Head-to-head comparison of cardiac troponin T and troponin I in patients without acute coronary syndrome: a systematic review

Background: Cardiac-specific troponin T (cTnT) and troponin I (cTnI) are considered diagnostically equal in patients with acute coronary syndrome (ACS). The aim of this systematic review was to compare the prevalence and prognostic strength of elevations of cTnT and cTnI in patients with other conditions than ACS.

Methods: A systemic review was conducted in concordance with the PRISMA guidelines. The studies were identified by searching PubMed, EMBASE and Cochrane Central Register, from May to August 2016. Studies measuring both cTnT and cTnI in populations without ACS were eligible.

Results: Twenty-nine studies were included (n?=?25,859). Seventeen studies reported on prognostic information with follow-up time ranging for 30?d–5?years. Elevation above the 99th percentile (reference value for a healthy population) in non-ACS population was reported to be 0–39% for cTnI and 40–100% for cTnT. Elevation of cTnT tends to be a superior predictor for all-cause mortality and elevation of cTnI tends to be a superior predictor for cardiovascular related mortality.

Discussion: In the absence of ACS, elevation of cTnT is more frequent than elevation of cTnI.

Conclusion: Both cTnT and cTnI elevations have important prognostic information regarding morbidity, cardiac mortality and all-cause mortality.     

Misoprostol treatment prevents hypoxia-induced cardiac dysfunction through a 14-3-3 and PKA regulatory motif on Bnip3

Systemic hypoxia is a common element in most perinatal emergencies and is a known driver of Bnip3 expression in the neonatal heart. Bnip3 plays a prominent role in the evolution of necrotic cell death, disrupting ER calcium homeostasis and initiating mitochondrial permeability transition (MPT). Emerging evidence suggests a cardioprotective role for the prostaglandin E1 analog misoprostol during periods of hypoxia, but the mechanisms for this protection are not completely understood. Using a combination of mouse and cell models, we tested if misoprostol is cardioprotective during neonatal hypoxic injury by altering Bnip3 function. Here we report that hypoxia elicits mitochondrial-fragmentation, MPT, reduced ejection fraction, and evidence of necroinflammation, which were abrogated with misoprostol treatment or Bnip3 knockout. Through molecular studies we show that misoprostol leads to PKA-dependent Bnip3 phosphorylation at threonine-181, and subsequent redistribution of Bnip3 from mitochondrial Opa1 and the ER through an interaction with 14-3-3 proteins. Taken together, our results demonstrate a role for Bnip3 phosphorylation in the regulation of cardiomyocyte contractile/metabolic dysfunction, and necroinflammation. Furthermore, we identify a potential pharmacological mechanism to prevent neonatal hypoxic injury.Subject terms: Cell death, Cardiovascular biology     

Language, Handedness, and Primate Brains: Did the Australopithecines Sign?

Evidence from comparative primate neuroanatomy, archaeology, and studies of vocalization systems of nonhuman primates suggests that human vocal language has a long evolutionary history and that there is continuity between our early primate ancestors' call systems and human speech. Old World monkeys exhibit cerebral asymmetries similar to those that appear related to human language. If arboreal monkeylike ancestors of humans were also characterized by cerebral asymmetry, then the fundamental asymmetry that forms the neurological substrate for human language may have been established through selection for simple "discrete" call systems in an arboreal habitat and would have occurred much longer ago than previously thought. The eventual shift from an arboreal to a terrestrial habitat was accompanied by increased complexity ("gradation") of vocal communication systems. The archaeological record of tools suggests that communication systems became still more complex under the selective pressures that led to bipedalism and that language had been selected for by the time that bipedalism was achieved. Contrary to the gestural hypothesis, right-handedness (which could not have preceded freeing of the hands) succeeded speech and may have been due to selective pressures for increased complexity of communication, causing a Field Effect upon the brain. [australopithecine, cerebral asymmetry, language, primate brains, right-handedness]     

Rescue of Citrus sudden death-associated virus in Nicotiana benthamiana plants from cloned cDNA: insights into mechanisms of expression of the three capsid proteins

Citrus sudden death-associated virus (CSDaV) is a member of the genus Marafivirus in the family Tymoviridae, and has been associated with citrus sudden death (CSD) disease in Brazil. Difficulties in the purification of CSDaV from infected citrus plants have prevented progress in the investigation of the role of this virus in CSD and an understanding of its molecular biology. In this work, we have constructed a full-length cDNA clone of CSDaV driven by the 35S promoter (35SRbz-CSDaV). Agrobacterium tumefaciens-mediated inoculation of 35SRbz-CSDaV in Nicotiana benthamiana plants enabled a fast recovery of large amounts of virions from the agroinfiltrated leaves, which allowed a better molecular characterization of CSDaV. In vivo analyses of mutant versions of 35SRbz-CSDaV revealed the expression strategies used by CSDaV for production of the capsid proteins (CPs). We showed that CSDaV virions contain three forms of CP, each of which is generated from the same coding sequence, but by different mechanisms. The major CPp21 is a product of direct translation by leaky scanning from the second start codon in the subgenomic RNA (sgRNA), whereas the minor CPs, p25 and p23, are produced by direct translation from the first start codon in the sgRNA and by trans-proteolytic cleavage processing derived from the p25 precursor, respectively. Together, these findings contribute to advance our understanding of CSDaV genome expression strategies. In addition, the construction and characterization of the CSDaV infectious clone represent important steps towards the investigation of the role of this virus in CSD and of its use as a tool for citrus biotechnology.     

DAT1 Polymorphism Determines L-DOPA Effects on Learning about Others’ Prosociality

Despite that a wealth of evidence links striatal dopamine to individualś reward learning performance in non-social environments, the neurochemical underpinnings of such learning during social interaction are unknown. Here, we show that the administration of 300 mg of the dopamine precursor L-DOPA to 200 healthy male subjects influences learning about a partners’ prosocial preferences in a novel social interaction task, which is akin to a repeated trust game. We found learning to be modulated by a well-established genetic marker of striatal dopamine levels, the 40-bp variable number tandem repeats polymorphism of the dopamine transporter (DAT1 polymorphism). In particular, we found that L-DOPA improves learning in 10/10R genoype subjects, who are assumed to have lower endogenous striatal dopamine levels and impairs learning in 9/10R genotype subjects, who are assumed to have higher endogenous dopamine levels. These findings provide first evidence for a critical role of dopamine in learning whether an interaction partner has a prosocial or a selfish personality. The applied pharmacogenetic approach may open doors to new ways of studying psychiatric disorders such as psychosis, which is characterized by distorted perceptions of others’ prosocial attitudes.