bluuebunny/crossref_metadata_2025 huggingface dataset:
The Hidden Potential of PDE4 Inhibitor Rolipram: A Multifaceted Examination of its Inhibition of MMP2/9 Reveals Therapeutic Implications
Authors: Bagchi Arka , Roy Analabha , Halder Anindya , Biswas Arunima
Published: May 2024

A PDE4 inhibitor, Rolipram, was previously found to down-regulate (in a manner dependent on cAMP-PKA) MMP2 and MMP9 levels, important markers of epithelial-to-mesenchymal transition in human breast cancer cell lines. However, zymographic studies revealed that rolipram could also alter the enzymatic activities of these MMPs, even in the presence of the PKA inhibitor H89. This calls for more detailed investigations of the inhibitory mechanism of rolipram on MMP2 and MMP9. The prediction of ligand-based targets through online reverse screening indicated that proteases are likely targets of rolipram. Computational molecular docking also demonstrated significant binding affinities of rolipram for both MMP2 and MMP9 proteins. Concurrently, a well-known inhibitor of MMPs, SB3CT, was utilized as a positive control for this study. The best models of the docked complexes were used as initial conditions for molecular dynamics (MD) simulations to explore their dynamic behavior and stability. In particular, both the MMP2-rolipram and MMP9-rolipram complexes were found to be stable and compact for the duration of the simulation (300 ns). Several stable hydrogen bonds were also detected between the proteins and rolipram.In vitroexperiments using primary cells from patients with breast cancer also showed that rolipram could alter the enzymatic activities of MMP2 and MMP9, independent of the cAMP-PKA signaling pathway. These observations indicate the ability of rolipram to control breast cancer by regressing the functions of MMP2 and MMP9, thus having ‘off-targets’ other than PDE4 to have direct control over proteins that are involved in the advancement of metastasis.
A novel expression domain ofextradenticleunderlies the evolutionary developmental origin of the chelicerate patella
Authors: Klementz Benjamin C. , Brenneis Georg , Hinne Isaac A. , Laumer Ethan M. , Neu Sophie M. , Hareid Grace M. , Gainett Guilherme , Setton Emily V.W. , Simian Catalina , Vrech David E. , Joyce Isabella , Barnett Austen A. , Patel Nipam H. , Harvey Mark S. , Peretti Alfredo V. , Gulia-Nuss Monika , Sharma Prashant P.
Published: May 2024

Neofunctionalization of duplicated gene copies is thought to be an important process underlying the origin of evolutionary novelty and provides an elegant mechanism for the origin of new phenotypic traits. One putative case where a new gene copy has been linked to a novel morphological trait is the origin of the arachnid patella, a taxonomically restricted leg segment. In spiders, the origin of this segment has been linked to the origin of the paralogdachshund-2, suggesting that a new gene facilitated the expression of a new trait. However, various arachnid groups that possess patellae do not have a copy ofdachshund-2, disfavoring the direct link between gene origin and trait origin. We investigated the developmental genetic basis for patellar patterning in the harvestmanPhalangium opilio, which lacksdachshund-2. Here, we show that the harvestman patella is established by a novel expression domain of the transcription factorextradenticle. Leveraging this definition of patellar identity, we surveyed targeted groups across chelicerate phylogeny to assess when this trait evolved. We show that a patellar homolog is present in Pycnogonida (sea spiders) and various arachnid orders, suggesting a single origin of the patella in the ancestor of Chelicerata. A potential loss of the patella is observed in Ixodida. Our results suggest that the modification of an ancient gene, rather than the neofunctionalization of a new gene copy, underlies the origin of the patella. Broadly, this work underscores the value of comparative data and broad taxonomic sampling when testing hypotheses in evolutionary developmental biology.
Age-Related KLHL22 Expression in Human MSCs and Regenerative Implications
Authors: Utley James , Briggs Daniel
Published: May 2024

Aging in human bone marrow-derived mesenchymal stromal cells (hMSCs) affects their regenerative capabilities and therapeutic efficacy, which are critical for successful cell-based regeneration therapies. In this study, we aimed to identify genetic markers of aging in hMSCs to better understand the impact of donor age on cell function. We conducted analysis on data from genome-wide microarray analysis on early-passage hMSCs isolated from the bone marrow of 61 donors aged between 17 and 84 years found in the GSE39540 public dataset. One such gene, identified asKLHL22 (ENSG00000099910), showed a significant negative correlation with age (p=0.032), with a regression slope of −0.0089 indicating decreased expression in older donors. TheR2R2 value of 0.243 suggests that approximately 24.3% of the expression variability of this gene can be explained by age. These findings are consistent with the known decline in tissue maintenance and regeneration capabilities in aging hMSCs and may reflect broader aging processes impacting cell-based therapies. Our results provide insight into the molecular basis of aging in hMSCs and highlight the potential of using gene expression profiles as markers to select more potent hMSCs for therapeutic applications. This gene signature could serve as a foundation for developing strategies to rejuvenate aged hMSCs, enhancing the efficacy of regenerative therapies.
Recruitment of CTCF to the SIRT1 promoter after Oxidative Stress mediates Cardioprotective Transcription
Authors: Wagner Tobias , Priyanka Priyanka , Micheletti Rudi , Friedman Meyer J. , Nair Sreejith J. , Gamliel Amir , Taylor Havilah , Song Xiaoyuan , Cho Miook , Oh Soohwan , Li Wenbo , Han Jeehae , Ohgi Kenneth A. , Abrass Madeline , D’Antonio-Chronowska Agnieszka , D’Antonio Matteo , Hazuda Helen , Duggirala Ravindranath , Blangero John , Ding Sheng , Guzmann Carlos , Frazer Kelly A. , Aggarwal Aneel K. , Zemljic-Harpf Alice E. , Rosenfeld Michael G. , Suh Yousin
Published: May 2024

