bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the role of stomatal dynamics on agronomic traits using aslac1-2 Zea maysmutant
Authors: Twohey Robert J. , Christenson Clay G. , Li Catherine , Bacher Harel , Calleja Sebastian , Pastor Bryan , Hanneman Marjorie , Wickes-Do Liam , Gore Michael A. , Pauli Duke , Moose Stephen P. , Studer Anthony J.
Published: January 2025

The production of staple food crops is becoming increasingly difficult due to the amount of freshwater needed to realize food security for a growing global population. Climate projections show hotter and drier growing seasons in traditionally productive agricultural regions, which will increase the demand for limited water resources. Thus, strategies to improve water use efficiency will only become more important for sustainable agriculture. At the leaf level, stomatal conductance has a large influence on transpirational water loss and therefore water use efficiency. The anion channel SLAC1 has been shown in several plant species to function as the primary mechanism for stomatal closure, which allows stomatal aperture to change dynamically in response to environmental stimuli. Given thatslac1is a single gene that can significantly alter stomatal conductance, it has the potential to serve as a control point for improving water use efficiency. Here we fully characterize aZea mays slac1-2mutant in multiple field environments. Interestingly, homozygousslac1-2hybrids did not show improved net CO2assimilation or increased grain yield despite having greater stomatal conductance compared to a wild-type hybrid. Net CO2assimilation and grain yield were either lower or similar inslac1-2compared to wild-type across environments. Furthermore, theslac1-2hybrid did not have increased nitrogen uptake. These results suggest that the C4carbon concentrating mechanism removes any stomatal conductance limitations to CO2assimilation, even in highly productive wild-typeZ. mayshybrids. Because theslac1-2hybrids eliminate stomatal conductance as a major variable for modulating water loss, future studies will be able to investigate alternate regulators of plant water potential to identify novel mechanisms for increasing water use efficiency.
Risk factors for renal stone development in adults with primary hyperparathyroidism: A protocol for a systematic review and meta-analysis
Authors: Jay Mohammad , Andrei Sorina , Hoang Peter , Samhat Hussein , Jones Roland , Fu Rui , Lipscombe Lorraine , Eskander Antoine
Published: January 2025

Background

Primary hyperparathyroidism (PHPT) is characterized by overactive parathyroid glands. Renal stones (RS) are a common complication of PHPT and is associated with increased morbidity. However, the risk factors for RS in PHPT are not well-established and the latest international PHPT guideline highlights the need for further research into this area.

Objective

We aim to summarize and meta-analyze the existing evidence on prespecified risk factors associated with RS in adults with PHPT.

Methods and Analysis

We will search MEDLINE, EMBASE, and Cochrane Central from inception. Two independent reviewers will screen studies and include prospective/retrospective cohort, case-control, and cross-sectional designs in adults (≥18 years) with PHPT. Randomized trials, conference abstracts, case reports, and commentaries will be excluded. Two reviewers will independently extract data on population characteristics, risk factors, RS outcomes, and assess risk of bias using the Quality in Prognostic Studies tool. A random-effects model will be used to pool odds ratios. We will separately pool adjusted (primary analyses) and unadjusted odds ratios (secondary analyses) with their corresponding 95% confidence intervals. Certainty will be evaluated with the Grading of Recommendations Assessment, Development, and Evaluation framework. Heterogeneity will be assessed using the I² statistic and publication bias will be evaluated with funnel plots.

Discussion

Early identification of patients with PHPT at high risk for RS can facilitate the implementation of preventive strategies and reduce morbidity. Furthermore, recognizing these risk factors can assist clinicians in prioritizing treatment for those at higher risk, ultimately improving patient outcomes.

Protocol registration

The protocol was registered in PROSPERO on November 14, 2024 (registration ID: CRD42024608180).

Funding

No source of financial funding was used.
Evidence of Resiliency in Maternal Health Services and Outcomes in Kono District, Sierra Leone during the COVID-19 Pandemic: An Observational Study
Authors: Boima Foday , Mekonnen Zeleke Abebaw , Koroma Manso M , Lado Marta , Chan Adrienne K. , Mishra Sharmistha , N’jai Alhaji U. , Molleh Bailah , Sevalie Stephen , Lakoh Sulaiman
Published: January 2025

Background

This study evaluated the resilience and outcomes of maternal health services during the COVID-19 pandemic in two health facilities in eastern Sierra Leone. Its aims to describe the use of maternal healthcare services and maternal and neonatal outcomes in these two facilities before, during, and after the COVID-19 pandemic.

Methods

The study involved analysis of routine programme data (March 2019 to February 2022) from two public-funded health facilities supported by a non-governmental organization (Partners In Health in Sierra Leone): Koidu Government Hospital and Wellbody Clinic. Aggregated and de-identified secondary data from the Partner In Health Maternal Health Database was abstracted using a standardized tool. Descriptive statistics and bivariable negative binomial regression were used to assess the association between time periods (before COVID-19 [March 2019 to February 2020], during COVID-19 emergency [March 2020 to February 2021], after COVID-19 emergency [March 2021 to February 2022) and outcomes each month (fourth antenatal care visit and facility deliveries).

