bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of factors associated with reproductive health seeking behaviours among adolescent mothers in Dodoma region
Authors: Mbwambo Eliwedi , Gibore Nyasiro
Published: May 2024

Background

Adolescent pregnancy poses a significant public health concern due to its association with high levels of maternal morbidity and mortality, particularly in sub-Saharan countries. For early detection and management of obstetric danger signs, appropriate health seeking behaviour on reproductive health among adolescent mother is highly recommended so as to decrease maternal mortality and morbidity related to pregnancy. This study aims to assess the factors influencing reproductive health-seeking behaviours among adolescent pregnant mothers in Dodoma region.

Methods

A community cross-sectional analytical study will be conducted, involving multistage sampling to recruit 604 adolescent pregnant mothers. Face-to-face interviews using structured questionnaires will be utilized to assess predisposing, enabling, and need factors, as well as knowledge and attitudes regarding obstetric danger signs. Data analysis will be performed using SPSS software version 25. Descriptive statistics will be used to analyse background information, while inferential statistics, including chi-square and logistic regression, will determine associations between variables.

Results

This study will display the trend in utilization of reproductive health as well as predisposing, need and enabling factor associated with health seeking behaviour. A statistically significant variable in the final model will be identified with a 95% confidence interval and a p-value of < 0.05.

Conclusions

This study will provide a clear picture of the level of knowledge, attitude, and health-seeking behaviour which is crucial for preventing delay number one of seeking health care immediately after experiencing complications also gives a picture of the role of healthcare workers in promoting health among vulnerable populations.
Review of publicly available state reimbursement policies for removal and reinsertion of Long-Acting Reversible Contraception
Authors: Okoroh Ekwutosi M. , Kroelinger Charlan D. , Sappenfield Olivia R. , Howland Julia F. , Romero Lisa M. , Uesugi Keriann , Cox Shanna
Published: May 2024

We examined reimbursement policies for the removal and reinsertion of long-acting reversible contraception (LARC). We conducted a standardized, web-based review of publicly available state policies for language on reimbursement of LARC removal and reinsertion. We also summarized policy language on barriers to reimbursement for LARC removal and reinsertion. Twenty-six (52%) of the 50 states had publicly available policies that addressed reimbursement for LARC removal. Of these, 14 (28%) included language on reimbursement for LARC reinsertion. Eleven states included language on barriers for reimbursement for removal and/or reinsertion: five state policies included language with other requirements for removal only, three policies included language with additional requirements for reinsertion only, and three included language with additional requirements for both. Three state policies specified no barriers be placed on reimbursement for removal and one specified no barriers be placed on reimbursement for reinsertion. Half of the states in the U.S. do not have publicly available policies on reimbursement for the removal and reinsertion of LARC devices. Inclusion of unrestricted access to these services is important for reproductive autonomy.
Functional role of myosin-binding protein H in thick filaments of developing vertebrate fast-twitch skeletal muscle
Authors: Mead Andrew F. , Wood Neil B. , Nelson Shane R. , Palmer Bradley M. , Yang Lin , Previs Samantha Beck , Ploysangngam Angela , Kennedy Guy G. , McAdow Jennifer F. , Tremble Sarah M. , Cipolla Marilyn J. , Ebert Alicia M. , Johnson Aaron N. , Gurnett Christina A. , Previs Michael J. , Warshaw David M.
Published: May 2024

Myosin-binding protein H (MyBP-H) is a component of the vertebrate skeletal muscle sarcomere with sequence and domain homology to myosin-binding protein C (MyBP-C). Whereas skeletal muscle isoforms of MyBP-C (fMyBP-C, sMyBP-C) modulate muscle contractility via interactions with actin thin filaments and myosin motors within the muscle sarcomere “C-zone,” MyBP-H has no known function. This is in part due to MyBP-H having limited expression in adult fast-twitch muscle and no known involvement in muscle disease. Quantitative proteomics reported here reveal MyBP-H is highly expressed in prenatal rat fast-twitch muscles and larval zebrafish, suggesting a conserved role in muscle development, and promoting studies to define its function. We take advantage of the genetic control of the zebrafish model and a combination of structural, functional, and biophysical techniques to interrogate the role of MyBP-H. Transgenic, FLAG-tagged MyBP-H or fMyBP-C both localize to the C-zones in larval myofibers, whereas genetic depletion of endogenous MyBP-H or fMyBP-C leads to increased accumulation of the other, suggesting competition for C-zone binding sites. Does MyBP-H modulate contractility from the C-zone? Globular domains critical to MyBP-C’s modulatory functions are absent from MyBP-H, suggesting MyBP-H may be functionally silent. However, our results suggest an active role. Small angle x-ray diffraction of intact larval tails revealed MyBP-H contributes to the compression of the myofilament lattice accompanying stretch or contraction, whilein vitromotility experiments indicate MyBP-H shares MyBP-C’s capacity as a molecular “brake”. These results provide new insights and raise questions about the role of the C-zone during muscle development.
A single dose of cocaine rewires the 3D genome structure of midbrain dopamine neurons
Authors: Szabó Dominik , Franke Vedran , Bianco Simona , Batiuk Mykhailo Y. , Paul Eleanor J. , Kukalev Alexander , Pfisterer Ulrich G. , Irastorza-Azcarate Ibai , Chiariello Andrea M. , Demharter Samuel , Zea-Redondo Luna , Lopez-Atalaya Jose P. , Nicodemi Mario , Akalin Altuna , Khodosevich Konstantin , Ungless Mark A. , Winick-Ng Warren , Pombo Ana
Published: May 2024

