Miracle-dz/UniFAR-FTUs huggingface dataset:
Profile of Small RNAs, vDNA Forms and Viral Integrations in Late Chikungunya Virus Infection of Aedes albopictus Mosquitoes

The Asian tiger mosquito Aedes albopictus is contributing to the (re)-emergence of Chikungunya virus (CHIKV). To gain insights into the molecular underpinning of viral persistence, which renders a mosquito a life-long vector, we coupled small RNA and whole genome sequencing approaches on carcasses and ovaries of mosquitoes sampled 14 days post CHIKV infection and investigated the profile of small RNAs and the presence of vDNA fragments. Since Aedes genomes harbor nonretroviral Endogenous Viral Elements (nrEVEs) which confers tolerance to cognate viral infections in ovaries, we also tested whether nrEVEs are formed after CHIKV infection. We show that while small interfering (si)RNAs are evenly distributed along the full viral genome, PIWI-interacting (pi)RNAs mostly arise from a ~1000 bp window, from which a unique vDNA fragment is identified. CHIKV infection does not result in the formation of new nrEVEs, but piRNAs derived from existing nrEVEs correlate with differential expression of an endogenous transcript. These results demonstrate that all three RNAi pathways contribute to the homeostasis during the late stage of CHIKV infection, but in different ways, ranging from directly targeting the viral sequence to regulating the expression of mosquito transcripts and expand the role of nrEVEs beyond immunity against cognate viruses.
Effects of Lippia citriodora Leaf Extract on Lipid and Oxidative Blood Profile of Volunteers with Hypercholesterolemia: A Preliminary Study

Lippia citriodora is a plant traditionally used for its anti-inflammatory, antioxidant and antispasmodic effects, as well as for additional biological activities proven in cell culture, animal studies and a small number of human clinical trials. The plant has also shown a marked improvement in blood lipid profile in some animal species. In the present preliminary study, we investigated the effect of a leaf extract on lipid and oxidative blood profile of hypercholesterolemic volunteers. Twelve adults received Lippia citriodora extract caps, containing 23% phenylpropanoids, (100 mg, once a day) for 16 weeks. Selected blood lipids and plasma oxidative markers were measured at baseline and after 4, 8 and 16 weeks of treatment. Compared with baseline, total cholesterol levels significantly decreased and high-density lipoprotein cholesterol increased, while low-density lipoprotein cholesterol and triglycerides showed only a downward trend. Oxidative status was improved due to a decrease in the concentration of total oxidant status, reactive oxygen metabolites and malondialdehyde, and a significant increase in ferric reducing ability of plasma, vitamin A and vitamin E. These preliminary results suggest that dietary supplementation with Lippia citriodora extract can improve the lipid profile, enhance blood antioxidant power, and could be a valuable natural compound for the management of human hypercholesterolemia.
Current State-of-the-Art and Unresolved Problems in Using Human Induced Pluripotent Stem Cell-Derived Dopamine Neurons for Parkinson’s Disease Drug Development

Human induced pluripotent stem (iPS) cells have the potential to give rise to a new era in Parkinson’s disease (PD) research. As a unique source of midbrain dopaminergic (DA) neurons, iPS cells provide unparalleled capabilities for investigating the pathogenesis of PD, the development of novel anti-parkinsonian drugs, and personalized therapy design. Significant progress in developmental biology of midbrain DA neurons laid the foundation for their efficient derivation from iPS cells. The introduction of 3D culture methods to mimic the brain microenvironment further expanded the vast opportunities of iPS cell-based research of the neurodegenerative diseases. However, while the benefits for basic and applied studies provided by iPS cells receive widespread coverage in the current literature, the drawbacks of this model in its current state, and in particular, the aspects of differentiation protocols requiring further refinement are commonly overlooked. This review summarizes the recent data on general and subtype-specific features of midbrain DA neurons and their development. Here, we review the current protocols for derivation of DA neurons from human iPS cells and outline their general weak spots. The associated gaps in the contemporary knowledge are considered and the possible directions for future research that may assist in improving the differentiation conditions and increase the efficiency of using iPS cell-derived neurons for PD drug development are discussed.
Come Back Skinfolds, All Is Forgiven: A Narrative Review of the Efficacy of Common Body Composition Methods in Applied Sports Practice

