Miracle-dz/UniFAR-FTUs huggingface dataset:
Allelic Variation in the Chloroplast Division Gene FtsZ2-2 Leads to Natural Variation in Chloroplast Size1[OPEN]

Genetic mapping in Arabidopsis and analysis of sequences in the 1001 Genomes database reveal allelic variation in a chloroplast division gene is associated with natural variation in chloroplast size. Chloroplast size varies considerably in nature, but the underlying mechanisms are unknown. By exploiting a near-isogenic line population derived from a cross between the Arabidopsis (Arabidopsis thaliana) accessions Cape Verde Islands (Cvi-1), which has larger chloroplasts, and Landsberg erecta (Ler-0), with smaller chloroplasts, we determined that the large-chloroplast phenotype in Cvi-1 is associated with allelic variation in the gene encoding the chloroplast-division protein FtsZ2-2, a tubulin-related cytoskeletal component of the contractile FtsZ ring inside chloroplasts. Sequencing revealed that the Cvi-1 FtsZ2-2 allele encodes a C-terminally truncated protein lacking a region required for FtsZ2-2 interaction with inner-envelope proteins, and functional complementation experiments in a Columbia-0 ftsZ2-2 null mutant confirmed this allele as causal for the increased chloroplast size in Cvi-1. Comparison of FtsZ2-2 coding sequences in the 1001 Genomes database showed that the Cvi-1 allele is rare and identified additional rare loss-of-function alleles, including a natural null allele, in three other accessions, all of which had enlarged-chloroplast phenotypes. The ratio of nonsynonymous to synonymous substitutions was higher among the FtsZ2-2 genes than among the two other FtsZ family members in Arabidopsis, FtsZ2-1, a close paralog of FtsZ2-2, and the functionally distinct FtsZ1-1, indicating more relaxed constraint on the FtsZ2-2 coding sequence than on those of FtsZ2-1 or FtsZ1-1. Our results establish that allelic variation in FtsZ2-2 contributes to natural variation in chloroplast size in Arabidopsis, and they also demonstrate that natural variation in Arabidopsis can be used to decipher the genetic basis of differences in fundamental cell biological traits, such as organelle size.
Diagnostic Impact of Intracranial Vessel Wall MRI in 205 Patients with Ischemic Stroke or TIA

This was a single-center, retrospective study of 205 consecutive patients who were referred for vessel wall MR imaging to clarify the etiology of an ischemic stroke or TIA. An expert panel classified stroke etiology before and after incorporating vessel wall MR imaging results using a modified Trial of Org 10172 in Acute Stroke Treatment system. Vessel wall MR imaging altered the etiologic classification in 55% (112/205) of patients. The proportion of patients classified as having intracranial arteriopathy not otherwise specified decreased from 31% to 4% (64/205 versus 9/205) and the proportion classified as having intracranial atherosclerotic disease increased from 23% to 57%. When vessel wall MR imaging is performed to clarify the etiology of a stroke or TIA, it frequently alters the etiologic classification, which is the basis for therapeutic decision-making. BACKGROUND AND PURPOSE: Secondary prevention of ischemic stroke depends on determining the cause of the initial ischemic event, but standard investigations often fail to identify a cause or identify multiple potential causes. The purpose of this study was to characterize the impact of intracranial vessel wall MR imaging on the etiologic classification of ischemic stroke. MATERIALS AND METHODS: This was a single-center, retrospective study of 205 consecutive patients who were referred for vessel wall MR imaging to clarify the etiology of an ischemic stroke or TIA. An expert panel classified stroke etiology before and after incorporating vessel wall MR imaging results using a modified Trial of Org 10172 in Acute Stroke Treatment system. We measured the proportion of patients with an altered etiologic classification after vessel wall MR imaging. RESULTS: The median age was 56 years (interquartile range = 44–67 years), and 51% (106/205) of patients were men. Vessel wall MR imaging altered the etiologic classification in 55% (112/205) of patients. The proportion of patients classified as having intracranial arteriopathy not otherwise specified decreased from 31% to 4% (64/205 versus 9/205; P < .001) and the proportion classified as having intracranial atherosclerotic disease increased from 23% to 57% (48/205 versus 116/205; P < .001). Conventional work-up classification as intracranial arteriopathy not otherwise specified was an independent predictor of vessel wall MR imaging impact (OR = 8.9; 95% CI, 3.0–27.2). The time between symptom onset and vessel wall MR imaging was not a predictor of impact. CONCLUSIONS: When vessel wall MR imaging is performed to clarify the etiology of a stroke or TIA, it frequently alters the etiologic classification. This is important because the etiologic classification is the basis for therapeutic decision-making.
Anticipatory Salivary Cortisol and State Anxiety Before Competition Predict Match Outcome in Division I Collegiate Wrestlers.

