bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adventive larval parasitoids reconstruct their close association with spotted-wing drosophila in the invaded North American range
Authors: Abram Paul K. , Franklin Michelle T. , Hueppelsheuser Tracy , Carrillo Juli , Grove Emily , Eraso Paula , Acheampong Susanna , Keery Laura , Girod Pierre , Tsuruda Matt , Clausen Martina , Buffington Matthew L. , Moffat Chandra E. 
Published: December 2021

AbstractTwo species of larval parasitoids of the globally invasive fruit pest, Drosophila suzukii (Diptera: Drosophilidae), Leptopilina japonica and Ganaspis brasiliensis (both Hymenoptera: Figitidae), were detected in British Columbia, Canada in 2019. Both are presumed to have been unintentionally introduced from Asia, however; the extent of their establishment across different habitats with diverse host plants used by D. suzukii was unclear. In addition, there was no knowledge of the temporal dynamics of parasitism of D. suzukii by these two parasitoids. We repeatedly sampled the fruits of known host plants of D. suzukii over the entire 2020 growing season in British Columbia. We documented the presence of L. japonica and G. brasiliensis and estimated the apparent percentage of D. suzukii parasitized. Across a large region of southwestern British Columbia, both L. japonica and G. brasiliensis were found to be very common across a variety of mostly unmanaged habitats over the entire course of the season (May-October) in the fruits of most host plants known to host D. suzukii larvae. The two parasitoids were responsible for more than 98% of D. suzukii larval parasitism and usually co-existed. Parasitism of D. suzukii was variable among hosts plants and sites (0-66% percent parasitism) and appeared to be time-structured. Our study demonstrates that the close association between the two larval parasitoids and D. suzukii that exists in Asia has evidently been reconstructed in North America, resulting in the highest parasitism levels of D. suzukii yet recorded outside of its area of origin.
High seroconversion rate and SARS-CoV-2 Delta neutralization in PLWHIV vaccinated with BNT162b2
Authors: Pourcher Valérie , Belin Lisa , Soulie Cathia , Rosenzwajg Michelle , Marot Stéphane , Lacombe Karine , Valin Nadia , Pialoux Gilles , Calin Ruxandra , Malet Isabelle , Zafilaza Karen , Tubiana Roland , Valantin Marc-Antoine , Klatzmann David , Calvez Vincent , Simon-Tillaux Noémie , Marcelin Anne-Geneviève 
Published: December 2021

AbstractObjectivesTo assess the humoral and cellular responses against SARS-CoV-2 Delta variant after BNT162b2 vaccination in PLWHIV.DesignMulticenter cohort study of PLWHIV, with a CD4 cell count <500/mm3 and a viral load <50 copies/ml on stable antiretroviral therapy for at least 3 months.MethodsAnti-SARS-CoV-2 Receptor Binding Domain IgG antibodies (anti-RBD IgG) were quantified and their neutralization capacity was evaluated using an ELISA (GenScript) and a virus neutralization test (VNT), against historical strain, Beta and Delta variants before vaccination (day 0) and one month after a complete vaccination schedule (M1).Results97 patients were enrolled in the study: 85 received 2 vaccine doses (11 previous COVID-19 and 1 premature exit). The seroconversion rate in anti-RBD IgG was 97% CI95[90%; 100%] at M1. Median (IQR) anti-RBD IgG titer was 0.97 (0.97-5.3) BAU/ml at D0 and 1219 (602-1929) at M1. Neutralizing antibodies (NAbs) capacity improved between D0 (15% CI95[8%; 23%]) and M1 (94% CI95[87%; 98%]) with the GenScript assay (p<0.0001). At M1, NAbs against historical strain, Beta and Delta variants were present in 82%, 77% and 84% patients respectively. The seroconversion rate and median anti-RBD IgG were 91% and 852 BAU/ml in patients with CD4<250/mm3 (n=13) and 98% and 1270 BAU/ml in patients with CD4>250/mm3 (n=64) (p=0.3994). 73% of patients with CD4<250 had NAbs and 97% of those with CD4>250 (p=0.0130). The NAbs against Beta variant was elicited in 50% in CD4<250 and in 81% in CD4>250 (p=0.0292). No change in CD4+ or CD8+ T cells count was observed while a decrease of CD19+ B cells count was observed (208 ±124 cells/mm3 at D0 vs 188 ±112 cells/mm3 at M1, p<0.01). No notable adverse effects or COVID-19 were reported.ConclusionsThese results show a high seroconversion rate with a Delta neutralization in PLWHIV patients after a complete BNT162b2 vaccination schedule.
Clinical Study Applying Machine Learning to Detect a Rare Disease: Results and Lessons Learned
Authors: Hersh William R. , Cohen Aaron M. , Nguyen Michelle M. , Bensching Katherine L. , Deloughery Thomas G. 
Published: December 2021

