Defective Visceral Adipose Tissue Adaptation in Gestational Diabetes Mellitus.

Context: Gestational diabetes mellitus (GDM) is a complex obstetric condition affecting localized glucose metabolism, resulting in systemic metabolic dysfunction.

Objective: This cross-sectional study aimed to explore visceral adipose tissue (VAT) as an integral contributor to GDM, focusing on elucidating the specific contribution of obesity and GDM pathology to maternal outcomes.

Methods: Fifty-six nulliparous pregnant women were recruited, including normal glucose tolerant (NGT) (n = 30) and GDM (n = 26) participants.

Nurses' knowledge, perceived challenges, and recommended solutions regarding premature infant care: A mixed method study in the referral and tertiary hospitals in Dar es salaam, Tanzania.

Background: There has been an increase in preterm birth of about 2% in a span of 14 years (2000-2014) mainly from Asia and Sub-Saharan Africa. Nursing care is very crucial and a lack of knowledge of health care providers is a contributing factor to morbidity and mortality. With the increasing number and investment of preterm infants towards attaining sustainable development goals (SDG) 3.

Depression and chronic kidney disease: a cross-sectional study based at Bugando Medical Centre, Northwestern Tanzania.

Introduction: psychosocial distress such as depression is prevalent among chronic kidney disease (CKD) patients. It is often overlooked despite of reducing the patient´s quality of life.

Methods: this was a cross-sectional study aimed to determine the prevalence and factors associated with depression among CKD patients, whereby a practical sampling technique was used among patients attending Bugando Medical Centre, a tertiary level hospital in Mwanza, Tanzania.

Self-Determination in Health Research: An Alaska Native Example of Tribal Ownership and Research Regulation.

Alaska Native (AN) and American Indian (AI) people are underrepresented in health research, yet many decline to participate in studies due to past researcher misconduct. Southcentral Foundation (SCF), an Alaska Native-owned and operated health care organization, is transforming the relationship between researchers and the tribal community by making trust and accountability required features of health research in AN/AI communities. In 1998, SCF assumed ownership from the federal government of health services for AN/AI people in south central Alaska and transformed the health system into a relationship-based model of care.

Exploring pathways to trust: a tribal perspective on data sharing.

The data-sharing policies of the National Institutes of Health aim to maximize public benefit derived from genetic studies by increasing research efficiency and use of a pooled data resource for future studies. Although broad access to data may lead to benefits for populations underrepresented in genetic studies, such as indigenous groups, tribes have ownership interest in their data. The Northwest-Alaska Pharmacogenetic Research Network, a partnership involving tribal organizations and universities conducting basic and translational pharmacogenetic research, convened a meeting to discuss the collection, management, and secondary use of research data, and of the processes surrounding access to data stored in federal repositories.

Community-based participatory research in a large cohort study of chronic diseases among Alaska native adults.

Background: In 2001, the National Cancer Institute (NCI) funded a project to develop methods to recruit American Indian and Alaska Native (AI/AN) adults for a prospective cohort study of chronic disease risk and protective factors.

Objective: We describe how the use of community-based participatory research (CBPR) principles led to more effective study design and implementation in a study in Alaska.

Methods: CBPR elements included collaboration between researchers and tribes at all stages of the project, capacity building through training AI/AN staff in research methods, and knowledge dissemination through presentations, newsletters, and individual and community health feedback based on results of the study.

Rapid folding of the prion protein captured by pressure-jump.

The conversion of the cellular form of the prion protein (PrP(C)) to an altered disease state, generally denoted as scrapie isoform (PrP(Sc)), appears to be a crucial molecular event in prion diseases. The details of this conformational transition are not fully understood, but it is perceived that they are associated with misfolding of PrP or its incapacity to maintain the native fold during its cell cycle. Here we present a tryptophan mutant of PrP (F198W), which has enhanced fluorescence sensitivity to unfolding/refolding transitions.

The elusive intermediate on the folding pathway of the prion protein.

A key molecular event in prion diseases is the conversion of the cellular conformation of the prion protein (PrP(C)) to an altered disease-associated form, generally denoted as scrapie isoform (PrP(Sc)). The molecular details of this conformational transition are not fully understood, but it has been suggested that an intermediate on the folding pathway of PrP(C) may be recruited to form PrP(Sc). In order to investigate the folding pathway of PrP we designed and expressed two mutants, each possessing a single strategically located tryptophan residue.

