Phenotype

This is a literature review about large granular lymphocyte leukemia (LGLL), a rare and misdiagnosed oncohematological disease, characterized by a clonal expansion of T-cells (T-LGLL) or NK-cells (NK-LGLL) in the bone marrow and/or peripheral blood. The clinical features of LGLL include cytopenias (anemia, neutropenia and thrombocytopenia), lymphocytosis (usually discrete), lymphadenopathy, hepatomegaly, splenomegaly, immune abnormalities and constitutional symptoms (fever, night sweats and weight loss). The diagnosis is based on the confirmation of the clonality of T-cells or NK-cells (polymerase chain reaction and Southern blot are the two methods most commonly used) and typical findings of the immunophenotypic analysis of peripheral blood lymphocytes (flow cytometry analyses for specific surface antigens). In contrast to the chronic and indolent course of T-LGLL, NK-LGLL has an acute presentation and poor clinical outcome. There are different current treatment options, depending on clinical presentation.

Hepatocarcinogenesis is under polygenic control. We analyzed gene expression patterns of dysplastic liver nodules (DNs) and hepatocellular carcinomas (HCCs) chemically-induced in F344 and BN rats, respectively susceptible and resistant to hepatocarcinogenesis. Expression profiles were performed by microarray and validated by quantitative RT-PCR and Western blot. Cluster analysis revealed two distinctive gene expression patterns, the first of which included normal liver of both strains and BN nodules, and the second one F344 nodules and HCC of both strains. We identified a signature predicting DN and HCC progression, characterized by highest expression of oncosuppressors Csmd1, Dmbt1, Dusp1, and Gnmt, in DNs, and Bhmt, Dmbt1, Dusp1, Gadd45g, Gnmt, Napsa, Pp2ca, and Ptpn13 in HCCs of resistant rats. Integrated gene expression data revealed highest expression of proliferation-related CTGF, c-MYC, and PCNA, and lowest expression of BHMT, DMBT1, DUSP1, GADD45g, and GNMT, in more aggressi...

Autism spectrum disorder (ASD) is a severe neuropsychiatric disease with strong genetic underpinnings. However, genetic contributions to autism are extremely heterogeneous, with many different loci underlying the disease to a different extent in different individuals. Moreover, the phenotypic expression (i.e., "penetrance") of these genetic components is also highly variable, ranging from fully penetrant point mutations to polygenic forms with multiple gene-gene and gene-environment interactions. Furthermore, many genes involved in ASD are also involved in intellectual disability, further underscoring their lack of specificity in phenotypic expression. We shall hereby review current knowledge on the genetic basis of ASD, spanning genetic/genomic syndromes associated with autism, monogenic forms due to copy number variants (CNVs) or rare point mutations, mitochondrial forms, and polygenic autisms. Finally, the recent contributions of genome-wide association and whole exome ...

BackgroundPrevious studies on self-esteem have focused exclusively on its psychosocial determinants. The goal of the present study is to clarify genetic v. environmental determinants of self-esteem.MethodParticipants were Caucasian women sampled from the Virginia Twin Register: 363 pairs of MZ and 238 pairs of DZ twins were available from the first wave of the study, and 430 pairs of MZ and 308 pairs of DZ twins from the second. Self-esteem was assessed with the Rosenberg's Self-Esteem Scale.ResultsUsing univariate twin analyses of self-esteem and a repeated measurement twin model, we found that self-esteem is a moderately heritable trait (heritability = 52% in the repeated measurement model); environmental influences are also very important, and are probably mostly not shared by members of a twin pair.ConclusionsAetiological models of self-esteem which examine only psychosocial factors are incomplete; genetic factors need to be integrated.

Very few studies regarding production of virulence factors in different predominant serotypes of uropathogenic Pseudomonas aeruginosa are available and they have not been correlated to in vivo pathogenicity in the urinary tract. This study was carriedout with the objective to analyze the phenotypic characters of uroisolates of P. aeruginosa in vitro and to study the association of these virulence traits with their ability to cause nephropathogenicity in mouse model of ascending urinary tract infection (UTI). Protease, elastase, alginate, haemolysin, pyochelin, pyoverdin and phopholipase C were measured using standard protocols in 18 uroisolates of P. aeruginosa isolated from patients suffering from complicated UTIs. An ascending model of pyelonephritis was established in Swiss Webster (LACA) female mice with these isolates. Quantitative bacterial count and histopathological evaluation of mouse renal tissue was done which were then assessed for a possible association with elaboration...

We determined the frequency distribution of Actinomyces spp. recovered in a routine clinical laboratory and investigated the clinical significance of accurate identification to the species level. We identified 92 clinical strains of Actinomyces, including 13 strains in the related Arcanobacterium-Actinobaculum taxon, by 16S rRNA gene sequence analysis and recorded their biotypes, sources, and disease associations. The clinical isolates clustered into

Mouse embryos lacking the retinoic acid receptor gene RXR(alpha) die in midgestation from hypoplastic development of the myocardium of the ventricular chambers and consequent cardiac failure. In this study, we address the issue of whether the RXRalpha gene is required in the cardiomyocyte lineage by generating mice that harbor a ventricular restricted deficiency in RXRalpha at the earliest stages of ventricular chamber specification. We first created a conditional ('floxed') allele of RXRalpha by flanking a required exon of the gene with loxP recombination sequences. To achieve ventricular myocardium-specific gene targeting, and to avoid potential transgenic artifacts, we employed a knock-in strategy to place cre recombinase coding sequences into the myosin light chain 2v (MLC2v) genomic locus, a gene which in the heart is expressed exclusively in ventricular cardiomyocytes at the earliest stages of ventricular specification. Crossing the MLC2v-cre allele with the floxed RXR...

