Miracle-dz/UniFAR-FTUs huggingface dataset:
Type‐2 diabetes: Current understanding and future perspectives

The rapid outbreak of type‐2 diabetes is one of the largest public health problems around the globe. Particularly, the developing nations are becoming the epicenters of cardiometabolic disorders owing to the change in lifestyle and diet preference besides genetic predisposition. Diabetes has become a major independent risk factor for cardiovascular diseases in South Asian countries including India. The pathogenesis of type‐2 diabetes primarily initiates with inadequacy of pancreatic islet β‐cells to respond to chronic fuel surfeit and hence causing glycemic load, insulin resistance, and obesity. Urban Indian life is threatened with unhealthy high calorie diet and sedentary habits, and thus impairing the metabolic status of “thin‐fat Indians” and rendering them more vulnerable to metabolic disorders. Furthermore, the metabolic dysfunction may be triggered off quite early in life due to poor maternal health and impairment in intrauterine programming and, particularly in rural India. The impaired fetal development affects the health status in later stage of life by promoting obesity, insulin resistance, type‐2 diabetes, and cardiovascular complications. Therefore, the preventive and therapeutic approaches focus on a holistic strategy to improve maternal and child health, promote balanced diet and physical exercise in combination with pharmacological intervention of reducing/checking hyperglycemia, obesity, and cardiovascular complications. This review summarizes the epidemiology, mechanisms, and risk factors for diabetes and cardiovascular disorders with a focus on the Indian subcontinent. © 2015 IUBMB Life, 67(7):506–513, 2015
Deubiquitinating enzymes in cellular signaling and disease regulation

Protein post‐translational modification by ubiquitin represents a complex signaling system that regulates many cellular events including proteostasis to intercellular communications. Deubiquitinating enzymes (DUBs) that specifically disassemble Ub‐chains or regulate ubiquitin homeostasis reside as a central component in ubiquitin signaling. Human genome encodes almost 100 DUBs and majority of them are not well characterized. Considerable progress has been made in the understanding of enzymatic mechanism; however, their cellular substrate specificity and regulation are largely unknown. Involvement of DUBs in disease regulation has been depicted since its discovery and several attempts have been made for evaluating DUBs as a drug target. In this review, we have updated briefly a new insight of DUBs activity, their cellular role, disease regulation, and therapeutic potential. © 2015 IUBMB Life, 67(7):544–555, 2015
Molecular regulation of cellular iron balance

Handling a life‐supporting yet redox‐active metal like iron represents a significant challenge to cells and organisms that must not only tightly balance intra‐ and extracellular iron concentrations but also chaperone it during its journey from its point of entry to final destinations, to prevent inappropriate generation of damaging reactive oxygen species. Accordingly, regulatory mechanisms have been developed to maintain appropriate cellular and body iron levels. In intracellular compartments, about 95% of iron is protein‐bound and the expression of the major proteins of iron metabolism is controlled by an integrated and dynamic system involving multilayered levels of regulation. However, dysregulation of iron homeostasis, which could result from both iron‐related and unrelated effectors, may occur and have important pathological consequences in a number of human disorders. In this review, we describe the current understanding of the mechanisms that keep cellular iron balance and outline recent advances that increased our knowledge of the molecular physiology of iron metabolism. © 2017 IUBMB Life, 69(6):389–398, 2017
Significance of circulatory DPP4 activity in metabolic diseases

Dipeptidyl peptidase 4 (DPP4), also known as CD26 is a type II transmembrane protein that is released from the cell membrane in a nonclassical secretory mechanism. This exopeptidase selectively degrades varieties of substrates including incretin hormones, growth factors, and cytokines. A significant detectable amount of DPP4 activity can be measured in plasma as well as in different tissues such as intestinal epithelium, vascular endothelium, lymphocytes, monocytes, kidney, liver, adipose, lung, thymus, spleen, prostate, etc. Enzymatically active circulatory DPP4 is shed from the plasma membrane via proteolytic cleavage, a process responsible for the enhanced plasma DPP4 levels and activity. Elevated circulatory DPP4 activity as well as levels has been found in wide spectrum of metabolic diseases including diabetes, obesity, cardiovascular diseases, and nonalcoholic fatty liver diseases. Moreover, recent preclinical studies have further expanded the repertoire for the usage of DPP4 inhibitors in the treatment of other metabolic diseases and in their consequent complications. In the present review we highlight the reason behind the elevated circulatory DPP4 levels in metabolic diseases with a focus on the tissue of origin. We also underscore the discrepancy of protein levels with enzyme activity of circulatory DPP4 in metabolic diseases. © 2018 IUBMB Life, 70(2):112–119, 2018
Isolation and characterization of 17 polymorphic microsatellite loci for the three‐toed woodpecker (Picoides tridactylus)

