Molecular genetics of <Emphasis Type="Italic">MARVELD2</Emphasis> and clinical phenotype in Pakistani and Slovak families segregating DFNB49 hearing loss

Pathogenic mutations of MARVELD2, encoding tricellulin, a tricelluar tight junction protein, cause autosomal recessive non-syndromic hearing loss (DFNB49) in families of Pakistan and Czech Roma origin. In fact, they are a significant cause of prelingual hearing loss in the Czech Roma, second only to GJB2 variants. Previously, we reported that mice homozygous for p.Arg497* variant of Marveld2 had a broad phenotypic spectrum, where defects were observed in the inner ear, heart, mandibular salivary gland, thyroid gland and olfactory epithelium. The current study describes the types and frequencies of MARVELD2 alleles and clinically reexamines members of DFNB49 families. We found that MARVELD2 variants are responsible for about 1.5 % (95 % CI 0.8–2.6) of non-syndromic hearing loss in our cohort of 800 Pakistani families. The c.1331+2T>C allele is recurrent. In addition, we identified a novel large deletion in a single family, which appears to have resulted from non-allelic homologous recombination between two similar Alu short interspersed elements. Finally, we observed no other clinical manifestations co-segregating with hearing loss in DFNB49 human families, and hypothesize that the additional abnormalities in the Marveld2 mutant mouse indicates a critical non-redundant function for tricellulin in other organ systems.     

APPLICATION OF RAPD MARKERS IN AN EXAMINATION OF HETEROSIS IN GELIDIUM VAGUM (RHODOPHYTA)1

Four morphologically indistinguishable isolates of monoecious Gelidium vagum Okamura were crossed reciprocally to obtain hybrids for a study on heterosis in this alga. Approximately 50% outcrossing was achieved by adding a small fragment of the designated female parent to a much larger quantity of designated male thallus in the crossing dish. Hybrids in the mixed population of isomorphic hybrid and inbred sporelings were identified by the presence of male-specific random amplified polymorphic DNA markers. Growth performance of hybrid tetrasporophytes was compared to that of their gametophytic parents and with inbred tetrasporophytes at near-optimum and sub-optimum temperature and density. In general, the hybrids showed growth superiority over inbred lines, particularly under sub-optimum conditions. In these experiments, the hybrid plants from cross 129 × 130 exhibited a 9.5–130% higher growth rate as compared to the mid-value of the related inbred tetrasporophytes, strongly suggesting the presence of heterosis.     

The Role of Anabolic Androgenic Steroids in Disruption of the Physiological Function in Discrete Areas of the Central Nervous System

Anabolic-androgenic steroids (AAS) abuse is often associated with a wide spectrum of adverse effects. These drugs are frequently abused by adolescents and athletes for esthetic purposes, as well as for improvement of their endurance and performances. In this literature review, we evaluated the correlation between AAS and anxiety or aggression. Two pathways are thought to be involved in AAS-induced behavioral disorders. Direct pathway via the amygdalo-fugal pathway, which connects the central nucleus of the amygdala to the brainstem, is involved in cognitive-emotive and homeostatic processes. The latter is modified by chronic AAS use, which subsequently leads to increased anxiety. Indirect pathways via the serotonergic, dopaminergic, and glutamatergic signals which are modified by AAS abuse in latero-anterior hypothalamus and can mediate the aggressive behavior. In conclusion, the molecular mechanisms underlying the behavioral alterations following AAS abuse is unclear and remains ambiguous as additional long-term studies aimed to understand the precise mechanisms are required.     

Studies on immobilized fungal spores for microbial transformation of steroids: 11 alpha-Hydroxylation of progesterone with immobilized spores of Aspergillus ochraceus G8 on polyacrylamide gel and other matrices

Hydroxylation in the 11 alpha-position in the progesterone molecule employing immobilized spores of Aspergillus ochraceus strain No. G8 (CDRI catalogue No.) was achieved. For immobilization the activity of the spores was evaluated on a variety of matrices such as alginate beads, epoxy resin beads, polyacrylamide gel, and collagen. Spores entrapped in polyacrylamide gel were found to be the most active. Studies of various parameters, e.g. monomer content, cell loading capacity, optimum pH, temperature, and substrate concentration, were carried out on polyacrylamide gel. In polyacrylamide, the entrapped spores normal decay pattern, as indicated by loss of activity, was observed after four uses. At the end of 15 cycles, the residual activity was found to be 18% of the original. It was possible to regenerate the activity by incubating the preparation in a nutrient medium. The regenerated spores showed increasing rate of loss of activity upon recycling.     

