14-3-3 proteins in neurodegeneration

Among the first reported functions of 14-3-3 proteins was the regulation of tyrosine hydroxylase (TH) activity suggesting a possible involvement of 14-3-3 proteins in Parkinson's disease. Since then the relevance of 14-3-3 proteins in the pathogenesis of chronic as well as acute neurodegenerative diseases, including Alzheimer's disease, polyglutamine diseases, amyotrophic lateral sclerosis and stroke has been recognized. The reported function of 14-3-3 proteins in this context are as diverse as the mechanism involved in neurodegeneration, reaching from basal cellular processes like apoptosis, over involvement in features common to many neurodegenerative diseases, like protein stabilization and aggregation, to very specific processes responsible for the selective vulnerability of cellular populations in single neurodegenerative diseases.Here, we review what is currently known of the function of 14-3-3 proteins in nervous tissue focussing on the properties of 14-3-3 proteins important in neurodegenerative disease pathogenesis.     

Comparative studies on beta-glucan hydrolases. Isolation and characterization of an exo(1 yields 3)-beta-glucanase from the snail, Helix pomatia.

An exo-β-glucan hydrolase, present in the digestive juice of the snail, Helix pomatia, has been purified to homogeneity by chromatography on Bio-Gel P-60, Sephadex G-200, DEAE-cellulose, and DEAE-Sephadex. The enzyme degrades β-(1 → 3)-linked oligosaccharides and polysaccharides, rapidly and to completion, or near completion, yielding glucose as the major product of enzyme action. Mixed linkage (1→3; 1→4)-β-glucans are also extensively degraded and β-(1→6)- and β-(1→4)-linked glucose polymers are slowly degraded by the enzyme. This enzyme differs from other exo-β-glucanases, reported previously, in the broadness of its substrate specificity. The K_m values for action on laminarin and lichenin are respectively 1.22 and 2.22 mg/ml; the maximum velocity of action on laminarin is approximately twice that on lichenin. The enzyme has a molecular weight of 82,000 as determined by polyacrylamide gel electrophoresis. Maximum activity is exhibited at pH 4.3 and at temperatures of 50–55 °C.     

DOCK9 induces membrane ruffles and Rac1 activity in cancer HeLa epithelial cells

Dedicator-of-cytokinesis (DOCK) proteins are a family of guanine-nucleotide exchange factors (GEF) for Rho GTPases. The DOCK-D homology subfamily comprises DOCK9, DOCK10, and DOCK11. DOCK9 and DOCK11 are GEFs for Cdc42 and induce filopodia, while DOCK10 is a dual GEF for Cdc42 and Rac1 and induces filopodia and ruffles. We provide data showing that DOCK9, the only one of the DOCK-D members that is not considered hematopoietic, is nevertheless expressed at high levels in T lymphocytes, as do DOCK10 and DOCK11, although unlike these, it is not expressed in B lymphocytes. To investigate DOCK9 function, we have created a stable HeLa clone with inducible expression of HA-DOCK9. Induction of expression of HA-DOCK9 produced loss of elongation and polygonal shape of HeLa cells. Regarding membrane protrusions, HA-DOCK9 prominently induced filopodia, but also an increase of membrane ruffles. The latter was consistent with an increase in the levels of activation of Rac1, suggesting that DOCK9 carries a secondary ability to induce ruffles through activation of Rac1.     

Hemocyanin gene family evolution in spiders (Araneae), with implications for phylogenetic relationships and divergence times in the infraorder Mygalomorphae

Hemocyanins are multimeric copper-containing hemolymph proteins involved in oxygen binding and transport in all major arthropod lineages. Most arachnids have seven primary subunits (encoded by paralogous genes a–g), which combine to form a 24-mer (4 × 6) quaternary structure. Within some spider lineages, however, hemocyanin evolution has been a dynamic process with extensive paralog duplication and loss. We have obtained hemocyanin gene sequences from numerous representatives of the spider infraorders Mygalomorphae and Araneomorphae in order to infer the evolution of the hemocyanin gene family and estimate spider relationships using these conserved loci. Our hemocyanin gene tree is largely consistent with the previous hypotheses of paralog relationships based on immunological studies, but reveals some discrepancies in which paralog types have been lost or duplicated in specific spider lineages. Analyses of concatenated hemocyanin sequences resolved deep nodes in the spider phylogeny and recovered a number of clades that are supported by other molecular studies, particularly for mygalomorph taxa. The concatenated data set is also used to estimate dates of higher-level spider divergences and suggests that the diversification of extant mygalomorphs preceded that of extant araneomorphs. Spiders are diverse in behavior and respiratory morphology, and our results are beneficial for comparative analyses of spider respiration. Lastly, the conserved hemocyanin sequences allow for the inference of spider relationships and ancient divergence dates.     

