bluuebunny/crossref_metadata_2025 huggingface dataset:
Mimicking opioid analgesia in cortical pain circuits
Authors: James Justin G. , McCall Nora M. , Hsu Alex I. , Oswell Corinna S. , Salimando Gregory J. , Mahmood Malaika , Wooldridge Lisa M. , Wachira Meghan , Jo Adrienne , Sandoval Ortega Raquel Adaia , Wojick Jessica A. , Beattie Katherine , Farinas Sofia A. , Chehimi Samar N. , Rodrigues Amrith , Ejoh Lindsay L. , Kimmey Blake A. , Lo Emily , Azouz Ghalia , Vasquez Jose J. , Banghart Matthew R. , Creasy Kate Townsend , Beier Kevin T. , Ramakrishnan Charu , Crist Richard C. , Reiner Benjamin C. , Deisseroth Karl , Yttri Eric A. , Corder Gregory
Published: April 2024

The anterior cingulate cortex plays a pivotal role in the cognitive and affective aspects of pain perception. Both endogenous and exogenous opioid signaling within the cingulate mitigate cortical nociception, reducing pain unpleasantness. However, the specific functional and molecular identities of cells mediating opioid analgesia in the cingulate remain elusive. Given the complexity of pain as a sensory and emotional experience, and the richness of ethological pain-related behaviors, we developed a standardized, deep-learning platform for deconstructing the behavior dynamics associated with the affective component of pain in mice—LUPE (Light aUtomated Pain Evaluator). LUPE removes human bias in behavior quantification and accelerated analysis from weeks to hours, which we leveraged to discover that morphine altered attentional and motivational pain behaviors akin to affective analgesia in humans. Through activity-dependent genetics and single-nuclei RNA sequencing, we identified specific ensembles of nociceptive cingulate neuron-types expressing mu-opioid receptors. Tuning receptor expression in these cells bidirectionally modulated morphine analgesia. Moreover, we employed a synthetic opioid receptor promoter-driven approach for cell-type specific optical and chemical genetic viral therapies to mimic morphine’s pain-relieving effects in the cingulate, without reinforcement. This approach offers a novel strategy for precision pain management by targeting a key nociceptive cortical circuit with on-demand, non-addictive, and effective analgesia.

Abstract Figure
Control of OPC proliferation and repopulation by the intellectual disability gene PAK1 under homeostatic and demyelinating conditions
Authors: Wang Yan , Kim Bokyung , Gong Shuaishuai , Park Joohyun , Zhu Meina , Wong Evelyn M. , Park Audrey Y. , Chernoff Jonathan , Guo Fuzheng
Published: April 2024

Appropriate proliferation and repopulation of oligodendrocyte progenitor cells (OPCs) determine successful (re)myelination in homeostatic and demyelinating brains. Activating mutations in p21-activated kinase 1 (PAK1) cause intellectual disability, neurodevelopmental abnormality, and white matter anomaly in children. It remains unclear if and how PAK1 regulates oligodendroglial development. Here, we report that PAK1 controls proliferation and regeneration of OPCs. Unlike differentiating oligodendrocytes, OPCs display high PAK1 activity which maintains them in a proliferative state by modulating PDGFRa-mediated mitogenic signaling. PAK1-deficient or kinase-inhibited OPCs reduce their proliferation capacity and population expansion. Mice carrying OPC-specific PAK1 deletion or kinase inhibition are populated with fewer OPCs in the homeostatic and demyelinated CNS than control mice. Together, our findings suggest that kinase-activating PAK1 mutations stall OPCs in a progenitor state, impacting timely oligodendroglial differentiation in the CNS of affected children and that PAK1 is a potential molecular target for replenishing OPCs in demyelinating lesions.
Can seminal fluid proteins be honest signals of sperm availability?
Authors: Michalak Piotr , Duneau David , Ferdy Jean-Baptiste
Published: April 2024

Seminal fluid proteins (Sfps) are produced by males, yet they have significant effects on female physiology and behaviour. Sfps are often viewed as a mechanism for males to manipulate female reproductive behaviours, but despite many studies identifying their varied effects and their molecular underpinnings, the ways males and females use Sfps remain unclear. In the most studied case ofDrosophila melanogasterparticular peptides within the seminal fluid have been identified to guide female reproduction: sex peptide (SP, Acp70A) is known to induce changes in egg production, oviposition and remating and is attached to sperm and continuously supplied for days after mating, while ovulation inducing peptide, ovulin (Acp26Aa), is a free peptide with only short term effects after mating. Using a biologically informed model we show how these peptides can synchronize sperm and egg release, hence reducing the number of unfertilized eggs a female lays. We further show that the exhaustion of SP might be the key signal of this synchronization. Finally, we demonstrate that sexual conflict over the regulation of female reproductive physiology by Sfps should be limited, with the primary conflict probably centring around the regulation of remating behaviour.
Identifying key amino acid types that distinguish paralogous proteins using Shapley value based feature subset selection
Authors: Machingal Pranav , Busi Rakesh , Hemachandra Nandyala , Balaji Petety V.
Published: April 2024