We describe primers and polymerase chain reaction conditions to amplify 17 di‐, tri‐ and tetranucleotide microsatellite loci from the three‐toed woodpecker (Picoides tridactylus). The primers were tested on 26 to 30 individuals from a single population breeding in southern Finland. The developed primer pairs yielded an average of 7.6 alleles per locus (range two to 15), an average observed heterozygosity of 0.69 (range 0.07 to 0.97), and an average polymorphic information content of 0.68 (range 0.06 to 0.90).
Dexamethasone reduces serum level of IL-17 in Bleomycin-A5-induced rats model of pulmonary fibrosis

Abstract Background: Pulmonary fibrosis is a chronic progressive disease with limited therapeutic options and inflammatory cytokines play important roles in the pathogenesis of pulmonary fibrosis. Material and method: Here, we investigated the changes of TGF-β1, IL-8, and IL-17 in the serum of bleomycin-A5-induced rats model of pulmonary fibrosis. 120 healthy male Wistar rats were randomly divided into three groups, the control group (n = 30), the model group (n = 45) and the dexamethasone (DEX) group (n = 45). The rats of both model group and DEX group were injected with Bleomycin-A5 (5 mg/kg) through tracheofistulization to induce pulmonary fibrosis, while the rats of the control group were injected with equivalent physiological saline. After operation, DEX (4 mg/kg) was given to the DEX group rats intraperitoneally once a day. Equivalent saline was administered to rats of both the control group and the model group. Results: On the 1st, 14th, and 28th day after operation, pathological changes of the lung tissues, and the levels of serum IL-8, TGF-β1, and IL-17 were measured. The concentrations of serum TGF-β1, IL-8, and IL-17 were significantly increased after bleomycin-A5 treatment, especially on the 14th day (p < .01). There was no significant difference between model group and DEX group in the serum level of TGF-β1 and IL-8, but DEX treatment significantly reduce serum IL-17 level (p < .01). Conclusions: DEX protect bleomycin-A5-induced pulmonary fibrosis in rats through reduced the level of IL-17 in serum.
Recent advances on biomedical applications of scaffolds in wound healing and dermal tissue engineering

Abstract The tissue engineering field has developed in response to the shortcomings related to the replacement of the tissues lost to disease or trauma: donor tissue rejection, chronic inflammation and donor tissue shortages. The driving force behind the tissue engineering is to avoid the mentioned issues by creating the biological substitutes capable of replacing the damaged tissue. This is done by combining the scaffolds, cells and signals in order to create the living, physiological, three-dimensional tissues. A wide variety of skin substitutes are used in the treatment of full-thickness injuries. Substitutes made from skin can harbour the latent viruses, and artificial skin grafts can heal with the extensive scarring, failing to regenerate structures such as glands, nerves and hair follicles. New and practical skin scaffold materials remain to be developed. The current article describes the important information about wound healing scaffolds. The scaffold types which were used in these fields were classified according to the accepted guideline of the biological medicine. Moreover, the present article gave the brief overview on the fundamentals of the tissue engineering, biodegradable polymer properties and their application in skin wound healing. Also, the present review discusses the type of the tissue engineered skin substitutes and modern wound dressings which promote the wound healing.
Delivery of nanoparticle‐complexed drugs across the vascular endothelial barrier via caveolae

