bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractIn 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

AbstractcAMP 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

AbstractFunctional 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

ABSTRACTBackgroundOutbreaks 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.MethodA 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.ResultsOur 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.ConclusionThis 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

ABSTRACTSpatial 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

ABSTRACTActin 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.
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

AbstractHemibiotrophic 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

AbstractThis 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.
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
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
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
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 SU(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