Miracle-dz/UniFAR-FTUs huggingface dataset:
Plasma immunoglobulin concentrations in a West African (Gambian) community and in a group of healthy British adults.

Plasma concentrations of IgG, IgA, IgM and IgD of 1123 members of a native West African (Gambian) community and of ninety-one British adults were measured using a single radial diffusion technique. The African plasmas showed changes of immunoglobulin concentration with age which were characteristic for each class. Gambian children attained adult levels of IgG by about the 5th year of age. Mean IgG concentration in Gambian adults was approximately twice that of the British adults. IgA was not detected in Gambian children in the first few days of life. British and Gambian adults showed a similar broad range of IgA concentrations, and in Gambians the range broadened progressively with increasing age. IgM was detected in all Gambian sera, including that from the youngest children. Values rose rapidly during the first 3 months of life. In Gambian adults a broad range of values was found, with higher values becoming more frequent in the elderly. IgM levels in some Gambian sera were conspicuously increased compared with the British sera, but the anticipated increase of 19S proteins in the ultra-centrifuge was not found. High IgM levels were not associated with evidence of infection with Trypanosoma gambiense, nor were the findings typical of Walden-strom's macroglobulinaemia. IgD was not detected in Gambian children less than 2 months of age, but a broad range of values was found in childhood and adolescence. In adults higher levels occurred less frequently and the distribution of levels was similar to that of the British population. The significance of these findings is discussed.
Encapsulation of curcumin in polyelectrolyte nanocapsules and their neuroprotective activity

Poor water solubility and low bioavailability of lipophilic drugs can be potentially improved with the use of delivery systems. In this study, encapsulation of nanoemulsion droplets was utilized to prepare curcumin nanocarriers. Nanosize droplets containing the drug were encapsulated in polyelectrolyte shells formed by the layer-by-layer (LbL) adsorption of biocompatible polyelectrolytes: poly-L-lysine (PLL) and poly-L-glutamic acid (PGA). The size of synthesized nanocapsules was around 100 nm. Their biocompatibility and neuroprotective effects were evaluated on the SH-SY5Y human neuroblastoma cell line using cell viability/toxicity assays (MTT reduction, LDH release). Statistically significant toxic effect was clearly observed for PLL coated nanocapsules (reduction in cell viability about 20%–60%), while nanocapsules with PLL/PGA coating did not evoke any detrimental effects on SH-SY5Y cells. Curcumin encapsulated in PLL/PGA showed similar neuroprotective activity against hydrogen peroxide (H2O2)-induced cell damage, as did 5 μM curcumin pre-dissolved in DMSO (about 16% of protection). Determination of concentration of curcumin in cell lysate confirmed that curcumin in nanocapsules has cell protective effect in lower concentrations (at least 20 times) than when given alone. Intracellular mechanisms of encapsulated curcumin-mediated protection engaged the prevention of the H2O2-induced decrease in mitochondrial membrane potential (MMP) but did not attenuate Reactive Oxygen Species (ROS) formation. The obtained results indicate the utility of PLL/PGA shell nanocapsules as a promising, alternative way of curcumin delivery for neuroprotective purposes with improved efficiency and reduced toxicity.
Isolation and characterization of Pseudomonas aeruginosa mutants blocked in the synthesis of pyoverdin

We have isolated and characterized by chemical and enzymatic analyses three distinct types of pyoverdin-defective (pvd) mutants of Pseudomonas aeruginosa PAO1. The pvd-1 mutant is an L-N5-hydroxyornithine (L-N5-OH-Orn) auxotroph unable to hydroxylate L-ornithine (L-Orn) in a cell-free system and requiring L-N5-OH-Orn for pyoverdin production. The other two types of mutants appear to be blocked in further steps of the biosynthetic pathway leading to pyoverdin, namely, the acylation of L-N5-OH-Orn (pvd-2) and chromophore synthesis (pvd-3). The different pvd mutations were all found to be located in the catA1 region at 47 min of the genetic map of P. aeruginosa PAO1.
Biological applications of X-ray microtomography: imaging micro- anatomy, molecular expression and organismal diversity

