bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening of Thalassemia Carriers, Hemoglobin Variants, and Comparison of Hematological Parameters between Children of Bangladesh and Forcibly Displaced Myanmar Nationals
Authors: Mahtarin Rumana , Azad Kasrina , Hossain Mohabbat , Aktar Mukta Mst. Sharmin , Habib Mohammad Tanbir , Siddik Abu Bakar , Sultana Nishat , Kawser Zannat , Kulsum Umme , Sultana Nusrat , Noor Farjana Akther , Mahdi Ahmad Zubair , Asaduzzaman Muhammad , Habib Md. Ahashan , Chowdhury Emran Kabir , Qadri Firdausi , Begum Mst. Noorjahan , Nurun Nabi A.H.M. 
Published: September 2023

AbstractThalassemia is a hereditary blood disorder with different severity spectrums. This study aimed to assess thalassemia screening rates between children of Bangladesh and selected camps of Forcibly Displaced Myanmar Nationals (FDMN) in Cox’s Bazar in Bangladesh and compare the hematological parameters among the screening groups. Complete blood count (CBC) analysis and hemoglobin electrophoresis for each participant were performed by collecting venous blood. Statistical analysis was employed for the comparison of parameters in blood. The thalassemia carrier and other hemoglobin variant rate in Bangladeshi children in selected areas have been found to be 20.7% and in FDMN children, the rate is 8.2%. Hematological differences are visualized among children of two nations. Intra-and interpopulation variances are highlighted in principal component analysis where higher variance (94.87%) in Bangladeshi children than FDMN children (80.68%). Receiver operating characteristics (ROC) and area under the curve (AUC) analyses revealed, RBC (0.761, 0.902, and 0.791) and RDW-CV are better model (0.819, 0.925, and 0.858) among the classifier of blood parameters. Pearson correlation shows distinguished covariation or association among the parameters. The outcome of the study highlights the discrepancies in levels of carriers in regions in Bangladesh and suggests further screening as well as population based molecular research to ensure better treatment strategies.
Targeted malaria elimination interventions reducePlasmodium falciparuminfections up to 3 kilometers away
Authors: Benjamin-Chung Jade , Li Haodong , Nguyen Anna , Heitmann Gabriella Barratt , Bennett Adam , Ntuku Henry , Prach Lisa M. , Tambo Munyaradzi , Wu Lindsey , Drakeley Chris , Gosling Roly , Mumbengegwi Davis , Kleinschmidt Immo , Smith Jennifer L. , Hubbard Alan , van der Laan Mark , Hsiang Michelle S. 
Published: September 2023

AbstractMalaria elimination interventions in low-transmission settings aim to extinguish hot spots and prevent transmission to nearby areas. In malaria elimination settings, the World Health Organization recommends reactive, focal interventions targeted to the area near malaria cases shortly after they are detected. A key question is whether these interventions reduce transmission to nearby uninfected or asymptomatic individuals who did not receive interventions. Here, we measured direct effects (among intervention recipients) and spillover effects (among non-recipients) of reactive, focal interventions delivered within 500m of confirmed malaria index cases in a cluster-randomized trial in Namibia. The trial delivered malaria chemoprevention (artemether lumefantrine) and vector control (indoor residual spraying with Actellic) separately and in combination using a factorial design. We compared incidence, infection prevalence, and seroprevalence between study arms among intervention recipients (direct effects) and non-recipients (spillover effects) up to 3 km away from index cases. We calculated incremental cost-effectiveness ratios accounting for spillover effects. The combined chemoprevention and vector control intervention produced direct effects and spillover effects. In the primary analysis among non-recipients within 1 km from index cases, the combined intervention reduced malaria incidence by 43% (95% CI 20%, 59%). In secondary analyses among non-recipients 500m-3 km from interventions, the combined intervention reduced infection by 79% (6%, 95%) and seroprevalence 34% (20%, 45%). Accounting for spillover effects increased the cost-effectiveness of the combined intervention by 37%. Our findings provide the first evidence that targeting hot spots with combined chemoprevention and vector control interventions can indirectly benefit non-recipients up to 3 km away.Significance StatementIn settings where malaria transmission is declining and approaching elimination, new malaria cases are clustered in space and time. Prior studies have found that targeting prophylactic antimalarial drugs and vector control in the area around newly detected malaria cases reduced community-wide malaria. Here, we found that when antimalarials and vector control were delivered as a combined strategy in the area near recent cases, malaria incidence was reduced up to 3 kilometers away among individuals who did not receive interventions. Accounting for these benefits to non-recipients increased cost-effectiveness of the intervention. Overall, our findings suggest that combined, targeted malaria interventions can reduce local transmission and support their use for malaria elimination.
USP48/USP31 Is a Nuclear Deubiquitinase that Potently Regulates Synapse Remodeling
Authors: Ma Qi , Ruan Hongyu , Dai Huihui , Yao Wei-Dong 
Published: September 2023