Site-specific nicking at the avian retrovirus LTR circle junction by the viral pp32 DNA endonuclease.

The avian retrovirus pp32 DNA endonuclease prefers to nick supercoiled DNA containing long terminal repeat (LTR) circle junction sequences at one or the other of two sites, each which mapped two nucleotides back from the circle junction. The sequence at the sites of nicking was (sequence: see text) where increases indicates the positions of the two alternative nicked sites. This site-specific nicking was observed when the circle junction LTR DNA was present in supercoiled form, the divalent metal ion was Mg2+ and the molar ratio of protein to DNA was low. The majority of other LTR DNA sites nicked by pp32 in the presence of Mg2+ were adjacent to or within the dinucleotide CA.     

Beryllium in the environment: Whether fatal for plant growth?

Beryllium could be a threatening heavy metal pollutant in the agro-ecosystem that may severely affect the performance of crops. Beryllium is used in various industries to make nuclear weapons and reactors, aircraft and space vehicle structures, instruments, and X-ray machines, and its entry into the environment is alarming for the productivity and sustainability of the ecosystem. In this review, we present a contemporary synthesis of the existing data regarding the toxic effects of beryllium on toxicity on biochemical and physiological processes in plants. Moreover, uptake, translocation, and assimilation of beryllium and its interaction with some essential mineral elements are also discussed. Although limited data are available regarding biochemical responses of plants to beryllium toxicity, we tried to clarify some basic physiological and biochemical steps that can be hampered by beryllium in plants. We linked our hypothetical concepts with previous evidence and provide a comprehensive summary of all possible remediation strategies that can be used for plants. Overall, we hope this review will be beneficial due to its practical implications and research directions.     

Beta-defensin-2 expression is regulated by TLR signaling in intestinal epithelial cells

The intestinal epithelium serves as a barrier to the intestinal flora. In response to pathogens, intestinal epithelial cells (IEC) secrete proinflammatory cytokines. To aid in defense against bacteria, IEC also secrete antimicrobial peptides, termed defensins. The aim of our studies was to understand the role of TLR signaling in regulation of beta-defensin expression by IEC. The effect of LPS and peptidoglycan on beta-defensin-2 expression was examined in IEC lines constitutively or transgenically expressing TLRs. Regulation of beta-defensin-2 was assessed using promoter-reporter constructs of the human beta-defensin-2 gene. LPS and peptidoglycan stimulated beta-defensin-2 promoter activation in a TLR4- and TLR2-dependent manner, respectively. A mutation in the NF-kappaB or AP-1 site within the beta-defensin-2 promoter abrogated this response. In addition, inhibition of Jun kinase prevents up-regulation of beta-defensin-2 protein expression in response to LPS. IEC respond to pathogen-associated molecular patterns with expression of the antimicrobial peptide beta-defensin-2. This mechanism may protect the intestinal epithelium from pathogen invasion and from potential invaders among the commensal flora.     

Regional assignment of human liver-type 6-phosphofructokinase to chromosome 21q22.3 by using somatic cell hybrids and a monoclonal anti-L antibody

Summary The three structural loci encoding human phosphofructokinase, a key regulatory enzyme of glycolysis, are located on separate chromosomes. The gene coding for the liver-type subunit PFKL has previously been assigned to chromosome 21. We have used a subunit- and human-specific monoclonal antibody to liver PFK to detect the expression of human PFKL in hamster x human hybrid cell lines. A cell line carrying an 8;21 translocation which contains all of chromosome 21 except the band 21q22.3 was negative for the expression of PFKL whereas cell lines carrying the reciprocal 8;21 translocation were positive. In addition, a cell line with a ring chromosome 21 containing a breakpoint which excluded the distal part of the q22.3 band was negative for expression of PFKL. These results indicate that human PFKL is located on chromosome 21q22.3.