Results

The study analyzed 3,204 fourth antenatal care visits and 7,369 deliveries over 36 months at both health facilities. Fourth antenatal care visits (from 947 to 920) and facility deliveries (from 2309 to 2221) decreased during COVID-19 compared to pre-COVID-19. However, maternal (from 32 to 23) and neonatal (36 to 26) deaths declined during COVID-19 compared to the pre-COVID-19 period at Koidu Government Hospital.

Conclusion

In Sierra Leone, the resources and efforts directed to the post-Ebola recovery strategy were tested during and after the COVID-19 pandemic. Our study demonstrates the resilience of maternal and neonatal services in two healthcare facilities in a less-affected region of Sierra Leone, to the anticipated disruptions due to the COVID-19 pandemic.
Exploring the Interplay of Poverty, Behavioral Factors, and Obesity: Implications for Diabetes Prevalence in the United States
Authors: Chatterjee Swarn
Published: January 2025

The prevalence of diabetes and obesity are a significant public health concern in the United States, with profound implications for millions of Americans. As of 2018, around 34.2 million individuals were diagnosed with diabetes, while an additional 88 million adults were classified as prediabetic, indicating a troubling trend exacerbated by rising obesity rates (Francis, 2021; Liu et al., 2023). Behavioral factors, including smoking, and heavy alcohol consumption are also associated with the prevalence of diabetes and obesity. This study uses geo-spatial county-level data obtained from merging the 2021 CDC PLACES dataset and the 2019 American Community Survey dataset to analyze the roles of smoking, poverty, and binge drinking on the prevalence of obesity and diabetes across the United States. The findings indicate that higher rates of poverty, smoking and alcohol consumption maybe associated with higher rates of obesity, and diversity at the county level. But, the findings of this study also suggest substantial regional variations in these associations.
Brain Age: A Promising Biomarker for Understanding Aging in the Context of Cognitive Reserve
Authors: Beheshti Iman
Published: January 2025

INTRODUCTION: Cognitive decline is a major concern in aging populations. Detecting it before clinical symptoms emerge remains a significant challenge. A precise, reliable, and non-invasive biomarker for cognitive health could revolutionize how we monitor normal aging and lifestyle impacts. Such a tool would not only identify individuals at risk of cognitive decline years before symptoms manifest but also aid in early interventions and treatments. METHODS: Longitudinal MRI data from 121 high cognitive reserve (HCR) individuals were compared to matched low cognitive reserve (LCR) individuals to evaluate four biomarkers for early cognitive decline and disease progression: brain age delta, cortical thickness, AD cortical signature, and hippocampal volume. Cross-sectional analyses were conducted at baseline, alongside longitudinal assessments spanning 1 to 12 years, to compare the performance and properties of these biomarkers. RESULTS: The brain age metric emerged as the most reliable biomarker, demonstrating a significant ability to differentiate between groups at baseline (β = 1.250, t = 3.521, p = 0.0009; linear regression model; AUC = 0.73). Furthermore, this biomarker maintained its robustness as the strongest predictor of group membership over a follow-up period of up to 12 years (β = 0.409, p = 0.025; mixed-effects model), underscoring its potential for longitudinal monitoring of cognitive decline. DISCUSSION: The brain age biomarker demonstrates potential as an effective indicator for early cognitive decline, capable of detecting changes years before clinical symptoms appear and tracking age-related brain and cognitive changes over time. These findings suggest that integrating MRI biomarkers with machine learning approaches could yield more accurate and reliable tools for assessing cognitive health, surpassing the limitations of relying solely on MRI biomarkers.
Prevalence of cancer-related cognitive impairment in pediatric patients and survivors of non-CNS cancers: A systematic review and meta-analysis
Authors: Semendric Ines , Barker Timothy Hugh , Haller Olivia Jane , Pollock Danielle , Collins-Praino Lyndsey E. , Whittaker Alexandra L.
Published: January 2025

Background: Neurocognitive toxicity is a common sequela of cancer and its treatment, with 40-60% of childhood cancer survivors experiencing cancer-related cognitive impairment (CRCI) following cancer and its treatment. CNS cancers and CNS-directed therapy are considered to pose the greatest risk; however, such impairment has also been reported in non-CNS cancers, the most commonly diagnosed in children. Despite initial findings, no formal systematic assimilation of evidence has previously reported estimates in pediatric populations, or identified the influence of cancer, treatment, and patient variables. Thus, this review aims to investigate the prevalence of CRCI in pediatric non-CNS cancers. Methods: A systematic search was conducted using PubMed via MEDLINE, Scopus, PsycINFO via OvidSP, and CINAHL via EBSCOhost. Simple proportional meta-analyses were performed using PERSyst, and the certainty of evidence was assessed employing GRADE. Results: Twenty-six studies contributed to two cognitive domains - (1) global cognitive function and intelligence, and (2) achievement, aptitude and school readiness. Pooled prevalence estimates suggest that survivors of non-CNS cancers experience impairments in measures of intelligence (12.46%-18.05%) and attention (9.83%-12.05%). Non-pooled prevalence estimates ranged from 0-67% in global cognitive function and intelligence, and 0-73% in achievement, aptitude and school readiness. Conclusion: Survivors of non-CNS cancers experience significant impairments in these cognitive domains; however, certainty of evidence is generally low to very low, warranting cautious interpretation of prevalence estimates. Implication for Cancer Survivors: Understanding the prevalence of CRCI following childhood cancer can inform survivorship strategies and provide impetus for provision of dedicated supports, such as rehabilitation and school reintegration supports.
Dynamic treatment regime in critical ill patients with high risk of antibiotic drug resistance, a cohort study
Authors: Liu Yiwei
Published: January 2025

