Miracle-dz/UniFAR-FTUs huggingface dataset:
Impaired Cytoskeletal and Membrane Biophysical Properties of Acanthocytes in Hypobetalipoproteinemia – A Case Study

Familial hypobetalipoproteinemia is a metabolic disorder mainly caused by mutations in the apolipoprotein B gene. In its homozygous form it can lead without treatment to severe ophthalmological and neurological manifestations. In contrast, the heterozygous form is generally asymptomatic but associated with a low risk of cardiovascular disease. Acanthocytes or thorny red blood cells (RBCs) are described for both forms of the disease. However, those morphological changes are poorly characterized and their potential consequences for RBC functionality are not understood. Thus, in the present study, we asked whether, to what extent and how acanthocytes from a patient with heterozygous familial hypobetalipoproteinemia could exhibit altered RBC functionality. Acanthocytes represented 50% of the total RBC population and contained mitoTracker-positive surface patches, indicating the presence of mitochondrial fragments. While RBC osmotic fragility, calcium content and ATP homeostasis were preserved, a slight decrease of RBC deformability combined with an increase of intracellular free reactive oxygen species were observed. The spectrin cytoskeleton was altered, showing a lower density and an enrichment in patches. At the membrane level, no obvious modification of the RBC membrane fatty acids nor of the cholesterol content were detected but the ceramide species were all increased. Membrane stiffness and curvature were also increased whereas transversal asymmetry was preserved. In contrast, lateral asymmetry was highly impaired showing: (i) increased abundance and decreased functionality of sphingomyelin-enriched domains; (ii) cholesterol enrichment in spicules; and (iii) ceramide enrichment in patches. We propose that oxidative stress induces cytoskeletal alterations, leading to increased membrane stiffness and curvature and impaired lipid lateral distribution in domains and spicules. In addition, ceramide- and spectrin-enriched patches could result from a RBC maturation defect. Altogether, the data indicate that acanthocytes are associated with cytoskeletal and membrane lipid lateral asymmetry alterations, while deformability is only mildly impaired. In addition, familial hypobetalipoproteinemia might also affect RBC precursors leading to disturbed RBC maturation. This study paves the way for the potential use of membrane biophysics and lipid vital imaging as new methods for diagnosis of RBC disorders.
Endocrinology of the Aging Prostate: Current Concepts

Benign prostate hyperplasia (BPH), one of the most common diseases in older men, adversely affects quality-of-life due to the presence of low urinary tract symptoms (LUTS). Numerous data support the presence of an association between BPH-related LUTS (BPH-LUTS) and metabolic syndrome (MetS). Whether hormonal changes occurring in MetS play a role in the pathogenesis of BPH-LUTS is a debated issue. Therefore, this article aimed to systematically review the impact of hormonal changes that occur during aging on the prostate, including the role of sex hormones, insulin-like growth factor 1, thyroid hormones, and insulin. The possible explanatory mechanisms of the association between BPH-LUTS and MetS are also discussed. In particular, the presence of a male polycystic ovarian syndrome (PCOS)-equivalent may represent a possible hypothesis to support this link. Male PCOS-equivalent has been defined as an endocrine syndrome with a metabolic background, which predisposes to the development of type II diabetes mellitus, cardiovascular diseases, prostate cancer, BPH and prostatitis in old age. Its early identification would help prevent the onset of these long-term complications.
Fecal Microbiota Transplantation Shows Marked Shifts in the Multi-Omic Profiles of Porcine Post-weaning Diarrhea