Because most DNA-binding transcription factors (dbTFs), including the architectural regulator CTCF, bind RNA and exhibit di-/multimerization, a central conundrum is whether these distinct properties are regulated post-transcriptionally to modulate transcriptional programs. Here, investigating stress-dependent activation ofSIRT1,encoding an evolutionarily-conserved protein deacetylase, we show that induced phosphorylation of CTCF acts as a rheostat to permit CTCF occupancy of low-affinity promoter DNA sites to precisely the levels necessary. This CTCF recruitment to the SIRT1 promoter is eliciting a cardioprotective cardiomyocyte transcriptional activation program and provides resilience against the stress of the beating heartin vivo. Mice harboring a mutation in the conserved low-affinity CTCF promoter binding site exhibit an altered, cardiomyocyte-specific transcriptional program and a systolic heart failure phenotype. This transcriptional role for CTCF reveals that a covalent dbTF modification regulating signal-dependent transcription serves as a previously unsuspected component of the oxidative stress response.
Molecular basis of the biogenesis of a protein organelle for ethanolamine utilization
Authors: Yang Mengru , Adegbite Oluwatobi , Chang Ping , Zhu Xiaojun , Li Yan , Dykes Gregory F. , Chen Yu , Savage Natasha , Hinton Jay C. D. , Lian Lu-Yun , Liu Lu-Ning
Published: May 2024

Many pathogenic bacteria use proteinaceous ethanolamine-utilization microcompartments (Eut BMCs) to facilitate the catabolism of ethanolamine, an abundant nutrient in the mammalian gut. The ability to metabolize ethanolamine gives pathogens a competitive edge over commensal microbiota which can drive virulence in the inflamed gut. Despite their critical functions, the molecular mechanisms underlying the synthesis of Eut BMCs in bacterial cells remain elusive. Here, we report a systematic study for dissecting the molecular basis underlying Eut BMC assembly inSalmonella. We determined the functions of individual building proteins in the structure and function of Eut BMCs and demonstrated that EutQ plays an essential role in both cargo encapsulation and Eut BMC formation through specific association with the shell and cargo enzymes. Furthermore, our data reveal that Eut proteins can self-assemble to form cargo and shell aggregates independentlyin vivo, and that the biogenesis of Eut BMCs follows a unique “Shell-first” pathway. Cargo enzymes exhibit dynamic liquid-like organization within the Eut BMC. These discoveries provide mechanistic insights into the structure and assembly of the Eut BMC, which serves as a paradigm for membrane-less organelles. It opens up new possibilities for therapeutic interventions for infectious diseases.
Harnessing homeostatically active RhoC at cell junctions preserves human endothelial barrier function during inflammation
Authors: Colás-Algora Natalia , Muñoz-Pinillos Pablo , Barroso Susana , Cacho-Navas Cristina , Caballero Álvaro , Cerro-Tello Gema , de Rivas Gema , González-Fernández Martín , Jiménez-Alfaro Ignacio , Fresno Manuel , Ribas Catalina , Paradela Alberto , López-Collazo Eduardo , Fernández José Jesús , Millán Jaime
Published: May 2024

Rho GTPases are molecular targets of bacterial toxins that modulate their enzymatic activity. RhoA, RhoB and RhoC are almost identical and play critical roles in generating actomyosin-mediated contractile forces that cause endothelial hyperpermeability during inflammation. Searching for new treatments to modulate endothelial integrity, we demonstrate that the specific and simultaneous activation of these three Rho GTPases with a chimeric recombinant toxin does not induce cell contraction but enhances homeostatic endothelial barrier function, increases reticular adherens junctions and preserves the microvascular endothelium in response to pathological inflammatory challengesin vitroandin vivo. This pro-barrier effect is specifically mediated by RhoC, whose activity is increased by cell confluence. The uniqueness of RhoC relies on an arginine 188 within its hypervariable region that determines its junctional localization, high homeostatic activity, and barrier-protective function. Quantitative proteomics revealed that RhoC regulates the expression of myosin light chain proteins and junction-stabilizing actomyosin. Thus, harnessing the activity of RhoC represents a potential therapy for strengthening endothelial barriers during pathological inflammation.
Long-term imaging of three-dimensional hyphal development using the ePetri dish
Authors: Zhang Oumeng , Dahlquist Nic , Leete Zachary , Xu Michael , Schneider Dean , Yang Changhuei
Published: May 2024