Cintineo, HP and Arent, SM. Anticipatory salivary cortisol and state anxiety before competition predict match outcome in Division I collegiate wrestlers. J Strength Cond Res XX(X): 000-000, 2019-Anticipation of exercise and other stressors has been shown to result in physiological and psychological changes, which include increased levels of cortisol and anxiety. Combat sports, in particular, typically elicit robust anticipatory responses because of the distinct nature of these sports. Therefore, the purpose of this investigation was to examine the relationship between state anxiety scores, anticipatory cortisol response, and performance outcomes in college wrestlers. A secondary purpose was to determine the correlation between anticipatory cortisol and state anxiety scores. Twenty-six collegiate wrestlers were recruited to undergo saliva collection and to complete the State Anxiety Inventory before a wrestling match and again on a rest day in a time-matched, control session. Univariate analyses revealed that both salivary cortisol and anxiety were greater before competition than on a rest day. In addition, it was found that losers had higher levels of anticipatory cortisol and anxiety compared with winners. A significant correlation between salivary cortisol and anxiety was found as well. These data show that higher cortisol and anxiety may negatively affect performance. Athletes and coaches should work together to determine optimal levels of arousal and should aim to replicate this during both training and competition to ensure consistently high levels of performance through appropriate preparation.
Leishmania mexicana Trypanothione Reductase Inhibitors: Computational and Biological Studies

Leishmanicidal drugs have many side effects, and drug resistance to all of them has been documented. Therefore, the development of new drugs and the identification of novel therapeutic targets are urgently needed. Leishmania mexicana trypanothione reductase (LmTR), a NADPH-dependent flavoprotein oxidoreductase important to thiol metabolism, is essential for parasite viability. Its absence in the mammalian host makes this enzyme an attractive target for the development of new anti-Leishmania drugs. Herein, a tridimensional model of LmTR was constructed and the molecular docking of 20 molecules from a ZINC database was performed. Five compounds (ZINC04684558, ZINC09642432, ZINC12151998, ZINC14970552, and ZINC11841871) were selected (docking scores −10.27 kcal/mol to −5.29 kcal/mol and structurally different) and evaluated against recombinant LmTR (rLmTR) and L. mexicana promastigote. Additionally, molecular dynamics simulation of LmTR-selected compound complexes was achieved. The five selected compounds inhibited rLmTR activity in the range of 32.9% to 40.1%. The binding of selected compounds to LmTR involving different hydrogen bonds with distinct residues of the molecule monomers A and B is described. Compound ZINC12151998 (docking score −10.27 kcal/mol) inhibited 32.9% the enzyme activity (100 µM) and showed the highest leishmanicidal activity (IC50 = 58 µM) of all the selected compounds. It was more active than glucantime, and although its half-maximal cytotoxicity concentration (CC50 = 53 µM) was higher than that of the other four compounds, it was less cytotoxic than amphotericin B. Therefore, compound ZINC12151998 provides a promising starting point for a hit-to-lead process in our search for new anti-Leishmania drugs that are more potent and less cytotoxic.
Solid-State Phase Transformations in Thermally Treated Ti–6Al–4V Alloy Fabricated via Laser Powder Bed Fusion

