Miracle-dz/UniFAR-FTUs huggingface dataset:
A broadly active fucosyltransferase LmjFUT1 whose mitochondrial localization and activity are essential in parasitic Leishmania

Significance Abundant surface glycoconjugates play key roles in the infectious cycle of protozoan parasites including Leishmania. Through defining biosynthetic pathways, we identified a fucosyltransferase FUT1 localized to the parasite mitochondrion, an atypical compartment for glycosyltransferases. FUT1 was essential for normal growth, requiring both mitochondrial localization and enzymatic activity. Loss of FUT1 in a single rare segregant (fut1s) showed extensive mitochondrial defects. Enzymatic tests showed FUT1 could fucosylate glycan and peptide substrates in vitro, although as yet the native substrate(s) are unknown. Trypanosomatid mitochondrial FUT1s may offer a facile system in the future for probing mitochondrial glycosylation in a setting uncomplicated by multiple isoforms targeted to diverse compartments, and its essentiality renders it an attractive chemotherapeutic target for these deadly parasites. Glycoconjugates play major roles in the infectious cycle of the trypanosomatid parasite Leishmania. While GDP-Fucose synthesis is essential, fucosylated glycoconjugates have not been reported in Leishmania major [H. Guo et al., J. Biol. Chem. 292, 10696–10708 (2017)]. Four predicted fucosyltransferases appear conventionally targeted to the secretory pathway; SCA1/2 play a role in side-chain modifications of lipophosphoglycan, while gene deletion studies here showed that FUT2 and SCAL were not essential. Unlike most eukaryotic glycosyltransferases, the predicted α 1–2 fucosyltransferase encoded by FUT1 localized to the mitochondrion. A quantitative “plasmid segregation” assay, expressing FUT1 from the multicopy episomal pXNG vector in a chromosomal null ∆fut1− background, established that FUT1 is essential. Similarly, “plasmid shuffling” confirmed that both enzymatic activity and mitochondrial localization were required for viability, comparing import-blocked or catalytically inactive enzymes, respectively. Enzymatic assays of tagged proteins expressed in vivo or of purified recombinant FUT1 showed it had a broad fucosyltransferase activity including glycan and peptide substrates. Unexpectedly, a single rare ∆fut1− segregant (∆fut1s) was obtained in rich media, which showed severe growth defects accompanied by mitochondrial dysfunction and loss, all of which were restored upon FUT1 reexpression. Thus, FUT1 along with the similar Trypanosoma brucei enzyme TbFUT1 [G. Bandini et al., bioRxiv, https://www.biorxiv. org/content/10.1101/726117v2 (2021)] joins the eukaryotic O-GlcNAc transferase isoform as one of the few glycosyltransferases acting within the mitochondrion. Trypanosomatid mitochondrial FUT1s may offer a facile system for probing mitochondrial glycosylation in a simple setting, and their essentiality for normal growth and mitochondrial function renders it an attractive target for chemotherapy of these serious human pathogens.
Proximal-to-Distal Sequences of Attack and Release Movements of Expert Pianists during Pressed-Staccato Keystrokes

Abstract The aims of this study were to i) evaluate proximal-to-distal sequencing (PDS) in pianists’ attack and release movements during pressed-staccato keystrokes, and ii) investigate if trunk motion facilitates PDS of upper-limb movements. Nine expert pianists performed a series of loud pressed-staccato keystrokes. Kinematic data was recorded with a 3 D motion capture system. PDS was assessed by comparing temporal organization of peak velocities from the pelvis to the wrist. Evidence of PDS was found across the kinematic chain. Pianists’ use of PDS differed mainly between scapula and shoulder movements. Trunk motion facilitated PDS by increasing anticipatory shoulder movements and by preceding shoulder-girdle attack and release movements. Implications might relate to research on performance optimization and injury prevention strategies.
Interferon drives HCV scarring of the epigenome and creates targetable vulnerabilities following viral clearance

Chronic HCV infection is a leading etiologic driver of cirrhosis and ultimately HCC. Of the approximately 71 million individuals chronically infected with HCV, 10%‐20% are expected to develop severe liver complications in their lifetime. Epigenetic mechanisms including DNA methylation and histone modifications become profoundly disrupted in disease processes including liver disease.
A’uwẽ (Xavante) social constructions of well-being in Central Brazil

