bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autosomal recessive SLC30A9 Mutations in a Proband with a Cerebro-Renal Syndrome and No Parental Consanguinity
Authors: Kleyner Robert , Mohammad Arif , Marchi Elaine , Horowitz Naomi , Haworth Andrea , King Brian , Gavin Maureen , Amble Karen , Velinov Milen , Lyon Gholson J. 
Published: July 2021

AbstractAn SLC30A9-associated cerebro-renal syndrome was first reported in consanguineous Bedouin kindred by Perez et al. in 2017. While the function of the gene has not yet been fully elucidated, it may be implicated in Wnt signaling, nuclear regulation, as well as cell and mitochondrial zinc regulation. In this research report, we present a female proband with two distinct, inherited autosomal recessive loss-of-function SLC30A9 variants from unrelated parents. To our knowledge, this is the first reported case of a possible SLC30A9-associated cerebro-renal syndrome in a non-consanguineous family. Furthermore, a limited statistical analysis was conducted to identify possible allele frequency differences between populations. Our findings provide further support for an SLC30A9-associated cerebro-renal syndrome and may help further clarify the gene’s function.
Cultural Adaptation of a Brief Intervention to Reduce Alcohol Use Among Injury Patients in Tanzania
Authors: Zimmerman Armand , Pesambili Msafiri , Phillips Ashley J. , Boshe Judith , Mmbaga Blandina T. , Pantalon Michael H. , Swahn Monica , Hirshon Jon Mark , Vissoci Joao Ricardo Nickenig , Staton Catherine A. 
Published: July 2021

AbstractBackgroundHarmful alcohol use is a leading risk factor for injury-related death and disability in low- and middle-income countries (LMICs). Brief negotiational interventions (BNIs) administered in emergency departments (EDs) to injury patients with alcohol use disorders (AUDs) are effective in reducing post-hospital alcohol intake and re-injury rates. However, most BNIs to date have been developed and implemented in high-income countries. The efficacy of BNIs in LMICs is largely unknown as few studies have undertaken the rigorous task of culturally adapting these interventions to new settings. Given the high prevalence of alcohol-related injury in the Kilimanjaro region of Tanzania, we culturally adapted a BNI to reduce post-injury alcohol use for implementation in this patient population.MethodsWe used an iterative, multiphase process to culturally adapt a high-income country standard of care BNI to the Tanzanian setting using the Intervention Mapping ADAPT framework. Our team consisted of local healthcare professionals with extensive experience in counseling patients who use alcohol, as well as an international team of academic and clinical professionals. Focus groups were used to inform culturally appropriate changes to the standard of care BNI protocol. Objective assessment of BNI delivery was performed to ensure adherence to the FRAMES model of motivational interviewing.ResultsWe developed the Punguza Pombe Kwa Afya Yako (PPKAY); a one-time, 15-minute nurse-led BNI that encourages safe alcohol use and motivates change in alcohol use behaviors among injury patients in the Kilimanjaro region of Tanzania. Adaptations to the original intervention protocol include changes regarding the interventionist, how a patient is greeted, how the topic of alcohol use is raised, how a patient is informed of their harmful alcohol use, how graphics are visualized within the intervention protocol, how behavior change is motivated, and which behavior changes are encouraged.ConclusionsThe PPKAY intervention is the first BNI to be culturally adapted for delivery to injury patients in an LMIC population. Our study demonstrates a unique approach to adapting substance use interventions for use in LMICs, and shows that cultural adaptation of alcohol use interventions is feasible even in settings where community knowledge regarding harmful alcohol use is limited. Our study prompts the need for further research and cultural adaptation of BNIs for other low-income communities at increased risk of alcohol-related harm.
Neuroprotective, antioxidant and antiproliferative activity of grapefruit IntegroPectin on SH-SY5Y cells
Authors: Nuzzo Domenico , Scordino Miriana , Scurria Antonino , Giardina Costanza , Giordano Francesco , Meneguzzo Francesco , Mudò Giuseppa , Pagliaro Mario , Picone Pasquale , Attanzio Alessandro , Raimondo Stefania , Ciriminna Rosaria , Di Liberto Valentina 
Published: July 2021

AbstractTested in vitro on SH-SY5Y neuroblastoma cells, grapefruit IntegroPectin is a powerful neuroprotective, antioxidant and antiproliferative agent. The strong antioxidant properties of grapefruit IntegroPectin, and its ability to preserve mitochondrial membrane potential and morphology, severely impaired in neurodegenerative disorders, make this new biopolymer highly soluble in water an attractive therapeutic agent for oxidative stress-associated brain disorders. Similarly, the ability of this new citrus pectin rich in naringin, linalool, linalool oxide and limonene adsorbed at the outer surface to inhibit cell proliferation or even kill, at high doses, neoplastic cells, coupled to its excellent health and safety profile, opens up new therapeutic strategies in cancer research. In order to take full advantage of its vast therapeutic and preventive potential, detailed studies of molecular mechanism involved in the antiproliferative and neuroprotective of IntegroPectin are urgently needed.
Manipulation of RNA Polymerase III by Herpes Simplex Virus-1
Authors: Dremel Sarah E. , Sivrich Frances L. , Tucker Jessica , Glaunsinger Britt A. , DeLuca Neal A. 
Published: July 2021

ABSTRACTRNA Polymerase III (Pol III) transcribes noncoding RNA, including transfer RNA (tRNA), and acts as a pathogen sensor during the innate immune response. To promote enhanced proliferation, the Pol III machinery is commonly targeted during cancer and viral infection. Herein we employ DM-RNA-Seq, 4SU-Seq, ChIP-Seq, and ATAC-Seq to characterize how Herpes Simplex Virus-1 (HSV-1) perturbs the Pol III landscape. We find that HSV-1 stimulates tRNA expression 10-fold, with mature tRNAs exhibiting a 2-fold increase within 12 hours of infection. Perturbation of host tRNA synthesis requires nuclear viral entry, but not synthesis of specific viral transcripts, nascent viral genomes, or viral progeny. Host tRNA with a specific codon bias were not targeted—rather increased transcription was observed from euchromatic, actively transcribed loci. tRNA upregulation is linked to unique crosstalk between the Pol II and III transcriptional machinery. While viral infection is known to mediate host transcriptional shut off and lead to a depletion of Pol II on host mRNA promoters, we find that Pol II binding to tRNA loci increases. Finally, we report Pol III and associated factors bind the HSV genome, which suggests a previously unrecognized role in HSV-1 gene expression. These data provide insight into novel mechanisms by which HSV-1 alters the host nuclear environment, shifting key processes in favor of the pathogen.
Characterization of early Alzheimer’s-like pathological alterations in non-human primates with aging: a pilot study
Authors: Jester Hannah , Gosrani Saahj , Ding Huiping , Zhou Xueyan , Ko Mei-Chuan , Ma Tao 
Published: July 2021

AbstractSporadic or late onset Alzheimer’s disease (LOAD) is a multifactorial neurodegenerative disease with aging the most known risk factor. Non-human primates (NHPs) may serve as an excellent model to study LOAD because of their close similarity to humans in many aspects including neuroanatomy and neurodevelopment. Recent studies reveal AD-like pathology in old NHPs. In this pilot study, we took advantage of brain samples from 6 Cynomolgus macaques that were divided into two groups: middle aged (average age 14.81 years) and older (average age 19.33 years). We found multiple AD-like pathological alteration in the prefrontal cortex (but not in the hippocampus) of the older NHPs including tau hyperphosphorylation, increased activity of AMP-activated protein kinase (AMPK), decreased expression of protein phosphatase 2A (PP2A), impairments in mitochondrial morphology and postsynaptic densities (PSDs) formation. These findings may provide insights into the factors contributing to the development of LOAD, particularly during the early stage transitioning from middle to old age. Future endeavors are warranted to elucidate mechanisms underlying the regional (and perhaps cellular) vulnerability with aging and the functional correlation of such pathological changes in NHPs.
Fast unconscious processing of emotional stimuli in early stages of the visual cortex
Authors: Carretié Luis , Fernández-Folgueiras Uxía , Álvarez Fátima , Cipriani Germán A. , Tapia Manuel , Kessel Dominique 
Published: July 2021