We view a protein as the composite of the standard 20 amino acids, ignoring their order in the protein sequence. With this view, we try to identify the important amino acid types that distinguish pairs of paralogous proteins, thereby playing a role in their functional difference. Using only the amino acid composition (AAC) as features and a linear classifier, we find that many pairs of paralogous protein families can be classified accurately. Next, we use an existing Shapley value-based feature subset selection algorithm, SVEA, to identify the important amino acid types that distinguish a pair of paralogous proteins. The SVEA algorithm assigns a score, Shapley value, to each feature, amino acid type, based on its contribution to the classifier’s training error. We identify the important distinguishing amino acid types as those whose Shapley value exceeds a data-driven threshold. We refer to these as the amino acid feature subset (AFS). We find that many paralog pairs can still be accurately classified using only theAFScomposition. We partitionAFSbased on the classifier weights to infer class-wise amino acid importance. We verify whether the identifiedAFSamino acids indeed play a role in the functional difference of the paralog pairs using various methods - multiple sequence alignment, 3D structure analysis, and supporting evidence from biology literature. We also discuss some consistencies observed in the Shapley value based ranking and theAFSwhen comparing theAFSof two different but related paralog pairs. We demonstrate the results for 15 pairs of paralogous proteins.
Notch dimerization provides robustness against environmental insults and is required for vascular integrity
Authors: Preusse Kristina , Cochran Kim , Dai Quanhui , Kopan Raphael
Published: April 2024

The Notch intracellular domain (NICD) regulates gene expression during development and homeostasis in a transcription factor complex that binds DNA either as monomer, or cooperatively as dimers. Mice expressingNotchdimerization-deficient (NDD) alleles of Notch1 and Notch2 have defects in multiple tissues that are sensitized to environmental insults. Here, we report that cardiac phenotypes and DSS (Dextran Sodium Sulfate) sensitivity in NDD mice can be ameliorated by housing mice under hypo-allergenic conditions (food/bedding). However, compound heterozygote NDD mice (N1RA/–; N2RA/–) in hypo-allergenic conditions subsequently develop severe hydrocephalus and hemorrhages. Further analysis revealed multiple vascular phenotypes in NDD mice including leakage, malformations of brain vasculature, and vasodilation in kidneys, leading to demise around P21. This mouse model is thus a hypomorphic allele useful to analyze vascular phenotypes and gene-environment interactions. The possibility of a non-canonical Notch signal regulating barrier formation in the gut, skin, and blood systems is discussed.
Loop Catalog: a comprehensive HiChIP database of human and mouse samples
Authors: Reyna Joaquin , Fetter Kyra , Ignacio Romeo , Ali Marandi Cemil Can , Rao Nikhil , Jiang Zichen , Figueroa Daniela Salgado , Bhattacharyya Sourya , Ay Ferhat
Published: April 2024

HiChIP enables cost-effective and high-resolution profiling of regulatory and structural loops. To leverage the increasing number of publicly available HiChIP datasets from diverse cell lines and primary cells, we developed the Loop Catalog (https://loopcatalog.lji.org), a web-based database featuring HiChIP loop calls for 1319 samples across 133 studies and 44 high-resolution Hi-C loop calls. We demonstrate its utility in interpreting fine-mapped GWAS variants (SNP-to-gene linking), in identifying enriched sequence motifs and motif pairs at loop anchors, and in network-level analysis of loops connecting regulatory elements (community detection). Our comprehensive catalog, spanning over 4M unique 5kb loops, along with the accompanying analysis modalities constitutes an important resource for studies in gene regulation and genome organization.
Genetic Deletion of Calcium-independent Phospholipase A2γ Protects Mice from Diabetic Nephropathy
Authors: Cybulsky Andrey V. , Papillon Joan , Guillemette Julie , Navarro-Betancourt José R. , Elimam Hanan , Fantus I. George
Published: April 2024

Calcium-independent phospholipase A2γ (iPLA2γ) is localized in glomerular epithelial cells (GECs)/podocytes at the mitochondria and endoplasmic reticulum, and can mediate release of arachidonic acid and prostanoids. Global knockout (KO) of iPLA2γ in mice did not cause albuminuria, but resulted in mitochondrial structural abnormalities and enhanced autophagy in podocytes. In acute glomerulonephritis, deletion of iPLA2γ exacerbated albuminuria and podocyte injury. This study addresses the role of iPLA2γ in diabetic nephropathy. Hyperglycemia was induced in male mice with streptozotocin (STZ). STZ induced progressive albuminuria in control mice (over 21 weeks), while albuminuria did not increase in iPLA2γ KO mice, remaining comparable to untreated groups. Despite similar exposure to STZ, the STZ-treated iPLA2γ KO mice developed a lower level of hyperglycemia compared to STZ-treated control. However, there was no significant correlation between the degree of hyperglycemia and albuminuria, and even iPLA2γ KO mice with greatest hyperglycemia did not develop significant albuminuria. Mortality at 21 weeks was greatest in diabetic control mice. Sclerotic glomeruli and enlarged glomerular capillary loops were increased significantly in diabetic control compared to diabetic iPLA2γ KO mice. Glomerular matrix was expanded in diabetic mice, with control exceeding iPLA2γ KO. Glomerular autophagy (increased LC3-II and decreased p62) was enhanced in diabetic iPLA2γ KO mice compared to control. Treatment of cultured GECs with H2O2resulted in increased cell death in control GECs compared to iPLA2γ KO, and the increase was slightly greater in medium with high glucose compared to low glucose. H2O2-induced cell death was not affected by inhibition of prostanoid production with indomethacin. In conclusion, mice with global deletion of iPLA2γ are protected from developing chronic glomerular injury in diabetic nephropathy. This is associated with increased glomerular autophagy.
Ancestral sequence reconstruction of the Mic60 Mitofilin domain reveals residues supporting respiration in yeast
Authors: Benning Friederike M. C. , Bell Tristan A. , Nguyen Tran H. , Syau Della , Connell Louise B. , Coughlin Margaret , Nordstrom Anja E. H. , Ericsson Maria , daCosta Corrie J. B. , Chao Luke H.
Published: April 2024