AbstractMachine learning has the potential to improve identification of patients for appropriate diagnostic testing and treatment, including those who have rare diseases for which effective treatments are available, such as acute hepatic porphyria (AHP). We trained a machine learning model on 205,571 complete electronic health records from a single medical center based on 30 known cases to identify 22 patients with classic symptoms of AHP that had neither been diagnosed nor tested for AHP. We offered urine porphobilinogen testing to these patients via their clinicians. Of the 7 who agreed to testing, none were positive for AHP. We explore the reasons for this and provide lessons learned for further work evaluating machine learning to detect AHP and other rare diseases.
International risk of SARS-CoV-2 Omicron variant importations originating in South Africa
Authors: Bai Yuan , Du Zhanwei , Xu Mingda , Wang Lin , Wu Peng , Lau Eric H. Y. , Cowling Benjamin J. , Meyers Lauren Ancel 
Published: December 2021

AbstractOmicron, a fast-spreading SARS-CoV-2 variant of concern reported to the World Health Organization on November 24, 2021, has raised international alarm. We estimated there is at least 50% chance that Omicron had been introduced by travelers from South Africa into all of the 30 countries studied by November 27, 2021.
MYH10 governs adipocyte function and adipogenesis through its interaction with GLUT4
Authors: Kislev N , Mor-Yossef Moldovan L , Barak R , Egozi M , Benayahu D 
Published: December 2021

AbstractAdipocyte differentiation is dependent on cytoskeletal remodeling processes that determine and maintain cellular shape and function. In turn, cytoskeletal proteins contribute to the filament-based network responsible for controlling adipocyte’s shape and promoting the intracellular trafficking of key cellular components. Currently, our understanding of these mechanisms remains incomplete. In this study, we identified the non-muscle myosin 10 (MYH10) as an important regulator of adipogenesis and adipocyte function through its interaction with the insulin dependent, Glucose transporter 4 (GLUT4). MYH10 depletion in preadipocytes resulted in impaired adipogenesis, with knockdown cells exhibiting disrupted morphology and reduced molecular adipogenic signals. MYH10 was shown to be in complex with GLUT4 in adipocytes, an interaction regulated by insulin induction. The missing adipogenic capacity of MYH10-KD cells was restored when they uptook GLUT4 vesicles up from neighbor wild-type cells in a co-culture system. Our results provide the first demonstration that MYH10 interacts with GLUT4 in cells and adipose tissue through the insulin pathway. The signaling cascade is regulated by the protein kinase C ζ (PKCζ), which interacts with MYH10 to modify the localization and interaction of both GLUT4 and MYH10 in adipocytes as PKCζ inhibition resulted in reduced GLUT4 and MYH10 translocation and interactions. Overall, our study establishes MYH10 as an essential regulator of GLUT4 translocation, affecting both adipogenesis and adipocyte function, highlighting its importance in future cytoskeleton-based studies in adipocytes.
The m6A reader YTHDF2 is a negative regulator for dendrite development and maintenance of retinal ganglion cells
Authors: Niu Fugui , Han Peng , Zhang Jian , She Yuanchu , Yang Lixin , Yu Jun , Zhuang Mengru , Tang Kezhen , Shi Yuwei , Yang Baisheng , Liu Chunqiao , Peng Bo , Ji Sheng-Jian 
Published: December 2021

AbstractThe precise control of growth and maintenance of the retinal ganglion cell (RGC) dendrite arborization is critical for normal visual functions in mammals. However, the underlying mechanisms remain elusive. Here we find that the m6A reader YTHDF2 is highly expressed in the mouse RGCs. Conditional knockout (cKO) of Ythdf2 in the retina leads to increased RGC dendrite branching, resulting in more synapses in the inner plexiform layer. Interestingly, the Ythdf2 cKO mice show improved visual acuity compared with control mice. We further demonstrate that Ythdf2 cKO in the retina protects RGCs from dendrite degeneration caused by the experimental acute glaucoma model. We identify the m6A-modified YTHDF2 target transcripts which mediate these effects. This study reveals mechanisms by which YTHDF2 restricts RGC dendrite development and maintenance. YTHDF2 and its target mRNAs might be valuable in developing new treatment approaches for glaucomatous eyes.Impact statementThe m6A reader YTHDF2 negatively regulates RGC dendrite branching through destabilizing its m6A-modified target mRNAs encoding proteins controlling dendrite development and maintenance. Ythdf2 cKO improves visual acuity and alleviates acute ocular hypertension-induced glaucoma in mice.
Improvement of beef cattle cow’s pregnancy rate using an effective dose of Galectin-1
Authors: Morani Erika da Silva Carvalho , Penha Helen Alves , Rey Fernando Sebastián Baldi , Rácoletta Marcelo 
Published: December 2021

