bluuebunny/crossref_metadata_2025_split huggingface dataset:
Within-host rates of insertion and deletion in the HIV-1 surface envelope glycoprotein
Authors: Palmer John , Novitsky Vlad , Ferreira Roux-Cil , Poon Art F. Y. 
Published: September 2023

AbstractUnder selection by neutralizing antibodies, the HIV-1 envelope glycoprotein gp120 undergoes rapid evolution within hosts, particularly in regions encoding the five variable loops (V1-V5). Indel polymorphisms are abundant in these loops, where they can facilitate immune escape by modifying the length, composition and glycosylation profile of these structures. Here, we present a comparative analysis of within-host indel rates and characteristics within the variable regions of gp120. We analyzed a total of 3,437 HIV-1 gp120 sequences sampled longitudinally from 29 different individuals using coalescent models in BEAST. Next, we used Historian to reconstruct ancestral sequences from the resulting tree samples, and fit a Poisson generalized linear model to the distribution of indel events to estimate their rates in the five variable loops. Overall, the mean insertion and deletion rates were 1.6 × 10−3and 2.5 × 10−3/ nt / year, respectively, with significant variation among loops. Insertions and deletions also followed similar length distributions, except for significantly longer indels in V1 and V4 and shorter indels in V5. Insertions in V1, V2, and V4 tended to create new N-linked glycosylation sites significantly more often than expected by chance, which is consistent with positive selection to alter glycosylation patterns.
Human force control may trade-off force error with central tendency and recency biases
Authors: Ryu Hansol X. , Srinivasan Manoj 
Published: September 2023

AbstractUnderstanding how humans control force is useful for understanding human movement behaviors and sensorimotor control. However, it is not well understood how the human nervous system handles different control criteria such as accuracy and energetic cost. We conducted force tracking experiments where participants applied force isometrically while receiving visual force feedback, tracking step changes in target forces. The experiments were designed to disambiguate different plausible objective function components. We found that force tracking error was largely explained by a trade-off between error-reducing tendency and force biases, but we did not need to include an effort-saving tendency. Central tendency bias, which is a shift towards the center of the task distribution, and recency bias, which is a shift towards recent action, were necessary to explain many of our observations. Surprisingly, we did not observe such biases when we removed force requirements for pointing to the target, suggesting that such biases may be task-specific. This study provides insights into the broader field of motor control and human perceptions where behavioral or perceptual biases are involved.
The larva and adult ofHelicoverpa armigerause differential gustatory receptors to sense sugars
Authors: Zhang Shuai-Shuai , Wang Pei-Chao , Ning Chao , Yang Ke , Li Guo-Cheng , Cao Lin-Lin , Huang Ling-Qiao , Wang Chen-Zhu 
Published: September 2023

AbstractAlmost all herbivorous insects feed on plants and use sucrose as a feeding stimulant, but the molecular basis of their sucrose reception remains unclear.Helicoverpa armigeraas a notorious crop pest worldwide mainly feeds on reproductive organs of many plant species in the larval stage, and its adult draws nectar. In this study, we determined that the sucrose sensory neurons located in the contact chemosensilla of larval maxillary galeae were 100–1000 times more sensitive to sucrose than those of adult antennae, tarsi and proboscis. Using theXenopusexpression system, we discovered that Gr10 highly expressed in the larval sensilla was specifically tuned to sucrose, while Gr6 highly expressed in the adult sensilla responded to fucose, sucrose and fructose. Moreover, using CRISPR/Cas9, we revealed that Gr10 was mainly used by larvae to detect lower sucrose, while Gr6 was primarily used by adults to detect higher sucrose and other saccharides, which results in differences in selectivity and sensitivity between larval and adult sugar sensory neurons. Our results demonstrate the sugar receptors in this moth are evolved to adapt towards the larval and adult foods with different types and amounts of sugar, and fill in a gap in sweet taste of animals.
Etifoxine inhibits NLRP3 inflammasome activity in human and murine myeloid cells
Authors: Osmond Jordan M. , Williams John B. , Matthews Paul M. , Owen David R. , Moore Craig S. 
Published: September 2023