ABSTRACT Well-being is a heterogeneous idea with inconsistent applicability to real-world circumstances. In this article, I explore A’uwẽ (Xavante) notions of social well-being from an ethnographic perspective. My data indicate many members of this Indigenous group understand wellness to involve not only health and harmony, but also certain modes of strife and inequality that are also viewed as desirable. A’uwẽ understandings of social wellness, including linkages to the environment, suggest that a broader and more locally contingent concept of social well-being than is evident in mainstream literature would benefit transcultural health efforts and policy involving Indigenous and other culturally distinct communities.
Prevalence and antifungal drug resistance of dermatophytes in the clinical samples from Pakistan.

Dermatophytosis is a major health problem all over the world including Pakistan. This is the first report of detection of dermatophytes and their antifungal drug resistance in the Northern and Western parts of Pakistan. A total of 154 samples were collected from different hospitals of Khyber Pakhtunkhwa, and out of them 136 samples were found positive. Tinea corporis (35%) was the most predominant type of infection followed by Tinea capitis (22%). The fungi identified in Tinea corporis infection types were identified as Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum. The fungi identified in Tinea capitis included Trichophyton violaceum, T. mentagrophytes, Microsporum ferrugineum. The gender wise distribution showed both males (52%) and females (48%) were infected with the fungi. More cases belonged to the rural parts of the country. Age wise distribution showed that the infection was more prevalent in the children and the prevalence decreased with the increase in age. The positive samples were checked against two antifungal agents: fluconazole and nystatin. Among 136 positive samples, none of the isolates showed resistance to nystatin while 7% of the samples showed resistance to fluconazole. The resistant isolates were then identified by amplifying the 18S rRNA gene, using universal primers (ITS1, ITS4). Among the 9 resistant isolates, 5 isolates were identified as Trichophyton spp. , 3 as Microsporum spp. and 1 as Epidermophyton spp.
Psychometric Properties of the High-Need Community-Dwelling Older Adults Screening Scale

This study aimed to verify the factorial structure, internal consistency, test-retest reliability, and discriminant validity of the High-need Community-dwelling Older Adults Screening Scale (HCOASS). A 20-item HCOASS covering five domains was used with a systematic random sample of 818 community-dwelling older adults. After the analyses, the Exploratory Factor Analysis suggested a removal of two items, resulting in 5 domains with 18 items, and the Confirmatory Factor Analysis yielded satisfactory results with Goodness of Fit Index of . 98. The HCOASS demonstrated acceptable internal consistency (Kuder-Richardson Formula 20 α = .75) and excellent test-retest reliability (0.94; 95% CI [0.91, 0.97]). The area under the Receiver Operating Characteristic (ROC) curve was 0.90 (95% CI [0.84, 0.95]) and the optimal cut-off score was 4/5. The HCOASS is a valid and reliable screening tool. It has the potential for consistent and efficient administration to be used by non-healthcare professionals in the community.
Longitudinal training models for entrusting students with independent patient care?: A systematic review

The participation of students from both undergraduate medical education (UGME) and postgraduate medical education (PGME) in independent patient care contributes to the development of knowledge, skills and the professional identity of students. A continuing collaboration between students and their preceptor might contribute to opportunities for students to independently provide patient care. In this systematic review, we aim to evaluate whether longitudinal training models facilitate the independent practice of students and what characteristics of longitudinal training models contribute to this process.
STING facilitates nuclear import of herpesvirus genome during infection

