Explore the vast range of titles available.

Considerable overlap has been identified in the risk factors, comorbidities and putative pathophysiological mechanisms of Alzheimer disease and related dementias (ADRDs) and type 2 diabetes mellitus (T2DM), two of the most pressing epidemics of our time. Much is known about the biology of each condition, but whether T2DM and ADRDs are parallel phenomena arising from coincidental roots in ageing or synergistic diseases linked by vicious pathophysiological cycles remains unclear. Insulin resistance is a core feature of T2DM and is emerging as a potentially important feature of ADRDs. Here, we review key observations and experimental data on insulin signalling in the brain, highlighting its actions in neurons and glia. In addition, we define the concept of 'brain insulin resistance' and review the growing, although still inconsistent, literature concerning cognitive impairment and neuropathological abnormalities in T2DM, obesity and insulin resistance. Lastly, we review evidence of intrinsic brain insulin resistance in ADRDs. By expanding our understanding of the overlapping mechanisms of these conditions, we hope to accelerate the rational development of preventive, disease-modifying and symptomatic treatments for cognitive dysfunction in T2DM and ADRDs alike.

Histologic chorioamnionitis is an inflammatory disorder of the placenta that commonly precedes preterm delivery. Preterm birth related to chorioamnionitis and fetal inflammation has been associated with a risk for serious inflammatory complications in infancy. In addition, preterm infants exposed to chorioamnionitis may be more susceptible to infection in the neonatal intensive care unit and possibly later in life. A significant body of work has established an association between chorioamnionitis and inflammatory processes. However, the potential consequences of this inflammation on postnatal immunity are less understood. In this review, we will discuss current knowledge regarding the effects of fetal exposure to inflammation on postnatal immune responses.

Photorespiration functions in part to support photosynthetic performance, especially under stress such as high light, yet the underlying mechanisms are poorly understood. To identify modulators of photorespiration under high light, we have isolated genetic suppressors of the photorespiratory mutant hpr1 ( hydroxypyruvate reductase 1 ) from Arabidopsis. A suppressor that partially rescues hpr1 is mapped to GLYR1 , which encodes the cytosolic glyoxylate reductase 1 that converts glyoxylate to glycolate. Independent glyr1 mutants also partially rescue hpr1 and another photorespiratory mutant, catalase 2 . Our genetic, transcriptomic and metabolic profiling analyses together reveal a connection between cytosolic glyoxylate and a non-canonical photorespiratory route mediated by HPR2, which we name the photorespiratory glyoxylate shunt. This shunt complements the canonical photorespiratory pathway and is especially critical when high photorespiratory fluxes are required and when the major photorespiratory pathway is deficient. Our findings support the metabolic flexibility of photorespiration and may help to improve crop performance under stress. Our understanding of the mechanisms underlying the role and regulation of photorespiration in plant response to high light is still limited. Here, the authors report a cytosolic glyoxylate shunt for photorespiration that can reduce carbon retention in the photorespiratory intermediates that are toxic to plants.

Retinal ganglion cells (RGCs) are the sole projection neurons connecting the retina to the brain and therefore play a critical role in vision. Death of RGCs during glaucoma, optic neuropathies and after ocular trauma results in irreversible loss of vision as RGCs do not regenerate in the human eye. Moreover, there are no FDA approved therapies that prevent RGC death and/or promote RGC survival in the diseased or injured eye. There is a critical need to better understand the molecular underpinnings of neuroprotection to develop effective therapeutic approaches to preserve damaged RGCs. Unlike in mammals, RGCs in zebrafish are resilient to optic nerve injury, even after complete transection of the optic nerve. Here, we leveraged this unique model and utilized single-cell RNA sequencing to characterize RGC responses to injury and identify putative neuroprotective and regenerative pathways. RGCs are heterogeneous and studies in mice have shown that there is differential resiliency across RGC subtypes. Our results demonstrated that all RGC subtypes are resilient to injury in zebrafish. Quantifying changes in gene expression revealed the upregulation of progenitor and regenerative markers in all RGC subtypes after injury as well as distinct early and late phases to the injury response. This shift in gene expression causes injury-responsive RGCs to resemble RGC subtype 3, a low frequency population of endogenous immature RGCs that are normally maintained in the wild-type, uninjured adult retina. A similar but restricted transcriptomic injury response in RGCs of the uninjured contralateral eye was also detected, highlighting a systemic RGC response to unilateral optic nerve injury. Taken together, these results demonstrate that zebrafish RGCs dedifferentiate in response to injury, and this may be a novel mechanism mediating their unique cell survival and regenerative capabilities.