Imaging three-dimensional microbial development and behavior over extended periods is crucial for advancing microbiological studies. Here, we introduce an upgraded ePetri dish system specifically designed for extended microbial culturing and 3D imaging, addressing the limitations of existing methods. Our approach includes a sealed growth chamber to enable long-term culturing, and a multi-step reconstruction algorithm that integrates 3D deconvolution, image filtering, ridge, and skeleton detection for detailed visualization of the hyphal network. The system effectively monitored the development of Aspergillus brasiliensis hyphae over a seven-day period, demonstrating the growth medium’s stability within the chamber. The system’s 3D imaging capability was validated in a volume of 5.5 mm × 4 mm × 0.5 mm, revealing a radial growth pattern of fungal hyphae. Additionally, we show that the system can identify potential filter failures that are undetectable with 2D imaging. With these capabilities, the upgraded ePetri dish represents a significant advancement in long-term 3D microbial imaging, promising new insights into microbial development and behavior across various microbiological research areas.
Structural and Dynamical Analyses of Apo and Cap-binding eIF4E: Anin silicoStudy
Authors: Hasegawa Karin , Burzachiello Justin , Connolly Liam , Kementzidis Georgios , Niu Ziyuan , Papadopoulos Evangelos , Aktas Bertal Huseyin , Deng Yuefan
Published: May 2024

Molecular dynamics (MD) simulations were utilized to investigate the dynamic behavior of eukaryotic translation initiation factor 4E (eIF4E) in its apo (ligand-free) and Cap-bound (complexed with mRNA Cap) forms. Specifically, we focused on the rearrangement of critical eIF4E residues, including W102, E103, W56, and key charged residues within the alpha helix, such as lysine and arginine. Three independent 1µsMD simulations were performed for four eIF4E structures based on an available Capbound eIF4E crystal structure (PDB: 4TPW) to sample protein conformations and explore metastable states. Metastable states were successfully sampled within the 1µstrajectories for all four structures; however, 2D-root-mean-square deviation (RMSD) and free-energy landscape (FEL) analyses indicate that additional trajectory data may be needed to fully explore the conformational space. Notably, the clearest state transitions were observed in the Cap-A simulations. Our data suggests that previously reported allosteric site eIF4E inhibitor 4EGI-1 stabilized the7mGTP-eIF4E interaction by binding to a site dorsal from the eIF4G binding site, facilitating stable protein states even after ligand removal and promoting cleaner state transitions in simulations. Root-mean-square fluctuation (RMSF) and distance analyses aligned consistently with experimental results, affirming the validity of our MD simulation system. Observations on apo and Cap eIF4E structures revealed structural changes in one of the alpha helices (i.e.,H3), particularly the transition from alpha helix to loop upon Cap binding. This transition was also observed during the cap to apo transition, where residues E105-R109 underwent structural rearrangements from loop to alpha helix. These findings support the strategy of designing agents targeting critical Cap-binding residues (W56, W102, E103) and H3 lysine residues (K106, K108) to disrupt the7mGTP-eIF4E interaction, potentially informing future drug design efforts targeting this oncogenic protein. Future work will focus on studying the apo to Cap transition using available eIF4E apo structures, such as PDB entry 2GPQ, to deepen our understanding of eIF4E’s metastable states during Cap binding.
Unilateral and Bilateral Theta Burst Stimulation for Treatment-Resistant Depression: Follow up on a Naturalistic Observation Study
Authors: Elnazali Mariam , Veerakumar Ashan , Blair Mervin , Pearce Emily L. , Kim Noah , Sebastian Sreya , Santo Jonathan B. , Rybak Iouri E. , Burhan Amer M.
Published: May 2024

Objectives

Theta burst stimulation (TBS) is a novel and faster modality of transcranial magnetic stimulation, which is showing promise as a treatment-resistant depression (TRD) treatment. Though TBS can be applied unilaterally or bilaterally, few studies have compared the effectiveness of both approaches in a naturalistic clinical sample. In this retrospective chart review, we aimed to: (1) replicate previous bilateral sequential TBS effectiveness in a larger cohort of patients at a single centre, (2) present treatment outcome data between unilateral and bilateral TBS approaches, (3) investigate baseline factors associated with our observed outcomes, and (4) examine the sustainability of response, with follow-up data up to 6 months from patients.

Methods

We included 161 patients who received TBS (unilateral: n = 64 (40%), 45.55 ± 14.25 years old, 55% females; bilateral: n = 97 (60%), 47.67 ± 15.11 years old, 58% females).

Results

Firstly, we observed 47% response and 34% remission in the bilateral group, replicating findings from a smaller naturalistic study from our group; patients receiving unilateral TBS displayed 36% response and 26% remission, with no significant differences found between unilateral and bilateral TBS in remission and response rates. Secondly, bilaterally stimulated patients needed fewer treatments than those stimulated unilaterally (27 vs 29 on average respectively,t[159] = 3.31,p= .001), and had significantly lower anxiety symptoms post treatment (GAD-7) relative to patients receiving unilateral stimulation,F(1,148) = 3.95,p=0.049. Thirdly, no baseline factors were found to predict treatment outcomes. Lastly, after six months, 69% of patients who met the response criteria did not require additional treatment or a change in medication.

Conclusions

Our findings support the efficacy and tolerability of TBS in TRD and indicate that bilateral TBS may have a superior anxiolytic effect and offer a slightly faster time to response.
Research involvement of medical students in a medical school of India: exploring knowledge, attitude, practices, and perceived barriers
Authors: Jha Abhinav , Shah Manas Ratan , Goyal Ritik , Dhamnetiya Deepak , Bharatwal Apoorv Amitabh , Jha Ravi Prakash , Renjhen Prachi
Published: May 2024

Introduction

Research in the medical discipline significantly impacts society by improving the general well-being of the population, through improvements in diagnostic and treatment modalities. However, of 579 Indian medical colleges, 332 (57.3%) did not publish a single paper from the year 2005 to 2014," indicating a limited contribution from medical fraternity In order to probe in to the cause of this a study was conducted to assess the knowledge, attitude, practices (KAP) and perceived barriers to research among students of a medical school in Delhi, India.