AbstractDeubiquitinases present locally at synapses regulate synaptic development, function, and plasticity. It remains largely unknown, however, whether deubiquitinases localized outside of the synapse control synapse remodeling. Here we identify ubiquitin specific protease 48 (USP48; formerly USP31) as a nuclear deubiquitinase mediating robust synapse removal. USP48 is expressed primarily during the first postnatal week in the rodent brain and is virtually restricted to nuclei, mediated by a conserved, 13-amino acid nuclear localization signal. When exogenously expressed, USP48, in a deubiquitinase and nuclear localization-dependent manner, induces striking filopodia elaboration, marked spine loss, and significantly reduced synaptic protein clustering in vitro, and erases ∼70% of functional synapses in vivo. USP48 interacts with the transcription factor NF-κB, deubiquitinates NF-κB subunit p65 and promotes its stability and activation, and up-regulates NF-κB target genes known to inhibit synaptogenesis. Depleting NF-κB prevents USP48-dependent spine pruning. These findings identify a novel nucleus-enriched deubiquitinase that plays critical roles in synapse remodeling.
Characteristics and functions of infection-enhancing antibodies to the N-terminal domain of SARS-CoV-2
Authors: Connor Ruth I. , Sakharkar Mrunal , Rappazzo C. Garrett , Kaku Chengzi I. , Curtis Nicholas C. , Shin Seungmin , Wieland-Alter Wendy F. , Weiner Joshua A. , Ackerman Margaret E. , Walker Laura M. , Lee Jiwon , Wright Peter F. 
Published: September 2023

ABSTRACTCharacterization of functional antibody responses to the N-terminal domain (NTD) of the SARS-CoV-2 spike (S) protein has included identification of both potent neutralizing activity and putative enhancement of infection. Fcγ-receptor (FcγR)-independent enhancement of SARS-CoV-2 infection mediated by NTD-binding monoclonal antibodies (mAbs) has been observedin vitro, but the functional significance of these antibodiesin vivois not clear. Here we studied 1,213 S-binding mAbs derived from longitudinal sampling of B-cells collected from eight COVID-19 convalescent patients and identified 72 (5.9%) mAbs that enhanced infection in a VSV-SARS-CoV-2-S-Wuhan pseudovirus (PV) assay. The majority (68%) of these mAbs recognized the NTD, were identified in patients with mild and severe disease, and persisted for at least five months post-infection. Enhancement of PV infection by NTD-binding mAbs was not observed using intestinal (Caco-2) and respiratory (Calu-3) epithelial cells as infection targets and was diminished or lost against SARS-CoV-2 variants of concern (VOC). Proteomic deconvolution of the serum antibody repertoire from two of the convalescent subjects identified, for the first time, NTD-binding, infection-enhancing mAbs among the circulating immunoglobulins directly isolated from serum (i.e., functionally secreted antibody). Functional analysis of these mAbs demonstrated robust activation of FcγRIIIa associated with antibody binding to recombinant S proteins. Taken together, these findings suggest functionally active NTD-specific mAbs arise frequently during natural infection and can last as major serum clonotypes during convalescence. These antibodies display diverse attributes that include FcγR activation, and may be selected against by mutations in NTD associated with SARS-CoV-2 VOC.
Immunogenicity and Efficacy of TNX-1800, A Live Virus Recombinant Poxvirus Vaccine Candidate, Against SARS-CoV-2 Challenge in Nonhuman Primates
Authors: Awasthi Mayanka , Macaluso Anthony , Myscofski Dawn , Prigge Jon , Koide Fusataka , Noyce Ryan S , Fogarty Siobhan , Stillwell Helen , Goebel Scott J , Daugherty Bruce , Nasar Farooq , Bavari Sina , Lederman Seth 
Published: September 2023