Whilst the assessment of body composition is routine practice in sport, there remains considerable debate on the best tools available, with the chosen technique often based upon convenience rather than understanding the method and its limitations. The aim of this manuscript was threefold: (1) provide an overview of the common methodologies used within sport to measure body composition, specifically hydro-densitometry, air displacement plethysmography, bioelectrical impedance analysis and spectroscopy, ultra-sound, three-dimensional scanning, dual-energy X-ray absorptiometry (DXA) and skinfold thickness; (2) compare the efficacy of what are widely believed to be the most accurate (DXA) and practical (skinfold thickness) assessment tools and (3) provide a framework to help select the most appropriate assessment in applied sports practice including insights from the authors’ experiences working in elite sport. Traditionally, skinfold thickness has been the most popular method of body composition but the use of DXA has increased in recent years, with a wide held belief that it is the criterion standard. When bone mineral content needs to be assessed, and/or when it is necessary to take limb-specific estimations of fat and fat-free mass, then DXA appears to be the preferred method, although it is crucial to be aware of the logistical constraints required to produce reliable data, including controlling food intake, prior exercise and hydration status. However, given the need for simplicity and after considering the evidence across all assessment methods, skinfolds appear to be the least affected by day-to-day variability, leading to the conclusion ‘come back skinfolds, all is forgiven’.
Biocompatibility and Pharmacological Effects of Innovative Systems for Prolonged Drug Release Containing Dexketoprofen in Rats

The present study reports on the in vivo biocompatibility investigation and evaluation of the effects of liposomes containing dexketoprofen in somatic sensitivity in rats. Method: The liposomes were prepared by entrapping dexketoprofen in vesicular systems stabilized with chitosan. The in vivo biocompatibility was evaluated after oral administration in white Wistar rats: Group I (DW): distilled water 0.3 mL/100 g body weight; Group II (DEX): dexketoprofen 10 mg/kg body weight (kbw); Group III (nano-DEX): liposomes containing dexketoprofen 10 mg/kbw. Blood samples were collected from caudal lateral vein one day and seven days after the substance administration, to assess the eventual hematological, biochemical, and immunological changes. The investigation of somatic pain reactivity was performed using the hot plate test, to count the latency time response evoked by the thermal paws’ noxious stimulation. Results: Original liposomes entrapping dexketoprofen, with mean size of 680 nm and good stability, were designed. Laboratory analysis indicated no substantial variances between the three treated groups. The treatment with liposomes containing dexketoprofen resulted in a prolongation of the latency time response, statistically significant in the interval between 90 min and 10 h, in the hot plate test. Conclusions: The use of liposomes with dexketoprofen proved a good in vivo biocompatibility in rats and prolonged analgesic effects in the hot plate test.
Influence of n-ZnO Morphology on Sulfur Crosslinking and Properties of Styrene-Butadiene Rubber Vulcanizates

This paper examines the influence of the morphology of zinc oxide nanoparticles (n-ZnO) on the activation energy, vulcanization parameters, crosslink density, crosslink structure, and mechanical properties in the extension of the sulfur vulcanizates of styrene-butadiene rubber (SBR). Scanning electron microscopy was used to determine the particle size distribution and morphology, whereas the specific surface area (SSA) and squalene wettability of the n-ZnO nanoparticles were adequately evaluated using the Brunauer–Emmet–Teller (BET) equation and tensiometry. The n-ZnO were then added to the SBR in conventional (CV) or efficient (EV) vulcanization systems. The vulcametric curves were plotted, from which the cure rate index (CRI) rate of the vulcanization and the activation energy were calculated. The influence on the mechanical properties of the SBR vulcanizates was stronger in the case of the EV curing system than when the CV curing system was used. Of the vulcanizates produced in the EV curing system, the best performance was detected for n-ZnO particles with a hybrid morphology (flat-ended rod-like particles on a “cauliflower” base) and high SSA. Vulcanizates produced using the CV curing system showed slightly better mechanical properties after the addition of nanoparticles with a “cauliflower” morphology than when the rod-like type were used, irrespective of their SSA. In general, nanoparticles with a rod-like structure reduced the activation energy and increased the speed of vulcanization, whereas the cauliflower type slowed the rate of the process and the vulcanizates required a higher activation energy, especially when using the EV system. The crosslink structures were also more clearly modified, as manifested by a reduction in the polysulfidic crosslink content, especially when n-ZnO activators with a rod-like morphology were applied.
Granger Causality on forward and Reversed Time Series