In eukaryotes, cellular respiration takes place in the cristae of mitochondria. The mitochondrial inner membrane protein Mic60, a core component of the mitochondrial contact site and cristae organizing system (MICOS), is crucial for the organization and stabilization of crista junctions and its associated functions. While the C-terminal Mitofilin domain of Mic60 is necessary for cellular respiration, the sequence determinants for this function have remained unclear. Here, we used ancestral sequence reconstruction to generate Mitofilin ancestors up to and including the last opisthokont common ancestor (LOCA). We found that yeast-lineage derived Mitofilin ancestors as far back as the LOCA rescue respiration. By comparing Mitofilin ancestors, we identified four residues sufficient to explain the respiratory difference between yeast- and animal-derived Mitofilin ancestors. Our results provide a foundation for investigating the conservation of Mic60-mediated cristae junction interactions.
Unraveling the Role of cAMP Signaling inGiardia: Insights into PKA-Mediated Regulation of Encystation and Subcellular Interactions
Authors: Shih Han-Wei , Alas Germain C.M. , Paredez Alexander R.
Published: April 2024

cAMP plays a crucial role as a second messenger in the stage transition of various protozoan parasites. This signaling pathway relies on multiple effectors, such as protein kinase A (PKA), exchange protein activated by cAMP (EPAC), and cAMP-response element binding protein (CREB) transcription factors, to initiate signal transduction in humans. Even thoughGiardiahas been observed to have only two adenylate cyclases (ACs) and a single cAMP effector, the specific functions of these components are not fully understood. In our previous research, we demonstrated the essential role of AC2-dependent cAMP signaling in the upregulation of the encystation program. Using NanoBit technology, we emphasized the significance of AC2-dependent cAMP biosynthesis in regulating the dissociation of PKAr and PKAc. In this study, our objectives are twofold: first, we used newly developed Split-Halo to examine subcellular interactions ofGlPKAr andGlPKAc; second, we investigated whether PKAc regulates encystation markers. Our findings revealed distinct subcellular locations whereGlPKAr andGlPKAc interacted during the trophozoite stage, including the flagella, basal bodies, and cytosol. Upon exposure to encystation stimuli, the interaction shifted from the flagella to the cytosol. Additionally, interaction occurred at an unidentified cell compartment between twelve to sixteen hours of encystation and persisted to the cyst stage. Knockdown ofGlPKAc resulted in the downregulation of encystation-specific genes, leading to the production of fewer viable and water-resistant cysts indicating a role for PKA in transcriptional regulation. These discoveries contribute to a deeper understanding of the cAMP signaling pathway and its pivotal role in governingGiardia’s encystation process.
CRISPR Screening Uncovers a Long-Range Enhancer forONECUT1in Pancreatic Differentiation and Links a Diabetes Risk Variant
Authors: Kaplan Samuel Joseph , Wong Wilfred , Yan Jielin , Pulecio Julian , Cho Hyein S. , Li Qianzi , Zhao Jiahui , Leslie-Iyer Jayanti , Kazakov Jonathan , Murphy Dylan , Luo Renhe , Dey Kushal K. , Apostolou Effie , Leslie Christina S. , Huangfu Danwei
Published: April 2024

Functional enhancer annotation is a valuable first step for understanding tissue-specific transcriptional regulation and prioritizing disease-associated non-coding variants for investigation. However, unbiased enhancer discovery in physiologically relevant contexts remains a major challenge. To discover regulatory elements pertinent to diabetes, we conducted a CRISPR interference screen in the human pluripotent stem cell (hPSC) pancreatic differentiation system. Among the enhancers uncovered, we focused on a long-range enhancer ∼664 kb from theONECUT1promoter, since coding mutations inONECUT1cause pancreatic hypoplasia and neonatal diabetes. Homozygous enhancer deletion in hPSCs was associated with a near-complete loss ofONECUT1gene expression and compromised pancreatic differentiation. This enhancer contains a confidently fine-mapped type 2 diabetes associated variant (rs528350911) which disrupts a GATA motif. Introduction of the risk variant into hPSCs revealed substantially reduced binding of key pancreatic transcription factors (GATA4, GATA6 and FOXA2) on the edited allele, accompanied by a slight reduction ofONECUT1transcription, supporting a causal role for this risk variant in metabolic disease. This work expands our knowledge about transcriptional regulation in pancreatic development through the characterization of a long-range enhancer and highlights the utility of enhancer discovery in disease-relevant settings for understanding monogenic and complex disease.
DISRUPTIONS IN LIVELIHOODS, HEALTHCARE ACCESS AND HEALTH OUTCOMES IN WEST AFRICA DURING EMERGING INFECTIOUS DISEASE OUTBREAKS
Authors: Ansumana Rashid , Bockarie Alfred S. , Konneh Monya , Haider Najmul , Cadmus Eniola , Korvah Alberta , Fayiah Joyce , Waka-Metzger Yolaine Kate , George Angella M. , Mallah Gassimu , Lamin Joseph M. , Dar Osman , Mayhew Susannah , Bah Doris , Bilivigoi Pepe , Maggasouba Nfaly , Cadmus Simeon , Alders Robyn
Published: April 2024

Background

Outbreaks of infectious diseases like Ebola virus disease, Lassa fever, and COVID-19 have severely strained infrastructural systems and social services across West Africa. We investigated the disruptions caused by emerging outbreaks on access to healthcare, health outcomes, and livelihoods in West Africa.