Laser Powder Bed Fusion (LPBF) technology was used to produce samples based on the Ti–6Al–4V alloy for biomedical applications. Solid-state phase transformations induced by thermal treatments were studied by neutron diffraction (ND), X-ray diffraction (XRD), scanning transmission electron microscopy (STEM) and energy-dispersive spectroscopy (EDS). Although, ND analysis is rather uncommon in such studies, this technique allowed evidencing the presence of retained β in α’ martensite of the as-produced (#AP) sample. The retained β was not detectable by XRD analysis, nor by STEM observations. Martensite contains a high number of defects, mainly dislocations, that anneal during the thermal treatment. Element diffusion and partitioning are the main mechanisms in the α ↔ β transformation that causes lattice expansion during heating and determines the final shape and size of phases. The retained β phase plays a key role in the α’ → β transformation kinetics.
Dorsal Barton fracture is a variation of dorsal radiocarpal dislocation: a clinical study

Dorsal Barton fractures may be better described as variants of dorsal radiocarpal dislocations. We aimed to better characterize these fractures by reviewing 111 patients in the ICUC® dataset who had a dorsally displaced, intra-articular distal radius fracture. We identified 13 patients with a dorsal Barton fracture on radiographs (dorsal articular margin fracture with radiocarpal subluxation and intact volar cortex). All patients with a dorsal Barton fracture had radial styloid involvement and volar cortical disruption that was subsequently identified on three-dimensional CT. Based on three-dimensional CT and intra-operative findings, none of the patients had classically described dorsal Barton fractures. All patients were treated using a volar exposure. A volar capsular tear was identified intra-operatively in three patients and the volar capsule repaired. This series supports the contention that dorsal Barton fractures are better characterized and treated as a variation of a dorsal radiocarpal dislocation. Level of evidence: IV
miR-26 suppresses adipocyte progenitor differentiation and fat production by targeting Fbxl19

In this study, Acharya et al. set out to identify the molecular mechanisms that regulate adipose tissue homeostasis. Through the use of gain- and loss-of-function approaches in vitro and in vivo the authors demonstrate that the miR-26 family inhibits APC differentiation and adipose tissue expansion through a cell-autonomous mechanism.
Does the Metabolically Healthy Obese Phenotype Protect Adults with Class III Obesity from Biochemical Alterations Related to Bone Metabolism?

Obesity negatively affects the relationship between markers and micronutrients of bone metabolism. Testing the hypothesis that the metabolically healthy obese phenotype might be protected by those alterations was the aim of this study. A cross-sectional study was carried out in adults with class III obesity classified in Metabolically Healthy Obese (MHO) and Metabolically Unhealthy Obese (MUHO), according to the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP ATP III) criteria. Anthropometric, biochemical, and clinical variables were analyzed for sample characterization. To evaluate bone metabolism, markers (alkaline phosphatase and parathyroid hormone—PTH) and related nutrients (vitamin D, vitamin B12, calcium, phosphorus, magnesium, potassium and zinc) were analyzed. A total of 223 adults with class III obesity aged 41.20 ± 10.15 years were included. The MHO phenotype was identified in 32.73% of the sample. After logistic regression, it was observed that inadequacies of calcium (OR: 4.11; 95% CI: 2.33–6.66), phosphorus (OR: 3.03; 95% CI: 1.98–5.79), vitamin D (OR: 5.01; 95% CI: 2.92–6.71) and PTH (OR: 5.45; 95% CI: 4.49–6.74) were significantly higher in the MUHO group compared to the MHO Group. This study showed that the MHO phenotype does not protect adults from alterations in markers and micronutrients of bone metabolism. However, the MUHO phenotype presents a higher risk for alterations related to bone metabolism, which can favor the emergence of metabolic bone diseases.
The torso-like gene functions to maintain the structure of the vitelline membrane in Nasonia vitripennis, implying its co-option into Drosophila axis formation

