bluuebunny/crossref_metadata_2025_split huggingface dataset:
Key Enzymes for the Mevalonate Pathway in the Cardiovascular System
Authors: Zhang Chi , Jin Dan-Dan , Wang Xi-Ying , Lou Lian , Yang Jian 
Published: February 2021

Abstract:
Isoprenylation is an important post-transcriptional modification of small GTPases required for their activation and function. Isoprenoids, including farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate, are indispensable for isoprenylation by serving as donors of a prenyl moiety to small G proteins. In the human body, isoprenoids are mainly generated by the mevalonate pathway (also known as the cholesterol-synthesis pathway). The hydroxymethylglutaryl coenzyme A reductase catalyzes the first rate-limiting steps of the mevalonate pathway, and its inhibitor (statins) are widely used as lipid-lowering agents. In addition, the FPP synthase is also of critical importance for the regulation of the isoprenoids production, for which the inhibitor is mainly used in the treatment of osteoporosis. Synthetic FPP can be further used to generate geranylgeranyl pyrophosphate and cholesterol. Recent studies suggest a role for isoprenoids in the genesis and development of cardiovascular disorders, such as pathological cardiac hypertrophy, fibrosis, endothelial dysfunction, and fibrotic responses of smooth-muscle cells. Furthermore, statins and FPP synthase inhibitors have also been applied for the management of heart failure and other cardiovascular diseases rather than their clinical use for hyperlipidemia or bone diseases. In this review, we focus on the function of several critical enzymes, including hydroxymethylglutaryl coenzyme A reductase, FPP synthase, farnesyltransferase, and geranylgeranyltransferase in the mevalonate pathway which are involved in regulating the generation of isoprenoids and isoprenylation of small GTPases, and their pathophysiological role in the cardiovascular system. Moreover, we summarize recent research into applications of statins and the FPP synthase inhibitors to treat cardiovascular diseases, rather than for their traditional indications respectively.
How We Assess Spatial Neglect Matters
Authors: Gillen Robert W. , Fusco-Gessick Benjamin , Harmon Erin Y. 
Published: February 2021

Objective
The aim of this study was to determine the prevalence and functional impact of unilateral spatial neglect on right hemisphere stroke patients in an inpatient rehabilitation facility using a multidimensional, functionally based behavioral measure (Catherine Bergego Scale [CBS]).

Design
This was a retrospective cohort study of 742 consecutive admissions of patients with right hemispheric stroke to an inpatient rehabilitation facility. Spatial neglect was assessed using the CBS. Functional impact of neglect was measured by hospital length of stay, Functional Independence Measure change per day, discharge destination, and number of falls.

Results
As measured by the CBS, 86% of the right hemisphere stroke patients had symptoms of spatial neglect. Moderate and severe neglect was associated with less Functional Independence Measure change per day and lower rates of community discharge. The presence of neglect was not significantly associated with fall rate or length of hospital stay after controlling for admission Functional Independence Measure scores and age. The “difficulty looking left” CBS item had the strongest relationship with total CBS scores and effectively predicted Functional Independence Measure change per day and discharge destination.

Conclusions
Using a sensitive measure, the CBS, rates of spatial neglect are extremely high in right hemisphere stroke patients entering inpatient rehabilitation. Both identification and determination of neglect severity are extremely important given their significant relationship to rehabilitation outcomes and discharge destinations.

To Claim CME Credits
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CME Objectives
Upon completion of this article, the reader should be able to (1) describe why carefully assessing spatial neglect in right hemisphere stroke patients is important; (2) identify multiple dimensions of spatial neglect assessed by the Catherine Bergego Scale and how this approach differs from traditional paper and pencil assessment methods; and (3) describe the relationship between spatial neglect as measured by the Catherine Bergego Scale and functional outcomes of right hemisphere stroke patients in inpatient rehabilitation settings.

