bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new paradigm for leprosy diagnosis based on host gene expression Insights from leprosy lesions transcriptomics
Authors: Leal-Calvo Thyago , Avanzi Charlotte , Mendes Mayara Abud , Benjak Andrej , Busso Philippe , Pinheiro Roberta Olmo , Sarno Euzenir Nunes , Cole Stewart T. , Moraes Milton O. 
Published: July 2021

AbstractTranscriptional profiling is a powerful tool to investigate and detect human diseases. In this study, we used bulk RNA-sequencing (RNA-Seq) to compare the transcriptomes in skin lesions of leprosy patients or controls affected by other dermal conditions such as granuloma annulare, a confounder for paucibacillary leprosy. We identified five genes capable of accurately distinguishing multibacillary and paucibacillary leprosy from other skin conditions. Indoleamine 2,3-dioxygenase 1 (IDO1) expression alone was highly discriminatory, followed byTLR10,BLK,CD38, andSLAMF7, whereas theHS3ST2andCD40LGmRNA separated multi- and paucibacillary leprosy. Finally, from the main differentially expressed genes (DEG) and enriched pathways, we conclude that paucibacillary disease is characterized by epithelioid transformation and granuloma formation, with an exacerbated cellular immune response, while multibacillary leprosy features epithelial-mesenchymal transition with phagocytic and lipid biogenesis patterns in the skin. These findings will help catalyze the development of better diagnostic tools and potential host-based therapeutic interventions. Finally, our data may help elucidate host-pathogen interplay driving disease clinical manifestations.Author SummaryDespite effective treatment, leprosy is still a significant public health issue in more than 120 countries, with more than 200 000 new cases yearly. The disease is caused mainly byMycobacterium leprae, a slow-growing bacillus still uncultivable in axenic media. This limitation has hampered basic research into host-pathogen interaction and the development of new diagnostic assays. Currently, leprosy is diagnosed clinically, with no standalone diagnostic assay accurate enough for all clinical forms. Here, we use RNA-seq transcriptome profiling in leprosy lesions and granuloma annulare to identify mRNA biomarkers with potential diagnostic applications. Also, we explored new pathways that can be useful in further understanding the host-pathogen interaction and how the bacteria bypass host immune defenses. We found thatIDO1, a gene involved with tryptophan catabolism, is an excellent candidate for distinguishing leprosy lesions from other dermatoses. Additionally, we observed that a previous signature of keratinocyte development and cornification negatively correlates with epithelial-mesenchymal transition genes in the skin, suggesting new ways in which the pathogen may subvert its host to survive and spread throughout the body. Our study identifies new mRNA biomarkers that can improve leprosy diagnostics and describe new insights about host-pathogen interactions in human skin.
Regeneration of humoral immunity from pluripotent stem cells by defined transcription factors
Authors: Zhang Qi , Wu Bingyan , Weng Qitong , Hu Fangxiao , Lin Yunqing , Xia Chengxiang , Peng Huan , Wang Yao , Liu Xiaofei , Liu Lijuan , Xiong Jiapin , Geng Yang , Zhao Yalan , Zhang Mengyun , Du Juan , Wang Jinyong 
Published: July 2021

SUMMARYRegeneration of humoral immunity from pluripotent stem cells (PSCs) is a crucial aim in translational medicine. However, reconstitution of complete, sustained, and functional B lymphopoiesis from PSCs has not yet been developed. Here, we successfully achieved regenerative B lymphopoiesis in B-cell deficient animals transplanted with PSC-derived hematopoietic progenitors (iHPCs) guided by synergistic expression ofRunx1, Hoxa9, andLhx2. Upon transplantation, the iHPCs immediately gave rise to pro/pre-B cells in recipients’ bone marrow, which were able to further differentiate into the entire B cell lineages, including innate B-1a, B-1b, MZ B cells, as well as adaptive FO B cells. In responding to antigen stimuli, the regenerative B cells produced adaptive humoral immune responses, sustained a prolonged antigen-specific antibody production, and formed immune-memory. Particularly, the regenerative B cells in spleen showed developing patterns of immunoglobulin chain-switch and hyper-mutation via a cross-talk with the host T follicular helper cells, which eventually formed T cell-dependent humoral responses. This study providesde novoevidence that B lymphopoiesis can be regenerated from PSCs via a HSC-independent approach, which provides insights into treating B-cell related humoral deficiencies using PSCs as unlimited cell resource.
Anaplerotic flux into the Calvin-Benson cycle. Hydrogen isotope evidence forin vivooccurrence in C3metabolism
Authors: Wieloch Thomas , Augusti Angela , Schleucher Jürgen 
Published: July 2021

