Evidence of Uncoupling between Renal Dysfunction and Injury in Cardiorenal Syndrome: Insights from the BIONICS Study

Objective

The objective of the study was to assess urinary biomarkers of renal injury for their individual or collective ability to predict Worsening renal function (WRF) in patients with acutely decompensated heart failure (ADHF).

Methods

In a prospective, blinded international study, 87 emergency department (ED) patients with ADHF were evaluated with biomarkers of cardiac stretch (B type natriuretic peptide [BNP] and its amino terminal equivalent [NT-proBNP], ST2), biomarkers of renal function (creatinine, estimated glomerular filtration rate [eGFR]) and biomarkers of renal injury (plasma neutrophil gelatinase associated lipocalin [pNGAL], urine kidney injury molecule-1 [KIM-1], urine N-acetyl-beta-D-glucosaminidase [NAG], urine Cystatin C, urine fibrinogen). The primary endpoint was WRF.

Results

26% developed WRF; baseline characteristics of subjects who developed WRF were generally comparable to those who did not. Biomarkers of renal function and urine biomarkers of renal injury were not correlated, while urine biomarkers of renal injury correlated between each other. Biomarker concentrations were similar between patients with and without WRF except for baseline BNP. Although plasma NGAL was associated with the combined endpoint, none of the biomarker showed predictive accuracy for WRF.

Conclusions

In ED patients with ADHF, urine biomarkers of renal injury did not predict WRF. Our data suggest that a weak association exists between renal dysfunction and renal injury in this setting (Clinicaltrials.gov NCT#0150153).     

Challenges and opportunities in the development of metal-based anticancer theranostic agents

Around 10 million fatalities were recorded worldwide in 2020 due to cancer and statistical projections estimate the number to increase by 60% in 2040. With such a substantial rise in the global cancer burden, the disease will continue to impose a huge socio-economic burden on society. Currently, the most widely used clinical treatment modality is cytotoxic chemotherapy using platinum drugs which is used to treat variety of cancers. Despite its clinical success, critical challenges like resistance, off-target side effects and cancer variability often reduce its overall therapeutic efficiency. These challenges require faster diagnosis, simultaneous therapy and a more personalized approach toward cancer management. To this end, small-molecule ‘theranostic’ agents have presented a viable solution combining diagnosis and therapy into a single platform. In this review, we present a summary of recent efforts in the design and optimization of metal-based small-molecule ‘theranostic’ anticancer agents. Importantly, we highlight the advantages of a theranostic candidate over the purely therapeutic or diagnostic agent in terms of evaluation of its biological properties.     

Genetic Studies of the Prp17 Gene of Saccharomyces Cerevisiae: A Domain Essential for Function Maps to a Nonconserved Region of the Protein

The PRP17 gene product is required for the second step of pre-mRNA splicing reactions. The C-terminal half of this protein bears four repeat units with homology to the β transducin repeat. Missense mutations in three temperature-sensitive prp17 mutants map to a region in the N-terminal half of the protein. We have generated, in vitro, 11 missense alleles at the β transducin repeat units and find that only one affects function in vivo. A phenotypically silent missense allele at the fourth repeat unit enhances the slow-growing phenotype conferred by an allele at the third repeat, suggesting an interaction between these domains. Although many missense mutations in highly conserved amino acids lack phenotypic effects, deletion analysis suggests an essential role for these units. Only mutations in the N-terminal nonconserved domain of PRP17 are synthetically lethal in combination with mutations in PRP16 and PRP18, two other gene products required for the second splicing reaction. A mutually allele-specific interaction between prp17 and snr7, with mutations in U5 snRNA, was observed. We therefore suggest that the functional region of Prp17p that interacts with Prp18p, Prp16p, and U5 snRNA is in the N terminal region of the protein.     

Metal ion binding sites in a group II intron core

Group II introns are catalytic RNA molecules that require divalent metal ions for folding, substrate binding, and chemical catalysis. Metal ion binding sites in the group II core have now been elucidated by monitoring the site-specific RNA hydrolysis patterns of bound ions such as Tb(3+) and Mg(2+). Major sites are localized near active site elements such as domain 5 and its surrounding tertiary interaction partners. Numerous sites are also observed at intron substructures that are involved in binding and potentially activating the splice sites. These results highlight the locations of specific metal ions that are likely to play a role in ribozyme catalysis.     

Mapping of a gene that regulates hemolysin production in Vibrio cholerae.

A gene that regulates the hemolysin structural gene (hly) was found to be tightly linked to the tox-1000 locus of Vibrio cholerae RJ1 and separated from hly by a large section of the V. cholerae genetic map. This hemolysin regulatory gene was designated hlyR.     

Kinetics of biosurfactant production by Pseudomonas aeruginosa strain BS2 from industrial wastes

Summary Batch kinetic studies were carried out on rhamnolipid biosurfactant production from synthetic medium, industrial wastes viz. distillery and whey waste as substrates. The results indicated that the specific growth rates ( _max) and specific product formation rates (V _max) from both the wastes are comparatively better than the synthetic medium, revealing that both the industrial wastes (distillery and whey) can be successfully utilized as substrates for biosurfactant production.     

Twin-core packed-bed reactors for organic-phase enzymatic esterification with water activity control

A method for the removal of water and the control of water activity, a _w, during enzymatic esterification is the use of salt hydrate pairs. When this technique is used on a laboratory scale, the recovery and reuse of the salt are not critical. Potential problems, such as the reactivity of some salts, can also be overcome simply by substituting another salt. However, if this technique is to be used on a larger scale, economic constraints would require salt recovery and restric the range of salts that could be used. In this article a twin-core packed-bed reactor — used for the esterification of an equimolar mixture of decanoic acid and dodecanol catalysed by lipase from Candida rugosa — which facilitates salt recovery and permits a _w control without direct contact between immobilized enzyme and salt, has been described. a _w control was maintained by using suitable salt hydrate mixtures in the inner core of the reactor. The substrate mixture was esterified by pumping it through the outer core of the reactor, which contained enzyme immobilized on a macroporous polypropylene support. Complete conversion, albeit at different rates, was obtained with a _w buffering at 0.48 and 0.8 by using hydrates of Na₄P₂O₇ and Na₂HPO₄.     

Identification,characterization, validation and cross-species amplification of genic-SSRs in Indian Mustard (<Emphasis Type="Italic">Brassica juncea</Emphasis>)

Brassica juncea is an economically important oilseed crop worldwide. It has limited genomic resources at present. We generated 47,962,057 expressed sequence reads which were assembled into 45,280 unigenes. A total of 4108 SSR loci (≥10 bp) were identified in these unigenes. Trinucleotide was the most frequent repeat unit (59.91 %) followed by di- (38.66 %), tetra - (0.71 %), hexa - (0.49 %) and pentanucleotide repeats (0.24 %). Primers were designed for 2863 SSR loci among which 460 were selected for primer synthesis. A total of 339 loci amplified successfully of which 134 (39.5 %) exhibited polymorphism among six B. juncea genotypes with PIC values ranging from 0.18 to 0.81. Further, 25 polymorphic SSRs were used for analysis of genetic variability in 25 genotypes of Brassicas and their wild relatives. Two to five alleles with PIC values 0.22–0.66 were detected at these loci. The dendrogram grouped the genotypes according to their known pedigree/systematic position.