Prediction of potential drug targets based on simple sequence properties

<p>Abstract</p> <p>Background</p> <p>During the past decades, research and development in drug discovery have attracted much attention and efforts. However, only 324 drug targets are known for clinical drugs up to now. Identifying potential drug targets is the first step in the process of modern drug discovery for developing novel therapeutic agents. Therefore, the identification and validation of new and effective drug targets are of great value for drug discovery in both academia and pharmaceutical industry. If a protein can be predicted in advance for its potential application as a drug target, the drug discovery process targeting this protein will be greatly speeded up. In the current study, based on the properties of known drug targets, we have developed a sequence-based drug target prediction method for fast identification of novel drug targets.</p> <p>Results</p> <p>Based on simple physicochemical properties extracted from protein sequences of known drug targets, several support vector machine models have been constructed in this study. The best model can distinguish currently known drug targets from non drug targets at an accuracy of 84%. Using this model, potential protein drug targets of human origin from Swiss-Prot were predicted, some of which have already attracted much attention as potential drug targets in pharmaceutical research.</p> <p>Conclusion</p> <p>We have developed a drug target prediction method based solely on protein sequence information without the knowledge of family/domain annotation, or the protein 3D structure. This method can be applied in novel drug target identification and validation, as well as genome scale drug target predictions.</p

Association between lifestyle factors and headache

Modification of lifestyle habits is a key preventive strategy for many diseases. The role of lifestyle for the onset of headache in general and for specific headache types, such as migraine and tension-type headache (TTH), has been discussed for many years. Most results, however, were inconsistent and data on the association between lifestyle factors and probable headache forms are completely lacking. We evaluated the cross-sectional association between different lifestyle factors and headache subtypes using data from three different German cohorts. Information was assessed by standardized face-to-face interviews. Lifestyle factors included alcohol consumption, smoking status, physical activity and body mass index. According to the 2004 diagnostic criteria, we distinguished the following headache types: migraine, TTH and their probable forms. Regional variations of lifestyle factors were observed. In the age- and gender-adjusted logistic regression models, none of the lifestyle factors was statistically significant associated with migraine, TTH, and their probable headache forms. In addition, we found no association between headache subtypes and the health index representing the sum of individual lifestyle factors. The lifestyle factors such as alcohol consumption, smoking, physical activity and overweight seem to be unrelated to migraine and TTH prevalence. For a judgement on their role in the onset of new or first attacks of migraine or TTH (incident cases), prospective cohort studies are required

Identifying Experimental Tool Use Through Confocal Microscopy

Characterizing use-wear traces quantitatively is a valid way to improve the capacity of use-wear analysis. This aim has been on specialists’ agenda since the beginning of the discipline. Micropolish quantification is especially important, as this type of trace allows the identification of worked materials. During the last decade, confocal microscopy has been used as a promising approach to address this question. Following previous efforts in plant microwear characterization (Ibáñez et al. Journal of Archaeological Science, 48, 96–103, 2014; Journal of Archaeological Science, 73, 62–81, 2016), here we test the capacity of the method for correctly grouping experimental tools used for working eight types of materials: bone, antler, wood, fresh hide, dry hide, wild cereals, domestic cereals, and reeds. We demonstrate, for the first time, that quantitative texture analysis of use-wear micropolish based on confocal microscopy can consistently identify tools used for working different contact materials. In this way, we are able to move toward using texture analysis as part of the standard functional analysis of prehistoric instruments.This study is part of the projects HAR2016-74999-P, HAR2015-68566-P, and HAR2016-81971-REDT funded by the Spanish Ministerio de Ciencia, Innovación y Universidades.Peer reviewe

Neanderthal Use of Fish, Mammals, Birds, Starchy Plants and Wood 125-250,000 Years Ago

Neanderthals are most often portrayed as big game hunters who derived the vast majority of their diet from large terrestrial herbivores while birds, fish and plants are seen as relatively unimportant or beyond the capabilities of Neanderthals. Although evidence for exploitation of other resources (small mammals, birds, fish, shellfish, and plants) has been found at certain Neanderthal sites, these are typically dismissed as unusual exceptions. The general view suggests that Neanderthal diet may broaden with time, but that this only occurs sometime after 50,000 years ago. We present evidence, in the form of lithic residue and use-wear analyses, for an example of a broad-based subsistence for Neanderthals at the site of Payre, Ardèche, France (beginning of MIS 5/end of MIS 6 to beginning of MIS 7/end of MIS 8; approximately 125–250,000 years ago). In addition to large terrestrial herbivores, Neanderthals at Payre also exploited starchy plants, birds, and fish. These results demonstrate a varied subsistence already in place with early Neanderthals and suggest that our ideas of Neanderthal subsistence are biased by our dependence on the zooarchaeological record and a deep-seated intellectual emphasis on big game hunting

Venous hemodynamics in neurological disorders: an analytical review with hydrodynamic analysis.

Venous abnormalities contribute to the pathophysiology of several neurological conditions. This paper reviews the literature regarding venous abnormalities in multiple sclerosis (MS), leukoaraiosis, and normal-pressure hydrocephalus (NPH). The review is supplemented with hydrodynamic analysis to assess the effects on cerebrospinal fluid (CSF) dynamics and cerebral blood flow (CBF) of venous hypertension in general, and chronic cerebrospinal venous insufficiency (CCSVI) in particular.CCSVI-like venous anomalies seem unlikely to account for reduced CBF in patients with MS, thus other mechanisms must be at work, which increase the hydraulic resistance of the cerebral vascular bed in MS. Similarly, hydrodynamic changes appear to be responsible for reduced CBF in leukoaraiosis. The hydrodynamic properties of the periventricular veins make these vessels particularly vulnerable to ischemia and plaque formation.Venous hypertension in the dural sinuses can alter intracranial compliance. Consequently, venous hypertension may change the CSF dynamics, affecting the intracranial windkessel mechanism. MS and NPH appear to share some similar characteristics, with both conditions exhibiting increased CSF pulsatility in the aqueduct of Sylvius.CCSVI appears to be a real phenomenon associated with MS, which causes venous hypertension in the dural sinuses. However, the role of CCSVI in the pathophysiology of MS remains unclear

The Human Phenotype Ontology in 2024: phenotypes around the world

\ua9 The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs