Parents’ posthumous use of daughter’s ovarian tissue: Ethical dimensions

In recent years, progress in cancer treatment has greatly increased the chances of recovery. Yet, treatment may have irreversible effects on patients’ fertility. In order to protect future fertility, preservation of ovarian tissue may be offered today even to very young girls, involving a surgical procedure that may be performed by minimally invasive laparoscopy, under general anesthesia. However, in the tragic event of a girl’s death, questions may arise regarding the possible use of the preserved ovarian tissue by her parents. Should posthumous reproductive use of ovarian tissue without the girl’s prior consent (due to her young age) be considered a violation of her rights? On the other hand, can it be argued that it is in the interest of a child who died young to leave a genetic trace through posthumous reproduction, because genetic continuity is in the interest of every human being? After presenting the relevant clinical facts, we explore the ethical dimensions of this possible practice through an analysis of the interests of the deceased, her parents, and the child that may be born posthumously.     

Role of divalent metals in the activation and regulation of insulin receptor tyrosine kinase

Multiple equilibrium equations were solved to separate the individual effects of ionic divalent metals, free nucleotides and their chelated species on insulin receptor tyrosine kinase (IRTK). Basal IRTK is activated by divalent metal cations when present in excess of that required for substrate formation, indicating the presence of a divalent cation-dependent regulatory site on the kinase. The activatory order for basal activity was Mn2+ greater than Co2+ greater than Mg2+ and Ca2+ = 0. The insulin-dependent activation of IRTK was minimal in the absence of excess free divalent metal, even when the concentration of MnATP or MgATP substrate present exceeded the apparent Km of the kinase. The activatory order for insulin-dependent activation of IRTK changed to Mg2+ greater than Mn2+ and Co2+ = 0. The titration of the MnCl2 saturation response at several concentrations of MgCl2 revealed that the insulin-dependent response of IRTK increases as a function of increasing MgCl2, while basal activity was unaffected. This enhancement of the responsiveness to insulin in the presence of both cations was not due to differing affinities of the kinase for substrate, as evidenced by nearly identical apparent Km values for MnATP and MgATP. The Mg2+-dependent increase in the response of the kinase to insulin may be due to Mg2+ inducing a stronger coupling between receptor and kinase than that observed with Mn2+ alone. The plotting of the effect of several concentrations of free divalent metals on substrate saturation curves revealed that an increase in either of the reactants increased the affinity of the insulin-activated kinase for the other respective reactant. Accordingly, free divalent metal and metal-ATP substrate interact with IRTK in a mutually inclusive manner. CaCl2 saturation curves in the presence of constant MnCl2 and increasing MgCl2 showed that the affinity of IRTK for Ca2+ decreases and the affinity for CaATP increased with increasing Mg2+. Our data suggests that IRTK contains three sites for interaction with divalent metal cations: a MeATP (active) site, a regulatory site, and a metal-dependent site acting to couple the receptor with the kinase.     

Consumer (dis-)interest in genetic ancestry testing: the roles of race,immigration, and ancestral certainty

Genetic ancestry testing (GAT) is marketed as a way to make up for missing knowledge about one’s ancestry. Previous research questions the GAT industry’s ability to fulfill this promise in terms of the validity and reliability of test results. We instead explore the demand side of GAT, evaluating who is most and least likely to express interest in GAT. Using data from an original, nationwide survey of over 100,000 American adults, we find that GAT interest is related to both self-identified race and immigrant generation, with Asian Americans and first-generation immigrants expressing the least interest. Our quantitative and qualitative evidence suggests interest is further shaped by a pre-existing sense of ancestral certainty, leading some individuals to decline GAT, even if it were free. How interest and ancestral certainty are patterned has implications for who is included in – and thus for the conclusions that can be drawn from – genetic ancestry databases.     

Conformational modifications of cyclic hexapeptide somatostatin analogs

A model for the bioactive conformation of the highly active cyclic hexapeptide somatostatin analog cyclo-(Pro-Phe-D-Trp-Lys-Thr-Phe) has been proposed. As a test of this model, several compounds containing lactam and N-Me amino acid conformational modifications in the Thr-Phe-Pro-Phe beta turn were synthesized. The N-Me alanine and sarcosine substitutions for proline gave highly active analogs, while lactam dipeptides in place of Phe-Pro decreased potency. 1H n.m.r. and CD spectra of these analogs illustrate the conformational effects in solution of these modifications. The results provide additional support for the proposed conformational model.     

Assessment of shikonin and acetyl-shikonin for mitigating quorum sensing potential of C. violaceum

Plant Growth Regulation - Shikonins (SK) and acetyl-shikonins (acetyl-SK) are known to possess great pharmaceutical potentials however, their ability to disrupt infectious bacterial communication...     

Somatostatin analogs which define the role of the lysine-9 amino group

Structure-activity studies of the lysine residue in the highly active cyclic hexapeptide somatostatin analog cyclo(Pro-Phe-D-Trp-Lys-Thr-Phe) confirm the importance of the lysine amino group for biological activity through the loss of activity seen on replacement of lysine by ornithine, arginine, histidine and p-amino phenylalanine. Three analogs containing thialysine, gamma- and delta-fluorolysine were equipotent to the parent as inhibitors of insulin, glucagon, and growth hormone release. The pKa's of the amino groups in these equiactive peptides ranged from 8.23-9.4. The lack of a correlation between the basicity of the amino groups and the biological activities suggests that deprotonation is not required for biological activity.