Methods

A cross-sectional study was conducted among medical students and the data on academic-cum-demographic information, assessment of knowledge, attitude, practices and barriers to research was collected using a pre-tested, semi-structured questionnaire. Chi-square test was used to check the association of various factors with the KAP of research. A p-value less than 0.05 was considered significant.

Results

A total of 402 (N) subjects were enrolled in the study. Majority were male (79.6%) and from clinical professional years (57%). Majority (266, 66.2%) of the subjects had adequate knowledge. Of the study subjects (61,15%) having inadequate knowledge of research, sixty percent were from pre- and para-clinical years, while around 70 % of those having good knowledge were from clinical professional years. However, only 16.9% of the participants had participated in a research project, and only 4.72% had authored a publication. Sixty one percent of study subjects having a positive attitude towards research, were from pre- and para-clinical years. Among the study subjects having a positive attitude towards research, over 60% were from pre- and para-clinical years. The barriers for conducting research were mostly; lack of funds/laboratory equipment/infrastructure (85.1%), lack of exposure to opportunities for research in the medical (MBBS) curriculum (83.8%), and lack of time (83.3%). There was a statistically significant association between knowledge and attitude towards research with a professional year of study.

Conclusions

The study revealed that while most of the students had a positive attitude towards research as well as an adequate knowledge of research, there was a poor level of participation in research. These challenges can be overcome by incorporating research as a part of the medical school curriculum from early years on, setting aside separate time for research, and establishing student research societies that can actively promote research.
Survival among cancer patients after a coalmine fire: Analysis of registry data in regional Victoria, Australia
Authors: Lane Tyler J , Yu Pei , Gao Caroline , Smith Catherine L , Loi Sherene , Kinsman Natasha , Ikin Jill , Guo Yuming , Sim Malcolm R. , Abramson Michael J.
Published: May 2024

Background

Air pollution is associated with poorer survival among cancer patients. However, much of the evidence is from studies of ambient air pollution rather than acute exposures like from fires. In this study, we examined the effect of a 2014 coalmine fire in regional Australia, which shrouded nearby communities in smoke for six weeks.

Methods

We analysed Victorian Cancer Registry data on new cancers diagnosed between January 2009 and February 2014, the start of the coalmine fire, and survival up to August 2019. Tumours were grouped by location and subtypes for breast and lung cancers. The exposure group was based on residence at diagnosis: Morwell (most exposure), the rest of Latrobe Valley (less exposure), and the rest of Victoria excluding Melbourne (little to no exposure). Those who were diagnosed in Morwell or the Latrobe Valley but died before the fire were classified as unexposed. Months of survival post-fire were compared using Cox proportional hazards frailty and discrete survival models.

Results

In Morwell 488 total cancers were diagnosed, 1738 in the rest of the Latrobe Valley, while 42,738 were unexposed. There was no detectable overall effect. However, there were significant reductions in survival among cancers of female reproductive organs in Morwell and breast in the rest of Latrobe Valley.

Conclusion

There were no overall changes in cancer survival and isolated increases in two subtypes, although not consistent across exposure sites. Reduced survival from female reproductive cancers were plausibly related to smoke exposure, though numbers were small and there is a high likelihood this was a chance finding. Otherwise, we found little evidence that medium-duration exposure to smoke from the Hazelwood coalmine fire shortened survival among cancer patients. However, owing to limited statistical power, we could not rule out an effect of smoke on cancer survival.
Spatial dynamics of peripheral and central nervous system infection by an interferon-inducing neuroinvasive virus
Authors: Laghi Valerio , Boucontet Laurent , Wiggett Hannah , Banerjee Payel , Simion Matthieu , Maggi Ludovico , Ciura Sorana , Guedj Jérémie , Colucci-Guyon Emma , Levraud Jean-Pierre
Published: May 2024

Organ-to-organ dissemination of viruses is a critical feature of host-virus interactions. In particular, neuroinvasive viruses are able to enter the central nervous systems (CNS), which may result in death or permanent neurological impairment. The complex mechanisms underpinning this spread are poorly understood, as they depend on a variety of parameters, including initial site of entry, route of access to the CNS, and immune responses. To better understand these phenomena, we analyzed the spatial dynamics of Sindbis virus (SINV) dissemination in transparent zebrafish larvae. Using fluorescent reporter viruses, we observed that SINV readily invaded the CNS after inoculation at various peripheral sites. From tail muscle, the virus used dorsal root ganglia (DRG) sensory neurons as a gateway to the spinal cord and further propagation to the brain. While peripheral infection was systematically transient, due to the key protective role of the strong and rapid type I interferon (IFN) response, CNS infection was persistent and more variable. Within the CNS, viral dissemination resulted both from long-distance axonal transport and short distance shedding, and IFN response was local, while it was systemic in the periphery. A mathematical model was built on this quantitative imaging foundation, that provided additional insight on the parameters of this infection, such as the rate of new virion production, estimated around 1 to 2 infective virions per productively infected cell per hour; the occurrences of CNS entry events, which was 2 to 3 per larva; or the impact of the IFN response, which did not only prevent new infections but accelerated the death of infected cells.
Aspartate/alanine aminotransferase ratio and development of chronic kidney disease in non-diabetic Japanese men and women
Authors: Okawa Yukari , Mitsuhashi Toshiharu , Suzuki Etsuji
Published: May 2024

Aim

The objective of this study was to explore the relationship between serum aspartate/alanine aminotransferase ratio (AST/ALT) and subsequent development of chronic kidney disease (CKD) in non-diabetic Japanese men and women in a 25-year follow-up study.