X-ray microtomographic imaging is coming into more widespread use in life sciences research. Micro-CT produces whole-volume images of intact samples with resolutions extending into the range of light microscopy and is most powerful in combination with other imaging techniques. The versatility of lab-based micro-CT systems makes them well-suited to a wide variety of applications in biological research, from comparative embryology and functional microanatomy to developmental paleontology. Simple contrast staining enables histologyscale 3D imaging of intact soft tissues in embryos, insects, and other soft-bodied specimens. The inherent size calibration of tomographic images offers the potential for quantitative analysis and modeling. Here I describe some current applications of x-ray microtomographic imaging to research in
Bone Morphogenetic Proteins and Adipocyte Differentiation

Bone morphogenetic proteins (BMPs) regulate many processes during embryogenesis and morphogenesis. However, the role of this family of proteins in adipogenesis appears to be underappreciated in the field of developmental biology. In the past fifteen years, our concept of adipose tissue has undergone a radical transformation: initially viewed as an inert mass for energy storage, adipose tissue is now seen as an endocrine organ with an important role in the regulation of wholebody energy homeostasis. Interest in adipocyte differentiation has increased markedly in the past few years with major emphasis on transcriptional controls during adipocyte formation. Clearly, much remains to be learned about adipogenesis. In this review, we summarize recent progress on the roles of BMPs in adipogenesis in mesenchymal stem cells and committed preadipocytes, and ultimately their potential involvement in the regulation of energy metabolism.
Neurogliaform cells in the molecular layer of the dentate gyrus as feed‐forward γ‐aminobutyric acidergic modulators of entorhinal–hippocampal interplay

Feed‐forward inhibition from molecular layer interneurons onto granule cells (GCs) in the dentate gyrus is thought to have major effects regulating entorhinal–hippocampal interactions, but the precise identity, properties, and functional connectivity of the GABAergic cells in the molecular layer are not well understood. We used single and paired intracellular patch clamp recordings from post‐hoc‐identified cells in acute rat hippocampal slices and identified a subpopulation of molecular layer interneurons that expressed immunocytochemical markers present in members of the neurogliaform cell (NGFC) class. Single NGFCs displayed small dendritic trees, and their characteristically dense axonal arborizations covered significant portions of the outer and middle one‐thirds of the molecular layer, with frequent axonal projections across the fissure into the CA1 and subicular regions. Typical NGFCs exhibited a late firing pattern with a ramp in membrane potential prior to firing action potentials, and single spikes in NGFCs evoked biphasic, prolonged GABAA and GABAB postsynaptic responses in GCs. In addition to providing dendritic GABAergic inputs to GCs, NGFCs also formed chemical synapses and gap junctions with various molecular layer interneurons, including other NGFCs. NGFCs received low‐frequency spontaneous synaptic events, and stimulation of perforant path fibers revealed direct, facilitating synaptic inputs from the entorhinal cortex. Taken together, these results indicate that NGFCs form an integral part of the local molecular layer microcircuitry generating feed‐forward inhibition and provide a direct GABAergic pathway linking the dentate gyrus to the CA1 and subicular regions through the hippocampal fissure. J. Comp. Neurol. 519:1476–1491, 2011. © 2010 Wiley‐Liss, Inc.
13C and 1H nuclear magnetic resonance studies of bradykinin and selected peptide fragments.

