Auxotrophic mutant of the cyanobacterium Nostoc muscorum showing absolute requirement of Cs+ or Rb+ for diazotrophy and autotrophy

Caesium-resistant (Cs(+)-R) mutant clones of the cyanobacterium Nostoc muscorum were characterized for diazotrophic growth in a medium devoid of Cs(+) or Rb(+) or both. Cs(+)-R phenotype suffered severe genetic damage of a pleiotropic nature affecting diazotrophic growth, chlorophyll a content, nitrogenase activity and photosynthetic O(2) evolution. Mutation leading to development of Cs(+)-R phenotype could be overcome by availability of Cs(+)/Rb(+). Parent and mutant strains were similar with respect to their Cs(+)/Rb(+) uptake. Available data suggests operation of an efficient coupling of the two incompatible reactions viz. oxygenic photosynthesis and oxygen sensitive N(2) fixation in this cyanobacterium.     

Role of ADAMTSL4 mutations in FBN1 mutation‐negative ectopia lentis patients

Ectopia lentis (EL) is genetically heterogeneous with both autosomal‐dominant and ‐recessive forms. The dominant disorder can be caused by mutations in FBN1, at the milder end of the type‐1 fibrillinopathies spectrum. Recently in a consanguineous Jordanian family, recessive EL was mapped to locus 1q21 containing the ADAMTSL4 gene and a nonsense mutation was found in exon 11 (c.1785T>G, p.Y595X). In this study, 36 consecutive probands with EL who did not fulfill the Ghent criteria for MFS were screened for mutations in FBN1 and ADAMTSL4. Causative FBN1 mutations were identified in 23/36 (64%) of probands while homozygous or compound heterozygous ADAMTSL4 mutations were identified in 6/12 (50%) of the remaining probands. Where available, familial screening of these families confirmed the mutation co‐segregated with the EL phenotype. This study confirms that homozygous mutations in ADAMTSL4 are associated with autosomal‐recessive EL in British families. Furthermore; the first compound heterozygous mutation is described resulting in a PTC and a missense mutation in the PLAC (protease and lacunin) domain. The identification of a causative mutation in ADAMTSL4 may allow the exclusion of Marfan syndrome in these families and guide the clinical management, of particular relevance in young children affected by EL. © 2010 Wiley‐Liss, Inc.     

Regulation of calmodulin-stimulated cyclic nucleotide phosphodiesterase (PDE1): review

The response of living cells to change in cell environment depends on the action of second messenger molecules. The two second messenger molecules cAMP and Ca2+ regulate a large number of eukaryotic cellular events. Calmodulin-stimulated cyclic nucleotide phosphodiesterase (PDE1) is one of the key enzymes involved in the complex interaction between cAMP and Ca2+ second messenger systems. Some PDE1 isozymes have similar kinetic and immunological properties but are differentially regulated by Ca2+ and calmodulin. Accumulating evidence suggests that the activity of PDE1 is selectively regulated by cross-talk between Ca2+ and cAMP signalling pathways. These isozymes are also further distinguished by various pharmacological agents. We have demonstrated a potentially novel regulation of PDE1 by calpain. This study suggests that limited proteolysis by calpain could be an alternative mechanism for the activation of PDE1. We have also shown PDE1 activity, expression and effect of calpain in the rat model in vitro of cardiac ischemia-reperfusion.     

Invasive pneumococcal disease caused by ceftriaxone-resistant Streptococcus pneumoniae in Taiwan

Background

Invasive pneumococcal disease (IPD) was associated with mortality, but the risk factors associated with mortality remains controversial.

Comparison of post-operative ICU sedation between dexmedetomidine and propofol in Indian population

Context:

Critically ill patients requiring mechanical ventilation frequently need sedatives and analgesics to facilitate their care. Dexmedetomidine, a short-acting alpha-2-agonist, possesses anxiolytic, anesthetic, hypnotic, and analgesic properties.