AbstractSeveral cortical and subcortical brain areas have been reported to be sensitive to the emotional content of subliminal stimuli. However, the timing of these activations remains unclear. Our scope was to detect the earliest cortical traces of visual unconscious processing by recording event-related potentials (ERPs) from 43 participants. Subliminal spiders (emotional) and wheels (neutral), sharing similar low-level visual parameters, were presented at two different locations (fixation and periphery). The differential (peak to peak) amplitude from CP1 (77 milliseconds from stimulus onset) to C2 (100 milliseconds), two early visual ERP components originated in V1/V2 according to source localization analyses, was analyzed via Bayesian and traditional analyses. Spiders elicited greater CP1-C2 amplitudes than wheels when presented at fixation. This fast effect of subliminal stimulation -not reported previously to the best of our knowledge-has implications in several debates: i) the amygdala cannot be mediating these effects, ii) latency of other evaluative structures recently proposed, such as the visual thalamus, is compatible with these results, iii) the absence of peripheral stimuli effects points to a relevant role of the parvocellular visual system in unconscious processing.
Panx1b modulates the luminance response and direction of motion in the zebrafish
Authors: Safarian Nickie , Houshangi-Tabrizi Sarah , Zoidl Christiane , Zoidl Georg R. 
Published: July 2021

AbstractPannexin1 (Panx1) can form ATP-permeable integral membrane channels that play roles in the physiology of the visual system. Two independent gene copies of Panx1, panx1a and panx1b, have been identified in the zebrafish with unique and shared properties and tissue expression patterns. Panx1a channels, located in horizontal cells of the outer retina, modulate light decrement detection through an ATP/pH-dependent mechanisms and adenosine/dopamine signaling. Here, we decipher how the strategic localization of Panx1b channels in the inner retina and ganglion cell layer modulates visually evoked motor behavior. We describe a panx1b knockout model generated by TALEN technology. The RNA-seq analysis of 6 days post-fertilization larvae is confirmed by Real-Time PCR and paired with testing of visual-motor behaviors. The Panx1b protein emerges as a modulator of the circadian clock system. The loss of panx1b also disrupts the retinal response to the abrupt loss of illumination and decreases the larval ability to follow leftward direction of motion in the dark. The evidence suggests that in the retina Panx1b contributes to the OFF pathways function, like Panx1a, though through different signaling mechanisms. In this process, the loss of Panx1b channels compromises the final output of luminance as well as direction of motion detector RGCs. In addition, the disruption of the circadian clock system in mutants suggests that Panx1b could participate in non-image forming processes in the inner retina.
Chronic release of tailless phage particles from Lactococcus lactis
Authors: Liu Yue , Alexeeva Svetlana , Bachmann Herwig , Martínez Jesús Adrián Guerra , Yeremenko Nataliya , Abee Tjakko , Smid Eddy J. 
Published: July 2021

AbstractLactococcus lactis strains residing in the microbial community of a complex dairy starter culture named “Ur” are hosts to prophages belonging to the family Siphoviridae. L. lactis strains (TIFN1 to TIFN7) showed detectable spontaneous phage production and release (109-1010 phage particles/mL) and up to 10-fold increases upon prophage induction, while in both cases we observed no obvious cell lysis, typically described for the lytic life cycle of Siphoviridae phages. Intrigued by this phenomenon, we investigated the host-phage interaction using strain TIFN1 (harboring prophage proPhi1) as a representative. We confirmed that during the massive phage release, all bacterial cells remain viable. Further, by monitoring phage replication in vivo, using a green fluorescence protein reporter combined with flow cytometry, we demonstrated that the majority of the bacterial population (over 80%) is actively producing phage particles when induced with mitomycin C. The released tailless phage particles were found to be engulfed in lipid membranes, as evidenced by electron microscopy and lipid staining combined with chemical lipid analysis. Based on the collective observations, we propose a model of phage-host interaction in L. lactis TIFN1, where the phage particles are engulfed in membranes upon release, thereby leaving the producing host intact. Moreover, we discuss possible mechanisms of chronic, or non-lytic release of LAB Siphoviridae phages and its impact on the bacterial host.
Dietary Patterns Among 13-17-Years Old School Adolescents: A National Comparison of the Three Geographical Regions in Bolivia
Authors: Villalta Noelia , Arauco Nattalia , Mamani Marisol , Illanes Daniel E , Singh Pramil , Moura Lenildo De , Sabaté Joan 
Published: July 2021

