bluuebunny/crossref_metadata_2025_split huggingface dataset:
The molecular diversity of hippocampal regions and strata at synaptic resolution revealed by integrated transcriptomic and proteomic profiling
Authors: Kaulich Eva , Waselenchuk Quinn , Fürst Nicole , Desch Kristina , Mosbacher Janus , Ciirdaeva Elena , Juengling Marcel , Tushev Georgi , Langer Julian , Schuman Erin M. 
Published: August 2024

ABSTRACTThe molecular diversity of neurons and their synapses underlies the different responses and plasticity profiles that drive all neural circuits and behavior. While the extent of this diversity has been partially revealed by transcriptomic and proteomic profiling, combined studies of neuronal transcripts and proteins are limited. Here, we used microdissection of mouse hippocampal subregions and CA1 strata and fluorescence-activated synaptosome sorting (FASS) to characterize the transcripts and proteins from different hippocampal neurons and their compartments with synaptic resolution. Parallel RNA-seq and LC-MS/MS of microdissections identified over 15,000 mRNA transcripts and 10,000 proteins, revealing thousands with local enrichment such as classes of glutamate receptors and voltage-gated potassium channels, myelin-associated molecules, and adhesion molecules. Synaptosome analysis further identified specific enrichment of molecules from collagen, ribosome, solute carrier, and receptor families at different synapses formed along CA1 neurons. By integrating mRNA and protein data, we defined clusters of co-regulated molecules such as adhesion and neurofilament proteins and transporter mRNAs, and found subsets of mRNA-protein pairs with strong correlation and anti-correlation in their abundance variation. Our findings comprise a rich resource on the molecular landscape of the hippocampus and its synapses that is accessible atsyndive.org, and highlight the coordinated organization of transcripts and proteins between regions, neuronal compartments, and synapses.
Drug-induced differential culturability in diverse strains ofMycobacterium tuberculosis
Authors: March Valerie F. A. , Maghradze Nino , Mchedlishvili Kakha , Avaliani Teona , Aspindzelashvili Rusudan , Avaliani Zaza , Kipiani Maia , Tukvadze Nestani , Jugheli Levan , Bouaouina Selim , Doetsch Anna , Goig Galo A. , Gagneux Sebastien , Borrell Sonia 
Published: August 2024

AbstractDifferential culturable bacteria grow in liquid culture medium but are unable to form colonies on solid medium. Differentially culturableMycobacterium tuberculosis(Mtb) bacteria, have been found in tuberculosis (TB) patient sputa. We hypothesized that antibiotic treatment can induce differential culturability in Mtb. We investigated the effect of exposure to TB drugs on Mtb culturability using clinical samples from an ongoing TB patient cohort and by conducting severalin vitroexperiments with a diverse set of Mtb strains. In patients, serial sputa were more likely to generate Mtb-positive cultures in liquid as opposed to solid medium, with this liquid culture bias extending up to 5 months post diagnosis. Experimentally, there was a disparity between bacterial time to positivity (TTP) and colony forming units (CFUs) when Mtb was exposed to isoniazid (INH) and rifampicin (RIF) alone or in combination. Cultures recovered from RIF treatment yielded more CFUs on agar plates, but INH-treated cultures had a faster TTP in liquid. Follow up experiments using a fluorescently labelled laboratory strain of Mtb revealed that CFUs overestimated killing by INH treatment. Here we provide evidence in Mtb that drug exposure affects culturability on solid medium, which has implications for treatment monitoring and drug-pathogen interaction studies.
Structures of TASK-1 and TASK-3 K2P channels provide insight into their gating and dysfunction in disease
Authors: Hall Peter-Rory , Jouen-Tachoire Thibault , Schewe Marcus , Proks Peter , Baukrowitz Thomas , Carpenter Elisabeth P. , Newstead Simon , Rödström Karin E.J. , Tucker Stephen J 
Published: August 2024

