Glucocorticoids modulate transformation by v-Src in a cell-specific manner

In Balb 3T3 murine fibroblasts infected with retroviruses carrying the v-src oncogene, treatment with the glucocorticoid hormone dexamethasone induces a 10-fold increase in the number of transformed foci and of anchorage-independent colonies. In contrast, in NIH-3T3-infected cells the number of foci and of colonies growing in soft agar is considerably reduced by the addition of the hormone. The effect of dexamethasone on both Balb 3T3 and NIH 3T3 cells is dose-dependent and mediated by specific receptors. The expression of glucocorticoid receptors as well as transactivation of a mouse mammary tumor virus promoter in the presence of dexamethasone is comparable in the two cell lines. Dexamethasone does not change the expression and kinase activity of v-Src proteins either in freshly infected Balb 3T3 and NIH 3T3 cells or in morphologically normal clones or in transformed foci derived from infected Balb 3T3 cells stably expressing v-Src. However, in cocultivation assays of phenotypically normal clones of v-Src expressing Balb 3T3 cells mixed with a large excess of parental Balb 3T3 cells, the hormone is able to rescue the ability to form transformed foci of these otherwise normal cells. The present data point out a new role of glucocorticoid hormones in controlling transformation in a cell-specific manner through epigenetic mechanisms.     

Increased susceptibility to apoptosis of CD56dimCD16+ NK cells induces the enrichment of IFN-gamma-producing CD56bright cells in tuberculous pleurisy

Tuberculous pleuritis is a good model for the study of specific cells at the site of active Mycobacterium tuberculosis (Mtb) infection. We investigated the frequency and phenotype of NK cells in paired samples of peripheral blood and pleural fluid (PF) from patients with tuberculosis (TB) or parapneumonic infection. We demonstrated for the first time a reduction of NK cells in PF from TB with an enrichment in the CD56brightCD16- subset. In agreement, in PF NK cells we observed an increased expression of CD94, NKG2A, CD62L, and CCR7 molecules and lower expression of Bcl-2 and perforin. The activation markers CD69 and HLA-DR were also increased. The enrichment in the CD56bright subset was due to an increased susceptibility to apoptosis of CD56+CD16+ NK cells mediated by heat-labile and stable soluble factors present in tuberculous effusions and not in PF from other etiologies. Furthermore, in TB patients, Mtb-induced IFN-gamma production by PF NK cells was not dependent on the presence of CD3+, CD19+, and CD14+ cells, suggesting a direct interaction of CD56bright cells with Mtb and/or the involvement of other accessory cells present at the site of Mtb infection.     

Targeted expression of RALT in mouse skin inhibits epidermal growth factor receptor signalling and generates a Waved-like phenotype

Although it has been clearly established that negative feedback loops have a fundamental role in the regulation of epidermal growth factor receptor (EGFR) signalling in flies, their role in the regulation of mammalian EGFR has been inferred only recently from in vitro studies. Here, we report on the forced expression of RALT/MIG-6, a negative feedback regulator of ErbB receptors, in mouse skin. A RALT transgene driven by the K14 promoter generated a dose-dependent phenotype resembling that caused by hypomorphic and antimorphic Egfr alleles-that is, wavy coat, curly whiskers and open eyes at birth. Ex vivo keratinocytes from K14-RALT mice showed reduced biochemical and biological responses when stimulated by ErbB ligands. Conversely, knockdown of RALT by RNA interference enhanced ErbB mitogenic signalling. Thus, RALT behaves as a suppressor of EGFR signalling in mouse skin.     

On the protonation equilibrium for the benzimidazole derivative Hoechst 33258: an electronic molecular orbital study

Hoechst 33258 and its deprotonated forms have been examined in the gas-phase and in solution using quantum mechanical methods. Ab initio calculations at the HF level have been used to investigate the more relevant geometrical trends of such species, while proton affinities and gas-phase basicities were derived from B3LYP and MP2 electronic energies. Solvation energies were calculated using a dielectric continuum model: MST. The Delta(p)K(a) values were estimated by combining the gas-phase basicities and the free energies of solvation. Comparison of these Delta(p)K(a) values with experimentally reported data have been used to highlight the advantages and limitations of this strategy.     

Hydrous and photosynthetic adaptations of common and durum wheat to saline stress

Seven varieties of bred wheat and seven varieties of durum wheat were cultivated in three different sites from the area of Errachidia (southeastern Morocco). These sites differ by the degree of salinity in the irrigation water. Results obtained showed that the reduction in leaf area is the principal strategy that makes it possible to attenuate the effects of the reduction in the availability of water under saline stress. Bread wheat, which limited the reduction in the leaf area, with the risk to undergo some hydrous problems, seems to better preserve its photosynthetic potentialities and grain productivity.     

Factors Associated with Occupational Needle Stick and Sharps Injuries among Hospital Healthcare Workers in Bale Zone,Southeast Ethiopia

Background

Needle stick and sharps injuries are occupational hazards to healthcare workers. Every day healthcare workers are exposed to deadly blood borne pathogens through contaminated needles and other sharp objects. About twenty blood borne pathogens can be transmitted through accidental needle stick and sharp injury. The study was conducted to determine the lifetime and past one year prevalence of needle stick and sharps injuries and factors associated with the past one year injuries among hospital healthcare workers in Southeast Ethiopia.

