Several human disorders, including Alzheimer’s disease (AD), are characterized by the aberrant formation of amyloid fibrils. In many cases, the amyloid core is flanked by disordered regions, known as fuzzy coat. The structural properties of fuzzy coats, and their interactions with their environments, however, have not been fully described to date. Here, we generate conformational ensembles of two brain-derived amyloid filaments of Aβ42, corresponding respectively to the familial and sporadic forms of AD. Our approach, called metadynamic electron microscopy metainference (MEMMI), provides a characterization of the transient interactions between the fuzzy coat and the cross-β core of the filaments. These calculations indicate that the familial AD filaments are less soluble than the sporadic AD filaments, and that the fuzzy coat contributes to solubilizing both types of filament. These results illustrate how the metainference approach can help analyze cryo-EM maps for the characterization of the properties of amyloid fibrils.

Mycobacterium tuberculosis (MTB) ESX-1, a type VII secretion system, is a key virulence determinant contributing to MTB’s survival within lung mononuclear phagocytes (MNPs), but its effect on MNP recruitment and differentiation remains unknown. Here, using multiple single-cell RNA sequencing techniques, we studied the role of ESX-1 in MNP heterogeneity and response in mice and murine bone marrow–derived macrophages (BMDM). We found that ESX-1 is required for MTB to recruit diverse MNP subsets with high MTB burden. Further, MTB induces a transcriptional signature of immune evasion in lung macrophages and BMDM in an ESX-1–dependent manner. Spatial transcriptomics revealed an up-regulation of permissive features within MTB lesions, where monocyte-derived macrophages concentrate near MTB-infected cells. Together, our findings suggest that MTB ESX-1 facilitates the recruitment and differentiation of MNPs, which MTB can infect and manipulate for survival. Our dataset across various models and methods could contribute to the broader understanding of recruited cell heterogeneity during MTB lung infection.

Հարկային մարմնում անձնակազմի կառավարման արդյունավետության բարձրացումը ենթադրում է առաջնահերթորեն դրա ճիշտ պլանավորում`կադրային ապահովվածության ընթացիկ իրավիճակի և ապագա պահանջի գնահատում: Ինչքան էլ կատարյալ լինի օրենսդրությունը, բարձր՝ տնտեսական ակտիվությունը, ազնիվ նախանշված գաղափաները, ցածր՝ հարկային եկամուտների նկատմամբ պետության պահանջարկը, պարզ է, որ հարկային քաղաքականության անմիջական կրողը, հարկային վարչարարությունն իրացնողը մարդն է՝ հարկային ծառայողը, որը, կրելով օրենսդրությամբ իրեն վերապահված պատասխանատվությունը, ունի սահմանափակ ունակություններ, մշտական շահադրդման կարիք: Повышение эффективности управления персоналом в налоговом органе предполагает, прежде всего, его правильное планирование, оценку текущего правового состояния кадровой безопасности и будущей востребованности. Каким бы совершенным ни было законодательство, высокая экономическая активность, честные плановые идеи, низкая потребность государства в налоговых поступлениях, ясно, что непосредственным носителем налоговой политики, тем, кто осуществляет налоговое администрирование, является человек, налогоплательщик. офицер, который, неся по закону возложенную на него в данный момент ответственность, имеет ограниченные возможности, нуждается в постоянном интересе. Поэтому возникает необходимость проанализировать экономико-правовую основу работы налогового служащего, чтобы рассказать об имеющихся пробелах и внести предложения по улучшению. Актуальность темы определяется изложенным выше. Increasing the effectiveness of HR management in the tax body, first of all, presupposes its correct planning - assessment of the current and future requirements of HR security. No matter how perfect the legislation is, how high economic activity is, how honest ideas are, and how low the state's demand for tax revenues is, it is clear that the direct bearer of tax policy, the one who implements tax administration is the person, the tax officer, who, while bearing the responsibility assigned to him by the legislation, has limited abilities and needs constant attention. Therefore, there is a need to analyze the economic and legal basis of the work organization of the tax officer, in order to reveal the existing gaps and make room for improvement.