Methods

The study included all middle-aged and older non-diabetic Japanese citizens who received health check-ups in Zentsuji, Kagawa, Japan (1998–2023). AST/ALT was classified into three categories: <1.0 (reference), 1.0–<1.5, and ≥1.5. Participant characteristics were compared by AST/ALT categories. The Weibull accelerated failure time model was used to examine the association between AST/ALT categories and subsequent CKD onset because the proportional hazards assumption was violated.

Results

Of 6309 men and 9192 women, 2966 men and 4395 women remained in the final cohort. After a mean follow-up of 7.50 years for men and 8.34 years for women, 33.7% of men and 34.0% of women developed CKD. Women had higher AST/ALT than men. In women, a dose-response relationship was observed, with a 9% shorter survival time to CKD onset for AST/ALT ≥1.5 compared with AST/ALT <1.0. In contrast, men had a shorter survival time to CKD onset by point estimates, but the 95% confidence intervals crossed 1 in all models.

Conclusions

In this study comparing the risks of CKD development in non-diabetic men and women by AST/ALT levels, a dose-response relationship was only observed in women. Differences in the distribution of AST/ALT by sex may have affected the results. Therefore, in non-diabetic Japanese women, AST/ALT may be used as an indicator of future CKD development.
Clinical Decision Support Opportunities among Clinicians Caring for People Receiving Invasive Mechanical Ventilation: A Cross-sectional Survey
Authors: Weissman Gary E. , Bishop Nicholas S. , Schmid Benjamin E. , Madden Vanessa , Pirracchio Romain , Jentzer Jacob C. , Riman Kathryn A. , Krutsinger Dustin C. , DiGiovine Bruno , Ungar Lyle H. , Halpern Scott D. , Auriemma Catherine L. , Valley Thomas S. , Kerlin Meeta Prasad
Published: May 2024

Treatment decisions for patients receiving invasive mechanical ventilation (IMV) are complex and depend simultaneously on the current ventilator settings, the function of multiple interrelated organ systems, and other treatments. An artificial intelligence (AI)-based clinical decision support system (CDSS) offers a promising approach to alleviate uncertainty in this complex management and provide personalized treatment recommendations. However, little is known about clinician preferences for which treatment decisions clinicians think would most benefit from a CDSS. Therefore, we conducted a cross-sectional electronic survey of practicing physicians, nurses, advanced practice providers, and respiratory therapists to identify key treatment decisions in IMV care. We sent the survey instrument to 132 clinicians across six geographically diverse health systems. Among 51 respondents (39% response rate), there were 24 (47%) physicians, 7 (14%) registered nurses, 8 (16%) advanced practice providers, and 12 (24%) respiratory therapists. Participants were from five US states including Pennsylvania, California, Michigan, Minnesota, and Nebraska. At least 50% of participants identified 18 distinct treatment decisions for IMV care asvery importantorabsolutely essential, including many that were outside of the ventilator settings themselves. The highest agreement about importance was for the decision to extubate (N=51, 100%), and the decisions to conduct a spontaneous awakening trial (N=48, 94%) and spontaneous breathing trial (N=48, 94%). The highest agreement about a decision beingnot importantor onlyslightly importantwas for the shape of the inspiratory flow pattern (N=15, 29%). These findings underscore the scope and complexity of clinical decision making across multidisciplinary teams in caring for people receiving IMV. Furthermore, they underscore the gap between important clinician-identified decisions and existing IMV CDSSs that provide suggestions for at most 5 ventilator settings without support for other related decisions. Future work is needed to identify which of these decisions might be most appropriate for inclusion in a CDSS to support IMV management.
Alcohol use and risk of dementia in diverse populations
Authors: Topiwala Anya , Levey Daniel F , Zhou Hang , Deak Joseph D. , Adhikari Keyrun , Ebmeier Klaus P , Bell Steven , Burgess Stephen , Nichols Thomas E. , Gaziano J Michael , Stein Murray , Gelernter Joel
Published: May 2024

Objective To examine the causal relationship between alcohol use and dementia risk across multiple ancestry groups. Design We triangulated evidence from observational and univariable and multivariable Mendelian randomization. Setting and participants Cross-ancestry observational analyses were conducted in two large prospective studies: the US Million Veteran Program and UK Biobank. One- and two-sample univariable and multivariable Mendelian randomization used de novo data from a genome-wide association study in Million Veteran Program plus publicly available data. Main outcome measure All-cause dementia. Results Among 559,559 participants (aged 56-72 years old at baseline) included in observational analyses, 14,540 received developed dementia and 48,034 died during follow-up. Observational associations between alcohol and dementia were U-shaped. Non-, heavy (>40 drinks per week - hazard ratio (HR)1.41; 95% confidence interval [CI], 1.15 to 1.74]) and dependent (1.51[1.42-1.60]) drinkers were at higher dementia risk than light drinkers. In contrast, genetic analyses revealed a monotonically increasing association between alcohol dose and dementia, with no evidence supporting a protective effect of any level of drinking. A two-fold increase in genetically-predicted alcohol use disorder prevalence was associated with a 16% increase in dementia cases (IVW OR=1.16[1.03-1.30]), and a one standard deviation increase in log-transformed drinks per week was associated with a 15% increase (IVW OR=1.15[1.03-1.27]). Conclusions Alcohol consumption has a causal role for dementia. These findings challenge a purported protective effect of moderate drinking. Reducing alcohol use could be an effective dementia prevention strategy.
Fine-mapping a genome-wide meta-analysis of 98,374 migraine cases identifies 181 sets of candidate causal variants
Authors: Hautakangas Heidi ,   FinnGen,   International Headache Genetics Consortium,   HUNT All-in Headache, Palotie Aarno , Pirinen Matti
Published: May 2024