Methods

An institutional based cross sectional study was conducted in December 2014 among healthcare workers in four hospitals of Bale zone, Southeast of Ethiopia. A total of 362 healthcare workers were selected randomly from each department in the hospitals. Data were collected using self-administered questionnaire. The collected data were entered into Epi-Info version 3.5 and analyzed using SPSS version 20.0. Multivariable logistic regression analysis was used to identify the independent effect of each independent variable on the outcome variable. Written informed consent was secured from the participants.

Results

The prevalence of lifetime needle stick and sharp injury was 37.1% with 95% CI of 32.0% to 42.5%. The prevalence of injury within the past one year was 19.1% with 95% CI of 14.9% to 23.3%. Emergency ward was a department with highest needle stick and sharp injury (31.7%). The main cause of injury was syringe needles (69.8%). Participants who practiced needle recapping had higher odds of needle stick and sharp injury within the past 12 months (AOR = 3.23, 95% CI: 1.78, 5.84) compared to their counterparts.

Conclusions

Nearly one out of five respondents had experienced needle stick and/or sharp injury at least once within past one year. There were practices and behaviors that put healthcare workers at risk of needle stick and sharp injury at the study area. Needle recapping was key modifiable risk behavior. Health policy makers and hospital administrators should formulate strategies to improve the working condition for healthcare workers and increase their adherence to universal precautions.     

Multiple ligand-specific conformations of the β2-adrenergic receptor

Seven-transmembrane receptors (7TMRs), also called G protein-coupled receptors (GPCRs), represent the largest class of drug targets, and they can signal through several distinct mechanisms including those mediated by G proteins and the multifunctional adaptor proteins β-arrestins. Moreover, several receptor ligands with differential efficacies toward these distinct signaling pathways have been identified. However, the structural basis and mechanism underlying this 'biased agonism' remains largely unknown. Here, we develop a quantitative mass spectrometry strategy that measures specific reactivities of individual side chains to investigate dynamic conformational changes in the β(2)-adrenergic receptor occupied by nine functionally distinct ligands. Unexpectedly, only a minority of residues showed reactivity patterns consistent with classical agonism, whereas the majority showed distinct patterns of reactivity even between functionally similar ligands. These findings demonstrate, contrary to two-state models for receptor activity, that there is significant variability in receptor conformations induced by different ligands, which has significant implications for the design of new therapeutic agents.     

Sex estimation based on deciduous and permanent dentition in a contemporary spanish population

Sex estimation of skeletal remains with satisfactory allocation accuracy represents an essential step in reconstructing the biological profile of unknown individuals in archaeological research and forensic practice. Teeth are among the most frequently recovered physical elements of an individual that remain after death due to their hardness, durability, and resistance to postmortem insults. This study was based on the deciduous and permanent dentition of 269 individuals (150 males and 119 females) from the Granada osteological collection of identified infants, young children, and adults (Granada, Spain). Mesiodistal, buccolingual, and diagonal crown and cervical diameters of both dentitions were measured, and logistic regression analyses were performed to create equations for sex discrimination. The results show that the first and second deciduous molars and the permanent canines are the teeth with the greatest sexual dimorphism, providing percentages of correct assignment of sex between 78.1 and 93.1% in deciduous dentition and between 79.4 and 92.6% in permanent teeth, depending on the dimensions used. The results indicate that this method may be applicable as an adjunct with other accepted procedures for sex estimation when fragmentary skeletal remains are encountered in archaeological excavations and in forensic contexts. Am J Phys Anthropol 152:163–164, 2013. © 2013 Wiley Periodicals, Inc.     

Current molecular aspects in the development and treatment of diabetes

Journal of Physiology and Biochemistry - Diabetes mellitus (DM) leads to microvascular, macrovascular, and neurological complications. Less is understood about the mechanisms of this disease that...     

Is the Cerebellum the Optimal Reference Region for Intensity Normalization of Perfusion MR Studies in Early Alzheimer’s Disease?

The cerebellum is the region most commonly used as a reference when normalizing the intensity of perfusion images acquired using magnetic resonance imaging (MRI) in Alzheimer’s disease (AD) studies. In addition, the cerebellum provides unbiased estimations with nuclear medicine techniques. However, no reports confirm the cerebellum as an optimal reference region in MRI studies or evaluate the consequences of using different normalization regions. In this study, we address the effect of using the cerebellum, whole-brain white matter, and whole-brain cortical gray matter in the normalization of cerebral blood flow (CBF) parametric maps by comparing patients with stable mild cognitive impairment (MCI), patients with AD and healthy controls. According to our results, normalization by whole-brain cortical gray matter enables more sensitive detection of perfusion abnormalities in AD patients and reveals a larger number of affected regions than data normalized by the cerebellum or whole-brain white matter. Therefore, the cerebellum is not the most valid reference region in MRI studies for early stages of AD. After normalization by whole-brain cortical gray matter, we found a significant decrease in CBF in both parietal lobes and an increase in CBF in the right medial temporal lobe. We found no differences in perfusion between patients with stable MCI and healthy controls either before or after normalization.