bluuebunny/crossref_metadata_2025_split huggingface dataset:
A redundant chloroplast protein is co-opted by potyvirids as the scaffold protein to mediate viral intercellular movement complex assembly
Authors: Qin Li , Liu Hongjun , Liu Peilan , Jiang Lu , Cheng Xiaofei , Li Fangfang , Shen Wentao , Dai Zhaoji , Cui Hongguang 
Published: October 2023

AbstractFor viruses in the familyPotyviridae(potyvirids), three virus-encoded proteins (P3N-PIPO, CI and CP) and several host components are known to coordinately regulate viral cell-to-cell movement. Here, we found that HCPro2 encoded by areca palm necrotic ring spot virus is involved in the intercellular movement, which could be functionally complemented by its counterpart HCPro from a potyvirus. The affinity purification and mass spectrum analysis identified several viral factors (including CI and CP) and a variety of host proteins that physically associate with HCPro2. We demonstrated that HCPro2 interacts with either CI or CPin planta, and the three form plasmodesmata (PD)-localized interactive complex in viral infection. Further, we screened HCPro2-associating host proteins, and identified a common host protein RbCS that mediates the interactions of HCPro2-CI, HCPro2-CP and CI-CP among the complex. Knockdown ofNbRbCSsimultaneously impairs the interactions of HCPro2-CI, HCPro2-CP and CI-CP, and significantly attenuates the intercellular movement and systemic infection for ANRSV and other three tested potyvirids. This study highlights that a nucleus-encoded chloroplast-targeted protein is hijacked by potyvirids as the scaffold protein to mediate the assembly of viral intercellular movement complex to promote viral infection.
The prion-like domain of the chloroplast RNA binding protein CP29A is required for cold-induced phase separation next to nucleoids and supports RNA splicing and translation during cold acclimation
Authors: Legen Julia , Lenzen Benjamin , Kachariya Nitin , Feltgen Stephanie , Gao Yang , Mergenthal Simon , Weber Willi , Klotzsch Enrico , Zoschke Reimo , Sattler Michael , Schmitz-Linneweber Christian 
Published: October 2023

AbstractArabidopsis thalianais capable of producing photosynthetic tissue with active chloroplasts at temperatures as low as 4°C, and this process depends on the presence of the nuclear-encoded, chloroplast-localized RNA-binding protein CP29A. In this study, we demonstrate that CP29A undergoes phase separation in vitro and in vivo in a temperature-dependent manner, which is mediated by a prion-like domain (PLD) located between the two RNA recognition motif (RRM) domains of CP29A. The resulting droplets display liquid-like properties and are found in close proximity to chloroplast nucleoids. The PLD is required to support chloroplast RNA splicing and translation in cold-treated tissue. Together, our findings suggest that plant chloroplast gene expression is compartmentalized by inducible condensation of CP29A at low temperatures, a mechanism that could play a crucial role for plant cold resistance.
HOIL-1L deficiency induces cell cycle alteration which causes immaturity of myocyte and fibrogenesis
Authors: Akagi Kentaro , Baba Shiro , Fujita Hiroaki , Fuseya Yasuhiro , Yoshinaga Daisuke , Kubota Hirohito , Kume Eitaro , Fukumura Fumiaki , Matsuda Koichi , Tanaka Takayuki , Hirata Takuya , Iwai Kazuhiro , Takita Junko 
Published: October 2023

AbstractHOIL-1L deficiency was recently reported to be one of the causes of myopathy and dilated cardiomyopathy (DCM). However, the mechanisms by which myopathy and DCM develop have not been clearly elucidated. Here, we sought to elucidate these mechanisms using the murine myoblast cell line C2C12 and disease-specific human induced pluripotent stem cells (hiPSCs). Myotubes were differentiated from control and HOIL-1L-KO C2C12 cells. Cardiomyocytes (CMs) were differentiated from control and patient-derived hiPSCs. We investigated the impact of HOIL-1L on differentiation of myotubes and CMs. Myotubes differentiated from HOIL-1L-KO C2C12 cells exhibited deteriorated differentiation and mitotic cell accumulation. CMs differentiaed from patient-derived hiPSCs had an abnormal morphology with a larger size and were excessively multinucleated compared with CMs differentiaed from control hiPSCs. Further analysis of hiPSC- derived CMs showed that HOIL-1L deficiency caused cell cycle alteration and mitotic cell accumulation. These results were supported by RNA sequencing of C2C12 cell-derived myotubes. In addition,SerpinE2, a cardiac fibrogenesis gene, was significantly upregulated in CMs differentiaed from patient-derived hiPSCs. These results demonstrate that abnormal cell maturation and fibrosis possibly contribute to the development of DCM and myopathy. In conclusion, HOIL-1L is an important intrinsic regulator of cell cycle-related myotube and CM maturation and cell proliferation.
Depressed Proximal Glycolysis in Myocardium Of Human Heart Failure with Preserved Ejection Fraction
Authors: Koleini Navid , Meddeb Mariam , Keykhaei Mohammad , Kwon Seoyoung , Zhao Liang , Hahn Virginia , Sharma Kavita , Pearce Erika L , Kass David A 
Published: October 2023