AbstractGalectins are mentioned in the literature as multifunctional molecules that participate in several biological processes such as adhesion, cell proliferation, and cycle, apoptosis, RNA processing, inflammatory process control, and reproductive physiological mechanisms. Galectin-1 has been referred to as a mediator involved in the prevention of early embryonic mortality in mammals. Exogenous GAL-1 (eGAL-1) can be found in Tolerana®. The objective of the study was to evaluate whether eGAL-1 can increase the pregnancy rate when used in an AI procedure (in a complementary artificial insemination procedure, using a second AI gun). The pregnancy rate was determined by the pregnancy condition through an ultrasound exam performed 25 to 35 days after the fixed-time artificial insemination (FTAI) of breeding cows (n=3,469 beef cows). The efficacy of GAL-1 was evaluated by comparing the pregnancy rate of the two groups (Treatment and Control Groups) in 107 contemporary groups (YG) established by the created statistical model. Based on the obtained results, it can be confirmed that the correct administration of a single dose of eGAL-1 can increase the probability of obtaining pregnancy in beef cows by up to 8.68% (p < 0.0001). The recommendation of the use of eGAL-1 during the FTAI procedure was reasonable in the beef cattle AI routine. On average, the complete procedure, using eGAL-1, took about 10 ± 5 seconds more time than the conventional procedure.
Atypical B cells upregulate co-stimulatory molecules during malaria and secrete antibodies with T follicular helper cell support
Authors: Hopp Christine S. , Skinner Jeff , Anzick Sarah L. , Tipton Christopher M. , Peterson Mary E. , Li Shanping , Doumbo Safiatou , Kayentao Kassoum , Ongoiba Aissata , Martens Craig , Traore Boubacar , Crompton Peter D. 
Published: December 2021

ABSTRACTSeveral infectious and autoimmune diseases are associated with an expansion of CD21-CD27- atypical B cells (atBCs). The function of atBCs remains unclear and few studies have investigated the biology of pathogen-specific atBCs during acute infection. Here, we performed longitudinal RNA-sequencing and flow cytometry analyses of Plasmodium falciparum (Pf)-specific B cells before and shortly after febrile malaria, with simultaneous analysis of influenza hemagglutinin (HA)-specific B cells as a comparator. B cell receptor-sequencing showed that Pf-specific atBCs, activated B cells (actBCs) and classical memory B cells share clonality and have comparable somatic hypermutation. In response to malaria, Pf-specific atBCs and actBCs expanded and upregulated molecules that mediate B-T cell interactions, suggesting that atBCs respond to T follicular helper (Tfh) cells. Indeed, in the presence of Tfh cells and Staphylococcal enterotoxin B, atBCs of malaria-exposed individuals differentiated into CD38+ antibody-secreting cells in vitro, suggesting that atBCs may actively contribute to humoral immunity to infectious pathogens.One Sentence SummaryThis study shows that atypical B cells actively respond to acute malaria and have the capacity to produce antibodies with T cell help.
Characterization of mutations causing steroid 21-hydroxylase deficiency in Brazilian and Portuguese populations
Authors: Prado Mayara J. , Singh Shripriya , Ligabue-Braun Rodrigo , Meneghetti Bruna V. , Rispoli Thaiane , Kopacek Cristiane , Monteiro Karina , Zaha Arnaldo , Rossetti Maria L. R. , Pandey Amit V. 
Published: December 2021