The endothelial cell monolayer lining the vessel wall forms a size‐selective, semi‐permeable barrier between the blood and tissue that must be crossed by blood borne therapeutic agents to reach diseased extravascular tissue. Nanoparticles engineered to carry drugs present an opportunity to enhance the specificity and efficacy of drug delivery. Therefore, an understanding of how these engineered nanoparticles are transported across the vessel wall will help us to more fully exploit this powerful therapeutic technology. Vascular endothelial cells are rich in caveolae, cell surface invaginations 50–100 nm in diameter that mediate endocytosis of lipids, proteins, and viruses. Caveolar invaginations pinch off to form intracellular vesicles that can transport cargo across the cell and release the cargo into the extravascular space via exocytosis. Here, we will review the current concepts and state of development for delivering engineered nanoparticles across the endothelium via the caveolae‐mediated pathway. © 2011 IUBMB IUBMB Life, 2011
Normatization of the Symbol Digit Modalities Test-Oral Version in a Latin American Country

The aim of this study was to standardize the Symbol Digit Modalities Test (SDMT)-Oral version in a healthy population living in Argentina and to analyze the influence that age, gender, and education have on the SDMT. Secondarily, it is intended to analyze the performance of patients with multiple sclerosis (MS) on this test. Two hundred ninety-seven healthy participants were evaluated; they had an average age of 39.28 years and 13.87 years of schooling; 77.8% were women. The sample was segmented according to age in three groups: younger than 35 years old, 36 to 50 years old, and 51 to 70 years old. The sample was also segmented according to years of schooling in three groups: 11 years or less, 12 to 16 years, and more than 16 years. All participants were evaluated with the oral version of the SDMT. A clinical sample of 111 patients with MS was also assessed. The mean on the SDMT for the total sample was 51.34 (SD = 12.76). The differences were significant between all groups, p < . 05, according to age. The participants with a higher level of education performed better than did those with moderate education and those with less schooling, p < . 05. There was a significant difference between patients with MS and healthy controls, p < . 01. The SDMT is influenced by age as well as by schooling, although not by gender. The norms displayed here will be useful to accurately evaluate the yield of the patients in the neuropsychological clinic when comparing them with their group of reference. It was also demonstrated that the SDMT can discriminate between patients with MS and healthy people.
Cooperativity and allostery in haemoglobin function

Tetrameric haemoglobins display a cooperative ligand binding behaviour, which has been attributed to the functional interrelationship between multiple ligand binding sites. The quantitative description of this feature was initially carried out with a phenomenological approach, which was limited to the functional effect of the occupancy by a ligand molecule of a binding site on further binding steps. However, subsequent development of structural–functional models for the description of the cooperativity in haemoglobin brought about a much deeper information on the interrelationships between ligand binding at the heme and structural variations occurring in the surrounding free subunits. This approach opened the way to the evolution of the concept of allostery, which is intended as the structural–functional effect exerted by the presence of a ligand in a binding site on other binding sites present in the same molecule. This concept can be applied to either sites for the same ligand (homotropic allostery) and for sites of different ligands (heterotropic allostery). Several models trying to take into account the continuous building up of structural and functional information on the physicochemical properties of haemoglobin have been developed along this line. © 2008 IUBMB IUBMB Life, 60(2): 112–123, 2008
Mechanisms of aging and energy metabolism in Caenorhabditis elegans

Aging studies on diverse species ranging from yeast to man have culminated in the delineation of several signaling pathways that influence the process of senescent decline and aging. While understanding these interlinked signal‐transduction cascades is becoming even more detailed and comprehensive, the cellular and biochemical processes they impinge upon to modulate the rate of senescent decline and aging have lagged considerably behind. This fundamental question is one of the most important challenges of modern aging research and has been the focus of recent research efforts. Emerging findings provide insight into the facets of cellular metabolism which can be fine‐tuned by upstream signaling events to ultimately promote longevity. Here, we survey the mechanisms regulating aging in the simple nematode worm Caenorhabditis elegans, aiming to highlight recent discoveries that shed light into the interface between aging signaling pathways and cellular energy metabolism. Our objective is to review the current understanding of the processes involved and discuss mechanisms that are likely conserved in higher organisms. © 2008 IUBMB IUBMB Life, 60(5): 315–322, 2008
A novel pathway from phosphorylation of tyrosine residues 239/240 of Shc, contributing to suppress apoptosis by IL‐3.

