Structure of the regulatory domain of the LysR family regulator NMB2055 (MetR-like protein) from Neisseria meningitidis

Copyright @ 2012 International Union of CrystallographyThe crystal structure of the regulatory domain of NMB2055, a putative MetR regulator from Neisseria meningitidis, is reported at 2.5 Å resolution. The structure revealed that there is a disulfide bond inside the predicted effector-binding pocket of the regulatory domain. Mutation of the cysteines (Cys103 and Cys106) that form the disulfide bond to serines resulted in significant changes to the structure of the effector pocket. Taken together with the high degree of conservation of these cysteine residues within MetR-related transcription factors, it is suggested that the Cys103 and Cys106 residues play an important role in the function of MetR regulators.This study is funded by the Medical Research Council, with additional finance from the Biotechnology and Biological Science Research Council

Pioneers in CNS inhibition: 2. Charles Sherrington and John Eccles on inhibition in spinal and supraspinal structures

This article reviews the contributions of the English neurophysiologist, Charles Scott Sherrington [1857–1952], and his Australian PhD trainee and collaborator, John Carew Eccles [1903–1997], to the concept of central inhibition in the spinal cord and brain. Both were awarded Nobel Prizes; Sherrington in 1932 for “discoveries regarding the function of neurons,” and Eccles in 1963 for “discoveries concerning the ionic mechanisms involved in excitation and inhibition in central portions of the nerve cell membrane.” Both spoke about central inhibition at their Nobel Prize Award Ceremonies. The subsequent publications of their talks were entitled “Inhibition as a coordinative factor” and “The ionic mechanism of postsynaptic inhibition”, respectively. Sherrington's work on central inhibition spanned 41 years (1893–1934), and for Eccles 49 years (1928–1977). Sherrington first studied central inhibition by observing hind limb muscle responses to electrical (peripheral nerve) and mechanical (muscle) stimulation. He used muscle length and force measurements until the early 1900s and electromyography in the late 1920s. Eccles used these techniques while working with Sherrington, but later employed extracellular microelectrode recording in the spinal cord followed in 1951 by intracellular recording from spinal motoneurons. This considerably advanced our understanding of central inhibition. Sherrington's health was poor during his retirement years but he nonetheless made a small number of largely humanities contributions up to 1951, one year before his death at the age of 94. In contrast, Eccles retained his health and vigor until 3 years before his death and published prolifically on many subjects during his 22 years of official retirement. His last neuroscience article appeared in 1994 when he was 91. Despite poor health he continued thinking about his life-long interest, the mind-brain problem, and was attempting to complete his autobiography in the last years of his life

Eruption of kimberlite magmas: physical volcanology, geomorphology and age of the youngest kimberlitic volcanoes known on earth (the Upper Pleistocene/ Holocene Igwisi Hills volcanoes, Tanzania)

The Igwisi Hills volcanoes (IHV), Tanzania, are unique and important in preserving extra-crater lavas and pyroclastic edifices. They provide critical insights into the eruptive behaviour of kimberlite magmas that are not available at other known kimberlite volcanoes. Cosmogenic 3He dating of olivine crystals from IHV lavas and palaeomagnetic analyses indicates that they are Upper Pleistocene to Holocene in age. This makes them the youngest known kimberlite bodies on Earth by >30 Ma and may indicate a new phase of kimberlite volcanism on the Tanzania craton. Geological mapping, Global Positioning System surveying and field investigations reveal that each volcano comprises partially eroded pyroclastic edifices, craters and lavas. The volcanoes stand 102 to 106 Pa s) for kimberlite, attributed to degassing and in-vent cooling. Each volcano is inferred to be the result of a small-volume, short-lived (days to weeks) monogenetic eruption. The eruptive processes of each Igwisi volcano were broadly similar and developed through three phases: (1) fallout of lithic-bearing pyroclastic rocks during explosive excavation of craters and conduits; (2) fallout of juvenile lapilli from unsteady eruption columns and the construction of pyroclastic edifices around the vent; and (3) effusion of degassed viscous magma as lava flows. These processes are similar to those observed for other small-volume monogenetic eruptions (e.g. of basaltic magma)

The association between major depressive disorder, use of antidepressants and bone mineral density (BMD) in men.

