bluuebunny/crossref_metadata_2025_split huggingface dataset:
Desynapsis in potato is caused byStMSH4mutant alleles and leads to either highly uniform unreduced pollen or sterility
Authors: Clot Corentin R. , Klein Dennis , Koopman Joey , Schuit Cees , Engelen Christel J.M. , Hutten Ronald C.B. , Brouwer Matthijs , Visser Richard G.F. , Juranić Martina , van Eck Herman J. 
Published: February 2023

AbstractThe balanced segregation of homologous chromosomes during meiosis is essential for fertility and is mediated by crossovers. A strong reduction of crossovers leads to desynapsis, a process in which pairing of homologous chromosomes is abolished before metaphase I. This results in a random segregation of univalent and the production of unbalanced and sterile gametes. However, if desynapsis is combined with another meiotic alteration that restitutes the first meiotic division, then uniform and balanced unreduced gametes, essentially composed of non-recombinant homologs, are produced. This mitosis-like division is of interest to breeders because it transmits most of the parental heterozygosity to the gametes. In potato, desynapsis is a recessive trait that was tentatively mapped to chromosome8. In this article, we have fine-mapped the position of the desynapsis locus and identifiedStMSH4, an essential component of the class I crossover pathway, as the most likely candidate gene. A seven base-pair insertion in the second exon ofStMSH4was found to be associated with desynapsis in our mapping population. We also identified a second allele with a 3820 base-pair insertion and confirmed that both alleles cannot complement each other. Such non-functional alleles appeared to be common in potato cultivars. More than half of the varieties we tested are carriers of mutational load at theStMSH4locus. With this new information, breeders can choose to remove desynaptic alleles from their germplasm to improve fertility or to use them to produce highly uniform unreduced gametes in alternative breeding schemes.
Single cell and spatial alternative splicing analysis with long read sequencing
Authors: Fu Yuntian , Kim Heonseok , Adams Jenea I. , Grimes Susan M. , Huang Sijia , Lau Billy T. , Sathe Anuja , Hess Paul , Ji Hanlee P. , Zhang Nancy R. 
Published: February 2023

AbstractLong-read sequencing has become a powerful tool for alternative splicing analysis. However, technical and computational challenges have limited our ability to explore alternative splicing at single cell and spatial resolution. The higher sequencing error of long reads, especially high indel rates, have limited the accuracy of cell barcode and unique molecular identifier (UMI) recovery. Read truncation and mapping errors, the latter exacerbated by the higher sequencing error rates, can cause the false detection of spurious new isoforms. Downstream, there is yet no rigorous statistical framework to quantify splicing variation within and between cells/spots. In light of these challenges, we developed Longcell, a statistical framework and computational pipeline for accurate isoform quantification for single cell and spatial spot barcoded long read sequencing data. Longcell performs computationally efficient cell/spot barcode extraction, UMI recovery, and UMI-based truncation- and mapping-error correction. Through a statistical model that accounts for varying read coverage across cells/spots, Longcell rigorously quantifies the level of inter-cell/spot versus intra-cell/ spot diversity in exon-usage and detects changes in splicing distributions between cell populations. Applying Longcell to single cell long-read data from multiple contexts, we found that intra-cell splicing heterogeneity, where multiple isoforms co-exist within the same cell, is ubiquitous for highly expressed genes. On matched single cell and Visium long read sequencing for a tissue of colorectal cancer metastasis to the liver, Longcell found concordant signals between the two data modalities. Finally, on a perturbation experiment for 9 splicing factors, Longcell identified regulatory targets that are validated by targeted sequencing.
The effects of inversion polymorphisms on patterns of neutral genetic diversity
Authors: Charlesworth Brian 
Published: February 2023

