bluuebunny/crossref_metadata_2025 huggingface dataset:
Endemic viral infections in immunocompromised hosts: Dengue, Chikungunya, Zika
Authors: Garnica Marcia , Ramos Jessica Fernandes , Machado Clarisse Martins
Published: June 2024

Purpose of review

Arbovirus infections are a challenge for immunocompromised hosts who travel to or live in endemic regions or who receive organs or tissues from donors who travel or live in such areas. This review addresses Dengue (DENV), Chikungunya (CHIKV), and Zika (ZIKV) infections in hematological patients, hematopoietic cell or solid organ transplant recipients, and people with HIV (PWH).

Recent findings

Transmission is mainly due through Aedes mosquito bite. DENV and ZIKV may also be transmitted through blood, tissues or donor grafts. Clinical manifestations are quite similar and diagnosis requires laboratory confirmation to provide appropriate management. The best diagnostic method is PCR since serology may present false negative results in immunocompromised patients, or cross-reactivity as in the case of DENV and ZIKV. There is no specific treatment for any of these infections.

Educational and preventive measures are the best strategy: vector control, knowledge of the vector's habits, protection against mosquito bites, avoiding travel to endemic areas or with a current epidemic, and avoiding nonvector transmission according to local recommendations for donor deferral. Vaccination, currently only available for DENV, has not yet been studied in immunocompromised patients and is not currently recommended.
Comparison of microRNA expression levels in patients with schizophrenia before and after electroconvulsive therapy
Authors: Usta Saglam Nazife Gamze , Duz Mehmet Bugrahan , Salman Yilmaz Seda , Ozen Mustafa , Balcioglu Ibrahim
Published: June 2024

Objective

Exploring the role of microRNAs in the antipsychotic efficacy of electroconvulsive therapy (ECT) will contribute to understanding the underlying mechanism through which ECT exerts its therapeutic effects. The primary objective of this study was to identify microRNA alterations before and after ECT in patients with schizophrenia.

Methods

We compared microarray-based microRNA profiles in peripheral blood from eight patients with schizophrenia before and after ECT and eight healthy controls. Then, we aimed to validate selected differentially expressed microRNAs in 30 patients with schizophrenia following a course of ECT, alongside 30 healthy controls by using quantitative reverse-transcription PCR.

Results

Microarray-based expression profiling revealed alterations in 681 microRNAs when comparing pre- and post-ECT samples. Subsequent quantitative reverse-transcription PCR analysis of the selected microRNAs (miR-20a-5p and miR-598) did not reveal any statistical differences between pre- and post-ECT samples nor between pre-ECT samples and those of healthy controls.

Conclusion

As neuroepigenetic studies on ECT are still in their infancy, the results reported in this study are best interpreted as exploratory outcomes. Additional studies are required to explore the potential epigenetic mechanisms underlying the therapeutic efficacy of ECT.
Towards a Yersinia pestis lipid A recreated in an Escherichia coli scaffold genome
Authors: McDonald Nathan , Antoshak Erin E.
Published: June 2024

Synthetic biology and genome engineering capabilities have facilitated the utilization of bacteria for myriad of applications ranging from medical treatments to biomanufacturing of complex molecules. The bacterial outer membrane, specifically the lipopolysaccharide (LPS), plays an integral role in the physiology, pathogenesis, and serves as a main target of existing detection assays for Gram-negative bacteria. Here we use CRISPR/Cas9 recombineering to insert Yersinia pestis lipid A biosynthesis genes into the genome of an Escherichia coli strain expressing the lipid IVa subunit. We successfully inserted three genes: kdsD, lpxM, and lpxP into the E. coli genome and demonstrated their expression via reverse transcription PCR (RT-PCR). Despite observing expression of these genes, analytical characterization of the engineered strain’s lipid A structure via MALDI-TOF mass spectrometry indicated that the Y. pestis lipid A was not recapitulated in the E. coli background. As synthetic biology and genome engineering technologies advance, novel applications and utilities for the detection and treatments of dangerous pathogens like Yersinia pestis will continue to be developed.
Campylobacter devanensis sp. nov., Campylobacter porcelli sp. nov., and Campylobacter vicugnae sp. nov., three novel Campylobacter lanienae-like species recovered from swine, small ruminants, and camelids
Authors: Miller William G. , Lopes Bruno S. , Ramjee Meenakshi , Jay-Russell Michele T. , Chapman Mary H. , Williams Tina G. , Wood Delilah F. , Gruntar Igor , Papić Bojan , Forbes Ken J.
Published: June 2024