OBJECTIVE: Both depression and use of antidepressants have been negatively associated with bone mineral density (BMD) but mainly in studies among postmenopausal women. Therefore, the aim of this study was to investigate these relationships in men. METHODS: Between 2006 and 2011, 928 men (aged 24-98 years) from the Geelong Osteoporosis Study completed a comprehensive questionnaire, clinical measurements and had BMD assessments at the forearm, spine, total hip and total body. Major depressive disorder (MDD) was identified using a structured clinical interview (SCID-I/NP). The cross-sectional associations between BMD and both MDD and antidepressant use were analyzed using multivariable linear regression. RESULTS: Of the study population, 84 (9.1%) men had a single MDD episode, 50 (5.4%) had recurrent episodes and 65 (7.0%) were using antidepressants at the time of assessment. Following adjustments, recurrent MDD was associated with lower BMD at the forearm and total body (-6.5%, P=0.033 and -2.5%, P=0.033, respectively compared to men with no history of MDD), while single MDD episodes were associated with higher BMD at the total hip (+3.4%, P=0.030). Antidepressant use was associated with lower BMD only in lower-weight men (<75-110 kg depending on bone site). CONCLUSIONS: Both depression and use of antidepressants should be taken into account as possible risk factors for osteoporosis in men

Dwarf Galaxy Formation Was Suppressed By Cosmic Reionization

A large number of faint galaxies, born less than a billion years after the big bang, have recently been discovered. The fluctuations in the distribution of these galaxies contributed to a scatter in the ionization fraction of cosmic hydrogen on scales of tens of Mpc, as observed along the lines of sight to the earliest known quasars. Theoretical simulations predict that the formation of dwarf galaxies should have been suppressed after cosmic hydrogen was reionized, leading to a drop in the cosmic star formation rate. Here we present evidence for this suppression. We show that the post-reionization galaxies which produced most of the ionizing radiation at a redshift z~5.5, must have had a mass in excess of ~10^{10.6+/-0.4} solar masses or else the aforementioned scatter would have been smaller than observed. This limiting mass is two orders of magnitude larger than the galaxy mass that is thought to have dominated the reionization of cosmic hydrogen (~10^8 solar masses). We predict that future surveys with space-based infrared telescopes will detect a population of smaller galaxies that reionized the Universe at an earlier time, prior to the epoch of dwarf galaxy suppression.Comment: 19 pages, 3 figures. Accepted for publication in Nature; press embargo until publishe

Successful Closed Reduction of a Dislocated Constrained Total Hip Arthroplasty: A Case Report and Literature Review

Many surgeons use acetabular components with constrained polyethylene liners to improve stability after total hip arthroplasty in patients with a history of hip dislocation. Surgical treatment is generally thought to be the only available option for the dislocated constrained liner. The success rate and clinical results of closed reduction for such patients is unclear. This report presents a case of a successful closed reduction of a dislocated constrained liner. Few papers have so far addressed closed reduction of a dislocated constrained liner. Furthermore, previous studies reported a variety of components. Publication of additional successful and unsuccessful case reports is therefore needed to help establish the optimal treatment protocol for a dislocated constrained liner

Paradigm of tunable clustering using binarization of consensus partition matrices (Bi-CoPaM) for gene discovery

