Investigations of Poly[(Styrene-Co-P-Methylstyrene)-Risobutylene- R-(Styrene-Co-P-Methylstyrene)] and Poly[(Acrylic Acid)-5-Styrene-Jb-Is0butylene-5-Styrene-Jb-(Acrylic Acid)]

The pMe study was conducted to understand the morphological and physical property changes that occur as the ratio of pMe to styrene is increased, effectively increasing the aliphatic units. By the introduction of pMe, the interface region becomes more blended/compatible as the pMe migrates to the interface. These pMe groups are theorized in effect to create multiple ‘anchors’ to distribute the loads experienced at the interface more effectively creating a synergistic effect on the final properties of the copolymers. The primary goals of the pentablock study were the characterization of unique membranes as related to the morphologies and physical properties of poly[(/-butyl acrylate)-Z\u3e-styrene-Z\u3e-isobutylene-b-styrene-b-(/-butyl acrylate)] and poly[(acrylic acid)- 6 -styrene-6 -isobutylene-Z\u3e-styrene-b-(acrylic acid)]. Specifically, the reaction to convert /-butyl acrylate to acrylic acid group as well as the anhydride ring formation and stability as it relates to morphology was explored. The overall morphologies of these pentablocks demonstrate more restrictions due to the architecture of the chain, and these three articulated phase morphologies create an opportunity for use in diffusion and charge transport in these polymers. Investigations in morphologies, physical properties, nanoindenation, permeation, diffusion, conductivity, and dielectric relaxation spectroscopy were conducted as a function of increasing acrylic acid in the pentablocks

Health Communication and Health Education: Empowering Students to Educate Their Communities

Objectives: After completing this project, students will be able to: (a) use health communication research and theory to create educational materials; (b) analyze an audience and develop creative educational materials based on audience characteristics; and (c) consult with key constituents during the development of educational material

Significance of the disulphide bonds of human growth hormone

Struktura hormonu wzrostu (GH, growth hormone) stabilizowana jest dwoma wiązaniami disiarczkowymi — C53-C165 o C182-C189w ludzkim GH. Naukowcy badają rolę tych cech strukturalnych od końca lat 60. ubiegłego stulecia. Początkowe badania sugerowały, żewspomniane wiązania disiarczkowe nie są istotne dla aktywności biologicznej GH. Jednak w wyniku zastosowania bardziej zaawansowanychtechnik badawczych, a także na podstawie danych uzyskanych u pacjentów będących nosicielami mutacji genu GH1 stwierdzono,że dla aktywności biologicznej GH konieczna jest obecność wiązania disiarczkowego między cysteiną w pozycji C53 i cysteiną w pozycjiC165. Z kolei przerwanie C-końcowego wiązania disiarczkowego (C182-C189) w niewielkim zakresie wpływa na siłę działania biologicznegoGH mimo stwierdzonego w kompleksowym badaniu in vitro obniżenia powinowactwa wiązania z receptorem GH i obniżenia trwałości.W celu potwierdzenia tych wyników autorzy otrzymali myszy transgeniczne, u których zachodzi ekspresja analogu ludzkiego GH —C189A, i stwierdzili prawidłowe działanie pobudzające wzrost i prawidłowy wpływ na lipolizę. W niniejszej pracy przedstawiamy nowedane i przegląd dotychczasowych danych na temat wiązań disiarczkowych w GH. Omawiany też istotne mutacje stwierdzane u pacjentówz zaburzeniami wzrastania.Growth hormone (GH) structure is stabilised by two disulphide bonds, C53-C165 and C182-C189 in human GH. Researchers have investigatedthe role of these structural features since the late 1960s. Early studies implied that the disulphide bonds would not be importantfor biological activity of GH. However, more advanced techniques, as well as clues from patients carrying mutations in their GH1 gene,have demonstrated that the integrity of the disulphide bond between cysteines C53 and C165 is required for biological activity of GH.In contrast, disruption of the C-terminal disulphide bond (C182-C189) has only modest effects on the biological potency of GH, despitedecreased binding affinity to GH receptor and reduced stability as shown by a comprehensive in vitro study.To confirm these results, we generated transgenic mice that express a human GH analogue, C189A, and observed normal growth-promotingand lipolytic activities. In this article, we present new data and review old results concerning the disulphide bonds of GH. We also discussrelevant mutations found in patients with growth disorders

Glutamate, and its relationship to task-induced functional connectivity in the human brain: A focus on schizophrenia