Summary-As the central carbon uptake pathway in photosynthetic cells, the Calvin-Benson cycle is among the most important biochemical cycles for life on Earth. A carbon flux of anaplerotic origin (i.e., through the chloroplast-localised oxidative branch of the pentose phosphate pathway) into the Calvin-Benson cycle was proposed recently.-Here, we measured intramolecular deuterium abundances in leaf starch ofHelianthus annuusgrown at varying ambient CO2concentrations,Ca. Additionally, we modelled deuterium fractionations expected for the anaplerotic pathway and compared modelled with measured fractionations.-We report deuterium fractionation signals at H1and H2of starch glucose. Below aCachange point, these signals increase with decreasingCaconsistent with modelled fractionations by anaplerotic flux. Under standard conditions (Ca=450 ppm corresponding to intercellular CO2concentrations,Ci, of 328 ppm), we estimate negligible anaplerotic flux. AtCa=180 ppm (Ci=140 ppm), more than 10% of the glucose 6-phosphate entering the starch biosynthesis pathway is diverted into the anaplerotic pathway.-In conclusion, we report evidence consistent with anaplerotic carbon flux into the Calvin-Benson cyclein vivo. We propose the flux may help to (i) maintain high levels of ribulose 1,5-bisphosphate under source-limited growth conditions to facilitate photorespiratory nitrogen assimilation required to build-up source strength and (ii) counteract oxidative stress.
Roscovitine exacerbates Mycobacterium abscessus infection by reducing NADPH oxidase-dependent neutrophil trafficking
Authors: Le Moigne Vincent , Rincon Daniela Rodriguez , Glatigny Simon , Dupont Christian M. , Langevin Christelle , Ali Said Amel Ait , Renshaw Stephen A. , Floto R. Andres , Herrmann Jean-Louis , Bernut Audrey 
Published: July 2021

AbstractPersistent neutrophilic inflammation associated with chronic pulmonary infection causes progressive lung injury and eventually death in individuals with cystic fibrosis (CF), a genetic disease caused by bi-allelic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.We therefore examined whether Roscovitine, a cyclin-dependent kinase inhibitor that (in other conditions) reduces inflammation while promoting host defence, might provide a beneficial effect in the context of CF.Herein, using CFTR-depleted zebrafish larvae as an innovative vertebrate model of CF immuno-pathophysiology, combined with murine and human approaches, we sought to determine the effects of Roscovitine on innate immune responses to tissue injury and pathogens in CF condition.We show that Roscovitine exerts anti-inflammatory and pro-resolution effects in neutrophilic inflammation induced by infection or tail amputation in zebrafish. Roscovitine reduces overactive epithelial ROS-mediated neutrophil trafficking, by reducing DUOX2/NADPH-oxidase activity, and accelerates inflammation resolution by inducing neutrophil apoptosis and reverse migration. Importantly, while Roscovitine efficiently enhances intracellular bacterial killing of Mycobacterium abscessus in human CF macrophages ex vivo, we found that treatment with Roscovitine results in worse infection in mouse and zebrafish models. By interfering with DUOX2/NADPH oxidase-dependent ROS production, Roscovitine reduces the number of neutrophils at infection sites, and consequently compromises granuloma formation and maintenance, favouring extracellular multiplication of M. abscessus and more severe infection.Our findings bring important new understanding of the immune-targeted action of Roscovitine and have significant therapeutic implications for safety targeting inflammation in CF.
The genetic origin of Daunians and the Pan-Mediterranean southern Italian Iron Age context
Authors: Aneli Serena , Saupe Tina , Montinaro Francesco , Solnik Anu , Molinaro Ludovica , Scaggion Cinzia , Carrara Nicola , Raveane Alessandro , Kivisild Toomas , Metspalu Mait , Scheib Christiana L , Pagani Luca 
Published: July 2021