AbstractThe strong reduction in the frequency of recombination in heterozygotes for an inversion and a standard gene arrangement causes the arrangements to become partially isolated genetically, resulting in sequence divergence between them and changes in the levels of neutral variability at nucleotide sites within each arrangement class. Previous theoretical studies on the effects of inversions on neutral variability have either assumed that the population is panmictic or that it is divided into two populations subject to divergent selection. Here, the theory is extended to a model of an arbitrary number of demes connected by migration, using a finite island model with the inversion present at the same frequency in all demes. Recursion relations for mean pairwise coalescent times are used to obtain simple approximate expressions for diversity and divergence statistics for an inversion polymorphism at equilibrium under recombination and drift, and for the approach to equilibrium following the sweep of an inversion to a stable intermediate frequency. The effects of an inversion polymorphism on patterns of linkage disequilibrium are also examined. The reduction in effective recombination rate caused by population subdivision can have significant effects on these statistics. The theoretical results are discussed in relation to population genomic data on inversion polymorphisms, with an emphasis onDrosophila melanogaster. Methods are proposed for testing whether or not inversions are close to recombination-drift equilibrium, and for estimating the rate of recombinational exchange in heterozygotes for inversions; difficulties involved in estimating the ages of inversions are also discussed.
Polarimetric response of second harmonic generation in microscopy of chiral fibrillar structures
Authors: Alizadeh Mehdi , Habach Fayez , Maciulis Mykolas , Kontenis Lukas , Bagdonas Saulius , Krouglov Serguei , Baranauskas Vytautas , Bulotiene Danute , Karabanovas Vitalijus , Rotomskis Ricardas , Akens Margarete K. , Barzda Virginijus 
Published: February 2023

AbstractPolarimetric second harmonic generation (SHG) microscopy is employed to study partially oriented fibrillar structures. The polarimetric SHG parameters are influenced by three-dimensional (3D) configuration of C6symmetry fibrilar structures in the focal volume (voxel) of a microscope. The achiral and chiral susceptibility tensor components ratios (R and C, respectively) are extracted from the linear polarization-in polarization-out (PIPO) measurements. The analytical derivations along with the polarimetric SHG microscopy results obtained from rat tail tendon, rabbit cornea, pig cartilage and meso-tetra (4-sulfonatophenyl) porphine (TPPS4) cylindrical aggregates demonstrate that SHG intensity is affected by parallel/antiparallel arrangements of the fibers, and R and C ratio values change by tilting the fibers out of image plane, as well as by crossing the fibers in 2D and 3D. The polarimetric microscopy results are consistent with the digital microscopy modeling of fibrillar structures. These results facilitate the interpretation of polarimetric SHG microscopy images in terms of 3D organization of fibrilar structures in each voxel of the samples.Statement of SignificancePolarimetric second harmonic generation (SHG) microscopy is used to study partially oriented C6symmetry chiral fibrillar structures. The linear polarization-in polarization-out (PIPO) SHG imaging is performed on rat tail tendon, rabbit cornea, pig cartilage tissues and meso-tetra (4-sulfonatophenyl) porphine (TPPS4) cylindrical aggregates. The study demonstrates that SHG intensity is affected by parallel/antiparallel arrangements of the fibers, and the achiral and chiral susceptibility component ratio values change by tilting the fibers out of image plane, as well as by crossing the fibers in 2D and 3D. The polarimetric microscopy results are consistent with the digital microscopy modeling of fibrillar structures. These results facilitate the interpretation of polarimetric SHG microscopy images in terms of 3D organization of fibrillar structures in each voxel of the samples.
Synthetic Cooling Agent in Oral Nicotine Pouch Products Marketed as “Flavor-Ban Approved”
Authors: Jabba Sairam V. , Erythropel Hanno C , Woodrow Jackson G. , Anastas Paul T , O’Malley Stephanie S. , Krishnan-Sarin Suchitra , Zimmerman Julie B , Jordt Sven E. 
Published: February 2023