Midbrain dopamine neurons (DNs) respond to a first exposure to addictive drugs and play key roles in chronic drug usage1–3. As the synaptic and transcriptional changes that follow an acute cocaine exposure are mostly resolved within a few days4,5, the molecular changes that encode the long-term cellular memory of the exposure within DNs remain unknown. To investigate whether a single cocaine exposure induces long-term changes in the 3D genome structure of DNs, we applied Genome Architecture Mapping and single nucleus transcriptomic analyses in the mouse midbrain. We found extensive rewiring of 3D genome architecture at 24 hours past exposure which remains or worsens by 14 days, outlasting transcriptional responses. The cocaine-induced chromatin rewiring occurs at all genomic scales and affects genes with major roles in cocaine-induced synaptic changes. A single cocaine exposure triggers extensive long-lasting changes in chromatin condensation in post-synaptic and post-transcriptional regulatory genes, for example the unfolding ofRbfox1which becomes most prominent 14 days post exposure. Finally, structurally remodeled genes are most expressed in a specific DN sub-type characterized by low expression of the dopamine auto-receptorDrd2, a key feature of highly cocaine-sensitive cells. These results reveal an important role for long-lasting 3D genome remodelling in the cellular memory of a single cocaine exposure, providing new hypotheses for understanding the inception of drug addiction and 3D genome plasticity.
CD13 Activation Assembles Signaling Complexes that Promote the Formation of Tunneling Nanotubes in Endothelial Cells
Authors: Meredith Emily , Aguilera Brian , McGurk Fraser , Zong Pengyu , Yue Lixia , Ghosh Mallika , Shapiro Linda H
Published: May 2024

Transmembrane CD13 assembles protein complexes at the plasma membrane to enable diverse cellular processes such as cell-cell adhesion, focal adhesion turnover, endocytosis and recycling of cell surface proteins. In this study, we demonstrate a novel CD13-dependent assembly platform that regulates phosphoinositide (PI) signal transduction during the formation of Tunneling Nanotubes (TNTs). TNTs are actin-based, membrane-delimited bridges that facilitate intercellular communication by connecting distant cells to physically transfer subcellular cargoes. TNTs form between various cell types under stress conditions, but few molecular TNT-inducers exist. Human Kaposi’s sarcoma-derived endothelial cells (KSECs) readily form stress-induced TNTs capable of transferring Ca2+and membrane molecules between cells, with clear accumulation of CD13 and actin at the base of the protrusions. Alternatively, CD13-null KSECs form fewer TNTs and Ca2+transfer is markedly reduced. Mechanistically, CD13-mediated TNT formation requires activation of CD13, Src, FAK and Cdc42 to allow tethering of the IQGAP1 and ARF6 complex at the membrane to activate the phosphatidylinositol-4-phosphate-5-kinase PI5K. This increases local phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) levels to promote the actin-polymerization and membrane protrusion necessary for TNT formation. Therefore, CD13 is a novel molecular PIP regulator and TNT trigger that will facilitate the dissection of downstream pathways and mechanisms regulating TNT formation.
Wheat Enhanced Disease Resistance EMS-Mutants Include Lesion-mimics With Adult Plant Resistance to Stripe Rust
Authors: Lunde China , Seong Kyungyong , Kumar Rakesh , Deatker Andrew , Chhabra Bhavit , Wang Meinan , Kaur Shivreet , Song Sarah , Palayur Ann , Davies Cole , Cumberlich William , Gill Upinder , Rawat Nidhi , Chen Xianming , Aoun Meriem , Mundt Christopher , Krasileva Ksenia V
Published: May 2024

Tetraploid durum wheatTriticum turgidumsubsp.durumcv ‘Kronos’ has extensive genetic variation resources, including a sequenced and cataloged ethyl methanesulfonate (EMS) mutagenized population. To utilize this allelic diversity, we screened over 2,000 mutant lines and identified over 30 enhanced disease resistance (EDR) mutants in a forward genetic field screen against stripe rust. Sixteen of the EDR lines have persistent resistance to stripe rust after four years, and several mutants showed differential disease responses against other fungal pathogens, indicating that the lines possess diverse alleles that affect multiple routes of pathogen suppression. Five of these 16 lines showed spontaneous lesion formation in the absence of pathogens. Only one showed a reduction in kernel weight under pathogen pressure, a testimony to the high mutational density that wheat can tolerate. Phenotypic selection for resistance at the adult stage identified useful EMS alleles for stripe rust resistance. The mutations in the 16 EDR lines were newly mapped to a recently released long-read Kronos genome to enhance their utility in molecular breeding for fungal resistance and for fundamental studies of plant-pathogen interactions.
Disulfide constrained Fabs overcome target size limitation for high-resolution single-particle cryo-EM
Authors: Kung Jennifer E. , Johnson Matthew C. , Jao Christine C. , Arthur Christopher P. , Tegunov Dimitry , Rohou Alexis , Sudhamsu Jawahar
Published: May 2024

