epigenetic change might give rise to a localized change in DNA sequence exerting the same functional effect, thereby converting an epigenetic to a genetic change. If the induced genetic change has phenotypic effects on which selection can act, then this hypothetical chain of events constitutes a potential route through which the environment might directly influence evolution.
Objective: To describe the current Ebola virus epidemic and the potential options for treatment and prevention of Ebola virus disease. Data Sources: A PubMed literature search (1976 through October ...20, 2014) was conducted using the search term Ebola. Study Selection and Data Extraction: Animal and human studies published in English were selected. Studies published within the past 5 years were the primary focus of this review. Data Synthesis: The current Ebola virus epidemic has primarily been contained in West Africa though it has subsequently spread to other areas, including the United States. The first patient in the United States infected with Ebola virus was diagnosed, treated, and expired in Texas. Two nurses caring for this patient also were diagnosed with Ebola virus and have been successfully treated. Treatment options for patients infected with Ebola virus are limited. Supportive therapy is centered on fluid resuscitation, electrolyte imbalance correction, treating complicating infections, and preventing complications of shock. Experimental therapies (ZMapp, brincidofovir, TKM-Ebola, and favipiravir) have been used during this current outbreak. Several medications such as amiodarone, chloroquine, and clomiphene may prevent the transmission of or treat Ebola virus. Different vaccine therapies are also in early-stage development. One of the vaccine strategies using recombinant vesicular stomatitis virus as a delivery vector has demonstrated efficacy when used for preexposure and postexposure prophylaxis. Conclusion: Ebola virus is highly virulent and fatal, and treatment options are limited. Several experimental and existing therapies may be options for preventing and treating Ebola virus disease.
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