Weaning is the most critical phase in pig production and is generally associated with significant impacts on intestinal morphology, structure, physiology, and immune responses, which can lead to subsequent production inefficiencies such as decreases in growth and intake and increases in morbidity and mortality. In the present study, we attempted to explore the effects of fecal microbiota transplantation (FMT) on the fecal microbiota, fecal metabolites, and transcriptome in the jejunum, colon, liver, spleen, and oral mucosa in piglets with post-weaning diarrhea and to evaluate the therapeutic potential of FMT in piglets with post-weaning diarrhea. We found that FMT partially relieved the symptoms of diarrhea in piglets, and microbiota analysis results indicated that unclassified_f_Prevotellaceae was identified as an FMT-associated bacterial family at 66 day and that the Shannon index in the healthy group at 34, 38, and 66 days were higher than that at 21 day. Functional enrichment analysis of the oral mucosa, liver, jejunum, and colon showed that most of the differentially expressed genes (DEGs) were enriched in the terms metabolic process, immune response, and inflammatory response. Moreover, the enriched fecal metabolites focused mostly on apoptosis, beta-alanine metabolism, glutathione metabolism, and sphingolipid metabolism. We tried to detect specific “metabolite-bacterium” pairs, such as “g_Catenisphaera-stigmastentriol,” “p_Bacteroidetes-(6beta,22E)-6-hydroxystigmasta-4,22-dien-3-one,” and “g_Prevotellaceae_NK3B31_group-stenocereol. ” Overall, the present study provides a theoretical basis for the alleviation of weaning stress and contributes to the realization of effective and sustainable application of FMT in the pig production industry in the future.
Employee-Athletes: Exploring the Elite Spanish Athletes' Perceptions of Combining Sport and Work

Researchers have studied the athletes' dual careers with the aim of helping them to combine the sport and the academic–vocational sphere. Most of this research has addressed the study–sport combination, but there is a lack of studies on the work–sport combination. The main objective of this research was to explore the subjective perceptions of Spanish elite athletes when attempting to combine their careers as professional athletes with a second profession or trade. Further, this study aims to identify the access to facilitating resources and the perception of obstacles and barriers to the development of a dual career. A qualitative approach was chosen to address these research questions. Interpretative phenomenological analysis was carried out on a sample of 18 elite athletes, and the data were collected using semi-structured interviews based on a set of superordinate and subordinate categories. The results showed that the athletes interviewed possessed valuable resources such as the transference of sports values to the work sphere. However, important barriers were highlighted such as the perception of sport institutions as absent entities in the work–sport combination. Thus, the study of this type of dual career seems to be one of the challenges facing the interested scientific community for the coming years.
Integrated Assessment of Nickel Electroplating Industrial Wastewater Effluent as a Renewable Resource of Irrigation Water Using a Hydroponic Cultivation System

Nickel, a micronutrient essential for plant growth and development, has been recognized as a metallic pollutant in wastewater. The concentration of nickel ions in the water course, exceeding the maximum tolerable limit, has called for an alarming attention, due to the bioaccumulative entry in the water–plant–human food chain, leaving a burden of deteriorative effects on visible characteristics, physiological processes, and oxidative stress response in plants. In this work, the renewable utilization of nickel electroplating industrial wastewater effluent (0, 5, 10, 25, 50, and 100%) as a viable source of irrigation water was evaluated using a hydroponic cultivation system, by adopting Lablab purpureus and Brassica chinensis as the plant models, in relation to the physical growth, physiological and morphological characteristics, photosynthetic pigments, proline, and oxidative responses. The elongation of roots and shoots in L. purpureus and B. chinensis was significantly inhibited beyond 25 and 5% of industrial wastewater. The chlorophyll-a, chlorophyll-b, total chlorophyll, and carotenoid contents, accompanied by alterations in the morphologies of xylem, phloem, and distortion of stomata, were recorded in the industrial wastewater-irrigated groups, with pronounced toxicity effects detected in B. chinensis. Excessive proline accumulation was recorded in the treated plant models. Ascorbate peroxidase (APX), guaiacol peroxidase (POD), and catalase (CAT) scavenging activities were drastically altered, with a profound upregulation effect in the POD activity in L. purpureus and both POD and APX in B. chinensis, predicting the nickel-induced oxidative stress. Conclusively, the diluted industrial wastewater effluent up to the optimum concentrations of 5 and 25%, respectively, could be feasibly reused as a renewable resource for B. chinensis and L. purpureus irrigation, verified by the minimal or negligible phytotoxic implications in the plant models. The current findings have shed light on the interruption of nickel-contaminated industrial wastewater effluent irrigation practice on the physical and biochemical features of food crops and highlighted the possibility of nutrient recycling via wastewater reuse in a sustainable soilless cultivation.
AKH Signaling in D. melanogaster Alters Larval Development in a Nutrient-Dependent Manner That Influences Adult Metabolism

