Normal aging and Alzheimer’s disease (AD) cause profound changes in the brain’s structure and function. AD in particular is accompanied by widespread cortical neuronal loss, and loss of connections ...between brain systems. This degeneration of neural pathways disrupts the functional coherence of brain activation. Recent innovations in brain imaging have detected characteristic disruptions in functional networks. Here we review studies examining changes in functional connectivity, measured through fMRI (functional magnetic resonance imaging), starting with healthy aging and then Alzheimer’s disease. We cover studies that employ the three primary methods to analyze functional connectivity—seed-based, ICA (independent components analysis), and graph theory. At the end we include a brief discussion of other methodologies, such as EEG (electroencephalography), MEG (magnetoencephalography), and PET (positron emission tomography). We also describe multi-modal studies that combine rsfMRI (resting state fMRI) with PET imaging, as well as studies examining the effects of medications. Overall, connectivity and network integrity appear to decrease in healthy aging, but this decrease is accelerated in AD, with specific systems hit hardest, such as the default mode network (DMN). Functional connectivity is a relatively new topic of research, but it holds great promise in revealing how brain network dynamics change across the lifespan and in disease.
There is increasing availability and use of unstructured and semi‐structured citizen science data in biodiversity research and conservation. This expansion of a rich source of ‘big data’ has sparked ...numerous research directions, driving the development of analytical approaches that account for the complex observation processes in these datasets.
We review outstanding challenges in the analysis of citizen science data for biodiversity monitoring. For many of these challenges, the potential impact on ecological inference is unknown. Further research can document the impact and explore ways to address it. In addition to outlining research directions, describing these challenges may be useful in considering the design of future citizen science projects or additions to existing projects.
We outline challenges for biodiversity monitoring using citizen science data in four partially overlapping categories: challenges that arise as a result of (a) observer behaviour; (b) data structures; (c) statistical models; and (d) communication. Potential solutions for these challenges are combinations of: (a) collecting additional data or metadata; (b) analytically combining different datasets; and (c) developing or refining statistical models.
While there has been important progress to develop methods that tackle most of these challenges, there remain substantial gains in biodiversity monitoring and subsequent conservation actions that we believe will be possible by further research and development in these areas. The degree of challenge and opportunity that each of these presents varies substantially across different datasets, taxa and ecological questions. In some cases, a route forward to address these challenges is clear, while in other cases there is more scope for exploration and creativity.
The emergence of new fungal pathogens makes the development of new antifungal drugs a medical imperative that in recent years motivates the talents of numerous investigators across the world. ...Understanding not only the structural families of these drugs but also their biological targets provides a rational means for evaluating the merits and selectivity of new agents for fungal pathogens and normal cells. An equally important aspect of modern antifungal drug development takes a balanced look at the problems of drug potency and drug resistance. The future development of new antifungal agents will rest with those who employ synthetic and semisynthetic methodology as well as natural product isolation to tackle these problems and with those who possess a clear understanding of fungal cell architecture and drug resistance mechanisms. This review endeavors to provide an introduction to a growing and increasingly important literature, including coverage of the new developments in medicinal chemistry since 2015, and also endeavors to spark the curiosity of investigators who might enter this fascinatingly complex fungal landscape.
The emergence of new fungal pathogens makes the development of new antifungal drugs a medical imperative that in recent years motivates the talents of numerous investigators across the world.
DEET (N, N-diethyl-meta-toluamide) is the most effective and widely used insect repellent, but its mechanism of action is both complex and controversial 1. DEET acts on insect smell 2–6 and taste ...7–11, and its olfactory mode of action requires the odorant co-receptor orco 2, 3, 6. We previously observed that orco mutant female Aedes aegypti mosquitoes are strongly attracted to humans even in the presence of DEET, but they are rapidly repelled after contacting DEET-treated skin 6. DEET inhibits food ingestion by Drosophila melanogaster flies, and this repellency is mediated by bitter taste neurons in the proboscis 9. Similar neurons were identified in the mosquito proboscis, leading to the hypothesis that DEET repels on contact by activating an aversive bitter taste pathway 10. To understand the basis of DEET contact chemorepellency, we carried out behavioral experiments and discovered that DEET acts by three distinct mechanisms: smell, ingestion, and contact. Like bitter tastants, DEET is a feeding deterrent when ingested, but its bitterness per se does not fully explain DEET contact chemorepellency. Mosquitoes blood fed on human arms treated with high concentrations of bitters, but rapidly avoided DEET-treated skin and did not blood feed. Insects detect tastants both through their proboscis and legs. We show that DEET contact chemorepellency is mediated exclusively by the tarsal segments of the legs and not the proboscis. This work establishes mosquito legs as the behaviorally relevant contact sensors of DEET. These results will inform the search for molecular mechanisms mediating DEET contact chemorepellency and novel contact-based insect repellents.