AbstractTASK-1 and TASK-3 are pH-sensitive Two-Pore Domain (K2P/KCNK) K+channels. Their functional roles make them promising targets for the treatment of multiple disorders including sleep apnea, pain and atrial fibrillation. Rare genetic mutations in these channels are also associated with neurodevelopmental and hypertensive disorders. A recent crystal structure of TASK-1 revealed a lower ‘X-gate’ that is a hotspot for missense gain-of-function mutations associated with DDSA (Developmental Delay with Sleep Apnea). However, the structural basis for gating in TASK channels and how they sense extracellular pH to regulate gating have not been fully elucidated. Here, we resolve structures for both the human TASK-1 and TASK-3 channels by cryoEM, as well as for a recurrent TASK-3 variant (G236R) associated withKCNK9Imprinting Syndrome (formerly referred to as Birk-Barel Syndrome). Combined with functional studies of the X-gating mechanism, these structures not only provide evidence for how a highly-conserved gating mechanism becomes defective in disease, but also provide further insight into the pathway of conformational changes that underlie the pH-dependent inhibition of TASK channel activity.
PDK-1/S6K and mTORC1 bypass systemic growth restrictions to promote regeneration
Authors: Maya Ananthakrishnan Vijayakumar , Nogay Liyne , Heckmann Lara , Grass Isabelle , Kierdorf Katrin , Büscher Jörg , Classen Anne-Kathrin 
Published: August 2024

AbstractTissue damage and inflammation trigger systemic signals that induce catabolic breakdown and nutrient release in distant organs, a process well-characterized in the context of tumor cachexia. While mechanisms allowing tumors to circumvent these systemic growth restrictions are known, the physiological processes that overcome inflammation-induced growth restrictions to support tissue repair and regeneration remain largely unexplored. In our study, we use a model of tissue inflammation and regeneration in developingDrosophilaimaginal discs to dissect the key metabolic and signaling adaptations that help tissue overcome systemic growth restrictions. Our findings reveal a unique metabolic strategy used by rapidly proliferating cells in the regenerating domain. Instead of relying on the conventional Insulin-PI3K-Akt signaling pathway, these cells utilize a JAK/STAT-PDK1-S6K axis. This adaptation facilitates sustained protein synthesis and cellular growth despite the systemic catabolism associated with low insulin signaling. Specifically, we find that catabolic breakdown of the fat body is driven by the insulin-binding factor Impl2, which is expressed at the site of inflammatory damage. Notably, regenerative proliferation is also supported by mTORC1 activity and is associated with the upregulation of amino acid transporters in proliferating cells of the regenerating domain. These amino acid transporters align with a specific amino acid metabolite signature in the hemolymph, revealing a specialized metabolic program that meets the demands of fast-proliferating cells. Our work provides insight into how regenerating tissues rewire signaling pathways and adapt their metabolic growth to coordinate tissue repair with a conserved systemic nutrient provision response. These findings have important implications for understanding human diseases such as chronic wounds and cancer.
Circadian clock disruption and growth of kidney cysts in autosomal dominant polycystic kidney disease
Authors: Jamadar Abeda , Ward Christopher J. , Remadevi Viji , Varghese Meekha M , Pabla Navjot S , Gumz Michelle L. , Rao Reena 
Published: August 2024

AbstractBackgroundAutosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in thePKD1andPKD2genes, and often progresses to kidney failure. ADPKD progression is not uniform among patients, suggesting that factors secondary to thePKD1/2gene mutation could regulate the rate of disease progression. Here we tested the effect of circadian clock disruption on ADPKD progression. Circadian rhythms are regulated by cell-autonomous circadian clocks composed of clock proteins. BMAL1 is a core constituent of the circadian clock.MethodsTo disrupt the circadian clock, we deletedBmal1gene in the renal collecting ducts of thePkd1RC/RC(RC/RC) mouse model of ADPKD (RC/RC;Bmal1f/f;Pkhd1cre, called DKO mice), and inPkd1knockout mouse inner medullary collecting duct cells (Pkd1Bmal1KO mIMCD3 cells). Only male mice were used.ResultsHuman nephrectomy ADPKD kidneys andPkd1KO mIMCD3 cells showed reducedBmal1gene expression compared to normal controls. When compared to RC/RC kidneys, DKO kidneys showed significantly altered clock gene expression, increased cyst growth, cell proliferation, apoptosis and fibrosis. DKO kidneys also showed increased lipogenesis and cholesterol synthesis-related gene expression, and increased tissue triglyceride levels compared to RC/RC kidneys. Similarly,in vitro, Pkd1Bmal1KO cells showed altered clock genes, increased lipogenesis and cholesterol synthesis-related genes, and reduced fatty-acid oxidation-related gene expression compared toPkd1KOcells. ThePkd1Bmal1KO cells showed increased cell proliferation compared toPkd1KOcells, which was rescued by pharmacological inhibition of lipogenesis.ConclusionRenal collecting duct specificBmal1gene deletion disrupts the circadian clock and triggers accelerated ADPKD progression by altering lipid metabolism-related gene expression.Key pointsLack of BMAL1, a circadian clock protein in renal collecting ducts disrupted the clock and increased cyst growth and fibrosis in an ADPKD mouse model.BMAL1 gene deletion increased cell proliferation by increasing lipogenesis in kidney cells.Thus, circadian clock disruption could be a risk factor for accelerated disease progression in patients with ADPKD.
Image Correlation Spectroscopy is a Robust Tool to Quantify Cellular DNA Damage Response
Authors: Gopal Angelica A. , Fernandez Bianca , Wiseman Paul W. , Dubach J. Matthew 
Published: August 2024

AbstractThe DNA Damage response (DDR) is both essential and highly complex. Evaluating the DDR is a critical aspect of cell biology. Counting DNA damage foci is one of the most common approaches to study the DDR. Yet, quantification of protein foci suffers from experimental limitations, subjectivity of analysis and is restricted to a handful of the hundreds of DDR proteins. Here we apply image correlation spectroscopy (ICS) to quantify the local clustering at sites of DNA damage directly. We found that ICS outperformed foci counting of traditional DDR markers and enabled quantification of other markers without the complex labeling procedures that are otherwise required. ICS analysis also provided insight into DDR protein recruitment that was previously undetectable. Further expansion incorporating analysis to cell cycle classification demonstrates a rapid, non-biased approach to fully study the DNA damage response within cells. ICS analysis presents an objective, quantitative image analysis technique to study the DNA damage response in unaltered cells that we expect will significantly enhance quantitative DNA damage response research.
The transcription factor Chronophage/BCL11A/B promotes intestinal stem cell proliferation and endocrine differentiation
Authors: King Emer Aisling , Jacobsen Eleanor , Woolner Nicholas , de Navascués Joaquín , Marshall Owen J , Korzelius Jerome 
Published: August 2024

AbstractTissue-resident Adult Stem Cells (ASCs) need to continuously adapt their rate of division and differentiation based on their tissue environment. However, the gene regulatory networks that govern these decisions in ASCs and how they respond to challenges such as infection are often not fully understood. We identify a novel role for the transcription factor (TF) Chronophage (Cph) in ISC proliferation and entero-endocrine (EE) cell differentiation. Cph is a Z2H2 zinc TF orthologous to mammalian BCL11A/B that are involved in regulating adult stem cell fate in various contexts. We show here that Cph is expressed in ISCs and EEs in theDrosophilaintestine. Increased levels of Cph correlates with increased ISC proliferation and EE differentiation.cphloss-of-function leads to impaired ISC proliferation. Cph levels are elevated during tumourigenesis as well as in ageing and infection conditions. Knockdown of Cph in a Notch-mutant tumour model reduces tumour size and incidence and extends lifespan. Mechanistically, Cph overexpression leads to an increase in enteroendocrine (EE) cells and DamID DNA-binding and qRT-PCR analysis reveals that Cph directly regulates the levels of key EE regulatory genes such as Prospero (pros) and Phyllopod (phyl). In addition, Cph directly regulates core cell cycle regulators such as E2F1 as well as the TF Nerfin-1 that controls ISC proliferation and maintenance. Together, these data support a role for Cph in finetuning the balance between differentiation and proliferation during entero-endocrine differentiation.
Empirical fits to inclusive electron-carbon scattering data obtained by deep-learning methods
Authors: Kowal Beata E. , Graczyk Krzysztof M. , Ankowski Artur M. , Banerjee Rwik Dharmapal , Prasad Hemant , Sobczyk Jan T. 
Published: August 2024