In this study, the information flow time arrow is investigated for stochastic data defined by vector autoregressive models. The time series are analyzed forward and backward by different Granger causality detection methods. Besides the normal distribution, which is usually required for the validity of Granger causality analysis, several other distributions of predictive errors are considered. A clear effect of a change in the order of cause and effect on the time-reversed series of unidirectionally connected variables was detected with standard Granger causality test (GC), when the product of the connection strength and the ratio of the predictive errors of the driver and the recipient was below a certain level, otherwise bidirectional causal connection was detected. On the other hand, opposite causal link was detected unconditionally by the methods based on the time reversal testing, but they were not able to detect correct bidirectional connection. The usefulness of the backward analysis is manifested in cases where falsely detected unidirectional connections can be rejected by applying the result obtained after the time reversal, and in cases of uncorrelated causally independent variables, where the absence of a causal link detected by GC on the original series should be confirmed on the time-reversed series.
Framing HIV and AIDS: how leaders of black religious institutions in New York City interpret and address sex and sexuality in their HIV interventions

Abstract This study explored how leaders of Black churches active in the fight against HIV conceptualised sex and sexuality when describing HIV interventions within their institutions. We analysed interviews with pastors and identified three frames through which leaders understood and communicated about sex and sexuality: (1) an evasive frame, in which participants avoided discussing behaviours and populations that have historically been disparaged within the church by emphasising involuntary risk exposure; (2) an agentic frame, which recognised sexual behaviour that differed from heteronormative conduct; and, (3) a pluralist frame, which allowed individuals to maintain their own beliefs about appropriate sexual conduct. Participants used frames to engage in a range of HIV interventions while upholding stigmatising beliefs about sexual behaviour and identity.
NMRK2 Gene Is Upregulated in Dilated Cardiomyopathy and Required for Cardiac Function and NAD Levels during Aging

Dilated cardiomyopathy (DCM) is a disease of multifactorial etiologies, the risk of which is increased by male sex and age. There are few therapeutic options for patients with DCM who would benefit from identification of common targetable pathways. We used bioinformatics to identify the Nmrk2 gene involved in nicotinamide adenine dinucleotde (NAD) coenzyme biosynthesis as activated in different mouse models and in hearts of human patients with DCM while the Nampt gene controlling a parallel pathway is repressed. A short NMRK2 protein isoform is also known as muscle integrin binding protein (MIBP) binding the α7β1 integrin complex. We investigated the cardiac phenotype of Nmrk2-KO mice to establish its role in cardiac remodeling and function. Young Nmrk2-KO mice developed an eccentric type of cardiac hypertrophy in response to pressure overload rather than the concentric hypertrophy observed in controls. Nmrk2-KO mice developed a progressive DCM-like phenotype with aging, associating eccentric remodeling of the left ventricle and a decline in ejection fraction and showed a reduction in myocardial NAD levels at 24 months. In agreement with involvement of NMRK2 in integrin signaling, we observed a defect in laminin deposition in the basal lamina of cardiomyocytes leading to increased fibrosis at middle age. The α7 integrin was repressed at both transcript and protein level at 24 months. Nmrk2 gene is required to preserve cardiac structure and function, and becomes an important component of the NAD biosynthetic pathways during aging. Molecular characterization of compounds modulating this pathway may have therapeutic potential.
The Effect of the Oleophobicity Deterioration of a Membrane Surface on Its Rejection Capacity: A Computational Fluid Dynamics Study