Migraine is a highly prevalent neurovascular disorder for which genome-wide association studies (GWAS) have identified over one hundred risk loci, yet the causal variants and genes remain mostly unknown. Here, we meta-analyzed three migraine GWAS including 98,374 cases and 869,160 controls and identified 122 independent risk loci of which 35 were new. Fine-mapping of a meta-analysis is challenging because some variants may be missing from some participating studies and accurate linkage disequilibrium (LD) information of the variants is often not available. Here, using the exact in-sample LD, we first investigated which statistics could reliably capture the quality of fine-mapping when only reference LD was available. We observed that the posterior expected number of causal variants best distinguished between the high- and low-quality results. Next, we performed fine- mapping for 102 autosomal risk regions using FINEMAP. We produced high-quality fine-mapping for 93 regions and defined 181 distinct credible sets. Among the high- quality credible sets were 7 variants with very high posterior inclusion probability (PIP > 0.9) and 2 missense variants with PIP > 0.5 (rs6330 inNGFand rs1133400 inINPP5A). For 35 association signals, we managed to narrow down the set of potential risk variants to at most 5 variants.
Longitudinal phase space diagnostics with a nonmovable corrugated passive wakefield streaker
Authors: Dijkstal Philipp , Qin Weilun , Tomin Sergey
Published: May 2024

Time-resolved diagnostics at free-electron laser (FEL) facilities, in particular electron beam longitudinal phase space (LPS) and FEL power profile measurements, provide information highly valuable for users, machine development studies, and beam setup. We investigate the slice energy resolution of passive streaker setups, in particular the effect of an energy chirp on the measured slice energy spread. Downstream of the hard x-ray SASE2 beamline at the European XFEL, these measurements are enabled by a single-plate nonmovable passive wakefield streaker, essentially a rectangular corrugated plate placed inside a vacuum chamber. We show measurements with a time resolution down to a few femtoseconds and an energy resolution down to a few MeVs.

Published by the American Physical Society
2024
Influence of chemical strains on the electrocaloric response, polarization morphology, tetragonality, and negative-capacitance effect of ferroelectric core-shell nanorods and nanowires
Authors: Morozovska Anna N. , Eliseev Eugene A. , Kovalenko Olha A. , Evans Dean R.
Published: May 2024

Using Landau-Ginzburg-Devonshire (LGD) approach, we proposed the analytical description of the influence of chemical strains on spontaneous polarization and the electrocaloric response in ferroelectric core-shell nanorods. We postulate that the nanorod core presents a defect-free single-crystalline ferroelectric material, and elastic defects are accumulated in the ultrathin shell, where they can induce tensile or compressive chemical strains. Finite-element modeling (FEM) based on the LGD approach reveals transitions of domain-structure morphology induced by chemical strains in the BaTiO3 nanorods. Namely, tensile chemical strains induce and support the single-domain state in the central part of the nanorod, while the curled domain structures appear near the unscreened or partially screened ends of the rod. The vortexlike domains propagate toward the central part of the rod and fill it entirely, when the rod is covered by a shell with compressive chemical strains above some critical value. The critical value depends on the nanorod sizes, aspect ratio, and screening conditions at its ends. Both analytical theory and FEM predict that the tensile chemical strains in the shell increase the nanorod polarization, lattice tetragonality, and electrocaloric response well above the values corresponding to the bulk material. The physical reason for the increase is strong electrostriction coupling between the mismatch-type elastic strains induced in the core by chemical strains in the shell. Comparison with earlier XRD data confirmed an increase of the tetragonality ratio in tensile BaTiO3 nanorods compared to the bulk material. Obtained analytical expressions, which are suitable for the description of strain-induced changes in a wide range of multiaxial ferroelectric core-shell nanorods and nanowires, can be useful for strain engineering of advanced ferroelectric nanomaterials for energy storage, harvesting, electrocaloric applications, and negative capacitance elements.