Significance Human cytomegalovirus (HCMV) establishes lifelong latent infection in 60 to 90% of the population worldwide and constitutes a serious global health burden. For a successful infection, HCMV must overcome physical barriers: the plasma membrane and the nuclear envelope. Here, we report that the immune adaptor protein stimulator of interferon genes (STING), typically located in the endoplasmic reticulum, is a crucial host factor involved in the nuclear entry of HCMV. Without STING, the interaction between viral capsid and nuclear pore complex is defective, and HCMV fails to deliver the viral genome into the nucleus. In monocytes, STING deficiency prevents a successful establishment of HCMV persistence. This study offers a perspective for understanding HCMV uncoating and for developing interventions against herpesvirus infection. Once inside the host cell, DNA viruses must overcome the physical barrier posed by the nuclear envelope to establish a successful infection. The mechanism underlying this process remains unclear. Here, we show that the herpesvirus exploits the immune adaptor stimulator of interferon genes (STING) to facilitate nuclear import of the viral genome. Following the entry of the viral capsid into the cell, STING binds the viral capsid, mediates capsid docking to the nuclear pore complex via physical interaction, and subsequently enables accumulation of the viral genome in the nucleus. Silencing STING in human cytomegalovirus (HCMV)-susceptible cells inhibited nuclear import of the viral genome and reduced the ensuing viral gene expression. Overexpressing STING increased the host cell’s susceptibility to HCMV and herpes simplex virus 1 by improving the nuclear delivery of viral DNA at the early stage of infection. These observations suggest that the proviral activity of STING is conserved and exploited by the herpesvirus family. Intriguingly, in monocytes, which act as latent reservoirs of HCMV, STING deficiency negatively regulated the establishment of HCMV latency and reactivation. Our findings identify STING as a proviral host factor regulating latency and reactivation of herpesviruses.
Transmantle Pressure Computed from MR Imaging Measurements of Aqueduct Flow and Dimensions

BACKGROUND AND PURPOSE: Measuring transmantle pressure, the instantaneous pressure difference between the lateral ventricles and the cranial subarachnoid space, by intracranial pressure sensors has limitations. The aim of this study was to compute transmantle pressure noninvasively with a novel nondimensional fluid mechanics model in volunteers and to identify differences related to age and aqueductal dimensions. MATERIALS AND METHODS: Brain MR images including cardiac-gated 2D phase-contrast MR imaging and fast-spoiled gradient recalled imaging were obtained in 77 volunteers ranging in age from 25–92 years of age. Transmantle pressure was computed during the cardiac cycle with a fluid mechanics model from the measured aqueductal flow rate, stroke volume, aqueductal length and cross-sectional area, and heart rate. Peak pressures during caudal and rostral aqueductal flow were tabulated. The computed transmantle pressure, aqueductal dimensions, and stroke volume were estimated, and the differences due to sex and age were calculated and tested for significance. RESULTS: Peak transmantle pressure was calculated with the nondimensional averaged 14.4 (SD, 6.5) Pa during caudal flow and 6.9 (SD, 2.8) Pa during rostral flow. It did not differ significantly between men and women or correlate significantly with heart rate. Peak transmantle pressure increased with age and correlated with aqueductal dimensions and stroke volume. CONCLUSIONS: The nondimensional fluid mechanics model for computing transmantle pressure detected changes in pressure related to age and aqueductal dimensions. This novel methodology can be easily used to investigate the clinical relevance of the transmantle pressure in normal pressure hydrocephalus, pediatric communicating hydrocephalus, and other CSF disorders.
Determinants and Dynamics of SARS-CoV-2 Infection in a Diverse Population: 6-Month Evaluation of a Prospective Cohort Study

Abstract Background We studied risk factors, antibodies, and symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a diverse, ambulatory population. Methods A prospective cohort (n = 831) previously undiagnosed with SARS-CoV-2 infection underwent serial testing (SARS-CoV-2 polymerase chain reaction, immunoglobulin G [IgG]) for 6 months. Results Ninety-three participants (11.2%) tested SARS-CoV-2-positive: 14 (15.1%) asymptomatic, 24 (25.8%) severely symptomatic. Healthcare workers (n = 548) were more likely to become infected (14.2% vs 5.3%; adjusted odds ratio, 2.1; 95% confidence interval, 1.4–3.3) and severely symptomatic (29.5% vs 6.7%). IgG antibodies were detected after 79% of asymptomatic infections, 89% with mild-moderate symptoms, and 96% with severe symptoms. IgG trajectories after asymptomatic infections (slow increases) differed from symptomatic infections (early peaks within 2 months). Most participants (92%) had persistent IgG responses (median 171 days). In multivariable models, IgG titers were positively associated with symptom severity, certain comorbidities, and hospital work. Dyspnea and neurologic changes (including altered smell/taste) lasted ≥ 120 days in ≥ 10% of affected participants. Prolonged symptoms (frequently more severe) corresponded to higher antibody levels. Conclusions In a prospective, ethnically diverse cohort, symptom severity correlated with the magnitude and trajectory of IgG production. Symptoms frequently persisted for many months after infection. Clinical Trials Registration. NCT04336215.
Morphometric analysis of astrocytes in vocal production circuits of common marmoset ( Callithrix jacchus )