High-resolution structures of proteins are critical to understanding molecular mechanisms of biological processes and in the discovery of therapeutic molecules. Cryo-EM has revolutionized structure determination of large proteins and their complexes1, but a vast majority of proteins that underlie human diseases are small (< 50 kDa) and usually beyond its reach due to low signal-to-noise images and difficulties in particle alignment2. Current strategies to overcome this problem increase the overall size of small protein targets using scaffold proteins that bind to the target, but are limited by inherent flexibility and not being bound to their targets in a rigid manner, resulting in the target being poorly resolved compared to the scaffolds3–11. Here we present an iteratively engineered molecular design for transforming Fabs (antibody fragments), into conformationally rigid scaffolds (Rigid-Fabs) that, when bound to small proteins (∼20 kDa), can enable high-resolution structure determination using cryo-EM. This design introduces multiple disulfide bonds at strategic locations, generates a well-folded Fab constrained into a rigid conformation and can be applied to Fabs from various species, isotypes and chimeric Fabs. We present examples of the Rigid Fab design enabling high-resolution (2.3–2.5 Å) structures of small proteins, Ang2 (26 kDa) and KRAS (21 kDa) by cryo-EM. The strategies for designing disulfide constrained Rigid Fabs in our work thus establish a general approach to overcome the target size limitation of single particle cryo-EM.
MAST-Decon: Smooth Cell-type Deconvolution Method for Spatial Transcriptomics Data
Authors: Luo Tianyou , Chen Jiawen , Wu Wenrong , Zhao Jinying , Yao Huaxiu , Zhu Hongtu , Li Yun
Published: May 2024

Abstract

Spatial transcriptomics (ST) technologies have gained increasing popularity due to their ability to provide positional context of gene expressions in a tissue. One major limitation of current commercially available ST methods such as the 10X Genomics Visium platform is the lack of single cell resolution. Cell type deconvolution for ST data is critical in order to fully reveal underlying biological mechanisms. Existing ST data deconvolution methods share two common limitations: first, few of them utilize spatial neighborhood information. Existing methods such as RCTD and SPOTlight intrinsically treat each spatial spot as independent of neighboring spots, although we anticipate nearby spots to share similar cell type compositions based on clinical evidence of tissue structures. Such limitation could be amplified when sequencing depths at single spots are relatively low so that borrowing information from neighboring spots is necessary in order to obtain reliable deconvolution results. Second, although Visium data provide us with a histological image which could add additional information regarding spot heterogeneity, most existing methods do not utilize this H&E image. To solve these two limitations, we developed Multiscale Adaptive ST Deconvolution (MAST-Decon), a smooth deconvolution method for ST data. MAST-Decon uses a weighted likelihood approach and incorporates both gene expression data, spatial neighborhood information and H&E image features by constructing different kernel functions to obtain a smooth deconvolution result. We showcased the strength of MAST-Decon through simulations based on real data, including a single-cell dataset of mouse brain primary visual cortex, and real-world Visium datasets to demonstrate its robust and superior performance compared with other state-of-the-art methods.
Arabidopsis Apoplast TET8 Positively Correlates to Leaf Senescence andtet3tet8Double Mutants are Delayed in Leaf Senescence
Authors: Zimmerman Jayde A. , Verboonen Benjamin , Harrison Hanson Andrew P. , Brusslan Judy A.
Published: May 2024

Extracellular vesicles (EVs) are membrane-bound exosomes secreted into the apoplast. Two distinct populations of EVs have been described in Arabidopsis: PEN1-associated and TET8-associated. We previously noted early leaf senescence in thepen1single andpen1pen3double mutant. Both PEN1 and PEN3 are abundant in EV proteomes suggesting EVs might regulate leaf senescence in soil-grown plants. We observed that TET8 is more abundant in the apoplast of early senescingpen1andpen1pen3mutant rosettes and in older WT rosettes. The increase in apoplast TET8 in thepen1mutant did not correspond to increasedTET8mRNA levels. In addition, apoplast TET8 was more abundant in the early leaf senescencemyb59mutant, meaning the increase in apoplast TET8 protein during leaf senescence is not dependent onpen1orpen3. Genetic analysis showed a significant delay in leaf senescence intet3tet8double mutants after six weeks of growth suggesting that these two tetraspanin paralogs operate additively and are positive regulators of leaf senescence. This is opposite of the effect ofpen1andpen1pen3mutants that show early senescence and suggest PEN1 to be a negative regulator of leaf senescence. Our work provides initial support that PEN1-associated EVs and TET8-associated EVs may have opposite effects on soil-grown plants undergoing age-related leaf senescence.
Robotic Imaging and Machine Learning Analysis of Seed Germination: Dissecting the Influence of ABA and DOG1 on Germination Uniformity
Authors: Eckhardt James , Xing Zenan , Subramanian Vish , Vaidya Aditya , Cutler Sean
Published: May 2024

