An advanced 10.6-micro laser communication experiment

Carbon dioxide laser capability of high data rate intersatellite communicatio

In HspA from Helicobacter pylori vicinal disulfide bridges are a key determinant of domain B structure

Helicobacter pylori produces a heat shock protein A (HspA) that is unique to this bacteria. While the first 91 residues (domain A) of the protein are similar to GroES, the last 26 (domain B) are unique to HspA. Domain B contains eight histidines and four cysteines and was suggested to bind nickel. We have produced HspA and two mutants: Cys94Ala and Cys94Ala/Cys111Ala and identified the disulfide bridge pattern of the protein. We found that the cysteines are engaged in three disulfide bonds: Cys51/Cys53, Cys94/Cys111 and Cys95/Cys112 that result in a unique closed loop structure for the domain

CMS: A web-based system for visualization and analysis of genome-wide methylation data of human cancers

DNA methylation of promoter CpG islands is associated with gene suppression, and its unique genome-wide profiles have been linked to tumor progression. Coupled with high-throughput sequencing technologies, it can now efficiently determine genome-wide methylation profiles in cancer cells. Also, experimental and computational technologies make it possible to find the functional relationship between cancer-specific methylation patterns and their clinicopathological parameters.Cancer methylome system (CMS) is a web-based database application designed for the visualization, comparison and statistical analysis of human cancer-specific DNA methylation. Methylation intensities were obtained from MBDCap-sequencing, pre-processed and stored in the database. 191 patient samples (169 tumor and 22 normal specimen) and 41 breast cancer cell-lines are deposited in the database, comprising about 6.6 billion uniquely mapped sequence reads. This provides comprehensive and genome-wide epigenetic portraits of human breast cancer and endometrial cancer to date. Two views are proposed for users to better understand methylation structure at the genomic level or systemic methylation alteration at the gene level. In addition, a variety of annotation tracks are provided to cover genomic information. CMS includes important analytic functions for interpretation of methylation data, such as the detection of differentially methylated regions, statistical calculation of global methylation intensities, multiple gene sets of biologically significant categories, interactivity with UCSC via custom-track data. We also present examples of discoveries utilizing the framework.CMS provides visualization and analytic functions for cancer methylome datasets. A comprehensive collection of datasets, a variety of embedded analytic functions and extensive applications with biological and translational significance make this system powerful and unique in cancer methylation research. CMS is freely accessible at: http://cbbiweb.uthscsa.edu/KMethylomes/

The molecular diversity of Luminal A breast tumors

Breast cancer is a collection of diseases with distinct molecular traits, prognosis, and therapeutic options. Luminal A breast cancer is the most heterogeneous, both molecularly and clinically. Using genomic data from over 1,000 Luminal A tumors from multiple studies, we analyzed the copy number and mutational landscape of this tumor subtype. This integrated analysis revealed four major subtypes defined by distinct copy-number and mutation profiles. We identified an atypical Luminal A subtype characterized by high genomic instability, TP53 mutations, and increased Aurora kinase signaling; these genomic alterations lead to a worse clinical prognosis. Aberrations of chromosomes 1, 8, and 16, together with PIK3CA, GATA3, AKT1, and MAP3K1 mutations drive the other subtypes. Finally, an unbiased pathway analysis revealed multiple rare, but mutually exclusive, alterations linked to loss of activity of co-repressor complexes N-Cor and SMRT. These rare alterations were the most prevalent in Luminal A tumors and may predict resistance to endocrine therapy. Our work provides for a further molecular stratification of Luminal A breast tumors, with potential direct clinical implications. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10549-013-2699-3) contains supplementary material, which is available to authorized users

Polymerization of hemoglobins in Arctic fish: Lycodes reticulatus and Gadus morhua.

In vitro, and possibly in vivo, hemoglobin polymerization and red blood cell sickling appear to be widespread in codfish. In this article, we show that the hemoglobins of the two Arctic fish Lycodes reticulatus and Gadus morhua also have the tendency to polymerize, as monitored by dynamic light scattering experiments. The elucidation of the primary structure of the single hemoglobin of the zoarcid L. reticulatus shows the presence of a large number of cysteyl residues in α and β chains. Their role in eliciting the ability to produce polymers was also addressed by MALDI-TOF and TOF-TOF mass spectrometry. The G.morhua globins are also rich in Cys, but unlike in L. reticulatus, polymerization does not seem to be disulfide driven. The widespread occurrence of the polymerization phenomenon displayed by hemoglobins of Arctic fish supports the hypothesis that this feature may bea response to stressful environmental conditions

