Evolutionary response to global change: Climate and land use interact to shape color polymorphism in a woodland salamander

Evolutionary change has been demonstrated to occur rapidly in human‐modified systems, yet understanding how multiple components of global change interact to affect adaptive evolution remains a critical knowledge gap. Climate change is predicted to impose directional selection on traits to reduce thermal stress, but the strength of directional selection may be mediated by changes in the thermal environment driven by land use. We examined how regional climatic conditions and land use interact to affect genetically based color polymorphism in the eastern red‐backed salamander (Plethodon cinereus). P. cinereus is a woodland salamander with two primary discrete color morphs (striped, unstriped) that have been associated with macroclimatic conditions. Striped individuals are most common in colder regions, but morph frequencies can be variable within climate zones. We used path analysis to analyze morph frequencies among 238,591 individual salamanders across 1,170 sites in North America. Frequency of striped individuals was positively related to forest cover in populations occurring in warmer regions (\u3e7°C annually), a relationship that was weak to nonexistent in populations located in colder regions (≤7°C annually). Our results suggest that directional selection imposed by climate warming at a regional scale may be amplified by forest loss and suppressed by forest persistence, with a mediating effect of land use that varies geographically. Our work highlights how the complex interaction of selection pressures imposed by different components of global change may lead to divergent evolutionary trajectories among populations

Intrinsically motivated graph exploration using network theories of human curiosity

Intrinsically motivated exploration has proven useful for reinforcement learning, even without additional extrinsic rewards. When the environment is naturally represented as a graph, how to guide exploration best remains an open question. In this work, we propose a novel approach for exploring graph-structured data motivated by two theories of human curiosity: the information gap theory and the compression progress theory. The theories view curiosity as an intrinsic motivation to optimize for topological features of subgraphs induced by the visited nodes in the environment. We use these proposed features as rewards for graph neural-network-based reinforcement learning. On multiple classes of synthetically generated graphs, we find that trained agents generalize to larger environments and to longer exploratory walks than are seen during training. Our method computes more efficiently than the greedy evaluation of the relevant topological properties. The proposed intrinsic motivations bear particular relevance for recommender systems. We demonstrate that curiosity-based recommendations are more predictive of human behavior than PageRank centrality for several real-world graph datasets, including MovieLens, Amazon Books, and Wikispeedia.Comment: 14 pages, 5 figures in main text, and 15 pages, 8 figures in supplemen

Prenatal urinary triclosan concentrations and child neurobehavior

Background: Exposure to triclosan, an antimicrobial chemical, is ubiquitous among pregnant women and may reduce thyroid hormone levels that are important for fetal neurodevelopment. Few studies have examined the association between prenatal triclosan exposure and children's neurobehavior. Objective: We investigated the relationship of prenatal urinary triclosan concentrations with children's behavior and cognitive abilities at age three years in a prospective pregnancy and birth cohort in Canada. Methods: We measured triclosan in urine samples collected at ~12 weeks of gestation in 794 Canadian women enrolled in a prospective pregnancy and birth cohort study (MIREC) from 2008 to 2011. Around age 3 years, we assessed children's cognitive abilities using the Wechsler Primary and Preschool Scale of Intelligence-III (WPPSIIII), and two scales of the Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P). Parents reported children's problem and reciprocal social behaviors using the Behavior Assessment System for Children-2 (BASC-2) and Social Responsiveness Scale-2 (SRS-2), respectively. Results: After adjusting for confounders using multivariable linear regression, triclosan was not associated with most of the 30 examined neurobehavioral scales. Each 10-fold increase in triclosan was associated with better WPPSI-III picture completion scores (β: 0.2; 95% CI: 0,0.5) and BASC-2 externalizing (β: −0.5; 95% CI: −1.1, 0) and hyperactivity (β: −0.6; 95% CI: −1.2, −0.1) scores, suggesting less externalizing and hyperactive behaviors. Child sex did not modify these associations. Conclusions: In this cohort, urinary triclosan concentrations measured once in early pregnancy were not associated with most assessed aspects of neurobehavior and weakly associated with a few others, but not in the hypothesized direction

Fusionless surgery in early-onset scoliosis

AbstractBackgroundSurgical treatment of early-onset scoliosis has greatly developed in recent years. Early-onset scoliosis covers a variety of etiologies (idiopathic, neurologic, dystrophic, malformative, etc.) with onset before the age of 5 years. Progression and severity threaten respiratory development and may result in respiratory failure in adulthood. Many surgical techniques have been developed in recent years, aiming to protect spinal and thoracic development.Material and methodsPresent techniques are based on one of two main principles. The first consists in posterior distraction of the spine in its concavity (single growing rod, or vertical expandable prosthetic titanium rib [VEPTR]), or on either side (dual rod); this requires iterative surgery, for lengthening, unless motorized using energy provided by a magnetic system. The second option is to use spinal growth force to lengthen the assembly; these techniques (Luque Trolley, Shilla), using a sliding assembly, are known as growth guidance.ResultsThese techniques are effective in controlling early scoliotic deformity, and to some extent restore spinal growth. However, they show a high rate of complications: infection, rod breakage, spinal fixation pull out and, above all, progressive spinal stiffness, reducing long-term efficacy. Respiratory gain is harder to assess, as thoracic expansion does not systematically improve respiratory function, particularly due to impaired compliance of the thoracic cage