Metabolism, growth, and development are intrinsically linked, and their coordination is dependent upon inter-organ communication mediated by anabolic, catabolic, and steroid hormones. In Drosophila melanogaster, the corpora cardiaca (CC) influences metabolic homeostasis through adipokinetic hormone (AKH) signaling. AKH has glucagon-like properties and is evolutionarily conserved in mammals as the gonadotropin-releasing hormone, but its role in insect development is unknown. Here we report that AKH signaling alters larval development in a nutrient stress-dependent manner. This activity is regulated by the locus dg2, which encodes a cGMP-dependent protein kinase (PKG). CC-specific downregulation of dg2 expression delayed the developmental transition from larval to pupal life, and altered adult metabolism and behavior. These developmental effects were AKH-dependent, and were observed only in flies that experienced low nutrient stress during larval development. Calcium-mediated vesicle exocytosis regulates ecdysteroid secretion from the prothoracic gland (PG), and we found that AKH signaling increased cytosolic free calcium levels in the PG. We identified a novel pathway through which PKG acts in the CC to communicate metabolic information to the PG via AKH signaling. AKH signaling provides a means whereby larval nutrient stress can alter developmental trajectories into adulthood.
Estimating Central Pulse Pressure From Blood Flow by Identifying the Main Physical Determinants of Pulse Pressure Amplification

Several studies suggest that central (aortic) blood pressure (cBP) is a better marker of cardiovascular disease risk than peripheral blood pressure (pBP). The morphology of the pBP wave, usually assessed non-invasively in the arm, differs significantly from the cBP wave, whose direct measurement is highly invasive. In particular, pulse pressure, PP (the amplitude of the pressure wave), increases from central to peripheral arteries, leading to the so-called pulse pressure amplification (ΔPP). The main purpose of this study was to develop a methodology for estimating central PP (cPP) from non-invasive measurements of aortic flow and peripheral PP. Our novel approach is based on a comprehensive understanding of the main cardiovascular properties that determine ΔPP along the aortic-brachial arterial path, namely brachial flow wave morphology in late systole, and vessel radius and distance along this arterial path. This understanding was achieved by using a blood flow model which allows for workable analytical solutions in the frequency domain that can be decoupled and simplified for each arterial segment. Results show the ability of our methodology to (i) capture changes in cPP and ΔPP produced by variations in cardiovascular properties and (ii) estimate cPP with mean differences smaller than 3.3 ± 2.8 mmHg on in silico data for different age groups (25–75 years old) and 5.1 ± 6.9 mmHg on in vivo data for normotensive and hypertensive subjects. Our approach could improve cardiovascular function assessment in clinical cohorts for which aortic flow wave data is available.
Elevated Brain Glutamate Levels in Bipolar Disorder and Pyruvate Carboxylase-Mediated Anaplerosis

In vivo 1H magnetic resonance spectroscopy studies have found elevated brain glutamate or glutamate + glutamine levels in bipolar disorder with surprisingly high reproducibility. We propose that the elevated glutamate levels in bipolar disorder can be explained by increased pyruvate carboxylase-mediated anaplerosis in brain. Multiple independent lines of evidence supporting increased pyruvate carboxylase-mediated anaplerosis as a common mechanism underlying glutamatergic hyperactivity in bipolar disorder and the positive association between bipolar disorder and obesity are also described.
New Stereoregularity in the Stereospecific Polymerization of Bulky Strained Olefins : Diheterotactic Polynorbornene