Complete /sup 13/C chemical shift assignments of the nonapeptide bradykinin have been made on the basis of pH titration studies and the examination of peptide fragments. Hysteresis effects previously reported for the /sup 13/C shifts of the Arg/sup 9/ resonances as a function of pH and interpreted to reflect an intramolecular salt bridge involving the Arg/sup 1/ guanido and the Arg/sup 9/ carboxyl (Ivanov, V. T., et al. (1975) Bioorg. Khim. 1, 1241; Proc. 4th Am. Pept. Symp. , 151) were not observed in the present study. Chemical shifts of the proline carbons indicate that the trans configuration about the three X-Pro peptide bonds is strongly favored in all cases, although the minor cis resonances accounting for approximately 10% of the proline intensity can also be observed. In addition, there appears to be no significant pH sensitivity of the cis reversible trans equilibria. Studies of the solvent dependence (water .-->. methanol) of the carbonyl shifts are consistent with the possibility of an intramolecular hydrogen bond involving the Ser/sup 6/ carbonyl oxygen. Preliminary /sup 1/H nuclear magnetic resonance studies of the amide proton region of bradykinin and the C-terminal tetrapeptide Ser-Pro-Phe-Arg are also reported. In the latter peptide, the Phe/sup 8/ andmore » Arg/sup 9/ amide proton resonances appear as two sets of resonances corresponding to the cis and trans configurations of the Ser-Pro bond. The temperature dependenceof the proton shifts of the amide resonances is independent of whether the Ser-Pro bond is cis or trans, indicating that any intramolecular hydrogen bonding existing only for the trans peptide is insufficient to significantly reduce this parameter. Measurements of the /sup 13/C spin-lattice relaxation times indicate rapid internal motion for all of the peptide side chains, supporting the interpretation that bradykinin exists in solution primarily in a disordered state. « less
Mobilization of small plasmids in Bacillus thuringiensis subsp. israelensis is accompanied by specific aggregation

Mobilizations of pBC16 and pAND006, containing the replicon of the Bacillus thuringiensis subsp. israelensis plasmid pTX14-3, between strains of B. thuringiensis subsp. israelensis were examined. Transconjugants appeared after a few minutes and reached a maximum frequency after approximately 2 h. Plasmid pBC16 was mobilized at a frequency approximately 200 times that of pAND006. However, pAND006 was consistently transferred, suggesting that the replicon of pTX14-3 is sufficient to sustain mobilization in B. thuringiensis subsp. israelensis. A specific protease-sensitive coaggregation between strains of B. thuringiensis subsp. israelensis was found to be unambiguously correlated with plasmid transfer. Two aggregation phenotypes, Agr+ and Agr-, were identified in this subspecies. Aggregation disappeared when the optical density of the mating mixture at 600 nm exceeded approximately 1, and it did not reappear upon dilution. Aggregation was shown to involve interactions of cells with opposite aggregation phenotypes, and evidence of a proteinaceous molecule on the surface of the Agr- that is cells involved in aggregation formation is presented. Matings and selection for the presence of two antibiotic resistance plasmids followed by identification of the host cell revealed that mobilization was unidirectional, from the Agr+ cell to the Agr- cell. The aggregation phenotype was found to be transferred with high frequency (approximately 100%) in broth matings, and the appearance of Agr- isolates from Agr+ strains suggested that the loci involved in aggregation formation are located on a plasmid. No excreted aggregation-inducing signals were detected in the supernatant or culture filtrate of either the donor, the recipient, or the mating mixture.
Patient-assessed versus physician-assessed disease severity and outcome in patients with nonspecific pain associated with major depressive disorder.

OBJECTIVES This post hoc analysis compared how patients and physicians estimate disease severity and global improvement during 8 weeks of treatment for major depressive disorder (MDD) with associated nonspecific pain. In addition, predictors of pain and depression were identified. METHOD Data were derived from a double-blind, placebo-controlled, multicenter, European study (conducted from May 2005 to May 2006) in adult outpatients with MDD (DSM-IV criteria) and moderate pain not attributable to a diagnosed organic pain syndrome (Brief Pain Inventory-Short Form [BPI-SF] average pain score ≥ 3). Patients were randomly assigned to duloxetine 60 mg/day or placebo and treated for 8 weeks. Physicians were asked to rate severity of depression by using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impressions-Severity of Illness (CGI-S) and CGI-Improvement (CGI-I) scales. Patients were asked to assess pain using the BPI-SF, psychological symptomatology (9 domains including depression) with the Symptom Checklist-90-Revised (SCL-90-R), and overall improvement with the Patient Global Impression of Improvement (PGI-I). Multivariate linear regressions were performed as post hoc analyses to identify predictors of disease assessment at baseline and at the end of the study using a last-observation-carried-forward approach. RESULTS All SCL-90-R domains improved during the 8 weeks of treatment. At baseline, the MADRS was associated only with the SCL-90-R obsessive-compulsive score, while the SCL-90-R depression score was associated with the BPI-SF average pain score and with many SCL-90-R subscores. The global impression of improvement was rated higher by the physicians than by the patients. At the end of the study, CGI-I was significantly associated with a decrease in depression severity (MADRS; p < .0001), younger age (p = .0005), and a decrease of the SCL-90-R interpersonal sensitivity score (p = .0359), but not with BPI-SF average pain. In contrast, patient-rated PGI-I was significantly associated with the SCL-90-R depressive domain (p < .0001), BPI-SF average pain (p = .0003), and the SCL-90-R anxiety domain (p = .0041) scores. CONCLUSION In patients with MDD associated with at least moderate nonspecific pain, physicians consider mainly the change in depressive symptoms as measured by MADRS in their CGI-I ratings, while patients also consider pain, depression, and anxiety in their PGI-I ratings. When treating depression and assessing treatment outcome, a broad spectrum of symptoms needs to be monitored. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00191919.
Molecular analysis of paternity shows promiscuous mating in female humpback whales (Megaptera novaeangliae, Borowski)