Employing the neural network framework, we obtain empirical fits to the electron-scattering cross sections for carbon over a broad kinematic region, extending from the quasielastic peak through resonance excitation to the onset of deep-inelastic scattering. We consider two different methods of obtaining such model-independent parametrizations and the corresponding uncertainties: based on the bootstrap approach and the Monte Carlo dropout approach. In our analysis, the χ2 defines the loss function, including point-to-point and normalization uncertainties for each independent set of measurements. Our statistical approaches lead to fits of comparable quality and similar uncertainties of the order of 7%. To test these models, we compare their predictions to test datasets excluded from the training process and theoretical predictions obtained within the spectral function approach. The predictions of both models agree with experimental measurements and theoretical calculations. We also perform a comparison to a dataset lying beyond the covered kinematic region, and find that the bootstrap approach shows better interpolation and extrapolation abilities than the one based on the dropout algorithm.

Published by the American Physical Society
2024
Dimensional reduction gauge and effective dimensional reduction in four-dimensional Yang-Mills theory
Authors: Tohme Kei , Suganuma Hideo 
Published: August 2024

Motivated by one-dimensional color-electric flux-tube formation in four-dimensional (4D) QCD, we investigate a possibility of effective dimensional reduction in the 4D Yang-Mills (YM) theory. We propose a new gauge fixing of “dimensional reduction (DR) gauge” defined so as to minimize RDR≡∫d4sTr[Ax2(s)+Ay2(s)], which has a residual gauge symmetry for the gauge function Ω(t,z) like 2D QCD on the t−z plane. We investigate effective dimensional reduction in the DR gauge using SU(3) quenched lattice QCD at β=6.0. The amplitude of Ax(s) and Ay(s) are found to be strongly suppressed in the DR gauge. We consider “tz-projection” of Ax,y(s)→0 for the gauge configuration generated in the DR gauge, in a similar sense to Abelian projection in the maximally Abelian gauge. By the tz-projection in the DR gauge, the interquark potential is not changed, and At(s) and Az(s) play a dominant role in quark confinement. In the DR gauge, we calculate a spatial correlation ⟨TrA⊥(s)A⊥(s+ra⊥)⟩(⊥=x,y) and estimate the spatial mass of A⊥(s)(⊥=x,y) as M≃1.7  GeV. It is conjectured that this large mass makes A⊥(s) inactive and realizes the dominance of At(s) and Az(s) in infrared region in the DR gauge. We also calculate the spatial correlation of two temporal link-variables and find that the correlation decreases as exp(−mr) with m≃0.6  GeV. Using a crude approximation, the 4D YM theory is reduced into an ensemble of 2D YM systems with the coupling of g2D=gm.

Published by the American Physical Society
2024
Neutrino phenomenology in the modular
S3
seesaw model
Authors: Behera Mitesh Kumar , Ittisamai Pawin , Pongkitivanichkul Chakrit , Uttayarat Patipan 
Published: August 2024

We have studied neutrino phenomenology in the supersymmetric type-I seesaw model endowed with the Γ2≃S3 modular symmetry. We have identified different realizations of the S3 modular symmetry, referred to as models A, B, C, and D. The four models are compatible with neutrino mass being inverted ordering (IO). Moreover, models A, B, and D can also accommodate normal ordering (NO) neutrino masses. We identify parameter space for each model compatible with neutrino oscillation at the 2−σ level. We then proceed to study the neutrino phenomenology of each model. We find that the lightest neutrino mass can be as light as 0.64 meV in the case of NO in model A and 50 meV in the case of IO in model D. The smallest effective electron neutrino mass attainable in our analysis is 8.8 meV in the case of NO (model A) and 50 meV for IO (model D). Finally, we note that the effective Majorana mass can be as small as 0.33 meV in the case of NO (model A) and 22 meV for IO (model D).