In a previous study characterizing Campylobacter strains deficient in selenium metabolism, 50 strains were found to be similar to, but distinct from, the selenonegative species Campylobacter lanienae. Initial characterization based on multilocus sequence typing and the phylogeny of a set of 20 core genes determined that these strains form three putative taxa within the selenonegative cluster. A polyphasic study was undertaken here to further clarify their taxonomic position within the genus. The 50 selenonegative strains underwent phylogenetic analyses based on the sequences of the 16S rRNA gene and an expanded set of 330 core genes. Standard phenotypic testing was also performed. All strains were microaerobic and anaerobic, Gram-negative, spiral or curved cells with some displaying coccoid morphologies. Strains were motile, oxidase, catalase, and alkaline phosphatase positive, urease negative, and reduced nitrate. Strains within each clade had unique phenotypic profiles that distinguished them from other members of the genus. Core genome phylogeny clearly placed the 50 strains into three clades. Pairwise average nucleotide identity and digital DNA–DNA hybridization values were all below the recommended cut-offs for species delineation with respect to C. lanienae and other related Campylobacter species. The data presented here clearly show that these strains represent three novel species within the genus, for which the names Campylobacter devanensis sp. nov. (type strain RM3662T=LMG 33097T=NCTC 15074T), Campylobacter porcelli sp. nov. (type strain RM6137T=LMG 33098T=CCUG 77054T=NCTC 15075T) and Campylobacter vicugnae sp. nov. (type strain RM12175T=LMG 33099T=CCUG 77055T=NCTC 15076T) are proposed.
Interaction between gene expression and morphokinetic parameters in undisturbed human embryo culture
Authors: Xiao Hui , Stevens Adam , Smith Helen L. , Szczesna Karolina , Keramari Maria , Horne Gregory , Dinnyes Andras , Kimber Susan J. , Lio Pietro , Brison Daniel R.
Published: June 2024

The clinical in vitro fertilisation (IVF) need for optimal culture conditions and improved selection of human embryos for transfer led to the development of time-lapse systems built into incubators to allow a stable, well-defined and undisturbed culture environment with continual monitoring of embryo development. Clinical data suggest that both undisturbed culture of embryos and selection algorithms based on time-lapse morphometric parameters can potentially improve embryo development and live birth rates. However, there remains a need to validate and understand the mechanisms underlying the potential benefits of the time-lapse technology in IVF. In this study, we compared the gene expression of human embryos grown in an undisturbed time-lapse system with a conventional incubator and showed that there is no fundamental difference in the developmental program of the undisturbed embryos, which provides important reassurance concerning the time-lapse technology. We then performed a network-based integrative analysis based on the undisturbed blastocyst transcriptomes and identified time-lapse parameter correlated genes. These showed cross talk with identified embryo development gene functional modules, suggesting potential molecular mechanisms underlying the clinical predictive capabilities of embryo time-lapse morphokinetic parameters for subsequent live birth. This study suggests methodologies for assessing the impact of additional predictive correlates of value for optimal embryo development and understanding their mechanisms of action.
Accelerating CAR T cell manufacturing with an automated next-day process
Authors: Ahmadi Mina , Putnam Nicholas , Dotson Max , Hayoun Danny , Fatima Nujhat , Padilla Jasmine , Nonterah Gertrude , de Mollerat du Jeu Xavier , Ji Yongchang
Published: June 2024

The traditional method of CAR T cell production involves lengthyex vivoculture times which can result in the reduction of crucial naïve T cell subsets. Moreover, traditional CAR T cell therapy manufacturing processes can prolong time-to-patient and contribute to disease progression. In this study, we describe an innovative and automated 24-hour CAR T manufacturing process that yields a higher percentage of naïve/stem-cell like T cells which have increased cytotoxic activity and cytokine release. The data supports the feasibility of implementing this streamlined manufacturing process in clinics. This approach also has the potential to enhance CAR T therapy efficacy and improve patient access to therapy.
Impact of Parental Time-Restricted Feeding on Offspring Metabolic Phenotypic Traits
Authors: Fan Yibo , Peng Xiangyuan , Tabassum Nishat I. , Cheng Xiangru , Selvaraji Sharmelee , Tran Vivian , Gibson Hughes Tayla A. , Wickramasinghe Buddhila , Jamal Abdulsatar , Dinh Quynh Nhu , Gelderblom Mathias , Drummond Grant R. , Sobey Christopher G. , Penman Jim , Johns Terrance G. , Vemuganti Raghu , Gunaratne Jayantha , Mattson Mark P. , Jo Dong-Gyu , Jelinic Maria , Arumugam Thiruma V.
Published: June 2024

A substantial body of research elucidates the mechanisms and health advantages associated with intermittent fasting (IF). However, the impact of parental IF on offspring remains unclear. Through an investigation involving four IF andad libitumcombinations of parental mating groups, we demonstrate that parental IF (daily time-restricted feeding) influences offspring’s metabolic health indicators in male and female offspring in distinct ways. We found that when both parents are on IF their offspring exhibit protection against the adverse effects of a high-fat, high-sugar, and high-salt diet in a sex-specific manner. This study underscores the potential significance of parental lifestyle modifications involving dietary restriction for the metabolic status of their children and their risk for obesity and diabetes.
Up-regulated transcriptional regulators in mutant RAS gene signatures: a time-resolved multi-omics study in generic epithelial cell models
Authors: Kasack Katharina , Metzger Patrick , Koch Heiner , Klinger Bertram , Malek Anastasia , Tchernitsa Oleg , Gross Alexander , Wruck Wasco , Györffy Balazs , Küster Bernhard , Sers Christine , Börries Melanie , Schäfer Reinhold
Published: June 2024