AbstractBackgroundUS sales of oral nicotine pouches (ONPs) have rapidly increased, with cool/mint-flavored ONPs the most popular. Restrictions on sales of flavored tobacco products have either been implemented or proposed by several US states and localities. Zyn, the most popular ONP brand, is marketing Zyn-”Chill” and Zyn-”Smooth” as “Flavor-Ban Approved”, probably to evade flavor bans. At present it is unclear whether these ONPs are indeed free of flavor additives that can impart pleasant sensations such as cooling.MethodsSensory cooling and irritant activities of “Flavor-Ban Approved” ONPs, Zyn-”Chill” and “Smooth”, along with “minty” varieties (Cool Mint, Peppermint, Spearmint, Menthol), were analyzed by Ca2+ microfluorimetry in HEK293 cells expressing the cold/menthol (TRPM8) or menthol/irritant receptor (TRPA1). Flavor chemical content of these ONPs was analyzed by GC/MS.ResultsZyn-”Chill” ONP extracts robustly activated TRPM8, with much higher efficacy (39-53%) than the mint-flavored ONPs. In contrast, mint-flavored ONP extracts elicited stronger TRPA1 irritant receptor responses than Zyn-”Chill” extracts. Chemical analysis demonstrated the presence of WS-3, an odorless synthetic cooling agent, in Zyn-”Chill” and several other mint-flavored Zyn-ONPsConclusionsSynthetic cooling agents such as WS-3 found in ‘Flavor-Ban Approved’ Zyn-“Chill” can provide a robust cooling sensation with reduced sensory irritancy, thereby increasing product appeal and use. The label “Flavor-Ban Approved” is misleading and may implicate health benefits. Regulators need to develop effective strategies for the control of odorless sensory additives used by the industry to bypass flavor bans.
SEG: Segmentation Evaluation in absence of Ground truth labels
Authors: Sims Zachary , Strgar Luke , Thirumalaisamy Dharani , Heussner Robert , Thibault Guillaume , Chang Young Hwan 
Published: February 2023

ABSTRACTIdentifying individual cells or nuclei is often the first step in the analysis of multiplex tissue imaging (MTI) data. Recent efforts to produce plug-and-play, end-to-end MTI analysis tools such as MCMICRO1– though groundbreaking in their usability and extensibility – are often unable to provide users guidance regarding the most appropriate models for their segmentation task among an endless proliferation of novel segmentation methods. Unfortunately, evaluating segmentation results on a user’s dataset without ground truth labels is either purely subjective or eventually amounts to the task of performing the original, time-intensive annotation. As a consequence, researchers rely on models pre-trained on other large datasets for their unique tasks. Here, we propose a methodological approach for evaluating MTI nuclei segmentation methods in absence of ground truth labels by scoring relatively to a larger ensemble of segmentations. To avoid potential sensitivity to collective bias from the ensemble approach, we refine the ensemble via weighted average across segmentation methods, which we derive from a systematic model ablation study. First, we demonstrate a proof-of-concept and the feasibility of the proposed approach to evaluate segmentation performance in a small dataset with ground truth annotation. To validate the ensemble and demonstrate the importance of our method-specific weighting, we compare the ensemble’s detection and pixel-level predictions – derived without supervision - with the data’s ground truth labels. Second, we apply the methodology to an unlabeled larger tissue microarray (TMA) dataset, which includes a diverse set of breast cancer phenotypes, and provides decision guidelines for the general user to more easily choose the most suitable segmentation methods for their own dataset by systematically evaluating the performance of individual segmentation approaches in the entire dataset.
Interplay between pollution and avian influenza virus in shorebirds and waterfowl
Authors: Ross Tobias A. , Zhang Junjie , Wille Michelle , Asimakopoulos Alexandros G. , Jaspers Veerle L. B. , Klaassen Marcel 
Published: February 2023

AbstractAnthropogenic pollution may disrupt wildlife immune function and increase susceptibility to, and ability to withstand, infection. Of particular concern is avian influenza virus (AIV), which in its low-pathogenic form is endemic in many wild bird populations, notably waterfowl and shorebirds, and in its high-pathogenic form poses a threat to wildlife, livestock and people. Many pollutants have immunomodulative properties, yet little is known about how these pollutants affect AIV infection risk specifically. We examined concentrations of known immunomodulatory compounds, per- and polyfluoroalkyl substances (PFASs), and assessed their influence on AIV infection in three reservoir species, red-necked stint (Calidris ruficollis, n=121), pacific black duck (Anas superciliosa, n=57) and grey teal (Anas gracilis, n= 62). Using data on viral prevalence (cloacal/oropharyngeal swabs) and seroprevalence (AIV anti-nucleoprotein antibodies), we found no significant effect of PFASs pollution (total PFASs <0.01 – 470 ng/g in red-necked stint, <0.01 – 600 ng/g in pacific black duck and 0.3 – 200 ng/g in grey teal) on infection status in our three species. This may be due to relatively low pollutant concentrations, but we cannot rule out possible population culling through a synergy of pollution and infection stressors. We therefore recommend further studies on infection incidence in more polluted populations or species.
Exercise alters cortico-basal ganglia network functional connectivity: A mesoscopic level analysis informed by anatomic parcellation defined in the mouse brain connectome
Authors: Wang Zhuo , Donahue Erin K. , Guo Yumei , Renteln Michael , Petzinger Giselle M. , Jakowec Michael W. , Holschneider Daniel P. 
Published: February 2023