Interleukin 3 (IL‐3) not only induces DNA synthesis of haematopoietic cells but also maintains their viability by suppressing apoptosis. IL‐3 stimulates tyrosine phosphorylation of the Shc adaptor protein and thereby formation of a complex of Shc with Grb2 at phosphorylated tyrosine (Y) residue 317‐Shc. This pathway is implicated in Ras/mitogen‐activated protein kinase (MAPK) activation towards c‐fos gene expression. We examined the possible involvement of Shc in the antiapoptotic activity of IL‐3. Conditional overexpression of the Shc SH2 domain, a dominant‐negative mutant of Shc, was found to induce apoptosis of IL‐3‐dependent Ba/F3 cells along with a reduction of c‐myc gene expression. Apoptosis was rescued by the exogenously introduced c‐myc gene. Since we identify novel tyrosine phosphorylation sites of Shc: Y239 and Y240, their role on cell survival was tested by mutational analysis. Ba/F3 cells expressing mutant Shc Y317F, which is unable to stimulate efficiently the Ras pathway, still showed resistance to apoptosis. However, cells expressing Shc Y239/240F, which is able to stimulate the Ras pathway, were sensitive to apoptosis. In these cells, induction of the c‐myc gene was reduced. These findings suggest that a new signalling pathway for cell survival is generated from Y239/240 of Shc to the nuclei involving c‐myc gene expression.
Discovery of single‐nucleotide polymorphisms (SNPs) in the uncharacterized genome of the ascomycete Ophiognomonia clavigignenti‐juglandacearum from 454 sequence data

The benefits from recent improvement in sequencing technologies, such as the Roche GS FLX (454) pyrosequencing, may be even more valuable in non‐model organisms, such as many plant pathogenic fungi of economic importance. One application of this new sequencing technology is the rapid generation of genomic information to identify putative single‐nucleotide polymorphisms (SNPs) to be used for population genetic, evolutionary, and phylogeographic studies on non‐model organisms. The focus of this research was to sequence, assemble, discover and validate SNPs in a fungal genome using 454 pyrosequencing when no reference sequence is available. Genomic DNA from eight isolates of Ophiognomonia clavigignenti‐juglandacearum was pooled in one region of a four‐region sequencing run on a Roche 454 GS FLX. This yielded 71 million total bases comprising 217 000 reads, 80% of which collapsed into 16 125 754 bases in 30 339 contigs upon assembly. By aligning reads from multiple isolates, we detected 298 SNPs using Roche’s GS Mapper. With no reference sequence available, however, it was difficult to distinguish true polymorphisms from sequencing error. Eagleview software was used to manually examine each contig that contained one or more putative SNPs, enabling us to discard all but 45 of the original 298 putative SNPs. Of those 45 SNPs, 13 were validated using standard Sanger sequencing. This research provides a valuable genetic resource for research into the genus Ophiognomonia, demonstrates a framework for the rapid and cost‐effective discovery of SNP markers in non‐model organisms and should prove especially useful in the case of asexual or clonal fungi with limited genetic variability.
Low back pain patients’ responses to videos of avoided movements

Fear avoidance (FA) has been identified as a risk factor for poor prognosis and a target for intervention in patients with low back pain (LBP), but the mechanisms involved need clarification. Experimental studies would benefit from the use of carefully developed and controlled stimuli representing avoided movements in back pain, and matched stimuli of movements to provide a credible control stimuli. Existing stimuli depicting avoided movements in LBP are static, do not include a set of control stimuli and do not control for possible systematic observer biases.
Skin swabbing as a new efficient DNA sampling technique in amphibians, and 14 new microsatellite markers in the alpine newt (Ichthyosaura alpestris)

