Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanobiology of Stem Cells: Implications for Vascular Tissue Engineering

Current challenges in vascular medicine (e.g., bypass grafting, stenting, and angioplasty.) have driven the field of vascular regenerative medicine. Bone marrow-derived mesenchymal stem cells (BMMSCs) are adult stem cells which may be a suitable cell source for vascular regenerative medicine applications. While it is well known that BMMSCs readily differentiate into musculoskeletal cells, recent studies have provided evidence for their differentiation into smooth muscle cells (SMCs) and endothelial cells (ECs). We and others have demonstrated the ability of the mechanical stimulus of cyclic stretch to drive BMMSC differentiation towards SMCs in vitro, but a rigorous, systematic analysis of other relevant forces is lacking. The working hypothesis that this work addressed is that mechanical stimuli relevant to the vasculature will guide BMMSC differentiation towards SMCs and ECs. To test this hypothesis, rat BMMSCs were exposed to physiologically relevant magnitudes and frequencies of a Mechanical Panel, which consisted of cyclic stretch, cyclic pressure, and shear stress, each applied in parallel to subcultures of BMMSCs. Quantitative changes in morphology, proliferation, and gene and protein expression were assessed to determine the differential effect of each stimulus in a dose- and frequency-dependant manner. Next, we investigated the importance of the duration of applied stimulation to BMMSC differentiation as well as tissue commitment (i.e., cell plasticity) following mechanical stimulation.Our results demonstrate that mechanical stimulation differentially altered BMMSC morphology, proliferation, and gene and protein expression towards the cardiovascular lineage while limiting expression for other lineages including bone, fat, and chondrocyte. This was particularly evident for cyclic stretch, which caused an elongated, spindle-shape and expression of the SMC proteins alpha-actin, calponin, and myosin heavy chain. Furthermore, we found that cyclic pressure and shear stress tended to increase endothelial gene expression when these stimuli are applied to confluent BMMSCs. While our findings as a whole tended to support our hypothesis, our data indicate that SMC protein expression is more readily increased by mechanical stimulation, and is highly variable, even without associated changes in gene expression. Future work employing systems biology approaches that take into consideration the resulting transcriptional and proteomic changes in BMMSCs from these mechanical stimuli will be necessary to more accurately identify how mechanical stimulation can be used as a tool for regenerative medicine.
Design of Multichannel Optical Splitter without Bends

The theory of a planar geometry splitter involving only parallel waveguide channels of rectangular cross-section is presented. The strictly parallel geometry allows for a semi-analytical analysis that makes possible the design of a splitter, which can divide an optical signal into uncoupled outputs carrying designated fractions of the input power. The theoretical intrinsic losses in the proposed splitter is shown to be minimal, and device design parameters are provided.
Investigation of Sip1 gene interactions in the development of the mammalian telencephalon