Antibiotic resistance threatens modern medicine, especially in critical care. This retrospective observational cohort study, based on MIMIC IV v2.0 database, included 2,532 ICU admissions with high risk antibiotic resistance. We aimed to find the optimal strategy for using high risk resisted antibiotics in critical ill patients by constructing a dynamic treatment regime (DTR) model with DWSurv method. The results showed that the DTR optimal model's suggestion differed from clinical practice. Clinical practice showed a sharp decline in high - risk resistance antibiotic administration, while the model suggested treatment with gaps in 7 days. Survival analysis indicated that the DTR model had a lower mortality rate. The more the clinical practice disobeyed the model's recommendation, the higher the 28 - day mortality (adjusted HR = 1.21, 95%CI: 1.12, 1.30, P<0.001). This study suggests that the DTR model might offer a new perspective on personalized antibiotic administration, but its clinical application remains to be further explored.
A novel lncRNA FAM151B-DT regulates autophagy and degradation of aggregation prone proteins
Authors: Renganathan Arun , Minaya Miguel A. , Broder Matthew , Alfradique-Dunham Isabel , Moritz Michelle , Bhagat Reshma , Marsh Jacob , Verbeck Anthony , Galasso Grant , Starr Emma , Agard David , Cruchaga Carlos , Karch Celeste M.
Published: January 2025

Neurodegenerative diseases share common features of protein aggregation along with other pleiotropic traits, including shifts in transcriptional patterns, neuroinflammation, disruptions in synaptic signaling, mitochondrial dysfunction, oxidative stress, and impaired clearance mechanisms like autophagy. However, key regulators of these pleotropic traits have yet to be identified. Here, we discovered a novel long non-coding RNA (lncRNA), FAM151B-DT, that is reduced in a stem cell model of frontotemporal dementia with tau inclusions (FTLD-tau) and in brains from FTLD-tau, progressive supranuclear palsy, Alzheimer's disease, and Parkinson's disease patients. We show that silencing FAM151B-DT in vitro is sufficient to enhance tau aggregation. To begin to understand the mechanism by which FAM151B-DT mediates tau aggregation and contributes to several neurodegenerative diseases, we deeply characterized this novel lncRNA and found that FAM151B-DT resides in the cytoplasm where it interacts with tau, α-synuclein, HSC70, and other proteins enriched in protein homeostasis. When silenced, FAM151B-DT blocks autophagy, leading to the accumulation of tau and α-synuclein. Importantly, we discovered that increasing FAM151B-DT expression is sufficient to promote autophagic flux, reduce phospho-tau and α-synuclein, and reduce tau aggregation. Overall, these findings pave the way for further exploration of FAM151B-DT as a promising molecular target for several neurodegenerative diseases.
X-Pro: A web-based tool to analyze the loss and gain of local interaction upon a point mutation on protein structures
Authors: Viswakarma Aman , Neelakanteswara Anurag , Thiyagarajan Saravanamuthu
Published: January 2025

Understanding how point mutations affect protein structures is critical for understanding their impacts on a protein’s function and, eventually their role in causing diseases or biological differences. In recent decades, structural inferences of missense mutations have gained significant attention due to their importance in understanding monogenic disorders. Making point mutations in silico is one of the simple bioinformatics tasks. Existing GUI-based open-source tools like PyMOL, Chimera, Discovery Studio, etc., have simplified this task so that it can be done with a few mouse clicks. However, this continues to be a difficult task for untrained biologists. Further, understanding the loss and gain of interactions caused by such mutations remains even more challenging to them. To address this, we have developed a simple web-browser-based application namedX-Prowherein a PDB structure, chain ID, residue number, and the target mutation are taken as inputs, along with mutation information. The tool runs PyMOL and LigPlot tools in the back-end, taking the site of mutation as the ligand and returning graphical images of the structure before and after in-silico point mutation, and a table listing the loss and gain of interactions arising from this mutation. The tool is available for users at the URLhttp://bts.ibab.ac.in/X-Pro.php.
Chloride intracellular channel (CLIC) protein function in S1P-induced Rac1 activation requires membrane localization of the C-terminus, but not thiol-transferase nor ion channel activities
Authors: Mao De Yu , Jesse Jordan J. , Shaye Daniel D. , Kitajewski Jan
Published: January 2025

