The College News, 1941-05-14, Vol. 27, No. 24

Bryn Mawr College student newspaper. Merged with The Haverford News in 1968 to form the Bi-college News (with various titles from 1968 on). Published weekly (except holidays) during the academic year

Genetic evaluation supports differential diagnosis in adolescent patients with delayed puberty

Context: Pubertal delay can be the clinical presentation of both idiopathic hypogonadotropic hypogonadism (IHH) and self-limited delayed puberty (SLDP). Distinction between these conditions is a common but important diagnostic challenge in adolescents. Objective: To assess whether gene panel testing can assist with clinical differential diagnosis and to allow accurate and timely management of delayed puberty patients. Design: Retrospective study. Methods: Patients presenting with delayed puberty to UK Paediatric services, followed up to final diagnosis, were included. Whole-exome sequencing was analysed using a virtual panel of genes previously reported to cause either IHH or SLDP to identify rarely predicted deleterious variants. Deleterious variants were verified by in silico prediction tools. The correlation between clinical and genotype diagnosis was analysed. Results: Forty-six patients were included, 54% with a final clinical diagnosis of SLDP and 46% with IHH. Red flags signs of IHH were present in only three patients. Fifteen predicted deleterious variants in 12 genes were identified in 33% of the cohort, with most inherited in a heterozygous manner. A fair correlation between final clinical diagnosis and genotypic diagnosis was found. Panel testing was able to confirm a diagnosis of IHH in patients with pubertal delay. Genetic analysis identified three patients with IHH that had been previously diagnosed as SLDP. Conclusion: This study supports the use of targeted exome sequencing in the clinical setting to aid the differential diagnosis between IHH and SLDP in adolescents presenting with pubertal delay. Genetic evaluation thus facilitates earlier and more precise diagnosis, allowing clinicians to direct treatment appropriately

Anarchy in the UK: Detailed genetic analysis of worker reproduction in a naturally occurring British anarchistic honeybee, Apis mellifera, colony using DNA microsatellites

Anarchistic behaviour is a very rare phenotype of honeybee colonies. In an anarchistic colony, many workers’ sons are reared in the presence of the queen. Anarchy has previously been described in only two Australian colonies. Here we report on a first detailed genetic analysis of a British anarchistic colony. Male pupae were present in great abundance above the queen excluder, which was clearly indicative of extensive worker reproduction and is the hallmark of anarchy. Seventeen microsatellite loci were used to analyse these male pupae, allowing us to address whether all the males were indeed workers’ sons, and how many worker patrilines and individual workers produced them. In the sample, 95 of 96 of the males were definitely workers’ sons. Given that ≈ 1% of workers’ sons were genetically indistinguishable from queen’s sons, this suggests that workers do not move any queen-laid eggs between the part of the colony where the queen is present to the area above the queen excluder which the queen cannot enter. The colony had 16 patrilines, with an effective number of patrilines of 9.85. The 75 males that could be assigned with certainty to a patriline came from 7 patrilines, with an effective number of 4.21. They were the offspring of at least 19 workers. This is in contrast to the two previously studied Australian naturally occurring anarchist colonies, in which most of the workers’ sons were offspring of one patriline. The high number of patrilines producing males leads to a low mean relatedness between laying workers and males of the colony. We discuss the importance of studying such colonies in the understanding of worker policing and its evolution

Network segregation in a model of misinformation and fact checking

Misinformation under the form of rumor, hoaxes, and conspiracy theories spreads on social media at alarming rates. One hypothesis is that, since social media are shaped by homophily, belief in misinformation may be more likely to thrive on those social circles that are segregated from the rest of the network. One possible antidote is fact checking which, in some cases, is known to stop rumors from spreading further. However, fact checking may also backfire and reinforce the belief in a hoax. Here we take into account the combination of network segregation, finite memory and attention, and fact-checking efforts. We consider a compartmental model of two interacting epidemic processes over a network that is segregated between gullible and skeptic users. Extensive simulation and mean-field analysis show that a more segregated network facilitates the spread of a hoax only at low forgetting rates, but has no effect when agents forget at faster rates. This finding may inform the development of mitigation techniques and overall inform on the risks of uncontrolled misinformation online

Pancreatic alpha cell mass in European subjects with type 2 diabetes

AIMS/HYPOTHESIS: Type 2 diabetes is a bi-hormonal disease characterised by relative hypoinsulinaemia and hyperglucagonaemia with elevated blood glucose levels. Besides pancreatic beta cell defects, a low number of beta cells (low beta cell mass) may contribute to the insufficient secretion of insulin. In this study our aim was to determine whether the alpha cell mass is also altered. METHODS: Using a point counting method, we measured the ratio of alpha to beta cell areas in pancreas samples obtained at autopsy from 50 type 2 diabetic subjects, whose beta cell mass had previously been found to be 36% lower than that of 52 non-diabetic subjects. RESULTS: The topography of alpha and beta cells was similar in both groups: many alpha cells were localised in the centre of the islets and the ratio of alpha/beta cell areas increased with islet size. The average ratio was significantly higher in type 2 diabetic subjects (0.72) than in non-diabetic subjects (0.42), with, however, a large overlap between the two groups. In contrast, the alpha cell mass was virtually identical in type 2 diabetic subjects (366 mg) and non-diabetic subjects (342 mg), and was not influenced by sex, BMI or type of diabetes treatment. CONCLUSIONS: The higher proportion of alpha to beta cells in the islets of some type 2 diabetic subjects is due to a decrease in beta cell number rather than an increase in alpha cell number. This imbalance may contribute to alterations in the normal inhibitory influence exerted by beta cells on alpha cells, and lead to the relative hyperglucagonaemia observed in type 2 diabete

Does hyperthermia constrain flight duration in a short-distance migrant?