Method

A mixed-methods approach was utilized, conducting extensive studies in Nigeria, Sierra Leone, Guinea, and Liberia through structured questionnaires, in-depth interviews with key informants, and focus group discussions. Using a device-to-cloud system guided by GIS for randomized sampling across the four nations, this technique allowed us to comprehensively analyze implications across imposed lifestyle changes on health and wellbeing due to disrupted healthcare.

Results

Our findings indicate drastic shifts in food consumption patterns and healthcare access. In Guinea, self-reported “Once Daily” meals astonishingly surged from 148 to 775 individuals (p<0.001), with analogous substantial increases observed in Liberia and Sierra Leone. Nigeria exhibited a varied response, with notable rises both in “Once Daily” and “Twice Daily” meal frequencies (p<0.001), reflecting broad dietary adaptations out of necessity. Additionally, there was a significant decrease in consumption of traditional protein sources like bushmeat, beef, and mutton, mainly because of disrupted supply chains and heightened concerns over food insecurity. Conversely, fish consumption slightly fell possibly due to its perceived safety or accessibility amidst the outbreak.

Healthcare services faced severe disruptions, particularly acute in Sierra Leone and Liberia compared to Guinea and Nigeria. The interruption of services drastically impacted everything from immunization rates to mental health, with a rise in reported anxiety and depression alongside public dissatisfaction towards the healthcare disruptions.

Conclusion

This study demonstrates the dramatic effects of infectious disease outbreaks on health access and diets in West Africa. The research calls for integrating health initiatives with social protection to strengthen the resilience of societies to meet all types of health challenges. It is imperative districts establish robust health systems and social security mechanisms to counter future public health crises.
LETSmix: a spatially informed and learning-based domain adaptation method for cell-type deconvolution in spatial transcriptomics
Authors: Zhan Yangen , Zhang Yongbing , Hu Zheqi , Wang Yifeng , Zhu Zirui , Du Sijing , Yan Xiangming , Li Xiu
Published: April 2024

Spatial transcriptomics (ST) has revolutionized our understanding of gene expression patterns by incorporating spatial context. However, many ST technologies operate on heterogeneous cell mixtures due to limited spatial resolution. To resolve cell type composition at each sequencing spot, several deconvolution methods have been proposed. Yet, these approaches often underutilize spatial context inherent in ST data and paired histopathological images, meanwhile overlooking domain variances between ST and reference single-cell RNA sequencing (scRNA-seq) data. Here, we present LETSmix, a novel deconvolution method that enhances spatial correlations within ST data using a tailored LETS filter, and employs a mixup-augmented domain adaptation strategy to address domain shifts. The performance of LETSmix was validated across diverse ST platforms and tissue types, including 10x Visium human dorsolateral prefrontal cortex, ST human pancreatic ductal adenocarcinoma, 10x Visium mouse liver, and Stereo-seq mouse olfactory bulb datasets. Our findings demonstrate that the proposed method accurately estimates cell type proportions and effectively maps them to the expected regions, establishing a new record among current state-of-the-art models. LETSmix is expected to serve as a robust tool for advancing studies on cellular composition and spatial architecture in spatial transcriptomics.

GRAPHICAL ABSTRACT
Probing the Molecular Interactions of A22 with Prokaryotic Actin MreB and Eukaryotic Actin: A Computational and Experimental Study
Authors: Kumar Anuj , Kukal Samiksha , Marepalli Anusha , Kumar Saran , Govindarajan Sutharsan , Pramanik Debabrata
Published: April 2024

Actin is a major cytoskeletal system that mediates the intricate organization of macromolecules within cells. The bacterial cytoskeletal protein MreB is a prokaryotic actin-like protein governing cell shape and intracellular organization in many rod-shaped bacteria including pathogens. MreB stands as a target for antibiotic development, and compounds like A22 and its analogue, MP265, are identified as potent inhibitors of MreB. The bacterial actin MreB shares structural homology with eukaryotic actin, despite lacking sequence similarity. It is currently not clear whether small molecules that inhibit MreB can act on the eukaryotic actin due to their structural similarity. In this study, we investigate the molecular interactions between A22 and both MreB and eukaryotic actin through molecular dynamics approach. Employing MD simulations and free energy calculations with an all-atom model, we unveil robust A22-MreB interaction and substantial binding affinity with eukaryotic actin. Experimental assays reveal A22’s toxicity to eukaryotic cells, including yeast and human glioblastoma cells. Microscopy analysis demonstrates profound effects of A22 on actin organization in human glioblastoma cells. Overall, this integrative computational and experimental study advances our understanding of A22’s mode of action and highlights its potential as a versatile tool for probing actin dynamics and as a candidate for therapeutic intervention in pathological conditions like cancer.
Topology-Driven Negative Sampling Enhances Generalizability in Protein-Protein Interaction Prediction
Authors: Chatterjee Ayan , Ravandi Babak , Haddadi Parham , Philip Naomi H. , Abdelmessih Mario , Mowrey William R. , Ricchiuto Piero , Liang Yupu , Ding Wei , Mobarec Juan C. , Eliassi-Rad Tina
Published: April 2024