Amyloid fibrils of mammalian prion protein induce axonal degeneration in NTERA2-derived terminally differentiated neurons.

Defects in axonal transport and synaptic dysfunctions are associated with early stages of several neurodegenerative diseases including Alzheimer's, Huntington's, Parkinson's, and prion diseases. Here, we tested the effect of full-length mammalian prion protein (rPrP) converted into three conformationally different isoforms to induce pathological changes regarded as early subcellular hallmarks of prion disease. We employed human embryonal teratocarcinoma NTERA2 cells (NT2) that were terminally differentiated into neuronal and glial cells and co-cultured together.

DNA vaccination can protect Cyprinus Carpio against spring viraemia of carp virus.

Several DNA constructs containing the spring viraemia of carp virus (SVCV) glycoprotein (G) gene were investigated for their ability to induce protection against SVCV following injection into myofibres. The constructs were pooled into four groups and co-injected with a plasmid encoding murine granulocyte-macrophage colony-stimulating factor. Group 1 contained one full-length and two truncated G constructs under the control of the cytomegalovirus (CMV) promoter.

Synthesis and structural characterization of a mimetic membrane-anchored prion protein.

During pathogenesis of transmissible spongiform encephalopathies (TSEs) an abnormal form (PrP(Sc)) of the host encoded prion protein (PrP(C)) accumulates in insoluble fibrils and plaques. The two forms of PrP appear to have identical covalent structures, but differ in secondary and tertiary structure. Both PrP(C) and PrP(Sc) have glycosylphospatidylinositol (GPI) anchors through which the protein is tethered to cell membranes.

Characterization of 2'-fluoro-RNA aptamers that bind preferentially to disease-associated conformations of prion protein and inhibit conversion.

We have isolated artificial ligands or aptamers for infectious prions in order to investigate conformational aspects of prion pathogenesis. The aptamers are 2'-fluoro-modified RNA produced by in vitro selection from a large, randomized library. One of these ligands (aptamer SAF-93) had more than 10-fold higher affinity for PrPSc than for recombinant PrPC and inhibited the accumulation of PrPres in near physiological cell-free conversion assay.

Stability and conformational properties of doppel, a prion-like protein, and its single-disulphide mutant.

Both prion protein and the structurally homologous protein doppel are associated with neurodegenerative disease by mechanisms which remain elusive. We have prepared murine doppel, and a mutant with one of the two disulphide bonds removed, in the expectation of increasing the similarity of doppel to prion protein in terms of conformation and stability. Unfolding studies of doppel and the mutant have been performed using far-UV CD over a range of solution conditions known to favour the alpha-->beta transformation of recombinant prion protein.

Structural changes of the prion protein in lipid membranes leading to aggregation and fibrillization.

Prion diseases are associated with a major refolding event of the normal cellular prion protein, PrP(C), where the predominantly alpha-helical and random coil structure of PrP(C) is converted into a beta-sheet-rich aggregated form, PrP(Sc). Under normal physiological conditions PrP(C) is attached to the outer leaflet of the plasma membrane via a GPI anchor, and it is plausible that an interaction between PrP and lipid membranes could be involved in the conversion of PrP(C) into PrP(Sc). Recombinant PrP can be refolded into an alpha-helical structure, designated alpha-PrP isoform, or into beta-sheet-rich states, designated beta-PrP isoform.

Mouse germline restriction of Oct4 expression by germ cell nuclear factor.

The POU-domain transcription factor Oct4 is essential for the maintenance of the mammalian germline. In this study, we show that the germ cell nuclear factor (GCNF), an orphan nuclear receptor, represses Oct4 gene activity by specifically binding within the proximal promoter. GCNF expression inversely correlates with Oct4 expression in differentiating embryonal cells.

Repression of Oct-4 during embryonic cell differentiation correlates with the appearance of TRIF, a transiently induced DNA-binding factor.

The Oct-4 gene encodes a transcription factor that is essential for maintaining the mouse germline. It is expressed during the earliest stages of embryogenesis, is downregulated during gastrulation, and is thereafter constrained to the germ cell lineage. Retinoic acid induced differentiation of embryonal carcinoma cells is also accompanied by a decrease in Oct-4 expression.

Mammalian granulocyte-macrophage colony-stimulating factor and some CpG motifs have an effect on the immunogenicity of DNA and subunit vaccines in fish.