The expression of mutated RAS genes drives extensive transcriptome alterations. Perturbation experiments have shown that the transcriptional responses to downstream effector pathways are partially unique and non-overlapping, suggesting a modular organization of the RAS-driven expression program. However, the relationship between individual deregulated transcription factors and the entire cancer cell-specific genetic program is poorly understood. To identify potential regulators of the RAS/MAPK-dependent fraction of the genetic program, we monitored transcriptome and proteome changes following conditional, time-resolved expression of mutant HRASG12Vin human epithelial cells during neoplastic conversion. High mobility group AT hook2 (HMGA2), an architectural chromatin modulating protein and oncofetal tumour marker, was recovered as the earliest upregulated transcription factor. Knock-down of HMGA2 reverted anchorage-independent growth and epithelial-mesenchymal transition not only in HRAS-transformed cells but also in an independent, KRASG12V-driven rat epithelial model. Moreover, HMGA2 silencing reverted the deregulated expression of 60% of RAS-responsive target genes. These features qualify HMGA2 as a master regulator of mutant RAS-driven expression patterns. The delayed deregulation of FOSL1, ZEB1 and other transcription factors with known oncogenic activity suggests that HMGA2 acts in concert with a network of regulatory factors to trigger full neoplastic conversion. Although transcription factors are considered difficult to drug, the central role of HMGA2 in the transcription factor network as well as its relevance for cancer prognosis has motivated attempts to block its function using small molecular weight compounds. The further development of direct HMGA2 antagonists may prove useful in cancer cells that have developed resistance to signalling chain inhibition.
Delayed dichromatism in waterfowl as a convenient tool for assessing vital rates
Authors: Tableau Adrien , Henderson Iain , Reeber Sébastien , Guillemain Matthieu , Maillard Jean-François , Caizergues Alain
Published: June 2024

Monitoring the number of individuals is by far the most popular strategy for studying the environmental factors that determine population dynamics and for measuring the effectiveness of management actions aimed at population recovery, control or eradication. Unfortunately, population size monitoring is inefficient in identifying the mechanisms underlying demographic processes and, in particular, in assessing the extent to which population growth rate is influenced by changes in adult survival rather than variations in reproductive parameters. In many waterfowl species, sexual dichromatism is observed in adults, while immatures of both sexes display a plumage pattern similar to that of adult females. In these species, the apparent proportion of males increases as the female-like immature males gradually take on the plumage of adult males. The difference between the apparent sex ratio before and after the young reach sexual maturity then provides information about the age ratio of a population. Using winter counts that distinguished between female-like and male-like individuals of two non-native populations of Ruddy duckOxyura jamaicensis, a species that exhibits such a plumage pattern, we present a non- invasive method based on the apparent sex ratio to split population growth rate into adult survival and recruitment rates (the latter also referred to as productivity). This method can correctly detect annual changes in vital rates, supporting the assumption that counts conducted in an appropriate time window reflect the age structure of a population. We exemplify how the respective contributions of survival and productivity to the population growth rate are essential for understanding the processes behind demo- graphic dynamics. Finally, we point out some best practices to correctly apply the “apparent sex ratio” method described here.
PIWIL1 is recruited to Centrosomes during Mitosis in Colorectal Cancer Cells and is linked to cell cycle progression
Authors: Garcia-Silva M.R. , Montenegro S. , Dacosta S. , Tosar J.P. , Cayota A
Published: June 2024

PIWI proteins, traditionally associated with germline development, have recently gained attention for their expression in various cancers, including colorectal cancer (CRC). However, the molecular mechanisms underlying their reactivation and impact on cancer initiation and progression remain elusive. Here, we found that PIWIL1 is expressed at relatively high levels in CRC-derived samples and cell lines, where it undergoes a dynamic re-localization to the centrosome during mitosis. Knockdown of PIWIL1 induces G2/M arrest associated to disruption of mitotic spindle and aberrant metaphase events, highlighting its role in cell cycle progression. We have also found that expression of PIWIL1 is lost during differentiation of Caco-2 cells into enterocytes and that PIWIL1 is expressed in cells at the base of intestinal crypts in normal human colon tissue, where intestinal stem cells are known to reside. Thus, it is possible that the presence of PIWIL1 in cancer cells reflects a physiological role of this protein in stem cell maintenance, what would argue in favor of the proposed stem cell origin of CRC. Supporting this view, dedifferentiation of human fibroblasts into induced pluripotent stem cells (iPSc) implies reactivation of PIWIL2 expression, another member of the PIWI protein family. Overall, our findings suggest a role of PIWIL1 in mediating cell cycle dynamics, both in colorectal cancer cells and possibly also in intestinal stem cells. In a broader aspect, we provide support for an involvement of PIWI proteins in somatic stem cell maintenance, expanding nongonadal functions for this protein family.
Development and Optimization of Genetic Manipulation Systems in Group I Clostridium botulinum
Authors: Amatsu Sho , Saito Kazuki , Miyata Shigeru , Zuka Masahiko , Nariya Hirofumi , Fujinaga Yukako
Published: June 2024

Clostridium botulinumcauses the disease botulism, and nontoxigenicClostridium sporogenesis closely related to group IC. botulinum.Despite its pathogenicity,C. botulinumremains poorly characterized. Genetic manipulation is critical for understanding bacterial physiology and disease. We compared the conjugal transformation efficiencies of seven strains, including group IC. botulinum(strains 62A, 7I03-H, Okra, Osaka05, 111) andC. sporogenes(strains JCM 1416T, ATCC 15579), and our results showed that few or no transformants were obtained in certain strains. In the present study, we demonstrate that our optimized protocol increases the efficiency of DNA transfer fromE. colidonor cells to recipient strains. In addition, we developed a novel conjugal suicide vector pXMTL that contains xylose-induciblemazFas a counter-selection marker, and can be transferred intoClostridiumspp. by conjugation. The allele-coupled exchange (ACE) system using pXMTL provides a rapid method for precise, markerless and scarless genome editing in group IC. botulinumandC. sporogenes.

