bluuebunny/crossref_metadata_2025 huggingface dataset:
Septin filament assembly assist the lateral organization of membranes
Authors: El Alaoui Fatima , Al-Akiki Isabelle , Ibanes Sandy , Lyonnais Sébastien , Sanchez-Fuentes David , Desgarceaux Rudy , Cazevieille Chantal , Blanchard Marie-Pierre , Parmeggiani Andrea , Carretero-Genevrier Adrian , Piatti Simonetta , Picas Laura
Published: March 2024

Compartmentalized interactions of plasma membrane components are essential to support many cell functions, from signaling to cell division, adhesion, migration, or phagocytosis. Cytoskeletal-membrane interactions play an important role in forming membrane compartments, and this feature has been primarily studied through the actin cytoskeleton. Unlike actin, septins directly interact with membranes, acting as scaffolds to recruit proteins to specific cellular locations and as structural diffusion barriers for membrane components. However, how septins interact with and remodel the local membrane environment is unclear. Here we combined minimal reconstituted systems based on fluorescence microscopy and quantitative atomic force microscopy together with live yeast cell imaging and STED microscopy to study septin-mediated membrane organization. Our results show that septins self-assembly into filament-based sub-micrometric patches and high-order structures prompt their membrane-organizing rolein vitroand in yeast cells, respectively. Furthermore, we show that the polybasic domain of Cdc11, in addition to the amphipathic helix of Cdc12, plays an essential role in supporting the membrane remodeling and curvature-sensing properties of yeast septins. Collectively, our work provides a framework for understanding the molecular mechanisms by which septins can support cellular functions intimately linked to membranes.
Contribution of the epididymis beyond fertilization: relevance of CRISP1 and CRISP3 for sperm DNA integrity and early embryo development
Authors: Sulzyk Valeria , Curci Ludmila , González Lucas N , Rebagliati Cid Abril , Weigel Muñoz Mariana , Cuasnicu Patricia S
Published: March 2024

Numerous reports show that the epididymis plays a key role in the acquisition of sperm fertilizing ability but less information exists on its contribution to embryo development. Evidence from our laboratory showed that mammalian CRISP (Cysteine-Rich Secretory Proteins), known to be expressed in the epididymis, to regulate calcium (Ca2+) channels and to participate in fertilization, may also be relevant for embryo development. More specifically, we found that males with simultaneous mutations inCrisp1andCrisp3genes exhibited normalin vivofertilization but impaired embryo development. In the present work, aimed to investigate the mechanisms underlying this reproductive phenotype, we observed that embryo development failure was not due to delayed fertilization as no differences in sperm transport within the female tract nor inin vivofertilization were found shortly after mating. The observation that impaired embryo development was also found in eggs fertilized by epididymal sperm either after uterine insemination orin vitrofertilization, revealed that the defects were already present at epididymal level. Of note, eggs fertilizedin vitroby mutant sperm exhibited impaired meiotic resumption not due to defects in Ca2+oscillations during egg activation, prompting us to examine potential sperm DNA defects. Interestingly, DNA fragmentation was found in cauda but not caput epididymal mutant sperm revealing that DNA integrity defects appear during epididymal maturation. Moreover, exposure of control sperm to mutant epididymal fluid significantly increased DNA fragmentation, indicating the relevance of the luminal environment for sperm DNA integrity. The finding that incubation of sperm with control epididymal fluid in the presence of Ca2+also increased DNA fragmentation together with the higher intracellular Ca2+levels detected in mutant sperm supports a dysregulation of Ca2+homeostasis as the main responsible for DNA fragmentation and subsequent early development failure of mutant males. Together, our results support the contribution of the epididymis beyond fertilization, identifying CRISP1 and CRISP3 as novel male factors relevant for DNA integrity and early embryo development. Given the existence of human functional homologues of CRISP and the incidence of DNA fragmentation in infertile men, we believe these findings not only provide relevant information on the impact of epididymal factors on embryonic development but will also contribute to a better understanding, diagnosis and treatment of human infertility.
Greater Role of Cognitive Impairment Over Fatigue in Post-COVID-19 Quality of Life: A Post-Hoc Analysis of a Randomized Controlled Trial
Authors: Kwan Angela T.H. , Lakhani Moiz , Le Gia Han , Singh Gurkaran , Teopiz Kayla M. , Guo Ziji , Ceban Felicia , Dhaliwal Kanwarpreet Kaur , Badulescu Sebastian , Ho Roger , Rhee Taeho Greg , Cao Bing , d’Andrea Giacomo , McIntyre Roger S.
Published: March 2024

Background

Post COVID-19 Condition (PCC) is a common and debilitating condition with significant reports of fatigue and psychosocial impairment globally. The extent to which cognitive symptoms and fatigue contribute to reduced quality of life in affected individuals remains clear.

Methods

This is a post-hoc analysis of a randomized, double-blind, placebo-controlled clinical trial that evaluated the effect of vortioxetine on cognitive function in adults with PCC. The post-hoc analysis herein aimed to determine the overall effect of baseline cognitive function [as measured by the Digit Symbol Substitution Test (DSST)] and baseline fatigue severity [as measured by the Fatigue Severity Scale (FSS)] on baseline health-related quality of life (HRQoL) [as measured by the 5-item World Health Organisation Well-Being Index (WHO-5)].