Astrocytes, the star‐shaped glial cells, are the most abundant non‐neuronal cell population in the central nervous system. They play a key role in modulating activities of neural networks, including those involved in complex motor behaviors. Common marmosets (Callithrix jacchus), the most vocal non‐human primate (NHP), have been used to study the physiology of vocalization and social vocal production. However, the neural circuitry involved in vocal production is not fully understood. In addition, even less is known about the involvement of astrocytes in this circuit. To understand the role, that astrocytes may play in the complex behavior of vocalization, the initial step may be to study their structural properties in the cortical and subcortical regions that are known to be involved in vocalization. Here, in the common marmoset, we identify all astrocytic subtypes seen in other primate's brains, including intralaminar astrocytes. In addition, we reveal detailed structural characteristics of astrocytes and perform morphometric analysis of astrocytes residing in the cortex and midbrain regions that are associated with vocal production. We found that cortical astrocytes in these regions illustrate a higher level of complexity when compared to those in the midbrain. We hypothesize that this complexity that is expressed in cortical astrocytes may reflect their functions to meet the metabolic/structural needs of these regions.
Comparative transcriptome provides strategy for phylogenetic analysis and SSR marker development in Chaenomeles

The genus Chaenomeles has long been considered as an important ornamental, herbal and cash plant and widely cultivated in East Asian. Traditional researches of Chaenomeles mainly focus on evolutionary relationships on phenotypic level. In this study, we conducted RNA-seq for 10 Chaenomeles germplasms supplemented with one related species Docynia delavayi (D. delavay) by Illumina HiSeq2500 platform. After de novo assemblies, we have generated unigenes for each germplasm with numbers from 40 084 to 48 487. By pairwise comparison of the orthologous sequences, 9 659 othologus within the 11 germplasms were obtained, with 6 154 othologous genes identified as single-copy genes. The phylogenetic tree was visualized to reveal evolutionary relationship for these 11 germplasms. GO and KEGG analyses were performed for these common single-copy genes to compare the functional similarities and differences. Selective pressure analysis based on 6 154 common single-copy genes reveals that 45 genes were under positive pressure selection. Most of them involved in plant disease defense system building process. 292 genes containing simple sequence repeats (SSRs) were used to develop SSR markers and compare their function in secondary metabolism pathways. Finally, 10 primers were chosen as SSR markers candidates for Chaenomeles germplasms by comprehensive screening. Our research provides new methodology and reference for future related research in Chaemomeles and is also useful for improvement, breeding and selection project in other related species.
Changes in Alcohol Consumption in Canada During the COVID-19 Pandemic: Associations With Anxiety and Self-Perception of Depression and Loneliness

Abstract Aim To examine whether changes in alcohol consumption in Canada since the start of the novel coronavirus disease (COVID-19) pandemic are associated with feelings of anxiety, depression, loneliness and/or with changes in employment due to COVID-19. Methods Data collection occurred between 29 May 2020 and 23 March 2021 via a web panel, AskingCanadians, which sampled 5892 adults (≥18 years of age). Data were collected on changes in alcohol consumption compared to before the pandemic (ordinal variable ranging from 1=‘much less alcohol’ to 5=‘much more alcohol’), anxiety (General Anxiety Disorder-7), self-perceived depression (Center for Epidemiologic Studies Depression Scale), self-perceived loneliness, changes in employment status due to COVID-19 and socio-demographic variables (age, gender, living situation, household income and urban vs rural residence). Multivariate associations were assessed using ordinal logistic regression. Effect modification by gender was tested using likelihood-ratio tests. Results Changes in alcohol consumption were positively associated with anxiety, feeling depressed and loneliness. In particular, people with mild to moderate (ordered Odds Ratio (OR):1.23, 95% Confidence Interval (CI):1.07, 1.62) or severe anxiety (ordered OR:1.49, 95% CI:1.15, 1.93) had a greater odds of increased drinking than did people with no to low levels of anxiety. Gender, age, household income, living situation and survey wave were also associated with changes in drinking. No effect modifications by gender were observed. Conclusion Given the health harms caused by alcohol use, public health practitioners and primary care physicians should focus health messaging to identify and support individuals at risk of increased alcohol consumption, especially people experiencing depression, loneliness or anxiety.
Concerns of Thalassemia Patients, Carriers, and their Caregivers in Malaysia: Text Mining Information Shared on Social Media