Seed germination research has evolved over the years, increasingly incorporating technology. Recent advances in phenotyping platforms have increased the accessibility of high throughput phenotyping technologies to more labs, leading to valuable insights into germination biology. These platforms benefit researchers by limiting manual labor and increasing the temporal resolution of imaging. Each of the platforms developed presents unique benefits and challenges, from scalability to price to computing resources. Performing experiments involving thousands of seeds remains a daunting task due to the limitations of current phenotyping platforms and image analysis pipelines. To overcome these challenges, we introduce SPENCER (Seed Phenotype Evaluation and Germination Curve Estimation Robot), a high-throughput phenotyping platform. SPENCER accommodates 32 rectangular petri plates, capable of assessing up to 8000 Arabidopsis seeds per experiment. Our design allows for high quality images while maintaining optimal humidity, crucial for precise germination assessment over longer experiments. The image analysis workflow incorporates advanced image analysis using semantic segmentation models trained for Arabidopsis and lettuce, providing researchers with accessible, reproducible, and efficient tools. We applied SPENCER to investigate the relative roles of DELAY OF GERMINATION 1 (DOG1) and abscisic acid (ABA) in Arabidopsis dormancy. DOG1 mutants exhibited rapid germination, whereas ANT application had a greater impact on the slower-germinating Ler ecotype. Our findings suggest that DOG1 plays a significant role in dormancy, particularly in non-dormant accessions, while ABA’s influence is more pronounced under stress conditions. Additionally, we explored germination uniformity, another agriculurally relevant trait, observing parallels with germination timing. SPENCER offers a powerful and accessible tool for dissecting complex biological traits in conjunction with chemical and genetic manipulations. Its scalability and versatility make it suitable for large-scale genetic and chemical germination screens.
Biological S0reduction at neutral (pH 6.9) and acidic (pH 3.8) conditions: Performance and microbial community shifts in a H2/CO2-fed bioreactor
Authors: Hidalgo-Ulloa Adrian , van der Graaf Charlotte M. , Sánchez-Andrea Irene , Weijma Jan , Buisman Cees J.N.
Published: May 2024

Sulfidogenesis is a promising technology for the selective recovery of chalcophile bulk metals (e.g. Cu, Zn, and Co) from metal-contaminated waters such as acid mine drainage (AMD) and metallurgy waste streams. The use of elemental sulfur (S0) instead of sulfate (SO42-) as electron acceptor reduces electron donor requirements four-fold, lowering process costs, and expands the range of operating conditions to more acidic pH. We previously reported autotrophic S0reduction using an industrial mesophilic granular sludge as inoculum under thermoacidophilic conditions. Here, we examined the effect of pH on the S0reduction performance of the same inoculum, in a continuously fed gas-lift reactor run at 30 °C under neutral (pH 6.9) and acidic (pH 3.8) conditions. Steady-state volumetric sulfide production rates (VSPR) dropped 2.3-fold upon transition to acidic pH, from 1.79 ± 0.18 g·L-1·d-1S2-·to 0.71 ± 0.07 g·L-1·d-1S2-· Microbial community analysis via 16S rRNA gene amplicon sequencing showed that at pH 6.9, the S0-reducing generaSulfurospirillum, Sulfurovum, Desulfurella, andDesulfovibriowere present at the highest relative abundance, while at pH 3.9Desulfurelladominated the sequenced reads. The detection of acetic acid and the relative abundance ofAcetobacteriumat pH 6.9 pointed towards acetogenesis, explaining the dominance of the heterotrophic genusSulfurospirillumin this H2and CO2–fed bioreactor.
Genetics, energetics and allostery during a billion years of hydrophobic protein core evolution
Authors: Escobedo Albert , Voigt Gesa , Faure Andre J , Lehner Ben
Published: May 2024

Protein folding is driven by the burial of hydrophobic amino acids in a tightly-packed core that excludes water. The genetics, biophysics and evolution of hydrophobic cores are not well understood, in part because of a lack of systematic experimental data on sequence combinations that do - and do not - constitute stable and functional cores. Here we randomize protein hydrophobic cores and evaluate their stability and function at scale. The data show that vast numbers of amino acid combinations can constitute stable protein cores but that these alternative cores frequently disrupt protein function because of allosteric effects. These strong allosteric effects are not due to complicated, highly epistatic fitness landscapes but rather, to the pervasive nature of allostery, with many individually small energy changes combining to disrupt function. Indeed both protein stability and ligand binding can be accurately predicted over very large evolutionary distances using additive energy models with a small contribution from pairwise energetic couplings. As a result, energy models trained on one protein can accurately predict core stability across hundreds of millions of years of protein evolution, with only rare energetic couplings that we experimentally identify limiting the transplantation of cores between highly diverged proteins. Our results reveal the simple energetic architecture of protein hydrophobic cores and suggest that allostery is a major constraint on sequence evolution.
A real-time biochemical assay for quantitative analyses of APOBEC-catalyzed DNA deamination
Authors: Belica Christopher A. , Carpenter Michael A. , Chen Yanjun , Brown William L. , Moeller Nicholas H. , Boylan Ian T. , Harris Reuben S. , Aihara Hideki
Published: May 2024

Over the past decade, the connection between APOBEC3 cytosine deaminases and cancer mutagenesis has become increasingly apparent. This growing awareness has created a need for biochemical tools that can be used to identify and characterize potential inhibitors of this enzyme family. In response to this challenge, we have developed a Real-time APOBEC3-mediated DNA Deamination (RADD) assay. This assay offers a single-step set-up and real-time fluorescent read-out, and it is capable of providing insights into enzyme kinetics and also offering a high-sensitivity and easily scalable method for identifying APOBEC3 inhibitors. This assay serves as a crucial addition to the existing APOBEC3 biochemical and cellular toolkit and possesses the versatility to be readily adapted into a high-throughput format for inhibitor discovery.
Analysis of Differentially expressed genes and Molecular pathways in Peanut Allergy Induced Dynamic Changes involved in Peanut-Specific Immune Responses: A Systematic and Bioinformatics Approach
Authors: Parmar Glory Simon , Gulati Manisha , Rabby Md Khoshnade , Merugu Ramchander , Mohanty Satabdi , Kulsum Umme , Pujari Dhanshree Gajanan , More Swapnja Rohit , Prakash Om , Bhore Priyanka Shrikant , Satish Deepshikha
Published: May 2024