We have established a novel and evolutionarily-conserved function for chloride intracellular channel proteins (CLICs) in regulating Rho/Rac GTPases downstream of G protein-coupled receptors (GPCRs). Endothelial CLIC1 and CLIC4 are rapidly and transiently re-localized from the cytoplasm to the plasma membrane in response to the GPCR ligand sphingosine-1-phosphate (S1P), and both CLICs are required to activate Rac1 in response to S1P, but how they perform this function remains unknown. Biochemical studies suggest that CLICs act as non-specific ion channels and/or as glutathione-S-transferases, dependent on N-terminal features,in vitro. Here we investigate CLIC functional domains and membrane localization requirements for their function in S1P-mediated Rac1 signaling. Structure-function analyses of CLIC function in endothelial cells demonstrate that CLIC1 and CLIC4-specific functions reside at their C-termini, and that the CLIC4 N-terminus encodes determinants required for S1P-induced re-localization to the plasma membrane but is dispensable for S1P-induced Rac1 activation when the C-terminus is localized to the plasma membrane via a heterologous signal. Our results demonstrate that the postulated ion channel and thiol-transferase activities of CLICs are not required for Rac1 activation and suggests that sequences in the CLIC C-termini are critical for this function. Given the importance of S1P signaling in vascular biology and disease, our work establishes a platform to further our understanding of the membrane-localized proteins required to link GPCR activity to Rho/Rac regulation.
Erythropoietin decreases apoptosis and promotes Schwann cell repair and phagocytosis following nerve crush injury in mice
Authors: Govindappa Prem Kumar , Ellur Govindaraj , Hegarty John P. , Gupta Akash , Rahul V. G. , Elfar John C.
Published: January 2025

After peripheral nerve trauma, insufficient clearance of phagocytic debris significantly hinders nerve regeneration. Without sufficient myelin debris clearance, Schwann cells (SCs) undergo increased apoptosis, impairing functional recovery. There is no treatment for peripheral nerve crush injury (PNCI). Erythropoietin (EPO) is an FDA-approved drug for anemia, which may help in the treatment of PNCI by transdifferentiating resident SCs into repair SCs (rSCs) and enhancing phagocytosis to facilitate the removal of cellular debris. For the first time, we conducted bulk RNA sequencing on mice with calibrated sciatic nerve crush injuries (SNCIs) on days 3, 5, and 7 post-SNCI to uncover transcriptomic changes with and without EPO treatment. We found EPO altered several biological pathways and associated genes, particularly those involved in cell apoptosis, differentiation, proliferation, phagocytosis, myelination, and neurogenesis. We validated the effects of EPO on SNCI on early (days 3/5) and intermediate (day 7) post-SNCI, and found EPO treatment reduced apoptosis (TUNEL), and enhanced SC repair (c-Jun and p75-NTR), proliferation (Ki67), and the phagocytosis of myelin debris by rSCs at crush injury sites. This improvement corresponded with an enhanced sciatic functional index (SFI). We also confirmed these findingsin-vitro. EPO significantly enhanced SC repair during early de-differentiation, marked by high c-Jun and p75-NTR protein levels, and later re-differentiation with high EGR2 and low c-Jun and p75-NTR levels. These changes occurred under lipopolysaccharide (LPS) stress at 24 and 72h, respectively, compared to LPS treatment alone. Under LPS stress, EPO also significantly increased rSCs proliferation and phagocytosis of myelin or dead SCs. In conclusion, our findings support EPO may enhance the function of rSCs in debris clearance as a basis for its possible use in treating nerve trauma.
History shapes regulatory and evolutionary responses to tigecycline in strains ofAcinetobacter baumanniifrom the pre- and post-antibiotic eras
Authors: Rokes Alecia B , Santos-Lopez Alfonso , Cooper Vaughn S
Published: January 2025

Evolutionary history encompasses genetic and phenotypic bacterial differences, but the extent to which history influences drug response and antimicrobial resistance (AMR) adaptation is unclear. Historical contingencies arise when elements from an organism’s past leave lasting effects on the genome, altering the paths available for adaptation. We utilize strains isolated before and after widespread antibiotic use to study the impact of deep historical differences shaped by decades of evolution in varying antibiotic and host pressures. We evaluated these effects by comparing immediate and adaptive responses of two strains ofAcinetobacter baumanniito the last-resort antibiotic, tigecycline (TGC). When grown in subinhibitory TGC, the two strains demonstrated divergent transcriptional responses suggesting that baseline transcript levels may dictate global responses to drug and their subsequent evolutionary trajectories. Experimental evolution in TGC revealed clear differences in population-genetic dynamics – with hard sweeps in populations founded by one strain and no mutations reaching fixation in the other strain. Transcriptomes of evolved populations no longer showed signatures of drug response, as was seen in the ancestors, suggesting that genetic adaptation may outweigh preexisting differences in transcriptional networks. Genetically, AMR was acquired through predictable mechanisms of increased efflux and drug target modification; however, the two strains adapted by mutations in different efflux regulators. Fitness tradeoffs of AMR were only observed in lineages evolved from the pre-antibiotic era strain, suggesting that decades of adaptation to antibiotics resulted in preexisting compensatory mechanisms in the more contemporary isolate, an important example of a beneficial effect of historical contingencies.

