The TERB1 MYB domain suppresses telomere erosion in meiotic prophase I.

The meiosis-specific telomere-binding protein TERB1 anchors telomeres to the nuclear envelope and drives chromosome movements for the pairing of homologous chromosomes. TERB1 has an MYB-like DNA-binding (MYB) domain, which is a hallmark of telomeric DNA-binding proteins. Here, we demonstrate that the TERB1 MYB domain has lost its canonical DNA-binding activity.

Structure of a meiosis-specific complex central to BRCA2 localization at recombination sites.

Meiotic cells invoke breast cancer susceptibility gene 2 (BRCA2) to repair programmed double-stranded DNA breaks and accomplish homologous recombination. The meiosis-specific protein MEILB2 facilitates BRCA2 recruitment to meiotic recombination sites. Here, we combine crystallography, biochemical analysis and a mouse meiosis model to reveal a robust architecture that ensures meiotic BRCA2 recruitment.

Interpreting Bibliometric Data.

Many academic analyses of good practice in the use of bibliometric data address only technical aspects and fail to account for and appreciate user requirements, expectations, and actual practice. Bibliometric indicators are rarely the only evidence put before any user group. In the present state of knowledge, it is more important to consider how quantitative evaluation can be made simple, transparent, and readily understood than it is to focus unduly on precision, accuracy, or scholarly notions of purity.

The BRCA2-MEILB2-BRME1 complex governs meiotic recombination and impairs the mitotic BRCA2-RAD51 function in cancer cells.

Breast cancer susceptibility gene II (BRCA2) is central in homologous recombination (HR). In meiosis, BRCA2 binds to MEILB2 to localize to DNA double-strand breaks (DSBs). Here, we identify BRCA2 and MEILB2-associating protein 1 (BRME1), which functions as a stabilizer of MEILB2 by binding to an α-helical N-terminus of MEILB2 and preventing MEILB2 self-association.

Structural biology of telomeres and telomerase.

Telomeres are protein-DNA complexes that protect chromosome ends from illicit ligation and resection. Telomerase is a ribonucleoprotein enzyme that synthesizes telomeric DNA to counter telomere shortening. Human telomeres are composed of complexes between telomeric DNA and a six-protein complex known as shelterin.

Dissecting the telomere-inner nuclear membrane interface formed in meiosis.

Tethering telomeres to the inner nuclear membrane (INM) allows homologous chromosome pairing during meiosis. The meiosis-specific protein TERB1 binds the telomeric protein TRF1 to establish telomere-INM connectivity and is essential for mouse fertility. Here we solve the structure of the human TRF1-TERB1 interface to reveal the structural basis for telomere-INM linkage.

An Acrobatic Substrate Metamorphosis Reveals a Requirement for Substrate Conformational Dynamics in Trypsin Proteolysis.

The molecular basis of enzyme catalytic power and specificity derives from dynamic interactions between enzyme and substrate during catalysis. Although considerable effort has been devoted to understanding how conformational dynamics within enzymes affect catalysis, the role of conformational dynamics within protein substrates has not been addressed. Here, we examine the importance of substrate dynamics in the cleavage of Kunitz-bovine pancreatic trypsin inhibitor protease inhibitors by mesotrypsin, finding that the varied conformational dynamics of structurally similar substrates can profoundly impact the rate of catalysis.

Serine protease inhibitor Kazal type 1 (SPINK1) drives proliferation and anoikis resistance in a subset of ovarian cancers.

Ovarian cancer represents the most lethal tumor type among malignancies of the female reproductive system. Overall survival rates remain low. In this study, we identify the serine protease inhibitor Kazal type 1 (SPINK1) as a potential therapeutic target for a subset of ovarian cancers.

Sequence and conformational specificity in substrate recognition: several human Kunitz protease inhibitor domains are specific substrates of mesotrypsin.

Mesotrypsin is an isoform of trypsin that is uniquely resistant to polypeptide trypsin inhibitors and can cleave some inhibitors rapidly. Previous studies have shown that the amyloid precursor protein Kunitz protease inhibitor domain (APPI) is a specific substrate of mesotrypsin and that stabilization of the APPI cleavage site in a canonical conformation contributes to recognition by mesotrypsin. We hypothesized that other proteins possessing potential cleavage sites stabilized in a similar conformation might also be mesotrypsin substrates.

The use and misuse of journal metrics and other citation indicators.

This article reviews the nature and use of the journal impact factor and other common bibliometric measures for assessing research in the sciences and social sciences based on data compiled by Thomson Reuters. Journal impact factors are frequently misused to assess the influence of individual papers and authors, but such uses were never intended. Thomson Reuters also employs other measures of journal influence, which are contrasted with the impact factor.

Food-induced cortisol secretion is mediated by central alpha-1 adrenoceptor modulation of pituitary ACTH secretion.

Food ingestion stimulates cortisol secretion in man, but the mechanism of this effect is unknown. We have investigated the possible role of adrenoceptors in the mediation of this effect. Six normal males were given continuous 3 h i.

The radioimmunoassay of placental protein 5 and circulating levels in maternal blood in the third trimester of normal pregnancy.

A radioimmunoassay has been developed for placental protein 5 (PP5), a product of the human placenta. Circulating concentrations of PP5 were measured in the third trimester of normal pregnancy in 400 women. Concentrations of PP5 showed a skewed distribution and rose progressively to reach a plateau in the last four weeks of pregnancy.

Is measurement of placental function and maternal weight worth while?

A prospective survey of 1029 women delivered during 1976 at St. Bartholomew's Hospital was undertaken to assess the predictive value of a variety of clinical, ultrasonic, and biochemical variables in the detection of high-risk pregnancies. The best antenatal predictors of fetal risk were severe pre-eclampsia, depressed maternal serum levels of human placental lactogen, low maternal weight at 32 weeks' gestation, and heavy smoking by the mother.