Gyroid cuticular structures in butterfly wing scales: biological photonic crystals

We present a systematic study of the cuticular structure in the butterfly wing scales of some papilionids (Parides sesostris and Teinopalpus imperialis) and lycaenids (Callophrys rubi, Cyanophrys remus, Mitoura gryneus and Callophrys dumetorum). Using published scanning and transmission electron microscopy (TEM) images, analytical modelling and computer-generated TEM micrographs, we find that the three-dimensional cuticular structures can be modelled by gyroid structures with various filling fractions and lattice parameters. We give a brief discussion of the formation of cubic gyroid membranes from the smooth endoplasmic reticulum in the scale's cell, which dry and harden to leave the cuticular structure behind when the cell dies. The scales of C. rubi are a potentially attractive biotemplate for producing three-dimensional optical photonic crystals since for these scales the cuticle-filling fraction is nearly optimal for obtaining the largest photonic band gap in a gyroid structure

Evidence that stimulation of gluconeogenesis by fatty acid is mediated through thermodynamic mechanisms

AbstractWe have studied the stimulatory effects of palmitate on the rate of glucose synthesis from lactate in isolated hepatocytes. Control of the metabolic flow was achieved by modulating the activity of enolase using graded concentrations of fluoride. Unexpectedly, palmitate stimulated gluconeogenesis even when enolase was rate-limiting. This stimulation was also observed when the activities of phosphoenolpyruvate carboxykinase and aspartate aminotransferase were modulated using graded concentrations of quinolinate and aminooxyacetate, respectively. Linear force-flow relationships were found between the rate of gluconeogenesis and indicators of cellular energy status (i.e. mitochondrial membrane and redox potentials and cellular phosphorylation potential). These findings suggest that the fatty acid stimulation of glucose synthesis is in part mediated through thermodynamic mechanisms

The differential diagnosis of chronic daily headaches: an algorithm-based approach

Chronic daily headaches (CDHs) refers to primary headaches that happen on at least 15 days per month, for 4 or more hours per day, for at least three consecutive months. The differential diagnosis of CDHs is challenging and should proceed in an orderly fashion. The approach begins with a search for “red flags” that suggest the possibility of a secondary headache. If secondary headaches that mimic CDHs are excluded, either on clinical grounds or through investigation, the next step is to classify the headaches based on the duration of attacks. If the attacks last less than 4 hours per day, a trigeminal autonomic cephalalgia (TAC) is likely. TACs include episodic and chronic cluster headache, episodic and chronic paroxysmal hemicrania, SUNCT, and hypnic headache. If the duration is ≥4 h, a CDH is likely and the differential diagnosis encompasses chronic migraine, chronic tension-type headache, new daily persistent headache and hemicrania continua. The clinical approach to diagnosing CDH is the scope of this review

Genetic variant effects on gene expression in human pancreatic islets and their implications for T2D

Most signals detected by genome-wide association studies map to non-coding sequence and their tissue-specific effects influence transcriptional regulation. However, key tissues and cell-types required for functional inference are absent from large-scale resources. Here we explore the relationship between genetic variants influencing predisposition to type 2 diabetes (T2D) and related glycemic traits, and human pancreatic islet transcription using data from 420 donors. We find: (a) 7741 cis-eQTLs in islets with a replication rate across 44 GTEx tissues between 40% and 73%; (b) marked overlap between islet cis-eQTL signals and active regulatory sequences in islets, with reduced eQTL effect size observed in the stretch enhancers most strongly implicated in GWAS signal location; (c) enrichment of islet cis-eQTL signals with T2D risk variants identified in genome-wide association studies; and (d) colocalization between 47 islet cis-eQTLs and variants influencing T2D or glycemic traits, including DGKB and TCF7L2. Our findings illustrate the advantages of performing functional and regulatory studies in disease relevant tissues

Genetic variant effects on gene expression in human pancreatic islets and their implications for T2D

Most signals detected by genome-wide association studies map to non-coding sequence and their tissue-specific effects influence transcriptional regulation. However, key tissues and cell-types required for functional inference are absent from large-scale resources. Here we explore the relationship between genetic variants influencing predisposition to type 2 diabetes (T2D) and related glycemic traits, and human pancreatic islet transcription using data from 420 donors. We find: (a) 7741 cis-eQTLs in islets with a replication rate across 44 GTEx tissues between 40% and 73%; (b) marked overlap between islet cis-eQTL signals and active regulatory sequences in islets, with reduced eQTL effect size observed in the stretch enhancers most strongly implicated in GWAS signal location; (c) enrichment of islet cis-eQTL signals with T2D risk variants identified in genome-wide association studies; and (d) colocalization between 47 islet cis-eQTLs and variants influencing T2D or glycemic traits, including DGKB and TCF7L2. Our findings illustrate the advantages of performing functional and regulatory studies in disease relevant tissues