A eukaryotic plasmid DNA carrying the AACGTT CpG motif in its ampR gene is a 'danger' signal for mice and caused an increase in the specific antibody titres of fish and mice after immunization with beta-galactosidase (beta-gal). A second pUC-based plasmid, which is inactive in mice and contains the GACGTC CpG motif in its cytomegalovirus (CMV) promoter, had no effect on antibody responses to beta-gal in either fish or mice. A synthetic oligonucleotide, which contains the GACGTT motif, potentiated antibody responses to co-administered beta-gal protein in mice, but not in fish.

The safety and longevity of DNA vaccines for fish.

A plasmid that contained the cytomegalovirus (CMV)-promoter-driven lacZ reporter gene (pCMV-lacZ) remained in the epaxial muscle of five of eight goldfish as covalently closed circles, the most functional form of plasmid, for at least 70 days at 22 degrees. It was not present in the gills or elsewhere by polymerase chain reaction and was not integrated. Its expressed protein, Escherichia coli beta-galactosidase (beta-gal), which was in the injected myofibres, was detected in all the fish at 4-21 days and in about half the fish from 28 days until the end of the experiment at 70 days.

DNA is as effective as protein at inducing antibody in fish.

Antiviral vaccines are needed for fish. 50 microg plasmid DNA in saline by the intramuscular route and 10 microg beta-gal protein in a commercial oil adjuvant by the peritoneal route induced serum antibody of the same titre and avidity in goldfish. The DNA expressed beta-gal under control of the immediate early promoter/enhancer gene of human cytomegalovirus.

Characterization of prokaryotic recombinant Aspergillus ribotoxin alpha-sarcin.

The Aspergillus ribonuclease alpha-sarcin is toxic to intact mammalian cells but the mechanism by which it enters the cells to reach its ribosomal RNA substrate is unclear. Here we have compared the cytotoxicity of alpha-sarcin to that of ricin, another catalytic toxin that targets the same rRNA sequence but whose mechanism of cell entry is better understood. Intact ricin binds to cell surface components and enters the cells by receptor-mediated endocytosis, whereas the catalytic polypeptide of ricin (the A chain or RTA) which, like alpha-sarcin, is unable to bind to surface components directly and enters cells by fluid phase uptake.

Retinoic acid-mediated down-regulation of Oct3/4 coincides with the loss of promoter occupancy in vivo.

Oct3/4, a hallmark of the earliest stages of embryogenesis, is expressed in undifferentiated embryonal carcinoma (EC) and embryonic stem (ES) cells. Oct3/4 gene expression is dependent on the promoter region, the proximal enhancer and the newly identified distal enhancer. We have analysed in vivo occupancy of these elements.

Regulation of the Oct-4 gene by nuclear receptors.

To unravel the network of transcription factors established during development it is important to understand how genes specifically expressed during embryogenesis are regulated. Oct-4 is a transcription factor whose expression is associated with an undifferentiated cell phenotype in the early mouse embryo and is downregulated when such cells differentiate. An enhancer in the upstream region of Oct-4 has previously been reported as being sufficient to mediate the cell-type specific expression and RA-dependent down-regulation in EC cells, although the enhancer contains no retinoic acid receptor (RAR) binding sites.

Neutrophil attractant protein-1 and monocyte chemoattractant protein-1 in human serum. Effects of intravenous lipopolysaccharide on free attractants, specific IgG autoantibodies and immune complexes.

We recently found that normal human sera contain IgG antibodies against two chemoattractants, neutrophil attractant protein-1 (NAP-1/IL-8) and monocyte chemoattractant protein-1 (MCP-1), as well as immune complexes of these proteins. Intravenously administered LPS was reported to cause a sharp rise in serum NAP-1 concentration. Our study was designed to determine if LPS also caused an increase in MCP-1 and to measure associated changes in concentrations of antibody and immune complex.

Neutrophil attractant protein-1-immunoglobulin G immune complexes and free anti-NAP-1 antibody in normal human serum.

After obtaining data indicating the presence of a neutrophil attractant protein-1 (NAP-1)-IgG complex in normal human serum, we developed sandwich ELISAs that could quantify NAP-1 and NAP-1-IgG in mixtures of the two moieties. The ELISA for free NAP-1 used a monoclonal capture antibody that did not bind NAP-1-IgG. The ELISA for NAP-1-IgG was based on omission of the anti-NAP-1 detection antibody (required for the free NAP-1 ELISA) and on interaction of phosphatase-conjugated anti-human IgG with the human NAP-1-IgG complex.