Importance

Group IC. botulinumandC. sporogenesexhibit low transformation efficiencies, and few or no transformants are yielded by some strains. In this study, we optimized the conjugation protocol to improve transformation efficiency. In addition, we developed a novel suicide vector pXMTL harboring a xylose-induciblemazFmarker, and can be transferred intoClostridiumspp. by conjugation. The combination of pXMTL and the optimized conjugation protocol provides a powerful tool for genetic manipulation of group IC. botulinumandC. sporogens.
Modelling COVID-19 in the North American region with a metapopulation network and Kalman filter
Authors: Perini Matteo , Yamana Teresa K. , Galanti Marta , Suh Jiyeon , Kaondera-Shava Roselyn , Shaman Jeffrey
Published: June 2024

Background

Metapopulation models provide platforms for understanding infectious disease dynamics and predicting clinical outcomes across interconnected populations, particularly for large epidemics and pandemics like COVID-19.

Methods

We developed a novel metapopulation model for simulating respiratory virus transmission in the North America region, specifically for the 96 states, provinces, and territories of Canada, Mexico and the United States. The model is informed by COVID-19 case data, which are assimilated using the Ensemble Adjustment Kalman filter (EAKF), a Bayesian inference algorithm, and commuting and mobility data, which are used to build and adjust the network and movement across locations on a daily basis.

Findings

This model-inference system provides estimates of transmission dynamics, infection rates, and ascertainment rates for each of the 96 locations from January 2020 to March 2021. The results highlight differences in disease dynamics and ascertainment among the three countries.

Interpretation

The metapopulation structure enables rapid simulation at large scale, and the data assimilation method makes the system responsive to changes in system dynamics. This model can serve as a versatile platform for modeling other infectious diseases across the North American region.

Funding

US Centers for Disease Control and Prevention Contract 75D30122C14289; US NIH Grant AI163023.
Smoking Cessation after Transitioning from Hospital to Community Stop Smoking Services: Insights from Real-world Data Analysis
Authors: Cherodian Rowan , Franklin Matthew , Baxter Susan , Chilcott James , Gillespie Duncan
Published: June 2024

Background

Patients seen by National Health Service (NHS) hospitals in England should now be asked if they smoke on admission. People who smoke should be treated for tobacco dependence in hospital, then offered support to quit outside of hospital. One way to support post-hospital quitting is through referring patients to community stop smoking services (CSSS). In 2024, the government announced a doubling of CSSS funding for five-years to improve reach and outcomes. Our study aimed to describe the quit rates of people referred from hospital to CSSS, alongside investigating individual characteristics associated with quitting success to inform the potential for more cost-effective, targeted support in the future.

Methods

The study was part of a service evaluation using real-world data collected via a CSSS electronic record system in England, which received referrals from hospital-based tobacco teams. We compared CSSS activity and quitting outcomes to local and national reporting data. Generalised Linear Models were used to investigate quitting outcomes 4-weeks after baseline in relation to demographic, socio-economic, nicotine dependence, intervention, and health factors hypothesised to be associated with quitting outcomes.

Results

Hospital-referred patients comprised 26% of CSSS referrals, tended to be older, with lower socio-economic status and more long-term health conditions. Overall quitting success by people who made a CSSS supported quit attempt was 61% at 4-weeks, slightly lower than local averages, but similar to national averages. Our analysis sample contained records of 1,326 quit attempts that were supported by CSSS. Of the variables investigated, we found that receiving free NHS prescriptions was consistently associated with lower quitting success (Odds Ratio [OR] 0.55, 95% Confidence Interval [CI] 0.33–0.92), potentially because this is a proxy for lower socio-economic and health status. After accounting for other factors, having cancer relative to no health conditions was associated with higher quitting success (OR 2.26, 95%CI 1.18–4.33).