It is widely assumed that the mating system of the humpback whale, Megaptera novaeangliae, is similar to that of most mammals in that it represents some form of polygyny or promiscuity, but this cannot be tested without observations of copulation or data on paternity of offspring. Microsatellite DNA markers were used to examine the paternity of calves born to individually identified mature female humpback whales from the Gulf of Maine. Skin biopsies were obtained from three females, and several (range: three to five) of their known offspring. Multiple paternity of offspring, indicated by the presence of at least three different paternal alleles, was evident in all three females at either three or four of the six microsatellite loci surveyed. Such promiscuous mating is expected given current knowledge of the social ecology of this species. It is also consistent with resightings of individually identified female humpbacks with different male associates during two or more breeding seasons.
Central amplification and fibromyalgia: Disorder of pain processing

Fibromyalgia (FM), a complex chronic pain disorder affecting a heterogeneous patient population, is an area of active basic and clinical research. Although diagnostic criteria for FM have been available for 2 decades, there remains no definitive diagnostic and no consensus regarding its etiology. Accumulating evidence suggests the underlying cause of FM pain results from abnormal pain processing particularly in the central nervous system rather than from dysfunction in peripheral tissues where pain is perceived. In this review, we examine recent studies investigating abnormalities in central pain processing as a component of FM in both preclinical models of generalized muscle hypersensitivity and clinical research in patients with FM. We focus our discussion on two areas where strong evidence exists for abnormalities in sensory signaling: the reduction of descending control, including suppression of descending inhibitory pathways and/or enhancement of descending facilitatory pathways, and changes in key neurotransmitters associated with central sensitization. Finally, we discuss currently available pharmacological treatments indicated for the management of pain in FM patients, based on their proposed mechanism of action and efficacy. © 2010 Wiley‐Liss, Inc.
The theoretical-empirical fit between three psychological wellness constructs : sense of coherence, learned resourcefulness and self-actualisation

The aim of this research was to investigate the theoretical-empirical fit between three psychological well-being constructs, namely sense of coherence, learned resourcefulness and self-actualisation in the work situation. Significant intercorrelations were found. Confirmatory factor analysis indicated a two-factor structure consisting of (1) self-actualisation and (2) sense of coherence / learned resourcefulness. The results confirm that, of these three concepts, self-actualisation forms a separate construct within the psychological well-being (and salutogenic) paradigms, but the results did not indicate a good fit between the theoretical model and the empirical reality of psychological well-ness. It is hoped that awareness of this information will facilitate more effective labour relations and handling of disputes in organisations.
Effect of treatment with the Molecular Adsorbents Recirculating System on arterial amino acid levels and cerebral amino acid metabolism in patients with hepatic encephalopathy

