Automated annotation of chemical names in the literature with tunable accuracy

<p>Abstract</p> <p>Background</p> <p>A significant portion of the biomedical and chemical literature refers to small molecules. The accurate identification and annotation of compound name that are relevant to the topic of the given literature can establish links between scientific publications and various chemical and life science databases. Manual annotation is the preferred method for these works because well-trained indexers can understand the paper topics as well as recognize key terms. However, considering the hundreds of thousands of new papers published annually, an automatic annotation system with high precision and relevance can be a useful complement to manual annotation.</p> <p>Results</p> <p>An automated chemical name annotation system, MeSH Automated Annotations (MAA), was developed to annotate small molecule names in scientific abstracts with tunable accuracy. This system aims to reproduce the MeSH term annotations on biomedical and chemical literature that would be created by indexers. When comparing automated free text matching to those indexed manually of 26 thousand MEDLINE abstracts, more than 40% of the annotations were false-positive (FP) cases. To reduce the FP rate, MAA incorporated several filters to remove "incorrect" annotations caused by nonspecific, partial, and low relevance chemical names. In part, relevance was measured by the position of the chemical name in the text. Tunable accuracy was obtained by adding or restricting the sections of the text scanned for chemical names. The best precision obtained was 96% with a 28% recall rate. The best performance of MAA, as measured with the F statistic was 66%, which favorably compares to other chemical name annotation systems.</p> <p>Conclusions</p> <p>Accurate chemical name annotation can help researchers not only identify important chemical names in abstracts, but also match unindexed and unstructured abstracts to chemical records. The current work is tested against MEDLINE, but the algorithm is not specific to this corpus and it is possible that the algorithm can be applied to papers from chemical physics, material, polymer and environmental science, as well as patents, biological assay descriptions and other textual data.</p

Bilinear R-parity violation with flavor symmetry

Bilinear R-parity violation (BRPV) provides the simplest intrinsically supersymmetric neutrino mass generation scheme. While neutrino mixing parameters can be probed in high energy accelerators, they are unfortunately not predicted by the theory. Here we propose a model based on the discrete flavor symmetry $A_4$ with a single R-parity violating parameter, leading to (i) correct Cabbibo mixing given by the Gatto-Sartori-Tonin formula, and a successful unification-like b-tau mass relation, and (ii) a correlation between the lepton mixing angles $\theta_{13}$ and $\theta_{23}$ in agreement with recent neutrino oscillation data, as well as a (nearly) massless neutrino, leading to absence of neutrinoless double beta decay.Comment: 16 pages, 3 figures. Extended version, as published in JHE

The Mycobacterium tuberculosis Phagosome Is a HLA-I Processing Competent Organelle

Mycobacterium tuberculosis (Mtb) resides in a long-lived phagosomal compartment that resists maturation. The manner by which Mtb antigens are processed and presented on MHC Class I molecules is poorly understood. Using human dendritic cells and IFN-γ release by CD8+ T cell clones, we examined the processing and presentation pathway for two Mtb–derived antigens, each presented by a distinct HLA-I allele (HLA-Ia versus HLA-Ib). Presentation of both antigens is blocked by the retrotranslocation inhibitor exotoxin A. Inhibitor studies demonstrate that, after reaching the cytosol, both antigens require proteasomal degradation and TAP transport, but differ in the requirement for ER–golgi egress and new protein synthesis. Specifically, presentation by HLA-B8 but not HLA-E requires newly synthesized HLA-I and transport through the ER–golgi. Phenotypic analysis of the Mtb phagosome by flow organellometry revealed the presence of Class I and loading accessory molecules, including TAP and PDI. Furthermore, loaded HLA-I:peptide complexes are present within the Mtb phagosome, with a pronounced bias towards HLA-E:peptide complexes. In addition, protein analysis also reveals that HLA-E is enriched within the Mtb phagosome compared to HLA-A2. Together, these data suggest that the phagosome, through acquisition of ER–localized machinery and as a site of HLA-I loading, plays a vital role in the presentation of Mtb–derived antigens, similar to that described for presentation of latex bead-associated antigens. This is, to our knowledge, the first description of this presentation pathway for an intracellular pathogen. Moreover, these data suggest that HLA-E may play a unique role in the presentation of phagosomal antigens