Unraveling the human interactome to uncover disease-specific patterns and discover drug targets hinges on accurate protein-protein interaction (PPI) predictions. However, challenges persist in machine learning (ML) models due to a scarcity of quality hard negative samples, shortcut learning, and limited generalizability to novel proteins. Here, we introduce a novel approach for strategic sampling of protein-protein non-interactions (PPNIs) by leveraging higher-order network characteristics that capture the inherent complementarity-driven mechanisms of PPIs. Next, we introduce UPNA-PPI (Unsupervised Pre-training of Node Attributes tuned for PPI), a high throughput sequence-to-function ML pipeline, integrating unsupervised pretraining in protein representation learning with topological PPNI samples, capable of efficiently screening billions of interactions. UPNA-PPI improves PPI prediction generalizability and interpretability, particularly in identifying potential binding sites locations on amino acid sequences, strengthening the prioritization of screening assays and facilitating the transferability of ML predictions across protein families and homodimers. UPNA-PPI establishes the foundation for a fundamental negative sampling methodology in graph machine learning by integrating insights from network topology.
Infection of Alfalfa Cotyledons by an Incompatible but Not a Compatible Species ofColletotrichumInduces Formation of Paramural Bodies and Secretion of EVs
Authors: Ghosh Suchismita , Regmi Kamesh C. , Stein Barry , Chen Jun , O’Connell Richard J. , Innes Roger W.
Published: April 2024

Hemibiotrophic fungi in the genusColletotrichumemploy a biotrophic phase invading host epidermal cells followed by a necrotrophic phase spreading through neighboring mesophyll and epidermal cells. We used serial block face scanning electron microscopy (SBF-SEM) to compare subcellular changes that occur inMedicago sativa(alfalfa) cotyledons during infection byColletotrichum destructivum(compatible onM. sativa) andC. higginsianum(incompatible onM. sativa). Three-dimensional reconstruction of serial images revealed that alfalfa epidermal cells infected withC. destructivumundergo massive cytological changes during the first 60 hours following inoculation to accommodate extensive intracellular hyphal growth. Conversely, inoculation with the incompatible speciesC. higginsianumresulted in no successful penetration events and frequent formation of papilla-like structures and cytoplasmic aggregates beneath attempted fungal penetration sites. Further analysis of the incompatible interaction using focused ion beam-scanning electron microcopy (FIB-SEM) revealed formation of large multivesicular body-like structures that appeared spherical and were not visible in compatible interactions. These structures often fused with the host plasma membrane, giving rise to paramural bodies that appeared to be releasing extracellular vesicles (EVs). Isolation of EVs from the apoplastic space of alfalfa leaves at 60h post inoculation showed significantly more vesicles secreted from alfalfa infected with incompatible fungus compared to compatible fungus, which in turn was more than produced by non-infected plants. Thus, the increased frequency of paramural bodies during incompatible interactions correlated with an increase in EV quantity in apoplastic wash fluids. Together, these results suggest that EVs and paramural bodies contribute to immunity during pathogen attack in alfalfa.
Isolation, characterization and antibiogram ofBacillus cereusfrom milk products
Authors: Yadav Pramod , Khurana Rajesh , Kumar Manesh , Yadav Ritu , Rinku
Published: April 2024

This study, conducted within the Department of Veterinary Public Health and Epidemiology (VPHE) at Lala Lajpat Rai University of Veterinary and Animal Sciences (LUVAS), undertook a comprehensive investigation into the prevalence, identification, characterization, and antibiotic resistance patterns of Bacillus cereus in milk products from various regions of Haryana, India.

Using a systematic sampling strategy, eight tehsils spanning two agroclimatic zones were selected for sample collection. A total of 200 samples were obtained from randomly selected shops within these tehsils. Each sample underwent pre-enrichment in Brain Heart Infusion (BHI) broth with a 1:10 dilution to facilitate the growth of any existingB. cereuscontaminants. Following pre-enrichment, streaking on selective PEMBA agar plates was performed for the isolation ofB. cereuscolonies. The presence of presumptiveB. cereuscolonies was confirmed through a series of biochemical tests, including gram staining, nitrate reduction, oxidase, indole, methyl red reduction, Voges Praskaur, and catalase tests.

Molecular analysis using the16SrRNAgene confirmed the presence of 88 positiveB. cereusisolates. Further characterization involved the differentiation ofB. cereusfrom Bacillus thuringiensis via the cry2 gene. Additionally, the study assessed the presence of virulence-associated genes, identifyinggyrB, cytk,hblA, andnheAgenes in the isolated strains.

Geographical variation inB. cereusprevalence was observed, with higher rates detected in certain tehsils such as Kalka (68%) and Panchkula (60%). Antibiotic sensitivity testing using Tryptone Soya Agar (TSA) broth for enrichment and Muller Hinton Agar (MHA) plates with 14 antibiotic discs revealed widespread resistance among the isolates. Notably, all isolates exhibited resistance to Ampicillin, Cefazolin, Methicillin, Polymyxin-B, and Penicillin, while displaying maximum sensitivity to Amikacin, Gentamycin, Levofloxacin, and Meropenem. Alarmingly, all isolates displayed multiple drug resistance (MDR), indicating resistance to three or more classes of antibiotics.

These findings underscore the urgent need for stringent food safety measures and surveillance protocols in dairy production and distribution. Effective interventions are imperative to mitigate the risk ofB. cereuscontamination and combat antibiotic resistance in milk products. Collaboration with the VPHE department at LUVAS and continued research efforts are essential to address emerging challenges and uphold food safety standards effectively.
Identification of causal influences in quantum processes
Authors: Friend Isaac , Kissinger Aleks
Published: April 2024

Recent years have seen great interest in extending causal inference concepts developed in the context of classical statistical models to quantum theory. So far, this program has only barely addressed causal identification, a type of causal inference problem concerned with recovering from observational data and qualitative assumptions the causal relationships generating the data, and hence the effects of hypothetical interventions. A major obstacle to a theory of causal identification in the quantum setting is the question of what should play the role of “observational data,” as any means of extracting data at a locus will almost certainly disturb the system. One might think that quantum measurements are already too much like interventions, so that the problem of causal identification is trivialized. This is not the case: when we fix a limited class of quantum measurement instruments (namely, the class of all projective measurements) to play the role of “observations,” there exist scenarios for which causal identification is impossible. In this paper, we present a framework, based on process theories (also known as strict symmetric monoidal categories), for studying quantum causal identification scenarios on the same footing as their classical counterparts. Within this framework, we present sufficient conditions for quantum causal identification in networks with unobserved confounding systems, including quantum analogs of the well-known “back-door” and “front-door” criteria. These results arise from a type of causal model designed to facilitate the transfer of inference techniques from the classical to the quantum setting.