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•DEET and bitters inhibit Aedes aegypti female mosquito sugar ingestion•Only DEET completely prevents blood feeding on contact•Repellency of DEET on skin contact is mediated by the tarsal segments of the legs•Any pair of legs can sense DEET to prevent mosquito biting
Dennis et al. show that while mosquitoes find DEET and bitters equally distasteful to ingest, only DEET repels mosquitoes on contact. This chemorepellency is mediated by the legs and not the proboscis. These results highlight the multi-modal repellency of DEET and may inform the design of new insect repellents that work on contact.
The recognition of a new yeast,
Candida auris
, in 2009 in East Asia, and its rapid global spread, was a reminder of the threats posed by multidrug-resistant fungal pathogens.
C. auris
had likely ...remained unrecognized for a long time as accurate tests were not available. The laboratory community responded to the
C. auris
challenge by publishing 35 new or revised diagnostic methods between 2014 and early 2021. The commercial sector also modified existing diagnostic devices. These
C. auris
diagnostic tests run the gamut from traditional culture-based differential and selective media, biochemical assimilations, and rapid protein profiles, as well as culture-independent DNA-based diagnostics. We provide an overview of these developments, especially the tests with validation data that were subsequently adopted for common use. We share a workflow developed in our laboratory to process over 37,000
C. auris
surveillance samples and 5,000
C. auris
isolates from the outbreak in the New York metropolitan area. Our preview covers new devices and diagnostic approaches on the horizon based on microfluidics, optics, and nanotechnology. Frontline laboratories need rapid, cheap, stable, and easy-to-implement tests to improve
C. auris
diagnosis, surveillance, patient isolation, admission screening, and environmental control. Among the urgent needs is a lateral flow assay or similar device for presumptive
C. auris
identification. All laboratories will benefit from devices that allow rapid antifungal susceptibility testing, including detection of mutations conferring drug resistance. Hopefully, multiplex test panels are on the horizon for synergy of
C. auris
testing with ongoing surveillance of other healthcare-associated infections.
C. auris
genome analysis has a proven role for outbreak investigations, and diagnostic laboratories need quick access to regional and national genome analysis networks.
Mapping connectivity in the developing brain Dennis, Emily L.; Thompson, Paul M.
International journal of developmental neuroscience,
November 2013, Letnik:
31, Številka:
7
Journal Article
Recenzirano
Odprti dostop
•We review recent work over the last 13 years in brain structural and functional connectivity.•We review research in typical development and neurodevelopmental disorders.•We expect that this review ...will help future researchers in the field of connectomics.
Recently, there has been a wealth of research into structural and functional brain connectivity, and how they change over development. While we are far from a complete understanding, these studies have yielded important insights into human brain development. There is an ever growing variety of methods for assessing connectivity, each with its own advantages. Here we review research on the development of structural and/or functional brain connectivity in both typically developing subjects and subjects with neurodevelopmental disorders. Space limitations preclude an exhaustive review of brain connectivity across all developmental disorders, so we review a representative selection of recent findings on brain connectivity in autism, Fragile X, 22q11.2 deletion syndrome, Williams syndrome, Turner syndrome, and ADHD. Major strides have been made in understanding the developmental trajectory of the human connectome, offering insight into characteristic features of brain development and biological processes involved in developmental brain disorders. We also discuss some common themes, including hemispheric specialization – or asymmetry – and sex differences. We conclude by discussing some promising future directions in connectomics, including the merger of imaging and genetics, and a deeper investigation of the relationships between structural and functional connectivity.