Conclusion

Ensuring patients continue seeking support to quit smoking after their interaction with hospital-based services can lead to quit rates comparable to other CSSS attendees who make a quit attempt. Our analyses highlight the importance of hospital and CSSS investment in improving the transfer of care between services.
Hayai-Annotation v3.0: A functional gene prediction tool that integrates orthologs and gene ontology for network analysis
Authors: Ghelfi Andrea , Isobe Sachiko
Published: June 2024

Hayai-Annotation v3, an R-package integrated with the R-Shiny browser interface, utilizes two methods for functional annotation: DIAMOND for sequence alignment using UniProtKB Plants as the database, and OrthoLoger, the official OrthoDB tool for ortholog inferences. The GO enrichment accuracy was assessed by a CAFA-evaluator, demonstrating that Hayai-Annotation v3's accuracy was comparable to that of the benchmark, BLAST2GO. We here propose a method to explore genome evolution and adaptation from a different perspective, by creating networks and heatmaps correlating orthologs with gene ontology (molecular function and biological process) from their co-occurrence tables. This approach enhances the ability to infer functions of uncharacterized genes by associating orthologs with gene ontology terms and the ability to visualize the distribution of gene numbers correlated with co-occurrence patterns across different species. To our knowledge, this is the first attempt to correlate orthologs with GO (MF and BP) to construct a gene network, providing a comprehensive, cross-species view of gene distribution and function. Hayai-Annotation v3 not only retains the convenience of previous versions but also enhances ortholog analysis functionality, allowing for evolutionary insights from gene sequences. Hayai-Annotation v3 is expected to contribute significantly to the future development of plant genome analysis.
Unique trajectory of gene family evolution from genomic analysis of nearly all known species in an ancient yeast lineage
Authors: Feng Bo , Li Yonglin , Liu Hongyue , Steenwyk Jacob L. , David Kyle T. , Tian Xiaolin , Xu Biyang , Gonçalves Carla , Opulente Dana A. , LaBella Abigail L. , Harrison Marie-Claire , Wolters John F. , Shao Shengyuan , Chen Zhaohao , Fisher Kaitlin J. , Groenewald Marizeth , Hittinger Chris Todd , Shen Xing-Xing , Rokas Antonis , Zhou Xiaofan , Li Yuanning
Published: June 2024

Gene gains and losses are a major driver of genome evolution; their precise characterization can provide insights into the origin and diversification of major lineages. Here, we examined gene family evolution of 1,154 genomes from nearly all known species in the medically and technologically important yeast subphylum Saccharomycotina. We found that yeast gene family and genome evolution are distinct from plants, animals, and filamentous ascomycetes and are characterized by small genome sizes and smaller gene numbers but larger gene family sizes. Faster-evolving lineages (FELs) in yeasts experienced significantly higher rates of gene losses—commensurate with a narrowing of metabolic niche breadth—but higher speciation rates than their slower-evolving sister lineages (SELs). Gene families most often lost are those involved in mRNA splicing, carbohydrate metabolism, and cell division and are likely associated with intron loss, metabolic breadth, and non-canonical cell cycle processes. Our results highlight the significant role of gene family contractions in the evolution of yeast metabolism, genome function, and speciation, and suggest that gene family evolutionary trajectories have differed markedly across major eukaryotic lineages.
PAK6 promotes neuronal autophagy by regulating TFEB nuclear translocation.
Authors: Agostini Francesco , Agostinis Rossella , Di Rocco Martina , Montefusco Sandro , Tombesi Giulia , Iannotta Lucia , Cogo Susanna , De Lazzari Federica , Tessari Isabella , Civiero Laura , Lobbestael Evy , Baekelandt Veerle , Sales Gabriele , Medina Diego Luis , Zhang Xiaomeng , Hinde Elizabeth , Martinelli Simone , Bisaglia Marco , Plotegher Nicoletta , Greggio Elisa
Published: June 2024

Autophagy is a highly conserved homeostatic process essential for the bulk degradation of cytoplasmic components and aggregated proteins. Multiple evidence indicates that impairment of (macro)autophagy leads to neurodegeneration, such as Parkinson disease (PD). Our previous work showed that p21 activated kinase 6 (PAK6) interacts with the PD-associated leucine-rich repeat kinase (LRRK2) to promote neurite outgrowth in the mouse striatum; still the function of PAK6 in the brain is largely unknown. Here, we found that downregulation of neuronal but not glialmbt, theD. melanogasterhomolog of PAK6, impairs autophagy-lysosomal function. PAK6 overexpression in cells and inC. elegansincreases transcription factor EB (TFEB) nuclear translocation in a kinase activity-dependent manner. Mechanistically, PAK6 forms a complex with TFEB to regulate its nuclear localization in a manner dependent on phosphorylation of and binding to 14-3-3 proteins and phosphorylation of TFEB at S467. In line with its ability to promote neuronal autophagy,mbtdownregulation exacerbates alpha-synuclein toxicity inDrosophiladopaminergic neurons. Moreover, PAK6 overexpression in thesubstantia nigraof mutant LRRK2 mice reduces the burden of phosphorylated alpha-synuclein in dopaminergic neurons. Altogether, our study uncovers a novel role of PAK6 as a positive regulator of autophagy via TFEB and suggests that modulating its activity may represent a way to selectively turn on autophagy in neurons, with implications for the treatment of neurodegenerative disorders.
Anin vitroassay of MCTS1-DENR-dependent re-initiation and ribosome profiling uncover the activity of MCTS2 and distinct function of eIF2D
Authors: Meurs Romane , De Matos Mara , Bothe Adrian , Guex Nicolas , Weber Tobias , Teleman Aurelio A. , Ban Nenad , Gatfield David
Published: June 2024

