Diversity and specificity of the mitogen-activated protein kinase phosphatase-1 functions

The balance of protein phosphorylation is achieved through the actions of a family of protein serine/threonine kinases called the mitogen-activated protein kinases (MAPKs). The propagation of MAPK signals is attenuated through the actions of the MAPK phosphatases (MKPs). The MKPs specifically inactivate the MAPKs by direct dephosphorylation. The archetypal MKP family member, MKP-1 has garnered much of the attention amongst its ten other MKP family members. Initially viewed to play a redundant role in the control of MAPK signaling, it is now clear that MKP-1 exerts profound regulatory functions on the immune, metabolic, musculoskeletal and nervous systems. This review focuses on the physiological functions of MKP-1 that have been revealed using mouse genetic approaches. The implications from studies using MKP-1-deficient mice to uncover the role of MKP-1 in disease will be discussed.     

Tunability of physical properties of (Cd:Zn)S thin film by Close Space Sublimation Process (CSSP)

The present paper reports on a systematic study of the influence of Zn alloying on the structural and optical properties of Cd1 xZnxS thin films. X-ray diffraction study for structural analysis reveals that the two binary compounds have been completely transformed into ternary compound with hexagonal (wurtzite) structure with preferred orientation along c-direction with (002) planes. The optical properties such as optical constants and band gap energy of the films were examined by using spectroscopic ellipsometer and Photospectrometery. It was found that the optical constants (n and k) decrease with the addition of Zn content in the alloy. It was also confirmed that the band gap increases with increasing Zn amount in the alloy and is attributed to quantum size effect in the grain size. Raman spectroscopy analysis shows one dominant phonon band at 326 cm 1, the so-called longitudinal optical (LO) mode for all the alloy composition (x). The appearance of a single phonon band in the Raman spectra established the formation of single phase hexagonal structured Cd1 xZnxS thin film. The LO band is asymmetrically broaden and high frequency shifted due to potential fluctuation caused by the dopant material. The AFM results showed that the surface roughness was decreased with increasing Zn content.     

Indomethacin and inhibition of protein kinase reactions

Indomethacin, an inhibitor of prostaglandin biosynthesis, is useful in studies aimed at understanding the metabolism and physiological function of prostaglandins. A recent report showing that indomethacin at 10(-7) M potently inhibits the cyclic AMP-dependent protein kinases (cAMP-PrK) from ileal mucosa in the presence or absence of cyclic AMP, suggests how indomethacin may antagonize prostaglandin action on ileal mucosa. It also suggests that indomethacin might be useful in studying the properties and functions of protein kinase reactions. Inhibitors of prostaglandin biosynthesis, such as sodium salicylate and acetylsalicylate, at concentrations near 10(-2) M, have been shown to inhibit bovine diaphragm protein kinase only in the presence of cAMP, while stimulating it in the absence of cAMP. We report here that complete inhibition of cAMP-PrKs by indomethacin requires a concentration of 10(-3) M and is not tissue-specific, and that the effect of indomethacin is concentration dependent above 2 x 10(-4) M for the cAMP-dependent, and above 10(-3) M for cAMP-independent PrKs. These results contrast previous ones.     

Formation of stable crystalline enzyme-substrate intermediates at sub-zero temperatures.

Sub-zero temperatures can be used to trap intermediates in enzyme-catalysed reactions using suitable cryosolvents. The feasibility of obtaining such intermediates in the crystalline state for X-ray diffraction studies has been demonstrated with several proteases, using specific substrates and optimal pH.     

Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function

Positional cloning of hereditary deafness genes is a direct approach to identify molecules and mechanisms underlying auditory function. Here we report a locus for dominant deafness, DFNA36, which maps to human chromosome 9q13-21 in a region overlapping the DFNB7/B11 locus for recessive deafness. We identified eight mutations in a new gene, transmembrane cochlear-expressed gene 1 (TMC1), in a DFNA36 family and eleven DFNB7/B11 families. We detected a 1.6-kb genomic deletion encompassing exon 14 of Tmc1 in the recessive deafness (dn) mouse mutant, which lacks auditory responses and has hair-cell degeneration. TMC1 and TMC2 on chromosome 20p13 are members of a gene family predicted to encode transmembrane proteins. Tmc1 mRNA is expressed in hair cells of the postnatal mouse cochlea and vestibular end organs and is required for normal function of cochlear hair cells.     

Circadian variation of serum testosterone in the adult male rat with a late morning acrophase

Summary Serum testosterone concentrations were measured in adult male Sprague-Dawley rats. A significant circadian testosterone rhythm (p<0.01) was found with peak values at 10.00 and 13.00 h.Supported in part by NIH, NCI Grant No. CA 15062 and NIH, NIAMDD Grant No. 5 RO1 AM11376.The authors would like to acknowledge the excellent technical assistance of Ms.Kris Strom.     

A simple method for determination of the proportion of 2C and 4C cells in a dormant embryo

Summary Pea embryos grown in the presence of 2.5 mM hydroxyurea from the beginning of imbibition showed a mitotic peak the height of which was considerably less than that of the control, material. Soon after the mitotic peak, there was a complete cessation of mitosis in the treated material. The extent of suppression of mitosis during the first post-dormancy cell cycle caused by hydroxyurea has been used to obtain an estimate of the relative proportion of 2C and 4C cells in the embryo.     

The family Leucospidae (Hymenoptera: Chalcidoidea) from the South of Saudi Arabia,with the first report of the genus Micrapion and description of Leucospis arabica sp. nov.

The family Leucospidae (Hymenoptera: Chalcidoidea) from Saudi Arabia is reviewed. Specimens were mainly collected from the south-western region of the country – Raydah (Abha, Asir), Sajid (Farasan Islands, Jazan) and Wadi Tourabah (Mandaq, Al Baha); and from Egypt – Wadi Khoshb (Sinai Peninsula), as well as a specimen (Leucospis elegans Klug) deposited in the Efflatoun Bey collection, Cairo University, Egypt. The genus Micrapion Kriechbaumer is here recorded for the first time from the fauna of the Arabian Peninsula, with a single species, M. clavaforme. Leucospis arabica Gadallah and Soliman sp. nov. (dorsigera group) is described. Leucospis africana (elegans group) is also newly recorded from the Saudi Arabian fauna, in addition to L. elegans which has been previously recorded. An illustrated key and a list of all leucospid species recorded and expected to occur in Saudi Arabia are provided.

www.zoobank.org/lsid:Zoobank.org:pub:40BEF37F-0D92-4AEF-9990-30C1CFC3A7A7     

Genome-wide association analysis identifies three new breast cancer susceptibility loci

Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for ～8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in ～70,000 cases and ～68,000 controls from 41 case-control studies and 9 breast cancer GWAS. We identified three new breast cancer risk loci at 12p11 (rs10771399; P = 2.7 × 10(-35)), 12q24 (rs1292011; P = 4.3 × 10(-19)) and 21q21 (rs2823093; P = 1.1 × 10(-12)). rs10771399 was associated with similar relative risks for both estrogen receptor (ER)-negative and ER-positive breast cancer, whereas the other two loci were associated only with ER-positive disease. Two of the loci lie in regions that contain strong plausible candidate genes: PTHLH (12p11) has a crucial role in mammary gland development and the establishment of bone metastasis in breast cancer, and NRIP1 (21q21) encodes an ER cofactor and has a role in the regulation of breast cancer cell growth.