Results

A total of 200 participants were enrolled in the primary trial. Due to missing baseline data, our statistical analysis included baseline measures of 147 individuals. Our generalized linear model analysis revealed a significant positive correlation between DSST-measured objective cognitive function and self-reported WHO-5-measured HRQoL (β = 0.069, 95% CI [0.006, 0.131],p= 0.032). In contrast, our analysis revealed a significant negative correlation between FSS and WHO-5 scores (β = -0.016, 95% CI [-0.021, –0.011],p< 0.001). The beta-coefficient ratio (βDSST/ βFSS= 0.069 / 0.016) is calculated as 4.313.

Conclusions

Overall, we observed that increased cognitive function was associated with increased HRQoL at baseline in adults with PCC. Moreover, we observed that increased severity of fatigue symptoms was associated with decreased HRQoL at baseline in adults with PCC. Furthermore, we observed that an improvement in cognitive function would have a four-fold greater impact on HRQoL than the effect generated by improvement in fatigue.
Genotype-specific differences in infertile men due to loss-of-function variants inM1APorZZSgenes
Authors: Rotte Nadja , Dunleavy Jessica E.M. , Runkel Michelle D. , Fietz Daniela , Pilatz Adrian , Kuss Johanna , Dicke Ann-Kristin , Winge Sofia B. , Persio Sara Di , Ruckert Christian , Nordhoff Verena , Schuppe Hans-Christian , Almstrup Kristian , Kliesch Sabine , Neuhaus Nina , Stallmeyer Birgit , O’Bryan Moira K. , Tüttelmann Frank , Friedrich Corinna
Published: March 2024

Male infertility and meiotic arrest have been linked toM1AP, the gene encoding meiosis I associated protein. In mice, M1AP interacts with the ZZS proteins SHOC1, TEX11, and SPO16, which promote DNA class I crossover formation during meiosis. To determine whether M1AP and ZZS proteins are involved in human male infertility by disrupting class I crossover formation, we screened for biallelic or hemizygous loss-of-function (LoF) variants in the encoding human genes to select men with a presumed protein deficiency; we compiled N=10 men forM1AP, N=4 forSHOC1, N=9 forTEX11,and the first homozygous LoF variant inSPO16in an infertile man. After in-depth characterisation of the testicular phenotype of these men, we identified gene-specific meiotic impairments: men with SHOC1, TEX11, or SPO16 deficiency shared an early meiotic arrest lacking haploid germ cells. All men with LoF variants inM1APexhibited a predominant metaphase I arrest with rare haploid round spermatids, and six men even produced sporadic elongated spermatids. These differences were explained by different recombination failures: abrogated SHOC1, TEX11, or SPO16 led to incorrect synapsis of homologous chromosomes and unrepaired DNA double-strand breaks (DSB). On the contrary, abolished M1AP did not affect synapsis and DSB repair but led to a reduced number of class I crossover events. Notably, medically assisted reproduction resulted in the birth of a healthy child, offering the possibility of fatherhood to men with LoF variants inM1AP. Our study establishes M1AP as an important, but not essential, functional enhancer in the network of ZZS-mediated meiotic recombination.
Challenges in Institutional Ethical Review Process and Approval for International Multicenter Clinical Studies in Lower and Middle-Income Countries: the case of PARITY Study
Authors: Baron Eliana Lopez , Abbas Qalab , Caporal Paula , Agulnik Asya , Attebery Jonah E. , Holloway Adrian , Kissoon Niranjan “Tex” , Mulgado-Aguas Celia Isabel , Amegan-Aho Kokou , Majdalani Marianne , Ocampo Carmen , Pascal Havugarurema , Miller Erika , Kanyamuhunga Aimable , Tekleab Atnafu Mekonnen , Bacha Tigist , González Sebastian , Bhutta Adnan T. , Kortz Teresa B. , Murthy Srinivas , Remy Kenneth E. ,   the Global Health Subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
Published: March 2024

Objectives

To describe the regulatory process, variability and challenges faced by pediatric researchers in low- and middle-income countries (LMICs) during the institutional review board (IRB) process of an international multicenter observational point prevalence study (Global PARITY).

Design

A 16-question multiple-choice online survey was sent to site principal investigators (PIs) at PARITY study participating centers to explore characteristics of the IRB process, costs, and barriers to research approval. A shorter survey was employed for sites that expressed interest in participating in Global PARITY and started the approval process, but ultimately did not participate in data collection (non-participating sites) to assess IRB characteristics.

Subjects

PIs from the Global PARITY Study

Interventions

None.

Results

Ninety-one sites pursued local IRB approval and 46 sites obtained IRB approval and completed data collection. Forty-six (100 %) participating centers and 21 (47%) non-participant centers completed the survey. Despite receiving approval from the study’s lead center and being categorized as a minimal risk study, 36 (78%) of the hospitals involved in PARITY study required their own full board review. There was a significant difference between participating and non-participating sites in IRB approval of a waiver consent and in the requirement for a legal review of the protocol. The greatest challenge to research identified by non-participating sites was a lack of research time and the lack of institutional support.