SummaryThe geographical location and shape of Apulia, a narrow land stretching out in the sea at the South of Italy, made this region a Mediterranean crossroads connecting Western Europe and the Balkans. Such movements culminated at the beginning of the Iron Age with the Iapygian civilization which consisted of three cultures: Peucetians, Messapians and Daunians. Among them, the Daunians left a peculiar cultural heritage, with one-of-a-kind stelae and pottery, but, despite the extensive archaeological literature, their origin has been lost to time. In order to shed light on this and to provide a genetic picture of Iron Age Southern Italy, we collected and sequenced human remains from three archaeological sites geographically located in Northern Apulia (the area historically inhabited by Daunians) and radiocarbon dated between 1157 and 275 calBCE. We find that Iron Age Apulian samples are still distant from the genetic variability of modern-day Apulians, they show a remarkable genetic heterogeneity, even though a few kilometers and centuries separate them, and they are well inserted into the Iron Age Pan-Mediterranean genetic landscape. Our study provides for the first time a window on the genetic make-up of pre-imperial Southern Italy, whose increasing connectivity within the Mediterranean landscape, would have contributed to laying the foundation for modern genetic variability. In this light, the genetic profile of Daunians may be compatible with an autochthonous origin, with plausible contributions from the Balkan peninsula.
The mechanism of MinD stability modulation by MinE in Min protein dynamics
Authors: Carlquist William C , Cytrynbaum Eric N 
Published: July 2021

AbstractThe patterns formed both in vivo and in vitro by the Min protein system have attracted much interest because of the complexity of their dynamic interactions given the apparent simplicity of the component parts. Despite both the experimental and theoretical attention paid to this system, the details of the biochemical interactions of MinD and MinE, the proteins responsible for the patterning, are still unclear. For example, no model consistent with the known biochemistry has yet accounted for the observed dual role of MinE in the membrane stability of MinD. Until now, a statistical comparison of models to the time course of Min protein concentrations on the membrane has not been carried out. Such an approach is a powerful way to test existing and novel models that are difficult to test using a purely experimental approach. Here, we extract time series from previously published fluorescence microscopy time lapse images of in vitro experiments and fit two previously described and one novel mathematical model to the data. We find that the novel model, which we call the Asymmetric Activation with Bridged Stability Model, fits the time-course data best. It is also consistent with known biochemistry and explains the dual MinE role via MinE-dependent membrane stability that transitions under the influence of rising MinE to membrane instability with positive feedback. Our results reveal a more complex network of interactions between MinD and MinE underlying Min-system dynamics than previously considered.
Early loss of endogenous NAD+ following rotenone treatment leads to Sarm1 activation that is ameliorated by PARP inhibition
Authors: Sarkar Ankita , Sur Malinki , Dutta Sourav , Dey Puja , Mukherjee Piyali 
Published: July 2021

