Effects of Growth Hormone Receptor Ablation in Corticotropin-Releasing Hormone Cells

Corticotropin-releasing hormone (CRH) cells are the dominant neuronal population responsive to the growth hormone (GH) in the paraventricular nucleus of the hypothalamus (PVH). However, the physiological importance of GH receptor (GHR) signaling in CRH neurons is currently unknown. Thus, the main objective of the present study was to investigate the consequences of GHR ablation in CRH-expressing cells of male and female mice. GHR ablation in CRH cells did not cause significant changes in body weight, body composition, food intake, substrate oxidation, locomotor activity, glucose tolerance, insulin sensitivity, counterregulatory response to 2-deoxy-D-glucose and ghrelin-induced food intake. However, reduced energy expenditure was observed in female mice carrying GHR ablation in CRH cells. The absence of GHR in CRH cells did not affect anxiety, circadian glucocorticoid levels or restraint-stress-induced corticosterone secretion and activation of PVH neurons in both male and female mice. In summary, GHR ablation, specifically in CRH-expressing neurons, does not lead to major alterations in metabolism, hypothalamic–pituitary–adrenal axis, acute stress response or anxiety in mice. Considering the previous studies showing that central GHR signaling regulates homeostasis in situations of metabolic stress, future studies are still necessary to identify the potential physiological importance of GH action on CRH neurons.     

Prediction of fatty acid composition of fresh and freeze-dried cheeses by visible–near-infrared reflectance spectroscopy

Visible–near-infrared reflectance spectroscopy was used to predict the fatty acid (FA) composition of 445 cows’ and goats’ fresh and freeze-dried cheeses. The FA composition of samples was analysed by reference method. Samples were scanned (400–2500 nm) and predictive equations were developed using modified partial least squares with both cross-validation and external validation. The coefficient of determination in external validation (R²V) and residual predictive deviation in the validation set (RPDV) were good for total saturated (0.89, 2.84), monounsaturated (0.90, 2.90), polyunsaturated (0.88, 2.54), trans (0.92, 3.24) FA, butyric (0.84, 2.43), capric (0.92, 2.96), myristic (0.89, 2.94), palmitic (0.91, 3.32), vaccenic (0.88, 2.63), and rumenic (0.90, 2.70) acids in fresh cheeses. Approximate or poor predictions were obtained for caproic, caprylic, lauric, stearic, oleic, linoleic, and linolenic acids (R²V0.80; RPDV2.08). The quantification was significantly more accurate for caprilic, capric, and linoleic acids with freeze-dried cheeses compared with fresh cheeses.     

Preliminary results of proton beam characterization for a facility of broad beam in vitro cell irradiation

The interaction of charged particles with living matter needs to be well understood for medical applications. Particularly, it is useful to study how ion beams interact with tissues in terms of damage, dose released and dose rate.One way to evaluate the biological effects induced by an ion beam is by the irradiation of cultured cells at a particle accelerator, where cells can be exposed to different ions at different energies and flux.In this paper, we report the first results concerning the characterization of a broad proton beam obtained with our 2 MV tandem accelerator. For broad beam in vitro cell irradiation, the beam has to be stable over time, uniform over a ∼0.5 cm² surface, and a dose rate ranging from 0.1 to 10 Gy/min must be achievable. Results concerning the level of achievement of these requirements are presented in this paper for a 1 MeV proton beam.     

Characterization of activated sludge exopolymers from various origins: a combined size-exclusion chromatography and infrared microscopy study

High-pressure size-exclusion liquid chromatography and infrared microscopy were coupled to investigate the molecular weight and nature of extracellular polymeric substances (EPS) from various activated sludges. Six main families of compounds (proteins, polysaccharides, organic acids, lipids, mineral phases) were found either as a single molecule or as associations. The molecular weight of proteins varied from small (10 kDa) to large (600 kDa) sizes, while all polysaccharides were smaller than 1 kDa. Association of different molecules implied the presence of species large in size. The EPS chromatographic fingerprints of sludge from various origins remained stable in normal operating conditions, but were drastically modified during settling crises. In poor settling conditions, the EPS with smaller molecular sizes always prevailed and large polymers were underrepresented. The EPS identified in activated sludge were collected in a chemical database which provides the basis for comparison of municipal and industrial wastewater treatment plants (WWTP).     