The transcriptional repressor Sip1, or Smad- interacting protein 1, has been shown to play a key role in early neurodevelopment. Mowat- Wilson Syndrome in humans is associated with mutations in Sip1. In the developing mouse cerebral cortex, it is expressed mostly in the differentiating field, and weakly in the proliferative zones. We found that stage and tissue specific ablation of Sip1 leads to several defects in the development of the neocortex. Deletion of Sip1 in cortical progenitors as well as exclusively in postmitotic cortical plate neurons, led to a reduction in the size of deep layer neuronal populations and precocious generation of cortical layers 2-5. Further studies showed that while the onset of neurogenesis is unaffected, this process ends prematurely in conditional Sip1 mutants. We also observed an increase in astrocyte production, and traced its origin to increased and ectopic proliferation of astrocytic progenitors at E17.5, and premature specification of glial precursors at E16.5. Furthermore, elevated proliferation in the cingulate cortex continued until early postnatal stages in the mutant. Our data suggest a possible non- cell autonomous effect of Sip1 on the specification of deep layer versus upper layer neuronal fate, and neuronal versus astrocytic fate of progenitors in the germinal zone, at early and late stages of development, respectively. Comparison of gene expression profile between wildtype and Sip1 conditional knockouts enabled us to identify the growth factors, Neurotrophin-3 (NT3) and Fgf9 as putative downstream targets of Sip1 in the cortex. During early corticogenesis, ablation of Sip1 induces interplay of NT3 and other as yet unconfirmed factor(s) leading to a premature switch in the fate of cortical neuronal precursors. Interestingly, treatment of cortical slices with Fgf9 in vitro led to enhanced production of Olig2 expressing glial precursors at the germinal zone, an effect that recapitulates the phenotyp! e of a Sip1- deficient neocortex. Our data indicate that lack of Sip1 in the cortical plate triggers an Fgf9- mediated signaling cascade back to the germinal zone, possibly via interaction with Fgfr2/3 on radial glial processes, to influence the onset of astrocytic specification. Altogether, our work provides the first evidence of neuron to progenitor feedback signaling in the neocortex, to regulate the fate of uncommitted precursors and ensure production of appropriate numbers of different neurons and glia. Moreover, we have established Sip1 as a key mediator of this mechanism by its negative regulation of expression of certain signaling molecules.
Fermenting cell walls of processed sugarcane pith by ruminal bacteria, protozoa and fungi.

The objectives of this study were to determine contribution of ruminal bacteria, protozoa and fungi to the fermentation of cell walls of sugarcane pith treated with low temperature steam (121oC, 120 min.) and or sulfuric acid (0.0, 6, 12 & 18 g/kg DM), and effectiveness of this method for increasing the feed value of sugarcane pith and negative effects of this method on rumen microorganisms. Gas production parameters were determined and cumulative gas production data were fitted to the exponential equation. The results showed that processing with low temperature steam resulted in significant increase in rate (C) and potential gas production (B) by all microbial fractions, as the highest (B) (112.9 mL) was for condition 18 g/kg of dry matter (DM) acid. The highest gas produced by total microorganism and rumen isolated bacteria was followed by fungi and protozoa fractions. In vitro cell wall degradation, organic matter digestibility (OMD) and metabolisable energy (ME) of sugarcane pith treated with steam and 18 g/kg acid was the highest and microbial biomass production (MB) was the lowest for all microbial groups. Therefore, it appears that the gas production parameters and degradability of sugarcane pith by rumen microbial fractions are influenced by low temperature steam and sulfuric acid treatment, bacterial group generates a larger volume of gas production than fungal or protozoan group and this method had no negative effect on rumen microorganisms. © 2011 Friends Science Publishers
Zinc and Iron Concentrations in Seeds of Wild, Primitive, and Modern Wheats

In the case of cultivated modern wheats, the variation in zinc and iron concentrations in seeds is relatively small. Moreover, environmental and management factors exert a greater effect on variation of micronutrient concentrations of modern cultivated wheats than genetic factors. Wild wheats might serve as an important source of new genetic material for increasing micronutrient concentrations in seeds. To investigate this, we studied the variation in zinc and iron concentrations in seeds of wild and primitive diploid wheats and wild tetraploid wheats. The variation was particularly large in the case of zinc. The highest concentrations of zinc were found in the seeds of ssp. boeoticum (178 mg/kg) and ssp. dicoccoides (159 mg/kg). The results demonstrate that the genetic variation in the concentrations of zinc and iron in cultivated modern tetraploid and hexaploid wheats is extremely low when compared with the variation found in wild diploid and tetraploid wheats. This suggests that wild wheats, particularly chromosomes 6A and 6B in the wild tetraploid wheats, can be considered a major source of genetic diversity for increasing zinc and iron density in the seeds of modern wheats. In view of the fact that the concentrations of protein in seeds are strongly and positively correlated with the concentrations of iron and particularly of zinc, selection and/or breeding for high zinc and iron levels in seeds may result in simultaneously high levels of protein.
Evaluation and validation of drug targets

