Association of Alpha B-Crystallin Genotypes with Oral Cancer Susceptibility, Survival, and Recurrence in Taiwan

BACKGROUND: Alpha B-crystallin (CRYAB) is a protein that functions as "molecular chaperone" in preserving intracellular architecture and cell membrane. Also, CRYAB is highly antiapoptotic. Abnormal CRYAB expression is a prognostic biomarker for oral cancer, while its genomic variations and the association with carcinogenesis have never been studied. METHODOLOGY/FINDING: Therefore, we hypothesized that CRYAB single nucleotide polymorphisms may be associated with oral cancer risk. In this hospital-based study, the association of CRYAB A-1215G (rs2228387), C-802G (rs14133) and intron2 (rs2070894) polymorphisms with oral cancer in a Taiwan population was investigated. In total, 496 oral cancer patients and 992 age- and gender-matched healthy controls were genotyped and analyzed. A significantly different frequency distribution was found in CRYAB C-802G genotypes, but not in A-1215G and intron2 genotypes, between the oral cancer and control groups. The CRYAB C-802G G allele conferred an increased risk of oral cancer (P = 1.49×10(-5)). Patients carrying CG/GG at CRYAB C-802G were of lower 5-year survival and higher recurrence rate than those of CC (P<0.05). CONCLUSION/SIGNIFICANCE: Our results provide the first evidence that the G allele of CRYAB C-802G is correlated with oral cancer risk and this polymorphism may be a useful marker for oral cancer recurrence and survival prediction for clinical reference

Meeting Report: Knowledge and Gaps in Developing Microbial Criteria for Inland Recreational Waters

The U.S. Environmental Protection Agency (EPA) has committed to issuing in 2012 new or revised criteria designed to protect the health of those who use surface waters for recreation. For this purpose, the U.S. EPA has been conducting epidemiologic studies to establish relationships between microbial measures of water quality and adverse health outcomes among swimmers. New methods for testing water quality that would provide same-day results will likely be elements of the new criteria. Although the epidemiologic studies upon which the criteria will be based were conducted at Great Lakes and marine beaches, the new water quality criteria may be extended to inland waters (IWs). Similarities and important differences between coastal waters (CWs) and IWs that should be considered when developing criteria for IWs were the focus of an expert workshop. Here, we summarize the state of knowledge and research needed to base IWs microbial criteria on sound science. Two key differences between CWs and IWs are the sources of indicator bacteria, which may modify the relationship between indicator microbes and health risk, and the relationship between indicators and pathogens, which also may vary within IWs. Monitoring using rapid molecular methods will require the standardization and simplification of analytical methods, as well as greater clarity about their interpretation. Research needs for the short term and longer term are described

Serotonin and corticosterone rhythms in mice exposed to cigarette smoke and in patients with COPD:implication for COPD-associated neuropathogenesis

The circadian timing system controls daily rhythms of physiology and behavior, and disruption of clock function can trigger stressful life events. Daily exposure to cigarette smoke (CS) can lead to alteration in diverse biological and physiological processes. Smoking is associated with mood disorders, including depression and anxiety. Patients with chronic obstructive pulmonary disease (COPD) have abnormal circadian rhythms, reflected by daily changes in respiratory symptoms and lung function. Corticosterone (CORT) is an adrenal steroid that plays a considerable role in stress and anti-inflammatory responses. Serotonin (5-hydroxytryptamine; 5HT) is a neurohormone, which plays a role in sleep/wake regulation and affective disorders. Secretion of stress hormones (CORT and 5HT) is under the control of the circadian clock in the suprachiasmatic nucleus. Since smoking is a contributing factor in the development of COPD, we hypothesize that CS can affect circadian rhythms of CORT and 5HT secretion leading to sleep and mood disorders in smokers and patients with COPD. We measured the daily rhythms of plasma CORT and 5HT in mice following acute (3 d), sub-chronic (10 d) or chronic (6 mo) CS exposure and in plasma from non-smokers, smokers and patients with COPD. Acute and chronic CS exposure affected both the timing (peak phase) and amplitude of the daily rhythm of plasma CORT and 5HT in mice. Acute CS appeared to have subtle time-dependent effects on CORT levels but more pronounced effects on 5HT. As compared with CORT, plasma 5HT was slightly elevated in smokers but was reduced in patients with COPD. Thus, the effects of CS on plasma 5HT were consistent between mice and patients with COPD. Together, these data reveal a significant impact of CS exposure on rhythms of stress hormone secretion and subsequent detrimental effects on cognitive function, depression-like behavior, mood/anxiety and sleep quality in smokers and patients with COPD

