Genetic variants in post myocardial infarction patients presenting with electrical storm of unstable ventricular tachycardia

Electrical storm (ES) is a life threatening clinical situation. Though a few clinical pointers exist, the occurrence of ES in a patient with remote myocardial infarction (MI) is generally unpredictable. Genetic markers for this entity have not been studied. In the present study, we carried out genetic screening in patients with remote myocardial infarction presenting with ES by next generation sequencing and identified 25 rare variants in 19 genes predominantly in RYR2, SCN5A, KCNJ11, KCNE1 and KCNH2, CACNA1B, CACNA1C, CACNA1D and desmosomal genes - DSP and DSG2 that could potentially be implicated in electrical storm. These genes have been previously reported to be associated with inherited syndromes of Sudden Cardiac Death. The present study suggests that the genetic architecture in patients with remote MI and ES of unstable ventricular tachycardia may be similar to that of Ion channelopathies. Identification of these variants may identify post MI patients who are predisposed to develop electrical storm and help in risk stratification.     

CRISPR Screens Uncover Genes that Regulate Target Cell Sensitivity to the Morphogen Sonic Hedgehog

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Water-mediated interactions enable smooth substrate transport in a bacterial efflux pump

Background

Efflux pumps of the Resistance-Nodulation-cell Division superfamily confer multi-drug resistance to Gram-negative bacteria. The most-studied polyspecific transporter belonging to this class is the inner-membrane trimeric antiporter AcrB of Escherichia coli. In previous studies, a functional rotation mechanism was proposed for its functioning, according to which the three monomers undergo concerted conformational changes facilitating the extrusion of substrates. However, the molecular determinants and the energetics of this mechanism still remain unknown, so its feasibility must be proven mechanistically.

Precocious ovarian recrudescence and induced off–season spawning of Heteropneustes fossilis by D-Lys6 salmon gonadotropin releasing hormone analog (sGnRH-A)

The feasibility of photothermal treatment and use of salmon gonadotropin releasing hormone analogue (sGnRH-A) for induced spawning of Heteropneustes fossilis outside the spawning season was investigated. Fish were maintained at 30° C and 14 h light (L)/10 h dark (D) for 60 days between the post-spawning season and preparatory season. Fish attained gonadal maturity 4 months earlier compared to the natural spawning season. Mature fish were induced to spawn by D-Lys⁶ sGnRH-A at a dose of 25 μg kg⁻¹ body weight. The eggs obtained were fertilizable. Injection of D-Lys⁶ sGnRH-A at different time points during the photodiurnal cycle did not influence the latency period and spawning of H. fossilis .     

Nod factors of Rhizobium are a key to the legume door

Symbiotic interactions between rhizobia and legumes are largely controlled by reciprocal signal exchange. Legume roots excrete flavonoids which induce rhizobial nodulation genes to synthesize and excrete lopo-oligosaccharide Nod factors. In turn, Nod factors provoke deformation of the root hairs and nodule primordium formation. Normally, rhizobia enter roots through infection threads in markedly curled root hairs. If Nod factors are responsible for symbiosis-specific root hair deformation, they could also be the signal for entry of rhizobia into legume roots. We tested this hypothesis by adding, at inoculation, NodNGR-factors to signal-production-deficient mutants of the broad-host-range Rhizobium sp. NGR234 and Bradyrhizobium japorticum strain USDA110. Between 10 ⁻⁷ M and 10⁻⁶ M NodNGR factors permitted these NodABC mutants to penetrate, nodulate and fix nitrogen on Vigna unguiculata and Glycine max, respectively. NodNGR factors also allowed Rhizobium fredii strain USDA257 to enter and fix nitrogen on Calopogonium caeruleum, a non-host. Detailed cytological investigations of V. unguiculata showed that the NodABC mutant UGR AnodABC, in the presence of NodNGR factors, entered roots in the same way as the wild-type bacterium. Since infection threads were also present in the resulting nodules, we conclude that Nod factors are the signals that permit rhizobia to penetrate legume roots via infection threads.     

Expression of mRNA for atrial natriuretic peptide receptor guanylate cyclase (ANPRA) in human retina

Summary 1. Guanylate cyclase plays an important role in the visual cycle. Here we report the mRNA expression for the atrial natriuretic peptide receptor type A form of guanylate cyclase (ANPRA) in human retina.2. Polymerase chain reaction using two sets of primers on the cDNAs reverse-transcribed from human retinal poly(A)⁺ RNA amplified two products under two different reaction conditions. The primers used in the reaction were designed from the reported sequence of human placental ANPRA cDNA.3. Sequencing of the amplified products showed 100% sequence homology to the human placental ANPRA gene. Northern blot analysis indicated the presence of a 4.4-kb ANPRA mRNA in human retina, similar to that present in human brain.     

