bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comprehensive analysis of grazing: Improving management for environmental health
Authors: Niederman Talia E. , Xu Ashley L. , Dreiss Lindsay M. 
Published: June 2023

AbstractIn an effort to combat the dual climate and biodiversity crises, the international community has put forth targets to reduce emissions and protect species. Habitat degradation is at the fore in driving species extinctions and carbon loss, creating an urgent need to examine our land-use practices if we are to meet international goals. Individual nations will have differing needs and approaches to reaching these objectives based on their landscapes, industries, and levels of historic overuse. In the United States, grazing is the leading land-use, making up approximately one-third of the country. Here we present a broad-scale analysis of how grazing effects the environment and examine how this land-use plays out across the U.S. This review can help policy makers and land managers strategically assess grazing lands as we work towards a national landscape that supports equitable ecosystem services, sustainable livelihoods, and climate resilience.HighlightsLivestock grazing can have a multitude of effects on local ecosystems often causing habitat degradation and loss. As this land-use makes up a third of U.S. lands, improving grazing practices could provide significant benefits for the environment.To our knowledge, this is the largest review of U.S. grazing to date. We explore how grazing affects six elements of the environment across the country.While the majority of literature discusses negative implications related to grazing, our results indicate that regions are affected differently, and that management and livestock-type also contribute to the overall environmental impact.
Clinical spine care partnerships between low- and high-resource countries: A scoping review
Authors: Lin Hannah , Halvorsen Kristin , Win Myat Thu , Yancey Michael , Rbil Nada , Chatterjee Abhinaba , Jivanelli Bridget , Khormaee Sariah 
Published: June 2023

AbstractBackgroundClinical collaboration between spine professionals in high-resource (HR) and low-resource (LR) countries may provide improvements in the accessibility, efficacy, and safety of global spine care. Currently, the scope and effectiveness of these collaborations remain unclear. In this review, we describe the literature on the current state of these partnerships to provide a framework for exploring future best practices.MethodsPubMed, Embase, and Cochrane Library were queried for articles on spine-based clinical partnerships between HR and LR countries published between 2000 and March 10, 2023. This search yielded 1528 total publications. After systematic screening, nineteen articles were included in the final review.ResultsAll published partnerships involved direct clinical care and 13/19 included clinical training of local providers. Most of the published collaborations reviewed involved one of four major global outreach organizations with the majority of sites in Africa. Participants were primarily physicians and physicians-in-training. Only 5/19 studies reported needs assessments prior to starting their partnerships. Articles were split on evaluative focus, with some only evaluating clinical outcomes and some evaluating the nature of the partnership itself.ConclusionsPublished studies on spine-focused clinical partnerships between HR and LR countries remain scarce. Those that are published often do not report needs assessments and formal metrics to evaluate the efficacy of such partnerships. Toward improving the quality of spine care globally, we recommend an increase in the quality and quantity of published studies involving clinical collaborations between HR and LR countries, with careful attention to reporting early needs assessments and evaluation strategies.
Computational analysis of long-range allosteric communications in CFTR
Authors: Ayca Ersoy , Bengi Altintel , Nurit Livnat Levanon , Nir Ben-Tal , Turkan Haliloglu , Oded Lewinson 
Published: June 2023

AbstractMalfunction of the CFTR protein results in cystic fibrosis, one of the most common hereditary diseases. CFTR functions as an anion channel, the gating of which is controlled by long- range allosteric communications. Allostery also has direct bearings on CF treatment: the most effective CFTR drugs modulate its activity allosterically. Herein, we integrated Gaussian Network Model, Transfer Entropy, and Anisotropic Normal Mode-Langevin dynamics and investigated the allosteric communications network of CFTR. The results are in remarkable agreement with experimental observations and mutational analysis and provide extensive novel insight. We identified residues that serve as pivotal allosteric sources and transducers, many of which correspond to disease causing mutations. We find that in the ATP-free form, dynamic fluctuations of the residues that comprise the ATP binding sites facilitate the initial binding of the nucleotide. Subsequent binding of ATP then brings to the fore and focuses dynamic fluctuations that were present in a latent and diffuse form in the absence of ATP. We demonstrate that drugs that potentiate CFTR’s conductance do so not by directly acting on the gating residues, but rather by mimicking the allosteric signal sent by the ATP binding sites. We have also uncovered a previously undiscovered allosteric “hotspot” located proximal to the docking site of the phosphorylated Regulatory (R) domain, thereby establishing a molecular foundation for its phosphorylation- dependent excitatory role. This study unveils the molecular underpinnings of allosteric connectivity within CFTR and highlights a novel allosteric “hotspot” that could serve as a promising target for the development of novel therapeutic interventions.
Engineering Yeast to Improve Heterologous Abscisic Acid Production
Authors: Otto Maximilian , Gossing Michael , David Florian , Siewers Verena 
Published: June 2023