Nationwide epidemiological study of severe gallstone disease in Taiwan

<p>Abstract</p> <p>Background</p> <p>Our study aimed to assess the nationwide trends in the incidence of severe gallstone disease in Taiwan among adults aged ≥20.</p> <p>Methods</p> <p>A retrospective longitudinal study was conducted using Taiwan National Health Insurance Research Database collected during 1997–2005. Patients with incident severe gallstone disease (acute cholecystitis, biliary pancreatitis, acute cholangitis) and gallstone-related procedures (elective and non-elective cholecystectomy, endoscopic retrograde cholangiopancreatography [ERCP]) that led to hospital admission were identified using ICD-9-CM diagnostic and procedure codes. Annual incidence rates of gallstone-related complications and procedures were calculated and their 95% confidence intervals (CI) were estimated assuming a Poisson distribution.</p> <p>Results</p> <p>The hospital admission rate for severe gallstone disease increased with advancing age and the age-standardized rate (95% CI) per 1000 population was 0.60 (0.59–0.60) for men and 0.59 (0.59–0.60) for women. Men had a higher rate of acute cholecystitis, probably due to the substantially lower rate of elective cholecystectomy among men than women. For those aged 20–39, hospital admissions for all gallstone-related complications and procedures increased significantly. For those aged ≥60, incidences of biliary pancreatitis, acute cholangitis, and hospital admission for gallstone receiving ERCP increased significantly without substantial change in the incidence of acute cholecystitis and despite a decreased rate of elective cholecystectomy.</p> <p>Conclusion</p> <p>This population-based study found a substantial increase in the rate of admission for severe gallstone disease among those aged 20–39. Concurrently, the incidences of biliary pancreatitis and acute cholangitis have risen among those aged ≥60.</p

Coevolved mutations reveal distinct architectures for two core proteins in the bacterial flagellar motor

Switching of bacterial flagellar rotation is caused by large domain movements of the FliG protein triggered by binding of the signal protein CheY to FliM. FliG and FliM form adjacent multi-subunit arrays within the basal body C-ring. The movements alter the interaction of the FliG C-terminal (FliGC) "torque" helix with the stator complexes. Atomic models based on the Salmonella entrovar C-ring electron microscopy reconstruction have implications for switching, but lack consensus on the relative locations of the FliG armadillo (ARM) domains (amino-terminal (FliGN), middle (FliGM) and FliGC) as well as changes during chemotaxis. The generality of the Salmonella model is challenged by the variation in motor morphology and response between species. We studied coevolved residue mutations to determine the unifying elements of switch architecture. Residue interactions, measured by their coevolution, were formalized as a network, guided by structural data. Our measurements reveal a common design with dedicated switch and motor modules. The FliM middle domain (FliMM) has extensive connectivity most simply explained by conserved intra and inter-subunit contacts. In contrast, FliG has patchy, complex architecture. Conserved structural motifs form interacting nodes in the coevolution network that wire FliMM to the FliGC C-terminal, four-helix motor module (C3-6). FliG C3-6 coevolution is organized around the torque helix, differently from other ARM domains. The nodes form separated, surface-proximal patches that are targeted by deleterious mutations as in other allosteric systems. The dominant node is formed by the EHPQ motif at the FliMMFliGM contact interface and adjacent helix residues at a central location within FliGM. The node interacts with nodes in the N-terminal FliGc α-helix triad (ARM-C) and FliGN. ARM-C, separated from C3-6 by the MFVF motif, has poor intra-network connectivity consistent with its variable orientation revealed by structural data. ARM-C could be the convertor element that provides mechanistic and species diversity.JK was supported by Medical Research Council grant U117581331. SK was supported by seed funds from Lahore University of Managment Sciences (LUMS) and the Molecular Biology Consortium

Alteration of gene expression profiles during mycoplasma-induced malignant cell transformation