Aims:

The objective of this study was to evaluate the efficacy and safety of dexmedetomidine in comparison to propofol in the management of sedation for post-operative intensive care unit (ICU) patients, as a sedative agent.

Settings and Design:

Teaching hospital, A phase III, prospective, open, randomized and comparative.

Materials and Methods:

Thirty patients who were ambulatory and who required the post-operative mechanical ventilation or post-operative sedation were enrolled, in which 15 patients received Dexmedetomidine and remaining 15 patients received propofol. All these patients were treated for the period of 8 to 24 h.

Statistical Analysis Used:

Data were analyzed using Student''s t-test and Chi-square test. The value of P < 0.05 was considered as statistically significant.

Results:

Demographic data were comparable. Pulse rate, respiratory rate and blood pressure were comparable. Depth of sedation and extubation time were similar. To maintain analgesia throughout the study period, patients receiving propofol infusions required significantly more analgesics than patients receiving Dexmedetomidine.

Conclusions:

Dexmedetomidine appears to be a safe and acceptable ICU sedative agent when both the clinician''s and patient''s perspectives are considered.     

Prestin,a cochlear motor protein,is defective in non-syndromic hearing loss

Prestin, a membrane protein that is highly and almost exclusively expressed in the outer hair cells (OHCs) of the cochlea, is a motor protein which senses membrane potential and drives rapid length changes in OHCs. Surprisingly, prestin is a member of a gene family, solute carrier (SLC) family 26, that encodes anion transporters and related proteins. Of nine known human genes in this family, three (SLC26A2, SLC26A3 and SLC26A4) are associated with different human hereditary diseases. The restricted expression of prestin in OHCs, and its proposed function as a mechanical amplifier, make it a strong candidate gene for human deafness. Here we report the cloning and characterization of four splicing isoforms for the human prestin gene (SLC26A5a, b, c and d). SLC26A5a is the predominant form of prestin whereas the others showed limited distribution associated with certain developmental stages. Based on the functional importance of prestin we screened for possible mutations involving the prestin gene in a group of deaf probands. We have identified a 5'-UTR splice acceptor mutation (IVS2-2A>G) in exon 3 of the prestin gene, which is responsible for recessive non-syndromic deafness in two unrelated families. In addition, a high frequency of heterozygosity for the same mutation was observed in these subjects, suggesting the possibility of semi-dominant influence of the mutation in causing hearing loss. Finally, the observation of this mutation only in the Caucasian probands indicated an association with a specific ethnic background. This study thereby reveals an essential function of prestin in human auditory processing.     

Adenovirus type 5 pseudotyped with adenovirus type 37 fiber uses sialic acid as a cellular receptor

For purposes of gene therapy, the tropism of adenovirus (Ad) serotype 5 vectors can be altered with fibers derived from alternative serotypes. However, there is currently limited information available on the cellular receptors used by the approximately 51 known Ad serotypes. Recently, alpha(2-->3)-linked sialic acid (2,3-SA) has been implicated as the cellular receptor for wild-type Ad37. However, some studies have demonstrated that wild-type Ad37 uses a 50-kDa protein and not sialic acid as its primary receptor for binding of human conjunctival cells. The sialic acid receptor has also been shown not to play a major role in the infection of these cells by an Ad5 virion pseudotyped with Ad37 fiber (Ad5.GFP.DeltaF/37F). In this study, we demonstrate that a similar virus (Ad5F37) can indeed use alpha(2-->3)-linked sialic acid as a cellular receptor. We also find that the receptor used by Ad5F37 is sensitive to proteases and that Ad5F37 can use integrin more efficiently than sialic acid for cell entry. Unlike Ad5 vectors, Ad5F37 does not efficiently employ the coxsackie and adenovirus receptor (CAR) to infect cells. Similar to Ad5, Ad5F37 infection of cells that form tight junctions can be enhanced by ethylenediaminetetraacetic acid (EDTA). These results have implications in the design of pseudotyped adenovirus vectors for gene therapy and may have particular use in the treatment of diseases involving breakdown of the blood-retinal barrier.