SIGNIFICANCE STATEMENT

Acinetobacter baumanniiis a high priority pathogen often causing multidrug resistant nosocomial infections. Many healthcare systems experience clonal outbreaks ofA. baumanniiinfections, yet treatment strategies are often strain-agnostic, ignoring the importance of strain differences. We show that historical differences between two strains, one isolated prior to widespread antibiotic use and the other following decades of selection to clinical conditions, dictate transcriptional patterns and response to a last-resort antibiotic and influence the genetic and phenotypic routes of resistance adaptation. While our study focuses on two reference strains ofA. baumannii,these findings can be more broadly applicable to other pathogenic organisms in which a better understanding of the forces influencing resistance adaptation is essential for combating the antimicrobial resistance crisis.
Prescribers' and Pharmacists' Perception of Adoption and Implementation of Electronic Prescribing and Medication Management System in Public Health Facilities of Dessie city, Northeast Ethiopia
Authors: Gebrehiwot Getachew Moges , Ebrahim Naser , Bayked Ewunetie Mekashaw , Yesuf Teshager Aklilu , Mohammed Solomon Ahmed
Published: January 2025

Medication errors are one of the major causes of preventable adverse drug effects. Errors associated with prescribing and dispensing are prevalent. Electronic prescribing (e-prescribing) offers a solution to mitigate these errors by enhancing legibility, dosing, and remote accessibility. This study aimed to investigate the perceptions of prescribers and pharmacists regarding the adoption and implementation of electronic prescribing (e-prescribing) and electronic medication management (EMM) systems in public health facilities of Dessie City administration, Northeast Ethiopia. A cross-sectional survey was conducted from April 20 to June 25, 2022, in public health facilities of Dessie City administration. A structured self-administered questionnaire was employed to collect data from 201 prescribers and pharmacists. The study was based on the unified theory of acceptance and use of technology model. Data were analyzed using SPSS version 25 and SmartPLS version 4.0. Nearly 34 (72.5%) of the respondents were males. The majority (88.6%) of the participants had a positive perception towards the use of e-prescribing and EMM systems. The mean score for performance expectancy, effort expectancy, and facilitating conditions were 4.29, 4.26, and 4.18, respectively. Perceived facilitating conditions (β = 0.271, p = 0.003), price value (β = 0.239, p = 0.002), performance expectancy (β = 0.237, p = 0.008), and effort expectancy (β = 0.176, p = 0.008) were found to affect the acceptance of e-prescribing and EMM systems among prescribers and pharmacists. Prescribers and pharmacists have a positive perception towards the use of e-prescribing and EMM systems. Perceived facilitating conditions, price value, performance expectancy, and effort expectancy significantly influence acceptance. The effect of perceived credibility on acceptance was fully mediated by performance expectancy.
Super-resolution microscopy of mitochondrial mRNAs
Authors: Stoldt Stefan , Maass Frederike , Weber Michael , Dennerlein Sven , Ilgen Peter , Gaertner Jutta , Canfes Aysenur , Schweighofer Sarah V. , Jans Daniel C. , Rehling Peter , Jakobs Stefan
Published: January 2025

Mitochondria contain their own DNA (mtDNA) and a dedicated gene expression machinery. As the mitochondrial dimensions are close to the diffraction limit of classical light microscopy, the spatial distribution of mitochondrial proteins and in particular of mitochondrial mRNAs remains underexplored. Here, we establish single-molecule fluorescence in situ hybridization (smFISH) combined with STED and MINFLUX super-resolution microscopy (nanoscopy) to visualize individual mitochondrial mRNA molecules and associated proteins. STED nanoscopy revealed the spatial relationships between distinct mRNA species and proteins such as the RNA granule marker GRSF1, demonstrating adaptive changes in mRNA distribution and quantity in challenged mammalian cells and patient-derived cell lines. Notably, STED-smFISH showed the release of mRNAs during apoptosis, while MINFLUX revealed the folding of the mRNAs into variable shapes, as well as their spatial proximity to mitochondrial ribosomes. These protocols are transferable to various cell types and open new avenues for understanding mitochondrial gene regulation in health and disease.
First genomic resource of ‘CandidatusPhytoplasma pyri’ associated to pear
Authors: Alessio Florencia Ivette , Bongiorno Vanina Aylen , von Backzo Oscar Hernan , Conci Luis Rogelio , Fernandez Franco Daniel
Published: January 2025

This study reports the draft genome ofCandidatusPhytoplasma pyri strain P1, isolated from Argentina, marking the first global sequencing of this species. The genome assembly consisted of 16 contigs, with a total length of 575,431 bp, a GC content of 20.35%, and 125X coverage. A total of 536 genes were annotated, including those related to metabolism, genetic information processing, and signaling. Phylogenetic analysis placed ‘CandidatusPhytoplasma pyri’ within the 16SrX group, supporting its classification as a distinct species from ‘CandidatusPhytoplasma mali’ and ‘CandidatusPhytoplasma prunorum’, despite their close evolutionary proximity. The investigation also identified 17 secreted proteins, including homologs of known effectors such as SAP39 and SAP41, as well as conserved proteins associated with virulence mechanisms. A homologue of the Imp immunodominant membrane protein was also characterized, revealing conserved gene organization across related strains. These findings contribute to the understanding of ‘CandidatusPhytoplasma pyri’ pathogenic and provide valuable genomic data for future research. This study highlights the importance of expanding phytoplasma genomics, as it provides a crucial first step in understanding ‘CandidatusPhytoplasma pyri’ and its role in plant pathology
Proximity labeling and orthogonal nanobody pulldown (ID-oPD) approaches to map the spinophilin interactome uncover a putative role for spinophilin in protein homeostasis
Authors: Claeboe Emily T. , Blake Keyana L. , Shah Nikhil R. , Morris Cameron W. , Hens Basant , Atwood Brady K. , Absalon Sabrina , Mosley Amber L. , Doud Emma H. , Baucum Anthony J.
Published: January 2025