Conclusions

Global collaborative research is crucial to increase our understanding of pediatric critical care conditions in hospitals of all resource-levels and IRBs are required to ensure that this research complies with ethical standards. Critical barriers restrict research activities in some resource limiting countries. Increasing the efficiency and accessibility of local IRB review could greatly impact participation of resource limited sites and enrollment of vulnerable populations.
The Adequacy of ANC services received and associated factors among Women of Reproductive Age in Tanzania
Authors: Tibenderana Jovin R. , Kessy Sanun Ally , Mlaponi Dosanto Felix , Mtenga John Elyas , Gimonge Jomo , Mwaitete Ndinagwe Lloyd , Moshi Fabiola V
Published: March 2024

Background

ANC continues to be a vital and crucial component of care for expectant mothers and their unborn children, not only by lowering maternal mortality but also perinatal deaths and connecting them to postnatal treatment. There are limited information about the adequate Antenatal Care (ANC) services coverage, therefore this study aimed at examining the proportion of ANC services coverage, distribution pattern and its associated factors obtained by women of reproductive age (WRA) in Tanzania.

Methods

This was analytical cross-sectional study among women of reproductive age in Tanzania, utilizing data from the Demographic and Health Surveys (DHS) 2022. Analysis considered the complex survey design through application of weights, clustering and strata. Modified Poisson regression models estimated the factors associated with adequate reception of ANC services among WRA in Tanzania. All analyses were performed in STATA software version 18.

Results

The proportion of WRA who had received adequate ANC component coverage was 41%. Distribution of ANC contents ranged from 0.5% to 41% for none to seven services respectively. Almost all women (96.1%) had their baby’s heartbeat checked. Various factors such as education, wealth index, age, residence, number of ANC visits and birth order were significantly associated with uptake of ANC services among WRA in Tanzania.

Conclusion

The overall findings suggest a notable disparity in the utilization of ANC services, as fewer than half of women of reproductive age (WRA) are receiving sufficient ANC coverage. Therefore, integrated approaches involving health care facilities and communities, innovative strategies targeting young adults, and strengthening the policy of four or more ANC visits with regular monitoring and data collection are recommended to improve ANC access, utilization, and alignment with WHO guidelines.
The prognostic value of mean platelet volume in patients with coronary artery disease: a systematic review with meta-analyses
Authors: Galimzhanov Akhmetzhan , Naung Tun Han , Sabitov Yersin , Perone Francesco , Kursat Tigen Mustafa , Tenekecioglu Erhan , Mamas Mamas A
Published: March 2024

Background

Mean platelet volume (MPV) is a widely available laboratory index, however its prognostic significance in patients with coronary artery disease (CAD) is still unclear. We intended to investigate and pool the evidence on the prognostic utility of admission MPV in predicting clinical outcomes in patients with CAD.

Methods

PubMed, Web of Science, and Scopus were the major databases used for literature search. The risk of bias was assessed using the quality in prognostic factor studies. We used random-effects pairwise analysis with the Knapp and Hartung approach supported further with permutation tests and prediction intervals (PIs).

Results

We identified 52 studies with 47066 patients. A meta-analysis of 9 studies with 14,864 patients demonstrated that 1 femtoliter increase in MPV values was associated with a rise of 29% in the risk of long-term mortality (hazard ratio (HR) 1.29, 95% confidence interval (CI) 1.22-1.37) in CAD as a whole. The results were further supported with PIs, permutation tests and leave-one-out sensitivity analyses. MPV also demonstrated its stable and significant prognostic utility in predicting long-term mortality as a linear variable in patients treated with percutaneous coronary intervention (PCI) and presented with acute coronary syndrome (ACS) (HR 1.29, 95% CI 1.20-1.39, and 1.29, 95% CI 1.19-1.39, respectively).

Conclusion

The meta-analysis found robust evidence on the link between admission MPV and the increased risk of long-term mortality in patients with CAD patients, as well as in patients who underwent PCI and patients presented with ACS.

PROSPERO number

CRD42023495287
Association between Insomnia Symptoms and Risk of Heart Failure: A Meta-analysis of Prospective Cohort Studies
Authors: Gao Juan , Han Le , Cao Hong-Shuai , Luo Xiao-Qin , Xu Li-Yue , Zhou Ying , Lian Zhe-Xun , Ren Jing-Yi
Published: March 2024

Background

Insomnia, as one of the most prevalent sleep disorders, is frequently linked to Heart failure (HF). However, the precise relationship and potential risk of HF events associated with insomnia and subtypes of symptoms necessitate further investigation.

Objective

This updated meta-analysis aimed to evaluate the associations between HF and various insomnia symptoms, including difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), early-morning awakening (EMA) and non-restorative sleep (NRS).

Methods

A comprehensive literature search was conducted in PubMed, Web of Science, Embase, and the Cochrane Library to identify prospective cohort studies from inception to October 2023. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to assess the correlation between insomnia and the risk of HF. Funnel plots and Egger’s tests were employed to assess publication bias.

Results

A total of 177,008 patients from seven eligible prospective cohort studies were included. The pooled minimally adjusted HR for HF was 1.26 (95% CI:1.09-1.45;P=0.001), indicating that insomnia was associated with increased risk of HF. Among the individual insomnia symptoms, only DIS showed a positive association with risk of HF (HR:1.14, 95% CI:1.04-1.25;P=0.005). DMS and NRS had no significant effect on the risk of HF (P>0.05). In the subgroup analysis including age, sex and BMI, there were no significant differences between each group.