ABSTRACTBackgroundMultiple sclerosis (MS) is a chronic neuroinflammatory disease that is characterized by immune-mediated demyelination within the central nervous system. NLRP3 inflammasome activation has been previously reported as a possible pathophysiological contributor to microglial activation and oligodendroglial loss in MS, particularly in progressive forms of the disease.MethodsUsing bothin vivoandin vitroapproaches, this report investigated the use of a previously described ligand of the 18kDa translocator protein (TSPO), etifoxine, as an immunomodulator that inhibits inflammasome activation in primary human and murine macrophages and microglia. To further elucidate pathologic relevance in the MS context, investigations were also performedex vivousing peripheral blood mononuclear cells and purified CD14+monocytes derived from secondary progressive MS patients.ResultsHerein, it is demonstrated that etifoxine attenuated clinical symptoms in a mouse model of MS and significantly inhibited NLRP3 inflammasome activation in human and murine myeloid-derived cellsin vitroby decreasing inflammasome-associated genes and inflammatory cytokine production. These anti-inflammatory effects of etifoxine were mediated independently of its previously described mechanisms related to engagement with TSPO and the GABAAreceptor. Furthermore, we observed a similar anti-inflammatory effect of etifoxine on MS patient-derived monocytes, which provides clinical relevance for the investigation of etifoxine as a potential therapeutic in progressive MS. Lastly, through the use of a gene array, we identified multiple signalling pathways in order to elucidate a novel mechanism whereby etifoxine may be inhibiting NLRP3 inflammasome activation.ConclusionsOur results suggest that the anti-inflammatory effects of etifoxine were mediated independently of its previously described mechanisms related to engagement with TSPO and the GABAAreceptor. Furthermore, we observed an anti-inflammatory effect in murine- and human-derived myeloid cells, as well as in MS patient-derived monocytes, which provides clinically relevant evidence to support the exploration of etifoxine as a possible form of therapy for secondary progressive MS.
Inverted transflection spectroscopy of live cells using metallic grating on elevated nanopillars
Authors: Mahalanabish Aditya , Huang Steven H. , Shvets Gennady 
Published: September 2023

ABSTRACTWater absorption of mid-infrared (MIR) radiation severely limits the options for vibrational spectroscopy of the analytes – including live biological cells – that must be probed in aqueous environments. While internal reflection elements, such as attenuated total reflection prisms and metasurfaces, partially overcome this limitation, such devices have their own limitations: high cost, incompatibility with standard cell culture workflows, limited spectral range, and small penetration depth into the analyte. In this work, we introduce an alternative live cell biosensing platform based on metallic nanogratings fabricated atop elevated dielectric pillars. For the MIR wavelengths that are significantly longer than the grating period, reflection-based spectroscopy enables broadband sensing of the analytes inside the trenches separating the dielectric pillars. Because the depth of the analyte twice-traversed by the MIR light excludes the highly absorbing thick water layer above the grating, we refer to the technique as Inverted Transflection Spectroscopy (ITS). We demonstrate the analytic power of ITS by measuring protein concentrations in solution. The ability of ITS to interrogate live cells that naturally wrap themselves around the grating is also exploited to characterize their adhesion kinetics.
Crop improvement can accelerate agriculture adaptation to societal demands and climate change
Authors: Messina Carlos D , Borras Lucas , Tang Tom , Cooper Mark 
Published: September 2023

AbstractA key question today is how to harmonize future crop improvement efforts for regenerative cropping systems that can mitigate further environmental degeneration and improve societal adaptation to climate change. Here we show that the US corn-belt based maize improvement system has been adapting to the changing climate. Analyses of the longest running field experiment (1990-2021) designed to quantify yield gains (37 hybrids sold from 1930 to 1990) demonstrate that rates of genetic gain were always positive and have increased over time (from 70 to 150 kg ha-1y-1in 1990 and 2021, respectively). Between 1930 and 2021 for the May through October period total rainfall for the U.S. corn belt increased 113 mm, and daily temperature amplitude decreased 1.3°C. At the same time, farmers modified their farming practices, helping modern hybrids to out-perform their older counterparts by a larger degree. In contrast to the conclusions reached by other observational studies, genetic gain estimates demonstrate that maize breeding and the production system are adapting to modern scenarios. Climate change is commonly linked to fears of food insecurity, but new cropping systems capable of providing food while regenerating resources such as water, the circularization of nutrients, and reduction of greenhouse gas emissions are possible.
PHYLOGENETIC ANALYSIS OF THErfbLOCUS GENES OF THE GENUSLeptospiraOF SEROGROUPS SERJOE, MINI AND HEBDOMADIS
Authors: Barros Setúbal Ruth Flávia , de Santana Souza Jorge Estefano , Venturim Cosate Maria Raquel , Sakamoto Tetsu 
Published: September 2023