A new semicrystalline polynorbornene was obtained by stereospecific polymerization with CrCl 2 (dppa)-MAO catalyst (dppa = bis(diphenylphosphino)amine). NMR, X-ray diffraction, and modeling techniques were used, concentrating on the soluble lower molecular weight fractions, to characterize the polymer structure. The polymer presents a 2,3-exo-diheterotactic stereochemistry never observed before in the polymerization of alkenes. High symmetry, low energy chain conformations accounting for 13 C NMR data are devised. Efficient crystalline packing models consistent with powder X-ray diffraction patterns and density requirements are proposed.
MAPKAP Kinase-2 Drives Expression of Angiogenic Factors by Tumor-Associated Macrophages in a Model of Inflammation-Induced Colon Cancer

Chronic inflammation increases the risk for colorectal cancer through a variety of mechanisms involving the tumor microenvironment. MAPK-activated protein kinase 2 (MK2), a major effector of the p38 MAPK stress and DNA damage response signaling pathway, and a critical regulator of pro-inflammatory cytokine production, has been identified as a key contributor to colon tumorigenesis under conditions of chronic inflammation. We have previously described how genetic inactivation of MK2 in an inflammatory model of colon cancer results in delayed tumor progression, decreased tumor angiogenesis, and impaired macrophage differentiation into a pro-tumorigenic M2-like state. The molecular mechanism responsible for the impaired angiogenesis and tumor progression, however, has remained contentious and poorly defined. Here, using RNA expression analysis, assays of angiogenesis factors, genetic models, in vivo macrophage depletion and reconstitution of macrophage MK2 function using adoptive cell transfer, we demonstrate that MK2 activity in macrophages is necessary and sufficient for tumor angiogenesis during inflammation-induced cancer progression. We identify a critical and previously unappreciated role for MK2-dependent regulation of the well-known pro-angiogenesis factor CXCL-12/SDF-1 secreted by tumor associated-macrophages, in addition to MK2-dependent regulation of Serpin-E1/PAI-1 by several cell types within the tumor microenvironment.
Correlation of Coagulation Parameters With Clinical Outcomes During the Coronavirus-19 Surge in New York: Observational Cohort

Importance COVID-19 has caused a worldwide illness and New York became the epicenter of COVID-19 in the United States from Mid-March to May 2020. Objective To investigate the coagulopathic presentation of COVID and its natural course during the early stages of the COVID-19 surge in New York. To investigate whether hematologic and coagulation parameters can be used to assess illness severity and death. Design Retrospective case study of positive COVID inpatients between March 20, 2020-March 31, 2020. Setting Montefiore Health System main hospital, Moses, a large tertiary care center in the Bronx. Participants Adult inpatients with positive COVID tests hospitalized at MHS. Exposure (for observational studies) Datasets of participants were queried for demographic (age, sex, socioeconomic status, and self-reported race and/or ethnicity), clinical and laboratory data. Main Outcome and Measures Relationship and predictive value of measured parameters to mortality and illness severity. Results Of the 225 in this case review, 75 died during hospitalization while 150 were discharged home. Only the admission PT, absolute neutrophil count (ANC) and first D-Dimer could significantly differentiate those who were discharged alive and those who died. Logistic regression analysis shows increased odds ratio for mortality by first D-Dimer within 48 hrs. of admission. The optimal cut-point for the initial D-Dimer to predict mortality was found to be 2.1 μg/mL. 15% of discharged patients required readmission and more than a third of readmitted patients died (5% of all initially discharged). Conclusion We describe here a comprehensive assessment of hematologic and coagulation parameters in COVID-19 and examine the relationship of these to mortality. We demonstrate that both initial and maximum D-Dimer values are biomarkers that can be used for survival assessments. Furthermore, D-Dimer may be useful to follow up discharged patients.
Ginsenoside Rc Ameliorates Endothelial Insulin Resistance via Upregulation of Angiotensin-Converting Enzyme 2