Conclusion

This meta-analysis confirms the link between insomnia and an increased risk of HF, particularly highlighting the importance of DIS as a potential predictor for HF.

Clinical Perspective

What is new?

Insomnia is ubiquitous and seriously affects people’s normal work, life, and health. At present, prospective cohort studies have suggested that insomnia can increase the risk of heart failure (HF). However, in our meta-analysis, we firstly found that only Difficulty Initiating Sleep (DIS) was directly associated with an increased HF incidence, rather than other insomnia subtypes. This is a very interesting which suggests that DIS has a greater impact on the incident of HF. In addition, this points us that in the subsequent treatment of insomnia, maybe we should pay more attention to the treatment of DIS.

What are the clinical implications?

As insomnia symptoms can be assessed and identified early and are relatively manageable, the study of the relationship between insomnia and HF has potential important clinical significance. If further research confirms that the improvement of insomnia symptoms, especially DIS symptoms, contributes to the prevention of HF or the prognosis of HF patients, it will provide another new “track” for the prevention and treatment of HF.
Discovery and chemical optimisation of a Potent, Bi-cyclic (Bicycle®) Antimicrobial Inhibitor ofEscherichia coliPBP3
Authors: Rowland Catherine E. , Newman Hector , Martin Tazmin T. , Dods Rachel , Bournakas Nikolaos , Wagstaff James M. , Lewis Nick , Stanway Steven J. , Balmforth Matthew , Kessler Celia , van Rietschoten Katerine , Bellini Dom , Roper David I. , Lloyd Adrian J. , Dowson Christopher G. , Skynner Michael J. , Beswick Paul , Dawson Michael J.
Published: March 2024

Penicillin binding proteins (PBPs) are well validated antimicrobial targets, but the prevalence of β-lactamase driven resistance and, more rarely, target-based mutations, necessitates new classes of PBP-targeting drugs. Here we describe the discovery and optimisation of novel, bicyclic peptide (Bicycle®) inhibitors ofE. coliPBP3 (EcPBP3) using a proprietary phage display platform, and their conjugation to linear antimicrobial peptides to confer outer membrane permeation. These molecules exhibited high-affinity binding toE. coliPBP3 and a viable spectrum of killing activity against clinically relevant species of the Enterobacterales. X-ray crystallography was used to explore the mode of binding to PBP3, enabling increased target affinity and improvement ofin vitrostability. These compounds bind to the transpeptidase active site cleft of PBP3 and represent a novel non-β-lactam chemical class of high affinity, non-covalent penicillin binding protein inhibitors.
Archaeogenetic analysis revealed East Eurasian paternal origin to the Aba royal family of Hungary
Authors: Varga Gergely I B , Maróti Zoltán , Schütz Oszkár , Maár Kitti , Nyerki Emil , Tihanyi Balázs , Váradi Orsolya , Ginguta Alexandra , Kovács Bence , Kiss Petra , Dosztig Monika , Gallina Zsolt , Török Tibor , Szabó János B. , Makoldi Miklós , Neparáczki Endre
Published: March 2024

The Aba family played a pivotal role in the early history of Medieval Hungary dominating extensive territories and giving rise to influential figures. We conducted an archaeogenetic examination of remains uncovered at the necropolis in Abasár, the political centre of the Aba clan, to identify Aba family members and shed light on their genetic origins. Utilizing Whole Genome Sequencing (WGS) data from 19 individuals, complemented by radiocarbon measurements, we identified 6 members of the Aba family who shared close kinship relations. Our analysis revealed that 4 males from this family carried identical N1a1a1a1a4∼ haplogroups. Significantly, our phylogenetic investigation traced this royal paternal lineage back to Mongolia, strongly suggesting its migration to the Carpathian Basin with the conquering Hungarians. Genome analysis, incorporating ADMIXTURE, Principal Component Analysis (PCA), and qpAdm, revealed East Eurasian patterns in the studied genomes, consistent with our phylogenetic results. Shared Identity by Descent (IBD) analysis confirmed the family kinship relations and shed light on further external kinship connections. It revealed that members of the Aba family were related to members of prominent Hungarian medieval noble families the Árpáds, Báthorys and Corvinus as well as to the first-generation immigrant elite of the Hungarian conquest.
SARS-CoV-2 infection activates inflammatory macrophages in vascular immune organoids
Authors: Chau Chiu Wang , To Alex , Au-Yeung Rex K.H. , Tang Kaiming , Xiang Yang , Ruan Degong , Zhang Lanlan , Wong Hera , Zhang Shihui , Au Man Ting , Chung Seok , Song Euijeong , Choi Dong-Hee , Liu Pentao , Yuan Shuofeng , Wen Chunyi , Sugimura Ryohichi
Published: March 2024

SARS-CoV-2 provokes devastating tissue damage by cytokine release syndrome and leads to multi-organ failure. Modeling the process of immune cell activation and subsequent tissue damage is a significant task. Organoids from human tissues advanced our understanding of SARS-CoV-2 infection mechanisms though, they are missing crucial components: immune cells and endothelial cells. This study aims to generate organoids with these components. We established vascular immune organoids from human pluripotent stem cells and examined the effect of SARS-CoV-2 infection. We demonstrated that infections activated inflammatory macrophages. Notably, the upregulation of interferon signaling supports macrophages role in cytokine release syndrome. We propose vascular immune organoids are a useful platform to model and discover factors that ameliorate SARS-CoV-2-mediated cytokine release syndrome.
Decreased cerebral blood flow in a supine position in patients with a history of syncope and presyncope during the Tilt Table Test
Authors: Cano V , González-Hermosillo JA , Murata Ch , Martínez-Rosas M , Hernández-Pacheco G
Published: March 2024

Objective

To analyze the hemodynamic response, cerebral blood flow, and the sympathovagal balance between patients with structurally healthy hearts who have a history of syncope and presyncope that exhibited signs or symptoms of presyncope without progressing to syncope during the tilt-table test, and a healthy group.