Drug target is one of the key factors for discovering and developing new drugs. To find and validate drug targets is a crucial technique required in drug discovery by the strategy of high throughput screening. Based on the knowledge of molecular biology, human genomics and proteomics, it has been predicted that 5000 to 10000 drug targets exist in human. So, it is important orocedure to evaluate and validate the drug targets.
The (Alt)right to rape: violated white masculinities in the Alt-right, and the film Nocturnal Animals

ABSTRACT This article begins with the troubling idea that aspects of contemporary mainstream representations might echo or encourage facets of arguments that work to further the Alt-right’s agenda, and it focuses in particular on the critically respected film Nocturnal Animals. The paper argues that contemporary screen representations like Manchester By the Sea and Nocturnal Animals replicate stories about white men supposedly violated by women and minorities. The Alt-right, a global political collective of organizations, has at its heart a shared grievance at the supposed violation and victimization of white heterosexual Christian masculinities, and this article seeks to highlight a disturbing overlap between Alt-right ideas and representations in popular screen representations in the USA. The analysis of Nocturnal Animals takes up the idea of white masculinity in crisis as outlined by Susan Jeffords, Richard Dyer, and Sean Redmond, considering its influence released just before President Donald Trump’s inauguration. The discussion considers the relationship of white masculinity in crisis with sexual violence, whilst exploring how a sense of grievance against women and minorities on the part of white men legitimizes and justifies violent and violating reactions. Nocturnal Animals is found to be a deeply misogynist text, which endorses aggrieved white masculinities.
Validation of the biological responses of reference drugs in the zebrafish embryo by electrocardiographic analysis and by novel phenotyping tools

Drug toxicities represent a major problem in drug discovery and development; therefore there is a push to develop new technologies to detect these early on. In this thesis I investigated the utility of zebrafish embryos and larvae in evaluating the biological activity of novel compounds and developed new methods for assaying the potential toxic effects of drugs \(in\) \(vivo\). An electrocardiogram (ECG) recording set-up for zebrafish embryos and larvae was developed to assay drug-induced cardiotoxicity. The set-up was validated by testing drugs known to induce cardiotoxicity in humans in zebrafish larvae. The results obtained were in agreement with those documented in humans demonstrating the utility of the zebrafish larva in detecting drug-induced cardiotoxicity. The zebrafish embryo was also found to be a useful model for probing the biological activity of novel and marketed compounds providing an insight into the relationship between chemical properties and biological effects. Additionally, the assessment of the anti-inflammatory activity of a set of reference drugs revealed that the zebrafish larva also presents a promising model for therapeutic drug screens. Overall, the results described in this thesis show that the zebrafish presents an effective, reliable and rapid model for assessing the biological activity of drugs \(in\) \(vivo\).
Biological role of fish antimicrobial peptides

In this review we will focus on the functions of known fish antimicrobial peptides (AMPs). Though there is significant information about the gene structure and transcript regulation of several fish AMPs the role of their synthetic or recombinant peptides is scarcely known. Thus, some studies have demonstrated the direct effect of fish AMPs, mainly -defensins, on fish immunostimulation as well as powerful antibacterial or antiviral peptides.
Detection of Platelet-Activating Antibodies Associated with Heparin-Induced Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a prothrombotic immune drug reaction caused by platelet-activating antibodies that in most instances recognize platelet factor 4 (PF4)/polyanion complexes. Platelet activation assays (i.e., functional assays) are more specific than immunoassays, since they are able to discern clinically relevant heparin-induced antibodies. All functional assays used for HIT diagnosis share the same principle, as they assess the ability of serum/plasma from suspected HIT patients to activate fresh platelets from healthy donors in the presence of several concentrations of heparin. Depending on the assay, donors’ platelets are stimulated either in whole blood (WB), platelet-rich plasma (PRP), or in a buffer medium (washed platelets, WP). In addition, the activation endpoint studied varies from one assay to another: platelet aggregation, membrane expression of markers of platelet activation, release of platelet granules. Tests with WP are more sensitive and serotonin release assay (SRA) is considered to be the current gold standard, but functional assays suffer from certain limitations regarding their sensitivity, specificity, complexity, and/or accessibility. However, the strict adherence to adequate preanalytical conditions, the use of selected platelet donors and the inclusion of positive and negative controls in each run are key points that ensure their performances.
Alterations in Vascular Function Associated With the Use of Combustible and Electronic Cigarettes