Spinophilin is a dendritic spine enriched scaffolding and protein phosphatase 1 targeting protein. To detail spinophilin interacting proteins, we created an Ultra-ID and ALFA-tagged spinophilin encoding construct that permits proximity labeling and orthogonal nanobody pulldown (ID-oPD) of spinophilin-associated protein complexes in heterologous cells. We identified 614 specific, and 312 specific and selective, spinophilin interacting proteins in HEK293 cells and validated a subset of these using orthogonal approaches. Many of these proteins are involved in mRNA processing and translation. In the brain, we determined that spinophilin mRNA is highly neuropil localized and that spinophilin may normally function to limit its own expression but promote the expression of other PSD-associated proteins. Overall, our use of an ID-oPD approach uncovers a novel putative role for spinophilin in mRNA translation and synaptic protein expression specifically within dendritic spines.
Pancreatic injury induces β−cell regeneration in axolotl
Authors: Powell Connor J. , Singer Hani D. , Juarez Ashley R. , Kim Ryan T. , Payzin-Dogru Duygu , Savage Aaron M. , Lopez Noah J. , Blair Steven J. , Abouelela Adnan , Dittrich Anita , Akeson Stuart G. , Jain Miten , Whited Jessica L.
Published: January 2025

Background

Diabetes is a condition characterized by a loss of pancreatic β−cell function which results in the dysregulation of insulin homeostasis. Using a partial pancreatectomy model in axolotl, we aimed to observe the pancreatic response to injury.

Results

Here we show a comprehensive histological assessment of pancreatic islets in axolotl. Following pancreatic injury, no apparent blastemal structure was observed. We found a significant, organ-wide increase in cellular proliferation post-resection in the pancreas compared to sham-operated controls. This proliferative response was most robust at the site of injury. We found that β−cells actively contributed to the increased rates of proliferation upon injury. β−cell proliferation manifested in increased β−cell mass in injured tissue at two weeks post injury. At four weeks post injury, we found organ-wide proliferation to be extinguished while proliferation at the injury site persisted, corresponding to pancreatic tissue recovery. Similarly, total β−cell mass was comparable to sham after four weeks.

Conclusions

Our findings suggest a non-blastema-mediated regeneration process takes place in the pancreas, by which pancreatic resection induces whole-organ β−cell proliferation without the formation of a blastemal structure. This process is analogous to other models of compensatory growth in axolotl, including liver regeneration.
Microscopy-Guided Spatial Proteomics Reveals Novel Proteins at the Mitochondria-Lipid Droplet Interface and Their Role in Lipid Metabolism
Authors: Lin Yen-Ming , Chong Weng Man , Huang Chun-Kai , Chang Hsiao-Jen , Cheung Chantal Hoi Yin , Liao Jung-Chi
Published: January 2025

Mitochondria-lipid droplet (LD) interactions play a critical role in lipid metabolism and the progression of metabolic diseases such as non-alcoholic fatty liver disease (NAFLD). However, the dynamic nature of these interactions has hindered the identification of novel protein constituents and their functional roles. Here, we employed Microscoop Mint, an advanced microscopy-guided spatial proteomics platform, to isolate proteins localized at mitochondria-LD contact sites in oleic acid (OA)-treated HepG2 cells, an in vitro model for studying fatty liver disease. Microscoop Mint integrates high-resolution image analysis and two-photon illumination to achieve precise biotinylation of proteins at subcellular regions of interest. Coupled with mass spectrometry, this approach identified a proteome enriched at the mitochondria-LD interface, including both well-characterized lipid-associated proteins and previously unrecognized candidates. Among the 373 common proteins identified across replicates, five novel candidates with no prior association to lipid metabolism were selected for validation. Immunofluorescence staining confirmed their localization at mitochondria-LD contact sites, with more pronounced association in OA-treated cells. Notably, suppression of one candidate, FHL3, led to reduced LD size, elongated mitochondrial morphology, and diminished mitochondria-LD interactions, suggesting its role in regulating fatty acid β-oxidation. Our findings demonstrate the utility of Microscoop Mint in unveiling novel molecular players at organelle contact sites. This study not only provides insights into the functional dynamics of mitochondria-LD interactions but also highlights potential therapeutic targets for lipid metabolic disorders and NAFLD.
Optimizing the quality of acoustophoretic separation by the in-flow mobility-ratio method
Authors: Baasch Thierry , Edthofer Alexander , Péroux Linda , Rengbrandt Olivia , Silversand Lovisa , Lenshof Andreas , Laurell Thomas
Published: January 2025

Achieving good acoustic particle or cell separation performance requires skilled operators, who must carefully fine-tune the input parameters (actuation voltages, flow rates, and flow split ratios). Often the fine-tuning is done by time-consuming parameter sweeps, which are tedious and expensive. Here, we present a straightforward model-based approach to determining input parameters that yield optimal separation performance. The optimal parameters are a function of the device performance, the material properties of the separation species (compressibility, density, size), and the properties of the buffer (compressibility and density). The device performance is assessed by a calibration step, while the material properties are combined into the mobility ratio and measured by the in-flow mobility-ratio method, which is introduced in this work. The optimal separation settings are validated by separating green fluorescent 7.8-μm particles from red fluorescent 4.9-μm particles.

