Elucidation of Directionality for Co-Expressed Genes: Predicting Intra-Operon Termination Sites

We present a novel framework for inferring regulatory and sequence-level information from gene co-expression networks. The key idea of our methodology is the systematic integration of network inference and network topological analysis approaches for uncovering biological insights. We determine the gene co-expression network of Bacillus subtilis using Affymetrix GeneChip time series data and show how the inferred network topology can be linked to sequence-level information hard-wired in the organism's genome. We propose a systematic way for determining the correlation threshold at which two genes are assessed to be co-expressed by using the clustering coefficient and we expand the scope of the gene co-expression network by proposing the slope ratio metric as a means for incorporating directionality on the edges. We show through specific examples for B. subtilis that by incorporating expression level information in addition to the temporal expression patterns, we can uncover sequence-level biological insights. In particular, we are able to identify a number of cases where (i) the co-expressed genes are part of a single transcriptional unit or operon and (ii) the inferred directionality arises due to the presence of intra-operon transcription termination sites.Comment: 7 pages, 8 figures, accepted in Bioinformatic

The Association of Cusp-Aligned Arcs With Plasma in the Magnetotail Implies a Closed Magnetosphere

We investigate a 15-day period in October 2011. Auroral observations by the Special Sensor Ultraviolet Spectrographic Imager instrument onboard the Defense Meteorological Satellite Program F16, F17, and F18 spacecraft indicate that the polar regions were covered by weak cusp-aligned arc (CAA) emissions whenever the interplanetary magnetic field (IMF) clock angle was small, |θ| < 45°, which amounted to 30% of the time. Simultaneous observations of ions and electrons in the tail by the Cluster C4 and Geotail spacecraft showed that during these intervals dense (≈1 cm−3) plasma was observed, even as far from the equatorial plane of the tail as |ZGSE| ≈ 13 RE. The ions had a pitch angle distribution peaking parallel and antiparallel to the magnetic field and the electrons had pitch angles that peaked perpendicular to the field. We interpret the counter-streaming ions and double loss-cone electrons as evidence that the plasma was trapped on closed field lines, and acted as a source for the CAA emission across the polar regions. This suggests that the magnetosphere was almost entirely closed during these periods. We further argue that the closure occurred as a consequence of dual-lobe reconnection. Our finding forces a significant re-evaluation of the magnetic topology of the magnetosphere during periods of northwards IMF

The association of cusp‐Aligned arcs with plasma in the magnetotail implies a closed magnetosphere

We investigate a 15-day period in October 2011. Auroral observations by the Special Sensor Ultraviolet Spectrographic Imager instrument onboard the Defense Meteorological Satellite Program F16, F17, and F18 spacecraft indicate that the polar regions were covered by weak cusp-aligned arc (CAA) emissions whenever the interplanetary magnetic field (IMF) clock angle was small, |θ| < 45°, which amounted to 30% of the time. Simultaneous observations of ions and electrons in the tail by the Cluster C4 and Geotail spacecraft showed that during these intervals dense (≈1 cm−3) plasma was observed, even as far from the equatorial plane of the tail as |ZGSE| ≈ 13 RE. The ions had a pitch angle distribution peaking parallel and antiparallel to the magnetic field and the electrons had pitch angles that peaked perpendicular to the field. We interpret the counter-streaming ions and double loss-cone electrons as evidence that the plasma was trapped on closed field lines, and acted as a source for the CAA emission across the polar regions. This suggests that the magnetosphere was almost entirely closed during these periods. We further argue that the closure occurred as a consequence of dual-lobe reconnection. Our finding forces a significant re-evaluation of the magnetic topology of the magnetosphere during periods of northwards IMF

A retrospective population-based study of childhood hospital admissions with record linkage to a birth defects registry

<p>Abstract</p> <p>Background</p> <p>Using population-based linked records of births, deaths, birth defects and hospital admissions for children born 1980–1999 enables profiles of hospital morbidity to be created for each child.</p> <p>Methods</p> <p>This is an analysis of a state-based registry of birth defects linked to population-based hospital admission data. Transfers and readmissions within one day could be taken into account and treated as one episode of care for the purposes of analyses (N = 485,446 children; 742,845 non-birth admissions).</p> <p>Results</p> <p>Children born in Western Australia from 1980–1999 with a major birth defect comprised 4.6% of live births but 12.0% of non-birth hospital admissions from 1980–2000. On average, the children with a major birth defect remained in hospital longer than the children in the comparison group for the same diagnosis. The mean and median lengths of stay (LOS) for admissions before the age of 5 years have decreased for all children since 1980. However, the mean number of admissions per child admitted has remained constant at around 3.8 admissions for children with a major birth defect and 2.2 admissions for all other children.</p> <p>Conclusion</p> <p>To gain a true picture of the burden of hospital-based morbidity in childhood, admission records need to be linked for each child. We have been able to do this at a population level using birth defect cases ascertained by a birth defects registry. Our results showed a greater mean LOS and mean number of admissions per child admitted than previous studies. The results suggest there may be an opportunity for the children with a major birth defect to be monitored and seen earlier in the primary care setting for common childhood illnesses to avoid hospitalisation or reduce the LOS.</p