Endocarditis of native aortic and mitral valves due to an organism identified as Corynebacterium accolens developed in a 73-year-old patient without predisposing factors. The organism was identified asC. accolensby biochemical identification, amplified rRNA gene restriction analysis, and DNA-DNA hybridization. This is the first case of C. accolens endocarditis reported, adding to the increasing number of Corynebacterium-related cases of endocarditis. Cases of endocarditis are rarely caused by corynebacteria. A total of 126 cases have been reviewed recently (4). Fifty-three ofthesecaseswererelatedtothepresenceofprostheticvalves, and 107 of the organisms were related to Corynebacterium species living commensally on the skin. Both associations may be ascribed to surgery or to the injection of drugs. Further- more,mostofthecasesoccurinpatientswithpreexistingheart disease or in patients who are parenteral drug users (4). The increase in the number of reports concerning Coryne- bacteriumi...

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337 1. Mechanism of Resistance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 339 2. Correlation Between Phenotypic and Genotypic Resistance . . . . . . . . . . . . . . . . . . . . . 341 3. Fitness of Resistant Virus . . . . . . . . . . . . . . . . . . . . ...

Extended-spectrum β-lactamases (ESBLs), e.g., ESBLs of the TEM or SHV type, compromise the efficacies of expanded-spectrum cephalosporins. An SHV non-ESBL that hydrolyzes only narrow-spectrum cephalosporins can be converted into an SHV ESBL through substitutions at three amino acid positions, 179, 238, or 238–240. In order to improve detection of SHV ESBLs, a novel method, based on real-time PCR monitored with fluorescently labeled hybridization probes and followed by melting curve analysis, was developed. It is able to (i) detect bla SHV genes with high degrees of sensitivity and specificity, (ii) discriminate between bla SHV non-ESBL and bla SHV ESBL , and (iii) categorize the SHV ESBL producers into three phenotypically relevant subgroups. This method, termed the SHV melting curve mutation detection method, represents a powerful tool for epidemiological studies with SHV ESBLs. It even has the potential to be used in the diagnostic microbiology laboratory, because up to 32 clinica...

The plant steroid hormones brassinosteroids (BRs) play important roles in plant growth and responses to stresses. The up-regulation of pathogen resistance by BR signaling has been analyzed, but the relationship between BR and insect herbivores remains largely unclear. BIL1/BZR1 is a BR master transcription factor known to be involved in the regulation of plant development through work conducted on a gain of function mutation. Here, we analyzed the function of BIL1/BZR1 in response to insect feeding and demonstrated that resistance against thrip feeding was increased in the bil1-1D/bzr1-1D mutant compared to wild-type. We generated Lotus japonicus transgenic plants that over-express the Arabidopsis bil1/bzr1 mutant, Lj-bil1/bzr1-OX. The Lj-bil1/bzr1-OX plants showed increased resistance to thrip feeding. The expression levels of the jasmoninc acid (JA)-inducible VSP genes were increased in both Arabidopsis bil1-1D/bzr1-1D mutants and L. japonicus Lj-bil1/bzr1-OX plants. The resistanc...

In an increasing proportion of cases, hepatocellular carcinoma (HCC) develops in patients with nonalcoholic fatty liver disease (NAFLD). Mutations in telomerase reverse transcriptase (hTERT) are associated with familial liver diseases. The aim of this study was to examine telomere length and germline hTERT mutations as associated with NAFLD-HCC. In 40 patients with NAFLD-HCC, 45 with NAFLD-cirrhosis and 64 healthy controls, peripheral blood telomere length was evaluated by qRT-PCR and hTERT coding regions and intron-exon boundaries sequenced. We further analyzed 78 patients affected by primary liver cancer (NAFLD-PLC, 76 with HCC). Enrichment of rare coding mutations (allelic frequency <0.001) was evaluated by Burden test. Functional consequences were estimated in silico and by over-expressing protein variants in HEK-293 cells. We found that telomere length was reduced in individuals with NAFLD-HCC versus those with cirrhosis (P = 0.048) and healthy controls (P = 0.0006), indepen...

The unc-22 gene is one of a set of genes identified using classical genetics that affect muscle structure and function in the free-living nematode Caenorhabditis elegans. Since cloning the unc-22 gene by transposon tagging, we have used conventional techniques combined with a set of Tc1 transposon insertion alleles to characterize the gene and its products. The gene extends over more than 20 kb of genomic sequence and produces a transcript of approximately 14 kb. A polyclonal antibody raised against an Escherichia coli beta-galactosidase-unc-22 fusion protein recognizes a polypeptide in nematode extracts that is between 500,000 and 600,000 daltons and labels the muscle A-band in indirect immunofluorescent microscopy. The Tc1-induced alleles have been used at every stage to verify these conclusions. The Tc1 insertions are spread over much of the region that contributes to the mature transcript; in most alleles, Tc1 sequences are incorporated into a composite unc-22-Tc1 transcript. Th...