AbstractHeart failure with preserved ejection fraction (HFpEF) accounts for >50% of all heart failure world-wide and remains a major unmet medical need. The most effective recently approved treatments were first developed for diabetes, suggesting metabolic defects are paramount. Myocardial metabolomics in human HFpEF has identified reduced fatty acid and branched chain amino acid catabolism, but the status of glycolysis is unknown. Here we performed targeted metabolomics and protein analysis of glycolytic pathway enzymes in myocardial biopsies of patients with HFpEF versus HF with reduced ejection fraction (HFrEF0 or non-failing controls. Glucose was increased in HFpEF myocardium, but immediate downstream glycolytic metabolites (glucose-6 phosphate, fructose 1,6 diphosphate), were more reduced in HFpEF than the other groups, as were their associated synthetic enzymes hexokinase and phosphofructokinase. Pyruvate was also reduced in HFpEF versus controls. These changes were either not present or substantially less so in HFrEF. Suppression of proximal glycolysis was also coupled to lower metabolites and proteins in the pentose phosphate pathway but was independent of diabetes or obesity. These findings support marked metabolic inflexibility in HFpEF and identifies very proximal blockade in glucose metabolism. Efforts to improve metabolic use of carbohydrates in HFpEF will likely need to target these proximal glycolytic enzymes.
Identification of watermelon genes involved in the ZYMV interaction through a miRNA bioinformatics analysis and characterization ofATRIPandRBOHB
Authors: Berbati Margarita , Bousali Maria , Kaldis Athanasios , Moravec Tomas , Karamitros Timokratis , Voloudakis Andreas 
Published: October 2023

AbstractSmall RNA sequencing of healthy and ZYMV-infected watermelon (21 dpi) was performed and bioinformatics analysis identified 353 miRNAs from which 22 known and 331 new miRNAs. Important information about their precursors, their length, the loci of which they originated on watermelon genome are provided. The ZYMV genome could be a target for mir396a-3p, miR8706a, and miR1886i-5p from the miRbase, but none of them was identified in the watermelon miRNAome. Furthermore, watermelon miRNAome does not contain a miRNA targeting ZYMV genome with an expectation score ≤ 3.5. There were 34 resistance genes (CC-NBS-LRR, TIR-NBS-LRR, TIR-NBS) predicted as targets of 32 miRNAs in healthy watermelon. For nine differentially expressed miRNAs the respective target genes (10 in total) were bioinformatically predicted. For cla-new_miR307 (upregulated upon ZYMV infection) and cla-miR166h-3p (downregulated upon ZYMV infection) the targets were predicted to beClaATRIPandClaRBOHB, respectively, withClaATRIPdownregulated andClaRBOHBupregulated upon ZYMV infection. ALSV-mediated VIGS ofClaATRIPrendered watermelon plants more resistant to ZYMV, whereas VIGS ofClaRBOHBresulted in higher levels of ZYMV titer in watermelon. These data suggest thatClaATRIPandClaRBOHBare a susceptibility and resistant gene, respectively. Our results provide new insights in watermelon miRNAome and could propose new strategies for generating resistant watermelon to ZYMV.HighlightsBioinformatics analysis in healthy and ZYMV-infected watermelon plants gave 353 miRNAs, 22 known and 331 new.The watermelon miRNAome identified in the present study does not appear to target the ZYMV genome (sense and reverse complement).The differential expression of ten genes of watermelon in relation to ZYMV infection was validated.The silencing of the two genes,ATRIPandRBOHB, through VIGS strongly suggested thatATRIPis a gene of susceptibility andRBOHBis a gene of resistance.
A Web Service for Automated Design of Multiple Types of Ribozymes Targeting RNA: from minimal hammerhead to aptazymes
Authors: Najeh Sabrine , Kharma Nawwaf , Vaudry-Read Thomas , Haurie Anita , Paslawski Christopher , Adams Daniel , Ferreira Steve , Perreault Jonathan 
Published: October 2023