In this work, the effects of the deteriorating affinity-related properties of membranes due to leaching and erosion on their rejection capacity were studied via computational fluid dynamics (CFD). The function of affinity-enhancing agents is to modify the wettability state of the surface of a membrane for dispersed droplets. The wettability conditions can be identified by the contact angle a droplet makes with the surface of the membrane upon pinning. For the filtration of fluid emulsions, it is generally required that the surface of the membrane is nonwetting for the dispersed droplets such that the interfaces that are formed at the pore openings provide the membrane with a criterion for the rejection of dispersals. Since materials that make up the membrane do not necessarily possess the required affinity, it is customary to change it by adding affinity-enhancing agents to the base material forming the membrane. The bonding and stability of these materials can be compromised during the lifespan of a membrane due to leaching and erosion (in crossflow filtration), leading to a deterioration of the rejection capacity of the membrane. In order to investigate how a decrease in the contact angle can lead to the permeation of droplets that would otherwise get rejected, a CFD study was conducted. In the CFD study, a droplet was released in a crossflow field that involved a pore opening and the contact angle was considered to decrease with time as a consequence of the leaching of affinity-enhancing agents. The CFD analysis revealed that the decrease in the contact angle resulted in the droplet spreading over the surface more. Furthermore, the interface that was formed at the entrance of the pore opening flattened as the contact angle decreased, leading the interface to advance more inside the pore. The droplet continued to pass over the pore opening until the contact angle reached a certain value, at which point, the droplet became pinned at the pore opening.
Assessment of the Origin and Diversity of Croatian Common Bean Germplasm Using Phaseolin Type, SSR and SNP Markers and Morphological Traits

Landraces represent valuable genetic resources for breeding programmes to produce high-yielding varieties adapted to stressful environmental conditions. Although the common bean (Phaseolus vulgaris L.) is an economically important food legume for direct human consumption worldwide, common bean production in Croatia is based almost exclusively on landraces and there is no common bean breeding program. Information on phaseolin type and results of population structure and genetic diversity obtained by analysis of SSR and SNP markers, in combination with the morphological characterization of 174 accessions of 10 common bean landraces (morphotypes), enabled thorough classification of accessions. The accessions were classified into phaseolin type H1 (“S”) of Mesoamerican origin and phaseolin types H2 (“H” or “C”) and H3 (“T”) of Andean origin. By applying distance- and model-based clustering methods to SSR markers, the accessions were classified into two clusters at K = 2 separating the accessions according to the centres of origin, while at K = 3, the accessions of Andean origin were further classified into two clusters of accessions that differed in phaseolin type (H2 and H3). Using SNP markers, model-based analysis of population structure was performed, the results of which were consistent with those of SSR markers. In addition, 122 accessions were assigned to 14 newly formed true-type morphogenetic groups derived from three different domestication events: (1) Mesoamerican (H1A) (“Biser”, “Kukuruzar”, “Tetovac”, “Trešnjevac”), (2) Andean—indeterminate type (H2B1) (“Dan noć”, “Sivi”, “Puter”, ”Sivi prošarani”, “Trešnjevac”) and (3) Andean—determinate type (H3B2) (“Bijeli”, “Dan noć”, “Puter”, “Trešnjevac”, “Zelenčec”). The rest of the accessions could represent putative hybrids between morphogenetic groups. The differences between the true-type groups of accessions were further analysed based on nine quantitative traits, and the subsets of traits that best distinguish among centres of origin (A: Mesoamerican, B: Andean) and genetic groups (H1A, H2B1, H3B2) were proposed.
The Reptation Mechanism in Tumor Imaging