Background: Liver failure is associated with low concentrations of branched‐chain amino acids and high concentrations of most other amino acids. In this study the effect of treatment with the Molecular Adsorbents Recirculating System (MARS) on arterial amino acid levels and cerebral amino acid metabolism was examined in patients with severe hepatic encephalopathy. Methods: The study included seven patients with hepatic encephalopathy from fulminant hepatic failure (FHF) and five patients with hepatic encephalopathy from acute‐on‐chronic liver failure (AoCLF). Cerebral blood flow and cerebral arteriovenous differences in amino acids were measured before and after 6 h of treatment with MARS. Results: During MARS treatment, the total arterial amino acid concentration decreased by 20% from 8.92 ± 7.79 mmol/L to 7.16 ± 5.64 mmol/L (P < 0.05). The concentration decreased in all amino acids with the exception of the branched‐chain amino acids. Fischer's ratio of branched‐chain to aromatic amino acids increased from 0.73 ± 0.47 to 0.91 ± 0.54 (P < 0.05). A net cerebral efflux of amino acids in patients with FHF (8.94 ± 8.34 μmol/100 g/min) as well as AoCLF (7.35 ± 24.97 μmol/100 g/min) was not affected by the MARS treatment. MARS had no effect on the cerebral metabolic rate of any single amino acid in either group. Conclusions: MARS treatment tends to normalize the arterial amino acid concentrations in patients with hepatic encephalopathy. Even though the overall reduction in plasma amino acids and improvement in amino acid dysbalance may well be beneficial, it was not accompanied by any immediate improvement in cerebral amino acid metabolism in patients with FHF or AoCLF.
NG2/CSPG4 Proteoglycan as a Novel Prognostic Indicator and Therapeutic Target in Malignant Cancer

This review article describes the interaction of Neuron-glia 2 Chondroitin Sulfate Proteoglycan 4 (NG2/CSPG4) in cancer cell matrix, and its role within the cancer cell matrix in promoting angiogenesis and its potential clinical use as a novel immune drug target. Malignant cancer is maintained by a cross-talk between the cancer cells and cancer cell matrix where the activated cancer cell matrix nurtures the advancing cancer cells by providing Extracellular Matrix (ECM), neovasculature and stimulatory growth factors. Researches in recent years have accumulated a wealth of novel insight into mechanisms by which how cancer cells are co-evolved with activated cancer cell matrix throughout cancer settings. Currently, the cancer cell matrix is considered as an important “effector” in carcinogenesis. Once tightly defined cell matrix in normal tissue occasionally becomes sabotaged, the inevitable malignant progression will flip on. NG2/CSPG4 is a big multifunctional transmembrane proteoglycan with limited expression in normal tissues and its unparalleled structural-functional diversity endows it with the ability to serve as critical mediator. We describe here how the manipulation of NG2/CSPG4 on the processes driving malignant cancer cell matrix activation promotes carcinogenesis through the alteration of cancer cell adhesion, infiltration, migration, proliferation and angiogenesis, and how it will be possibile to design a decisive strategy for the development of a novel therapy specifically targeting this macromolecule for malignant cancer treatment.
SYNTHETIC PEPTIDE F 2 A 4K-NS MIMICS FGF-2 IN VITRO AND IS ANGIOGENIC IN VIVO *

A multi-domain synthetic peptide, F2A4-K-NS, mimicked the action of recombinant human FGF-2 (rhFGF-2) in vitro and in an in vivo model of angiogenesis. Like rhFGF-2, F2A4-K-NS was quantitatively shown to bind to FGF receptors in a cell-free receptor binding assay using a chimeric FGFR1 (IIIc)/Fc and monitored by surface plasmon resonance (SPR), and also shown to bind to heparin using biotinylated low molecular weight heparin in a similar SPR assay. In vitro, F2A4-K-NS triggered signal transduction as monitored by the stimulation of ERK1/2 phosphorylation in human umbilical cord endothelial cells. In cell based assays, it increased cell migration, cell proliferation, and gelatinase secretion; endpoints associated with FGF-2 stimulation. Furthermore, these in vitro effects were mediated with quantities of F2A4-K-NS that were similar to that of rhFGF-2. In vivo, F2A4-K-NS was angiogenic at doses of 40and 400 ng/implant in a subcutaneous implant assay as determined by morphologic scoring, hemoglobin content, and histology. These results support the hypothesis that F2A4-K-NS is a mimetic of FGF-2 that can substitute for FGF-2 in vitro and in vivo. A synthetic mimetic of FGF-2, such as F2A4-K-NS, could be a useful tool in studying mechanisms of cell activation and potentially in various therapeutic applications.