Objectives The main aim of this study was to use text mining on social media to analyze information and gain insight into the health-related concerns of thalassemia patients, thalassemia carriers, and their caregivers. Methods Posts from two Facebook groups whose members consisted of thalassemia patients, thalassemia carriers, and caregivers in Malaysia were extracted using the Data Miner tool. In this study, a new framework known as Malay-English social media text pre-processing was proposed for performing the steps of pre-processing the noisy mixed language (Malay-English language) of social media posts. Topic modeling was used to identify hidden topics within posts shared among members. Three different topic models—latent Dirichlet allocation (LDA) in GenSim, LDA in MALLET, and latent semantic analysis—were applied to the dataset with and without stemming using Python. Results LDA in MALLET without stemming was found to be the best topic model for this dataset. Eight topics were identified within the posts shared by members. Of those eight topics, four were newly discovered by this study, and four others corresponded to the findings of previous studies that used an interview approach. Conclsions Topic 2 (the challenges faced by thalassemia patients) was found to be the topic with the highest attention and engagement. Healthcare practitioners and other concerned parties should make an effort to build a stronger support system related to this issue for those affected by thalassemia.
Forest stand and canopy development unaltered by 12 years of CO2 enrichment*

Abstract Canopy structure—the size and distribution of tree crowns and the spatial and temporal distribution of leaves within them—exerts dominant control over primary productivity, transpiration and energy exchange. Stand structure—the spatial arrangement of trees in the forest (height, basal area and spacing)—has a strong influence on forest growth, allocation and resource use. Forest response to elevated atmospheric CO2 is likely to be dependent on the canopy and stand structure. Here, we investigated elevated CO2 effects on the forest structure of a Liquidambar styraciflua L. stand in a free-air CO2 enrichment experiment, considering leaves, tree crowns, forest canopy and stand structure. During the 12-year experiment, the trees increased in height by 5 m and basal area increased by 37%. Basal area distribution among trees shifted from a relatively narrow distribution to a much broader one, but there was little evidence of a CO2 effect on height growth or basal area distribution. The differentiation into crown classes over time led to an increase in the number of unproductive intermediate and suppressed trees and to a greater concentration of stand basal area in the largest trees. A whole-tree harvest at the end of the experiment permitted detailed analysis of canopy structure. There was little effect of CO2 enrichment on the relative leaf area distribution within tree crowns and there was little change from 1998 to 2009. Leaf characteristics (leaf mass per unit area and nitrogen content) varied with crown depth; any effects of elevated CO2 were much smaller than the variation within the crown and were consistent throughout the crown. In this young, even-aged, monoculture plantation forest, there was little evidence that elevated CO2 accelerated tree and stand development, and there were remarkably small changes in canopy structure. Questions remain as to whether a more diverse, mixed species forest would respond similarly.
Microbial food: microorganisms repurposed for our food

Sustainable food production is a key to solve complicated and intertwined issues of overpopulation, climate change, environment and sustainability. Microorganisms, which have been routinely consumed as a part of fermented foods and more recently as probiotic dietary supplements, can be repurposed for our food to present a sustainable solution to current food production system. This paper begins with three snapshots of our future life with microbial foods. Next, the importance, possible forms, and raw materials (i.e. microorganisms and their carbon and energy sources) of microbial foods are discussed. In addition, the production strategies, further applications and current limitations of microbial foods are discussed.