Error management theory and the adaptive significance of transgenerational maternal‐stress effects on offspring phenotype

It is well established that circulating maternal stress hormones (glucocorticoids, GCs) can alter offspring phenotype. There is also a growing body of empirical work, within ecology and evolution, indicating that maternal GCs link the environment experienced by the mother during gestation with changes in offspring phenotype. These changes are considered to be adaptive if the maternal environment matches the offspring's environment and maladaptive if it does not. While these ideas are conceptually sound, we lack a testable framework that can be used to investigate the fitness costs and benefits of altered offspring phenotypes across relevant future environments. We present error management theory as the foundation for a framework that can be used to assess the adaptive potential of maternal stress hormones on offspring phenotype across relevant postnatal scenarios. To encourage rigorous testing of our framework, we provide field‐testable hypotheses regarding the potential adaptive role of maternal stress across a diverse array of taxa and life histories, as well as suggestions regarding how our framework might provide insight into past, present, and future research. This perspective provides an informed lens through which to design and interpret experiments on the effects of maternal stress, provides a framework for predicting and testing variation in maternal stress across and within taxa, and also highlights how rapid environmental change that induces maternal stress may lead to evolutionary traps.     

Structure and refinement at 1.8 A resolution of the aspartic proteinase from Rhizopus chinensis

The structure of rhizopuspepsin (EC 3.4.23.6), the aspartic proteinase from Rhizopus chinensis, has been refined to a crystallographic R-factor of 0.143 at 1.8 A resolution. The positions of 2417 protein atoms have been determined with a root-mean-square (r.m.s.) error of 0.12 A. In the final model, the r.m.s. deviation from ideality for bond distances is 0.010 A, and for angle distances it is 0.034 A. During the course of the refinement, a calcium ion and 373 water molecules, of which 17 are internal, have been located. The active aspartate residues, Asp35 and Asp218, are involved in similar hydrogen-bonding interactions with neighboring residues and with several water molecules. One water molecule is located between the two carboxyl groups of the catalytic aspartate residues in a tightly hydrogen-bonded position. The refinement resulted in an unambiguous interpretation of the highly mobile "flap", a beta-hairpin loop region that projects over the binding pocket. Large solvent channels are formed when the molecules pack in the crystal, exposing the binding pocket and making it easily accessible. Intermolecular contacts involve mainly solvent molecules and a few protein atoms. The three-dimensional structure of rhizopuspepsin closely resembles other aspartic proteinase structures. A detailed comparison with the structure of penicillopepsin showed striking similarities as well as subtle differences in the active site geometry and molecular packing.     

Gossypol and testicular lipids of adult rats

Testicular lipids act as source of energy, structural components of spermatozoa and precursors of androgen biosynthesis. Treatment with antispermatogeneic agents cause accumulation of testicular lipids. Gossypol, an effective antispermatogenic agent causes marked accumulation of testicular neutral lipids. It did not affect testicular phospholipids. Gossypol treatment did not bring about marked changes in the key enzymes like HMG Co A reductase, glucose-6-phosphate dehydrogenase malic enzyme and cytosolic isocitrate dehydrogenase involved in sterol biosynthesis. Thus, gossypol brings about marked accumulation of glycerides and esterified cholesterol in the testis due to its effect on spermatogenic elements of adult rats.     

Evaluating Khaya senegalensis for Dipeptidyl Peptidase-IV Inhibition Using in Vitro Analysis and Molecular Dynamic Simulation of Identified Bioactive Compounds

The dipeptidyl peptidase-IV (DPP-IV) inhibitory activity of Khaya senegalensis extracts was evaluated. The DPP-IV from a rat kidney was purified to a purification fold of 2.3. Among extracts from K. senegalensis, the hexane extract had the best DPP-IV inhibitory activity, with IC₅₀ value of 1.56±0.61 μg/mL and was fractionated to eleven fractions (A–K). Fraction I had the best DPP-IV inhibition via uncompetitive pattern. GC-MS analysis of fraction I showed that the major bioactive compounds were 3-amino-3-hydroxyimino-N-phenylpropanamide ( 1 ) and 11-(2-cyclopenten-1-yl)undecanoic acid ( 2 ), with good binding affinities toward DPP-IV, based on molecular docking,. They were then subjected to molecular dynamic simulation using WEBGRO and utilizing a GROMACS system for 100 ns. The 3-amino-3-hydroxyimino-N-phenylpropanamide-DPP-IV complex was more stable and compact than the other complex. K. senegalensis contains compounds like 1 that might be used for the design of new DPP-IV inhibitors.     

Effect of gossypol on tissue levels of glutathione and thiobarbituric acid reactive products in rats.