低能离子束对微生物细胞的刻蚀与损伤研究

以耐辐射异常微球菌和大肠杆菌为试材,用显微扫描电镜（ＳＥＭ）和电子自旋共振（ＥＳＲ）波谱仪研究了２０ｋｅＶ的Ｎ＾＋离子注入对其细胞的作用。结果表明,Ｎ＾＋离子注入对两种微生物既存在着直接作用的刻蚀损伤又存在着能量沉积所产生自由基的间接作用;对细胞的直接刻蚀作用是导致ＤＮＡ损伤和生物诱变的主要原因,而自由基所引起的主要是ＤＮＡ以外生物大分子的损伤和细胞的膜脂过氧化。随着注入剂量增大,两种微生物细胞受     

Energetic challenges unmask the role of ovarian hormones in orchestrating ingestive and sex behaviors

Effects of ovarian hormones on sex and ingestive behavior are well studied, and yet, their role in diverting attention from food to sex has not been examined directly, possibly because these functions are masked under conditions of excessive food abundance typical of the laboratory. Female Syrian hamsters were either fed ad libitum or food-restricted to 75% of their ad libitum intake for 8 days and then tested every day of the estrous cycle for their preference for males versus food, food hoarding and food intake in an apparatus designed to mimic aspects of their natural habitat. The food-restricted, but not the fed females, varied significantly over the estrous cycle in appetitive behaviors, which included their preference for males versus food and in the amount of food hoarded, with low food hoarding and high male preference on the night of ovulation. In contrast, there were no significant differences between restricted and ad libitum-fed females in the consummatory behaviors, namely, food intake or lordosis duration. In ovariectomized females, estradiol plus progesterone treatment delayed food restriction-stimulated hoarding and hastened feeding-inhibited hoarding without affecting food intake or lordosis duration. In summary, energy restriction and the presence of males unmasked an effect that was obscured in the normal laboratory conditions characterized by isolation and an over abundance of readily available food. These results are consistent with the idea that ovarian hormones orchestrate appetites for food and sex to optimize reproductive success under fluctuating energetic conditions.     

Methicillin-resistant Staphylococcus aureus: a pervasive pathogen highlights the need for new antimicrobial development

Staphylococcus aureus (S. aureus) has entered the spotlight as a globally pervasive drug-resistant pathogen. While historically associated exclusively with hospital-acquired infections in immunocompromised hosts, the methicillin-resistant form of S. aureus has been spreading throughout communities since the 1990s. Indeed, it has now become a common household term: MRSA. S. aureus has developed numerous mechanisms of virulence and strategies to evade the human immune system, including a host of surface proteins, secreted enzymes, and toxins. In hospital intensive care units, the proportion of MRSA-related S. aureus infections has increased strikingly from just 2 percent in 1974 to 64 percent in 2004. Its presence in the community has been rising similarly, posing a significant public health burden. The growing incidence of MRSA unfortunately has been met with dwindling efforts to develop new, more effective antibiotics. The continued emergence of resistant strains of bacteria such as MRSA demands an urgent revival of the search for new antibiotics.     

Comparative cellular localization of corticotropin and melanotropin in lerot adenohypophysis (Eliomys quercinus)

Summary Corticotropin and melanotropin producing cells were localized in the adenohypophysis of normal Lerots by using antibodies against synthetic corticotropins (anti 1–24 ACTH, anti 17–39 ACTH, anti 25–39 ACTH), and melanotropins (anti MSH, anti MSH). All the anticorticotropin sera stained the same cells both in the anterior lobe and in the intermediate lobe. The anti MSH serum only stained a few cells, exclusively located in the intermediate lobe. These MSH cells were not stained with anticorticotropin antibodies. The anti MSH serum revealed all the cells stained with anticorticotropin and anti MSH sera. Absorption tests showed that the 4–10 heptapeptide common to ACTH and MSH, is not responsible for the immunohistochemical staining. The staining of only some corticotrophs with the anti 4–10 ACTH serum might indicate the presence in these cells of a peptide with an accessible 4–10 site. These results are discussedWe thank A. Pillez for technical assistance (C.N.R.S.). This work was supported by a grant from U.E.R. III Lille 1976Attaché de Recherche INSERM