Level
Advanced

Accreditation
The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
The Association of Academic Physiatrists designates this journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
The UCR Minicore: a valuable resource for cowpea research and breeding
Authors: Muñoz-Amatriaín María , Lo Sassoum , Herniter Ira A. , Boukar Ousmane , Fatokun Christian , Carvalho Márcia , Castro Isaura , Guo Yi-Ning , Huynh Bao-Lam , Roberts Philip A. , Carnide Valdemar , Close Timothy J. 
Published: February 2021

ABSTRACTIncorporation of new sources of genetic diversity into plant breeding programs is crucial for continuing to improve yield and quality, as well as tolerance to abiotic and biotic stresses. A minicore (the “UCR Minicore”) composed of 368 worldwide accessions of cultivated cowpea has been assembled, having been derived from the University of California, Riverside cowpea collection. High-density genotyping with 51,128 SNPs followed by principal component and genetic assignment analyses identified six subpopulations in the UCR Minicore, mainly differentiated by cultivar group and geographic origin. All six subpopulations were present to some extent in West African material, suggesting that West Africa is a center of diversity for cultivated cowpea. Additionally, population structure analyses supported two routes of introduction of cowpea into the U.S.: (1) from Spain to the southwest U.S. through Northern Mexico, and (2) from Africa to the southeast U.S. via the Caribbean. Genome-wide association studies (GWAS) of important agronomic traits including flowering time, resulted in the identification of significant SNPs for all traits and environments. The mapping resolution achieved by high-density genotyping of this diverse minicore collection allowed the identification of strong candidate genes, including orthologs of the ArabidopsisFLOWERING LOCUS T.In summary, this diverse, yet compact cowpea collection constitutes a suitable resource to identify loci controlling complex traits, consequently providing markers to assist with breeding to improve this crop of high relevance to global food and nutritional security.
Identifying the genetic basis and molecular mechanisms underlying phenotypic correlation between complex human traits using a gene-based approach
Authors: Gu Jialiang , Fuller Chris , Zheng Jiashun , Li Hao 
Published: February 2021

AbstractPhenotypic correlations between complex human traits have long been observed based on epidemiological studies. However, the genetic basis and underlying mechanisms are largely unknown. The recent accumulation of GWAS data has made it possible to analyze the genetic similarity between human traits through comparative analysis. Here we developed a gene-based approach to measure genetic similarity between a pair of traits and to delineate the shared genes/pathways, through three steps: 1) translating SNP-phenotype association profile to genephenotype association profile by integrating GWAS with eQTL data; 2) measuring the similarity between a pair of traits by a normalized distance between the two gene-phenotype association profiles; 3) delineating genes/pathways supporting the similarity. Application of this approach to a set of GWAS data covering 59 human traits detected significant similarity between many known and unexpected pairs of traits; a significant fraction of them are not detectable by SNP based similarity measures. Examples include Height and Schizophrenia, Cancer and Alzheimer’s Disease, and Rheumatoid Arthritis and Crohn’s disease. Functional analysis revealed specific genes/pathways shared by these pairs. For example, Height and Schizophrenia are co-associated with genes involved in neural development, skeletal muscle regeneration, protein synthesis, magnesium homeostasis, and immune response, suggesting growth and development as a common theme underlying both traits. Our approach can detect yet unknown relationships between complex traits and generate mechanistic hypotheses, and has the potential to improve diagnosis and treatment by transferring knowledge from one disease to another.
Neuroprotective and Mitoprotective Effects of Lemon IntegroPectin on SH-SY5Y Cells
Authors: Nuzzo Domenico , Picone Pasquale , Giardina Costanza , Scordino Miriana , Mudò Giuseppa , Pagliaro Mario , Scurria Antonino , Meneguzzo Francesco , Ilharco Laura M. , Fidalgo Alexandra , Presentato Alessandro , Alduina Rosa , Ciriminna Rosaria , Di Liberto Valentina 
Published: February 2021

AbstractLemon IntegroPectin obtained via hydrodynamic cavitation of organic lemon processing waste in water shows significant neuroprotective activityin vitro, as first reported in this study investigating the effects of both lemon IntegroPectin and commercial citrus pectin on cell viability, cell morphology, reactive oxygen species (ROS) production and mitochondria perturbation induced by treatment of neuronal SH-SY5Y human cells with H2O2. Mediated by ROS including H2O2and its derivatives, oxidative stress alters numerous cellular processes, including mitochondrial regulation and cell signaling, propagating cellular injury that leads to incurable neurodegenerative diseases. These results, and the absence of toxicity of this new pectic substance rich in adsorbed flavonoids and terpenes, support further investigations to verify its activity in preventing, retarding, or even curing neurological diseases.
Modeling changes in vascular and extracellular matrix integrity that can occur in decellularized kidneys after implantation
Authors: Corridon Peter R. 
Published: February 2021