While some migratory birds perform non-stop flights of over 11 000 km, many species only spend around 15% of the day in flight during migration, posing a question as to why flight times for many species are so short. Here, we test the idea that hyperthermia might constrain flight duration (FD) in a short-distance migrant using remote biologging technology to measure heart rate, hydrostatic pressure and body temperature in 19 migrating eider ducks (Somateria mollissima), a short-distance migrant. Our results reveal a stop-and-go migration strategy where migratory flights were frequent (14 flights day(−1)) and short (15.7 min), together with the fact that body temperature increases by 1°C, on average, during such flights, which equates to a rate of heat storage index (HSI) of 4°C h(−1). Furthermore, we could not find any evidence that short flights were limited by heart rate, together with the fact that the numerous stops could not be explained by the need to feed, as the frequency of dives and the time spent feeding were comparatively small during the migratory period. We thus conclude that hyperthermia appears to be the predominant determinant of the observed migration strategy, and suggest that such a physiological limitation to FD may also occur in other species. This article is part of the themed issue ‘Moving in a moving medium: new perspectives on flight’

Ultralong C100 Mycolic Acids Support the Assignment of Segniliparus as a New Bacterial Genus

Mycolic acid-producing bacteria isolated from the respiratory tract of human and non-human mammals were recently assigned as a distinct genus, Segniliparus, because they diverge from rhodococci and mycobacteria in genetic and chemical features. Using high accuracy mass spectrometry, we determined the chemical composition of 65 homologous mycolic acids in two Segniliparus species and separately analyzed the three subclasses to measure relative chain length, number and stereochemistry of unsaturations and cyclopropyl groups within each class. Whereas mycobacterial mycolate subclasses are distinguished from one another by R groups on the meromycolate chain, Segniliparus species synthesize solely non-oxygenated α-mycolates with high levels of cis unsaturation. Unexpectedly Segniliparus α-mycolates diverge into three subclasses based on large differences in carbon chain length with one bacterial culture producing mycolates that range from C58 to C100. Both the overall chain length (C100) and the chain length diversity (C42) are larger than previously seen for mycolic acid-producing organisms and provide direct chemical evidence for assignment of Segniliparus as a distinct genus. Yet, electron microscopy shows that the long and diverse mycolates pack into a typical appearing membrane. Therefore, these new and unexpected extremes of mycolic acid chemical structure raise questions about the modes of mycolic acid packing and folding into a membrane

The Amyloidogenic V122I Transthyretin Variant in Elderly Black Americans

BACKGROUND: Approximately 4% of black Americans carry a valine-to-isoleucine substitution (V122I) in the transthyretin protein, which has been associated with late-onset restrictive amyloid cardiomyopathy and increased risks of death and heart failure. METHODS: We determined genotype status for the transthyretin gene (TTR) in 3856 black participants in the Atherosclerosis Risk in Communities study and assessed clinical profiles, mortality, and the risk of incident heart failure in V122I TTR variant carriers (124 participants [3%]) versus noncarriers (3732 participants). Cardiac structure and function and features suggestive of cardiac amyloidosis were assessed in participants who underwent echocardiography during visit 5 (2011 to 2013), when they were older than 65 years of age. RESULTS: After 21.5 years of follow-up, we did not detect a significant difference in mortality between carriers (41 deaths, 33%) and noncarriers (1382 deaths, 37%; age- and sex-stratified hazard ratio among carriers, 0.99; 95% confidence interval [CI], 0.73 to 1.36; P=0.97). The TTR variant was associated with an increased risk of incident heart failure (age- and sex-stratified hazard ratio, 1.47; 95% CI, 1.03 to 2.10; P=0.04). On echocardiography at visit 5, carriers (46 participants) had worse systolic and diastolic function, as well as a higher level of N-terminal pro–brain natriuretic peptide, than noncarriers (1194 participants), although carriers had a low prevalence (7%) of overt manifestations of amyloid cardiomyopathy. CONCLUSIONS: We did not detect a significant difference in mortality between V122I TTR allele carriers and noncarriers, a finding that contrasts with prior observations; however, the risk of heart failure was increased among carriers. The prevalence of overt cardiac abnormalities among V122I TTR carriers was low. (Funded by the National Heart, Lung, and Blood Institute and others.

Sensitivity of projected long-term CO 2 emissions across the Shared Socioeconomic Pathways

Scenarios showing future greenhouse gas emissions are needed to estimate climate impacts and the mitigation efforts required for climate stabilization. Recently, the Shared Socioeconomic Pathways (SSPs) have been introduced to describe alternative social, economic and technical narratives, spanning a wide range of plausible futures in terms of challenges to mitigation and adaptation. Thus far the key drivers of the uncertainty in emissions projections have not been robustly disentangled. Here we assess the sensitivities of future CO 2 emissions to key drivers characterizing the SSPs. We use six state-of-the-art integrated assessment models with different structural characteristics, and study the impact of five families of parameters, related to population, income, energy efficiency, fossil fuel availability, and low-carbon energy technology development. A recently developed sensitivity analysis algorithm allows us to parsimoniously compute both the direct and interaction effects of each of these drivers on cumulative emissions. The study reveals that the SSP assumptions about energy intensity and economic growth are the most important determinants of future CO 2 emissions from energy combustion, both with and without a climate policy. Interaction terms between parameters are shown to be important determinants of the total sensitivities