Glutamate is the brain’s major excitatory neurotransmitter mediating both neuroplasticity and network function (Zhou & Danbolt, 2014). Basal glutamate (Glu) measured using proton magnetic resonance spectroscopy (1H-MRS) provides insight into a region’s density of neuropil related to the glutamatergic system. Moreover, given the role of glutamate in mediating brain network function, Glu levels may play a role in the brain’s functional connectivity (FC), which is typically estimated from functional magnetic resonance imaging (fMRI) time series data. These questions converge when considering the clinical syndrome of schizophrenia (SCZ). Patients with SCZ show abnormalities in basal Glu in the hippocampus and prefrontal cortex (Tebartz et al., 2013). They also show functional dys-connectivity across brain networks induced by tasks of learning (Baajour et al., 2020). Yet, no investigations have systematically assessed relationships between basal Glu and task-induced FC in healthy controls (HC), and possibly altered relationships in SCZ. Here, we will explore relationships between Glu (hippocampus and prefrontal cortex) and whole-brain functional connectivity derived from fMRI data acquired using a specifically tailored learning task (Ravishankar et al., 2019). Data was acquired in a single session in 72 participants (36 SCZ and 36 HC). From Glu quantitated in the hippocampus and the prefrontal cortex (LC Model, Woodcock et al., 2018), we will explore statistical relationships to FC estimated across a 90-node brain network, using a combination of clustering and graph theoretic methods, and address whether these relationships differ between HC and SCZ

Inflammatory and Glutamatergic Homeostasis Are Involved in Successful Aging

Whole body studies using long-lived growth hormone receptor gene disrupted or knock out (GHR-KO) mice report global GH resistance, increased insulin sensitivity, reduced insulin-like growth factor 1 (IGF-1), and cognitive retention in old-age, however, little is known about the neurobiological status of these mice. The aim of this study was to determine if glutamatergic and inflammatory markers that are altered in aging and/or age-related diseases and disorders, are preserved in mice that experience increased healthspan. We examined messenger ribonucleic acid (mRNA) expression levels in the brain of 4- to 6-, 8- to 10-, and 20- to 22-month GHR-KO and normal aging control mice. In the hippocampus, glutamate transporter 1 (GLT-1) and anti-inflammatory nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB)-p50 were elevated in 8- to 10-month GHR-KO mice compared with age-matched controls. In the hypothalamus, NFκB-p50, NFκB-p65, IGF-1 receptor (IGF-1R), glutamate/aspartate transporter (GLAST), and 2-amino-3-(5-methyl-3-oxo 2,3-dihydro-1,2 oxazol-4-yl) propanoic acid receptor subunit 1 (GluA1) were elevated in 8- to 10- and/or 20- to 22-month GHR-KO mice when comparing genotypes. Finally, interleukin 1-beta (IL-1β) mRNA was reduced in 4- to 6- and/or 8- to 10-month GHR-KO mice compared with normal littermates in all brain areas examined. These data support the importance of decreased brain inflammation in early adulthood and maintained homeostasis of the glutamatergic and inflammatory systems in extended longevity

Excessive growth hormone expression in male GH transgenic mice adversely alters bone architecture and mechanical strength

Patients with acromegaly have a higher prevalence of vertebral fractures despite normal bone mineral density (BMD), suggesting that GH overexpression has adverse effects on skeletal architecture and strength. We used giant bovine GH (bGH) transgenic mice to analyze the effects of high serum GH levels on BMD, architecture, and mechanical strength. Five-month-old hemizygous male bGH mice were compared with age- and sex-matched nontransgenic littermates controls (NT; n=16/group). Bone architecture and BMD were analyzed in tibia and lumbar vertebrae using microcomputed tomography. Femora were tested to failure using three-point bending and bone cellular activity determined by bone histomorphometry. bGH transgenic mice displayed significant increases in body weight and bone lengths. bGH tibia showed decreases in trabecular bone volume fraction, thickness, and number compared with NT ones, whereas trabecular pattern factor and structure model index were significantly increased, indicating deterioration in bone structure. Although cortical tissue perimeter was increased in transgenic mice, cortical thickness was reduced. bGH mice showed similar trabecular BMD but reduced trabecular thickness in lumbar vertebra relative to controls. Cortical BMD and thickness were significantly reduced in bGH lumbar vertebra. Mechanical testing of femora confirmed that bGH femora have decreased intrinsic mechanical properties compared with NT ones. Bone turnover is increased in favor of bone resorption in bGH tibia and vertebra compared with controls, and serum PTH levels is also enhanced in bGH mice. These data collectively suggest that high serum GH levels negatively affect bone architecture and quality at multiple skeletal sites

Differential inhibition of postnatal brain, spinal cord and body growth by a growth hormone antagonist

BACKGROUND: Growth hormone (GH) plays an incompletely understood role in the development of the central nervous system (CNS). In this study, we use transgenic mice expressing a growth hormone antagonist (GHA) to explore the role of GH in regulating postnatal brain, spinal cord and body growth into adulthood. The GHA transgene encodes a protein that inhibits the binding of GH to its receptor, specifically antagonizing the trophic effects of endogenous GH. RESULTS: Before 50 days of postnatal age, GHA reduces spinal cord weight more than brain weight, but less than body weight. Thereafter, GHA ceases to inhibit the increase in body weight, which approaches control levels by day 150. In contrast, GHA continues to act on the CNS after day 50, reducing spinal cord growth to a greater extent and for a longer duration than brain growth. CONCLUSIONS: Judging from its inhibition by GHA, GH differentially affects the magnitude, velocity and duration of postnatal growth of the brain, spinal cord and body. GH promotes body enlargement more than CNS growth early in postnatal life. Later, its CNS effects are most obvious in the spinal cord, which continues to exhibit GH dependence well into adulthood. As normal CNS growth slows, so does its inhibition by GHA, suggesting that reduced trophic effects of GH contribute to the postnatal slowing of CNS growth. GHA is a highly useful tool for studying the role of endogenous GH on organ-specific growth during aging