Ribosomes scanning from the mRNA 5′ cap to the start codon may initiate at upstream open reading frames (uORFs), decreasing protein biosynthesis. Termination at a uORF can lead to re-initiation, where the 40S subunit resumes scanning and initiates another translation event downstream. In mammals, the noncanonical translation factors MCTS1-DENR participate in re-initiation at specific uORFs, but knowledge of othertrans-acting factors and uORF features influencing re-initiation is limited. Here, we describe a cell-free re-initiation assay using HeLa cell lysates. Comparingin vivoandin vitrore-initiation activities on uORF-containing model reporters, we validate that MCTS1-DENR-dependent re-initiation is accurately recapitulatedin vitro. Using this system and ribosome profiling in cultured cells, we found that knockdown of the homolog eIF2D causes widespread gene expression deregulation unrelated to uORF translation, suggesting distinct functions from MCTS1-DENR. Additionally, we identified MCTS2, encoded by a retrogene copy ofMcts1, as an alternative DENR partner that promotes re-initiationin vitro, providing a plausible explanation for the striking clinical differences associated withDenrvs.Mcts1mutations in humans. Our findings on re-initiation and the new assay provide valuable insights and a powerful tool for future research on uORF features andtrans-acting factors.
Application of machine learning in a rodent malaria model for rapid, accurate, and consistent parasite counts
Authors: Yanik Sean , Yu Hang , Chaiyawong Nattawat , Adewale-Fasoro Opeoluwa , Dinis Luciana Ribeiro , Narayanasamy Ravi Kumar , Lee Elizabeth C. , Lubonja Ariel , Li Bowen , Jaeger Stefan , Srinivasan Prakash
Published: June 2024

Rodent malaria models serve as important preclinical antimalarial and vaccine testing tools. Evaluating treatment outcomes in these models often requires manually counting parasite-infected red blood cells (iRBCs), a time-consuming process, which can be inconsistent between individuals and labs. We have developed an easy-to-use machine learning (ML)-based software, Malaria Screener R, to expedite and standardize such studies by automating the counting ofPlasmodiumiRBCs in rodents. This software can process Giemsa-stained blood smear images captured by any camera-equipped microscope. It features an intuitive graphical user interface that facilitates image processing and visualization of the results. The software has been developed as a desktop application that processes images on standard Windows and Mac OS computers. A previous ML model created by the authors designed to countP. falciparum-infected human RBCs did not perform well countingPlasmodium-infected mouse RBCs. We leveraged that model by loading the pre-trained weights and training the algorithm with newly collected data to targetP. yoeliiandP. bergheimouse iRBCs. This new model reliably measured bothP. yoeliiandP. bergheiparasitemia (R2= 0.9916). Additional rounds of training data to incorporate variances due to length of Giemsa staining, microscopes etc, have produced a generalizable model, meeting WHO Competency Level 1 for the sub-category of parasite counting using independent microscopes. Reliable, automated analyses of blood-stage parasitemia will facilitate rapid and consistent evaluation of novel vaccines and antimalarials across labs in an easily accessiblein vivomalaria model.
Spatial Single-cell Analysis Decodes Cortical Layer and Area Specification
Authors: Qian Xuyu , Coleman Kyle , Jiang Shunzhou , Kriz Andrea J. , Marciano Jack H. , Luo Chunyu , Cai Chunhui , Manam Monica Devi , Caglayan Emre , Otani Aoi , Ghosh Urmi , Shao Diane D. , Andersen Rebecca E. , Neil Jennifer E. , Johnson Robert , LeFevre Alexandra , Hecht Jonathan L. , Miller Michael B. , Sun Liang , Stringer Carsen , Li Mingyao , Walsh Christopher A.
Published: June 2024

The human cerebral cortex, pivotal for advanced cognitive functions, is composed of six distinct layers and dozens of functionally specialized areas1,2. The layers and areas are distinguished both molecularly, by diverse neuronal and glial cell subtypes, and structurally, through intricate spatial organization3,4. While single-cell transcriptomics studies have advanced molecular characterization of human cortical development, a critical gap exists due to the loss of spatial context during cell dissociation5,6,7,8. Here, we utilized multiplexed error-robust fluorescence in situ hybridization (MERFISH)9, augmented with deep-learning-based cell segmentation, to examine the molecular, cellular, and cytoarchitectural development of human fetal cortex with spatially resolved single-cell resolution. Our extensive spatial atlas, encompassing 16 million single cells, spans eight cortical areas across four time points in the second and third trimesters. We uncovered an early establishment of the six-layer structure, identifiable in the laminar distribution of excitatory neuronal subtypes by mid-gestation, long before the emergence of cytoarchitectural layers. Notably, while anterior-posterior gradients of neuronal subtypes were generally observed in most cortical areas, a striking exception was the sharp molecular border between primary (V1) and secondary visual cortices (V2) at gestational week 20. Here we discovered an abrupt binary shift in neuronal subtype specification at the earliest stages, challenging the notion that continuous morphogen gradients dictate mid-gestation cortical arealization6,10. Moreover, integrating single-nuclei RNA-sequencing and in situ whole transcriptomics revealed an early upregulation of synaptogenesis in V1-specific Layer 4 neurons, suggesting a role of synaptogenesis in this discrete border formation. Collectively, our findings underscore the crucial role of spatial relationships in determining the molecular specification of cortical layers and areas. This work not only provides a valuable resource for the field, but also establishes a spatially resolved single-cell analysis paradigm that paves the way for a comprehensive developmental atlas of the human brain.
Flat-band engineering of quasi-one-dimensional systems via supersymmetric transformations
Authors: Jakubský V. , Zelaya K.
Published: June 2024