Magnetic fields are ubiquitous in the Universe. The energy density of these fields is typically comparable to the energy density of the fluid motions of the plasma in which they are embedded, making magnetic fields essential players in the dynamics of the luminous matter. The standard theoretical model for the origin of these strong magnetic fields is through the amplification of tiny seed fields via turbulent dynamo to the level consistent with current observations. However, experimental demonstration of the turbulent dynamo mechanism has remained elusive, since it requires plasma conditions that are extremely hard to re-create in terrestrial laboratories. Here we demonstrate, using laser-produced colliding plasma flows, that turbulence is indeed capable of rapidly amplifying seed fields to near equipartition with the turbulent fluid motions. These results support the notion that turbulent dynamo is a viable mechanism responsible for the observed present-day magnetization. Exploring astrophysical turbulent effects in laboratory plasma is challenging due to high threshold values of relevant parameters, such as the magnetic Reynolds number. Here the authors demonstrate the turbulent dynamo effect at large magnetic Reynolds numbers in laser-generated magnetized plasma.

Assemblies formed by solid particles at interfaces have been widely studied because they serve as models of molecular phenomena, including molecular self-assembly. Solid particles adsorbed at interfaces also provide a means of stabilizing liquid-liquid emulsions and synthesizing materials with tunable mechanical, optical, or electronic properties. Whereas many past studies have investigated colloids at interfaces of isotropic liquids, recently, new types of intercolloidal interactions have been unmasked at interfaces of liquid crystals (LCs): The long-range ordering of the LCs, as well as defects within the LCs, mediates intercolloidal interactions with symmetries that differ from those observed with isotropic liquids. Herein, we report the decoration of interfaces formed between aqueous phases and nematic LCs with prescribed densities of solid, micrometer-sized particles. The microparticles assemble into chains with controlled interparticle spacing, consistent with the dipolar symmetry of the defects observed to form about each microparticle. Addition of a molecular surfactant to the aqueous phase results in a continuous ordering transition in the LC, which triggers reorganization of the microparticles, first by increasing the spacing between microparticles within chains and ultimately by forming two-dimensional arrays with local hexagonal symmetry. The ordering transition of the microparticles is reversible and is driven by surfactant-induced changes in the symmetry of the topological defects induced by the microparticles. These results demonstrate that the orderings of solid microparticles and molecular adsorbates are strongly coupled at the interfaces of LCs and that LCs offer the basis of methods for reversible, chemosensitive control of the interfacial organization of solid microparticles.

This brief report provides an introduction to the topic of cognitive functioning in late-life depression (LLD). In addition to providing a review of the literature, we present a framework for understanding the heterogeneity of cognitive outcomes in this highly prevalent disorder. In addition, we discuss the relationship between LLD and dementia, and highlight the importance of regularly assessing cognitive functioning in older adults who present with depressive symptoms. If cognitive deficits are discovered during a neuropsychological assessment, we recommend referral to a geriatric psychiatrist or cognitive neurologist, for evaluation and treatment of the patient’s symptoms. (JINS, 2014, 20, 1–7)