ABSTRACT Axis specification is a fundamental developmental process. Despite this, the mechanisms by which it is controlled across insect taxa are strikingly different. An excellent example of this is terminal patterning, which in Diptera such as Drosophila melanogaster occurs via the localized activation of the receptor tyrosine kinase Torso. In Hymenoptera, however, the same process appears to be achieved via localized mRNA. How these mechanisms evolved and what they evolved from remains largely unexplored. Here, we show that torso-like, known for its role in Drosophila terminal patterning, is instead required for the integrity of the vitelline membrane in the hymenopteran wasp Nasonia vitripennis. We find that other genes known to be involved in Drosophila terminal patterning, such as torso and Ptth, also do not function in Nasonia embryonic development. These findings extended to orthologues of Drosophila vitelline membrane proteins known to play a role in localizing Torso-like in Drosophila; in Nasonia these are instead required for dorso–ventral patterning, gastrulation and potentially terminal patterning. Our data underscore the importance of the vitelline membrane in insect development, and implies phenotypes caused by knockdown of torso-like must be interpreted in light of its function in the vitelline membrane. In addition, our data imply that the signalling components of the Drosophila terminal patterning systems were co-opted from roles in regulating moulting, and co-option into terminal patterning involved the evolution of a novel interaction with the vitelline membrane protein Torso-like. This article has an associated First Person interview with the first author of the paper. Summary: In the parasitic wasp Nasonia, Tsl, a key component of the process that defines the termini of the embryo of Drosophila, has a function in the structure of the vitelline membrane.
Effect modification by gender of the influence of obstructive sleep apnoea characteristics on dyslipidaemia in China: a cross-sectional study

Objectives Obstructive sleep apnoea (OSA) characteristics differ by gender, possibly affecting any association between OSA and dyslipidaemia. We explored whether gender influenced any association between OSA characteristics and dyslipidaemia. Methods/Design This was a cross-sectional, large-scale hospital-based study. Male and female risks of dyslipidaemia by OSA characteristics were assessed with logistic regression. Additive interactions were measured using three indices: the relative excess risk due to interaction, the attributable proportion due to interaction and the synergy index. Multiplicative interaction was evaluated via logistic regression. Setting A single secondary-care setting in China. Participants 3760 patients with OSA. Primary and secondary outcome measures Outcomes were male and female risks of dyslipidaemia, and the associated additive and multiplicative interactions between the apnoea–hypopnea index (AHI), the oxygen-desaturation index (ODI), the microarousal index (MAI), and gender. Results After controlling for confounding factors, males (but not females) with AHIs>30 were at higher risk of hyper-total cholesterol (TC), hypo-high-density lipoprotein cholesterol (HDL-C) status and a hyper-TC/HDL-C ratio than males with AHIs≤30. Positive additive interactions were evident between the male gender and AHI on a hyper-TC/HDL-C ratio and hypo-HDL-C status. Males with ODIs>40.1 were at higher risk of hypo-HDL-C status and a hyper-TC/HDL-C ratio than males with ODIs≤40.1. Positive additive and multiplicative interactions were evident between male gender and ODI on hyper-TC/HDL-C ratio. Males with MAIs>28.6 were at higher risk of hyper-TC and hyper-low-density lipoprotein cholesterol status than males with MAIs≤28.6, but no statistically significant interactions were apparent between gender and MAI. Conclusions Males (but not females) with higher AHIs, ODIs or MAIs were at higher risks of some measures of dyslipidaemia. Positive interactions between male and severe OSA or intermittent hypoxia on some measures of dyslipidaemia were apparent. Thus, dyslipidaemia should be evaluated in patients with OSA, especially males with severe OSA or intermittent hypoxia.
Fully Integrated Design of a Stretchable Solid‐State Lithium‐Ion Full Battery

A solid‐state lithium‐ion battery, in which all components (current collector, anode and cathode, electrolyte, and packaging) are stretchable, is introduced, giving rise to a battery design with mechanical properties that are compliant with flexible electronic devices and elastic wearable systems. By depositing Ag microflakes as a conductive layer on a stretchable carbon–polymer composite, a current collector with a low sheet resistance of ≈2.7 Ω □−1 at 100% strain is obtained. Stretchable electrodes are fabricated by integrating active materials with the elastic current collector. A polyacrylamide–“water‐in‐salt” electrolyte is developed, offering high ionic conductivity of 10−3 to 10−2 S cm−1 at room temperature and outstanding stretchability up to ≈300% of its original length. Finally, all these components are assembled into a solid‐state lithium‐ion full cell in thin‐film configuration. Thanks to the deformable individual components, the full cell functions when stretched, bent, or even twisted. For example, after stretching the battery to 50%, a reversible capacity of 28 mAh g−1 and an average energy density of 20 Wh kg−1 can still be obtained after 50 cycles at 120 mA g−1, confirming the functionality of the battery under extreme mechanical stress.
Long‐term survival of dogs treated for gallbladder mucocele by cholecystectomy, medical management, or both