321. Deletion of Mutated GAA Repeats from the Intron 1 of the Frataxin Gene Using the CRISPR System Restores the Protein Expression in a Friedreich Ataxia Model

The CRISPR system is now widely used as a molecular tool to edit the genome. We used this technique in Friedreich Ataxia (FRDA), an inherited autosomal disease known to cause a decrease of the mitochondrial frataxin protein. Genetic analysis revealed a GAA repeat expansion within the intron 1 of the frataxin (FXN) gene. We used cells derived from the YG8sR mouse model where the mouse frataxin gene is knockout but contain a human FXN mutated transgene on one allele. We then deleted the GAA trinucleotide repeat using 2 specific guide RNAs (gRNAs) co-expressed with either S. pyogenes (Sp) or S. aureus (Sa) Cas9. We were able to monitored an increase up to 2-fold of frataxin mRNA and protein levels in clone cells. We also confirmed these results in vivo using DNA electroporation in the Tibialis anterior muscle of the YG8R mice. Ongoing in vivo investigation of a systemically injected AAV-DJ vector expressing the SaCas9 and 2 successful selected gRNAs in the mouse model YG8sR will hopefully provide more details answers on the efficacy of the approach and give us preliminary data to go forward for clinical trial. The deletion of the GAA repeats expansion then might be a highly valuable gene therapy approach for FRDA patients

A new physiological model for studying the effect of chest compression and ventilation during cardiopulmonary resuscitation: The Thiel cadaver

BACKGROUND: Studying ventilation and intrathoracic pressure (ITP) induced by chest compressions (CC) during Cardio Pulmonary Resuscitation is challenging and important aspects such as airway closure have been mostly ignored. We hypothesized that Thiel Embalmed Cadavers could constitute an appropriate model. METHODS: We assessed respiratory mechanics and ITP during CC in 11 cadavers, and we compared it to measurements obtained in 9 out-of-hospital cardiac arrest patients and to predicted values from a bench model. An oesophageal catheter was inserted to assess chest wall compliance, and ITP variation (ΔITP). Airway pressure variation (ΔPaw) at airway opening and ΔITP generated by CC were measured at decremental positive end expiratory pressure (PEEP) to test its impact on flow and ΔPaw. The patient\u27s data were derived from flow and airway pressure captured via the ventilator during resuscitation. RESULTS: Resistance and Compliance of the respiratory system were comparable to those of the out-of-hospital cardiac arrest patients (C 42 ± 12 vs C 37.3 ± 10.9 mL/cmHO and Res 17.5 ± 7.5 vs Res 20.2 ± 5.3 cmHO/L/sec), and remained stable over time. During CC, ΔITP varied from 32 ± 12 cmHO to 69 ± 14 cmHO with manual and automatic CC respectively. Transmission of ΔITP at the airway opening was significantly affected by PEEP, suggesting dynamic small airway closure at low lung volumes. This phenomenon was similarly observed in patients. CONCLUSION: Respiratory mechanics and dynamic pressures during CC of cadavers behave as predicted by a theoretical model and similarly to patients. The Thiel model is a suitable to assess ITP variations induced by ventilation during CC

Strong Morita Equivalence and Imprimitivity Theorems

The purpose of this thesis is to give an exposition of two topics, mostly following the books \cite{R & W} and \cite{Wil}. First, we wish to investigate crossed product $C^*$-algebras in its most general form. Crossed product $C^*$-algebras are $C^*$-algebras which encode information about the action of a locally compact Hausdorff group $G$ as automorphisms on a $C^*$-algebra $A$. One of the prettiest example of such a dynamical system that I have observed in the wild arises in the gauge-invariant uniqueness theorem \cite{Rae}, which assigns to every $C^*$-algebra $C^*(E)$ associated with a graph $E$ a \emph{gauge action} of the unit circle \T to automorphisms on $C^*(E)$. Group $C^*$-algebras also arise as a crossed product of a dynamical system. I found crossed products in its most general form very abstract and much of its constructions motivated by phenomena in a simpler case. Because of this, much of the initial portion of this exposition is dedicated to the action of a discrete group on a unital $C^*$-algebra, where most of the examples are given. I must admit that I find calculations of crossed products when one has an indiscrete group $G$ acting on our $C^*$-algebra daunting except under very simple cases. This leads to our second topic, on imprimitivity theorems of crossed product $C^*$-algebras. Imprimitivity theorems are machines that output (strong) Morita equivalences between crossed products. Morita equivalence is an invariant on $C^*$-algebras which preserve properties like the ideal structure and the associated $K$-groups. For example, no two commutative $C^*$-algebras are Morita equivalent, but $C(X) \otimes M_n$ is Morita equivalent to $C(X)$ whenever $n$ is a positive integer and $X$ is a compact Hausdorff space. Notice that Morita equivalence can be used to prove that a given $C^*$-algebra is simple. All this leads to our concluding application: Takai duality. The set-up is as follows: we have an action $\alpha$ of an abelian group $G$ on a $C^*$-algebra $A$. On the associated crossed product $A \rtimes_\alpha G$, there is a dual action \Hat{\alpha} from the Pontryagin dual \Hat{G}. Takai duality states that the iterated crossed product (A \rtimes_\alpha G) \rtimes \Hat{G} is isomorphic to A \otimes \calK(L^2(G)) in a canonical way. This theorem is used to show for example that all graph $C^*$-algebras are nuclear or to establish theorems on the $K$-theory on crossed product $C^*$-algebras