Oś hormon wzrostu–insulinopodobny czynnik wzrostu a karcynogeneza

  The growth hormone (GH) and insulin-like growth factor (IGF) system plays an important role in the regulation of cell proliferation, differentiation, apoptosis, and angiogenesis. In terms of cell cycle regulation, the GH-IGF system induces signalling pathways for cell growth that compete with other signalling systems that result in cell death; thus the final effect of these opposed forces is critical for normal and abnormal cell growth. The association of the GH-IGF system with carcinogenesis has long been hypothesised, mainly based on in vitro studies and the use of a variety of animal models of human cancer, and also on epidemiological and clinical evidence in humans. While ample experimental evidence supports a role of the GH-IGF system in tumour promotion and progression, with several of its components being currently tested as central targets for cancer therapy, the strength of evidence from patients with acromegaly, GH deficiency, or treated with GH is much weaker. In this review, we will attempt to consolidate this data. (Endokrynol Pol 2016; 67 (4): 414–426)    Oś hormon wzrostu (GH)–insulinopodobny czynnik wzrostu (IGF) odgrywa istotną rolę w regulacji proliferacji i różnicowania komórek, apoptozy i angiogenezy. Oś GH–IGF wpływa na regulację cyklu komórkowego przez pobudzenie szlaku wzrostu komórki w stosunku do szlaków sygnałowych prowadzących do śmierci komórki, a ostateczny efekt oddziaływania tych dwóch sił ma podstawowe znaczenie dla prawidłowego lub nieprawidłowego wzrostu komórki. Hipotezy na temat powiązań osi GH–IGF z karcynogenezą pojawiły się wiele lat temu, głównie w oparciu o wyniki badań in vitro oraz badań z wykorzystaniem różnych zwierzęcych modeli raka występującego u ludzi. Chociaż liczne dane doświadczalne potwierdzają rolę osi GH–IGF sprzyjającą rozwojowi i progresji nowotworów, a nad kilkoma składowymi tej osi trwają obecnie badania oceniające ich przydatność jako główne cele terapii przeciwnowotworowej, to jednak siła dowodów uzyskanych u chorych z akromegalią, niedoborem GH lub osób leczonych GH jest znacznie słabsza. W niniejszej pracy przeglądowej spróbowano zebrać wszystkie te dane. (Endokrynol Pol 2016; 67 (4): 414–426)

Reduced mammary gland carcinogenesis in transgenic mice expressing a growth hormone antagonist

Several reports have provided evidence that body size early in life is positively correlated with risk of subsequent breast cancer, but the biological basis for this relationship is unclear. We examined tumour incidence in transgenic mice expressing a growth hormone (GH) antagonist and in non-transgenic littermates following exposure to dimethylbenz[a]anthracene (DMBA), a well characterized murine mammary gland carcinogen. The transgenic animals had lower IGF-I levels, were smaller in terms of body size and weight, and exhibited decreased tumour incidence relative to controls. The demonstration that both body size early in life and breast cancer incidence are influenced by experimental perturbation of the GH–IGF-I axis in a transgenic model provides evidence that variability between individuals with respect to these hormones underlies the relationship between body size early in life and breast cancer risk observed in epidemiological studies. © 2001 Cancer Research Campaign http://www.bjcancer.co

A proteomic approach to obesity and type 2 diabetes

The incidence of obesity and type diabetes 2 has increased dramatically resulting in an increased interest in its biomedical relevance. However, the mechanisms that trigger the development of diabetes type 2 in obese patients remain largely unknown. Scientific, clinical and pharmaceutical communities are dedicating vast resources to unravel this issue by applying different omics tools. During the last decade, the advances in proteomic approaches and the Human Proteome Organization have opened and are opening a new door that may be helpful in the identification of patients at risk and to improve current therapies. Here, we briefly review some of the advances in our understanding of type 2 diabetes that have occurred through the application of proteomics. We also review, in detail, the current improvements in proteomic methodologies and new strategies that could be employed to further advance our understanding of this pathology. By applying these new proteomic advances, novel therapeutic and/or diagnostic protein targets will be discovered in the obesity/Type 2 diabetes areaThis work is funded by Ministerio de Ciencia e Innovación (BFU2011–27492), Fondos de Investigación Sanitaria (PI1302195), Centro de Investigación Biomédica en Red Fisiopatología de Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III and Fundación de Endocrinología y Nutrición. Dr. Elena López Villar is supported by ISCIII Spanish Health System (SNS BOE 2012) and she is Delegate of HUPO (Human Proteome Organization) supporting clinical proteomic studies at Hospital Niño Jesús of Madrid, Spain, to improve diagnosis and therapies via researc