Peanut allergy poses a significant global health concern, triggering hypersensitivity reactions upon exposure to peanuts. Understanding the molecular mechanisms governing peanut-specific immune responses is imperative for developing effective therapeutic approaches. This study aimed to investigate differentially expressed genes (DEGs) and associated molecular pathways implicated in peanut allergy-induced immune responses. Employing a systematic and bioinformatics-driven approach, we analyzed gene expression profiles from peanut-allergic individuals and healthy controls using RNAseq Next-Generation Sequencing (NGS) data. Enrichment analysis of DEGs revealed their involvement in various inflammatory conditions, including autoinflammatory, allergic, and respiratory disorders. Additionally, pathway enrichment analysis highlighted perturbed molecular pathways such as Asthma, IL-17 signaling pathway, and Inflammatory bowel diseases, underscoring their role in modulating peanut-specific immune responses. Protein-protein interaction network analysis identified central regulatory hubs, elucidating the intricate molecular interplay underlying the immune response to peanut allergens. Overall, our findings offer comprehensive insights into the molecular landscape of peanut allergy, delineating key DEGs and pathways associated with peanut-specific immune responses. This systematic and bioinformatics-driven approach enhances our understanding of allergic reactions to peanuts, providing potential targets for the development of novel therapeutic interventions and diagnostic biomarkers for peanut allergy management.
Lipoprotein(a) metabolomic and proteomic features and atherosclerotic cardiovascular disease in young, healthy adults
Authors: Goonewardena Sascha N. , Jurga Tomasz , Lloyd-Jones Donald , Damodaran Dilna , Thyagarajan Bharat , Jacobs David R. , Shore Supriya , Brandt Eric J. , Clish Clary , Tanriverdi Kahraman , Freedman Jane E. , Emmer Brian T. , Wilkins John T. , Do Ron , Bittner Vera A. , Rosenson Robert S. , Shah Ravi V. , Murthy Venkatesh L.
Published: May 2024

Background

Elevated lipoprotein (a) [Lp(a)] is associated with a higher risk of atherosclerotic cardiovascular disease (ASCVD) events. Although Lp(a) is a genetically determined risk factor, the metabolomic and proteomic features that may mediate or be associated with this risk are unknown.

Methods

In young, healthy Coronary Artery Risk Development in Young Adults (CARDIA) participants, we defined the relationships between year 7 (Y7) Lp(a) and metabolomic (n=563)/proteomic (n=184) features, derived quantitative Lp(a)-omic scores from these features, and related these quantitative scores to ASCVD phenotypes.

Results

CARDIA participants had a mean age of 32 years at Y7 in this study and a median follow-up of 27.1 years. In the overall cohort (n=3920), Y7 Lp(a) levels were associated prospectively with ASCVD phenotypes at year 25 (Y25), including hs-CRP, coronary artery calcification (CAC), and incident CHD. In the subcohort (n=2290) that had measurements of Lp(a), proteomics, and metabolomics, Y7 Lp(a) levels were associated with distinct proteomic and metabolomic features indicative of immune responses, lipoprotein metabolism, atherogenesis, and arginine/steroid biosynthesis. Using machine learning approaches, Lp(a) metabolomic, proteomic, and transomic quantitative scores were derived. The Y7 Lp(a) transomic score was more strongly associated with Y25 incident CAC (standardized β = 0.29, p=0.04), hs-CRP (standardized β = 0.18, p =0.0008), and incident any CHD (standardized β = 0.51, p = 0.05), than the Y7 Lp(a) concentration itself (no significant associations).

Conclusions

To our knowledge, this is the first study to identify relationships between Lp(a) and associated metabolomic/proteomic features in young, healthy adults and joint associations with ASCVD phenotypes. The multi-omics approaches employed here provide insight into the pathobiology of Lp(a)-driven ASCVD and enable more nuanced mechanistic risk assessment compared with Lp(a) concentrations alone.
Seed endophytes of malting barley from different locations are shaped differently and are associated with malt quality traits
Authors: Ajayi Oyeyemi , Mahalingam Ramamurthy
Published: May 2024

Maximizing microbial functions for improving crop performance requires better understanding of the important drivers of plant-associated microbiomes. However, it remains unclear the forces that shapes microbial structure and assembly, and how plant seed-microbiome interactions impact grain quality. In this work, we characterized the seed endophytic microbial communities of malting barley from different geographical locations and investigated associations between bacterial species diversity and malt quality traits. Host genotype, location, and interactions (genotype x location) significantly impacted the seed endophytic microbial communities. Taxonomic composition analysis identified the most abundant genera for bacterial and fungal communities to be Bacillus (belonging to phylum Firmicutes) and Blumeria (belonging to phylum Ascomycota), respectively. We observed that a greater proportion of bacterial amplicon sequence variants (ASVs) were shared across genotypes and across locations while the greater proportion of the fungal ASVs were unique to each genotype and location. Association analysis showed a negative correlation between alpha diversity indices (Faith PD and Shannon indices) and malt quality traits for barley protein (BP), free amino nitrogen (FAN), diastatic power (DP) and alpha amylase (AA). In addition, most of the bacterial genera were significantly negatively associated with malt extract (ME) -a key trait for maltsters and brewers. We conclude that barley genotype, location, and their interactions shape the seed endophytic microbiome and is key to microbiome manipulation and management during barley production and/or malting.
Genetically recoding respiratory syncytial virus to visualize nucleoprotein dynamics and virion assembly
Authors: Mitrovich Margaret D. , Vahey Michael D.
Published: May 2024