Hearing loss is the most common sensory disorder and because of its high genetic heterogeneity, implementation of Massively Parallel Sequencing (MPS) in diagnostic laboratories is greatly improving the possibilities of offering optimal care to patients. We present the results of a two-year period of molecular diagnosis that included 207 French families referred for non-syndromic hearing loss. Our multi-step strategy involved (i) DFNB1 locus analysis, (ii) MPS of 74 genes, and (iii) additional approaches including Copy Number Variations, in silico analyses, minigene studies coupled when appropriate with complete gene sequencing, and a specific assay for STRC . This comprehensive screening yielded an overall diagnostic rate of 48%, equally distributed between DFNB1 (24%) and the other genes (24%). Pathogenic genotypes were identified in 19 different genes, with a high prevalence of GJB2 , STRC , MYO15A , OTOF , TMC1 , MYO7A and USH2A . Involvement of an Usher gene was reported in 16% of the genotyped cohort. Four de novo variants were identified. This study highlights the need to develop several molecular approaches for efficient molecular diagnosis of hearing loss, as this is crucial for genetic counselling, audiological rehabilitation and the detection of syndromic forms.

The thermal state of permafrost in South America is poorly understood compared to other regions, largely due to a scarcity of in situ data. This study presents the first coordinated regional compilation of borehole temperature records from high-altitude mountain permafrost sites in the Central Andes (3500 to 5250 m; 27–34° S), providing a baseline assessment of ground thermal conditions. Measurements from 53 boreholes along a north–south transect at the Chilean–Argentine border reveal ground thermal characteristics similar to those in other mountain permafrost regions, including high spatial and temporal variability, correlations with altitude and slope aspect, and distinct thermal attributes of rock glaciers. These observations suggest that the ground thermal regime of the Central Andes is shaped by similar processes, a perspective that previously lacked data support. The high temporal variability observed in the short records (< 9 years) reflects short-term microclimatic fluctuations and topo-climatic attributes unique to the Andean cryosphere. These include hyper-arid conditions, intense solar radiation, limited vegetative cover and organic matter, less massive ice (except in rock glaciers), and mountain topography in a Southern Hemisphere location. The susceptibility of the area to regional climatic phenomena (such as Southern Annular Mode (SAM), El Niño–Southern Oscillation (ENSO) and Pacific Decadal Oscillation (PDO)) suggests that long-term trends can only be determined from extended datasets spanning several decades. This study highlights the need for ongoing ground temperature monitoring and emphasizes the importance of collaboration between industry, governments and scientists to advance understanding of a key climate change indicator in a data-scarce region.

Documentaries are the primary means by which many people observe the behavior of wild primates. By influencing layperson perceptions of wild primates, documentaries could impact viewer conservation-related beliefs and behaviors and, therefore, the well-being of wild primates. To investigate such portrayals, we examined documentaries depicting the four species that were most represented in documentaries: rhesus macaque, chimpanzee, ring-tailed lemur, and mountain gorilla. For each documentary, we continuously coded behavior, conducted scan samples of age-sex classes at 3-min intervals, and made ad libitum observations of inaccuracies and misleading content. We expected that representation of age-sex classes and activity budgets in documentaries would differ from those reported in the primary literature for the same species in the wild. In addition, we expected inaccurate depictions for every species. For ring-tailed lemurs, adult males were underrepresented in documentaries. For macaques, chimpanzees, and gorillas, representation of age-sex classes did not differ significantly from observations in the wild. Documentary depictions of activity budgets differed from researcher accounts of wild primate behavior for rhesus macaques, chimpanzees, and mountain gorillas, but not for ring-tailed lemurs. In general, documentaries overrepresented traveling and social behaviors such as play and grooming. Documentaries, especially docudramas, may have emphasized traveling because such footage allows storyline narration, whereas the emphasis on social behavior was likely due to the appeal of such footage to audiences. Inaccuracies were documented for all four species, with rhesus macaques having the most inaccuracies. We propose that primatologists have an ethical imperative to enhance the accuracy of primate portrayals to audiences.