ABSTRACTThe basal ganglia are important modulators of the cognitive and motor benefits of exercise. However, the neural networks underlying these benefits remain poorly understood. Our study systematically analyzed exercise-associated changes in functional connectivity in the cortico-basal ganglia-thalamic network during the performance of a new motor task, with regions-of-interest defined based on mesoscopic domains recently defined in the mouse brain structural connectome. Mice were trained on a motorized treadmill for six weeks or remained sedentary (control), thereafter undergoing [14C]-2-deoxyglucose metabolic brain mapping during wheel walking. Regional cerebral glucose uptake (rCGU) was analyzed in 3-dimensional brains reconstructed from autoradiographic brain sections using statistical parametric mapping. Functional connectivity was assessed by inter-regional correlation of rCGU. Compared to controls, exercised animals showed broad decreases in rCGU in motor areas, but increases in limbic areas, as well as the visual and association cortices. In addition, exercised animals showed (i) increased positive connectivity within and between the motor cortex and caudoputamen (CP), (ii) newly emerged negative connectivity of the substantia nigra pars reticulata with the globus pallidus externus, and CP, and (iii) reduced functional connectivity of the prefrontal cortex (PFC). Increased functional connectivity in the motor circuit in the absence of increases in rCGU strongly suggests greater network efficiency, which is also supported by the reduced involvement of PFC-mediated cognitive control during the performance of a new motor task. Our study delineates exercise-associated changes in functional circuitry at the subregional level and provides a framework for understanding the effects of exercise on new motor learning.
Anticancer effect of zanubrutinib in HER2-positive breast cancer cell lines
Authors: Dostálová Hana , Jorda Radek , Řezníčková Eva , Kryštof Vladimír 
Published: February 2023

AbstractSmall molecule Bruton’s tyrosine kinase (BTK) inhibitors have been developed for the treatment of various haemato-oncological diseases, and ibrutinib was approved as the first BTK inhibitors for anticancer therapy in 2013. Previous reports proved the receptor kinase human epidermal growth factor receptor 2 (HER2) to be a valid off-target kinase of ibrutinib and potentially other irreversible BTK inhibitors, as it possesses a druggable cysteine residue in the active site of the enzyme. These findings suggest ibrutinib as a candidate drug for repositioning in HER2-positive breast cancer (BCa). This subtype of breast cancer belongs to one of the most common classes of breast tumours, and its prognosis is characterized by a high rate of recurrence and tumour invasiveness. Based on their similar kinase selectivity profiles, we investigated the anticancer effect of zanubrutinib, evobrutinib, tirabrutinib and acalabrutinib in different BCa cell lines and sought to determine whether it is linked with targeting the epidermal growth factor receptor family (ERBB) pathway. We found that zanubrutinib is a potential inhibitor of the HER2 signalling pathway, displaying an antiproliferative effect in HER2-positive BCa cell lines. Zanubrutinib effectively inhibits the phosphorylation of proteins in the ERBB signalling cascade, including the downstream kinases Akt and ERK, which mediate key signals ensuring the survival and proliferation of cancer cells. We thus propose zanubrutinib as another suitable candidate for repurposing in HER2-amplified solid tumours.
Epigenetic regulation of innate immune genes and enhanced interleukin-10 expression underlie chronic subclinicalPlasmodium chabaudiinfection
Authors: de Souza Silva Leandro , Nguyen Yen Anh H. , Monks Brian G. , Forconi Catherine S. , Crabtree Juliet N. , Rodriguez Tomás , De Paula Tamburro Nelsy , Sontheimer Erik J. , Horvath Gabor L. , Abdullah Zeinab , Latz Eicke , Caffrey Daniel R. , Kurt-Jones Evelyn A. , Gazzinelli Ricardo T. , Fitzgerald Katherine A. , Golenbock Douglas T. 
Published: February 2023

