A growing number of organopnictogen redox catalytic methods have emergedespecially within the past 10 yearsthat leverage the plentiful reversible two-electron redox chemistry within Group 15. The ...goal of this Perspective is to provide readers the context to understand the dramatic developments in organopnictogen catalysis over the past decade with an eye toward future development. An exposition of the fundamental differences in the atomic structure and bonding of the pnictogens, and thus the molecular electronic structure of organopnictogen compounds, is presented to establish the backdrop against which organopnictogen redox reactivityand ultimately catalysisis framed. A deep appreciation of these underlying periodic principles informs an understanding of the differing modes of organopnictogen redox catalysis and evokes the key challenges to the field moving forward. We close by addressing forward-looking directions likely to animate this area in the years to come. What new catalytic manifolds can be developed through creative catalyst and reaction design that take advantage of the intrinsic redox reactivity of the pnictogens to drive new discoveries in catalysis?
Abstract Falls are one of the major causes of mortality and morbidity in older adults. Every year, an estimated 30–40% of patients over the age of 65 will fall at least once. Falls lead to moderate ...to severe injuries, fear of falling, loss of independence and death in a third of those patients. The direct costs alone from fall related injuries are a staggering 0.1% of all healthcare expenditures in the United States and up to 1.5% of healthcare costs in European countries. This figure does not include the indirect costs of loss of income both to the patient and caregiver, the intangible losses of mobility, confidence, and functional independence. Numerous studies have attempted to define the risk factors for falls in older adults. The present review provides a brief summary and update of the relevant literature, summarizing demographic and modifiable risk factors. The major risk factors identified are impaired balance and gait, polypharmacy, and history of previous falls. Other risk factors include advancing age, female gender, visual impairments, cognitive decline especially attention and executive dysfunction, and environmental factors. Recommendations for the clinician to manage falls in older patients are also summarized.
Parkinson's disease (PD) is a common, debilitating neurodegenerative disease. Gait disturbances are a frequent cause of disability and impairment for patients with PD. This article provides a brief ...introduction to PD and describes the gait changes typically seen in patients with this disease. A major focus of this report is an update on the study of the fractal properties of gait in PD, the relationship between this feature of gait and stride length and gait variability, and the effects of different experimental conditions on these three gait properties. Implications of these findings are also briefly described. This update highlights the idea that while stride length, gait variability, and fractal scaling of gait are all impaired in PD, distinct mechanisms likely contribute to and are responsible for the regulation of these disparate gait properties.
Amy Ko, a computer scientist at the University of Washington in Seattle, invokes a long-running US quiz show to describe the tool's limitations, writing on the Mastodon social-media site: "ChatGPT is ...like a desperate former Jeopardy contestant who stopped following pop culture in 2021 but really wants to get back into the game, and is also a robot with no consciousness, agency, morality, embodied cognition, or emotional inner life." ...ChatGPT and related tools based on large language models (LLMs), which include Microsoft Bing and GitHub Copilot, are incredibly powerful programming aids, but must be used with caution. According to a study2 co-authored by linguist Emily Morgan at the University of California, Davis, chatbots - like the human-written code on which they were trained - often create what she calls "simple, stupid bugs". Iza Romanowska, a complexity scientist who studies ancient civilizations at the Aarhus Institute ofAdvanced Studies in Denmark, has used ChatGPT to produce code in a language called NetLogo. Because there's less online code written in NetLogo than in the languages Python and R, ChatGPT is less fluent in it.
Aims
Diffuse alveolar damage (DAD) is a ubiquitous finding in inpatient coronavirus disease 2019 (COVID‐19)‐related deaths, but recent reports have also described additional atypical findings, ...including vascular changes. An aim of this study was to assess lung autopsy findings in COVID‐19 inpatients, and in untreated severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐positive individuals who died in the community, in order to understand the relative impact of medical intervention on lung histology. Additionally, we aimed to investigate whether COVID‐19 represents a unique histological variant of DAD by comparing the pathological findings with those of uninfected control patients.
Methods and results
Lung sections from autopsy cases were reviewed by three pulmonary pathologists, including two who were blinded to patient cohort. The cohorts included four COVID‐19 inpatients, four cases with postmortem SARS‐CoV‐2 diagnoses who died in the community, and eight SARS‐CoV‐2‐negative control cases. DAD was present in all but one SARS‐CoV‐2‐positive patient, who was asymptomatic and died in the community. Although SARS‐CoV‐2‐positive patients were noted to have more focal perivascular inflammation/endothelialitis than control patients, there were no significant differences in the presence of hyaline membranes, fibrin thrombi, airspace organisation, and ‘acute fibrinous and organising pneumonia’‐like intra‐alveolar fibrin deposition between the cohorts. Fibrinoid vessel wall necrosis, haemorrhage and capillaritis were not features of COVID‐19‐related DAD.
Conclusions
DAD is the primary histological manifestation of severe lung disease in COVID‐19 patients who die both in hospital and in the community, suggesting no contribution of hyperoxaemic mechanical ventilation to the histological changes. There are no distinctive morphological features with which to confidently differentiate COVID‐19‐related DAD from DAD due to other causes.
The advent of single-cell chromatin accessibility profiling has accelerated the ability to map gene regulatory landscapes but has outpaced the development of scalable software to rapidly extract ...biological meaning from these data. Here we present a software suite for single-cell analysis of regulatory chromatin in R (ArchR; https://www.archrproject.com/ ) that enables fast and comprehensive analysis of single-cell chromatin accessibility data. ArchR provides an intuitive, user-focused interface for complex single-cell analyses, including doublet removal, single-cell clustering and cell type identification, unified peak set generation, cellular trajectory identification, DNA element-to-gene linkage, transcription factor footprinting, mRNA expression level prediction from chromatin accessibility and multi-omic integration with single-cell RNA sequencing (scRNA-seq). Enabling the analysis of over 1.2 million single cells within 8 h on a standard Unix laptop, ArchR is a comprehensive software suite for end-to-end analysis of single-cell chromatin accessibility that will accelerate the understanding of gene regulation at the resolution of individual cells.