AbstractTNX-1800 is a synthetically derived live chimeric Horsepox Virus (rcHPXV) vaccine expressing Wuhan SARS-CoV-2 spike (S) protein. The primary objective of this study was to evaluate the immunogenicity and efficacy of TNX-1800 in two nonhuman primate species challenged with USA-WA1/2020 SARS-CoV-2. TNX-1800 vaccination was well tolerated, as indicated by the lack of serious adverse events or significant changes in clinical parameters. A single dose of TNX-1800 generated robust humoral responses in African Green Monkeys and Cynomolgus Macaques, as measured by the total binding anti-SARS-CoV-2 S IgG and neutralizing antibody titers against the USA-WA1/2020 strain. In Cynomolgus Macaques, a single dose of TNX-1800 induced a strong interferon-gamma (IFN-γ) mediated T cell response, promoting both pathogen clearance in the upper and lower airways and generation of systemic neutralizing antibody response against WA strain SARS-CoV-2. Future studies will assess the efficacy of TNX-1800 against newly emerging variants and demonstrate its safety in humans.
Exportin 1 is required for the reproduction and maize mosaic virus accumulation in its insect vectorPeregrinus maidis
Authors: Xavier Cesar A. D. , Tyson Clara , Kerner Leo M. , Whitfield Anna E. 
Published: September 2023

ABSTRACTExportin 1 (XPO1) is the major karyopherin-β nuclear receptor mediating the nuclear export of hundreds of proteins and some classes of RNA and regulates several critical processes in the cell, including but not limited to, cell-cycle progression, transcription, translation, oncogenesis and longevity. Viruses have co-opted XPO1 to promote nucleocytoplasmic transport of viral proteins and RNA. Maize mosaic virus (MMV) is anAlphanucleorhabdovirustransmitted in a circulative propagative manner by the corn planthopper,Peregrinus maidis. MMV replicates in the nucleus of plant and insect hosts, and it remains unknown whether MMV co-optsP. maidis XPO1(PmXPO1) to complete its life cycle. Because XPO1 plays multiple regulatory roles in cell functions and virus infection, we hypothesized that RNAi-mediated silencing ofXPO1would simultaneously and negatively affect MMV accumulation and insect physiology. AlthoughPmXPO1expression was not modulated during MMV infection,PmXPO1knockdown negatively affected MMV accumulation inP. maidisat 12 and 15 days after microinjection. Likewise,PmXPO1knockdown negatively affectedP. maidissurvival and reproduction.PmXPO1exhibited tissue specific expression patterns with higher expression in the ovaries compared to the guts of adult females. Survival rate was significantly lower forPmXPO1knockdown females, compared to controls, but no effect was observed for males. Adult females withPmXPO1knockdown were heavier and had a larger abdomen compared to controls at 4, 8 and 12 days after dsRNA microinjection. Consistent with an increase in weight, glyceride content specifically and significantly increased inPmXPO1knockdown female planthoppers. Ovary development was significantly inhibited, and mature eggs were not observed in adult females withPmXPO1knockdown. Consistent with a major role ofPmXPO1 in ovary function and egg production, oviposition and egg hatch in plants was dramatically reduced in dsRNAPmXPO1treated insects compared with control. Altogether, these results suggest thatPmXPO1is a positive regulator ofP. maidisreproduction and that it plays a proviral role in the insect vector supporting MMV infection.
Sex dimorphism in the aged metabolic phenotype of smoothelin-like 1 (SMTNL1) deficient mice
Authors: Murali Megha , Alabi Nikolay , Chelikani Prasanth K. , MacDonald Justin A. 
Published: September 2023

