Exploring Knowledge and Perceptions of Polio Disease and Its Immunization in Polio High-Risk Areas of Pakistan.

Pakistan is one of the few countries where poliovirus transmission still persists, despite intensive efforts to eradicate the disease. Adequate vaccination coverage is essential to achieve polio eradication, but misconceptions about polio vaccines have hindered vaccination efforts. To address this issue, we conducted a mixed-methods study to explore knowledge and perceptions regarding polio disease and immunization in high-risk areas of Pakistan.

Targeting focal adhesion kinase overcomes erlotinib resistance in smoke induced lung cancer by altering phosphorylation of epidermal growth factor receptor.

EGFR-based targeted therapies have shown limited success in smokers. Identification of alternate signaling mechanism(s) leading to TKI resistance in smokers is critically important. We observed increased resistance to erlotinib in H358 NSCLC (non-small cell lung carcinoma) cells chronically exposed to cigarette smoke (H358-S) compared to parental cells.

Integrating transcriptomic and proteomic data for accurate assembly and annotation of genomes.

Complementing genome sequence with deep transcriptome and proteome data could enable more accurate assembly and annotation of newly sequenced genomes. Here, we provide a proof-of-concept of an integrated approach for analysis of the genome and proteome of Anopheles stephensi, which is one of the most important vectors of the malaria parasite. To achieve broad coverage of genes, we carried out transcriptome sequencing and deep proteome profiling of multiple anatomically distinct sites.

SILAC-based quantitative proteomic analysis reveals widespread molecular alterations in human skin keratinocytes upon chronic arsenic exposure.

Chronic exposure to arsenic is associated with dermatological and nondermatological disorders. Consumption of arsenic-contaminated drinking water results in accumulation of arsenic in liver, spleen, kidneys, lungs, and gastrointestinal tract. Although arsenic is cleared from these sites, a substantial amount of residual arsenic is left in keratin-rich tissues including skin.

Chronic exposure to cigarette smoke leads to activation of p21 (RAC1)-activated kinase 6 (PAK6) in non-small cell lung cancer cells.

Epidemiological data clearly establishes cigarette smoking as one of the major cause for lung cancer worldwide. Recently, targeted therapy has become one of the most preferred modes of treatment for cancer. Though certain targeted therapies such as anti-EGFR are in clinical practice, they have shown limited success in lung cancer patients who are smokers.

The Leicester cerebral haemodynamics database: normative values and the influence of age and sex.

Normative values of physiological parameters hold significance in modern day clinical decision-making. Lack of such normative values has been a major hurdle in the translation of research into clinical practice. A large database containing uniform recordings was constructed to allow more robust estimates of normative ranges and also assess the influence of age and sex.

Is dynamic cerebral autoregulation measurement using transcranial Doppler ultrasound reproducible in the presence of high concentration oxygen and carbon dioxide?

Reliability of cerebral blood flow velocity (CBFV) and dynamic cerebral autoregulation estimates (expressed as autoregulation index: ARI) using spontaneous fluctuations in blood pressure (BP) has been demonstrated. However, reliability during co-administration of O2 and CO2 is unknown. Bilateral CBFV (using transcranial Doppler), BP and RR interval recordings were performed in healthy volunteers (seven males, four females, age: 54  ±  10 years) on two occasions over 9  ±  4 d.

Improving fluid balance monitoring on the wards.

Clinical experience and nursing metrics have consistently identified poor documentation of fluid balance monitoring at Milton Keynes University Hospital, compromising patient safety and quality of care. This project aimed to increase the percentage of fluid balance charts correctly completed on the wards. Three areas for improvement were identified: understanding the importance of good fluid balance monitoring, correct identification of patients requiring monitoring, and ease of completion of fluid balance charts.

Macrophage migration inhibitory factor - a therapeutic target in gallbladder cancer.

Background: Poor prognosis in gallbladder cancer is due to late presentation of the disease, lack of reliable biomarkers for early diagnosis and limited targeted therapies. Early diagnostic markers and novel therapeutic targets can significantly improve clinical management of gallbladder cancer.

Methods: Proteomic analysis of four gallbladder cancer cell lines based on the invasive property (non-invasive to highly invasive) was carried out using the isobaric tags for relative and absolute quantitation labeling-based quantitative proteomic approach.