Abstract Background Gallbladder mucoceles (GBM) typically are treated by cholecystectomy. Medical management rarely has been reported and medical and surgical management have not been compared. Hypothesis/Objectives To compare survival of dogs treated for GBM by medical management or cholecystectomy or both. Animals Eighty‐nine client‐owned dogs diagnosed with GBM that received cholecystectomy or medical treatment or both from 2011 to 2017. Methods Potential cases were identified by searching the medical records database. Data collected included signalment, clinicopathologic results, treatments, and ultrasonographic images and reports. Dogs were grouped according to the treatment received (medical management, surgical treatment, or both) that was chosen at the discretion of the attending veterinarian. Survival analysis was performed and prognostic variables identified and compared between treatment groups. Results Of dogs surviving at least 14 days after diagnosis, median survival times were 1802 (95% confidence interval [CI], 855‐not reached) days, 1340 (95% CI, 444‐1340) days, and 203 (95% CI, 18‐525) days, for the surgical, medical, and medical then surgical treatment groups, respectively, and differed significantly (P < .0001). Gallbladder mucocele type (P = .05), serum alkaline phosphatase activity (P = .0001), and serum creatinine (P = .002) and phosphorus (P = .04) concentrations were associated with decreased survival across groups. Suspicion of biliary rupture on abdominal ultrasound (AUS) examination was correlated with increased survival in the surgical group (P = .02). Conclusions and clinical importance Cholecystectomy for the treatment of GBM results in the best long‐term survival in dogs surviving the immediate postoperative period (14 days) compared to medical management. Although medical management is associated with shorter survival compared to surgical treatment, it is a reasonable alternative when surgery cannot be pursued.
Protection from Amyloid β Peptide–Induced Memory, Biochemical, and Morphological Deficits by a Phosphodiesterase-4D Allosteric Inhibitor

Recent imaging studies of amyloid and tau in cognitively normal elderly subjects imply that Alzheimer’s pathology can be tolerated by the brain to some extent due to compensatory mechanisms operating at the cellular and synaptic levels. The present study investigated the effects of an allosteric inhibitor of phosphodiesterase-4D (PDE4D), known as BPN14770 (2-(4-((2-(3-Chlorophenyl)-6-(trifluoromethyl)pyridin-4-yl)methyl)phenyl)acetic Acid), on impairment of memory, dendritic structure, and synaptic proteins induced by bilateral microinjection of oligomeric amyloid beta (Aβ1–42 into the hippocampus of humanized PDE4D (hPDE4D) mice. The hPDE4D mice provide a unique and powerful genetic tool for assessing PDE4D target engagement. Behavioral studies showed that treatment with BPN14770 significantly improved memory acquisition and retrieval in the Morris water maze test and the percentage of alternations in the Y-maze test in the model of Aβ impairment. Microinjection of oligomeric Aβ1–42 caused decreases in the number of dendrites, dendritic length, and spine density of pyramid neurons in the hippocampus. These changes were prevented by BPN14770 in a dose-dependent manner. Furthermore, molecular studies showed that BPN14770 prevented Aβ-induced decreases in synaptophysin, postsynaptic density protein 95, phosphorylated cAMP-response element binding protein (CREB)/CREB, brain-derived neurotrophic factor, and nerve growth factor inducible protein levels in the hippocampus. The protective effects of BPN14770 against Aβ-induced memory deficits, synaptic damage, and the alteration in the cAMP-meditated cell signaling cascade were blocked by H-89 (N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride), an inhibitor of protein kinase A. These results suggest that BPN14770 may activate compensatory mechanisms that support synaptic health even with the onset of amyloid pathology in Alzheimer’s disease. SIGNIFICANCE STATEMENT This study demonstrates that a phosphodiesterase-4D allosteric inhibitor, BPN14770, protects against memory loss and neuronal atrophy induced by oligomeric Aβ1–42. The study provides useful insight into the potential role of compensatory mechanisms in Alzheimer’s disease in a model of oligomeric Aβ1–42 neurotoxicity.