Multiple regions within 8q24 independently affect risk for prostate cancer

After the recent discovery that common genetic variation in 8q24 influences inherited risk of prostate cancer, we genotyped 2,973 SNPs in up to 7,518 men with and without prostate cancer from five populations. We identified seven risk variants, five of them previously undescribed, spanning 430 kb and each independently predicting risk for prostate cancer (P = 7.9 x 10(-19) for the strongest association, and P < 1.5 x 10(-4) for five of the variants, after controlling for each of the others). The variants define common genotypes that span a more than fivefold range of susceptibility to cancer in some populations. None of the prostate cancer risk variants aligns to a known gene or alters the coding sequence of an encoded protein.     

A gene in the multidrug and toxic compound extrusion (MATE) family confers aluminum tolerance in sorghum

Crop yields are significantly reduced by aluminum toxicity on highly acidic soils, which comprise up to 50% of the world's arable land. Candidate aluminum tolerance proteins include organic acid efflux transporters, with the organic acids forming non-toxic complexes with rhizosphere aluminum. In this study, we used positional cloning to identify the gene encoding a member of the multidrug and toxic compound extrusion (MATE) family, an aluminum-activated citrate transporter, as responsible for the major sorghum (Sorghum bicolor) aluminum tolerance locus, Alt(SB). Polymorphisms in regulatory regions of Alt(SB) are likely to contribute to large allelic effects, acting to increase Alt(SB) expression in the root apex of tolerant genotypes. Furthermore, aluminum-inducible Alt(SB) expression is associated with induction of aluminum tolerance via enhanced root citrate exudation. These findings will allow us to identify superior Alt(SB) haplotypes that can be incorporated via molecular breeding and biotechnology into acid soil breeding programs, thus helping to increase crop yields in developing countries where acidic soils predominate.     

Field and laboratory observations on reproductive aspects of Pseudopaludicola ameghini (Cope, 1887) (Leptodactylidae: Leiuperinae)

ABSTRACT

The genus Pseudopaludicola includes small-sized anurans, widely distributed throughout South America. Twenty-three out of the 25 species occur in Brazil. Although described more than a century ago, from mid-southern Mato Grosso state, central Brazil, Pseudopaludicola ameghini is poorly known. Here we describe the characteristics of reproductive site, amplexus, egg-laying behaviour, eggs and tadpoles of P. ameghini based on specimens and observations performed in the vicinities of the type locality. Pairs of P. ameghini reproduce in shallow and slow groundwater established on hydromorphic terrains, in open environments amidst the Brazilian Cerrado savanna. Reproductive activity occurred between 17:00 and 21:00 h at two sites studied from December 2013 to April 2014. Amplexus is axillary. Eggs are spherical, with a mean diameter of 5.1 mm (yolk plus jelly envelope). Oviposition occurs in shallow sites at a depth of nearly 2.0 cm. Females deposit their eggs one at a time, directly onto sediment at the bottom of waterbodies or attached to submerged vegetation. The tadpole body is oval in dorsal view and globular/depressed in lateral view; eyes are large and dorsally positioned. Nares are large, round, with a small apophysis on marginal rim, dorsally positioned, near the eyes. The spiracle is short, with posterodorsal opening. The oral disc is anteroventral, emarginated laterally, with one dorsal and two ventral gaps; the tooth row formula is 2(2)/2(1), and the upper jaw sheath is ‘arc’ shaped. Pseudopaludicola ameghini has a unique behaviour of oviposition among members of the genus. The differences in reproductive pattern and larval characteristics of P. mystacalis and P. ameghini reinforce the taxonomic validity of the latter, questioned until recently.     

Approaches to identify and characterize microProteins and their potential uses in biotechnology

MicroProteins are small proteins that contain a single protein domain and are related to larger, often multi-domain proteins. At the molecular level, microProteins act by interfering with the formation of higher order protein complexes. In the past years, several microProteins have been identified in plants and animals that strongly influence biological processes. Due to their ability to act as dominant regulators in a targeted manner, microProteins have a high potential for biotechnological use. In this review, we present different ways in which microProteins are generated and we elaborate on techniques used to identify and characterize them. Finally, we give an outlook on possible applications in biotechnology.     