Chronic exposure to chewing tobacco selects for overexpression of stearoyl-CoA desaturase in normal oral keratinocytes.

Chewing tobacco is a common practice in certain socio-economic sections of southern Asia, particularly in the Indian subcontinent and has been well associated with head and neck squamous cell carcinoma. The molecular mechanisms of chewing tobacco which leads to malignancy remains unclear. In large majority of studies, short-term exposure to tobacco has been evaluated.

Calcium calmodulin dependent kinase kinase 2 - a novel therapeutic target for gastric adenocarcinoma.

Gastric cancer is one of the most common gastrointestinal malignancies and is associated with poor prognosis. Exploring alterations in the proteomic landscape of gastric cancer is likely to provide potential biomarkers for early detection and molecules for targeted therapeutic intervention. Using iTRAQ-based quantitative proteomic analysis, we identified 22 proteins that were overexpressed and 17 proteins that were downregulated in gastric tumor tissues as compared to the adjacent normal tissue.

Phosphotyrosine profiling identifies ephrin receptor A2 as a potential therapeutic target in esophageal squamous-cell carcinoma.

Esophageal squamous-cell carcinoma (ESCC) is one of the most common malignancies in Asia. Currently, surgical resection of early-stage tumor is the best available treatment. However, most patients present late when surgery is not an option.

Silencing of high-mobility group box 2 (HMGB2) modulates cisplatin and 5-fluorouracil sensitivity in head and neck squamous cell carcinoma.

Dysregulation of protein expression is associated with most diseases including cancer. MS-based proteomic analysis is widely employed as a tool to study protein dysregulation in cancers. Proteins that are differentially expressed in head and neck squamous cell carcinoma (HNSCC) cell lines compared to the normal oral cell line could serve as biomarkers for patient stratification.

Annotation of the zebrafish genome through an integrated transcriptomic and proteomic analysis.

Accurate annotation of protein-coding genes is one of the primary tasks upon the completion of whole genome sequencing of any organism. In this study, we used an integrated transcriptomic and proteomic strategy to validate and improve the existing zebrafish genome annotation. We undertook high-resolution mass-spectrometry-based proteomic profiling of 10 adult organs, whole adult fish body, and two developmental stages of zebrafish (SAT line), in addition to transcriptomic profiling of six organs.

A draft map of the human proteome.

The availability of human genome sequence has transformed biomedical research over the past decade. However, an equivalent map for the human proteome with direct measurements of proteins and peptides does not exist yet. Here we present a draft map of the human proteome using high-resolution Fourier-transform mass spectrometry.

Proteogenomic analysis of pathogenic yeast Cryptococcus neoformans using high resolution mass spectrometry.

Background: Cryptococcus neoformans, a basidiomycetous fungus of universal occurrence, is a significant opportunistic human pathogen causing meningitis. Owing to an increase in the number of immunosuppressed individuals along with emergence of drug-resistant strains, C. neoformans is gaining importance as a pathogen.

SILAC-based quantitative proteomic analysis of gastric cancer secretome.

Purpose: Gastric cancer is a commonly occurring cancer in Asia and one of the leading causes of cancer deaths. However, there is no reliable blood-based screening test for this cancer. Identifying proteins secreted from tumor cells could lead to the discovery of clinically useful biomarkers for early detection of gastric cancer.

NetSlim: high-confidence curated signaling maps.

We previously developed NetPath as a resource for comprehensive manually curated signal transduction pathways. The pathways in NetPath contain a large number of molecules and reactions which can sometimes be difficult to visualize or interpret given their complexity. To overcome this potential limitation, we have developed a set of more stringent curation and inclusion criteria for pathway reactions to generate high-confidence signaling maps.

Role of CIPK6 in root growth and auxin transport.

In our recent publication, we have shown that a T-DNA insertion in Arabidopsis CIPK6 gene encoding a CBL-interacting protein kinase caused reduction in expression of the gene and emergence of lateral roots. The change in phenotype in the mutant line was likely due to reduction in shoot-to-root acropetal and the root tip basipetal auxin transport. Here we report identification of a homozygous knockout line of AtCIPK6 (atcipk6) with no detectable expression of the gene in normal growth condition.