AbstractLeptospirosis is a zoonosis of great impact on public health since it is considered a notifiable disease occurring mainly in tropical regions with poor sanitation and vulnerable socioeconomic conditions. It is caused by bacteria of the genus Leptospira and phylum Spirochaetes and contamination occurs through direct or indirect contact with the contaminating agent. In addition to taxonomic classification, which is performed through sequencing and the analysis of some marker genes, such as 16S rRNA andsecY, they are usually classified based on their antigenic characteristics into serogroups and serovars. This kind of classification is largely applied in epidemiological studies and vaccine development. Despite its importance, few studies have been conducted to understand the evolutionary dynamics of the emergence or change of serology in this genus. In view of this, we applied phylogenetic methods in order to understand the evolutionary processes involving the serology of the genus. To this end, sequences of genes comprising therfblocus from samples of serogroups Sejroe, Mini, and Hebdomadis (34 samples) were extracted and submitted to the phylogenetic pipeline, resulting in the inference of 75 maximum likelihood trees. Topology tests showed that most of the gene trees are significantly different from the species tree. We could depict the occurrence of lateral gene transfer betweenL. borgpeterseniiandL. kirschneri; andL. interrogansandL. weilli. In this analysis, no evidence was found for the lateral gene transfer between samples of the Hardjo serovar ofL. interrogansandL. borgpetersenii. Thus, it is also suggested that the occurrence of horizontal transfer of genes from therfblocus between distinct species is less frequent than expected.
Consistent specificity and efficiency of tamoxifen-mediated cre induction across ages
Authors: Kellogg Collyn M. , Pham Kevin , Ko Sunghwan , Cox Jillian E. J. , Machalinski Adeline H. , Stout Michael B. , Sharpe Amanda L. , Beckstead Michael J. , Chucair-Elliott Ana J. , Ocañas Sarah R. , Freeman Willard M. 
Published: September 2023

SummaryTemporally controlling cre recombination through tamoxifen (Tam) induction has many advantages for biomedical research. Most studies report Tam induction at early post-natal/juvenile (<2 m.o.) mouse ages, but age-related neurodegeneration and aging studies can require cre induction in older mice (>12 m.o.). While anecdotally reported as problematic, there are no published comparisons of Tam mediated cre induction at early and late ages. Here, microglial-specific Cx3cr1creERT2mice were crossed to a floxed NuTRAP reporter to compare cre induction at early (3-6 m.o.) and late (20 m.o.) ages. Specificity and efficiency of microglial labeling at 21-22 m.o. were identical in mice induced with Tam at 3-6 m.o. or 20 m.o. of age. Age-related microglial translatomic changes were also similar regardless of Tam induction age. Each cre and flox mouse line should be validated independently, however, these findings demonstrate that Tam-mediated cre induction can be performed even into older mouse ages.
Leukemic mutation FLT3-ITD is retained in dendritic cells and disrupts their homeostasis leading to expanded Th17 frequency
Authors: Flynn Patrick A , Long Mark D , Kosaka Yoko , Mulkey Jessica S , Coy Jesse L , Agarwal Anupriya , Lind Evan F 
Published: September 2023