AbstractSarm1 is an evolutionary conserved innate immune adaptor protein that has emerged as a primary regulator of programmed axonal degeneration over the past decade. In vitro structural insights have revealed that although Sarm1 induces energy depletion by breaking down NAD+, it is also allosterically inhibited by NAD+. However, how NAD+ levels modulate the activation of intracellular Sarm1 has not been elucidated so far. This study focuses on understanding the events leading to Sarm1 activation in both neuronal and non-neuronal cells using the mitochondrial complex I inhibitor rotenone. Here we report the regulation of rotenone-induced cell death by loss of NAD+ that may act as a “biological trigger” of Sarm1 activation. Our study revealed that early loss of endogenous NAD+ levels arising due to PARP1 hyperactivation preceded Sarm1 induction following rotenone treatment. Interestingly, replenishing NAD+ levels by the PARP1 inhibitor, PJ34 restored mitochondrial homeostasis and prevented subsequent Sarm1 activation in rotenone treated cells. These cellular data were further validated in Drosophila melanogaster where a significant reduction in rotenone mediated loss of locomotor abilities and reduced dSarm expression was observed in the flies following PARP inhibition. Taken together, these observations not only uncovers a novel regulation of Sarm1 induction by endogenous NAD+ levels but also point towards an important understanding on how PARP inhibitors could be repurposed in the treatment of mitochondrial complex I deficiency disorders mediated by Sarm1.
TRAK adaptors coordinate the recruitment and activation of dynein and kinesin to control mitochondrial transport
Authors: Canty John T. , Hensley Andrew , Yildiz Ahmet 
Published: July 2021

AbstractIn neurons, mitochondria are transported to distal regions for supplying energy and buffer Ca2+. Mitochondrial transport is mediated by Miro and TRAK adaptors that recruit kinesin and dynein-dynactin. To understand how mitochondria are transported by these opposing motors and stalled at regions with elevated Ca2+, we reconstituted the mitochondrial transport machinery in vitro. We show that the coiled-coil domain of TRAK activates dynein-dynactin motility, but kinesin requires an additional factor to efficiently transport Miro/TRAK. Unexpectedly, TRAK adaptors that recruit both motors move towards kinesin’s direction, whereas kinesin is excluded from binding TRAK transported by dynein-dynactin. The assembly and motility of the transport machinery are not affected by Ca2+. Instead, the mitochondrial docking protein syntaphilin is sufficient to oppose the forces generated by kinesin and stall the motility. Our results provide mechanistic insight into how mitochondria are transported by the coordinated action of motors and statically anchored to regions with high neuronal activity.
Sociological and spatial dynamics of an evolving Parisian open drug scene: the case of the “Colline du Crack”
Authors: Jangal Candy , Lovera Mathieu , Dambélé Sayon , Jauffret-Roustide Marie 
Published: July 2021

Purpose
In November 2019, an open drug scene, commonly called “Colline du crack” and located in Paris was forcibly closed after 10 years of existence. This paper aims to understand how that space has evolved over the years to become a major hub for drug use.

Design/methodology/approach
The authors used a qualitative approach that included interviews with 52 people who use drugs (PWUD) and 54 field professionals and ethnographic observations. The authors asked questions about the evolution of the major sites of crack visibility in Paris and about social representations related to these spaces. They compared their datas with datas drawn from gray literature.

Findings
La Colline emerged on an isolated slope, away from police repression and local anti-crack organizations. In the beginning, it was a discrete, communal space regulated by PWUD. Starting in 2015, social transformations in the neighborhood turned la Colline into a central hub for dealing and using crack. La Colline became an open scene which led to its evacuation in 2019.

Originality/value
This paper contributes to literature on community building of drug consumers. The authors are also using a wide variety of methodological tools.
Supporting health literacy in adolescent populations: distinguishing pedagogies for sun safety education in schools
Authors: Barwood Donna 
Published: July 2021

PurposeThe aim of this paper is to distinguish pedagogies supporting critical health literacy development in adolescent populations. Specifically, for sun safety education in schools.Design/methodology/approachThe paper draws on an exploratory intrinsic case study design to qualitatively examine the learning conditions that Pre-Service Teachers' (PsTs) mobilise to advance Health Literary (HL) in learning activities.FindingsThis paper presents data that shows the different ways thirty Pre-Service Teachers (PsTs) in Western Australia conceptualise HL in sun safety education for Year 7 students (12–13 years old). Examination of three consecutive lesson plans categorised learning activities (n = 444) according to HL competencies. Data shows that the PsTs pedagogically advance HL but are constrained when conceptualising learning to support critical HL. Further examination of the lesson plans of the 11 PsTs who pedagogically advanced learning to support a critical level of health literacy, distinguished the learning conditions and pedagogies supporting critically health literate adolescents.Originality/valueBy distinguishing pedagogies to situate individual and social health within broader societal goals, the paper identifies teacher education institutions as key players enabling young people to socially advocate healthier living, particularly, regarding melanoma and non-melanoma incidence.
Revisiting critical factors of logistics outsourcing relationship: a multiple-case study approach
Authors: Thai Vinh Van , Rahman Shams , Tran Dong Mai 
Published: July 2021