AbstractAbscisic acid (ABA) is a high-value product with agricultural, medical and nutritional applications. We previously constructed an ABA cell factory by expressing the ABA metabolic pathway fromBotrytis cinereain the biotechnological workhorseSaccharomyces cerevisiae.In this study, we aimed to improve ABA production and explored various rational engineering targets mostly focusing on increasing the activity of two rate-limiting cytochrome P450 monooxygenases of the ABA pathway, BcABA1 and BcABA2. We evaluated the effects of overexpression and knock-down of cell membrane transporters, expression of heterologous cytochrome b5, overexpression of a rate-limiting heme biosynthesis gene and overexpression or knock-out of genes involved in ER membrane homeostasis. One of the genes involved in ER membrane homeostasis,PAH1, was identified as the most promising engineering target. Knock-out ofPAH1improved ABA titers, but also caused a sever growth defect. By replacing thePAH1promoter with a weak minimal promoter, it was possible to mediate the growth defect while still improving ABA production.In this report we were able to improve the ABA cell factory and furthermore provide valuable insights for future studies aiming to engineer cytochrome P450 monooxygenases.One-sentence summaryIn this study we explored various strategies to improve heterologous abscisic acid production inSaccharomyces cerevisiaeand identified fine-tuning of thePAH1gene as a promising engineering strategy.
CDK8 inhibitors antagonize HIV-1 reactivation and promote provirus latency in T cells
Authors: Horvath Riley M. , Brumme Zabrina L. , Sadowski Ivan 
Published: June 2023

AbstractLatent HIV-1 provirus represents a barrier towards a cure for infection, but is dependent upon the host RNA Pol II machinery for expression. We find that inhibitors of the RNA Pol II mediator kinases CDK8/19, Senexin A and BRD6989, inhibit induction of HIV-1 expression in response to latency reversing agents and T cell signaling agonists. These inhibitors were found to impair recruitment of RNA Pol II to HIV-1 LTR. HIV-1 expression in response to several latency reversal agents was impaired upon disruption ofCDK8by shRNA or gene knockout. However, the effects of CDK8 depletion did not entirely mimic CDK8/19 kinase inhibition suggesting that the mediator kinases are not functionally redundant. Furthermore, treatment of CD4+PBMCs isolated from people living with HIV-1 and who are receiving ART with Senexin A inhibited induction of virus replication in response to T cell stimulation by PMA and ionomycin. These observations indicate that the mediator kinases CDK8 and CDK19, play a significant role for regulation of HIV-1 transcription, and that small molecule inhibitors of these enzymes may contribute to therapies designed to promote deep latency involving the durable suppression of provirus expression.
Structural proteomics of a bacterial mega membrane protein complex: FtsH-HflK-HflC
Authors: Akkulak Hatice , İnce H. Kerim , Goc Gunce , Lebrilla Carlito B. , Kabasakal Burak V. , Ozcan Sureyya 
Published: June 2023