Published by the American Physical Society
2024
Dissipative and dispersive cavity optomechanics with a frequency-dependent mirror
Authors: Monsel Juliette , Ciers Anastasiia , Manjeshwar Sushanth Kini , Wieczorek Witlef , Splettstoesser Janine
Published: April 2024

An optomechanical microcavity can considerably enhance the interaction between light and mechanical motion by confining light to a subwavelength volume. However, this comes at the cost of an increased optical loss rate. Therefore, microcavity-based optomechanical systems are placed in the unresolved-sideband regime, preventing sideband-based ground-state cooling. A pathway to reduce optical loss in such systems is to engineer the cavity mirrors, i.e., the optical modes that interact with the mechanical resonator. In our work, we analyze such an optomechanical system, whereby one of the mirrors is strongly frequency dependent, i.e., a suspended Fano mirror. This optomechanical system consists of two optical modes that couple to the motion of the suspended Fano mirror. We formulate a quantum-coupled-mode description that includes both the standard dispersive optomechanical coupling as well as dissipative coupling. We solve the Langevin equations of the system dynamics in the linear regime showing that ground-state cooling from room temperature can be achieved even if the cavity is not in the resolved-sideband regime, but achieves effective sideband resolution through strong-optical-mode coupling. Importantly, we find that the cavity output spectrum needs to be properly analyzed with respect to the effective laser detuning to infer the phonon occupation of the mechanical resonator. Our work also predicts how to reach the regime of nonlinear quantum optomechanics in a Fano-based microcavity by engineering the properties of the Fano mirror.

Published by the American Physical Society
2024
Hadronic structure on the light front. VIII. Light scalar and vector mesons
Authors: Liu Wei-Yang , Shuryak Edward , Zahed Ismail
Published: April 2024

We use the QCD instanton vacuum model to discuss the emergence of the light scalar and vector mesons on the light front. We take into account both the instanton and anti-instanton single and molecular interactions on the light quarks, in the form of nonlocal effective interactions. Although the molecular induced interactions are suppressed by a power of the packing fraction, they are still sufficient to bind the vector mesons, while keeping most of the scalar spectrum relatively unchanged. We explicitly derive the light front distribution amplitudes and partonic functions for the scalar and vector mesons, and compare them after pertinent QCD evolution, to the available empirical and lattice measured counterparts. The Dirac electric form factors for both the pion and ρ meson are derived, and shown to compare well with current data.

Published by the American Physical Society
2024
QCD corrections to the Darwin coefficient in inclusive semileptonic
B→Xuℓν¯ℓ
decays
Authors: Moreno Daniel
Published: April 2024

In this paper, we compute αs corrections to the matching coefficients of the dimension-six operators in the heavy quark expansion of the inclusive semileptonic heavy hadron decay rate and leptonic invariant mass spectrum with a massless quark and both a massive or massless lepton in the final state, analytically. The obtained results can be applied to the inclusive semileptonic B→Xuℓν¯ℓ (ℓ=e, μ, τ) and D→Xℓν¯ℓ (ℓ=e, μ) decays. The main application of our results is the background subtraction of the B→Xuℓν¯ℓ decay in the measurement of the B→Xcℓν¯ℓ decay, which is important for the precise extraction of Vcb and R(D(*)). They also play a role in the computation of lifetimes of heavy hadrons.

Published by the American Physical Society
2024
Spectrum of the molecular pentaquarks
Authors: Wang Bo , Chen Kan , Meng Lu , Zhu Shi-Lin
Published: April 2024

We investigate the mass spectrum of the molecular pentaquarks composed of a baryon and a meson. We establish the underlying relations among the near-threshold interactions of the molecular tetraquark and pentaquark systems. We find the existence of the molecule candidates in the ΣcD¯(*), DD*, and DD¯* systems indicates a substantial presence of the hadronic molecules in the heavy baryon plus heavy meson systems ( refers to the hadrons with the c and/or

s

quarks). We make an exhaustive prediction of the possible bound/virtual molecular states in the systems: Σc(*)D¯(*), Σc(*)D(*), Ξc(′,*)D¯(*), Ξc(′,*)D(*), Σc(*)K*, Σc(*)K¯*, Ξc(′,*)K*, Ξc(′,*)K¯*, Ξcc(*)D¯(*), Ξcc(*)D(*), Ξcc(*)K*, Ξcc(*)K¯*, Σ(*)D¯(*), Σ(*)D(*), Ξ(*)D¯(*), Ξ(*)D(*), Σ(*)K*, Σ(*)K¯*, Ξ(*)K*, Ξ(*)K¯*. Hunting for the predicted states in experiments will significantly deepen our understanding of the formation mechanism of the hadronic molecules, and shed light on the manifestation of flavor symmetry in the low-energy residual strong interactions.