AbstractIntroductionBolivia is considered one to the most biodiverse countries in the world. It has three ecological floors or geographical regions (highlands, plains and valleys) with very different climatic and cultural characteristics. Traditionally dietary patterns varied in each region. Because two-thirds of premature deaths are associated with behaviors that begin in adolescence, understanding dietary patterns among adolescents is important to improving health. The aim of this study was to identify dietary patterns of adolescents in the different geographical regions of Bolivia.MethodologyData were obtained from the World Health Organization’s Global School-based Student Health Survey 2018 that assesses risky behaviors and protective factors in students aged 13 to 17 years old. It uses an observational cross-sectional method and included 7945 adolescents in schools that were representative of all students in this age group in each of the three geographical regions in Bolivia.Results3.9% of students in Bolivia are food insecure, with the highest percentage in the highlands (4.6%) and the lowest in the plains (3.1%). Adolescents in the highlands consume vegetables and fruits more frequently than adolescents in the plains and valleys. Water consumption in the valleys was 19.6% students who drink 1-3 glasses/d. Dairy consumption ≥2 in 7 days is higher in the highlands and lower in the valleys. Consumption of soft drinks at ≥1 glass per day is 34.3% in the plains and 30.1% in the valleys. Junk food consumption ≥1 in 7 days was 62.0% with a greater presence on the plains at 65.7%.ConclusionThe highlands revealed a greater presence of protective factors than the other regions. The valley, despite having greater access to fruits and vegetables, has a greater presence of risky behaviors. Teenagers in the plains have greater exposure to advertising and access to junk food at school.
Obesity, Ethnicity, and Covid-19 Mortality: A population-based cohort study of 12.6 Million Adults in England
Authors: Yates Thomas , Summerfield Annabel , Razieh Cameron , Banerjee Amitava , Chudasama Yogini , Davies Melanie J , Gillies Clare , Islam Nazrul , Lawson Claire , Mirkes Evgeny , Zaccardi Francesco , Khunti Kamlesh , Nafilyan Vahé 
Published: July 2021

AbstractImportanceObesity and ethnicity are well characterised risk factors for severe COVID-19 outcomes, but the differential effects of obesity on COVID-19 outcomes by race/ethnicity has not been examined robustly in the general population.ObjectiveTo investigate the association between body mass index (BMI) and COVID-19 mortality across different ethnic groups.Design, Setting, and ParticipantsThis is a retrospective cohort study using linked national Census, electronic health records and mortality data for English adults aged 40 years or older who were alive at the start of pandemic (24thJanuary 2020).ExposuresBMI obtained from electronic health records. Self-reported ethnicity (white, black, South Asian, other) was the effect-modifying variable.Main Outcomes and MeasuresCOVID-19 related death identified by ICD-10 codes U07.1 or U07.2 mentioned on the death certificate from 24thJanuary 2020 until December 28th2020.ResultsThe analysis included white (n = 11,074,708; mean age 61.9 [±13.4] years; 54% women), black (n = 416,542; 56.4 [±11.7] years; 57% women), South Asian (621,691; 55.7 [±12.4] years; 51% women) and other (n = 478,196; 55.3 [±11.6] years; 55% women) ethnicities with linked BMI data. The association between BMI and COVID-19 mortality was stronger in ethnic minority groups. Compared to a BMI of 22.5 kg/m2in white ethnicities, the adjusted HR for COVID-19 mortality at a BMI of 30 kg/m2in white, black, South Asian and other ethnicities was 0.95 (95% CI: 0.87-1.03), 1.72 (1.52-1.94), 2.00 (1.78-2.25) and 1.39 (1.21-1.61), respectively. The estimated risk of COVID-19 mortality at a BMI of 40 kg/m2in white ethnicities (HR = 1.73) was equivalent to the risk observed at a BMI of 30.1 kg/m2, 27.0 kg/m2, and 32.2 kg/m2in black, South Asian and other ethnic groups, respectively.ConclusionsThis population-based study using linked Census and electronic health care records demonstrates that the risk of COVID-19 mortality associated with obesity is greater in ethnic minority groups compared to white populations.QuestionDoes the association between BMI and COVID-19 mortality vary by ethnicity?FindingsIn this study of 12.6 million adults, BMI was associated with COVID-19 in all ethnicities, but with stronger associations in ethnic minority populations such that the risk of COVID-19 mortality for a BMI of 40 kg/m2in white ethnicities was observed at a BMI of 30.1 kg/m2, 27.0 kg/m2, and 32.2 kg/m2in black, South Asian and other ethnicities, respectively.MeaningBMI is a stronger risk factor for COVID-19 mortality in ethnic minorities. Obesity management is therefore a priority in these populations.
Age-related Cellular and Microstructural Changes in the Rotator Cuff Enthesis
Authors: Long Zeling , Nakagawa Koichi , Wang Zhanwen , Amadio Peter C. , Zhao Chunfeng , Gingery Anne 
Published: July 2021