ABSTRACTRibosoft 2.0 is the second version of a web service to design different types oftrans-acting conventional and allosteric ribozymes. The web service is publicly available athttps://ribosoft2.fungalgenomics.ca/. Ribosoft 2.0 uses template secondary structures that can be submitted by users to design ribozymes in accordance with parameters provided by the user. The generated designs specifically target a transcript (or, generally, an RNA sequence) given by the user. Herein, sixty ribozymes of different types were tested on two different mRNAs, with a majority shown to be active. We have also generated and proved the activity of the firsttrans-acting aptazyme designedin silico.
Positive Transfer of the Whisper Speech Transformer to Human and Animal Voice Activity Detection
Authors: Gu Nianlong , Lee Kanghwi , Basha Maris , Ram Sumit Kumar , You Guanghao , Hahnloser Richard H. R. 
Published: October 2023

ABSTRACTThis paper introduces WhisperSeg, utilizing the Whisper Transformer pre-trained for Automatic Speech Recognition (ASR) for human and animal Voice Activity Detection (VAD). Contrary to traditional methods that detect human voice or animal vocalizations from a short audio frame and rely on careful threshold selection, WhisperSeg processes entire spectrograms of long audio and generates plain text representations of onset, offset, and type of voice activity. Processing a longer audio context with a larger network greatly improves detection accuracy from few labeled examples. We further demonstrate a positive transfer of detection performance to new animal species, making our approach viable in the data-scarce multi-species setting.1
Localization of Cadherins in the postnatal cochlear epithelium and their relation to space formation
Authors: Beaulac Holly J. , Munnamalai Vidhya 
Published: October 2023

AbstractThe sensory epithelium of the cochlea, the organ of Corti, has complex cytoarchitecture consisting of mechanosensory hair cells intercalated by epithelial support cells. The support cells provide important trophic and structural support to the hair cells. Thus, the support cells must be stiff yet compliant enough to withstand and modulate vibrations to the hair cells. Once the sensory cells are properly patterned, the support cells undergo significant remodeling from a simple epithelium into a structurally rigid epithelium with fluid-filled spaces in the murine cochlea. Cell adhesion molecules such as cadherins are necessary for sorting and connecting cells in an intact epithelium. To create the fluid-filled spaces, cell adhesion properties of adjoining cell membranes between cells must change to allow the formation of spaces within an epithelium. However, the dynamic localization of cadherins has not been properly analyzed as these spaces are formed. There are three cadherins that are reported to be expressed during the first postnatal week of development when the tunnel of Corti forms in the cochlea. In this study, we characterize the dynamic localization of cadherins that are associated with cytoskeletal remodeling at the contacting membranes of the inner and outer pillar cells flanking the tunnel of Corti.Key findingsF-actin remodeling occurs between E18.5 to P7 in the cochlear sensory epithelium.Transient changes of F-actin cytoskeleton drives epithelial morphogenesis.Fluid-filled spaces in epithelium is driven by changes in cell adhesion.
Mfsd7b facilitates choline uptake and missense mutations affect choline transport function
Authors: Thuy Ha Hoa Thi , Sukumar Viresh Krishnan , Bao Chua Jonathan Wei , Nguyen Dat T. , Nguyen Toan Q. , Kim Lim Lina Hsiu , Cazenave-Gassiot Amaury , Nguyen Long N. 
Published: October 2023

