Prediction of peptide and protein propensity for amyloid formation

Understanding which peptides and proteins have the potential to undergo amyloid formation and what driving forces are responsible for amyloid-like fiber formation and stabilization remains limited. This is mainly because proteins that can undergo structural changes, which lead to amyloid formation, are quite diverse and share no obvious sequence or structural homology, despite the structural similarity found in the fibrils. To address these issues, a novel approach based on recursive feature selection and feed-forward neural networks was undertaken to identify key features highly correlated with the self-assembly problem. This approach allowed the identification of seven physicochemical and biochemical properties of the amino acids highly associated with the self-assembly of peptides and proteins into amyloid-like fibrils (normalized frequency of β-sheet, normalized frequency of β-sheet from LG, weights for β-sheet at the window position of 1, isoelectric point, atom-based hydrophobic moment, helix termination parameter at position j+1 and ΔGº values for peptides extrapolated in 0 M urea). Moreover, these features enabled the development of a new predictor (available at http://cran.r-project.org/web/packages/appnn/index.html) capable of accurately and reliably predicting the amyloidogenic propensity from the polypeptide sequence alone with a prediction accuracy of 84.9 % against an external validation dataset of sequences with experimental in vitro, evidence of amyloid formation

The population genomics of begomoviruses: global scale population structure and gene flow

<p>Abstract</p> <p>Background</p> <p>The rapidly growing availability of diverse full genome sequences from across the world is increasing the feasibility of studying the large-scale population processes that underly observable pattern of virus diversity. In particular, characterizing the genetic structure of virus populations could potentially reveal much about how factors such as geographical distributions, host ranges and gene flow between populations combine to produce the discontinuous patterns of genetic diversity that we perceive as distinct virus species. Among the richest and most diverse full genome datasets that are available is that for the dicotyledonous plant infecting genus, <it>Begomovirus</it>, in the Family Geminiviridae. The begomoviruses all share the same whitefly vector, are highly recombinogenic and are distributed throughout tropical and subtropical regions where they seriously threaten the food security of the world's poorest people.</p> <p>Results</p> <p>We focus here on using a model-based population genetic approach to identify the genetically distinct sub-populations within the global begomovirus meta-population. We demonstrate the existence of at least seven major sub-populations that can further be sub-divided into as many as thirty four significantly differentiated and genetically cohesive minor sub-populations. Using the population structure framework revealed in the present study, we further explored the extent of gene flow and recombination between genetic populations.</p> <p>Conclusions</p> <p>Although geographical barriers are apparently the most significant underlying cause of the seven major population sub-divisions, within the framework of these sub-divisions, we explore patterns of gene flow to reveal that both host range differences and genetic barriers to recombination have probably been major contributors to the minor population sub-divisions that we have identified. We believe that the global <it>Begomovirus </it>population structure revealed here could facilitate population genetics studies into how central parameters of population genetics namely selection, recombination, mutation, gene flow, and genetic drift shape the global begomovirus diversity.</p

Phase 2 of CATALISE: a multinational and multidisciplinary Delphi consensus study of problems with language development: Terminology

BACKGROUND: Lack of agreement about criteria and terminology for children's language problems affects access to services as well as hindering research and practice. We report the second phase of a study using an online Delphi method to address these issues. In the first phase, we focused on criteria for language disorder. Here we consider terminology. METHODS: The Delphi method is an iterative process in which an initial set of statements is rated by a panel of experts, who then have the opportunity to view anonymised ratings from other panel members. On this basis they can either revise their views or make a case for their position. The statements are then revised based on panel feedback, and again rated by and commented on by the panel. In this study, feedback from a second round was used to prepare a final set of statements in narrative form. The panel included 57 individuals representing a range of professions and nationalities. RESULTS: We achieved at least 78% agreement for 19 of 21 statements within two rounds of ratings. These were collapsed into 12 statements for the final consensus reported here. The term ‘Language Disorder’ is recommended to refer to a profile of difficulties that causes functional impairment in everyday life and is associated with poor prognosis. The term, ‘Developmental Language Disorder’ (DLD) was endorsed for use when the language disorder was not associated with a known biomedical aetiology. It was also agreed that (a) presence of risk factors (neurobiological or environmental) does not preclude a diagnosis of DLD, (b) DLD can co-occur with other neurodevelopmental disorders (e.g. ADHD) and (c) DLD does not require a mismatch between verbal and nonverbal ability. CONCLUSIONS: This Delphi exercise highlights reasons for disagreements about terminology for language disorders and proposes standard definitions and nomenclature