We introduce a systematic method to spectrally design quasi-one-dimensional crystal models described by the Dirac equation in the low-energy regime. The method is based on the supersymmetric transformation applied to an initially known pseudo-spin-1/2 model. This allows one to extend the corresponding supersymmetric partner so that the new model describes a pseudo-spin-1 system. The spectral design allows the introduction of a flat band and discrete energies at will into the new model. The results are illustrated in three examples where the Su-Schriefer-Heeger chain is locally converted into a stub lattice.

Published by the American Physical Society
2024
Signature of nonminimal scalar-gravity coupling with an early matter domination on the power spectrum of gravitational waves
Authors: Nikandish Amirsalar , Rostam Zadeh Shiva , Naderi Reza , Elahi Fatemeh , Mehrabpour Hadi
Published: June 2024

The signal strength of primordial gravitational waves experiencing an epoch of early scalar domination, due to an oscillating scalar field, is reduced with respect to radiation domination. In this paper, we demonstrate that the specific pattern of this reduction is sensitive to the coupling between the dominant field and gravity. When this coupling is zero, the impact of early-matter domination on gravitational waves is solely attributed to the alteration of the Hubble parameter and the scale factor. In the presence of nonzero couplings, on the other hand, the evolution of primordial gravitational waves is directly affected as well, resulting in a distinct steplike feature in the power spectrum of the gravitational wave as a function of frequency. This feature serves as a smoking gun signature of this model. Although the aforementioned results are obtained numerically, we also provide an analytical expression of the power spectrum to illustrate its dependence on the model parameters and initial conditions. Furthermore, we provide analytical relations that specify the frequency interval in which the step occurs. We compare the analytical estimates with numerical analysis and show they match well.

Published by the American Physical Society
2024
Considerations on the relaxation time in shear-driven jamming
Authors: Hedström Lucas , Olsson Peter
Published: June 2024

We study the jamming transition in a model of elastic particles under shear at zero temperature, with a focus on the relaxation time τ1. This relaxation time is from two-step simulations where the first step is the ordinary shearing simulation and the second step is the relaxation of the energy after stopping the shearing. τ1 is determined from the final exponential decay of the energy. Such relaxations are done with many different starting configurations generated by a long shearing simulation in which the shear variable γ slowly increases. We study the correlations of both τ1, determined from the decay, and the pressure, p1, from the starting configurations as a function of the difference in γ. We find that the correlations of p1 are longer lived than the ones of τ1 and find that the reason for this is that the individual τ1 is controlled both by p1 of the starting configuration and a random contribution which depends on the relaxation path length—the average distance moved by the particles during the relaxation. We further conclude that it is γτ, determined from the correlations of τ1, which is the relevant one when the aim is to generate data that may be used for determining the critical exponent that characterizes the jamming transition.

Published by the American Physical Society
2024
How the UTAUT motivates consumers' continuous use of green FinTech: the moderation effect of consumer social responsibility and long-term orientation
Authors: Lin Rong-Rong , Lee Jung-Chieh
Published: June 2024

Purpose

Green financial technology (FinTech) has received attention for promoting green finance investment and sustainable development. However, how consumer social responsibility and long-term orientation influence the continuance intention of green FinTech users remains unknown in the literature. To fill this gap, consumer social responsibility and long-term orientation are combined with the unified theory of acceptance and use of technology to develop a research model to investigate their moderating effects on the continuance intention of green FinTech users.

Design/methodology/approach

A random probability sampling method was adopted, and 377 valid responses were collected to verify the proposed model. Partial least squares structural equation modeling was employed for the data analysis.

Findings

Performance expectancy, effort expectancy, social influence and facilitating conditions have significant positive impacts on the continuance intentions of green FinTech users. Surprisingly, consumer social responsibility enhances the effects of performance expectancy and social influence on continuance intention but negatively moderates the effect of facilitating conditions on continuance intention. Moreover, a long-term orientation can increase the impact of facilitating conditions on continuance intention but decrease the impact of performance expectancy on continuance intention.

Originality/value

This paper proposes a research model that reveals how consumer social responsibility and long-term orientation moderate the relationship between the unified theory of acceptance and use of technology (UTAUT) and the continuance intention of green FinTech users to fill a gap in the literature.
M&M: accelerating and re-energising its SUV business in India
Authors: Gupta Praveen , Mittal Rajkumari , Dayal Smita
Published: June 2024

Learning outcomes

This case study will help students of business management learn the dynamics of strategic decision-making frameworks in a competitive market. After working through the case and assignment questions, the students will be able to understand the 5C framework for strategic decision-making in the context of sports utility vehicles (SUV) segment of Indian automobile industry; identify the opportunities and challenges of the competitive SUV market for long-term survival and growth; and devise a suitable strategic plan incorporating the factors which drive the change in the dynamic automobile industry.