Background Electronic cigarettes (e‐cigarettes) have been proposed as a potential harm reduction tool for combustible cigarette smokers. The majority of adult e‐cigarette users continue to smoke combustible cigarettes and are considered dual users. The vascular impact of e‐cigarettes remains incompletely defined. Methods and Results We examined the association of e‐cigarette use with measures of vascular function and tonometry, preclinical measures of cardiovascular injury. As part of the CITU (Cardiovascular Injury due to Tobacco Use) study, we performed noninvasive vascular function testing in individuals without known cardiovascular disease or cardiovascular disease risk factors who were nonsmokers (n=94), users of combustible cigarettes (n=285), users of e‐cigarettes (n=36), or dual users (n=52). In unadjusted analyses, measures of arterial stiffness including carotid‐femoral pulse wave velocity, augmentation index, carotid‐radial pulse wave velocity, and central blood pressures differed across the use groups. In multivariable models adjusted for age, sex, race, and study site, combustible cigarette smokers had higher augmentation index compared with nonusers (129.8±1.5 versus 118.8±2.7, P=0.003). The augmentation index was similar between combustible cigarette smokers compared with sole e‐cigarette users (129.8±1.5 versus 126.2±5.9, P=1.0) and dual users (129.8±1.5 versus 134.9±4.0, P=1.0). Endothelial cells from combustible cigarette smokers and sole e‐cigarette users produced less nitric oxide in response to A23187 stimulation compared with nonsmokers, suggestive of impaired endothelial nitric oxide synthase signaling. Conclusions Our findings suggest that e‐cigarette use is not associated with a more favorable vascular profile. Future longitudinal studies are needed to evaluate the long‐term risks of sustained e‐cigarette use.
Therapeutic Physical Exercise Post-Treatment in Breast Cancer: A Systematic Review of Clinical Practice Guidelines

Advances achieved in diagnosis and improvements in treatment for breast cancer have resulted in a favourable survival rate. Therapeutic physical exercise (TPE) is presented as an intervention strategy that seeks to improve the functional capabilities of the subject. To analyse if clinical practice guidelines recommend therapeutic physical exercise to reduce the adverse effects of treatment in breast cancer survivors, and on what level of scientific evidence are these recommendations based. This systematic review was prepared by searching nine electronic databases to identify eligible studies. Thirteen met the criteria for inclusion. The Appraisal of Guidelines for Research and Evaluation (AGREE II) scale was used to analyse the quality of Clinical Practice Guideline (CPGs). The percentages obtained ranged between 30.07% and 75.70%. Specifically, the highest degree of evidence could be found in the application of TPE to offset adverse effects leading to effects such as: an increase in the quality of life, fatigue reduction, and reduction in body weight alterations. TPE is presented as an optimal intervention strategy to alleviate the negative effects that patients with breast cancer suffer as a result of the treatments received. The level of evidence that supports this claim is very strong for the majority of the side effects analysed. However, this evidence is not always included in the clinical practice guidelines.
Cucumber gibberellin 1-oxidase/desaturase initiates novel gibberellin catabolic pathways