AbstractDendritic cells (DC) are mediators of adaptive immune responses to pathogens and tumors. DC development is determined by signaling through the receptor tyrosine kinase Fms-like tyrosine kinase 3 (FLT3) in bone marrow myeloid progenitors. Recently the naming conventions for DC phenotypes have been updated to distinguish between “Conventional” DCs (cDCs) and plasmacytoid DCs (pDCs). Activating mutations of FLT3, including Internal Tandem Duplication (FLT3-ITD), are associated with poor prognosis for leukemia patients. To date, there is little information on the effects of FLT3-ITD in DC biology. We examined the cDC phenotype and frequency in bone marrow aspirates from patients with acute myeloid leukemia (AML) to understand the changes to cDCs associated with FLT3-ITD. When compared to healthy donor (HD) we found that a subset of FLT3-ITD+ AML patient samples have overrepresented populations of cDCs and disrupted phenotypes. Using a mouse model of FLT3-ITD+ AML, we found that cDCs were increased in percentage and number compared to control wild-type (WT) mice. Single cell RNA-seq identified FLT3-ITD+ cDCs as skewed towards a cDC2 T-bet-phenotype, previously shown to promote Th17 T cells. We assessed the phenotypes of CD4+ T cells in the AML mice and found significant enrichment of both Treg and Th17 CD4+ T cells. Furthermore, co-culture of AML mouse- derived DCs and naïve OT-II cells preferentially skewed T cells into a Th17 phenotype. Together, our data suggests that FLT3-ITD+ leukemia-associated cDCs polarize CD4+ T cells into Th17 subsets, a population that has been shown to be negatively associated with survival in solid tumor contexts. This illustrates the complex tumor microenvironment of AML and highlights the need for further investigation into the effects of FLT3-ITD mutations on DC phenotypes.
A fine-scale genetic map of the Japanese population
Authors: Takayama Jun , Makino Satoshi , Funayama Takamitsu , Ueki Masao , Narita Akira , Murakami Keiko , Orui Masatsugu , Ishikuro Mami , Obara Taku ,   the Tohoku Medical Megabank Project Study Group, Kuriyama Shinichi , Yamamoto Masayuki , Tamiya Gen 
Published: September 2023

AbstractGenetic maps are fundamental resources for linkage and association studies. A fine-scale genetic map can be constructed by inferring historical recombination events from the genome-wide structure of linkage disequilibrium—a non-random association of alleles among loci—by using population-scale sequencing data. We constructed a fine-scale genetic map and identified recombination hotspots from 10,092,573 bi-allelic high-quality autosomal markers segregating among 150 unrelated Japanese individuals. These individuals’ genotypes were determined by high-coverage (30×) whole-genome sequencing, and the genotype quality was carefully controlled by using their parents’ and offspring’s genotypes. The pedigree information was also utilized for haplotype phasing. The resulting genome-wide recombination rate profiles were concordant with those of the HapMap worldwide population on a broad scale, and the resolution was much improved. We identified 9487 recombination hotspots and confirmed the enrichment of previously known motifs in the hotspots. Moreover, we demonstrated that the Japanese genetic map improved the haplotype phasing and genotype imputation accuracy for the Japanese population. The construction of a population-specific genetic map will help make genetics research more accurate.
Measuring Depression, and Its Association with Substance Use, during an Adherence Study of Patients Treated for Tuberculosis in Haitian Prisons
Authors: Ekwebelem Lovette C. , Bury Margarette R. , Prophete Edwin J. , Duverger Karine , Bircher Patrick M. , Spaulding Anne C. 
Published: September 2023

AbstractPurposeDiagnosed depression is prevalent in prisons of affluent countries; literature on depression screening in prisons of low-resource nations is sparse. Haiti has experienced multiple recent disasters, which could have both somatic and mental health consequences. To surveil its prisons for depression, ethnoculturally appropriate scales could be helpful.Design/methodology/approachWe performed a cross-sectional analysis of symptoms of depression and its associations among participants in a 2019-2020 tuberculosis treatment adherence project across 6 Haitian prisons. To measure depression, we piloted the use of the Zanmi-Lasante Depression Symptom Inventory (ZLDSI) scale in a carceral setting. We calculated its Cronbach alpha in this setting and generated binary logistic models to study the associations of depression with basic demographic variables; use of cigarettes, marijuana, and alcohol; and incarceration history. We then performed a multivariate logistic regression to determine if substance use and education predicted depression, after adjusting for age.FindingsFifty subjects were recruited; age ranged from 18 to 59 years. Adherence to TB medication was recorded as above 99% in all subjects. The Cronbach alpha score for the ZLDSI scale in this population was 0.77, signifying the good fit of the scale for this population. A ZLDSI score ≥13.0 has been associated with depression; 66% of participants had scores of 13.0 or greater, mean 13.9 (S.D. 8.2). Multivariate analysis showed significant associations between depression, alcohol consumption, age, and income.Originality/ConclusionWe believe this study represents the first measurement of depressive symptoms in a Haitian prison population; it found symptoms common.
Healthcare system barriers impacting the care of Canadians with myalgic encephalomyelitis: a scoping review
Authors: Hussein Said , Eiriksson Lauren , MacQuarrie Maureen , Merriam Scot , Dalton Maria , Stein Eleanor , Twomey Rosie 
Published: September 2023