AbstractRotator cuff injuries increase with age. The enthesis is the most frequent site of rotator cuff injury and degeneration. Understanding age-related changes of the enthesis are essential to determine the mechanism of rotator cuff injuries, degeneration, and to guide mechanistically driven therapies. In this study, we explored age-related cellular changes of the rotator cuff enthesis in young, mature, and aged rats. Here we found that the aged enthesis is typified by an increased mineralized zone and decreased non-mineralized zone. Proliferation, migration, and colony forming potential of rotator cuff derived cells (RCECs) was attenuated with aging. The tenogenic and chondrogenic potential were significantly reduced, while the osteogenic potential increased in aged RCECs. The adipogenic potential increased in RCECs with age. This study explores the cellular differences found between young, mature, and aged rotator cuff enthesis cells and provides a basis for further delineation of mechanisms and potential therapeutics for rotator cuff injuries.
Roles of proteins containing immunoglobulin-like domains in the conjugation of bacterial plasmids
Authors: Hüttener Mário , Hergueta Jon , Bernabeu Manuel , Prieto Alejandro , Aznar Sonia , Merino Susana , Tomás Joan , Juárez Antonio 
Published: July 2021

AbstractHorizontal transfer of bacterial plasmids generates genetic variability and contributes to the dissemination of the genes that enable bacterial cells to develop antimicrobial resistance (AMR). Several aspects of the conjugative process have long been known, namely, those related to the proteins that participate in the establishment of cell-to-cell contact and to the enzymatic processes associated with the processing of plasmid DNA and its transfer to the recipient cell. In this work, we describe the role of newly identified proteins that influence the conjugation of several plasmids. Genes encoding high-molecular-weight proteins that contain one or several immunoglobulin-like domains (Big) are located in the transfer regions of several plasmids that usually harbor AMR determinants. These Big proteins are exported to the external medium and target two extracellular organelles: the flagella and the conjugative pili. The plasmid-encoded Big proteins facilitate conjugation by reducing cell motility and facilitating cell-to-cell contact by binding both to the flagella and to the conjugative pilus. They use the same export machinery as that used by the conjugative pilus components. In the examples characterized in this paper, these proteins influence conjugation at environmental temperatures (i.e., 25°C). This suggests that they may play relevant roles in the dissemination of plasmids in natural environments. Taking into account that they interact with outer surface organelles, they could be targeted to control the dissemination of different bacterial plasmids carrying AMR determinants.
Transcriptional Regulatory Features associated with Coccidioides immitis phase transition
Authors: Duttke Sascha , Beyhan Sinem , Singh Rajendra , Neal Sonya , Viriyakosol Suganya , Fierer Joshua , Kirkland Theo N , Stajich Jason E , Benner Christopher , Carlin Aaron F. 
Published: July 2021

AbstractCoccidioidomycosis (Valley Fever) is an emerging endemic fungal infection with a rising incidence and an expanding geographic range. It is caused by Coccidiodes, which are thermally dimorphic fungi that grow as mycelia in soil but transition in the lung to form pathogenic spherules. The regulatory mechanisms underlying this transition are not understood. Exploiting capped small (cs)RNA-seq, which identifies actively initiated stable and unstable transcripts and thereby detects acute changes in gene regulation with remarkable sensitivity, here we report the changes in architectural organization and key sequence features underlying phase transition of this highly pathogenic fungus. Spherule transition was accompanied by large-scale transcriptional reprogramming, functional changes in transcript isoforms, and a massive increase in promoter-distal transcription of ncRNAs. Analysis of spherule-activated regulatory elements revealed a motif predicted to recruit a WOPR family transcription factor, which are known regulators of virulence in other fungi. We identify CIMG_02671 as a C. immitis WOPR homologue and show that it activates transcription in a WOPR motif-dependent manner, suggesting it is an important regulator of pathogenic phase transition. Collectively, this also highlights csRNA-seq as a powerful means to identify transcriptional mechanisms that control pathogenesis.