Transcriptional Reprogramming in Nonhuman Primate (Rhesus Macaque) Tuberculosis Granulomas

In response to Mtb infection, the host remodels the infection foci into a dense mass of cells known as the granuloma. The key objective of the granuloma is to contain the spread of Mtb into uninfected regions of the lung. However, it appears that Mtb has evolved mechanisms to resist killing in the granuloma. Profiling granuloma transcriptome will identify key immune signaling pathways active during TB infection. Such studies are not possible in human granulomas, due to various confounding factors. Nonhuman Primates (NHPs) infected with Mtb accurately reflect human TB in clinical and pathological contexts.We studied transcriptomics of granuloma lesions in the lungs of NHPs exhibiting active TB, during early and late stages of infection. Early TB lesions were characterized by a highly pro-inflammatory environment, expressing high levels of immune signaling pathways involving IFNgamma, TNFalpha, JAK, STAT and C-C/C-X-C chemokines. Late TB lesions, while morphologically similar to the early ones, exhibited an overwhelming silencing of the inflammatory response. Reprogramming of the granuloma transcriptome was highly significant. The expression of approximately two-thirds of all genes induced in early lesions was later repressed.The transcriptional characteristics of TB granulomas undergo drastic changes during the course of infection. The overwhelming reprogramming of the initial pro-inflammatory surge in late lesions may be a host strategy to limit immunopathology. We propose that these host profiles can predict changes in bacterial replication and physiology, perhaps serving as markers for latency and reactivation

Vascular disrupting agents in clinical development

Growth of human tumours depends on the supply of oxygen and nutrients via the surrounding vasculature. Therefore tumour vasculature is an attractive target for anticancer therapy. Apart from angiogenesis inhibitors that compromise the formation of new blood vessels, a second class of specific anticancer drugs has been developed. These so-called vascular disrupting agents (VDAs) target the established tumour vasculature and cause an acute and pronounced shutdown of blood vessels resulting in an almost complete stop of blood flow, ultimately leading to selective tumour necrosis. As a number of VDAs are now being tested in clinical studies, we will discuss their mechanism of action and the results obtained in preclinical studies. Also data from clinical studies will be reviewed and some considerations with regard to the future development are given

Pregnant Behind Bars: Meeting the Nutrition Needs of Incarcerated Pregnant Women

The number of women involved in the criminal justice system has increased dramatically over the past 20 years. Due to their marginalized background, incarcerated women have a complex set of health-related needs. This is especially true of those who are pregnant, a particularly vulnerable, high-risk group. Although guidelines have been developed that recommend pregnancy screening, provision of dietary supplements, regular nutritious meals, and nutritional counseling for incarcerated pregnant women, jail policies and health care protocols often fail to heed these recommendations. In this chapter, we discuss the nutritional needs of pregnant incarcerated women as well as breastfeeding in the context of the criminal justice system and consider some of the challenges in developing programming and policies to address these health-related needs. We also present findings from the William & Mary Healthy Beginnings Project, a nutrition intervention program developed for pregnant incarcerated women in Southeastern Virginia. Assessment of this program suggests that through the development of protocols and polices that consider the health-related needs of pregnant women, correctional facilities could play a pivotal role in helping incarcerated women develop healthier habits to better care for themselves and their newborns.https://scholarworks.wm.edu/asbookchapters/1106/thumbnail.jp