RNA viruses possess small genomes encoding a limited repertoire of essential and often multifunctional proteins. Although genetically tagging viral proteins provides a powerful tool for dissecting mechanisms of viral replication and infection, it remains a challenge. Here, we leverage genetic code expansion to develop a recoded strain of respiratory syncytial virus (RSV) in which the multifunctional nucleoprotein is site-specifically modified with an unnatural amino acid. The resulting virus replicates exclusively in cells capable of amber stop codon suppression and is amenable to labeling with tetrazine-modified fluorophores, achieving high signal-to-background. We use this tool to visualize the transfer of nucleoprotein complexes from cytoplasmic condensates directly to budding viral filaments at the cell surface and to cytoplasmic compartments containing viral surface proteins, suggesting multiple pathways for viral assembly.
Bile acids activate the antibacterial T6SS1 in the gut pathogenVibrio parahaemolyticus
Authors: Schiffmann Sarah , Mass Shir , Salomon Dor
Published: May 2024

The marine bacteriumVibrio parahaemolyticusis a major cause of seafood-borne gastroenteritis in humans and of acute hepatopancreatic necrosis disease in shrimp. Bile acids, produced by the host and modified into secondary bile acids by commensal bacteria in the gastrointestinal tract, induce the virulence factors leading to disease in humans and shrimp. Here, we show that secondary bile acids also activate this pathogen’s type VI secretion system 1 (T6SS1), a toxin-delivery apparatus mediating interbacterial competition. This finding implies thatVibrio parahaemolyticusexploits secondary bile acids to activate its virulence factors and identify the presence of commensal bacteria that it needs to outcompete in order to colonize the host.

Importance

Bacterial pathogens often manipulate their host and cause disease by secreting toxic proteins. However, to successfully colonize a host, they must also remove commensal bacteria that reside in it and may compete with them over resources. Here, we find that the same host-derived molecules that activate the secreted virulence toxins in a gut bacterial pathogen,Vibrio parahaemolyticus, also activate an antibacterial toxin delivery system that targets such commensal bacteria. These findings suggest that a pathogen can use one cue to launch a coordinated, trans-kingdom attack that enables it to colonize a host.
Coumarin as a general switching auxiliary to prepare photochromic and spontaneously blinking fluorophores
Authors: Jradi Fadi M. , English Brian P. , Brown Timothy A. , Aaron Jesse , Khuon Satya , Galbraith James A. , Galbraith Catherine G. , Lavis Luke D.
Published: May 2024

Single-molecule localization microscopy (SMLM) uses activatable or switchable fluorophores to create non-diffraction limited maps of molecular location in biological samples. Despite the utility of this imaging technique, the portfolio of appropriate labels for SMLM remains limited. Here, we describe a general strategy for the construction of “glitter bomb” labels by simply combining rhodamine and coumarin dyes though an amide bond. Condensation of theortho-carboxyl group on the pendant phenyl ring of rhodamine dyes with a 7-aminocoumarin yields photochromic or spontaneously blinking fluorophores depending on the parent rhodamine structure. We apply this strategy to prepare labels useful super-resolution experiments in fixed cells using different attachment techniques. This general glitter bomb strategy should lead to improved labels for SMLM, ultimately enabling the creation of detailed molecular maps in biological samples.
An N-terminal domain specifies developmental control by the SMAX1-LIKE family of transcriptional co-repressors inArabidopsis thaliana
Authors: Chang Sun Hyun , George Wesley J. , Nelson David C.
Published: May 2024

SMAX1-LIKE (SMXL) proteins are transcriptional co-repressors that regulate many aspects of plant growth and development. Proteins from the SMAX1- and SMXL78-clades of this family are targeted for degradation after karrikin or strigolactone perception, triggering downstream responses. We investigated how SMXL proteins control development.SMXL7can partially replicateSMAX1function in seeds and seedlings, butSMAX1cannot replaceSMXL7in shoot branching control. Therefore, the distinct roles of these genes arise from differences in protein activity more than expression. Analysis of chimeras and domain deletions of SMAX1 and SMXL7 proteins revealed that an N-terminal domain is necessary and sufficient to specify developmental functions. We screened 158 transcription factors for interactions with SMAX1. The N-terminal domain is necessary and/or sufficient for the majority of candidate interactions. These discoveries enable cross-wiring of karrikin and strigolactone control of plant development and lay a foundation for understanding how SMXL proteins evolved functional differences.
A novel motif in calcimembrin/C16orf74 dictates multimeric dephosphorylation by calcineurin
Authors: Bradburn Devin A. , Reis Joana C. , Qayyum Shariq , Viennet Thibault , Arthanari Haribabu , Cyert Martha S.
Published: May 2024