ABSTRACTSmoothelin-like 1 (SMTNL1) is expressed in smooth and skeletal muscle tissues as well as a variety of steroid hormone-sensitive tissues. SMTNL1 can play a sex-dependent regulatory role in skeletal muscle metabolism in mice. Previous studies have documented appreciable changes in muscle morphology and metabolic function of young male mice with genetic deletion ofSmtnl1. SMTNL1 can also impact the energy metabolism and insulin sensitivity of female mice during pregnancy. Therefore, we investigated the metabolic outcome of global SMTNL1 knockout (KO) in male and female mice with advancing age using a comprehensive lab animal monitoring system (CLAMS). With ageing, body weight gain was markedly higher with a concomitant increase in whole body adiposity as well as specific white adipose depots in the absence of SMTNL1. Moreover, this genotypic difference in whole body adiposity was greater in the female cohort. The deletion of SMTNL1 was also associated with delayed satiety in mice fed a high fat diet, which was more pronounced in the female mice. A significant genotypic difference was also revealed for the metabolic energy balance in 12 month old animals of both sexes. The KO animals were metabolically less efficient and displayed a preference for carbohydrate catabolism. However, reduced glucose tolerance was observed only in the female group with the deletion of SMTNL1. Taken together, the current findings establish a novel role for SMTNL1 in modulating adiposity and energy metabolism with ageing in a sex dimorphic way.
A role for the ATP-dependent DNA ligase Lig E ofNeisseria gonorrhoeaein biofilm formation
Authors: Pan Jolyn , Hicks Joanna , Williamson Adele 
Published: September 2023

ABSTRACTThe ATP-dependent DNA ligase Lig E is present as an accessory DNA ligase in numerous proteobacterial genomes, including many disease-causing species. Here we have constructed a genomic Lig E knock-out in the obligate human pathogenNeisseria gonorrhoeaeand characterised its growth and infection characteristics. This demonstrates thatN. gonorrhoeaeLig E is a non-essential gene and its deletion does not cause defects in replication or survival of DNA-damaging stressors. Knock-out strains were partially defective in biofilm formation on an artificial surface as well as adhesion to epithelial cells which coupled with the predicted extracellular/ periplasmic location of Lig E indicates a role in extracellular DNA joining. In addition toin vivocharacterisation, we have recombinantly expressed and assayedN. gonorrhoeaeLig E and determined the crystal structure of the enzyme-adenylate engaged with DNA substrate in an open non-catalytic conformation, providing insight into the binding dynamics of these minimal DNA ligases.
Serotonin predictively encodes value
Authors: Harkin Emerson F. , Grossman Cooper D. , Cohen Jeremiah Y. , Béïque Jean-Claude , Naud Richard 
Published: September 2023

AbstractThein vivoresponses of dorsal raphe nucleus (DRN) serotonin neurons to emotionally-salient stimuli are a puzzle. Existing theories centred on reward, surprise, or uncertainty individually account for some aspects of serotonergic activity but not others. Here we find a unifying perspective in a biologically-constrained predictive code for cumulative future reward, a quantity called state value in reinforcement learning. Through simulations of trace conditioning experiments common in the serotonin literature, we show that our theory, called value prediction, intuitively explains phasic activation by both rewards and punishments, preference for surprising rewards but absence of a corresponding preference for punishments, and contextual modulation of tonic firing—observations that currently form the basis of many and varied serotonergic theories. Next, we re-analyzed data from a recent experiment and found serotonin neurons with activity patterns that are a surprisingly close match: our theory predicts the marginal effect of reward history on population activity with a precision ≪0.1 Hz neuron−1. Finally, we directly compared against quantitative formulations of existing ideas and found that our theory best explains both within-trial activity dynamics and trial-to-trial modulations, offering performance usually several times better than the closest alternative. Overall, our results show that previous models are not wrong, but incomplete, and that reward, surprise, salience, and uncertainty are simply different faces of a predictively-encoded value signal. By unifying previous theories, our work represents an important step towards understanding the potentially heterogeneous computational roles of serotonin in learning, behaviour, and beyond.
Age-related STAT3 signaling regulates severity of respiratory syncytial viral infection in human bronchial epithelial cells
Authors: Zhao Caiqi , Wang Wei , Bai Yan , Amonkar Gaurang , Mou Hongmei , Olejnik Judith , Hume Adam J , Mühlberger Elke , Fang Yinshan , Que Jianwen , Fearns Rachel , Ai Xingbin , Lerou Paul H. 
Published: September 2023