Methodology

A retrospective study was conducted on patients attending the dysautonomia clinic of a tertiary care center. Individuals of both sexes aged 15 to 50 years were included. Patients with positive tests for VVS, OH, or POTS, and those with negative results were excluded. As a healthy group, healthy volunteers without a personal history of syncope or presyncope and with a negative tilt-table test were included.

Statistical Analysis

Categorical variables were expressed as percentages and quantitative variables as mean ± standard deviation. Repeated measures ANOVA, the χ2 test, and effect size using Glass’s Δ were used for group comparisons. A P-value < 0.05 was considered statistically significant. The R software, RStudio, and the effsize package were used for analysis.

Results

The main finding was a significant decrease in cerebral blood flow secondary to an increase in cerebral vascular resistance in patients from a supine position at the start and throughout the test, compared to the control group.

Conclusion

The analysis of cerebral hemodynamics allows for the identification of a subpopulation of patients who exhibit decreased cerebral blood flow from a supine position during the tilt-table test while maintaining cardiovascular stability without progressing to syncope.
Stable, multigenerational transmission of the bean seed microbiome despite abiotic stress
Authors: Sulesky-Grieb Abby , Simonin Marie , Bintarti A. Fina , Marolleau Brice , Barret Matthieu , Shade Ashley
Published: March 2024

Seed microbiomes initiate plant microbiome assembly, but the consequences of environmental conditions of the parent plant for seed microbiome assembly and transmission are unknown. We tracked endophytic seed bacterial communities of common bean lines exposed to drought or excess nutrients, and discovered stable transmission of 22 bacterial members regardless of parental plant treatment. This study provides insights into the maintenance of plant microbiomes across generations, even under challenging environmental stress.
The branched receptor binding complex ofAckermannviridaephages promotes adaptative host recognition
Authors: Sørensen Anders Nørgaard , Woudstra Cedric , Kalmar Dorottya , Poppeliers Jorien , Lavigne Rob , Sørensen Martine Camilla Holst , Brøndsted Lone
Published: March 2024

Bacteriophages may express multiple receptor binding proteins, enabling the recognition of distinct and diverse bacterial receptors for infection of a broad range of strains.Ackermannviridaephages recognize diverse O-antigens or K-antigens as receptors by expressing multiple tail spike proteins (TSPs). These TSPs interact and form a branched protein complex protruding from the baseplate attached to the distal tail. Here, we aimed to mimic the evolution of the TSP complex by studying the acquisition of new TSPs without disrupting the functionality of the complex. Using kuttervirus phage S117 as a backbone, we demonstrated the acquisition of entiretspgenes fromKuttervirusandAgtrevirusphages within theAckermannviridaefamily. A fifth TSP was designed to interact with the complex and provide new host recognition to expand the branched TSP complex. Interestingly, the acquisition oftsp5resulted in new variants of the branched TSP complex due to the exchange or deletion oftspgenes. Overall, our study provides novel insight into the development of the branched TSP complex, enablingAckermannviridaephages to adapt to new hosts.
Human CCDC51 and yeast Mdm33 are functionally conserved mitochondrial inner membrane proteins that demarcate a subset of organelle fission events
Authors: Edington Alia R. , Connor Olivia M. , Marlar-Pavey Madeleine , Friedman Jonathan R.
Published: March 2024

Mitochondria are highly dynamic double membrane-bound organelles that exist in a semi- continuous network. Mitochondrial morphology arises from the complex interplay of numerous processes, including opposing fission and fusion dynamics and the formation of highly organized cristae invaginations of the inner membrane. While extensive work has examined the mechanisms of mitochondrial fission, it remains unclear how fission is coordinated across two membrane bilayers and how mitochondrial inner membrane organization is coupled with mitochondrial fission dynamics. Previously, the yeast protein Mdm33 was implicated in facilitating fission by coordinating with inner membrane homeostasis pathways. However, Mdm33 is not conserved outside fungal species and its precise mechanistic role remains unclear. Here, we use a bioinformatic approach to identify a putative structural ortholog of Mdm33 in humans, CCDC51 (also called MITOK). We find that the mitochondrial phenotypes associated with altered CCDC51 levels implicate the protein in mitochondrial fission dynamics. Further, using timelapse microscopy, we spatially and temporally resolve Mdm33 and CCDC51 to a subset of mitochondrial fission events. Finally, we show that CCDC51 can partially rescue yeast Δmdm33cells, indicating the proteins are functionally analogous. Our data reveal that Mdm33/CCDC51 are conserved mediators of mitochondrial morphology and suggest the proteins play a crucial role in maintaining normal mitochondrial dynamics and organelle homeostasis.
Development and Validation of Genome-Informed and Multigene-based qPCR and LAMP Assays for Accurate Detection ofDickeya solani: A Critical Quarantine Pathogen Threatening Potato Industry
Authors: Dobhal Shefali , Santillana Gem , Stulberg Michael J. , Arizala Dario , Alvarez Anne M. , Arif Mohammad
Published: March 2024

