Erythropoietin protects intestinal epithelial barrier function and lowers the incidence of experimental neonatal necrotizing enterocolitis

The impermeant nature of the intestinal barrier is maintained by tight junctions (TJs) formed between adjacent intestinal epithelial cells. Disruption of TJs and loss of barrier function are associated with a number of gastrointestinal diseases, including neonatal necrotizing enterocolitis (NEC), the leading cause of death from gastrointestinal diseases in preterm infants. Human milk is protective against NEC, and the human milk factor erythropoietin (Epo) has been shown to protect endothelial cell-cell and blood-brain barriers. We hypothesized that Epo may also protect intestinal epithelial barriers, thereby lowering the incidence of NEC. Our data demonstrate that Epo protects enterocyte barrier function by supporting expression of the TJ protein ZO-1. As immaturity is a key factor in NEC, Epo regulation of ZO-1 in the human fetal immature H4 intestinal epithelial cell line was examined and demonstrated Epo-stimulated ZO-1 expression in a dose-dependent manner through the PI3K/Akt pathway. In a rat NEC model, oral administration of Epo lowered the incidence of NEC from 45 to 23% with statistical significance. In addition, Epo treatment protected intestinal barrier function and prevented loss of ZO-1 at the TJs in vivo. These effects were associated with elevated Akt phosphorylation in the intestine. This study reveals a novel role of Epo in the regulation of intestinal epithelial TJs and barrier function and suggests the possible use of enteral Epo as a therapeutic agent for gut diseases.     

Metal‐responsive RNA polymerase extracytoplasmic function (ECF) sigma factors

In order to survive, bacteria must adapt to multiple fluctuations in their environment, including coping with changes in metal concentrations. Many metals are essential for viability, since they act as cofactors of indispensable enzymes. But on the other hand, they are potentially toxic because they generate reactive oxygen species or displace other metals from proteins, turning them inactive. This dual effect of metals forces cells to maintain homeostasis using a variety of systems to import and export them. These systems are usually inducible, and their expression is regulated by metal sensors and signal‐transduction mechanisms, one of which is mediated by extracytoplasmic function (ECF) sigma factors. In this review, we have focused on the metal‐responsive ECF sigma factors, several of which are activated by iron depletion (FecI, FpvI and PvdS), while others are activated by excess of metals such as nickel and cobalt (CnrH), copper (CarQ and CorE) or cadmium and zinc (CorE2). We focus particularly on their physiological roles, mechanisms of action and signal transduction pathways.     

Use of time-lapse microscopy to visualize rapid movement of the replication origin region of the chromosome during the cell cycle in Bacillus subtilis

We describe the use of time-lapse fluorescence microscopy to visualize the movement of the DNA replication origin and terminus regions on the Bacillus subtilis chromosome during the course of the cell cycle. The origin and terminus regions were tagged with a cassette of tandem lac operator repeats and visualized through the use of a fusion of the green fluorescent protein to the LacI repressor. We have discovered that origin regions abruptly move apart towards the cell poles during a brief interval of the cell cycle. This movement was also seen in the absence of cell wall growth and in the absence of the product of the parB homologue spo0J . The origin regions moved apart an average distance of 1.4 μm in an 11 min period of abrupt movement, representing an average velocity of 0.17 μm min⁻¹. and reaching a maximum velocity of greater than 0.27 μm min⁻¹. The terminus region also exhibited a striking pattern of movement but not as far or a rapid as the origin region. These results provide evidence for a mitotic-like motor that is responsible for segregation of the origin regions of the chromosomes.     

Different Thermostability of Skeletal Muscle Glyceraldehyde-3-phosphate Dehydrogenase from Hibernating and Euthermic Jerboa （Jaculus orientalis）

D Glyceraldehyde 3 phosphatedehydrogenase(GAPDH ,EC 1.2 .1.12 )isakeyenzymeoftheglycolyticpathwaythatispresentinthecytosolofallorganismssofarstudied[1] .TheglycolyticGAPDHhasbeenremarkablyconservedduringevolution ,havingahomotetramericstructurewithsubunitsof 35 - 37kD[1] .GAPDHhasbeenisolatedfromavarietyofspecies[2 ] ,includingmesophilic ,moderatelythermophilicandhyperthermophilicmicroorganisms[3 ] .Theseenzymes ,whichdifferinthermalstability ,havebeenshowntobehighlysimilarinaminoacidse…     

Organellar proteomics of human platelet dense granules reveals that 14-3-3zeta is a granule protein related to atherosclerosis

Dense granules, a type of platelet secretory organelle, are known to accumulate high concentrations of small molecules such as calcium, adenine nucleotides, serotonin, pyrophosphate, and polyphosphate. Protein composition of these granules has been obscure, however. In this paper, we use proteomics techniques to describe, for the first time, the soluble protein composition of platelet dense granules. We have isolated highly enriched human platelet dense granule fractions that have been analyzed using two proteomics methods. Using this approach, we have identified 40 proteins, and most of them, such as actin-associated proteins, glycolytic enzymes, and regulatory proteins, have not previously been related to the organelle. We have focused our efforts on studying 14-3-3zeta, a member of a conserved family of proteins that interact with hundreds of different proteins. We have demonstrated that 14-3-3zeta is localized mostly on dense granules and that it is secreted after platelet activation. As some proteins secreted from activated platelets could promote the development of atherosclerosis and thrombosis, we have studied the expression of 14-3-3zeta in sections of human abdominal aorta of patients with aneurysm, identifying it at the atherosclerotic plaques. Together, our results reveal new details of the composition of the platelet dense granule and suggest an extracellular function for 14-3-3zeta associated with atherosclerosis.     