Regulation of axon guidance by slit and netrin signaling in the Drosophila ventral nerve cord

Netrin and Slit signaling systems play opposing roles during the positioning of longitudinal tracts along the midline in the ventral nerve cord of Drosophila embryo. It has been hypothesized that a gradient of Slit from the midline interacts with three different Robo receptors to specify the axon tract positioning. However, no such gradient has been detected. Moreover, overexpression of Slit at the midline has no effect on the positioning of these lateral tracts. In this article, we show that Slit is present outside of the midline along the longitudinal and commissural tracts. Sli from the midline, in a Robo-independent manner, is initially taken up by the commissural axon tracts when they cross the midline and is transported along the commissural tracts into the longitudinal connectives. These results are not consistent with a Sli gradient model. We also find that sli mRNA is maternally deposited and embryos that are genetically null for sli can have weaker guidance defects. Moreover, in robo or robo3 mutants, embryos with normal axon tracts are found and such robo embryos reach pupal stages and die, while robo3 mutant embryos develop into normal individuals and produce eggs. Interestingly, embryos from robo3 homozygous individuals fail to develop but have axon tracts ranging from normal to various defects: robo3 phenotype, robo phenotype, and slit-like phenotype, suggesting a more complex functional role for these genes than what has been proposed. Finally, our previous results indicated that netrin phenotype is epistatic to sli or robo phenotypes. However, it seems likely that this previously reported epistatic relationship might be due to the partial penetrance of the sli, robo, robo3 (or robo2) phenotypes. Our results argue that double mutant epistasis is most definitive only if the penetrance of the phenotypes of the mutants involved is complete.     

Use of radioimmunotherapy in stem cell transplantation and posttransplantation: focus on yttrium 90 ibritumomab tiuxetan

Although autologous stem cell transplantation (ASCT) produces prolonged disease-free survival in many patients with non-Hodgkin's lymphoma (NHL), relapse remains the most common cause of treatment failure. Because of the potential benefit of adding targeted irradiation to conditioning regimens, clinical trials are testing the safety and efficacy of combining radioimmunotherapy with yttrium 90 ibritumomab tiuxetan or iodine 131 tositumomab and chemotherapy, either as replacement for total body irradiation or in addition to standard high-dose chemotherapy (HDC) regimens. Current strategies include using standard or escalated doses of radioimmunoconjugates with HDC before ASCT in patients with relapsed or refractory B-cell NHL. We reviewed the safety and efficacy of (90)Y ibritumomab tiuxetan as part of the conditioning regimen before ASCT. Preliminary data from phase 1 and 2 trials show that (90)Y ibritumomab tiuxetan may be safely added to HDC preparative regimens for high-risk B-cell NHL. Additionally, comparisons of outcomes with radioimmunotherapy and ASCT with historical controls suggest that it may be more effective than conventional regimens. Results of (90)Y ibritumomab tiuxetan alone posttransplantation in select patients who have relapsed after HDC and ASCT are also encouraging. Studies of (90)Y ibritumomab tiuxetan in the setting of allogeneic stem cell transplantation appear promising as well.     

Patterned biofunctional poly(acrylic acid) brushes on silicon surfaces

Protein patterning was carried out using a simple procedure based on photolithography wherein the protein was not subjected to UV irradiation and high temperatures or contacted with denaturing solvents or strongly acidic or basic solutions. Self-assembled monolayers of poly(ethylene glycol) (PEG) on silicon surfaces were exposed to oxygen plasma through a patterned photoresist. The etched regions were back-filled with an initiator for surface-initiated atom transfer radical polymerization (ATRP). ATRP of sodium acrylate was readily achieved at room temperature in an aqueous medium. Protonation of the polymer resulted in patterned poly(acrylic acid) (PAA) brushes. A variety of biomolecules containing amino groups could be covalently tethered to the dense carboxyl groups of the brush, under relatively mild conditions. The PEG regions surrounding the PAA brush greatly reduced nonspecific adsorption. Avidin was covalently attached to PAA brushes, and biotin-tagged proteins could be immobilized through avidin-biotin interaction. Such an immobilization method, which is based on specific interactions, is expected to better retain protein functionality than direct covalent binding. Using biotin-tagged bovine serum albumin (BSA) as a model, a simple strategy was developed for immobilization of small biological molecules using BSA as linkages, while BSA can simultaneously block nonspecific interactions.