AbstractA method was established to identify alterations in vascular patency and extracellular matrix integrity of decellularized porcine kidney scaffolds. These scaffolds were perfused with blood at physiologically normal (500 and 650 ml/min) and abnormal (200 ml/min) rates. Variations in venous outflow were then assessed over 24 hours. Angiographic data confirmed that standard arterial branching patterns and the integrity of the extracellular matrix were considerably disrupted. Scaffolds subjected to normal arterial perfusion rates observed drops in venous outflow across the 24 hours. These reductions rose from roughly 40% after 12 hours to 60% after 24 hours. At the end of the test period, regardless of the underlying damage that occurred, the kidneys appeared intact on the surface, and there were no apparent signs of clotting. In comparison, venous flow rates decreased by 80 to 100% across the 24 hours in acellular scaffolds subjected to a far lower perfusion rate of 200 ml/min. These kidneys also appeared intact after 24 hours of perfusion, but presented several arterial, venous, and ureteral clots. The results of this study provide insight into circumstances that limit scaffold viability and provide a simplified model to analyze other conditions that can better prepare scaffolds for long-term transplantation.
Effects of Perinatal Fluoxetine Exposure on Novelty-induced Social and Non-Social Investigation Behaviors in a Seminatural Environment
Authors: Sylte Ole Christian , Johansen Jesper Solheim , Heinla Indrek , Houwing Danielle J , Olivier Jocelien DA , Heijkoop Roy , Snoeren Eelke MS 
Published: February 2021

AbstractSelective serotonin reuptake inhibitors (SSRIs) are increasingly prescribed as medication for various affective disorders during pregnancy. SSRIs cross the placenta and affect serotonergic neurotransmission in the fetus, but the neurobehavioral consequences for the offspring remain largely unclear. Recent rodent research has linked perinatal SSRI exposure to alterations in both social and non-social aspects of behavior. However, this research has mainly focused on behavior within simplified environments. The current study investigates the effects of perinatal SSRI exposure on social and non-social investigation behaviors of adult rat offspring upon introduction to a novel seminatural environment with unknown conspecifics. During the perinatal period (gestational day 1 until postnatal day 21), rat dams received daily treatment with either an SSRI (fluoxetine, 10 mg/kg) or vehicle. Adult male and female offspring were observed within the first hour after introduction to a seminatural environment. The results showed that perinatal fluoxetine exposure altered aspects of non-social investigation behaviors, while not altering social investigation behaviors. More specifically both fluoxetine exposed males and females spent more total time on locomotor activity than controls. Furthermore, fluoxetine exposed females spent less time exploring objects and specific elements in the environment. The data suggest that perinatal exposure to SSRIs leads to a quicker, less detailed investigation strategy in novel environments, and that the alteration is mostly pronounced in females.
Medicago SPX1 and SPX3 regulate phosphate homeostasis, mycorrhizal colonization and arbuscule degradation
Authors: Wang Peng , Snijders Roxane , Kohlen Wouter , Liu Jieyu , Bisseling Ton , Limpens Erik 
Published: February 2021

AbstractTo acquire sufficient mineral nutrients such as phosphate (Pi) from the soil, most plants engage in a symbiosis with arbuscular mycorrhizal (AM) fungi. Attracted by plant-secreted strigolactones, the fungi colonize the roots and form highly-branched hyphal structures called arbuscules inside inner cortex cells. It is essential that the host plant controls the different steps of this interaction to maintain its symbiotic nature. However, how plants sense the amount of Pi obtained from the fungus and how this determines the arbuscule lifetime is far from understood. Here, we show thatMedicago truncatulaSPX-domain containing proteins SPX1 and SPX3 regulate root phosphate starvation responses as well as fungal colonization and arbuscule degradation.SPX1andSPX3are induced upon phosphate starvation but become restricted to arbuscule-containing cells upon establishment of the symbiosis. Under Pi-limiting conditions they facilitate the expression of the strigolactone biosynthesis geneDWARF27, which correlates with increased fungal branching by root exudates and increased root colonization. Later, in the arbuscule-containing cells SPX1 and SPX3 redundantly control the timely degradation of arbuscules. This regulation does not seem to involve direct interactions with known transcriptional regulators of arbuscule degradation. We propose a model where SPX1 and SPX3 control arbuscule degeneration in a Pi-dependent manner via a yet-to-identify negative regulator.
Abscisic-acid-dependent regulation ofArabidopsis thalianaammonium transport relies on ABI1 control of CIPK23 and AMT1
Authors: Ganz Pascal , Porras-Murillo Romano , Ijato Toyosi , Menz Jochen , Straub Tatsiana , Stührwohldt Nils , Moradtalab Narges , Ludewig Uwe , Neuhäuser Benjamin 
Published: February 2021