Published by the American Physical Society
2024
Light Dirac neutrino portal dark matter with gauged
U(1)B−L
symmetry
Authors: Das Nayan , Borah Debasish
Published: April 2024

We propose a gauged U(1)B−L version of the light Dirac neutrino portal dark matter. The U(1)B−L symmetry provides a UV completion by naturally accommodating three right-handed neutrinos from anomaly cancellation requirements which, in combination with the left-handed neutrinos, form the sub-eV Dirac neutrinos after electroweak symmetry breaking. The particle content and the gauge charges are chosen in such a way that light neutrinos remain purely Dirac and dark matter, a gauge singlet Dirac fermion, remain stable. We consider both thermal and nonthermal production possibilities of dark matter and correlate the corresponding parameter space with the one within reach of future cosmic microwave background (CMB) experiments sensitive to enhanced relativistic degrees of freedom ΔNeff. The interplay of dark matter, CMB, structure formation and other terrestrial constraints keep the scenario very predictive leading the U(1)B−L parameter space into tight corners.

Published by the American Physical Society
2024
New physics couplings from angular coefficient functions of
B¯→D*(Dπ)ℓν¯ℓ
Authors: Colangelo Pietro , De Fazio Fulvia , Loparco Francesco , Losacco Nicola
Published: April 2024

The Belle Collaboration has recently measured the complete set of angular coefficient functions for the exclusive decays B¯→D*(Dπ)ℓν¯ℓ, with ℓ=e, μ, in four bins of the parameter w=mB2+mD*2−q22mBmD*, with q the lepton pair momentum [M. T. Prim (Belle Collaboration), ]. Under the assumption that physics beyond the Standard Model does not contribute to such modes, the measurements are useful to determine the hadronic form factors describing the B→D* matrix elements of the Standard Model weak current, and to improve the determination of |Vcb|. On the other hand, they can be used to assess the impact of possible new physics contributions. In a bottom-up approach, we extend the Standard Model effective Hamiltonian governing this mode with the inclusion of the full set of Lorentz invariant d=6 operators compatible with the gauge symmetry of the theory. The measured angular coefficient functions can tightly constrain the couplings in the generalized Hamiltonian. We present the first results of this analysis, discussing how improvements can be achieved when more complete data on the angular coefficient functions will be available.

Published by the American Physical Society
2024
Exact and leading order radiative effects in semi-inclusive deep inelastic scattering
Authors: Akushevich Igor , Srednyak Stanislav , Ilyichev Alexander
Published: April 2024

Radiative effects in semi-inclusive hadron leptoproduction of unpolarized particles are calculated within the leading order approximation. The contributions of the infrared-free sum of the effects of real and virtual photon emission as well as the contribution of the exclusive radiative tail are considered. It is demonstrated how the obtained formulas in the leading log approximation can be obtained using the standard approach of the leading log approximation as well as from the exact expressions for the radiative correction of the lowest order. The method of the electron structure function is used to calculate the higher order corrections. The results are analytically compared to the results obtained by other groups. Numeric illustrations are given in the kinematics of the modern experiments at Jefferson Laboratory.

Published by the American Physical Society
2024
Particle discrimination in a NaI crystal using the COSINUS remote TES design
Authors: Angloher G. , Bharadwaj M. R. , Dafinei I. , Di Marco N. , Einfalt L. , Ferroni F. , Fichtinger S. , Filipponi A. , Frank T. , Friedl M. , Fuss A. , Ge Z. , Heikinheimo M. , Hughes M. N. , Huitu K. , Kellermann M. , Maji R. , Mancuso M. , Pagnanini L. , Petricca F. , Pirro S. , Pröbst F. , Profeta G. , Puiu A. , Reindl F. , Schäffner K. , Schieck J. , Schmiedmayer D. , Schwertner C. , Stahlberg M. , Stendahl A. , Stukel M. , Tresca C. , Wagner F. , Yue S. , Zema V. , Zhu Y. , Bento A. , Canonica L. , Garai A. ,   COSINUS Collaboration
Published: April 2024

The COSINUS direct dark matter experiment situated at Laboratori Nazionali del Gran Sasso in Italy is set to investigate the nature of the annually modulating signal detected by the DAMA/LIBRA experiment. COSINUS has already demonstrated that sodium iodide crystals can be operated at mK temperature as cryogenic scintillating calorimeters using transition edge sensors, despite the complication of handling a hygroscopic and low melting point material. With results from a new COSINUS prototype, we show that particle discrimination on an event-by-event basis in NaI is feasible using the dual-channel readout of both phonons and scintillation light. The detector was mounted in the novel remoTES design and operated in an above-ground facility for 9.06  g·d of exposure. With a 3.7 g NaI crystal, e−/γ events could be clearly distinguished from nuclear recoils down to the nuclear recoil energy threshold of 20 keV.

Published by the American Physical Society
2024
SKA sensitivity to sub-GeV dark matter decay: Synchrotron radio emissions in white dwarf magnetospheres
Authors: Kadota Kenji , Kisaka Shota
Published: April 2024

We investigate the potential of the Square Kilometre Array (SKA) in detecting synchrotron radiation emitted from the decay of sub-GeV dark matter (dark matter with masses below the GeV scale) in the presence of strong magnetic fields. As a concrete setup, we consider scenarios where the magnetosphere of a magnetic white dwarf overlaps with dense dark matter environments, such as those surrounding a primordial black hole. Our study reveals that the encounters of compact objects such as white dwarfs and black holes offer a promising avenue for upcoming radio telescopes to probe the properties of light dark matter, which has been less explored compared with more conventional heavier (masses above the GeV scale) dark matter.