Published by the American Physical Society
2024
Muonium state exchange dynamics in
n
-type GaAs
Authors: Yokoyama K. , Lord J. S. , Mengyan P. W. , Goeks M. R. , Lichti R. L. 
Published: August 2024

Muonium (Mu), a pseudoisotope of hydrogen with a positively charged muon in place of the proton, takes the form Mu+,0,− (like isolated hydrogen, i.e., H+,0,−) in semiconductors. The specifics of the charge state depend on the local electronic environment of the host. After initial muon implantation, generated Mu centers interact with free charge carriers and electronic spins, transition between sites, and form a dynamic network of state exchange. We identified the model of Mu dynamics in n-type GaAs using the density matrix simulation method and photoexcited muon spin spectroscopy technique. Fitting to the dark and illuminated μSR data provided transition rates between Mu states, revealing the underlying mechanisms at play between the Mu centers (cf. isolated H) and the host. Deduced capture/scattering cross sections of the Mu states reflected the microscopic dynamics of Mu. Illumination studies enabled us to measure interactions between Mu and minority carriers, which would be unavailable in dark measurements without heating. The methodology developed in this study may be applied to other semiconductor systems for a deeper understanding of the Mu state exchange dynamics.

Published by the American Physical Society
2024
Implications of crop yield distributions for multiperil crop insurance rating in Ghana: a lasso model application
Authors: Addey Kwame Asiam , Jatoe John Baptist D. 
Published: August 2024

PurposeThe objective of this paper is to examine crop yield predictions and their implications on MPCI in Ghana. Farmers in developing countries struggle with their ability to deal with agricultural risks. Providing aid for farmers and their households remains instrumental in combatting poverty in Africa. Several studies have shown that correctly understanding and implementing risk management strategies will help in the poverty alleviation agenda.Design/methodology/approachThis study examines the importance of crop yield distributions in Ghana and its implication on multiperil crop insurance (MPCI) rating using the Lasso regression model. A Bonferroni test was employed to test the independence of crop yields across the regions while the Kruskal-Wallis H test was conducted to examine statistical differences in mean yields of crops across the ten regions. The Bayesian information criteria and k-fold cross-validation methods are used to select an appropriate Lasso regression model for the prediction of crop yields. The study focuses on the variability of the threshold yields across regions based on the chosen model.FindingsIt is revealed that threshold yields differ significantly across the regions in the country. This implies that the payment of claims will not be evenly distributed across the regions, and hence regional disparities need to be considered when pricing MPCI products. In other words, policymakers may choose to assign respective weights across regions based on their threshold yields.Research limitations/implicationsThe primary limitation is the unavailability of regional climate data which could have helped in a better explanation of the variation across the regions.Originality/valueThis is the first study to examine the implications of regional crop yield variations on multiperil crop insurance rating in Ghana.
Exploring the impact of family, school and society on the perception and reputation of vocational training in Pakistan:a statistical analysis
Authors: Rehman Nadia , Huang Xiao , Sarwar Uzma , Fatima Hani , Maqbool Samra 
Published: August 2024

PurposeThe Technical Education and Vocational Training Authority (TEVTA) plays a crucial role in the socioeconomic development of a country. Still, it is often stigmatized as a secondary choice in the Global South. This study explored the interrelationships and impacts of factors such as family, school, and society on the perception and reputation of TEVTA.Design/methodology/approachBy employing quantitative methods, the analysis focused on how family, society, and school support influence these perceptions and reputations within TEVTA programs. Social Cognitive Theory is the theoretical underpinning of this study, in which 350 students from 13 TEVTA institutes participated by filling out questionnaires. The data was analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM) and IBM SPSS 28.FindingsThis study indicates that family and societal influences significantly shape students' perceptions, confirming their pivotal role in enhancing the reputation of these programs. School support also emerged as a critical factor, significantly impacting students' perceptions but not directly influencing the programs' reputation. The analysis underscores the importance of understanding the sociocultural context to develop effective strategies for the TEVTA sector in Pakistan. This clear understanding is essential for developing effective strategies to improve the reputation of TEVTA programs in this setting. Moreover, this research offers policy suggestions to make vocational education more attractive and accessible to diverse students, ultimately contributing to the country's socioeconomic development.Originality/valueThis study applied Social Cognitive Theory (SCT) to explore how individual thoughts, environmental influences (such as family, school, and society), and behaviors interact within the context of TEVTA programs. This approach fills gaps in current research and offers a clearer understanding of what affects TEVTA's perception and reputation.