SummaryAmmonium uptake at plant roots is regulated at the transcriptional, post-transcriptional and post-translational levels. Phosphorylation by the protein kinase CIPK23 transiently inactivates the ammonium transporters (AMT1s) but the phosphatases activating AMT1s remain unknown. Here, we have identified the PP2C phosphatase ABI1 as an activator of AMTs inArabidopsis thaliana. We show that high external ammonium concentrations elevate the stress phytohormone abscisic acid (ABA) by de-glycosylation. Active ABA is sensed by ABI1-PYL complexes followed by the inactivation of ABI1 activating CIPK23. Under favourable growth conditions, ABI1 reduces AMT1 phosphorylation, both by binding and inactivating CIPK23, and by the direct dephosphorylation of AMT1s. Thus, ABI1 is a positive regulator of ammonium uptake, coupling nutrient acquisition to abiotic stress signalling. Elevated ABA reduces ammonium uptake during stress situations, such as ammonium toxicity, whereas ABI1 reactivates AMT1s under favourable growth conditions.
A molecular framework for control of oriented cell division in the Arabidopsis embryo
Authors: Vaddepalli Prasad , de Zeeuw Thijs , Strauss Sören , Bürstenbinder Katharina , Liao Che-Yang , Smith Richard , Weijers Dolf 
Published: February 2021

SummaryPremitotic control of cell division orientation is critical for plant development, as cell walls prevent extensive cell remodelling or migration. Whilst many divisions are proliferative and add cells to existing tissues, some divisions are formative, and generate new tissue layers or growth axes. Such formative divisions are often asymmetric in nature, producing daughters with different fates. We have previously shown that in theArabidopsis thalianaembryo, developmental asymmetry is correlated with geometric asymmetry, creating daughter cells of unequal volume. Such divisions are generated by division planes that deviate from a default “minimal surface area” rule. Inhibition of auxin response leads to reversal to this default, yet the mechanisms underlying division plane choice in the embryo have been unclear. Here we show that auxin-dependent division plane control involves alterations in cell geometry, but not in cell polarity or nuclear position. Through transcriptome profiling, we find that auxin regulates genes controlling cell wall and cytoskeleton properties. We confirm the involvement of microtubule (MT)-binding proteins in embryo division control. Topology of both MT and Actin cytoskeleton depend on auxin response, and genetically controlled MT or Actin depolymerization in embryos leads to disruption of asymmetric divisions, including reversion to the default. Our work shows how auxin-dependent control of MT- and Actin cytoskeleton properties interacts with cell geometry to generate asymmetric divisions during the earliest steps in plant development.
Ectomycorrhizas accelerate decomposition to a greater extent than arbuscular mycorrhizas in a northern deciduous forest
Authors: Carteron Alexis , Cichonski Fabien , Laliberté Etienne 
Published: February 2021