Copyright @ 2013 Abu-Jamous et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Clustering analysis has a growing role in the study of co-expressed genes for gene discovery. Conventional binary and fuzzy clustering do not embrace the biological reality that some genes may be irrelevant for a problem and not be assigned to a cluster, while other genes may participate in several biological functions and should simultaneously belong to multiple clusters. Also, these algorithms cannot generate tight clusters that focus on their cores or wide clusters that overlap and contain all possibly relevant genes. In this paper, a new clustering paradigm is proposed. In this paradigm, all three eventualities of a gene being exclusively assigned to a single cluster, being assigned to multiple clusters, and being not assigned to any cluster are possible. These possibilities are realised through the primary novelty of the introduction of tunable binarization techniques. Results from multiple clustering experiments are aggregated to generate one fuzzy consensus partition matrix (CoPaM), which is then binarized to obtain the final binary partitions. This is referred to as Binarization of Consensus Partition Matrices (Bi-CoPaM). The method has been tested with a set of synthetic datasets and a set of five real yeast cell-cycle datasets. The results demonstrate its validity in generating relevant tight, wide, and complementary clusters that can meet requirements of different gene discovery studies.National Institute for Health Researc

A distortion of very--high--redshift galaxy number counts by gravitational lensing

The observed number counts of high-redshift galaxy candidates have been used to build up a statistical description of star-forming activity at redshift z >~ 7, when galaxies reionized the Universe. Standard models predict that a high incidence of gravitational lensing will probably distort measurements of flux and number of these earliest galaxies. The raw probability of this happening has been estimated to be ~ 0.5 percent, but can be larger owing to observational biases. Here we report that gravitational lensing is likely to dominate the observed properties of galaxies with redshifts of z >~ 12, when the instrumental limiting magnitude is expected to be brighter than the characteristic magnitude of the galaxy sample. The number counts could be modified by an order of magnitude, with most galaxies being part of multiply imaged systems, located less than 1 arcsec from brighter foreground galaxies at z ~ 2. This lens-induced association of high-redshift and foreground galaxies has perhaps already been observed among a sample of galaxy candidates identified at z ~ 10.6. Future surveys will need to be designed to account for a significant gravitational lensing bias in high-redshift galaxy samples.Comment: Nature, Jan. 13, 2011 issue (in press

Examining the demographic profile and attitudes of citizens, in areas where organised crime groups proliferate

Whilst studies refer to the community impact of Organized Crime (OC), no survey currently exists to examine the views of those citizens who reside in areas where Organized Crime Groups (OCGs) proliferate. 431 questionnaires from households co-existing in high density OCGs areas were analysed in relation to: a) demographic information; b) views on the community and the police; and c) how they expected other residents to react to illegal incidents. Overall respondents thought the average citizen would refuse to intervene in 10% - 48% of illegal incidents, with the specific case influencing whether and how they would respond. The analysis then compared three communities who lived in high density OCG areas with a control community (n=343). The ‘OCG’ communities were more likely to report low collective efficacy and were least likely to expect their neighbours to confront a crime in action. Conversely, whilst the control group showed higher levels of collective efficacy and expected the average resident more likely to confront illegal behaviour, this trend did not extend to street drug dealing and serious crime associated with OC. The study discusses the unreported intimidation associated with OCGs and the challenges of policing hostile environments

Integrated method for quantitative morphometry and oxygen transport modelling in striated muscle

Identifying structural limitations in O2 transport is primarily restricted by current methods employed to characterise the nature of physiological remodelling. Inadequate resolution or breadth of available data has impaired development of routine diagnostic protocols and effective therapeutic strategies. Understanding O2 transport within striated muscle faces major challenges, most notably in quantifying how well individual fibres are supplied by the microcirculation, which has necessitated exploring tissue O2 supply using theoretical modelling of diffusive exchange. Having identified capillary domains as a suitable model for the description of local O2 supply, and requiring less computation than numerically calculating the trapping regions that are supplied by each capillary via biophysical transport models, we sought to design a high throughput method for histological analysis. We present an integrated package that identifies optimal protocols for identification of important input elements, processing of digitised images with semi-automated routines, and incorporation of these data into a mathematical modelling framework with computed output visualised as the tissue partial pressure of O2 (PO2) distribution across a biopsy sample. Worked examples are provided using muscle samples from experiments involving rats and humans