ABSTRACTRecent advances in mass spectrometry (MS) yielding sensitive and accurate measurements along with developments in software tools have enabled the characterization of complex systems routinely. Thus, structural proteomics and cross-linking mass spectrometry (XL-MS) have become a useful method for structural modeling of protein complexes. Here we utilized commonly used XL-MS software tools to elucidate the protein interactions within a membrane protein complex containing FtsH, HflK, and HflC, over-expressed inE.coli. The MS data were processed using MaxLynx, MeroX, MS Annika, xiSEARCH, and XlinkX software tools. The number of identified inter- and intra-protein cross-links varied among software. Each interaction was manually checked using the raw MS and MS/MS data and distance restraints to verify inter- and intra-protein cross-links. A total of 37 inter-protein and 148 intra-protein cross-links were determined in the FtsH-HflK-HflC complex. The 59 of them were new interactions on the lacking region of recently published structures. These newly identified interactions, when combined with molecular docking and structural modeling, present opportunities for further investigation. The results provide valuable information regarding the complex structure and function to decipher the intricate molecular mechanisms underlying the mega FtsH-HflK-HflC complex.Abstract FigureGraphical AbstractThe overall workflow of XL-MS analysis: the steps of XL-MS studies applied to the two samples taken from different stages of purification process of mega membrane protein complex FtsH-HflC-HflK.
Oxygen production via NO dismutation in different ammonia oxidizers
Authors: Hernández-Magaña A. Elisa , Canfield Donald E. , Kraft Beate 
Published: June 2023

AbstractAmmonia oxidizing archaea (AOA) are widespread and highly abundant in nature. Despite their typical aerobic metabolism, they can be abundant in ecosystems where oxygen is scarce. Recent observations revealed that the AOA isolateNitrosopumilus maritimusproduces oxygen and dinitrogen at nanomolar concentrations, upon oxygen depletion through nitric oxide (NO) dismutation. Here, we explore NO dismutation capability in other ammonia oxidizers with different phylogenetic affinities and from different environmental settings. The organisms explored include three marine AOA, one soil AOA and two soil ammonia-oxidizing bacteria (AOB). Upon oxygen depletion all isolates accumulated oxygen. In incubations with15N tracers with ongoing oxygen accumulation, the AOA strainsNitrosopumilus adriaticusandNitrosopumilus viennensisproduced46N2O from nitrite. Transient46N2O accumulation followed by30N2production was detected in the AOA strainsNitrosopumilus piranensisandNitrosopumilussp. CCS1, supporting the earlier observation that NO-dismutation is a common metabolism in AOA, albeit with physiological variations between different strains. An important physiological variable is the capability to reduce N2O to N2. The finding of oxygen production in several AOA, as well as AOB, indicates that this process is widely distributed among the tree of life and adds an explanation for their abundance in oxygen-depleted environments.
Segmental Duplications Drive the Evolution of Accessory Regions in a Major Crop Pathogen
Authors: van Westerhoven A.C. , Aguilera-Galvez C. , Nakasato-Tagami G. , Shi-Kunne X. , Martinez de la Parte E. , Chavarro-Carrero E. , Meijer H.J.G. , Feurtey A. , Maryani N. , Ordóñez N. , Schneiders H. , Nijbroek K. , Wittenberg A. H. J. , Hofstede R. , García-Bastidas F. , Sørensen E.H. , Swennen R. , Drenth A. , Stukenbrock E.H. , Kema G.H.J. , Seidl M.F. 
Published: June 2023

AbstractMany pathogens evolved compartmentalized genomes with conserved core and variable accessory regions which carry effector genes mediating virulence. The fungal plant pathogenFusarium oxysporumhas such accessory regions often spanning entire chromosomes. The presence of specific accessory regions influences the host range, and horizontal transfer of some accessory regions can modify the pathogenicity of the receiving strain. However, understanding how these accessory regions evolve in strains that infect the same host remains limited.Here, we define the pan-genome of 69 diverseFusariumstrains that cause Fusarium wilt of banana, a significant constraint to global banana production. In this diverse panel ofFusariumstrains infecting banana, we analyzed the diversity and evolution of the accessory regions.Accessory regions inFusariumstrains infecting the same banana cultivar are highly diverse, and we could not identify any shared genomic regions and in planta induced effectors. We demonstrate that segmental duplications drive the evolution of accessory regions. Furthermore, we show that recent segmental duplications and aneuploidy occur specifically in accessory chromosomes and cause the expansion of accessory regions inF. oxysporum.Taken together we conclude that extensive recent duplications drive the evolution of accessory regions inFusarium, which contribute to the evolution of virulence.
Impact of Point Mutation on Shiga-like Toxin 1: A Molecular Dynamics Simulation Study
Authors: Tabassum Nisat , Paul Bristi Rani , Saddam Md. , Uddin Helal Md Mostofa , Paul Susanta 
Published: June 2023