AbstractSubclinical (asymptomatic) parasitemia is very common amongstPlasmodium-infected individuals. The immunological mechanisms underlying subclinical parasitemia remain elusive. We investigated the immune regulatory mechanisms behind chronic asymptomaticPlasmodiuminfection using mice lacking humoral immunity (µMT−/−mice). µMT−/−mice became chronically infected, despite lacking outward signs of disease, and exhibited increased macrophage numbers, decreased dendritic and CD4 cells, massive hemozoin accumulation in the spleen and bone marrow, and inadequate hematopoiesis. These changes were accompanied by high circulating levels of interleukin-10 (IL-10), enhanced chromatin accessibility of the STAT3 promoter, and enhanced STAT3 binding to the IL-10 promoter in macrophages. Inhibition of IL-10 signaling, despite promoting parasite clearance, resulted in a proinflammatory response, weight loss, and mortality. These results suggest that epigenetic changes induced by chronicP. chabaudiinfection lead to high levels of circulating IL-10, protecting chronically infected mice against an excessive inflammatory response to high levels of blood-stage parasites.Author summaryMalaria is a life-threatening disease with a range of symptoms, and it is induced in humans by infections with different species ofPlasmodium. Highly prevalent in endemic regions, asymptomaticPlasmodiuminfections are related to long-term exposure to the parasite due to multiple infections and have been demonstrated in human and mouse studies to be associated with elevated levels of IL-10. However, how IL-10 levels remain elevated in the circulation in individuals over the long term has not been determined. We used a mouse model of chronic asymptomaticPlasmodiuminfection to investigate the mechanisms by which IL-10 levels are elevated during chronic asymptomatic infection. Our results show that epigenetic changes in immune genes of myeloid origin could be responsible for the elevated levels of IL-10, and that IL-10 signaling protected chronically infected mice from a severe inflammatory response induced by the infection.
Not only age affects cardiovascular parameters, salivary biomarkers, and their correlation, but the level of physical conditioning changes this behavior in the elderly
Authors: Venâncio de Camargos Phabloo José de , Justino Allisson Benatti , Oliveira Gonçalves Luis Carlos , de Barros Rafael Joviano Souza , Sordi Bortolini Miguel Junior , Espindola Foued Salmen , de Magalhães Neto Aníbal Monteiro 
Published: February 2023

ABSTRACTTo compare the physical conditioning, hemodynamic, and salivary biomarkers between elderly athletes and the physically active elderly. 14 men: EA (n = 8) and PAE (n = 6). Collection times (T0; TE; T5; T15). A negative correlation was found between SF and cardiovascular parameters, BL, and STP in both groups, but this was almost double among PAE. For HR and SBP, there was a faster recovery in EA. The EA increase was correlated with SBP, while for PAE it was correlated with HR. BL showed an increase in TE, reaching 481% in EA and 639% in PAE. SNO showed a similar increase for the groups at the TE, but at T5, while EA already showed a reduction, PAE saw a 94% increase, with a slower decay for this group at T15. The SF presented the negative Δ% was almost double in PAE, with a quick recovery already at T5 for EA and levels still negative at all times for PAE. For SIgA-s, there was an increase of 37% in EA and only 7% at the TE in PAE; 41% in EA and 15% in PAE for T5; and 26% in EA and 14% in PAE at T15. SA showed a higher peak in EA (TE) and less acute in PAE (T5) but there was a decrease among both at T15. STP increased by 126% in EA and 438% in PAE, already showing a return at T5 for EA, but increasing by 213% in PAE. Negative levels were reached at T15 for EA but levels remained high in PAE. Levels of physical conditioning affect cardiovascular parameters, salivary biomarkers, and their correlation within the over-60s.