AbstractBackgroundMyalgic encephalomyelitis (ME, also known as chronic fatigue syndrome or ME/CFS) is a debilitating, complex, multi-system illness. Developing a comprehensive understanding of the multiple and interconnected barriers to optimal care will help advance strategies and care models to improve quality of life for people living with ME in Canada.ObjectivesTo: (1) identify and systematically map the available evidence; (2) investigate the design and conduct of research; (3) identify and categorize key characteristics; and (4) identify and analyze knowledge gaps related to healthcare system barriers for people living with ME in Canada.MethodsThe protocol was preregistered in July 2022. Peer-reviewed and grey literature was searched, and patient partners retrieved additional records. Eligible records were Canadian, included people with ME/CFS and included data or synthesis relevant to healthcare system barriers.ResultsIn total, 1821 records were identified, 406 were reviewed in full, and 21 were included. Healthcare system barriers arose from an underlying lack of consensus and research on ME and ME care; the impact of long-standing stigma, disbelief, and sexism; inadequate or inconsistent healthcare provider education and training on ME; and the heterogeneity of care coordinated by family physicians.ConclusionsPeople living with ME in Canada face significant barriers to care, though this has received relatively limited attention. This synthesis, which points to several areas for future research, can be used as a starting point for researchers, healthcare providers and decision-makers who are new to the area or encountering ME more frequently due to the COVID-19 pandemic.FundingThis study was funded by the University of Calgary (VPR Catalyst Grant) and the Interdisciplinary Canadian Collaborative ME (ICanCME) Research Network (New Frontier ME Discovery Grant).
Texture-based Probability Mapping in cardiac LGE Images: A novel automatic assessment of myocardial injury following revascularized STEMI
Authors: Frøysa Vidar , Berg Gøran J. , Singsaas Erlend , Eftestøl Trygve , Woie Leik , Ørn Stein 
Published: September 2023

AbstractBackgroundScar size is critical to left ventricular (LV) remodeling and adverse outcomes following myocardial infarction (MI). Late Gadolinium-enhancement (LGE) in cardiac magnetic resonance imaging is the gold standard for assessing MI size. Texture-based probability mapping (TPM) is a novel machine learning-based analysis of LGE images. This proof-of-concept study investigates the potential clinical implications of temporal changes in TPM during the first year following an acute revascularized MI.Methods41 patients with first-time acute ST-elevation MI were included in this study. All patients had a single-vessel disease and were successfully revascularized by primary percutaneous coronary intervention. LGE images were obtained two days, one week, two months, and one year post-MI. MI size by TPM was compared with manual LGE-based MI calculation, LV remodeling, and biomarkers.ResultsTPM showed a significant increase in infarct size from the second month through the first year (p<0.01). MI size estimated by TPM at all different time points demonstrated strong correlations with peak Troponin T levels. At one week, TPM assessment correlated positively with maximum C-reactive protein (r=0.54, p<0.01), and at two months, TPM positively correlated with N-Terminal Pro Brain Natriuretic Peptide.ConclusionThis proof-of-concept study suggests that TPM may provide additional information to conventional LGE-based MI analysis of scar formation, LV remodeling, and biomarkers following an acute revascularized MI.HighlightsTexture-based probability mapping (TPM) was used to analyze consecutive cardiac magnetic resonance images acquired during the first year after ST-elevation myocardial infarction (STEMI).TPM size was related to biomarkers of inflammation, myocardial injury and stress.TPM is a step toward automatic image processing.