This study introduces a novel DNA sampling method in amphibians using skin swabs. We assessed the relevancy of skin swabs relevancy for genetic studies by amplifying a set of 17 microsatellite markers in the alpine newt Ichthyosaura alpestris, including 14 new polymorphic loci, and a set of 11 microsatellite markers in Hyla arborea, from DNA collected with buccal swabs (the standard swab method), dorsal skin swabs and ventral skin swabs. We tested for quality and quantity of collected DNA with each method by comparing electrophoresis migration patterns. The consistency between genotypes obtained from skin swabs and buccal swabs was assessed. Dorsal swabs performed better than ventral swabs in both species, possibly due to differences in skin structure. Skin swabbing proved to be a useful alternative to buccal swabbing for small or vulnerable animals: by drastically limiting handling, this method may improve the trade‐off between the scientific value of collected data, individual welfare and species conservation. In addition, the 14 new polymorphic microsatellites for the alpine newt will increase the power of genetic studies in this species. In four populations from France (n = 19–25), the number of alleles per locus varied from 2 to 16 and expected heterozygosities ranged from 0.04 to 0.91. Presence of null alleles was detected in two markers and two pairs displayed gametic disequilibrium. No locus appeared to be sex‐linked.
Isolation and characterization of microsatellite loci for the Potentilla core group (Rosaceae) using 454 sequencing

Microsatellites are valuable markers for the analysis of genetic diversity, linkage mapping or genotyping. The limited availability of microsatellites for the genus Potentilla (Rosaceae) stipulated the isolation of markers from a representative (Potentilla pusilla Host) of the Potentilla core group that constitutes the most species‐rich evolutionary lineage within the genus. Thousand four hundred and seventy‐six simple sequence repeat (SSR) containing candidate sequences were isolated from a single‐type line using 454 sequencing. Seventy‐four functional microsatellite markers were developed from 200 sequences selected for suitable priming sites flanking microsatellite repeats referring to a 37% primer‐to‐marker conversion ratio. Seventy‐two markers were polymorphic. These numbers confirm the increased efficiency of pyrosequencing over traditional isolation techniques in the development of microsatellites. Amplification primer sequences and the sequences of corresponding target fragments are provided for all functional markers, and molecular polymorphisms estimated for four accessions of P. pusilla and among seven core group species represented by 14 individuals are reported. Cross‐species transferability ranged between 86.4% and 97.3% among the studied taxa, and 57, 11 and six of the selected primer pairs amplified fragments of expected size and number in seven, six and five of the species, respectively. Reproducibility of the molecular phenotypes was 97.0%, which was inferred using a replicate sample of P. pusilla.
Birth outcome and HIV infection among labouring women in Assosa Hospital, Southwest Ethiopia.

Background: Perinatal mortality rate is a sensitive indicator of quality of care provided to women in pregnancy, at and after childbirth and to the newborns in the first week of life. Regular prenatal audit would help in identifying all the factors that play a role in causing prenatal deaths and thus help take appropriate interventions to reduce the avoidable once, at least. Knowledge of mothers’ HIV positive status provides an entry point for appropriate care of the mothers, HIV exposed infants and other family members including children. Objectives: To assess birth outcomes and the magnitude of HIV infection among labouring mothers in Assosa hospital. Method: An institution-based cross-sectional survey was conducted in Assosa hospital from September 2008 to August 2009. A total of 581 labouring women were interviewed using a pretested structured questionnaire. Results: Data was obtained from 581 mothers. HIV infection among labouring women was 6.5%. Mothers, who had primary education [AOR=4.76, 95%CI= 1.81-12.52], no formal education [AOR=3.05, 95%CI= 1.08-8.64], mothers with two or more pregnancies [AOR=2.64, 95%CI= 1.08-6.49], and Muslims [AOR=0.32,95%CI= 0.13-0.82] were the independent predictors of HIV infection. There were 525 live births. The prenatal deaths were 69, making an overall prenatal mortality of 119 per 1000 total births. Bivariate analysis showed that rural women, women who had no ANC visit, mothers aged 30 years and above, with no formal education, housewives, Berta women of in ethnic group and Muslim were crudely associated with higher risk of prenatal mortality. Conclusion: The study identified high level of perinatal mortality and HIV infection. This study calls for effective antenatal care, delivering service, and a coordinated referral system and community interventions including HIV counseling, testing (VCT), treatment and support.