Innovation and market structure in the dynamics of the pharmaceutical industry and biotechnology: towards a history-friendly model

This paper is a first attempt at modelling the long-term dynamicsof market structure and innovation in the pharmaceutical industryin a history-friendly way. The model examines the relationshipsbetween the nature of the search space, demand, the patternsof competition, and industry evolution in the age of randomscreening and in the age of molecular biology, and shows thatconcentration in the pharmaceutical industry is shaped by lackof cumulativeness in innovative activities and market fragmentation.The model conforms to our appreciative understanding and respondsto changes in parameters concerning demand, costs, economiesof scale, opportunity conditions and the relative advantagesof new biotechnology firms (NBFs) vis-à-vis incumbents.With the exception of cost increases, the model is quite robustto these changes in its essential features: it is quite difficultto raise substantially concentration and to have NBFs displacingincumbents.     

Optical-fiber surface-plasmon resonance sensor with multiple resonance peaks

We report on an optical fiber surface plasmon resonance sensor that exhibits multiple resonance peaks. The sensor is based on a uniform-waist single-mode tapered fiber coated on one side with a thin metal layer. Owing to the asymmetry of the sensor structure, the different hybrid surface plasmon modes supported by the semicircular layer can be excited by the fundamental fiber mode. As a result, the sensor transmission spectrum exhibits several dips that depend on the taper waist diameter. The advantages of a plasmon resonance sensor with multiple dips are discussed.     

Emerging treatments in myopathies

Outstanding improvement has been made in the molecular understanding of several muscle diseases with the application of molecular biological techniques to the investigation of human disorders. The identification of genetic mutations has improved considerably the diagnostic approach to muscular dystrophies, mitochondrial myopathies and ion channel disorders. Important results have been achieved in the field of inflammatory myopathies. With a few exceptions, therapies available are nonspecific and rarely represent a cure for the disease. Molecular medicine offers an opportunity to design new therapeutic strategies based on the pathogenic mechanisms underlying each disease.     

Ventricular remodeling in coronary artery disease

OBJECTIVE: To examine knowledge and practices in relation to sexually transmissible diseases (STDs) of general practitioners (GPs) in Victoria, Australia. METHOD: A questionnaire was distributed to 520 Victorian GPs randomly selected from the Australian Medical Publishing Company (AMPCo) database of Australian medical practitioners. RESULTS: A response rate of 85% was obtained. While sexual health consultations were common for Victorian GPs, STD caseloads were generally low. Knowledge of clinical features of symptomatic STDs and of important STD epidemiology was generally good although there was a lower awareness of the asymptomatic nature of the most prevalent STDs in Victoria. Diagnostic tests were generally selected appropriately although many GPs did not perform the gold standard combination of tests required for adequate differential diagnosis. Level of STD STD knowledge was related to frequency of advising about safe sex, diagnosing STDs, and younger practitioner age. Attendance at any of a number of postgraduate courses of relevance to the management of STDs was not related to better STD knowledge overall. CONCLUSIONS: Prevention and detection of STDs in general practice involve risk assessment and screening of asymptomatic patients as well as effective treatment of symptomatic patients and their contacts. Results presented here suggest that GPs have good knowledge and use appropriate investigations for patients presenting with symptoms of an STD. The low levels of awareness of the asymptomatic nature of many STDs and other particular aspects of STD knowledge and practice should be addressed in undergraduate and postgraduate medical education programmes.     

Selective deamidation of ribonuclease A. Isolation and characterization of the resulting isoaspartyl and aspartyl derivatives

Selective deamidation of proteins and peptides is a reaction of great interest, whether it has physiological significance as in protein aging, or occurs as a disturbing event in the preparation of natural or recombinant proteins. Deamidation of bovine pancreatic ribonuclease A, RNase A, a classical model protein, has been reported to occur only after denaturation of the protein, or under harsh conditions. In this paper convenient procedures are described for selective deamidation of Asn67 in native RNase A under mild conditions. Furthermore, for the first time, both products of deamidation were isolated: the aspartyl and the isoaspartyl containing protein derivatives. Replacement of Asn67 with either residue lowers the catalytic activity of the enzyme, on RNA and on model substrates, except when a dinucleotide with a purine on the 5' side is the substrate. In the latter case an intriguing increase in the specificity constant is observed. The Asp67 derivative was found to refold, after full denaturation and reduction, at the same rate as the fully amidated protein, whereas the iso-Asp67 derivative refolded at half that rate. It is hypothesized that this effect is due to a delayed formation of disulfide 65-72 for the presence of the abnormal isopeptide bond between residues 67 and 68.