Mitochondria dynamism: of shape,transport and cell migration

Mitochondria are highly dynamic and functionally versatile organelles that continuously fragment and fuse in response to different physiological needs of the cell. The list of proteins that strictly regulate the morphology of these organelles is constantly growing, adding new players every day and new pieces to the comprehension and elucidation of this complex machinery. The structural complexity of mitochondria is only paralled by their functional versatility. Indeed, changes in mitochondria shape play critical roles in vertebrate development programmed cell death and in various processes of normal cell physiology, such as calcium signaling, reactive oxygen species production, and lifespan. Here, we present the latest findings on the regulation of mitochondrial dynamics and some of their physiological roles, focusing on cell migration. In cells where migration represents a crucial function in their physiology, such as T and tumoral metastatic cells, mitochondria need to be fragmented and recruited to specific subcellular regions to make movement possible. In depth analysis of this role of mitochondrial dynamics should help in identifying potential targeted therapy against cancer or in improving the immune system’s efficiency.     

Model–proxy comparison for overshoot phenomenon of Atlantic thermohaline circulation at Bφlling–Allerφd

The overshoot phenomenon of the Atlantic thermohaline circulation （THC） is a transient climate response to meltwater forcing and could induce intense climate change by increasing the magnitudes of Atlantic THC changes at the end of meltwater discharges. This phenomenon was formally presented with the successfully simulated Bolling-Allerod （BA） event in the first transient simulation of the last deglaciation with fully coupled model NCAR-CCSM3 （TraCE-21K）. Currently, not all proxy records of Atlantic THC support the occurrence of the THC overshoot at BA. Commonly used THC proxy from Bermuda Rise （GGC5） does not exhibit THC overshoot at BA but other proxies such as TTR-451 at Eirik Drift do. How to interpret this regional discrepancy of proxy records is a key question for the validation of the Atlantic THC overshoot at BA. Here, we show that the vigor of deep circulation varies regionally during the Atlantic THC overshoot at BA in TraCE-21K simulation, and this regional discrepancy in the simulation is consistent with that in the marine sediment records in North Atlantic. The consistent model-proxy evidence supports the occurrence of Atlantic THC overshoot at BA.     

Base excision repair and design of small molecule inhibitors of human DNA polymerase β

Base excision repair (BER) can protect a cell after endogenous or exogenous genotoxic stress, and a deficiency in BER can render a cell hypersensitive to stress-induced apoptotic and necrotic cell death, mutagenesis, and chromosomal rearrangements. However, understanding of the mammalian BER system is not yet complete as it is extraordinarily complex and has many back-up processes that complement a deficiency in any one step. Due of this lack of information, we are unable to make accurate predictions on therapeutic approaches targeting BER. A deeper understanding of BER will eventually allow us to conduct more meaningful clinical interventions. In this review, we will cover historical and recent information on mammalian BER and DNA polymerase β and discuss approaches toward development and use of small molecule inhibitors to manipulate BER. With apologies to others, we will emphasize results obtained in our laboratory and those of our collaborators.     

Estimation and Forecasting of Locally Stationary Processes

This paper develops a state space framework for the statistical analysis of a class of locally stationary processes. The proposed Kalman filter approach provides a numerically efficient methodology for estimating and predicting locally stationary models and allows for the handling of missing values. It provides both exact and approximate maximum likelihood estimates. Furthermore, as suggested by the Monte Carlo simulations reported in this work, the performance of the proposed methodology is very good, even for relatively small sample sizes. Copyright © 2011 John Wiley & Sons, Ltd.     

To Escape the ‘Finishing the Biology Syllabus Syndrome’: An Action Research Exploratory Study in Explicit Modelling for Malaysian Biology Teacher Training

In this paper an exploratory two phase action research of one teacher educator’s attempt at explicit modelling is portrayed. The first phase elicited opinions of pre-service Biology teachers at the end of a semester. Based on the findings of the first phase, the second phase facilitated the pre-service Biology teacher sample to alleviate their ‘finishing the syllabus syndrome’ which they had picked up from their school days. The explicit modelling planned for the second phase was based upon the modelling theory of Albert Bandura. The study indicates that the explicit modelling endeavoured appeared to have some effect upon the motivation and the symbolising, vicarious, forethought, self-regulation and self-reflection capabilities of the pre-service Biology teachers. The ‘finishing the syllabus mentality’ where the presentation of content was significant, showed signs of weakening at the end of the second phase.