The porin and the permeating antibiotic: A selective diffusion barrier in gram-negative bacteria

Gram-negative bacteria are responsible for a large proportion of antibiotic resistant bacterial diseases. These bacteria have a complex cell envelope that comprises an outer membrane and an inner membrane that delimit the periplasm. The outer membrane contains various protein channels, called porins, which are involved in the influx of various compounds, including several classes of antibiotics. Bacterial adaptation to reduce influx through porins is an increasing problem worldwide that contributes, together with efflux systems, to the emergence and dissemination of antibiotic resistance. An exciting challenge is to decipher the genetic and molecular basis of membrane impermeability as a bacterial resistance mechanism. This Review outlines the bacterial response towards antibiotic stress on altered membrane permeability and discusses recent advances in molecular approaches that are improving our knowledge of the physico-chemical parameters that govern the translocation of antibiotics through porin channel

The Sleeping Brain's Influence on Verbal Memory: Boosting Resistance to Interference

Memories evolve. After learning something new, the brain initiates a complex set of post-learning processing that facilitates recall (i.e., consolidation). Evidence points to sleep as one of the determinants of that change. But whenever a behavioral study of episodic memory shows a benefit of sleep, critics assert that sleep only leads to a temporary shelter from the damaging effects of interference that would otherwise accrue during wakefulness. To evaluate the potentially active role of sleep for verbal memory, we compared memory recall after sleep, with and without interference before testing. We demonstrated that recall performance for verbal memory was greater after sleep than after wakefulness. And when using interference testing, that difference was even more pronounced. By introducing interference after sleep, this study confirms an experimental paradigm that demonstrates the active role of sleep in consolidating memory, and unmasks the large magnitude of that benefit

A systematic review of complex system interventions designed to increase recovery from depression in primary care

BACKGROUND: Primary care is being encouraged to implement multiprofessional, system level, chronic illness management approaches to depression. We undertook this study to identify and assess the quality of RCTs testing system level depression management interventions in primary care and to determine whether these interventions improve recovery. METHOD: Searches of Medline and Cochrane Controlled Register of Trials. 'System level' interventions included: multi-professional approach, enhanced inter-professional communication, scheduled patient follow-up, structured management plan. RESULTS: 11 trials met all inclusion criteria. 10 were undertaken in the USA. Most focussed on antidepressant compliance. Quality of reporting assessed using CONSORT criteria was poor. Eight trials reported an increase in the proportion of patients recovered in favour of the intervention group, yet did not account for attrition rates ranging from 5 to 50%. CONCLUSION: System level interventions implemented in the USA with patients willing to take anti-depressant medication leads to a modest increase in recovery from depression. The relevance of these interventions to countries with strong primary care systems requires testing in a randomised controlled trial

Depression and anxiety, an Indicated Prevention (DIP) protocol in homes for the elderly: feasibility and (cost) effectiveness of a stepped care programme

BACKGROUND: Depressive and anxiety disorders are a very common, serious and underdetected problem in homes for the elderly. Elderly persons in residential homes are at high risk for developing major depressive and anxiety disorders, and, therefore, deserve attention with regard to prevention. METHODS/DESIGN: This protocol describes a randomised trial on the feasibility and (cost) effectiveness of a stepped-care programme for prevention of depressive and anxiety disorders in homes for the elderly. The main outcome measure is the incidence of depressive and anxiety disorder in one year with a two years follow up. Secondary outcomes are symptoms of depression and anxiety, quality of life, direct health care costs and satisfaction with treatment. DISCUSSION: The number of studies examining the effects of preventive interventions on the incidence of mental disorders in the elderly population is very small. However, indicated prevention by means of a stepped-care programme seems to be an important option for decreasing the burden of illness for residents and their caregivers. This study contributes to the body of knowledge in this field. Positive effects may contribute to further use and development of tailored, (cost-) effective and easy to use interventions in a preventive stepped-care programme. TRIAL REGISTRATION: The Dutch Cochrane Centre, ISRCTN2754073

Structural Optimization and De Novo Design of Dengue Virus Entry Inhibitory Peptides

Viral fusogenic envelope proteins are important targets for the development of inhibitors of viral entry. We report an approach for the computational design of peptide inhibitors of the dengue 2 virus (DENV-2) envelope (E) protein using high-resolution structural data from a pre-entry dimeric form of the protein. By using predictive strategies together with computational optimization of binding “pseudoenergies”, we were able to design multiple peptide sequences that showed low micromolar viral entry inhibitory activity. The two most active peptides, DN57opt and 1OAN1, were designed to displace regions in the domain II hinge, and the first domain I/domain II beta sheet connection, respectively, and show fifty percent inhibitory concentrations of 8 and 7 µM respectively in a focus forming unit assay. The antiviral peptides were shown to interfere with virus:cell binding, interact directly with the E proteins and also cause changes to the viral surface using biolayer interferometry and cryo-electron microscopy, respectively. These peptides may be useful for characterization of intermediate states in the membrane fusion process, investigation of DENV receptor molecules, and as lead compounds for drug discovery