The Gender Congruency Effect across languages in bilinguals: A meta-analysis

In the study of gender representation and processing in bilinguals, two contrasting perspectives exist: integrated vs. the autonomous (Costa, Kovacic, Fedorenko, & Caramazza, 2003). In the former, cross-linguistic interactions during the selection of grammatical gender values are expected; in the latter, they are not. To address this issue, authors have typically explored the cross-linguistic Gender Congruency Effect (GCE: a facilitation on the naming or translation of second language [L2] nouns when their first language [L1] translations are of the same gender, in comparison to those of a different gender). However, the literature suggests that this effect is sometimes difficult to observe and might vary as a function of variables such as the syntactic structure produced to translate or name the target (bare nouns vs. noun phrases), the phonological gender transparency of both languages (whether or not they have phonological gender cues associated with the ending letter [e.g., “–a” for feminine words and “–o” for masculine words in Romance languages]), the degree of L2 proficiency, and task requirements (naming vs. translation). The aim of the present quantitative meta-analysis is to examine the robustness of the cross-linguistic GCE obtained during language production. It involves 25 experiments from 11 studies. The results support a bilingual gender-integrated view, in that they show a small but significant GC effect regardless of the variables mentioned above.This paper was funded through the state budget with reference IF / 00784/2013 / CP1158 / CT0013. The study has also been partially supported by the FCT and the Portuguese Ministry of Science, Technology and Higher Education through national funds and co-financed by FEDER through COMPETE2020 under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007653). Government of Spain—Ministry of Education, Culture and Sports—through the Training program for Academic Staff (Ayudas para la Formación del Profesorado Universitario, FPU grant BOE-B-2017-2646), the research project (reference PSI2015-65116-P) granted by the Spanish Ministry of Economy and Competitiveness, and the grant for research groups (reference ED431B 2019/2020) from the Galician Government, as well as by the FCT (Foundation for Science and Technology, Portugal) through the state budget (reference IF / 00784/2013 / CP1158 / CT0013). Finally, the study has also been partially supported by the FCT and the Portuguese Ministry of Science, Technology and Higher Education through national funds and co-financed by FEDER through COMPETE2020 under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007653

Fumarate Reductase Activity Maintains an Energized Membrane in Anaerobic Mycobacterium tuberculosis

Oxygen depletion of Mycobacterium tuberculosis engages the DosR regulon that coordinates an overall down-regulation of metabolism while up-regulating specific genes involved in respiration and central metabolism. We have developed a chemostat model of M. tuberculosis where growth rate was a function of dissolved oxygen concentration to analyze metabolic adaptation to hypoxia. A drop in dissolved oxygen concentration from 50 mmHg to 0.42 mmHg led to a 2.3 fold decrease in intracellular ATP levels with an almost 70-fold increase in the ratio of NADH/NAD+. This suggests that re-oxidation of this co-factor becomes limiting in the absence of a terminal electron acceptor. Upon oxygen limitation genes involved in the reverse TCA cycle were upregulated and this upregulation was associated with a significant accumulation of succinate in the extracellular milieu. We confirmed that this succinate was produced by a reversal of the TCA cycle towards the non-oxidative direction with net CO2 incorporation by analysis of the isotopomers of secreted succinate after feeding stable isotope (13C) labeled precursors. This showed that the resulting succinate retained both carbons lost during oxidative operation of the TCA cycle. Metabolomic analyses of all glycolytic and TCA cycle intermediates from 13C-glucose fed cells under aerobic and anaerobic conditions showed a clear reversal of isotope labeling patterns accompanying the switch from normoxic to anoxic conditions. M. tuberculosis encodes three potential succinate-producing enzymes including a canonical fumarate reductase which was highly upregulated under hypoxia. Knockout of frd, however, failed to reduce succinate accumulation and gene expression studies revealed a compensatory upregulation of two homologous enzymes. These major realignments of central metabolism are consistent with a model of oxygen-induced stasis in which an energized membrane is maintained by coupling the reductive branch of the TCA cycle to succinate secretion. This fermentative process may offer unique targets for the treatment of latent tuberculosis