Published by the American Physical Society
2025
Confinement-Higgs and deconfinement-Higgs transitions in three-dimensional Z(2) LGT
Authors: Allés B. , Borisenko O. , Papa A.
Published: January 2025

We reexamine by numerical simulation the phase structure of the three-dimensional Abelian lattice gauge theory with Z(2) gauge fields coupled to Z(2)-valued Higgs fields. Concretely, we explore two different order parameters which are able to distinguish the three phases of the theory: (i) the Fredenhagen-Marcu operator used to discriminate between deconfinement and confinement/Higgs phases and (ii) the Greensite-Matsuyama overlap operator proposed recently to distinguish confinement and Higgs phases. The latter operator is an analog of the overlap Edwards-Anderson order parameter for spin glasses. According to it, the Higgs phase is realized as a glassy phase of the gauge system. For this reason standard tricks for simulations of spin-glass phases are utilized in this work, namely tempered Monte Carlo and averaging over replicas. In addition, we also present results for a certain definition of distance between Higgs field configurations. Finally, we calculate various gauge-invariant correlation functions in order to extract the corresponding masses.

Published by the American Physical Society
2025
Cosmological constraints on dark neutrino towers
Authors: Anchordoqui Luis A. , Antoniadis Ignatios , Lüst Dieter , Peñaló Castillo Karem
Published: January 2025

We reexamine a dynamical dark matter model with Kaluza-Klein (KK) towers of gravitons and neutrinos fitting together in the dark dimension. We show that even though gravitational decays of neutrino KK towers have little impact in cosmology, the weak decay channel could have significant cosmological effects. Taking conservative upper bounds on the dark matter decay rate into two photons before reionization and on the number of effective extra neutrino species ΔNeff, we derive constraints on the conversion rate from active to sterile species despite the dependence of the mixing angle on the KK mode mass. We also provide counterarguments to a recent claim suggesting that the bounds on ΔNeff rule out micron-sized extra dimensions.

Published by the American Physical Society
2025
Islands for black holes in a hybrid quantum state
Authors: Potaux Yohan , Sarkar Debajyoti , Solodukhin Sergey N.
Published: January 2025

Following our previous work on hybrid quantum states in the Russo-Susskind-Thorlacius model, we study its most interesting solution representing a completely regular spacetime with the structure of causal diamond, containing an apparent horizon and radiation at infinity. Adapting recent computations of radiation entropy in terms of the entropy of entanglement, we find that this entropy follows a Page curve. This confirms our previous result [], which was obtained by directly calculating the thermodynamic entropy of radiation at infinity. We also investigate the presence of a possible island in these systems and find that it does not seem to play a role in contributing to the generalized black hole entropy.

Published by the American Physical Society
2025
Hidden Zeros Are Equivalent to Enhanced Ultraviolet Scaling, and Lead to Unique Amplitudes in
Tr(ϕ3)
Theory
Authors: Rodina Laurentiu
Published: January 2025

We investigate the hidden amplitude zeros which describe a nontrivial vanishing of scattering amplitudes on special external kinematics. We first prove that every type of hidden zero is equivalent to what we call a “subset” enhanced scaling under Britto-Cachazo-Feng-Witten shifts for any rational function built from planar Lorentz invariants Xij=(pi+pi+1+⋯+pj−1)2. This directly applies to Tr(ϕ3), nonlinear sigma models, or Yang-Mills-scalar amplitudes, revealing a novel type of enhanced UV scaling in these theories. We also use this observation to prove the conjecture that Tr(ϕ3) amplitudes are uniquely fixed by the zeros, up to an overall normalization, when assuming an ordered and local propagator structure and trivial numerators. In this context, unitarity (residue factorization) may be viewed as a consequence of the zeros. For Yang-Mills theory, we conjecture the zeros, combined with the Bern-Carrasco-Johansson color-kinematic duality in the form of amplitude relations, uniquely fix the ⌊n/2⌋ distinct polarization structures of n-point gluon amplitudes. Our approach opens a new avenue for understanding previous similar uniqueness results, and also extending them beyond tree level for the first time.

Published by the American Physical Society
2025
Symmetric Mass Generation with Four SU(2) Doublet Fermions
Authors: Butt Nouman , Catterall Simon , Hasenfratz Anna
Published: January 2025

We study a single exactly massless staggered fermion in the fundamental representation of an SU(2) gauge group. We utilize an nHYP-smeared fermion action supplemented with additional heavy Pauli-Villars fields that serve to decrease lattice artifacts. The phase diagram exhibits a clear two-phase structure with a conformal phase at weak coupling and a novel new phase, the symmetric mass generation (SMG) phase, appearing at strong coupling. The SMG phase is confining with all states gapped and chiral symmetry unbroken. Our finite size scaling analysis provides strong evidence that the phase transition between these two phases is continuous, which would allow for the existence of a continuum SMG phase. Furthermore, the renormalization group flows are consistent with a β function that vanishes quadratically at the new fixed point, suggesting that the Nf=4 flavor SU(2) gauge theory lies at the opening of the conformal window.