AbstractThe causative agent of gastroenteritis is Shiga toxin, which belongs to a functionally and structurally associated protein family despite each individual having a unique amino acid sequence. After entering the ER lumen and relocating the toxic domain to the cytoplasm, they alter the large subunit of rRNA, preventing protein synthesis and ribosomal damage. Shiga-like toxin-1 (SLT-1) subunit B targets glycolipid receptor Gb3, which plays a significant role in cytotoxicity. Though the mutational effect on subunit B is important for cytotoxicity study, we lack better understanding. Our present study targets the mutational impact of glycine protein at their 62thamino acid sequence of subunit B. For example, how it can alter the receptor-binding capacity and virulence. We used in silico method with GROMACS software suite (version 5.2, 2020.1) on Google Colab for a 100ns (100,000ps) simulation period and UCSF Chimera software for visualizing mutant and wild-type structure similarities. Surprisingly, RMSD, RMSF, and Rg trajectories from the simulation analysis indicated a more stable and compact mutant structure than the wild type. Principle component analysis (PCA) and SASA were visualized for the entire 100ns, which pointed towards homogeneity between both structures and more solvent accessibility in the mutant structure. This mutation may elevate receptor-binding and virulence capacity. Moreover, this finding can offer a better insight for future vaccine production.
Limiting Pool and Actin Architecture Controls Myosin Cluster Sizes in Adherent Cells
Authors: Chou Wen-hung , Molaei Mehdi , Wu Huini , Oakes Patrick W. , Beach Jordan R. , Gardel Margaret L. 
Published: June 2023

AbstractThe actomyosin cytoskeleton generates mechanical forces that power important cellular processes, such as cell migration, cell division, and mechanosensing. Actomyosin self-assembles into contractile networks and bundles that underlie force generation and transmission in cells. A central step is the assembly of the myosin II filament from myosin monomers, regulation of which has been extensively studied. However, myosin filaments are almost always found as clusters within the cell cortex. While recent studies characterized cluster nucleation dynamics at the cell periphery, how myosin clusters grow on stress fibers remains poorly characterized. Here, we utilize a U2OS osteosarcoma cell line with endogenously tagged myosin II to measure the myosin cluster size distribution in the lamella of adherent cells. We find that myosin clusters can grow with Rho-kinase (ROCK) activity alone in the absence of myosin motor activity. Time-lapse imaging reveals that myosin clusters grow via increased myosin association to existing clusters, which is potentiated by ROCK-dependent myosin filament assembly. Enabling myosin motor activity allows further myosin cluster growth through myosin association that is dependent on F-actin architecture. Using a toy model, we show that myosin self-affinity is sufficient to recapitulate the experimentally observed myosin cluster size distribution, and that myosin cluster sizes are determined by the pool of myosin available for cluster growth. Together, our findings provide new insights into the regulation of myosin cluster sizes within the lamellar actomyosin cytoskeleton.
Autonomous and non-cell autonomous etiology of ciliopathy associated structural birth defects
Authors: Francis Richard , San Agustin Jovenal T , Szabo Rogers Heather L. , Cui Cheng , Jonassen Julie A. , Eguether Thibaut , Follit John A. , Lo Cecilia W. , Pazour Gregory J. 
Published: June 2023

AbstractCiliopathies are associated with wide spectrum of structural birth defects (SBD), indicating important roles for cilia in development. Here we provide novel insights into the temporospatial requirement for cilia in SBDs arising from deficiency inIft140, an intraflagellar transport protein regulating ciliogenesis.Ift140deficient mice exhibit cilia defects accompanied by wide spectrum of SBDs including macrostomia (craniofacial defects), exencephaly, body wall defects, tracheoesophageal fistula, randomized heart looping, congenital heart defects (CHD), lung hypoplasia, renal anomalies, and polydactyly. Tamoxifen inducible CAG-Cre deletion of a floxedIft140allele between E5.5 to 9.5 revealed early requirement forIft140in left-right heart looping regulation, mid to late requirement for cardiac outflow septation and alignment, and late requirement for craniofacial development and body wall closure. Surprisingly, CHD was not observed with four Cre drivers targeting different lineages essential for heart development, but craniofacial defects and omphalocele were observed with Wnt1-Cre targeting neural crest and Tbx18-Cre targeting epicardial lineage and rostral sclerotome through which trunk neural crest cells migrate. These findings revealed cell autonomous role of cilia in cranial/trunk neural crest mediated craniofacial and body wall closure defects, while non-cell autonomous multi-lineage interactions underlie CHD pathogenesis, revealing unexpected developmental complexity for CHD associated with ciliopathy.
Metabolic adaptations leading to lignification in wheat roots under salinity stress
Authors: Dissanayake Bhagya M. , Staudinger Christiana , Ranathunge Kosala , Munns Rana , Rupasinghe Thusitha W. , Taylor Nicolas L. , Millar A. Harvey 
Published: June 2023