Type 2 diabetes mellitus (T2DM) is a major health concern which may cause cardiovascular complications. Insulin resistance (IR), regarded as a hallmark of T2DM, is characterized by endothelial dysfunction. Ginsenoside Rc is one of the main protopanaxadiol-type saponins with relatively less research on it. Despite researches confirming the potent anti-inflammatory and antioxidant activities of ginsenoside Rc, the potential benefits of ginsenoside Rc against vascular complications have not been explored. In the present study, we investigated the effects of ginsenoside Rc on endothelial IR and endothelial dysfunction with its underlying mechanisms using high glucose- (HG-) cultured human umbilical vein endothelial cells (HUVECs) in vitro and a type 2 diabetic model of db/db mice in vivo. The results showed that ginsenoside Rc corrected the imbalance of vasomotor factors, reduced the production of Ang (angiotensin) II, and activated angiotensin-converting enzyme 2 (ACE2)/Ang-(1–7)/Mas axis in HG-treated HUVECs. Besides, ginsenoside Rc improved the impaired insulin signaling pathway and repressed oxidative stress and inflammatory pathways which constitute key factors leading to IR. Interestingly, the effects of ginsenoside Rc on HG-induced HUVECs were abolished by the selective ACE2 inhibitor MLN-4760. Furthermore, ginsenoside Rc exhibited anti-inflammatory as well as antioxidant properties and ameliorated endothelial dysfunction via upregulation of ACE2 in db/db mice, which were confirmed by the application of MLN-4760. In conclusion, our findings reveal a novel action of ginsenoside Rc and demonstrate that ginsenoside Rc ameliorated endothelial IR and endothelial dysfunction, at least in part, via upregulation of ACE2 and holds promise for the treatment of diabetic vascular complications.
Herpes Simplex Virus Type 1 Neuronal Infection Triggers the Disassembly of Key Structural Components of Dendritic Spines

Herpes simplex virus type 1 (HSV-1) is a widespread neurotropic virus. Primary infection of HSV-1 in facial epithelium leads to retrograde axonal transport to the central nervous system (CNS) where it establishes latency. Under stressful conditions, the virus reactivates, and new progeny are transported anterogradely to the primary site of infection. During the late stages of neuronal infection, axonal damage can occur, however, the impact of HSV-1 infection on the morphology and functional integrity of neuronal dendrites during the early stages of infection is unknown. We previously demonstrated that acute HSV-1 infection in neuronal cell lines selectively enhances Arc protein expression - a major regulator of long-term synaptic plasticity and memory consolidation, known for being a protein-interaction hub in the postsynaptic dendritic compartment. Thus, HSV-1 induced Arc expression may alter the functionality of infected neurons and negatively impact dendritic spine dynamics. In this study we demonstrated that HSV-1 infection induces structural disassembly and functional deregulation in cultured cortical neurons, an altered glutamate response, Arc accumulation within the somata, and decreased expression of spine scaffolding-like proteins such as PSD-95, Drebrin and CaMKIIβ. However, whether these alterations are specific to the HSV-1 infection mechanism or reflect a secondary neurodegenerative process remains to be determined.
Greater Reliance on Cerebral Palsy-Specific Muscle Synergies During Gait Relates to Poorer Temporal-Spatial Performance Measures

Children with cerebral palsy typically exhibit reduced complexity of muscle coordination patterns during walking; however, the specific patterns that characterize their gait abnormalities are still not well documented. This study aimed to identify the specific repertoire of muscle coordination patterns in children with CP during walking compared to same-aged peers without CP and their relationships to gait performance. To identify muscle coordination patterns, we extracted muscle synergies from 10 children with CP and 10 age-matched typically developing children (TD). K-mean clustering and discriminant analyses of all extracted synergies were used to group similar synergies. Then, weight-averaged z-scores were quantified for each cluster to determine their group-specific level. In this cohort, 10 of the 17 distinct clusters were largely CP-specific while six clusters were seen mainly in TD, and one was non-specific. CP-specific clusters generally showed merging of two TD synergies, excessive antagonist co-activation, decreased muscle activation compared to TD, and complex or atypical pattern. Significant correlations were found between weight-averaged z-scores and step length asymmetry, cadence asymmetry, self-selected treadmill speed and AP-COM displacement of the pelvis such that greater CP-specificity of muscle synergies was related to poorer performance, thus indicating that CP-specific synergies can influence motor dysfunction.