AbstractDeficiency of Cytochrome P450 Steroid 21-hydroxylase (CYP21A2) represents 90% of cases in congenital adrenal hyperplasia (CAH), an autosomal recessive disease caused by defects in cortisol biosynthesis. Computational prediction along with functional studies are often the only way to classify variants to understand the links to disease-causing effects. Here we investigated the pathogenicity of uncharacterized variants in the CYP21A2 gene reported in the Brazilian and Portuguese populations. Physicochemical alterations, residue conservation, and effect on protein structure were accessed by computational analysis. The enzymatic performance was obtained by functional assay with the wild-type and mutant CYP21A2 proteins expressed in HEK293 cells. Computational analysis showed that p.W202R, p.E352V, and p.R484L have severely impaired the protein structure, while p.P35L, p.L199P, and p.P433L have moderate effects. The p.W202R, p.E352V, p.P433L, and p.R484L variants showed residual 21OH activity consistent with the simple virilizing phenotype. The p.P35L and p.L199P variants showed partial 21OH efficiency associated with the non-classical phenotype. Additionally, p.W202R, p.E352V and p.R484L also modified the protein expression level. We have determined how the selected CYP21A2 gene mutations affect the 21OH activity through structural and activity alteration contributing to the future diagnosis and management of 21OH deficiency.
MacroH2A impedes metastatic growth by enforcing a discrete dormancy program in disseminated cancer cells
Authors: Sun Dan , Filipescu Dan , Hasson Dan , Singh Deepak K. , Carcamo Saul , Khalil Bassem , Miles Brett A. , Westra William , Sproll Karl Christoph , Bernstein Emily , Aguirre-Ghiso Julio A. 
Published: December 2021

AbstractMacroH2A variants have been associated with tumor suppression through inhibition of proliferation and metastasis, as well as their role in cellular senescence. However, their role in regulating the dormant state of disseminated cancer cells (DCCs) remains unclear. Here we reveal that solitary dormant DCCs display increased levels of macroH2A variants in head and neck squamous cell carcinoma PDX models and patient samples compared to proliferating primary or metastatic lesions. We further demonstrate that microenvironmental and stress adaptive signals such as TGFβ2 and p38α/β, which induce DCC dormancy, upregulate macroH2A expression. Functionally, we find that overexpression of macroH2A variants is sufficient to induce tumor cells into dormancy and notably, inducible expression of the macroH2A2 variant suppresses the growth of DCCs into overt metastasis. However, this dormant state does not require well-characterized dormancy factors such as DEC2 and NR2F1, suggesting alternate pathways. Our transcriptomic analyses reveal that macroH2A2 overexpression inhibits E2F, RAS and MYC signaling programs, while upregulating inflammatory cytokines commonly secreted by senescent cells. Taken together, our results demonstrate that macroH2A2 enforces a stable dormant phenotype in DCCs by activating a select subset of dormancy and senescence genes that limit metastasis initiation.
Scalable image-based visualization and alignment of spatial transcriptomics datasets
Authors: Preibisch Stephan , Innerberger Michael , León-Periñán Daniel , Karaiskos Nikos , Rajewsky Nikolaus 
Published: December 2021

AbstractWe present STIM, an imaging-based computational framework focused on visualizing and aligning high-throughput spatial sequencing datasets. STIM is built on the powerful, scalable ImgLib2 and BigDataViewer (BDV) image data frameworks and thus enables novel development or transfer of existing computer vision techniques to the sequencing domain characterized by datasets with irregular measurement-spacing and arbitrary spatial resolution, such as spatial transcriptomics data generated by multiplexed targeted hybridization or spatial sequencing technologies. We illustrate STIM’s capabilities by representing, interactively visualizing, 3D rendering, automatically registering and segmenting publicly available spatial sequencing data from 13 serial sections of mouse brain tissue, and from 19 sections of a human metastatic lymph node.
A slow dynamic RNA switch regulates processing of microRNA-21
Authors: Shortridge Matthew D. , Yang Wen , Walker Matthew J. , Varani Gabriele 
Published: December 2021

AbstractThe microRNAs are non-coding RNAs which post-transcriptionally regulate the expression of a majority of eukaryotic genes, and whose dysregulation is a driver of many human diseases. Here we report the discovery of a very slow (0.1 sec) conformational rearrangement at the Dicer cleavage site of pre-miR-21 which regulates the relative concentration of readily processed and inefficiently processed structural states. We show this dynamic switch is affected by single nucleotide mutations and can be biased by small molecule and peptide ligands, which can direct the microRNA to occupy the inefficiently processed state and reduce processing efficiency. This result reveals a new mechanism of RNA regulation and suggests a chemical approach to suppressing or activating pathogenic microRNAs by selective stabilization of the unprocessed or processed state.
Live imaging of the Cryptosporidium parvum lifecycle reveals direct development of male and female gametes from type one meronts
Authors: English Elizabeth D. , Guérin Amandine , Tandel Jayesh , Striepen Boris 
Published: December 2021