AbstractAnalysis of salinity tolerance processes in wheat has focused on salt exclusion from shoots while root phenotypes have received limited attention. Here we consider the varying phenotypic response of four bread wheat varieties that differ in their type and degree of salt tolerance and consider in detail their molecular responses to salinity and changes in root cell wall lignification. These varieties were Westonia introgressed withNax1andNax2root sodium transporters (HKT1;5-A) that reduce Na+accumulation in leaves, as well as the ‘tissue tolerant’ Portugese landrace Mocho de Espiga Branca that has a mutation in the homologous geneHKT1;5-Dand has high Na+concentration in leaves. These three varieties were compared with the more salt-sensitive cultivar Gladius. Through the use of root structural analysis, ion concentrations, as well as differential proteomics and targeted metabolomics we provide an integrated view of the wheat root response to salinity. We show different metabolic re-arrangements in energy conversion, primary metabolic machinery and phenylpropanoid pathway leading to monolignol production in a genotype and genotype by treatment dependent manner that alters the extent and localisation of root lignification which correlated with an improved capacity of wheat roots to cope better under salinity stress.
Characterising genome composition and large structural variation in banana varietal groups
Authors: Higgins Janet , Osorio-Guarín Jaime Andrés , Olave-Achury Carolina , Toloza-Moreno Deisy Lisseth , Enriquez Ayda , Palma Federica Di , Yockteng Roxana , De Vega José J. 
Published: June 2023

ABSTRACTBackgroundBananas and plantains (Musaspp.)are one of the most important crops worldwide. The cultivated varieties are vegetatively propagated, and their diversity is essentially fixed over time. Nevertheless, millennia of diversification and selection have led to hundreds of edible varieties.M. acuminataandM. balbisianarespectively provided the A and B subgenomes that mostly constitute these varieties. Here we aimed to characterise chromosomal exchanges and structural variation among lineages to understand shared foundational events and identify sources of allelic diversity in introgressed loci for genetic improvement.MethodsWe identified clonal somatic groups among 188 banana and plantain accessions introduced for cropping in Colombia, using admixture, principal component, and phylogenetic analyses. We established a new alignment-based metric, namedRelative Averaged Alignment(RAA), to infer subgenome composition (AA, AAB, etc.). We later used comparisons in read coverage along conserved chromosomal windows between the A, B, and S subgenomes to identify introgressions.ResultsIn our panel, we identify ten varietal groups composed of somatic clones, plus three groups of tetraploid accessions. We demonstrated RAA can be used to infer subgenome composition in the total genome and individual chromosomes. We identified 20 introgressions, several newly reported, among the AAB and ABB varieties. We did not observe B-donor introgression in any AA/AAA varietal groups. We identified variation in length in at least two introgressions, a B-donor introgression in chromosome 7 between the “Maoli” and a “Popoulu” subdivisions, and an S-donor (M. schizocarpa) introgression in chromosome 2 in four varietal groups with different compositions (AAA, AAB, ABB, and AA).ConclusionsThe extensive distribution of introgressions and the variation in the length of some introgressions between varieties support that the emergence of many varieties can be attributed to intricate founding events, which encompassed multiple instances of hybridisation and subsequent residual backcrossing. We also showed the contribution ofM. schizocarpato four cultivated varieties, and proposed subdivision-specific intergenomic recombination in chromosome 7 between subgroups Maoli and Popoulu plantains. Introgressed loci over these 20 introgressions likely provide an extensive resource of allelic diversity to further explore their contribution to disease resistance, climatic adaption, etc. and potential for exploiting in breeding and genome editing.