Phylogenetic analyses of complete mitochondrial genome sequences suggest a basal divergence of the enigmatic rodent <Emphasis Type="Italic">Anomalurus</Emphasis>

Background  

Phylogenetic relationships between Lagomorpha, Rodentia and Primates and their allies (Euarchontoglires) have long been debated. While it is now generally agreed that Rodentia constitutes a monophyletic sister-group of Lagomorpha and that this clade (Glires) is sister to Primates and Dermoptera, higher-level relationships within Rodentia remain contentious.     

Reactive oxygen species and epidermal growth factor are antagonistic cues controlling SHP-2 dimerization

The SHP-2 tyrosine phosphatase plays key regulatory roles in the modulation of the cell response to growth factors and cytokines. Over the past decade, the integration of genetic, biochemical, and structural data has helped in interpreting the pathological consequences of altered SHP-2 function. Using complementary approaches, we provide evidence here that endogenous SHP-2 can dimerize through the formation of disulfide bonds that may also involve the catalytic cysteine. We show that the fraction of dimeric SHP-2 is modulated by growth factor stimulation and by the cell redox state. Comparison of the phosphatase activities of the monomeric self-inhibited and dimeric forms indicated that the latter is 3-fold less active, thus pointing to the dimerization process as an additional mechanism for controlling SHP-2 activity. Remarkably, dimers formed by different SHP-2 mutants displaying diverse biochemical properties were found to respond differently to epidermal growth factor (EGF) stimulation. Although this differential behavior cannot be rationalized mechanistically yet, these findings suggest a possible regulatory role of dimerization in SHP-2 function.     

Impact of extreme temperatures on daily mortality in Madrid (Spain) among the 45–64 age-group

This paper analyses the relationship between extreme temperatures and mortality among persons aged 45–64 years. Daily mortality in Madrid was analysed by sex and cause, from January 1986 to December 1997. Quantitative analyses were performed using generalised additive models, with other covariables, such as influenza, air pollution and seasonality, included as controls. Our results showed that impact on mortality was limited for temperatures ranging from the 5th to the 95th percentiles, and increased sharply thereafter. During the summer period, the effect of heat was detected solely among males in the target age group, with an attributable risk (AR) of 13.3% for circulatory causes. Similarly, NO₂ concentrations registered the main statistically significant associations in females, with an AR of 15% when circulatory causes were considered. During winter, the impact of cold was exclusively observed among females having an AR of 7.7%. The magnitude of the AR indicates that the impact of extreme temperature is by no means negligible.Julio Díaz is adviser to the Madrid Autonomous University General Foundation, on behalf of the Department of Education for Sustainable Development, Madrid City Council, Madrid, Spain     

CD9, a tetraspanin target for cancer therapy?

In the present minireview, we intend to provide a brief history of the field of CD9 involvement in oncogenesis and in the metastatic process of cancer, considering its potential value as a tumor-associated antigenic target. Over the years, CD9 has been identified as a favorable prognostic marker or predictor of metastatic potential depending on the cancer type. To understand its implications in cancer beside its use as an antigenic biomarker, it is essential to know its physiological functions, including its molecular partners in a given cell system. Moreover, the discovery that CD9 is one of the most specific and broadly expressed markers of extracellular membrane vesicles, nanometer-sized entities that are released into extracellular space and various physiological body fluids and play a role in intercellular communication under physiological and pathological conditions, notably the establishment of cancer metastases, has added a new dimension to our knowledge of CD9 function in cancer. Here, we will discuss these issues as well as the possible cancer therapeutic implications of CD9, their limitations, and pitfalls.     

Sperm design and sperm function

Spermatozoa vary enormously in their form and dimensions, both between and within species, yet how this variation translates into fertilizing efficiency is not known. Sperm swimming velocity is a key determinant of male fertilization success, but previous efforts to identity which sperm phenotypic traits are associated with swimming velocity have been unsuccessful. Here, we examine the relationship between the size of several sperm components and sperm swimming velocity in natural populations of red deer (Cervus elaphus hispanicus) where selective pressures to enhance male reproductive success are expected to be strong. Our results show that there is little within-male and considerable between-male variation in sperm dimensions. Spermatozoa with longer midpieces swim more slowly, a finding which does not support the hypothesis that the size of the midpiece determines the amount of energy which is translated into swimming speed. In contrast, spermatozoa with elongated heads, and those in which the relative length of the rest of the flagellum is longer, swim faster. Thus, the hydrodynamic shape of the head and the forces generated by the relative size of the rest of the flagellum seem to be the key determinants of sperm swimming velocity.