Microresonator dispersion plays a crucial role in shaping the nonlinear dynamics of microcavity solitons. Here, we introduce and validate a method for dispersion engineering through modulating a portion of the inner edge of ring waveguides. We demonstrate that such partial modulation has a broadband effect on the dispersion profile, whereas modulation on the entire resonator’s inner circumference leads to mode splitting primarily affecting one optical mode. The impact of spatial modulation amplitude, period, and number of modulations on the mode splitting profile is also investigated. Through the integration of four modulated sections with different modulation amplitudes and periods, we achieve mode splitting across more than 50 modes over a spectral range exceeding 100 nm in silicon nitride resonators. These results highlight both the simplicity and efficacy of our method in achieving flatter dispersion profiles.

Antibody-dodging norovirus variant may be helping drive a rise in outbreaks

This paper describes two new species of Rhaphidophora from Yunnan, China. The illustrations, descriptions and diagnosis are provided based on the specimens deposited in Guangxi Normal University. The two new species have distinctive male epiprocts.

ABSTRACT School-based occupational therapists provide a range of services with collaborative consultation amongst interdisciplinary team members being one of their responsibilities. One perspective that has not been thoroughly examined within previous research is the administrators’ perceptions of the occupational therapists’ roles and responsibilities within the school setting, which may impact how therapists can implement alternative service delivery models for effective staffing. This study aimed to determine administrators’ perceptions of the workload model used for staffing for school-based occupational therapists, to explore their understanding of the school-based occupational therapists’ role and responsibilities, and to understand their perceptions regarding collaborative consultation. An anonymous electronic survey was distributed to public school administrators within Rhode Island. The survey was created using the Qualtrics platform and the data was analyzed using descriptive statistics. The results show that most administrators believe that school-based occupational therapists should be involved in all three tiers of the multi-tiered system of support (MTSS). Approximately 20% of administrators report that they are not at all familiar with the workload model. Many respondents feel that there are barriers to using alternative service delivery models, with staff being unclear as to how to transition to an alternative service delivery model being noted as the biggest barrier (63.2%). This study fills a void in the literature where administrators’ perspectives regarding alternative service delivery models and their views on collaborative consultation in relation to the school-based occupational therapists’ role were not explored. Understanding administrators’ perspectives can guide future research and help practitioners that are seeking to transition to a workload/staffing model.

Historical narratives tell us as much about the present as they do about the past—and the grand narrative of psychedelics in the ancient world is no exception. “What is soma?” is a perennial question for historians of psychedelics as they investigate this mysterious psychoactive sacrament of early India. Documented in Sanskrit texts starting in the late Bronze Age, it is reputed to be among the oldest and most venerable psychedelics—yet the material substance of soma remains unidentified. Although soma’s fame in modernity arises from scholarly engagement with Sanskrit texts, the resulting narrative of psychedelic history reveals more about the twentieth-century discourse on plants and drugs than it does about the original Indian sources. This essay interrogates the history of psychedelics through the historiography of the soma question.

The law and policy surrounding psychedelic substances in the United States is in its infancy. At the time of writing, two states, Oregon and Colorado, have passed laws that create legal access points for regulated psychedelic substances and do not require a doctor’s recommendation or prescription for access. Several psychedelic substances are also being researched by pharmaceutical companies in the United States within the Food and Drug Administration’s (FDA) drug approval process. Additionally, there is federally permitted religious and spiritual use for certain psychedelic churches, as other authors in this volume discuss. Whether as a possible medicine at the federal level, a quasi-medicine/recreational substance at the state level or as a sacrament used in a spiritual community, psychedelics are administered in what I describe as a “facilitated use model.” In this model, an individual is given a psychedelic substance in a controlled setting under the supervision of a trained facilitator or clinician. As of now, there are no other models for access to regulated psychedelics in the United States outside of a “facilitated use model.”