AbstractIt has been proposed that ectomycorrhizal (EcM) fungi slow down decomposition by competing with free-living saprotrophs for organic nutrients and other soil resources (known as the “Gadgil effect”), thereby increasing soil carbon sequestration. As such, this Gadgil effect should depend on soil organic matter age and quality, but this remains unstudied. In addition, the Gadgil effect is not expected to occur in arbuscular mycorrhizal (AM) forests since AM fungi cannot access directly nutrients from soil organic matter, yet few direct comparisons between EcM and AM forests have been made. We performed a two-year reciprocal decomposition experiment of soil organic horizons (litter - L, fragmented - F, humic - H) in adjacent temperate deciduous forests dominated by EcM or AM trees. Litterbags were made of different mesh sizes allowing or excluding ingrowth of external fungal hyphae, which are primarily mycorrhizal in these forests other than for the most-recent superficial litter horizon. As expected, organic matter originating from deeper horizons and from EcM forests was of lower quality (e.g. higher lignin to nitrogen ratios) and decomposed more slowly. However, contrary to the Gadgil effect, organic matter exposed to external fungal hyphae (i.e. primarily mycorrhizal) actually decomposed faster in both forest types, and this effect was strongest in EcM forests, particularly in the F horizon. Unexpectedly, organic matter decomposition was faster in EcM than in AM forests, regardless of organic matter origin. Overall, our study reinforces the view that temperate EcM forests store greater amounts of soil organic carbon than AM forests, but suggests that this is due to factors other than the Gadgil effect.
Generating controlled gusts using vortex rings
Authors: Gupta Dipendra , Sane Sanjay P. , Arakeri Jaywant H. 
Published: February 2021

ABSTRACTThe control and stability of flying and swimming animals is typically determined by measuring their responses to discrete gust perturbations. For the rigorous measurement and analysis of such responses, it is necessary to generate gusts that are precise, controllable and repeatable. Here, we present a method to generate discrete gusts under laboratory conditions using a vortex ring. Unlike other methods of gust generation, the vortex ring can be well characterized and is highly controllable. We first outline the theoretical basis for the design of a gust generator, and then describe an apparatus that we developed to generate discrete gusts. As a case study, we tested the efficacy of this method on freely-flying soldier fliesHermetia illucens. The method described here can be used to study diverse phenomena ranging from natural flight and swimming in insects, birds, bats and fishes, to the artificial flight of drones and micro-aerial vehicles.
A masculinizing supergene underlies an exaggerated male reproductive morph in a spider
Authors: Hendrickx Frederik , De Corte Zoë , Sonet Gontran , Belleghem Steven M. Van , Köstlbacher Stephan , Vangestel Carl 
Published: February 2021

AbstractIn many species, individuals can develop into strikingly different morphs, which are determined by a simple Mendelian locus. How selection shapes loci that control complex phenotypic differences remains poorly understood. In the spiderOedothorax gibbosus, males either develop into a ‘hunched’ morph with conspicuous head structures or as a fast developing ‘flat’ morph with a female-like appearance. We show that the hunched-differs from the flat-determining allele by a hunch-specific genomic fragment of approximately 3 megabases. This fragment comprises dozens of genes that duplicated from genes found at different chromosomes. All functional duplicates, includingdoublesex- a key sexual differentiation regulatory gene, show male-specific expression, which illustrates their combined role as a masculinizing supergene. Our findings demonstrate how extensive indel polymorphisms and duplications of regulatory genes may contribute to the evolution of co-adapted gene clusters, sex-limited reproductive morphs, and the enigmatic evolution of exaggerated sexual traits in general.
Signaling amplitude molds theRasmutation tropism of urethane
Authors: Li Siqi , Counter Christopher M. 
Published: February 2021

AbstractRAS genes are commonly mutated in cancers yet despite many possible mutations, cancers have a ‘tropism’ towards a specific subset. As driver mutations, these patterns ostensibly originate from normal cells. High oncogenic RAS activity causes oncogenic stress and different oncogenic mutations can impart different levels of activity. Here we show that changing rare codons to common in the murineKrasgene to increase translation shifts tumors induced by the carcinogen urethane from arising from canonical Q61to biochemically less active G12Krasdriver mutations, despite the carcinogen still being biased towards generating Q61mutations. Loss of p53 to blunt oncogenic stress partially reversed this effect, restoring Q61mutations. Finally, transcriptional analysis revealed similar signaling amongst tumors driven by different mutations andKrasalleles. These finding suggest that the RAS mutation tropism of urethane is largely product of selection in normal cells for mutations promoting proliferation without causing oncogenic stress.Impact statementThe bias towards specificKrasdriver mutations during urethane carcinogenesis appears to arise predominantly from the selection of a narrow window of oncogenic signaling in normal cells.