Calcineurin, the Ca2+/calmodulin-activated protein phosphatase, recognizes substrates and regulators via short linear motifs, PxIxIT and LxVP, which dock to distinct sites on calcineurin and determine calcineurin distribution and catalysis, respectively. Calcimembrin/C16orf74 (CLMB), an intrinsically disordered microprotein whose expression correlates with poor cancer outcomes, targets calcineurin to membranes where it may promote oncogenesis by shaping calcineurin signaling. We show that CLMB associates with membranes via lipidation, i.e. N-myristoylation and reversible S-acylation. Furthermore, CLMB contains an unusual composite ‘LxVPxIxIT’ motif, that binds the PxIxIT-docking site on calcineurin with extraordinarily high affinity when phosphorylated,33LxVPxIxITxx(p)T44. Calcineurin dephosphorylates CLMB to decrease this affinity, but Thr44 is protected from dephosphorylation when PxIxIT-bound. We propose that CLMB is dephosphorylated in multimeric complexes, where one PxIxIT-bound CLMB recruits calcineurin to membranes, allowing a second CLMB to engage via its LxVP motif to be dephosphorylated.In vivoandin vitrodata, including nuclear magnetic resonance (NMR) analyses of CLMB-calcineurin complexes, supports this model. Thus, the CLMB composite motif imposes unique properties to calcineurin signaling at membranes including sensitivity to CLMB:calcineurin ratios, CLMB phosphorylation and dynamic S-acylation.
Patterns of morbidity and mortality among neonates admitted in Mirwais regional hospital, Kandahar, Afghanistan
Authors: Tareen Zarghoon , Tareen Ahmad Tameem , Amirzada Mohammad Essa , Zafare Nik Mohammad
Published: May 2024

ABSTRUCT

Background

Neonatal health is a critical global concern that reflects the national and global progress and challenges of health systems. Neonatal morbidity and mortality are major global public health problems.

Methods

We conducted a hospital-based cross-sectional descriptive study of all neonates admitted to the NICU of the pediatric ward of Mirwais Regional Hospital between March 2023 and February 2024.

The objective of this study was to determine the pattern of neonatal morbidity and mortality as well as to compute case fatality rates in Mirwais Regional Hospital in Kandahar City, Afghanistan.

Results

In our study, there were 3387 newborns admitted to the neonatal ward of Mirwais Regional Hospital over a one-year period (from March 2023 to February 2024). Prematurity was the most common reason for admission to the neonatal ward (1048/3387, 30.9 %). Other common conditions included neonatal sepsis (909/3387, 26.8%), birth asphyxia (785/3387, 23.1%), jaundice (466/3387, 13.7%), and tetanus (9/3387, 0.3%). Surgical causes contributed to (170/3387, 5.0%) morbidities.

The overall mortality rate was 13.0% (442/ 3387). The major causes of mortality were premature birth (39.8%, 176/442), birth asphyxia (25.6%, 113/442), and neonatal sepsis (22.1%, 98/442). Other causes of mortality were neonatal jaundice (7.9%, 35/442), neonatal tetanus (0.9%, 4/442), and surgical disease (3.6%, 16/442). Neonatal tetanus had the highest mortality rate (44.4%).

Conclusion

Prematurity was the most common reason for admission, followed by birth asphyxia, neonatal sepsis, and jaundice. The overall mortality rate was 13%. Prematurity is a leading cause of neonatal mortality. Neonatal tetanus has a high mortality rate.

Author summary

Neonates were defined as those the in first 28 days of life. In humans, they are more vulnerable to diseases than any other age group. Neonatal morbidity and mortality are major public health problems with approximately 3.1 million babies worldwide dying each year in the first month of life. The main goal of this study was to estimate the types of neonatal morbidity and mortality in Merwais Regional Hospital, located in Kandahar City, Afghanistan. This study found that premature birth (birth before 37 weeks of gestation) was the most common reason for admission to the neonatal ward. Other common conditions include neonatal sepsis, birth asphyxia, neonatal jaundice, and neonatal tetanus. The overall mortality rate was high in the present study. The main cause of mortality was prematurity, followed by birth asphyxia and neonatal sepsis. Interventions should be planned and implemented at different levels in the community to prevent and reduce the incidence of neonatal diseases and deaths.
Immune signaling induced by plant Toll/interleukin-1 receptor (TIR) domains is thermostable
Authors: Demont Héloïse , Remblière Céline , Deslandes Laurent , Bernoux Maud
Published: May 2024

Plant disease is a major threat in agriculture and climate change is predicted to intensify it. Above the optimal plant’s growth range, plant immunity and in particular immune responses induced by nucleotide-binding leucine rich repeat receptors (NLRs) are dampened, but the underlying molecular mechanisms remains elusive. NLRs usually contain an N-terminal signaling domain, such as Toll/interleukin-1 receptor (TIR) domain, which is self-sufficient to trigger immune signaling. By using inducible Arabidopsis transgenic lines expressing TIR-containing NLRs (TNLs) or corresponding isolated TIR domains from Arabidopsis RPS4 and flax L6 NLRs, we showed that immune signaling induced downstream of TNL activation is not affected by an elevation of temperature. Conditional activation of TNL- and isolated TIR-mediated immune responses follow the same signaling route at permissive temperature (EDS1/RNLs requirement and activation of the salicylic acid sector). Yet, this signaling pathway is maintained under elevated temperature (30°C) when induced by isolated TIRs, but not full-length TNLs. This work underlines the need to further study how NLRs are impacted by an increase of temperature, which is particularly important to improve the resilience of plant disease resistance in a warming climate.
Mining the biosynthetic landscape of lactic acid bacteria unearths a new family of RiPPs assembled by a novel type of ThiF-like adenylyltransferases
Authors: Wang Mengjiao , Wu Mengyue , Han Meng , Niu Xiaogang , Fan Aili , Zhu Shaozhou , Tong Yigang
Published: May 2024