The genetic architecture of type 2 diabetes

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes

Associations between Prenatal Urinary Biomarkers of Phthalate Exposure and Preterm Birth: A Pooled Study of 16 US Cohorts

Importance: Phthalate exposure is widespread among pregnant women and may be a risk factor for preterm birth. Objective: To investigate the prospective association between urinary biomarkers of phthalates in pregnancy and preterm birth among individuals living in the US. Design, Setting, and Participants: Individual-level data were pooled from 16 preconception and pregnancy studies conducted in the US. Pregnant individuals who delivered between 1983 and 2018 and provided 1 or more urine samples during pregnancy were included. Exposures: Urinary phthalate metabolites were quantified as biomarkers of phthalate exposure. Concentrations of 11 phthalate metabolites were standardized for urine dilution and mean repeated measurements across pregnancy were calculated. Main Outcomes and Measures: Logistic regression models were used to examine the association between each phthalate metabolite with the odds of preterm birth, defined as less than 37 weeks of gestation at delivery (n = 539). Models pooled data using fixed effects and adjusted for maternal age, race and ethnicity, education, and prepregnancy body mass index. The association between the overall mixture of phthalate metabolites and preterm birth was also examined with logistic regression. G-computation, which requires certain assumptions to be considered causal, was used to estimate the association with hypothetical interventions to reduce the mixture concentrations on preterm birth. Results: The final analytic sample included 6045 participants (mean [SD] age, 29.1 [6.1] years). Overall, 802 individuals (13.3%) were Black, 2323 (38.4%) were Hispanic/Latina, 2576 (42.6%) were White, and 328 (5.4%) had other race and ethnicity (including American Indian/Alaskan Native, Native Hawaiian, >1 racial identity, or reported as other). Most phthalate metabolites were detected in more than 96% of participants. Higher odds of preterm birth, ranging from 12% to 16%, were observed in association with an interquartile range increase in urinary concentrations of mono-n-butyl phthalate (odds ratio [OR], 1.12 [95% CI, 0.98-1.27]), mono-isobutyl phthalate (OR, 1.16 [95% CI, 1.00-1.34]), mono(2-ethyl-5-carboxypentyl) phthalate (OR, 1.16 [95% CI, 1.00-1.34]), and mono(3-carboxypropyl) phthalate (OR, 1.14 [95% CI, 1.01-1.29]). Among approximately 90 preterm births per 1000 live births in this study population, hypothetical interventions to reduce the mixture of phthalate metabolite levels by 10%, 30%, and 50% were estimated to prevent 1.8 (95% CI, 0.5-3.1), 5.9 (95% CI, 1.7-9.9), and 11.1 (95% CI, 3.6-18.3) preterm births, respectively. Conclusions and Relevance: Results from this large US study population suggest that phthalate exposure during pregnancy may be a preventable risk factor for preterm delivery

ACTINIDE PRODUCTION FROM XENON BOMBARDMENTS OF CURIUM-248

Production cross sections for many actinide nuclides formed in the reaction of /sup 129/Xe and /sup 132/Xe with /sup 248/Cm at bombarding energies slightly above the coulomb barrier were determined using radiochemical techniques to isolate these products. These results are compared with cross sections from a /sup 136/Xe + /sup 248/Cm reaction at a similar energy. When compared to the reaction with /sup 136/Xe, the maxima in the production cross section distributions from the more neutron deficient projectiles are shifted to smaller mass numbers, and the total cross section increases for the production of elements with atomic numbers greater than that of the target, and decreases for lighter elements. These results can be explained by use of a potential energy surface (PES) which illustrates the effect of the available energy on the transfer of nucleons and describes the evolution of the di-nuclear complex, an essential feature of deep-inelastic reactions (DIR), during the interaction. The other principal reaction mechanism is the quasi-elastic transfer (QE). Analysis of data from a similar set of reactions, /sup 129/Xe, /sup 132/Xe, and /sup 136/Xe with /sup 197/Au, aids in explaining the features of the Xe + Cm product distributions, which are additionally affected by the depletion of actinide product yields due to deexcitation by fission. The PES is shown to be a useful tool to predict the general features of product distributions from heavy ion reactions