Dickeya solani, one of the most aggressive pectinolytic phytopathogens, causes blackleg disease in potatoes, resulting in significant economic losses and adversely impacting one of the world’s most important food crops. The diagnostics methods are critical in monitoring the latent infection for international trade of potato seed-tubers and in implementation of control strategies. Our study employed a whole-genome comparative approach, identifying unique target gene loci (LysR and TetR family of transcriptional regulators gene regions), design loop-mediated isothermal amplification (LAMP) and a multi-gene-based multiplex TaqMan qPCR assays for specific detection and differentiation ofD. solani. Both methods underwent meticulous validation with extensive inclusivity and exclusivity panels, exhibiting 100% accuracy and no false positives or negatives. The LAMP method demonstrated the detection limit of 100 fg and 1 CFU per reaction using pure genomic DNA and crude bacterial cell lysate, respectively. The qPCR detection limit was 1 pg, 100 fg and 10 fg with Quadplex, triplex and singleplex, respectively. None of the assay showed any inhibitory effect after adding host DNA (in qPCR) or crude lysate (in LAMP). The assays proved robust and reproducible in detecting the target pathogen in infected samples, with the LAMP assay being field-deployable due to its simplicity and rapid results acquisition within approximately 8.92 minutes. The reproducibility was confirmed by performing the assay in two independent laboratories. These developed assays offer a robust, rapid, and reliable solution for routine testing, with applications in phytosanitary inspection and epidemiological studies.

IMPORTANCE

Dickeya solani, one of the most aggressive soft rots causing-bacteria and a quarantine pathogen, poses a severe threat to food security by causing substantial economic losses to potato industry. Accurate and timely detection of this bacteria is vital for monitoring latent infections, particularly for international trade of potato seed tubers, and for implementing effective control strategies. In this research we have developed a LAMP and a multi-gene-based multiplex TaqMan qPCR assays for specific detection ofD. solani. These assays, characterized by their precision, rapidity, and robustness, are crucial for distinguishingD. solanifrom related species. Offering unparalleled sensitivity and specificity, these assays are indispensable for phytosanitary inspection and epidemiological monitoring, providing a powerful tool for management of this threatening pathogen.
Asynchronous microexon splicing ofLSD1andPHF21Aduring neurodevelopment
Authors: Nagai Masayoshi , Porter Robert S. , Hughes Elizabeth , Saunders Thomas L. , Iwase Shigeki
Published: March 2024

LSD1 histone H3K4 demethylase and its binding partner PHF21A, a reader protein for unmethylated H3K4, both undergo neuron-specific microexon splicing. The LSD1 neuronal microexon weakens H3K4 demethylation activity and can alter the substrate specificity to H3K9 or H4K20. Meanwhile, the PHF21A neuronal microexon interferes with nucleosome binding. However, the temporal expression patterns of LSD1 and PHF21A splicing isoforms during brain development remain unknown. In this work, we report that neuronal PHF21A isoform expression precedes neuronal LSD1 isoform expression during human neuron differentiation and mouse brain development. The asynchronous splicing events resulted in stepwise deactivation of the LSD1-PHF21A complex in reversing H3K4 methylation. We further show that the enzymatically inactive LSD1-PHF21A complex interacts with neuron-specific binding partners, including MYT1-family transcription factors and post-transcriptional mRNA processing proteins such as VIRMA. The interaction with the neuron-specific components, however, did not require the PHF21A microexon, indicating that the neuronal proteomic milieu, rather than the microexon-encoded PHF21A segment, is responsible for neuron-specific complex formation. These results indicate that the PHF21A microexon is dispensable for neuron-specific protein-protein interactions, yet the enzymatically inactive LSD1-PHF21A complex might have unique gene-regulatory roles in neurons.
Adaptive Optics in an Oblique Plane Microscope
Authors: McFadden Conor , Marin Zach , Chen Bingying , Daetwyler Stephan , Xiaoding Wang , Rajendran Divya , Dean Kevin M. , Fiolka Reto
Published: March 2024

Adaptive optics (AO) can restore diffraction limited performance when imaging beyond superficial cell layersin vivoandin vitro, and as such is of interest for advanced 3D microscopy methods such as light-sheet fluorescence microscopy (LSFM). In a typical LSFM system, the illumination and detection paths are separate and subject to different optical aberrations. To achieve optimal microscope performance, it is necessary to sense and correct these aberrations in both light paths, resulting in a complex microscope system. Here, we show that in an oblique plane microscope (OPM), a type of LSFM with a single primary objective lens, the same deformable mirror can correct both the illumination and fluorescence detection. Besides reducing the complexity, we show that AO in OPM also restores the relative alignment of the light-sheet and focal plane, and that a projection imaging mode can stabilize and improve the wavefront correction in a sensorless AO format. We demonstrate OPM with AO on fluorescent nanospheres and by imaging the vasculature and cancer cells in zebrafish embryos embedded in a glass capillary, restoring diffraction limited resolution and improving the signal strength twofold.
Impact of the continuum Coulomb interaction in quantum-orbit-based treatments of high-order above-threshold ionization
Authors: Rook T. , Habibović D. , Rodriguez L. Cruz , Milošević D. B. , Faria C. Figueira de Morisson
Published: March 2024