AbstractCryptosporidium is a leading infectious cause of diarrhea around the world associated with waterborne outbreaks, community spread, or zoonotic transmission. The parasite has significant impact on early childhood mortality, and infection is both consequence and cause of malnutrition and stunting. There is currently no vaccine, and treatment options are very limited. Cryptosporidium is a member of the Apicomplexa, and as typical for this protist phylum relies on asexual and sexual reproduction. In contrast to other Apicomplexa, like malaria parasite Plasmodium, Cryptosporidium’s entire lifecycle unfolds in a single host in less than three days. Here we establish a model to image lifecycle progression in living cells, and observe, track, and compare nuclear division of asexual and sexual stage parasites. We establish the length and sequence of the cell cycles of all stages and map the developmental fate of parasites across multiple rounds of invasion and egress. We determine that the parasite executes an intrinsic program of three generations of asexual replication, followed by a single generation of sexual stages that is independent of environmental stimuli. We find no evidence for a morphologically distinct intermediate stage (the tetraploid type II meront) but demonstrate direct development of gametes from 8N type I meronts. The progeny of each meront is collectively committed to either asexual or sexual fate, but importantly, meronts committed to sexual fate give rise to both males and females. We define a Cryptosporidium lifecycle matching Tyzzer’s original description and inconsistent with the coccidian lifecycle now shown in many textbooks.
A predictive microfluidic model of human glioblastoma to assess trafficking of blood-brain barrier penetrant nanoparticles
Authors: Straehla Joelle P. , Hajal Cynthia , Safford Hannah C. , Offeddu Giovanni S. , Boehnke Natalie , Dacoba Tamara G. , Wyckoff Jeffrey , Kamm Roger D. , Hammond Paula T. 
Published: December 2021

AbstractThe blood-brain barrier represents a significant challenge for the treatment of high-grade gliomas, and our understanding of drug transport across this critical biointerface remains limited. To advance preclinical therapeutic development for gliomas, there is an urgent need for predictive in vitro models with realistic blood-brain barrier vasculature. Here, we report a vascularized human glioblastoma (GBM) model in a microfluidic device that accurately recapitulates brain tumor vasculature with self-assembled endothelial cells, astrocytes, and pericytes to investigate the transport of targeted nanotherapeutics across the blood-brain barrier and into GBM cells. Using modular layer-by-layer assembly, we functionalized the surface of nanoparticles with GBM-targeting motifs to improve trafficking to tumors. We directly compared nanoparticle transport in our in vitro platform with transport across mouse brain capillaries using intravital imaging, validating the ability of the platform to model in vivo blood-brain barrier transport. We investigated the therapeutic potential of functionalized nanoparticles by encapsulating cisplatin and showed improved efficacy of these GBM-targeted nanoparticles both in vitro and in an in vivo orthotopic xenograft model. Our vascularized GBM model represents a significant biomaterials advance, enabling in-depth investigation of brain tumor vasculature and accelerating the development of targeted nanotherapeutics.Significance StatementThe blood-brain barrier represents a major therapeutic challenge for the treatment of glioblastoma, and there is an unmet need for in vitro models that recapitulate human biology and are predictive of in vivo response. Here we present a new microfluidic model of vascularized glioblastoma featuring a tumor spheroid in direct contact with self-assembled vascular networks comprised of human endothelial cells, astrocytes, and pericytes. This model was designed to accelerate the development of targeted nanotherapeutics, and enabled rigorous assessment of a panel of surface-functionalized nanoparticles designed to exploit a receptor overexpressed in tumor-associated vasculature. Trafficking and efficacy data in the in vitro model compared favorably to parallel in vivo data, highlighting the utility of the vascularized glioblastoma model for therapeutic development.
Financial inclusion and small enterprise growth in Africa: emerging perspectives and research agenda
Authors: Kuada John 
Published: December 2021

PurposeThe purposes of the paper are to review the stream of studies that link financial inclusion to small enterprise growth in Sub-Sahara Africa (SSA) to identify the research gaps they provide and to prepare an agenda for future research in the field.Design/methodology/approachThe study employs systematic literature search method to identify relevant literature from journals. The study then adopts a narrative approach for the review, highlighting the findings from the prior studies and gaps requiring research attention.FindingsThe discussions reveal that there is a need for future studies that can unpack small enterprise growth determinants, identify growth-enabling entrepreneurial characteristics and examine the contextual variabilities that shape their effectiveness.Originality/valueThere is currently no comprehensive/integrated review exploring the link between financial inclusion and small enterprise growth in SSA. The review, therefore, provides insights that contribute to the development of this stream of research.