Published by the American Physical Society
2024
Limitations of mean-field approximations in describing shift-current and injection-current in materials
Authors: Sato Shunsuke A. , Rubio Angel
Published: May 2024

We theoretically and computationally investigate bulk photovoltaic effects, with a specific focus on shift-current and injection-current. Initially, we perform a numerical analysis of the direct current (dc) induced by a laser pulse with a one-dimensional model, utilizing mean-field theories such as time-dependent Hartree–Fock and time-dependent Hartree methods. Our numerical results, obtained with mean-field theories, reveal that the dc component of the current, as a second-order nonlinear effect, exists even after irradiation with linearly polarized light as a second-order nonlinear effect, indicating the generation of injection-current. Conversely, when we employ the independent-particle approximation, no injection-current is generated by linearly polarized light. To develop the microscopic understanding of injection-current within the mean-field approximation, we further analyze the dc component of the current with the perturbation theory, employing the mean-field approximations, the independent-particle approximation, and the exact solution of the many-body Schrödinger equation. The perturbation analysis clarifies that the injection-current induced by linearly polarized light under the mean-field approximations is an artifact caused by population imbalance, created through quantum interference from unphysical self-excitation pathways. Therefore, investigation of many-body effects on the bulk photovoltaic effects have to be carefully conducted in mean-field schemes due to potential contamination by unphysical dc current. Additionally, we perform the first-principles electron dynamics calculation for BaTiO3 based on the time-dependent density functional theory, and we confirm that the above findings from the one-dimensional model calculation and the perturbation analysis apply to realistic systems.

Published by the American Physical Society
2024
Toward the quark mass dependence of
Tcc+
from lattice QCD
Authors: Collins Sara , Nefediev Alexey , Padmanath M. , Prelovsek Sasa
Published: May 2024

The DD* scattering phase shifts in the Tcc+=ccu¯d¯ channel are extracted from lattice QCD for five different charm quark masses and a fixed light-quark mass corresponding to mπ≃280  MeV. The phase shifts are analyzed employing two approaches: effective range expansion and Lippmann-Schwinger equation derived in the effective field theory. In the latter case, the results imply an attraction at short range parametrized by contact terms and a slight repulsion at long range mediated by one-pion exchange with mπ>mD*−mD. The poles in the amplitude across the complex energy plane are extracted and their trajectories are discussed as the charm quark mass is varied. Two complex conjugate poles corresponding to a resonance below threshold are found for mc close to the physical value. They turn into a pair of virtual states at the largest mc studied. With further increasing mc, one virtual pole representing Tcc+ is expected to move towards the two-body threshold and turn into a bound state. The light-quark mass dependence of the Tcc+ pole is briefly discussed using the data on DD* scattering from other lattice collaborations.

Published by the American Physical Society
2024
Searching for gluon quartic gauge couplings at muon colliders using the autoencoder
Authors: Zhang Yu-Ting , Wang Xin-Tong , Yang Ji-Chong
Published: May 2024

One of the difficulties one has to face in the future phenomenological studies of new physics (NP), is the need to deal with increasing amounts of data. It is therefore increasingly important to improve the efficiency in the phenomenological study of NP. Whether it is the use of the Standard Model effective field theory (SMEFT), the use of machine learning (ML) algorithms, or the use of quantum computing, all are means of improving the efficiency. In this paper, we use a ML algorithm, the autoencoder (AE), to study the dimension-8 operators in the SMEFT which contribute to the gluon quartic gauge couplings (gQGCs) at muon colliders. The AE is one of the ML algorithms that has the potential to be accelerated by the quantum computing. It is found that the AE-based anomaly detection algorithm can be used as event selection strategy to study the gQGCs at the muon colliders, and is effective compared with traditional event selection strategies.

Published by the American Physical Society
2024
Exploring solar neutrino oscillation parameters with the liquid scintillator counter at Yemilab with a comparison to JUNO
Authors: Bakhti Pouya , Rajaee Meshkat , Seo Seon-Hee , Shin Seodong
Published: May 2024

We investigate the sensitivities of the liquid scintillator counter (LSC) at Yemilab and JUNO to solar neutrino oscillation parameters, focusing on θ12 and Δm212. We compare the potential of JUNO with LSC at Yemilab utilizing both reactor and solar data in determining those parameters. We find that the solar neutrino data of LSC at Yemilab is highly sensitive to θ12 enabling its determination with a higher precision compared to reactor experiments. Our study also reveals that if Δm212 is larger, with a value close to the best-fit value of KamLAND, JUNO reactor data will have about two times better precision than the reactor LSC at Yemilab. On the other hand, if Δm212 is smaller and closer to the best-fit value of solar neutrino experiments, the precision of the reactor LSC at Yemilab will be better than JUNO.

Published by the American Physical Society
2024
Spontaneous breaking of the
SO(2N)
symmetry in the Gross-Neveu model
Authors: Han SangEun , Herbut Igor F.
Published: May 2024

The canonical Gross-Neveu model for N two-component Dirac fermions in 2+1 dimensions suffers a continuous phase transition at a critical interaction gc1∼1/N at large N, at which its continuous symmetry SO(2N) is preserved and a discrete (Ising) symmetry becomes spontaneously broken. A recent mean-field calculation, however, points to an additional transition at a different critical gc2∼−Ngc1, at which SO(2N)→SO(N)×SO(N). To study the latter phase transition we rewrite the Gross-Neveu interaction g(ψ¯ψ)2 in terms of three different quartic terms for the single (L=1) 4N-component real (Majorana) fermion, and then extend the theory to L>1. This allows us to track the evolution of the fixed points of the renormalization group transformation starting from L≫1, where one can discern three distinct critical points which correspond to continuous phase transitions into (1) SO(2N)-singlet mass-order-parameter, (2) SO(2N)-symmetric-tensor mass-order-parameters, and (3) SO(2N)-adjoint nematic-order-parameters, down to L=1 value that is relevant to the standard Gross-Neveu model. Below the critical value of Lc(N)≈0.35N for N≫1 only the Gross-Neveu critical point (1) still implies a diverging susceptibility for its corresponding (SO(2N)-singlet) order parameter, whereas the two new critical points that existed at large L ultimately become equivalent to the Gaussian fixed point at L=1. We interpret this metamorphosis of the SO(2N)-symmetric-tensor fixed point from critical to spurious as an indication that the transition at gc2 in the original Gross-Neveu model is turned first-order by fluctuations.