PurposeThis paper aims to examine critical factors of successful logistics outsourcing relationship from the perspectives of both LSPs and shippers employing case studies in Singapore and Vietnam as examples of well-established and growing logistics outsourcing markets.Design/methodology/approachThe case study design is adopted to empirically examine logistics outsourcing practices. Data were collected through in-depth interviews with senior managers from four cases in Singapore and seven cases in Vietnam. These case organisations are engaged comprehensively in logistics outsourcing activities and encompass both international firms that have their local operations and those local firms whose operations expand internationally.FindingsResults suggest that the success of logistics outsourcing may depend on five strategic factors and five operational factors, with some of them being the same between LSPs and shippers in both countries and in line with the literature. There also seemed to be a difference between logistics outsourcing practitioners in a developed country (Singapore), and those in a developing country (Vietnam), in which factors, i.e. having the right people and management support, business processes integration and cultural intelligence, tend to be emphasised and practised more in the former. A strategy matrix of logistics outsourcing was mapped accordingly.Research limitations/implicationsThe generalisation of this study would require further empirical examination from more quantitative research, for example, the use of surveys with shippers who engage with LSPs.Practical implicationsFindings from this research can assist managers in charge of outsourcing to reflect on their practices and devise and implement appropriate strategies for successful logistics outsourcing. Especially for growing logistics outsourcing markets and not-yet-standardised practices like Vietnam, the findings of this research are significant as they provide policy and managerial insights into how logistics outsourcing can be performed successfully. Specifically, adequate guidelines and resources including training relating to strategic factors of logistics outsourcing must be provided.Originality/valueThis research is one of the first studies that categorise success factors of logistics outsourcing into strategic and operational factors and postulates their conceptualisation in a strategy matrix that can be applied in future research.
Association of individual and device usage factors with musculoskeletal disorders amongst handheld devices users during homestay due to pandemic
Authors: Jain Rahul , Rana Kunj Bihari , Meena Makkhan Lal 
Published: July 2021

PurposeThe COVID-19 pandemic is spreading in India and different parts of the world. The outbreak delivered not only the condition of dying from infection but also forced people (especially office workers and students) to perform all working (office work, classes, assignments, etc.) and non-working activities (leisure activities such as social media, gaming, etc.) at home using handheld devices (HHDs). In this situation, HHD usage for longer durations is mainly responsible for work-related health issues. Therefore, the paper aims to explore HHD usage patterns and musculoskeletal disorders (MSDs) amongst HHD users during homestay and the impact of individual and HHD usage–related factors on MSDs.Design/methodology/approachFrom different states of India, 651 people (especially HHD users from universities and industries) were sampled by using systematic cluster random sampling. In addition, an online questionnaire was used to collect data on the prevalence and risk factors of MSDs. Finally, mean comparisons and chi-square analysis was used to analyse the collected data.FindingsThe prevalence rate of MSDs was higher in upper body parts as compared to the lower body parts. The association of gender with MSDs in various body parts was substantial. The time spent on various working and non-working activities using HHDs was significantly associated with MSDs in upper body parts.Practical implicationsHomestay work may be used as an alternative working arrangement, and the risk factors that have the most significant impact on the health of HHD users may be identified by organizations. The findings suggest the proper use of HHDs as per their essential need with intermediate recreational activities.Originality/valueIt is observed that the musculoskeletal health of office workers and university students is a cause for concern during homestay. The current study provides the prevalence of MSDs experienced by HHD users and the association of individual and HHD usage factors with MSDs.