A common polymorphism in SCN5A gene is associated with dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is characterized by ventricular dilatation and impaired systolic function, which may proceed into congestive heart failure. Although DCM is a final common pathway of various acquired diseases, up to 50% of cases are reported to be idiopathic (i.e., without any obvious aetiological trigger) and approximately 20% of DCM cases display familial prevalence. More than 20 genes are associated with DCM in humans, although DCM genetic tests present low diagnostic sensibility (< 20%). DCM associated genes encode structural proteins of cardiomyocytes and ion channels. These last include SCN5A, which encodes the alpha subunit of the major Na+ channel in the heart, Nav1.5. Dilated cardiomyopathy with SCN5A mutations has been generally associated with reduced expression of the cardiac sodium channel Nav1.5. We hypothesized that the p.H558R polymorphism could be a genetic risk factor in dilated cardiomyopathy, as the R minor allele of this polymorphism has been shown to alter SCN5A function, by reducing depolarizing sodium current and modulating the biological effects of concomitant SCN5A mutations. We recruited 134 DCM patients (50 with familial DCM -FDCM-, 58 with idiopatic DCM and 26 patients affected by post-ischemic DCM) and 168 age, ethnicity, and gender matched controls. The mean age at diagnosis was 45+12 y., with a mean follow-up of 8.2+5.5 y. SCN5A was subject to comprehensive mutation scanning in all cases and to targeted genotyping of a common loss-of-function p.H558R polymorphism in controls. The Hardy-Weinberg law was applied to analyze distribution of SCN5A p.H558R genotypes. Association between the three genotypes and categorical variables were tested using the χ2 test or Fisher’s exact test. Mutation scanning of all SCN5A translated exons in 134 DCM patients reveals one novel mutation (c.A1383T, p.M463L) in a patient with idiopatic DCM. This mutation was absent in 350 unrelated chromosomes from matched healthy control and it produced a change in a highly conserved residue among species and isoforms. The major finding of this study was a significant difference in frequencies of the three p.H558R genotypes in familial DCM compared to normal controls: HH 40 vs 49%, HR 36 vs 44%, RR 24 vs 7%; p = 0.004). 60% of familial DCM subjects had at least one R allele compared with 51% of controls. The minor R allele frequency was 42% in familial DCM compared with 29% in the normal controls. Notably, compared with the HH and HR genotype, the RR genotype confers an OR for developing DCM in familial cases of 4.1 (95% CI 1.7-9.9; p = 0.001). Six FDCM patients carrying RR genotype (50%) experienced serious arrhythmic events; unlike in the remaining FDCM the percentage of patients who developed arrhythmic events was 29%. In conclusion, our data demonstrate that: (1) mutations in coding regions of SCN5A are not a common cause for DCM; (2) the SCN5A p.558RR genotype is associated with dilated cardiomyopathy in patients with familial DCM. This result may help to early identify candidates to develop DCM among asymptomatic relatives of FDCM patients in families without an identified mutation

Management of low-risk thyroid cancers: Is active surveillance a valid option? a systematic review of the literature

Thyroid cancer is the most common endocrine malignancy, representing 2.9% of all new cancers in the United States. It has an excellent prognosis, with a five-year relative survival rate of 98.3%.Differentiated Thyroid Carcinomas (DTCs) are the most diagnosed thyroid tumors and are characterized by a slow growth rate and indolent course. For years, the only approach to treatment was thyroidectomy. Active surveillance (AS) has recently emerged as an alternative approach; it involves regular observation aimed at recognizing the minority of patients who will clinically progress and would likely benefit from rescue surgery. To better clarify the indications for active surveillance for low-risk thyroid cancers, we reviewed the current management of low-risk DTCs with a systematic search performed according to a PRISMA flowchart in electronic databases (PubMed, Web of Science, Scopus, and EMBASE) for studies published before May 2021. Fourteen publications were included for final analysis, with a total number of 4830 patients under AS. A total of 451/4830 (9.4%) patients experienced an increase in maximum diameter by >3 mm; 609/4830 (12.6%) patients underwent delayed surgery after AS; metastatic spread to cervical lymph nodes was present in 88/4213 (2.1%) patients; 4/3589 (0.1%) patients had metastatic disease outside of cervical lymph nodes. Finally, no subject had a documented mortality due to thyroid cancer during AS. Currently, the American Thyroid Association guidelines do not support AS as the first-line treatment in patients with PMC; however, they consider AS to be an effective alternative, particularly in patients with high surgical risk or poor life expectancy due to comorbid conditions. Thus, AS could be an alternative to immediate surgery for patients with very-low-risk tumors showing no cytologic evidence of aggressive disease, for high-risk surgical candidates, for those with concurrent comorbidities requiring urgent intervention, and for patients with a relatively short life expectancy

A real benefit of an extended neonatal screening

Methylenetetrahydrofolate Reductase (MTHFR) deficiency, is avery rare congenital defect of folate metabolism, inherited in an autosomal recessive pattern included in newbornscreening (NBS) programs in Italy. It is caused by mutations in the MTHFRgene and is characterized by elevatedplasma homocysteine and borderline-low or normal methionine levels, causing severe neurological signs, recurrentapnoea, microcephaly and convulsions, generally during the neonatal period. An early treatment may prevent theclinical manifestations with a positive impact on patient’s health. We report a new case of MTHFRdeficiency, identified during NBS that showed hypomethioninemia 4.6 μmol/L (r.i.6-20). The second level-test revealed hyperhomocysteinemia (106.7 μM, r.i. 5-15). The whole sequencing of theMTHFRgene showed two missense mutation: c.176G>C (p.Trp59Ser), reported as disease causing and the novelc.1769T>G (p.Leu590Arg), classified as likely pathogenetic. The baby was immediately treated with vitamin B12,folate and betaine; after 12 months of follow-up he has no signs or symptoms of the disease. In conclusion, this case report highlights the importance of NBS for inborn errors of metabolism and genetic analysis,that can prevent the establishment of a serious disorder of folate metabolism