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are chemically diverse natural products of ribosomal origin. These peptides, which frequently act as signals or antimicrobials, are biosynthesized by conserved enzymatic machineries, making genome mining a powerful strategy for unearthing previously uncharacterized members of their class. Herein, we investigate the untapped biosynthetic potential of Lactobacillales (i.e. lactic acid bacteria) – an order of Gram-positive bacteria closely associated with human life, including pathogenic species and industrially-relevent fermenters of dairy products. Through genome mining methods, we systematically explored the distribution and diversity of ThiF-like adenylyltransferases-utilizing RiPP systems in lactic acid bacteria and identified a number of unprecedented biosynthetic gene clusters. In one of these clusters, we found a previously undescribed group of macrocyclic imide biosynthetic pathways containing multiple transporters and may be involved in potential quorum sensing (QS) system. Through in vitro assays, we determined that one such adenylyltranferase specifically catalyzes the intracyclization of its precursor peptide through macrocyclic imide formation. Incubating the enzyme with various primary amines revealed it could effectively amidate the C-terminus of the precursor peptide. This new transformation adds to the growing list of Nature’s peptide macrocyclization strategies and expands the impressive catalytic repertoire of the adenylyltransferase family. The diverse RiPP systems identified herein represent a vast, unexploited landscape for discovery of novel class of natural products and potential QS systems.

Abstract Figure

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Hypocotyl Development in Arabidopsis and other Brassicaceae Displays Evidence of Photoperiodic Memory
Authors: Ronald James , Lock Sarah C.L , Claydon Will , Zhu Zihao , McCarthy Kayla , Pendlington Elizabeth , Redmond Ethan J. , Vong Gina Y.W. , Stanislas Sanoj P. , Davis Seth J. , Quint Marcel , Ezer Daphne
Published: May 2024

Sensing and responding to photoperiod changes is essential for plants to adapt to seasonal progression. Most of our understanding of how plants sense photoperiodic changes is through studies on flowering time. However, other aspects of plant development are regulated by the photoperiod, including hypocotyl elongation. Unlike flowering, hypocotyl elongation displays a greater plasticity to changes in the photoperiod with increases in daylength causing greater inhibition of growth until a threshold is met. Previous studies have only looked at hypocotyl development in the context of a stationary photoperiod. It is unknown if changes in the photoperiod during development influence hypocotyl elongation. Here, we developed a physiological assay to investigate this question. We have discovered that hypocotyl elongation is influenced by a memory of past photoperiod exposure in Arabidopsis and Brassicaceae cultivars used for microgreen agriculture. Photoperiodic memory persisted for multiple days, although it weakened over time, and the strength of the memory was dependent on the genetic background. We identified that phyB and ELF3, key regulators of hypocotyl development, were required for photoperiodic memory. Finally, we identified that the circadian clock is unlikely to function as a repository for photoperiodic memory as circadian rhythms quickly re-aligned with the new photoperiod. In summary, our work highlights for the first-time evidence of a photoperiodic memory that can control plant development.
How emotional contexts modulate item memory in individuals with high and low negative affect and worry
Authors: Becker Nina , Kühn Simone , Olsson Andreas
Published: May 2024

Emotional stimuli are usually remembered with high confidence. Yet, it remains unknown whether—in addition to memory for the emotional stimulus itself—memory for a neutral stimulus encountered just after an emotional one can be enhanced. Further, little is known about the interplay between emotion elicited by a stimulus and emotion relating to affective dispositions. To address these questions, we examined (1) how emotional valence and arousal of a context image preceding a neutral item image affect memory of the item, and (2) how such memory modulation is affected by two hallmark features of emotional disorders: trait negative affect and tendency to worry. In two experiments, participants encoded a series of trials in which an emotional (negative, neutral, or positive) context image was followed by a neutral item image. In experiment 1 (n= 42), items presented seconds after negative context images were remembered better and with greater confidence compared to those presented after neutral and positive ones. Arousal ratings of negative context images were higher compared to neutral and positive ones and the likelihood of correctly recognizing an item image was related to higher arousal of the context image. In experiment 2 (n= 59), better item memory was related to lower trait negative affect. Participants with lower trait negative affect or tendency to worry displayed higher confidence compared to those with high negative affect or tendency to worry. Our findings describe an emotional “carry-over” effect elicited by a context image that enhances subsequent item memory on a trial-by-trial basis, however, not in individuals with high trait negative affect who seem to have a general memory disadvantage.
Ultrafast Raman thermometry in driven
YBa2Cu3O6.48
Authors: Chou T.-H. , Först M. , Fechner M. , Henstridge M. , Roy S. , Buzzi M. , Nicoletti D. , Liu Y. , Nakata S. , Keimer B. , Cavalleri A.
Published: May 2024

Signatures of photoinduced superconductivity have been reported in cuprate materials subjected to a coherent phonon drive. A “cold” superfluid was extracted from the transient Terahertz conductivity and was seen to coexist with “hot” uncondensed quasiparticles, a hallmark of a driven-dissipative system of which the interplay between coherent and incoherent responses is not well understood. Here, time resolved spontaneous Raman scattering was used to probe the lattice temperature in the photoinduced superconducting state of YBa2Cu3O6.48. An increase in lattice temperature of up to 140 K was observed by measuring the time dependent Raman scattering intensity of an undriven “spectator” phonon mode. This value is consistent with the estimated increase in quasiparticle temperature measured under the same excitation conditions. These temperature changes provide quantitative information on the nature of the driven state and its decay, and may suggest a strategy to optimize this effect.

Published by the American Physical Society
2024