Second harmonic generation is the lowest-order wave-wave nonlinear interaction occurring in, e.g., optical, radio, and magnetohydrodynamic systems. As a prototype behavior of waves, second harmonic ...generation is used broadly, e.g., for doubling Laser frequency. Second harmonic generation of Rossby waves has long been believed to be a mechanism of high-frequency Rossby wave generation via cascade from low-frequency waves. Here, we report the observation of a Rossby wave second harmonic generation event in the atmosphere. We diagnose signatures of two transient waves at periods of 16 and 8 days in the terrestrial middle atmosphere, using meteor-radar wind observations over the European and Asian sectors during winter 2018-2019. Their temporal evolution, frequency and wavenumber relations, and phase couplings revealed by bicoherence and biphase analyses demonstrate that the 16-day signature is an atmospheric manifestation of a Rossby wave normal mode, and its second harmonic generation gives rise to the 8-day signature. Our finding confirms the theoretically-anticipated Rossby wave nonlinearity.
Ten years ago we first proposed the Alzheimer's disease (AD) mitochondrial cascade hypothesis. This hypothesis maintains that gene inheritance defines an individual's baseline mitochondrial function; ...inherited and environmental factors determine rates at which mitochondrial function changes over time; and baseline mitochondrial function and mitochondrial change rates influence AD chronology. Our hypothesis unequivocally states in sporadic, late-onset AD, mitochondrial function affects amyloid precursor protein (APP) expression, APP processing, or beta amyloid (Aβ) accumulation and argues if an amyloid cascade truly exists, mitochondrial function triggers it. We now review the state of the mitochondrial cascade hypothesis, and discuss it in the context of recent AD biomarker studies, diagnostic criteria, and clinical trials. Our hypothesis predicts that biomarker changes reflect brain aging, new AD definitions clinically stage brain aging, and removing brain Aβ at any point will marginally impact cognitive trajectories. Our hypothesis, therefore, offers unique perspective into what sporadic, late-onset AD is and how to best treat it. This article is part of a Special Issue entitled: Misfolded Proteins, Mitochondrial Dysfunction, and Neurodegenerative Diseases.
•The mitochondrial cascade hypothesis argues that bioenergetic dysfunction mediates Alzheimer's disease (AD).•It assumes that AD-associated biomarker changes reflect brain aging.•It assumes that a recently proposed AD clinical classification scheme stages brain aging.•It assumes that removing Aβ from symptomatic or presymptomatic individuals will marginally impact cognition.
The rapid expansion of next‐generation sequencing has yielded a powerful array of tools to address fundamental biological questions at a scale that was inconceivable just a few years ago. Various ...genome‐partitioning strategies to sequence select subsets of the genome have emerged as powerful alternatives to whole‐genome sequencing in ecological and evolutionary genomic studies. High‐throughput targeted capture is one such strategy that involves the parallel enrichment of preselected genomic regions of interest. The growing use of targeted capture demonstrates its potential power to address a range of research questions, yet these approaches have yet to expand broadly across laboratories focused on evolutionary and ecological genomics. In part, the use of targeted capture has been hindered by the logistics of capture design and implementation in species without established reference genomes. Here we aim to (i) increase the accessibility of targeted capture to researchers working in nonmodel taxa by discussing capture methods that circumvent the need of a reference genome, (ii) highlight the evolutionary and ecological applications where this approach is emerging as a powerful sequencing strategy and (iii) discuss the future of targeted capture and other genome‐partitioning approaches in the light of the increasing accessibility of whole‐genome sequencing. Given the practical advantages and increasing feasibility of high‐throughput targeted capture, we anticipate an ongoing expansion of capture‐based approaches in evolutionary and ecological research, synergistic with an expansion of whole‐genome sequencing.
A growing variety of "genotype-by-sequencing" (GBS) methods use restriction enzymes and high throughput DNA sequencing to generate data for a subset of genomic loci, allowing the simultaneous ...discovery and genotyping of thousands of polymorphisms in a set of multiplexed samples. We evaluated a "double-digest" restriction-site associated DNA sequencing (ddRAD-seq) protocol by 1) comparing results for a zebra finch (Taeniopygia guttata) sample with in silico predictions from the zebra finch reference genome; 2) assessing data quality for a population sample of indigobirds (Vidua spp.); and 3) testing for consistent recovery of loci across multiple samples and sequencing runs. Comparison with in silico predictions revealed that 1) over 90% of predicted, single-copy loci in our targeted size range (178-328 bp) were recovered; 2) short restriction fragments (38-178 bp) were carried through the size selection step and sequenced at appreciable depth, generating unexpected but nonetheless useful data; 3) amplification bias favored shorter, GC-rich fragments, contributing to among locus variation in sequencing depth that was strongly correlated across samples; 4) our use of restriction enzymes with a GC-rich recognition sequence resulted in an up to four-fold overrepresentation of GC-rich portions of the genome; and 5) star activity (i.e., non-specific cutting) resulted in thousands of "extra" loci sequenced at low depth. Results for three species of indigobirds show that a common set of thousands of loci can be consistently recovered across both individual samples and sequencing runs. In a run with 46 samples, we genotyped 5,996 loci in all individuals and 9,833 loci in 42 or more individuals, resulting in <1% missing data for the larger data set. We compare our approach to similar methods and discuss the range of factors (fragment library preparation, natural genetic variation, bioinformatics) influencing the recovery of a consistent set of loci among samples.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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