We perform a systematic comparison between photoelectron momentum distributions computed with the rescattered quantum-orbit strong-field approximation (RQSFA) and the Coulomb quantum-orbit strong-field approximation (CQSFA). We exclude direct, hybrid, and multiply scattered CQSFA trajectories and focus on the contributions of trajectories that undergo a single act of rescattering. For this orbit subset, one may establish a one-to-one correspondence between the RQSFA and CQSFA contributions for backscattered and forward-scattered trajectory pairs. We assess the influence of the Coulomb potential on the ionization and rescattering times of specific trajectory pairs, kinematic constraints determined by rescattering, and quantum interference between specific pairs of trajectories. We analyze how the Coulomb potential alters their ionization and return times, and their interference in photoelectron momentum distributions. We show that Coulomb effects are not significant for high or medium photoelectron energies and shorter orbits, while for lower momentum ranges or longer electron excursion times in the continuum, the residual Coulomb potential is more important. We also assess the agreement of both theories for different field parameters and show that it improves with the increase of the wavelength.

Published by the American Physical Society
2024
Collinear-spin machine learned interatomic potential for
Fe7Cr2Ni
alloy
Authors: Shenoy Lakshmi , Woodgate Christopher D. , Staunton Julie B. , Bartók Albert P. , Becquart Charlotte S. , Domain Christophe , Kermode James R.
Published: March 2024

We have developed a machine learned interatomic potential for the prototypical austenitic steel Fe7Cr2Ni, using the Gaussian approximation potential (GAP) framework. This GAP can model the alloy's properties with close to density functional theory (DFT) accuracy, while at the same time allowing us to access larger length and time scales than expensive first-principles methods. We also extended the GAP input descriptors to approximate the effects of collinear spins (spin GAP), and demonstrate how this extended model successfully predicts structural distortions due to antiferromagnetic and paramagnetic spin states. We demonstrate the application of the spin GAP model for bulk properties and vacancies and validate against DFT. These results are a step towards modeling the atomistic origins of ageing in austenitic steels with higher accuracy.

Published by the American Physical Society
2024
Localization, fractality, and ergodicity in a monitored qubit
Authors: Pöpperl Paul , Gornyi Igor V. , Saakian David B. , Yevtushenko Oleg M.
Published: March 2024

We study the statistical properties of a single two-level system (qubit) subject to repetitive ancilla-based measurements. This setup is a fundamental minimal model for exploring the intricate interplay between the unitary dynamics of the system and the nonunitary stochasticity introduced by quantum measurements, which is central to the phenomenon of measurement-induced phase transitions. We demonstrate that this “toy model” harbors remarkably rich dynamics, manifesting in the distribution function of the qubit's quantum states in the long-time limit. We uncover a compelling analogy with the phenomenon of Anderson localization, albeit governed by distinct underlying mechanisms. Specifically, the state distribution function of the monitored qubit, parameterized by a single angle on the Bloch sphere, exhibits diverse types of behavior familiar from the theory of Anderson transitions, spanning from complete localization to almost uniform delocalization, with fractality occurring between the two limits. By combining analytical solutions for various special cases with two complementary numerical approaches, we achieve a comprehensive understanding of the structure delineating the “phase diagram” of the model. We categorize and quantify the emergent regimes and identify two distinct phases of the monitored qubit: ergodic and nonergodic. Furthermore, we identify a genuinely localized phase within the nonergodic phase, where the state distribution functions consist of delta peaks, as opposed to the delocalized phase characterized by extended distributions. Identification of these phases and demonstration of transitions between them in a monitored qubit are our main findings.

Published by the American Physical Society
2024
Learning Conservation Laws in Unknown Quantum Dynamics
Authors: Zhan Yongtao , Elben Andreas , Huang Hsin-Yuan , Tong Yu
Published: March 2024

We present a learning algorithm for discovering conservation laws given as sums of geometrically local observables in quantum dynamics. This includes conserved quantities that arise from local and global symmetries in closed and open quantum many-body systems. The algorithm combines the classical shadow formalism for estimating expectation values of observable and data analysis techniques based on singular value decompositions and robust polynomial interpolation to discover all such conservation laws in unknown quantum dynamics with rigorous performance guarantees. Our method can be directly realized in quantum experiments, which we illustrate with numerical simulations, using closed and open quantum system dynamics in a Z2 gauge theory and in many-body localized spin chains.