Published by the American Physical Society
2025
Atomic Description of the Reciprocal Action between Supercoils and Melting Bubbles on Linear DNA
Authors: Burman Matthew , Noy Agnes
Published: January 2025

Although the mechanical response of DNA to physiological torsion and tension is well characterized, the detailed structures are not yet known. By using molecular dynamics simulations on linear DNA with 300 base-pairs, we provide, for the first time, the conformational phase diagram at atomic resolution. Our simulations also reveal the dynamics and diffusion of supercoils. We observe a new state in negative supercoiling, where denaturation bubbles form in adenine/thymine-rich regions independently of the underlying DNA topology. We thus propose sequence-dependent bubbles could position plectonemes in longer DNA.

Published by the American Physical Society
2025
Neural Density Functional Theory of Liquid-Gas Phase Coexistence
Authors: Sammüller Florian , Schmidt Matthias , Evans Robert
Published: January 2025

We use supervised machine learning together with the concepts of classical density functional theory to investigate the effects of interparticle attraction on the pair structure, thermodynamics, bulk liquid-gas coexistence, and associated interfacial phenomena in many-body systems. Local learning of the one-body direct correlation functional is based on Monte Carlo simulations of inhomogeneous systems with randomized thermodynamic conditions, randomized planar shapes of the external potential, and randomized box sizes. Focusing on the prototypical Lennard-Jones system, we test predictions of the resulting neural attractive density functional across a broad spectrum of physical behavior associated with liquid-gas phase coexistence in bulk and at interfaces. We analyze the bulk radial distribution function g(r) obtained from automatic differentiation and the Ornstein-Zernike route and determine (i) the Fisher-Widom line, i.e., the crossover of the asymptotic (large distance) decay of g(r) from monotonic to oscillatory, (ii) the (Widom) line of maximal correlation length, (iii) the line of maximal isothermal compressibility, and (iv) the spinodal by calculating the poles of the structure factor in the complex plane. The bulk binodal and the density profile of the free liquid-gas interface are obtained from density functional minimization and the corresponding surface tension from functional line integration. We also show that the neural functional describes accurately the phenomena of drying at a hard wall and of capillary evaporation for a liquid confined in a slit pore. Our neural framework yields results that improve significantly upon standard mean-field treatments of interparticle attraction. Comparison with independent simulation results demonstrates a consistent picture of phase separation even when restricting the training to supercritical states only. We argue that phase coexistence and its associated signatures can be discovered as emerging phenomena via functional mappings and educated extrapolation.

Published by the American Physical Society
2025
Simulating Chemistry with Fermionic Optical Superlattices
Authors: Gkritsis Fotios , Dux Daniel , Zhang Jin , Jain Naman , Gogolin Christian , Preiss Philipp M.
Published: January 2025

We show that quantum-number-preserving ansatzes for variational optimization in quantum chemistry find an elegant mapping to ultracold fermions in optical superlattices. Using native Hubbard dynamics, trial ground states of molecular Hamiltonians can be prepared and their molecular energies measured in the lattice. The scheme requires local control over interactions and chemical potentials and global control over tunneling dynamics, but foregoes the need for optical tweezers, shuttling operations, or long-range interactions. We describe a complete compilation pipeline from the molecular Hamiltonian to the sequence of lattice operations, thus providing a concrete link between quantum simulation and chemistry. Our work enables the application of recent quantum algorithmic techniques, such as double factorization and quantum tailored coupled cluster, to present-day fermionic optical lattice systems with significant improvements in the required number of experimental repetitions. We provide detailed quantum resource estimates for small nontrivial hardware experiments.

Published by the American Physical Society
2025
The chemical theory of valence
Authors: Brown Ian David
Published: January 2025

Relaxing the restriction that valence can only adopt integer values removes the distinction between ionic and covalent bonds, resulting in a simple and powerful valence theory using the concept of the bonding strength of an element, defined as the ratio of its atomic valence to its average coordination number. Bonding strength, closely related to electronegativity, determines which atoms form stable bonds and the chemical properties of the resulting compounds of both organic and inorganic compounds.
Applications of lean principles in the operations of architectural and engineering design firms: an exploratory study in Singapore
Authors: Gao Shang , Low Sui Pheng , Tok Samuel Keen Wei
Published: January 2025

Purpose

The Toyota Way was developed as an efficiency framework to streamline Toyota Motor Corporation’s operational procedures. The collection of Toyota Way principles is often termed “lean”. Over the last few years, nonmanufacturing organisations have begun to recognise the value and applicability of lean methods for their operations. Architectural and engineering design (AED) firms are no exception. This study aims to explore the perspectives of employees at AED firms on the implementation of lean production principles (LPPs) into their operations. Due to the limited resources available to facilitate our measurement of employees’ views regarding the adoption of lean approaches, this study adopts a more scoped approach to employees’ perceptions of these principles within AED firms.

Design/methodology/approach

Fifty-two respondents participated in the survey. The interviewees were from firm A and firm B, an architecture firm and an engineering firm, and were chosen to help us gain a more in-depth understanding of their views regarding the LPPs.

Findings

Our study indicates that AED offices were unfamiliar with the concepts of lean principles, even though they were aware of its importance in their daily operations. Despite their scepticism about the implementation of lean concepts, some lean principles are implemented in their own fields of work.

Originality/value

This study complements earlier work on lean design that investigated the use of a particular lean technique by looking at the lean principles where some are implemented to a large extent, and some are not.