Female mosquitoes of some species are generalists and will blood-feed on a variety of vertebrate hosts, whereas others display marked host preference. Anopheles gambiae and Aedes aegypti have evolved ...a strong preference for humans, making them dangerously efficient vectors of malaria and Dengue haemorrhagic fever. Specific host odours probably drive this strong preference because other attractive cues, including body heat and exhaled carbon dioxide (CO2), are common to all warm-blooded hosts. Insects sense odours via several chemosensory receptor families, including the odorant receptors (ORs), membrane proteins that form heteromeric odour-gated ion channels comprising a variable ligand-selective subunit and an obligate co-receptor called Orco (ref. 6). Here we use zinc-finger nucleases to generate targeted mutations in the orco gene of A. aegypti to examine the contribution of Orco and the odorant receptor pathway to mosquito host selection and sensitivity to the insect repellent DEET (N,N-diethyl-meta-toluamide). orco mutant olfactory sensory neurons have greatly reduced spontaneous activity and lack odour-evoked responses. Behaviourally, orco mutant mosquitoes have severely reduced attraction to honey, an odour cue related to floral nectar, and do not respond to human scent in the absence of CO2. However, in the presence of CO2, female orco mutant mosquitoes retain strong attraction to both human and animal hosts, but no longer strongly prefer humans. orco mutant females are attracted to human hosts even in the presence of DEET, but are repelled upon contact, indicating that olfactory- and contact-mediated effects of DEET are mechanistically distinct. We conclude that the odorant receptor pathway is crucial for an anthropophilic vector mosquito to discriminate human from non-human hosts and to be effectively repelled by volatile DEET.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Fungal infections are a major cause of skin and mucosal membrane disease. Immunocompromised individuals, such as those undergoing chemotherapy, are most susceptible to fungal infections. With a ...growing population of immunocompromised patients, there are many reports of increasing numbers of infections and of fungal strains resistant to current antifungals. One way to treat drug-resistant infections is to administer combinations of drugs to patients. Azoles are the most prescribed antifungals, as they are broad-spectrum and orally bioavailable. Terfenadine (TERF) and ebastine (EBA) are second-generation antihistamines, with EBA being used in many countries. In this study, we explored combinations of seven azole antifungals and two antihistamines (TERF and EBA) against a panel of 13 Candida fungal strains. We found 55 out of 91 combinations tested of TERF and EBA against the various fungal strains to be synergistic with the azoles. To evaluate the efficiency of these combinations to inhibit fungal growth, we performed time-kill assays. We also investigated the ability of these combinations to disrupt biofilm formation. Finally, we tested the specificity of the combinations towards fungal cells by mammalian cytotoxicity assays. These findings suggest a potential new strategy for targeting drug-resistant Candida infections.
Fungi cause serious nosocomial infections including candidiasis and aspergillosis, some of which display reduced susceptibility to current antifungals. Inorganic compounds have been found to be ...beneficial against various medical ailments but have yet to be applied to fungal infections. Here, we explore the activity of linear and square-planar gold(I)−phosphine complexes against a panel of 28 fungal strains including Candida spp., Cryptococcus spp., Aspergillus spp., and Fusarium spp. Notably, two square-planar gold(I) complexes with excellent broad-spectrum activity display potent antifungal effects against strains of Candida auris, an emerging multidrug-resistant fungus that presents a serious global health threat. To characterize the biological activity of these gold(I) complexes, we used a series of time–kill studies, cytotoxicity and hemolysis assays, as well as whole-cell uptake and development of resistance studies.
Abstract
Air pollution is a major environmental threat to public health; we know little, however, about its effects on adolescent brain development. Exposure to air pollution co-occurs, and may ...interact, with social factors that also affect brain development, such as early life stress (ELS). Here, we show that severity of ELS and fine particulate air pollution (PM2.5) are associated with volumetric changes in distinct brain regions, but also uncover regions in which ELS moderates the effects of PM2.5. We interviewed adolescents about ELS events, used satellite-derived estimates of ambient PM2.5 concentrations, and conducted longitudinal tensor-based morphometry to assess regional changes in brain volume over an approximately 2-year period (N = 115, ages 9–13 years at Time 1). For adolescents who had experienced less severe ELS, PM2.5 was associated with volumetric changes across several gray and white matter regions. Fewer effects of PM2.5 were observed for adolescents who had experienced more severe ELS, although occasionally they were in the opposite direction. This pattern of results suggests that for many brain regions, moderate to severe ELS largely constrains the effects of PM2.5 on structural development. Further theory and research is needed on the joint effects of ELS and air pollution on the brain.
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