Published by the American Physical Society
2024
Efficient end-to-end simulation of time-dependent coherent X-ray scattering experiments
Authors: Goel Himanshu , Chubar Oleg , Li Ruizi , Wiegart Lutz , Rakitin Max , Fluerasu Andrei
Published: March 2024

Physical optics simulations for beamlines and experiments allow users to test experiment feasibility and optimize beamline settings ahead of beam time in order to optimize valuable beam time at synchrotron light sources like NSLS-II. Further, such simulations also help to develop and test experimental data processing methods and software in advance. The Synchrotron Radiation Workshop (SRW) software package supports such complex simulations. We demonstrate how recent developments in SRW significantly improve the efficiency of physical optics simulations, such as end-to-end simulations of time-dependent X-ray photon correlation spectroscopy experiments with partially coherent undulator radiation (UR). The molecular dynamics simulation code LAMMPS was chosen to model the sample: a solution of silica nanoparticles in water at room temperature. Real-space distributions of nanoparticles produced by LAMMPS were imported into SRW and used to simulate scattering patterns of partially coherent hard X-ray UR from such a sample at the detector. The partially coherent UR illuminating the sample can be represented by a set of orthogonal coherent modes obtained by simulation of emission and propagation of this radiation through the coherent hard X-ray (CHX) scattering beamline followed by a coherent-mode decomposition. GPU acceleration is added for several key functions of SRW used in propagation from sample to detector, further improving the speed of the calculations. The accuracy of this simulation is benchmarked by comparison with experimental data.
Benchmarking lean construction conformance in Pakistan’s construction industry
Authors: Aslam Mughees , Baffoe-Twum Edmund , Malik Sohail
Published: March 2024

Purpose

Lean construction (LC) is an innovative approach in the construction industry that has shown significant success in developed countries. Although LC has potential in the construction sector of Pakistan, it has not been extensively explored. This study aims to address this knowledge gap by identifying and predicting current lean practices and assessing the strengths and weaknesses of LC implementation in Pakistan.

Design/methodology/approach

Using robust statistical methods to analyze 92 valid responses, the study reveals that approximately 54% of lean practices are currently in use in the construction industry of Pakistan, with a population mean ranging from 52.7% to 55.6%.

Findings

Surprisingly, the research identifies instances where some construction firms in Pakistan are implementing LC practices, even though they have only a limited understanding of its underlying principles. Notably, certain subprinciples, such as visual management, top management commitment to change, employee training, process cycle time reduction and production optimization, are less integrated within the construction industry. Exploring the possibility of implementing LC, recommendations for strategies to implement LC in Pakistan are suggested, aligning with the conceptual model proposed by the researchers.

Originality/value

The novelty of this work offers insights that can serve as a comprehensive guide for developing nations. It provides a structured approach to assess and benchmark LC practices, which, in turn, can contribute to a more efficient and effective construction industry. Moreover, the strategies proposed in this research can aid developing countries in the efficient implementation of LC. This will have a positive implication for both economic and developmental outcomes.
Do not forget about me, do not forget about you. Usability of a mobile app for professional identity formation
Authors: Olivares-Olivares Silvia Lizett , Turrubiates Corolla Miriam Lizzeth , Nigenda Alvarez Juan Pablo , Mejía Gaviria Natalia , Lema-Velez Mariana , Villarreal Rodríguez Miguel Angel , Franco Ayala Luis Carlos , Trujillo Maza Elena María , Barriga Cosmelli Isabel , Puschel Illanes Klaus
Published: March 2024

Purpose

Professional Identity Formation is the dynamic evolution to “think, act and feel” to become part of a professional community. This document presents the development and the study that aimed to assess the usability of a m-Learning Identity App (MLIA) focused on the formation of professional identity among undergraduate medical students.

Design/methodology/approach

MLIA development included four phases: Conceptual, prototype, pilot and implementation, before further deployment. The conceptual model was designed by eight faculty members from three Latin American universities. The prototype was developed and tested with stakeholders. The pilot was performed during 5 weeks before the implementation. Cross-sectional data collected during implementation from 138 medical students who completed a survey to assess the usability of MLIA are presented. During deployment, 977 posts were made on Professional Identity Formation, and examples of these posts are presented.

Findings

The prototype and pilot phases demanded improvements. The survey explored (1) Familiarity, (2) Perceived ease of use, (3) Perceived usefulness for Professional Identity Formation, (4) Satisfaction, (5) Intention to reuse (6) Digital aesthetics and (7) Safety. Results from the usability assessment suggest that students perceived MLIA as a secure space with positive aesthetics and ease of use.

Research limitations/implications

Important limitations of the present study include, firstly, that it does not provide information on the effectiveness of the MLIA in shaping professional identity in medical students, it focuses exclusively on its development (conceptual model, prototype, pilot and implementation) and usability. Secondly, the study design did not consider a control group and, therefore, does not provide information on how the App compares with other strategies addressing self-reflection and sharing of meaningful experiences related to professional identity.

Originality/value

MLIA introduces a different approach to education, simulating a secure, easy-to-use, social media with a friendly interface in a safe environment to share academic and motivational moments, transitioning from being to becoming a professional.
Class modality transition during COVID-19 pandemic: implications for unforeseen events
Authors: Wen Lei , Mi Danya , Moon Daehyun
Published: March 2024

Purpose

This study aims to examine student perceptions regarding the mid-semester transition from face-to-face to online delivery in an accounting course during spring 2020.

Design/methodology/approach

Due to the COVID-19 pandemic, numerous universities and colleges worldwide transitioned from face-to-face instruction to online delivery during spring 2020. We find some evidence in line with prior literature that COVID-19 affected student learning experience from various aspects.

Findings

Thanks in part to effective teaching techniques implemented by the instructor during the transition, including online lecture videos recorded by the instructor, online class materials, early posting of answer keys, frequent communication through emails and bonus points for watching lecture videos, students still perceived their learning outcomes positively in general.

Originality/value

These teaching techniques can be used to enhance student learning experience and satisfaction during class modality transitions in unforeseen circumstances, for both hybrid and online business courses.