Published by the American Physical Society
2024
Black hole perturbation theory meets
CFT2
: Kerr-Compton amplitudes from Nekrasov-Shatashvili functions
Authors: Bautista Yilber Fabian , Bonelli Giulio , Iossa Cristoforo , Tanzini Alessandro , Zhou Zihan
Published: April 2024

We present a novel study of Kerr Compton amplitudes in a partial wave basis in terms of the Nekrasov-Shatashvili (NS) function of the confluent Heun equation (CHE). Remarkably, NS-functions enjoy analytic properties and symmetries that are naturally inherited by the Compton amplitudes. Based on this, we characterize the analytic dependence of the Compton phase shift in the Kerr spin parameter and provide a direct comparison to the standard post-Minkowskian (PM) perturbative approach within general relativity (GR). We also analyze the universal large frequency behavior of the relevant characteristic exponent of the CHE—also known as the renormalized angular momentum—and find agreement with numerical computations. Moreover, we discuss the analytic continuation in the harmonics quantum number ℓ of the partial wave, and show that the limit to the physical integer values commutes with the PM expansion of the observables. Finally, we obtain the contributions to the tree-level, point-particle, gravitational Compton amplitude in a covariant basis through O(aBH8), without the need to take the superextremal limit for Kerr spin.

Published by the American Physical Society
2024
Reflection coefficient of a reflectionless kink
Authors: Evslin Jarah , Liu Hui
Published: April 2024

Classically, reflectionless kinks transmit all incident radiation. Recently, we have used an analyticity argument together with a solution of the Lippmann-Schwinger equation to write down the leading quantum correction to the reflection probability. The argument was fast, but rather indirect. In the present paper, we calculate the reflection coefficient and probability by methodically grinding through the Schrödinger picture time evolution. We find the same answer. This answer contains contributions not considered in the traditional calculation of meson-kink scattering in 1991. However, as a result of these contributions, our total result is zero in the case of the Sine-Gordon model, and so it is consistent with integrability.

Published by the American Physical Society
2024
Toward a neutrino-limited dark matter search with crystalline xenon
Authors: Chen Hao , Gibbons Ryan , Haselschwardt S. J. , Kravitz Scott , Xia Qing , Sorensen Peter
Published: April 2024

Experiments searching for weakly interacting massive particle dark matter are now detecting background events from solar neutrino-electron scattering. However, the dominant radioactive background in state-of-the-art experiments such as LZ and XENONnT is beta decays from radon contamination. In spite of careful detector material screening, radon progenitor atoms are ubiquitous and long-lived, and radon is extremely soluble in liquid xenon. We propose a change of phase and demonstrate that crystalline xenon offers more than a factor ×500 exclusion against radon ingress, compared with the liquid state. This level of radon exclusion would allow crystallized versions of existing experiments to probe spin-independent cross sections near 10−47  cm2 in roughly 11 years, as opposed to the 35 years required otherwise.

Published by the American Physical Society
2024
Complete determination of
SU(3)F
amplitudes and strong phase in
Λc+→Ξ0K+
Authors: Geng Chao-Qiang , He Xiao-Gang , Jin Xiang-Nan , Liu Chia-Wei , Yang Chang
Published: April 2024

The BESIII collaboration has recently reported the first time measurement of the decay asymmetry α(Λc+→Ξ0K+)=0.01±0.16(stat)±0.03(syst) and also a sizable phase shift of δP−δS=−1.55±0.25 or 1.59±0.25 between S- and P-wave amplitudes. This implies significant strong phase shifts in the decay amplitudes. The strong phases indicate the existence of rescattering or loop effects, which are challenging to calculate due to nonperturbative effects. By employing the flavor

S

U

(

3

)

F

symmetry and applying the Körner-Pati-Woo theorem to reduce the number of parameters, we find that the current data already allow us to obtain, for the first time, model-independent decay amplitudes and their strong phases. The establishment of the existence of sizable strong phases opens a window for future investigations into CP violation. In our fit, a notable discrepancy emerges in the branching ratio of Ξc0→Ξ−π+. The direct relationship between Γ(Λc+→Λe+νe) and Γ(Ξc0→Ξ−e+νe), along with newly discovered SU(3)F relations, collectively suggests an underestimation of B(Ξc0→Ξ−π+) in experimental findings.

Published by the American Physical Society
2024
Maximizing quantum-computing expressive power through randomized circuits
Authors: Yang Yingli , Zhang Zongkang , Wang Anbang , Xu Xiaosi , Wang Xiaoting , Li Ying
Published: April 2024

In the noisy intermediate-scale quantum era, variational quantum algorithms (VQAs) have emerged as a promising avenue to obtain quantum advantage. However, the success of VQAs depends on the expressive power of parametrized quantum circuits, which is constrained by the limited gate number and the presence of barren plateaus. In this paper, we propose and numerically demonstrate an approach for VQAs, utilizing randomized quantum circuits to generate the variational wave function. We parametrize the distribution function of these random circuits using artificial neural networks and optimize it to find the solution. This random-circuit approach presents a trade-off between maximizing the expressive power of the variational wave function and minimizing the associated time cost, specifically the sampling cost of quantum circuits. Given a fixed gate number, we can systematically increase the expressive power by extending the quantum-computing time. With a sufficiently large permissible time cost, the variational wave function can approximate any quantum state with arbitrary accuracy. Furthermore, we establish explicit relationships between expressive power, time cost, and gate number for variational quantum eigensolvers. These results highlight the promising potential of the random-circuit approach in achieving a high expressive power in quantum computing.

Published by the American Physical Society
2024