Effect of smoking on the gingival capillary density: assessment of gingival capillary density with orthogonal polarization spectral imaging

Microvascular changes because of smoking are frequently presumed in models because of the negative effect of smoking portrayed on the microcirculation. We hypothesized that cigarette smoke might lead to a decrease in gingival capillary density. Capillary density was assessed with orthogonal polarization spectral (OPS) imaging, a technique using special optics by which a virtual light source is created at a depth of 1 mm within the mucosa. The light is absorbed by haemoglobin, resulting in an image of the capillaries in negative contrast. The gingival capillary density was measured in 20 healthy male dental students with a mean age of 25. Ten of the students were smokers and 10 were non-smokers. In each subject six images of the right maxillary pre-molar region were obtained, and the mean gingival capillary density was determined through the use of K&K software technology. The mean capillary density in smokers was 69.3 +/- 8.9 capillaries per visual field compared with a mean capillary density in non-smokers of 60.6 +/- 5.4 (p=0.33). No significant differences were found between the gingival capillary density of smokers and non-smoker

The University of the West Indies-Seismic Research Centre Volcano Monitoring Network: Evolution since 1953 and Challenges in Maintaining a State-of-the-Art Network in a Small Island Economy

The Seismic Research Centre (SRC), formerly known as the Seismic Research Unit (SRU), of the University of the West Indies is located on the island of Trinidad in the Eastern Caribbean. The centre has been operating its volcanological and seismological surveillance network since 1953. Since that time, the network has been upgraded five times resulting in five generations of seismic network topologies (i.e., Classes). Class 1 consisted of autonomously operated photographic recording stations, a purely analogue configuration. From Class 2 to Class 5 (current class) the network has continuously grown in scope, sophistication and capability. The evolution of the network was carried out using a combination of state-of-the-art instruments as well as trailing edge technology (e.g., analogue transmission) used in a manner that allows for sustainability. In this way, the network has been able to address the scientific and technical challenges associated with operating in an island arc subduction zone which is exposed to other natural hazards such as hurricanes. To counter its operational constrains the SRC has developed several strategies, which contribute to: (i) expand the network to meet the demand for more timely and accurate surveillance of geohazards, (ii) broaden the range of monitoring techniques (e.g., cGPS, geochemical), (iii) capture research grade scientific data and (iv) reduce operational costs

Clinical characteristics and outcomes after new-onset seizure among Zambian children with HIV during the antiretroviral therapy era

ObjectiveThis study describes clinical profiles including human immunodeficiency virus (HIV) disease history and seizure etiology among children living with HIV presenting with new-onset seizure during the era of antiretroviral therapy (ART) in Zambia. 30-day mortality and cause of death are also reported.MethodsChildren living with HIV (CLWHIV) with new-onset seizures were prospectively evaluated at one large urban teaching hospital and two non-urban healthcare facilities. Interviews with family members, review of medical records, and where needed, verbal autopsies were undertaken. Two clinicians who were not responsible for the patients’ care independently reviewed all records and assigned seizure etiology and cause of death with adjudication as needed.ResultsFrom April 2016 to June 2019, 73 children (49 urban, 24 rural) were identified. Median age was 6 years (IQR 2.2-10.0) and 39 (53%) were male children. Seizures were focal in 36 (49%) and were often severe, with 37% presenting with multiple recurrent seizures in the 24 hours before admission or in status epilepticus. Although 36 (49%) were on ART at enrollment, only 7 of 36 (19%) were virally suppressed. Seizure etiologies were infectious in over half (54%), with HIV encephalitis, bacterial meningitis, and tuberculous meningitis being the most common. Metabolic causes (19%) included renal failure and hypoglycemia. Structural lesions identified on imaging accounted for 10% of etiologies and included stroke and non-accidental trauma. No etiology could be identified in 12 (16%) children, most of whom died before the completion of clinical investigations. Twenty-two (30%) children died within 30 days of the index seizure.SignificanceDespite widespread ART roll out in Zambia, new-onset seizure in CLWHIV occurs in the setting of advanced, active HIV disease. Seizure severity/burden is high as is early mortality. Enhanced programs to assure early ART initiation, improve adherence, and address ART failure are needed to reduce the burden of neurological injury and premature death in CLWHIV.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/172838/1/epi412595_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/172838/2/epi412595.pd