AbstractMFSD7b belongs to the Major Facilitator Superfamily of transporters that transport small molecules. Two isoforms of MFSD7b have been identified and they are reported to be heme exporters that play a crucial role in maintaining the cytosolic and mitochondrial heme levels, respectively. Mutations of MFSD7b (also known as FLVCR1) have been linked to retinitis pigmentosa, posterior column ataxia, and hereditary sensory and autonomic neuropathy. Although MFSD7b functions have been linked to heme detoxification by exporting excess heme from erythroid cells, it is ubiquitously expressed with a high level in the kidney, gastrointestinal tract, lungs, liver, and brain. Here, we showed that MFSD7b functions as a facilitative choline transporter. Expression of MFSD7b slightly but significantly increased choline import, while its knockdown reduced choline influx in mammalian cells. The influx of choline transported by MFSD7b is dependent on the expression of choline metabolizing enzymes such as choline kinase (CHKA), but it is independent from gradient of cations. Additionally, we showed that choline transport function of Mfsd7b is conserved from fly to man. Employing our transport assays, we showed that missense mutations of MFSD7b caused reduced choline transport functions. Our results show that MFSD7b functions as a facilitative choline transporter in mammalian cells.
A mobile intron facilitates interference competition between co-infecting viruses
Authors: Birkholz Erica A. , Morgan Chase J. , Laughlin Thomas G. , Lau Rebecca K. , Prichard Amy , Rangarajan Sahana , Meza Gabrielle N. , Lee Jina , Armbruster Emily G. , Suslov Sergey , Pogliano Kit , Meyer Justin R. , Villa Elizabeth , Corbett Kevin D. , Pogliano Joe 
Published: October 2023

AbstractMobile introns containing homing endonucleases are widespread in nature and have long been assumed to be selfish elements that provide no benefit to the host organism. These genetic elements are common in viruses, but whether they confer a selective advantage is unclear. Here we studied a mobile intron in bacteriophage ΦPA3 and found its homing endonuclease gp210 contributes to viral competition by interfering with the virogenesis of co-infecting phage ΦKZ. We show that gp210 targets a specific sequence in its competitor ΦKZ, preventing the assembly of progeny viruses. This work reports the first demonstration of how a mobile intron can be deployed to engage in interference competition and provide a reproductive advantage. Given the ubiquity of introns, this selective advantage likely has widespread evolutionary implications in nature.
Demographic profile, risk stratification, clinical characteristics, and treatment outcome of patients with multiple myeloma: A five-year retrospective study at a tertiary hospital in Ethiopia
Authors: Haile Ephrem , Tasew Adugna , Gebremedhin Amha , Sherif Abdulaziz , Tadesse Fissehatsion 
Published: October 2023

AbstractBackgroundPatients with multiple myeloma are being seen at an increasing frequency in different indigenous African population. However, local data regarding the demographic profile, clinical characteristics, risk stratification, and treatment outcome of these patients is lacking. This study was designed to fill this existing gap in our setup. Hence, it will aid in the revision of treatment guidelines based on local data on the efficacy of existing treatment regimens and risk stratification of patients with a newly diagnosed multiple myeloma.MethodsA single centered Hospital-based retrospective Cohort study was conducted from January 2015 to December 2019. Eighty patients with newly diagnosed MM who received non-proteasome inhibitor-based therapy at TASH, Addis Ababa, Ethiopia were analyzed in the study.ResultsOut of the 80 patients in this cohort, 51(63.8%) of the patients were males (M: F ratio 1.76:1)and the median age at diagnosis was 52 years. The commonest complications identified were anemia (56.3%) and pathologic fracture (55%). The commonest comorbid conditions were; systemic hypertension (24%), CKD (6.3%), and diabetes (5%). The median Progression-Free Survival (PFS) and Overall Survival (OS) of patients were found to be 17.5 and 20 months respectively. This study also identified factors like advanced DS stage, presence of plasmacytoma, renal dysfunction, elevated serum LDH, high levels of serum protein, and monoclonal M-protein to have adverse implication on the OS and PFS of patients.ConclusionMultiple Myeloma is more common in the male population group and our patients are younger than the western population. Myeloma treatment regimens like CP and CPT are found to be less effective in our patients than in patients elsewhere. This is likely to be due to the advanced stage at presentation. In resource-limited setups, where determination of cytogenetic features of myeloma is difficult, different clinical and laboratory parameters can still serve as prognostic markers of treatment outcome & patient survival.Competing InterestsThe authors declare that they have no competing interests
Knowledge, Attitude and Utilisation of Modern Contraceptives among Female Senior High School Students in the Kpando Municipality, Ghana
Authors: Debuo Der Amanda , Tarkang Elvis Enowbeyang 
Published: October 2023