BACKGROUND: Mycoplasmas are the smallest microorganisms capable of self-replication. Our previous studies show that some mycoplasmas are able to induce malignant transformation of host mammalian cells. This malignant transformation is a multistage process with the early infection, reversible and irreversible stages, and similar to human tumor development in nature. The purpose of this study is to explore mechanisms for this malignant transformation. METHODS: To better understand mechanisms for this unique process, we examined gene expression profiles of C3H cells at different stages of the mycoplasma-induced transformation using cDNA microarray technology. A total of 1185 genes involved in oncogenesis, apoptosis, cell growth, cell-cycle regulation, DNA repair, etc. were examined. Differences in the expression of these genes were compared and analyzed using the computer software AtlasImage. RESULTS: Among 1185 genes screened, 135 had aberrant expression at the early infection stage, 252 at the reversible stage and 184 at the irreversible stage. At the early infection stage, genes with increased expression (92 genes) were twice more than those with decreased expression (42 genes). The global gene expression at the reversible stage appeared to be more volatile than that at any other stages but still resembled the profile at the early infection stage. The expression profile at the irreversible stage shows a unique pattern of a wide range of expression levels and an increased number of expressing genes, especially the cancer-related genes. Oncogenes and tumor suppressors are a group of molecules that showed significant changes in expression during the transformation. The majority of these changes occurred in the reversible and irreversible stages. A prolonged infection by mycoplasmas lead to the expression of more cancer related genes at the irreversible stage. CONCLUSION: The results indicate that the expression profiles correspond with the phenotypic features of the cells in the mycoplasma induced transformation process. The early mycoplasma infection stage shares a common phenomenon with many other acute infections, genes with increased expression significantly outnumbering those with decreased expression. The reversible stage is a transition stage between benignancy and malignancy at the molecular level. Aberrant expression of oncogenes and tumor repressors plays a key role in mycoplasma-induced malignant transformation

Radiative Transfer for Exoplanet Atmospheres

Remote sensing of the atmospheres of distant worlds motivates a firm understanding of radiative transfer. In this review, we provide a pedagogical cookbook that describes the principal ingredients needed to perform a radiative transfer calculation and predict the spectrum of an exoplanet atmosphere, including solving the radiative transfer equation, calculating opacities (and chemistry), iterating for radiative equilibrium (or not), and adapting the output of the calculations to the astronomical observations. A review of the state of the art is performed, focusing on selected milestone papers. Outstanding issues, including the need to understand aerosols or clouds and elucidating the assumptions and caveats behind inversion methods, are discussed. A checklist is provided to assist referees/reviewers in their scrutiny of works involving radiative transfer. A table summarizing the methodology employed by past studies is provided.Comment: 7 pages, no figures, 1 table. Filled in missing information in references, main text unchange

Inflammatory myofibroblastic tumor of the lung- a case report

A 45-year-old man presented with a six-month history of progressive dyspnea with productive cough and wheezing. The patient was a heavy smoker and had a history of tongue cancer, hypertension, and asthma. Chest X-ray and computed tomography showed a mass lesion in the left hilar region and total collapse of the upper left lobe of the lung. Bronchoscopy revealed a whitish solid tumor obstructing the left upper lobe bronchus. Positron emission tomography showed increased tracer uptake in the lesion. A thoracoscopic lobectomy of the left upper lobe of the lung was performed. The final pathologic diagnosis was inflammatory myofibroblastic tumor

Neurochemical Properties of the Synapses in the Pathways of Orofacial Nociceptive Reflexes

The brainstem premotor neurons of the facial nucleus (VII) and hypoglossal (XII) nucleus can integrate orofacial nociceptive input from the caudal spinal trigeminal nucleus (Vc) and coordinate orofacial nociceptive reflex (ONR) responses. However, the synaptoarchitectures of the ONR pathways are still unknown. In the current study, we examined the distribution of GABAergic premotor neurons in the brainstem local ONR pathways, their connections with the Vc projections joining the brainstem ONR pathways and the neurochemical properties of these connections. Retrograde tracer fluoro-gold (FG) was injected into the VII or XII, and anterograde tracer biotinylated dextran amine (BDA) was injected into the Vc. Immunofluorescence histochemical labeling for inhibitory/excitatory neurotransmitters combined with BDA/FG tracing showed that GABAergic premotor neurons were mainly distributed bilaterally in the ponto-medullary reticular formation with an ipsilateral dominance. Some GABAergic premotor neurons made close appositions to the BDA-labeled fibers coming from the Vc, and these appostions were mainly distributed in the parvicellular reticular formation (PCRt), dorsal medullary reticular formation (MdD), and supratrigeminal nucleus (Vsup). We further examined the synaptic relationships between the Vc projecting fibers and premotor neurons in the VII or XII under the confocal laser-scanning microscope and electron microscope, and found that the BDA-labeled axonal terminals that made asymmetric synapses on premotor neurons showed vesicular glutamate transporter 2 (VGluT2) like immunoreactivity. These results indicate that the GABAergic premotor neurons receive excitatory neurotransmission from the Vc and may contribute to modulating the generation of the tonic ONR