Bioactive gibberellins (GAs) are central regulators of plant growth and development, including seed development. GA homeostasis is achieved via complex biosynthetic and catabolic pathways, whose exact activities remain to be elucidated. Here, we isolated two cDNAs from mature or imbibed cucumber seeds with high sequence similarity to known GA 3-oxidases. We found that one enzyme (designated here CsGA3ox5) has GA 3-oxidation activity. However, the second enzyme (designated CsGA1ox/ds) performed multiple reactions, including 1β-oxidation and 9,11-desaturation of GAs, but was lacking the 3-oxidation activity. CsGA1ox/ds overexpression in Arabidopsis plants resulted in severely dwarfed plants that could be rescued by the exogenous application of bioactive GA4, confirming that CsGA1ox/ds catabolizes GAs. Substitution of three amino acids in CsGA1ox/ds, Phe93, Pro106, and Ser202, with those typically conserved among GA 3-oxidases, Tyr93, Met106, and Thr202, respectively, conferred GA 3-oxidase activity to CsGA1ox/ds and thereby augmented its potential to form bioactive GAs in addition to catabolic products. Accordingly, overexpression of this amino acid–modified GA1ox/ds variant in Arabidopsis accelerated plant growth and development, indicating that this enzyme variant can produce bioactive GAs in planta. Furthermore, a genetically modified GA3ox5 variant in which these three canonical GA 3-oxidase amino acids were changed to the ones present in CsGA1ox/ds was unable to convert GA9 to GA4, highlighting the importance of these three conserved amino acids for GA 3-oxidase activity.
Perception of a Haptic Stimulus Presented Under the Foot Under Workload

It is clear that the haptic channel can be exploited as a communication medium for several tasks of everyday life. Here we investigated whether such communication can be altered in a cognitive load situation. We studied the perception of a vibrotactile stimulus presented under the foot when the attention is loaded by another task (cognitive load). The results demonstrated a significant influence of workload on the perception of the vibrotactile stimulus. Overall, we observed that the average score in the single-task (at rest) condition was greater than the overall mean score in the dual-task conditions (counting forwards, counting backwards, and walking). The walking task was the task that most influenced the perception of the vibrotactile stimulus presented under the foot.
Emerging hemorrhage control and resuscitation strategies in trauma: endovascular to extracorporeal.

This article reviews four emerging endovascular hemorrhage control and extracorporeal perfusion techniques for management of trauma patients with profound hemorrhagic shock including hemorrhage-induced traumatic cardiac arrest. These include resuscitative endovascular balloon occlusion of the aorta (REBOA), selective aortic arch perfusion (SAAP), extracorporeal life support (ECLS), and emergency preservation and resuscitation (EPR). The pre-clinical and clinical studies underpinning the use of each of these techniques are summarized. We also present an integrated conceptual framework for how these emerging technologies may be used in the future care of trauma patients in both resource-rich and austere environments. LEVEL OF EVIDENCE: N/A.
Corticosterone Induces HMGB1 Release in Primary Cultured Rat Cortical Astrocytes: Involvement of Pannexin-1 and P2X7 Receptor-Dependent Mechanisms

A major risk factor for major depressive disorder (MDD) is stress. Stress leads to the release of high-mobility group box-1 (HMGB1), which in turn leads to neuroinflammation, a potential pathophysiological basis of MDD. The mechanism underlying stress-induced HMGB1 release is not known, but stress-associated glucocorticoids could be involved. To test this, rat primary cultured cortical astrocytes, the most abundant cell type in the central nervous system (CNS), were treated with corticosterone and HMGB1 release was assessed by Western blotting and ELISA. Significant HMGB1 was released with treatment with either corticosterone or dexamethasone, a synthetic glucocorticoid. HMGB1 translocated from the nucleus to the cytoplasm following corticosterone treatment. HMGB1 release was significantly attenuated with glucocorticoid receptor blocking. In addition, inhibition of pannexin-1, and P2X7 receptors led to a significant decrease in corticosterone-induced HMGB1 release. Taken together, corticosterone stimulates astrocytic glucocorticoid receptors and triggers cytoplasmic translocation and extracellular release of nuclear HMGB1 through a mechanism involving pannexin-1 and P2X7 receptors. Thus, under conditions of stress, glucocorticoids induce astrocytic HMGB1 release, leading to a neuroinflammatory state that could mediate neurological disorders such as MDD.