SUMMARYRespiratory syncytial virus (RSV) can cause severe disease especially in infants; however, mechanisms of age-associated disease severity remain elusive. Here, employing human bronchial epithelium models generated from tracheal aspirate-derived basal stem cells of neonates and adults, we investigated whether age regulates RSV-epithelium interaction to determine disease severity. We show that following RSV infection, only neonatal epithelium model exhibited cytopathy and mucus hyperplasia, and neonatal epithelium had more robust viral spread and inflammatory responses than adult epithelium. Mechanistically, RSV-infected neonatal ciliated cells displayed age-related impairment of STAT3 activation, rendering susceptibility to apoptosis, which facilitated viral spread. In contrast, SARS-CoV-2 infection of ciliated cells had no effect on STAT3 activation and was not affected by age. Taken together, our findings identify an age-related and RSV-specific interaction with neonatal bronchial epithelium that critically contributes to severity of infection, and STAT3 activation offers a potential strategy to battle severe RSV disease in infants.
Causal evidence of coherent theta rhythms in the modulation of multiregional brain communication
Authors: Ferraro Gino Del , Qiao Shaoyu , Sedillo J. Isaac , Pesaran Bijan 
Published: September 2023

AbstractNeuromodulatory interventions seek to treat neuropsychiatric disorders by manipulating multiregional communication across the mesolimbic mood network. Modulations of multiregional communication are rarely measured directly and are often inferred from correlated neural activity such as neural coherence. Whether and how neural coherence reflects dynamic multiregional communication remains unclear. To address this limitation, we performed a causal-correlation analysis of theta-frequency (4-10 Hz) rhythms and mesolimbic multiregional communication. Selectively stimulating sender sites while recording from receiver sites revealed a mechanism of dynamic multiregional communication involving theta-coherent neural dynamics across a network of sender-receiver-modulator sites. Modulator site activity was highly theta-coherent with the receiver site activity, less theta-coherent with sender site activity, site specific and not shared by neighboring sites in the same region. These results reveal fundamental mechanisms of dynamic multiregional communication and support the use of theta-coherence as a target for neuromodulatory interventions in the mesolimbic mood network.
The CASwitch: a synthetic biology solution for high-performance inducible gene expression systems in biotechnology
Authors: De Carluccio Giuliano , Fusco Virginia , di Bernardo Diego 
Published: September 2023

AbstractInducible gene expression systems can be used to control the expression of a gene of interest by means of a small-molecule. One of the most common designs involves engineering a small-molecule responsive transcription factor (TF) and its cognate promoter, which often results in a compromise between minimal uninduced background expression (leakiness) and maximal induced expression. Here, we focussed on an alternative strategy using quantitative synthetic biology to mitigate leakiness while maintaining high expression, without modifying neither the TF nor the promoter. Through mathematical modelling and experimental validations, we designed the CASwitch, a mammalian synthetic gene circuit based on combining two well-known network motifs: the Coherent Feed-Forward Loop (CFFL) and the Mutual Inhibition (MI). The CASwitch combines the CRISPR-Cas endoribonuclease CasRx with the state-of-the-art Tet-On3G inducible gene system to achieve high performances. To demonstrate the potentialities of the CASwitch, we applied it to three different scenarios: enhancing a whole-cell biosensor, controlling expression of a toxic gene and inducible production of Adeno-Associated Virus (AAV) vectors.
Loss of cilia after neurulation impacts brain development and neuronal activity in larval zebrafish
Authors: D’Gama Percival P. , Jeong Inyoung , Nygård Andreas Moe , Trinh Anh-Tuan , Yaksi Emre , Jurisch-Yaksi Nathalie 
Published: September 2023

ABSTRACTCilia are slender, hair-like structures extending from cell surfaces and playing essential roles in diverse physiological processes. Within the nervous system, primary cilia contribute to signaling and sensory perception, while motile cilia facilitate cerebrospinal fluid flow. Here, we investigated the impact of ciliary loss on neural circuit development using a zebrafish line displaying ciliogenesis defects. We found that cilia loss after neurulation affects neurogenesis and brain morphology, and lead to altered gene expression profiles. Using whole brain calcium imaging, we measured reduced light-evoked and spontaneous neuronal activity in all brain regions. By shedding light on the intricate role of cilia in neural circuit formation and function in the zebrafish, our work highlights their evolutionary conserved role in the brain and set the stage for future analysis of ciliopathy models.