Published by the American Physical Society
2024
Analytically separating the source of the Teukolsky equation
Authors: Spiers Andrew
Published: May 2024

Recent gravitational wave detections from black hole mergers have underscored the critical role black hole perturbation theory and the Teukolsky equation play in understanding the behavior of black holes. The separable nature of the Teukolsky equation has long been leveraged to study the vacuum linear Teukolsky equation; however, as theory and measurements advance, solving the sourced Teukolsky equation is becoming a frontier of research. In particular, second-order calculations, such as in quasinormal mode and self-force problems, have extended sources. This paper presents a novel method for analytically separating the Teukolsky equation’s source, aimed to improve efficiency. Separating the source is a nontrivial problem due to the angular and radial mixing of generic quantities in Kerr spacetime. We provide a proof-of-concept demonstration of our method and show that it is accurate, separating the Teukolsky source produced by the stress-energy tensor of an ideal gas cloud surrounding a Kerr black hole. The detailed application of our method is provided in an accompanying notebook. Our approach opens up a new avenue for accurate black hole perturbation theory calculations with sources in both the time and frequency domain.

Published by the American Physical Society
2024
Irreversible vierbein postulate: Emergence of spacetime from quantum phase transition
Authors: Maitiniyazi Yadikaer , Matsuzaki Shinya , Oda Kin-ya , Yamada Masatoshi
Published: May 2024

We formulate a model for quantum gravity based on the local Lorentz symmetry and general-coordinate invariance. A key idea is the irreversible vierbein postulate that a tree-level action for the model at a certain energy scale does not contain an inverse vierbein. Under this postulate, only the spinor becomes a dynamical field, and no gravitational background field is introduced in the tree-level action. In this paper, after explaining the transformation rules of the local Lorentz and general-coordinate transformations in detail, a tree-level action is defined. We show that fermionic fluctuations can induce a nonvanishing gravitational background field.

Published by the American Physical Society
2024
Post-Newtonian multipoles from the next-to-leading post-Minkowskian gravitational waveform
Authors: Georgoudis Alessandro , Heissenberg Carlo , Russo Rodolfo
Published: May 2024

We consider the frequency-domain leading order and next-to-leading order post-Minkowskian waveforms obtained from the tree-level and one-loop amplitudes describing the scattering of two massive scalar objects and the emission of one graviton. We explicitly calculate their post-Newtonian (PN) limit obtaining an expansion up to the third subleading PN order in all ingredients: the tree-level amplitude, the odd and even parts of the real one-loop kernel, and the Compton or “rescattering” cuts, thus reaching 3PN precision for the latter. We provide explicit expressions for the multipole decomposition of these results in the center-of-mass frame and compare them with the results obtained from the classical multipolar post-Minkowskian method. We find perfect agreement between the two, once the Bondi-Metzner-Sachs supertranslation frame is properly adjusted and the infrared divergences due to rescattering are suitably subtracted in dimensional regularization. This shows that the approach proposed in Georgoudis [An eikonal-inspired approach to the gravitational scattering waveform, 089] can be applied beyond the soft-regime ensuring the agreement between amplitude-based and multipolar post-Minkowskian results for generic frequencies.

Published by the American Physical Society
2024
New Constraint for Isotropic Lorentz Violation from LHC Data
Authors: Amram David , Bouzoud Killian , Chanon Nicolas , Hansen Hubert , Ribeiro Marcos R. , Schreck Marco
Published: May 2024

New calculations for the kinematics of photon decay to fermions under an isotropic violation of Lorentz invariance (LV), parametrized by the standard-model extension, are presented in this Letter and used to interpret prompt photon production in LHC data. The measurement of inclusive prompt photon production at the LHC Run 2, with photons observed up to a transverse energy of 2.5 TeV, provides the lower bound κ˜tr>−1.06×10−13 on the isotropic coefficient κ˜tr at 95% confidence level. This result improves over the previous bound from hadron colliders by a factor of 55. The calculations for the kinematics of photon decay have further potential use to constrain LV coefficients from the appearance of fermion pairs.

Published by the American Physical Society
2024
Predicting Rubisco-Linker Condensation from Titration in the Dilute Phase
Authors: Payne-Dwyer Alex , Kumar Gaurav , Barrett James , Gherman Laura K. , Hodgkinson Michael , Plevin Michael , Mackinder Luke , Leake Mark C. , Schaefer Charley
Published: May 2024

The condensation of Rubisco holoenzymes and linker proteins into “pyrenoids,” a crucial supercharger of photosynthesis in algae, is qualitatively understood in terms of “sticker-and-spacer” theory. We derive semianalytical partition sums for small Rubisco-linker aggregates, which enable the calculation of both dilute-phase titration curves and dimerization diagrams. By fitting the titration curves to surface plasmon resonance and single-molecule fluorescence microscopy data, we extract the molecular properties needed to predict dimerization diagrams. We use these to estimate typical concentrations for condensation, and successfully compare these to microscopy observations.

Published by the American Physical Society
2024