AbstractBackgroundAdolescent fertility regulation and pregnancy prevention is one of the most important healthcare issues of the twenty-first century. Contraceptive can potentially improve the quality of the lives of adolescents and their economic welfare by preventing unwanted pregnancies. Volta Region records one of the highest prevalence of teenage pregnancy and adolescents aged 15-19 years are the least acceptors of contraceptives in the Region. This study determined the knowledge, attitude and utilisation of modern contraceptives among female senior high school students in the Kpando Municipality.MethodsA descriptive cross-sectional design was employed in this study with a stratified sample of 270 participants. Data were collected using a self-administered questionnaire and analysed using Stata Version 16. Descriptive statistics such as frequencies and percentages were used to summarise the data. Logistic regression analyses were used to test the association between the dependent and independent variables at the 0.05 significance level at a 95% confidence interval.ResultsThe participants had adequate knowledge of modern contraceptives (78.5%) and their major source of information was the school (59.7%) with the most commonly known contraceptive being the condom (86.3%). School of attendance (AOR= 0.29), religion (AOR= 0.25), marital status (AOR= 0.47) and programme of study were significantly associated with knowledge of modern contraceptives. The attitude of respondents was also favourable (63%) but the majority reported that modern contraceptives could lead to bareness in the future (59.3%). Only school of attendance was significantly associated with attitude (AOR= 2.04). However, current utilisation of modern contraceptives was low (24.2%) and the majority revealed their source of modern contraceptives to be the pharmacy (63.1%). Also, school of attendance (AOR= 2.36), age (AOR= 2.45), marital status (AOR= 41.81) and grade level (AOR= 2.13) were significantly associated with the utilisation of modern contraceptives.ConclusionThere was adequate knowledge and favourable attitude regarding contraceptives. However, utilisation was low. Health promotion campaigns to improve contraceptive use among SHS students in Kpando Municipality should target those in the lower grade levels, those between the ages of 12 and 17, those who are currently not in any relationship and include all students regardless of their programme of study.
Inferring plasticity rules from single-neuron spike trains using deep learning methods
Authors: Wang Xingyun , Béïque Jean-Claude , Naud Richard 
Published: October 2023

AbstractSynaptic plasticity is a core basis for learning and adaptation. Determining how synapses are altered by local signals – the learning rules – is the hinge about which brain activity pivots. A large number of in vitro characterizations have focused on restricted sets of core properties, but it remains to be established which if any of the known learning rules is most consistent with changes in activity patterns in behaving animals. To address this question, we hypothesize that the correlation between features of the activity of a single post-synaptic neuron and subsequent changes of the representations could be used to detect the underlying learning rule. Because this correlation is expected to be diluted in the notoriously large variability of brain activity, we test here learning rule inference based on passive observations of single neurons using deep artificial neural networks. Using simulated data, we found that both transformers, temporal convolutional networks, and SVM could classify learning rules far above the chance level, with transformers achieving the best overall accuracy. This performance can be achieved despite the presence of noise and representational drift. We further investigated the features used by the algorithms to perform the classification and found the deep net used inner temporal differences of distinct learning rules to separate learning trajectories. We also find, however, that the classification accuracy is sensitive to alterations in network properties. Our work illustrates that distinct learning rules’ generate distinguishable trajectories of responses, but warns against using simulation-trained classifiers to infer learning rules from real data.
RECLUSIVE CHANDELIERS: FUNCTIONAL ISOLATION OF DENTATE AXO-AXONIC CELLS AFTER EXPERIMENTAL STATUS EPILEPTICUS
Authors: Proddutur Archana , Nguyen Susan , Yeh Chia-Wei , Gupta Akshay , Santhakumar Vijayalakshmi 
Published: October 2023

SummaryAxo-axonic cells (AACs) provide specialized inhibition to the axon initial segment (AIS) of excitatory neurons and can regulate network output and synchrony. Although hippocampal dentate AACs are structurally altered in epilepsy, physiological analyses of dentate AACs are lacking. We demonstrate that parvalbumin neurons in the dentate molecular layer express PTHLH, an AAC marker, and exhibit morphology characteristic of AACs. Dentate AACs show high-frequency, non-adapting firing but lack persistent firing in the absence of input and have higher rheobase than basket cells suggesting that AACs can respond reliably to network activity. Early after pilocarpine-induced status epilepticus (SE), dentate AACs receive fewer spontaneous excitatory and inhibitory synaptic inputs and have significantly lower maximum firing frequency. Paired recordings and spatially localized optogenetic stimulation revealed that SE reduced the amplitude of unitary synaptic inputs from AACs to granule cells without altering reliability, short-term plasticity, or AIS GABA reversal potential. These changes compromised AAC-dependent shunting of granule cell firing in a multicompartmental model. These early post-SE changes in AAC physiology would limit their ability to receive and respond to input, undermining a critical brake on the dentate throughput during epileptogenesis.