Case overview/synopsis

The case study talks about the dilemma faced by Mahindra and Mahindra (M&M), a subsidiary of Mahindra Group. M&M, one of the leading auto manufacturers and pioneers of SUVs in India, has been facing a storm across its business in the past few years. While M&M is making a concerted effort to go back on the road to success, its rivals are not standing idly either. Consumer behaviour towards the purchase of cars is changing at a fast pace, and sales of utility vehicles have surpassed the sales of passenger vehicles in the recent past. M&M, whose work culture is a blend of being friendly and performance-oriented to “Rise”, is prepared to take advantage of any opportunity presented by shifting market trends. Following the 10% increase in SUV registrations in 2023, the business is making many attempts to reclaim the ground it is losing in the Indian market. After dropping from its highest position of 53% in FY 2012 to 15% in FY 2021, M&M’s market share increased to 18% in FY 2023. M&M launched a new logo for its SUV portfolio in August 2021 and launched many SUVs back-to-back, such as Thar, Bolero, XUV700 and Scorpion-N, to face the competition. In 2023, M&M chartered the first position in SUVs by revenue, with a market share of 19.1% and ready for 2024 with six new SUVs. The way M&M performed in 2023 is evidence of its primary objective, which is to offer authentic SUVs to lead the SUV market in revenue share. However, there are still many obstacles in the way. When consumers have so many options from rivals such as Hyundai, KIA Motors and TATA Motors, would it be easy for M&M to bring back its SUVs to the market?

Complexity academic level

The case study is designed for use in a postgraduate-level course in the subjects – strategic management/marketing management. The case study provides an opportunity to discuss how a company can create a unique selling proposition for its product to sustain its growth in a competitive market, when consumers have so many options from rivals.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 11: Strategy
Perspectives of accounting professionals about the adoption of IFRS for SMEs: the case of Romania
Authors: Marina Alexandra-Gabriela , Tiron-Tudor Adriana
Published: June 2024

Purpose

The aim of the study is to highlight the perspectives of accounting professionals in Romania on adopting a single set of financial reporting standards for small and medium-sized entities (SMEs).

Design/methodology/approach

The study included a combination of qualitative and quantitative methodologies. A qualitative approach was employed to examine the perspectives of accounting professionals on their inclination toward international standards for SMEs or national regulations. The quantitative approach involved doing content analysis on interviews to provide empirical support for the implementation of these standards in a national context.

Findings

Romanian accounting professionals want an improvement in financial reporting, but not necessarily through the use of an international standard. And although the level of convergence between the International Financial Reporting Standard (IFRS) for SMEs and national regulations is medium, it is not desirable to apply an international financial reporting standard for SMEs.

Originality/value

This study stands out as one of the few papers that delve into the perspectives of accounting professionals about adopting IFRS for SMEs in a specific country, offering a unique and engaging perspective.
Investigating the factors affecting educators’ adoption of learning analytics using the UTAUT model
Authors: El Alfy Shahira , Kehal Mounir
Published: June 2024

Purpose

The research aims at examining educators’ perceptions, attitudes and behavioral intentions toward learning analytics (LA) and the role of self-instruction within the proposed model for LA adoption.

Design/methodology/approach

A quantitative approach is utilized in which a questionnaire is designed as a tool for data collection and partial least squares structural equation modeling (PLS-SEM) is used for data analysis and model testing.

Findings

Results show that performance expectancy and effort expectancy have a significant effect on educators’ attitudes, which in turn significantly affect educators’ behavioral intentions. Self-instruction mediates the relationship between educators’ attitudes and behavioral intentions. The attitude towards LA mediates the relationship between LA performance expectancy and educators’ self-instruction. The research model explains 54% of the variance in learning analysis adoption.

Originality/value

Findings open a path for research on pedagogical factors affecting LA adoption and guide education managers toward facilitating LA adoption. The tested model contributes to LA and teaching and learning literature by highlighting the role of educators’ self-instruction in LA adoption.
Identifying the dominant influencing factors of secondary lining cracking risk in an operating mountain tunnel
Authors: Peng Zhangtao , Fang Qian , Ai Qing , Jiang Xiaomo , Wang Hui , Huang Xingchun , Yuan Yong
Published: June 2024

Purpose

A risk-based method is proposed to identify the dominant influencing factors of secondary lining cracking in an operating mountain tunnel with weak surrounding rock.

Design/methodology/approach

Based on the inspection data from a mountain tunnel in Southwest China, a lognormal proportional hazard model is established to describe the statistical distribution of secondary lining cracks. Then, the model parameters are obtained by using the Bayesian regression method, and the importance of influencing factors can be sorted based on the absolute values of the parameters.

Findings

The results show that the order of importance of the influencing factors of secondary lining cracks is as follows: location of the crack on the tunnel profile, rock mass grade of the surrounding rock, time to completion of the secondary lining, and void behind the secondary lining. Accordingly, the location of the crack on the tunnel profile and rock mass grade of the surrounding rock are the two most important influencing factors of secondary lining cracks in the investigated mountain tunnel, and appropriate maintenance measures should be focused on these two aspects.

Originality/value

This study provides a general and effective reference for identifying the dominant influencing factors of secondary lining cracks to guide the targeted maintenance in mountain tunnels.