Introduction Results An extended worm-chain polymer undergoes reptation in selfdiffusion (1). Reptation is movement along a tube that follows the contour path of the polymer (2,3). Likewise, in a small force field, a reptating polymer will move around obstacles and through a fibrous matrix. This is the principle by which DNA is separated according to length in gel electrophoresis (4). Such a mechanism may be operative in the uptake of reptating polymers by tumors through the action of convection and the porous nature of the tumor endothelium and the adjacent extracellular matrix (5). The optimum exploitation of this mechanism may allow significantly higher enhancement of tumors than seen with small molecular weight contrast agents or with globular protein contrast agents Theoretical The observed tumor enhancements as a function of chain length are shown in Fig. 1. There is a maximum in tumor enhancement at N 450. The solid line is the theoretical prediction with one free parameter the enhancement value at a particular chain length as a scaling reference In the curve shown, the reference value used was that for N 613, the best determined value ( n=9, 90%+/20%). The blood circulation decay rates where determined from measurements of blood levels at various times after injection, (time constant of 15 minutes for the short chain and 14 hours for the longer chains). Finally, a correction for biphasic behavior of blood circulation for the longer chains was incorporated in the full treatment, of which eqn. 1 is a simplified version.
Impact of high dietary energy on obesity and oxidative stress in domestic pigeons

Abstract Obesity is associated with increased risk of oxidative stress in humans and laboratory animals but information regarding obesity‐induced oxidative stress in birds is lacking. Therefore, this study aimed to investigate the influence of high‐energy diets (HED) on obesity and oxidative stress in domestic pigeons. Forty‐five adult clinically healthy‐domestic male pigeons were randomly assigned to three equal dietary groups including low (2,850 kcal/kg), medium (3,150 kcal/kg) and high (3,450 kcal/kg) energy diets (named low energy diet, medium‐energy diet and HED, respectively). All birds received formulated diets for 60 consecutive days. Several parameters such as feed intake, body weight (BW), average weight gain (AWG) and total weight gain were determined. Serum concentrations of triglyceride (TG), total cholesterol (TC), high‐, low‐ and very‐low‐density lipoprotein cholesterols, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were evaluated at days 0, 30 and 60; and serum levels of total antioxidant capacity (T‐AOC), malondialdehyde (MDA) and cortisol were also measured at day 60. On day 60, five pigeons from each group were randomly euthanized and some parameters such as weight and relative weight of liver, breast muscle, and abdominal fat were determined. Furthermore, hepatic total fat content was also evaluated. BW, AWG, total weight, and circulating TG, TC, ALT, AST, ALP, MDA and cortisol in HED were significantly higher than other groups. Serum T‐AOC in HED was significantly lower than the other groups. In conclusion, this study showed that increasing dietary energy up to 3,450 kcal/kg in pigeons led to obesity and oxidative stress in them. Accordingly, it could be stated that HED and obesity induce oxidative stress in pigeon and controlling the dietary energy intake of pigeons is necessary to prevent oxidative stress in them.
Lipid-Based Nanocarriers for Ophthalmic Administration: Towards Experimental Design Implementation

Nanotherapeutics based on biocompatible lipid matrices allow for enhanced solubility of poorly soluble compounds in the treatment of ophthalmic diseases, overcoming the anatomical and physiological barriers present in the eye, which, despite the ease of access, remains strongly protected. Micro-/nanoemulsions, solid lipid nanoparticles (SLN) or nanostructured lipid carriers (NLC) combine liquid and/or solid lipids with surfactants, improving drug stability and ocular bioavailability. Current research and development approaches based on try-and-error methodologies are unable to easily fine-tune nanoparticle populations in order to overcome the numerous constraints of ocular administration routes, which is believed to hamper easy approval from regulatory agencies for these systems. The predictable quality and specifications of the product can be achieved through quality-by-design (QbD) implementation in both research and industrial environments, in contrast to the current quality-by-testing (QbT) framework. Mathematical modelling of the expected final nanoparticle characteristics by variation of operator-controllable variables of the process can be achieved through adequate statistical design-of-experiments (DoE) application. This multivariate approach allows for optimisation of drug delivery platforms, reducing research costs and time, while maximising the understanding of the production process. This review aims to highlight the latest efforts in implementing the design of experiments to produce optimised lipid-based nanocarriers intended for ophthalmic administration. A useful background and an overview of the different possible approaches are presented, serving as a starting point to introduce the design of experiments in current nanoparticle research.