Gossypol was administered in pubertal and adult rats and lipid peroxide formation and GSH levels were estimated in different tissues like liver, testis, heart and kidney. Gossypol caused low generation of lipid peroxides, measured as thiobarbituric acid reactive products (TBAR), without causing significant changes in tissue glutathione (GSH) levels. This effect was more pronounced in liver and testis as compared to other tissues. In vitro effect of gossypol to inhibit lipid peroxidation as observed in vivo suggested that binding of gossypol to plasma membranes may result in inhibition of lipid peroxide generation.     

Characterization of neuropeptide Y binding sites in rat cardiac ventricular membranes

Neuropeptide Y (NPY) binding sites in rat cardiac ventricular membranes have been characterized in detail. 125I-NPY bound to the membranes with high affinity. Binding was saturable, reversible and specific, and depended on time, pH and temperature. Analysis of the binding data obtained under optimal conditions, 2 hr, 18 degrees C and at pH 7.5, revealed the presence of low and high affinity binding sites. The high affinity binding sites had an apparent dissociation constant (Kd) of 0.38 nM and a binding capacity (Bmax) of 7.13 fmol/mg protein. The apparent Kd and Bmax for low affinity binding sites were 22.34 nM and 261.25 fmol/mg protein, respectively. Peptides unrelated to NPY did not compete with 125I-NPY for the binding sites even at 1 microM concentrations, whereas homologous peptides, peptide YY (PYY) and pancreatic polypeptide (PP), and NPY(13-36) inhibited 125I-NPY binding but with lower potency compared to NPY. 125I-NPY binding was sensitive to the nonhydrolyzable GTP analog, Gpp(NH)p, suggesting that the NPY receptor is coupled to the adenylate cyclase system. The ventricular membrane receptor characterized in this study may play an important role in mediating the physiological effects of NPY in the heart.     

Fear and lethality in snowshoe hares: the deadly effects of non‐consumptive predation risk

Predators play a critical, top–down role in shaping ecosystems, driving prey population and community dynamics. Traditionally, studies of predator‐prey interactions have focused on direct effects of predators, namely the killing of prey. More recently, the non‐consumptive effects of predation risk are being appreciated; e.g. the ‘ecology of fear’. Prey responses to predation risk can be morphological, behavioural, and physiological, and are assumed to come at a cost to prey fitness. However, few studies have examined the relationship between predation risk and survival in wild animals. We tested the hypothesis that predation risk itself could reduce survival in wild‐caught snowshoe hares. We exposed female snowshoe hares to a simulated predator (a trained dog) during gestation only, and measured adult survival and, in surviving females, their ability to successfully wean offspring. We show for the first time in a wild mammal that the risk of predation can itself be lethal. Predation risk reduced adult female survival by 30%, and had trans‐generational effects, reducing offspring survival to weaning by over 85% – even though the period of risk ended at birth. As a consequence of these effects the predator‐exposed group experienced a decrease in number, while the control group substantially increased. Challenges remain in determining the importance of risk‐induced mortality in natural field settings; however, our findings show that non‐lethal predator encounters can influence survival of both adults and offspring. Future work is needed to test these effects in free‐living animals.     

Patient and System-Related Delays of Emergency Medical Services Use in Acute ST-Elevation Myocardial Infarction: Results from the Third Gulf Registry of Acute Coronary Events (Gulf RACE-3Ps)

Background

Little is known about Emergency Medical Services (EMS) use and pre-hospital triage of patients with acute ST-elevation myocardial infarction (STEMI) in Arabian Gulf countries.

Methods

Clinical arrival and acute care within 24 h of STEMI symptom onset were compared between patients transferred by EMS (Red Crescent and Inter-Hospital) and those transferred by non-EMS means. Data were retrieved from a prospective registry of 36 hospitals in 6 Arabian Gulf countries, from January 2014 to January 2015.

Results

We enrolled 2,928 patients; mean age, 52.7 (SD ±11.8) years; 90% men; and 61.7% non-Arabian Gulf citizens. Only 753 patients (25.7%) used EMS; which was mostly via Inter-Hospital EMS (22%) rather than direct transfer from the scene to the hospital by the Red Crescent (3.7%). Compared to the non-EMS group, the EMS group was more likely to arrive initially at a primary or secondary health care facility; thus, they had longer median symptom-onset-to-emergency department arrival times (218 vs. 158 min; p˂.001); they were more likely to receive primary percutaneous coronary interventions (62% vs. 40.5%, p = 0.02); they had shorter door-to-needle times (38 vs. 42 min; p = .04); and shorter door-to-balloon times (47 vs. 83 min; p˂.001). High EMS use was independently predicted mostly by primary/secondary school educational levels and low or moderate socioeconomic status. Low EMS use was predicted by a history of angina and history of percutaneous coronary intervention. The groups had similar in-hospital deaths and outcomes.

Conclusion

Most acute STEMI patients in the Arabian Gulf region did not use EMS services. Improving Red Crescent infrastructure, establishing integrated STEMI networks, and launching educational public campaigns are top health care system priorities.