Alteration of neuromuscular function in squash

The alteration in neuromuscular function of knee extensor muscles was characterised after a squash match in 10 trained players. Maximal voluntary contraction (MVC) and surface EMG activity of vastus lateralis (VL) and vastus medialis (VM) muscles were measured before and immediately after a 1-h squash match. M-wave and twitch contractile properties were analysed following single stimuli. MVC declined (280.5 ± 46.8 vs. 233.6 ± 35.4 N m, ?16%; P < 0.001) after the exercise and this was accompanied by an impairment of central activation, as attested by decline in voluntary activation (76.7 ± 10.4 vs. 71.3 ± 9.6%, ?7%; P < 0.05) and raw EMG activity of the two vastii (?17%; P < 0.05), whereas RMS/M decrease was lesser (VL: ?5%; NS and VM: ?12%; P = 0.10). In the fatigued state, no significant changes in M-wave amplitude (VL: ?9%; VM: ?5%) or duration were observed. Following exercise, the single twitch was characterised by lower peak torque (?20%; P < 0.001) as well as shorter half-relaxation time (?13%; P < 0.001) and reduced maximal rate of twitch tension development (?23%; P < 0.001) and relaxation (?17%; P < 0.05). A 1-h squash match play caused peripheral fatigue by impairing excitation–contraction coupling, whereas sarcolemmal excitability seems well preserved. Our results also emphasise the role of central activation failure as a possible mechanism contributing to the torque loss observed in knee extensors. Physical conditioners should consider these effects when defining their training programs for squash players.     

Cadmium Alters the Biotransformation of Carcinogenic Aromatic Amines by Arylamine N-Acetyltransferase Xenobiotic-Metabolizing Enzymes: Molecular,Cellular, and in Vivo Studies

Background

Cadmium (Cd) is a carcinogenic heavy metal of environmental concern. Exposure to both Cd and carcinogenic organic compounds, such as polycyclic aromatic hydrocarbons or aromatic amines (AAs), is a common environmental problem. Human arylamine N-acetyltransferases (NATs) are xenobiotic-metabolizing enzymes that play a key role in the biotransformation of AA carcinogens. Changes in NAT activity have long been associated with variations in susceptibility to different cancers in relation with exposure to certain AAs.

Objective

We explored the possible interactions between Cd and the NAT-dependent biotransformation of carcinogenic AAs.

Methods

We exposed purified enzymes, lung epithelial cells, and mouse models to Cd and subsequently analyzed NAT-dependent metabolism of AAs.

Results

We found that Cd, at biologically relevant concentrations, impairs the NAT-dependent acetylation of carcinogenic AAs such as 2-aminofluorene (2-AF) in lung epithelial cells. NAT activity was strongly impaired in the tissues of mice exposed to Cd. Accordingly, mice exposed to Cd and 2-AF displayed altered in vivo toxicokinetics with a significant decrease (~ 50%) in acetylated 2-AF in plasma. We found that human NAT1 was rapidly and irreversibly inhibited by Cd [median inhibitory concentration (IC₅₀) ≈ 55 nM; rate inhibition constant (k_inact) = 5 × 10⁴ M⁻¹ · sec⁻¹], with results of acetyl coenzyme A (acetyl-CoA) protection assays indicating that Cd-mediated inhibition was due to the reaction of metal with the active-site cysteine residue of the enzyme. We found similar results for human NAT2, although this isoform was less sensitive to inactivation (IC₅₀ ≈ 1 μM; k_inact = 1 × 10⁴ M⁻¹ · sec⁻¹).

Conclusions

Our data suggest that Cd can alter the metabolism of carcinogenic AAs through the impairment of the NAT-dependent pathway, which may have important toxicological consequences.     

Influence of sildenafil on micturition and urethral tone in ovariectomized and non-ovariectomized mice

IntroductionNitric oxide synthases (NOSs) and estrogen receptors are expressed in the female urethra.AimWe aimed to assess the impact of sildenafil on micturition behavior, urethral tone according to the hormonal status and to determine the implications of the neuronal isoform of NOS (nNOS).MethodsFour‐week‐old C57/BL6 female mice were sham‐operated or ovariectomized. Six weeks later, they were injected intraperitoneally by any combination of sildenafil, 7‐nitroindazole (7‐NI)—a potent selective nNOS inhibitor—or the corresponding vehicles. The mice were then subjected to micturition behavior and leak point pressure studies. Urethral histomorphometry was performed.Main Outcome MeasuresThe main outcome measures were micturition behavior, leak point pressure, and histomorphometry.ResultsIn sham‐operated and ovariectomized animals, sildenafil did not impact micturition, although it decreased urethral resistance 10‐fold. nNOS inhibition by 7‐NI reduced the number of micturitions and increased residual volume and leak point pressure. It abrogated sildenafil‐induced drop in urethral resistances. Hormonal status did not influence the structure of the urethral layers.Conclusions.Irrespective of the hormonal status, sildenafil decreased leak point pressure by a nNOS‐mediated mechanism. Gamé X, Bouali O, Allard J, Gourdy P, Escourrou G, Tack I, Rischmann P, Arnal J‐F, and Malavaud B. Influence of sildenafil on micturition and urethral tone in ovariectomized and non‐ovariectomized mice. J Sex Med 2012;9:466–471.     

Performance Analysis of a High-Order Discontinuous Galerkin Method Application to the Reverse Time Migration

This work pertains to numerical aspects of a finite element method based discontinuous functions. Our study focuses on the Interior Penalty Discontinuous Galerkin method (IPDGM) because of its high-level of flexibility for solving the full wave equation in heterogeneous media. We assess the performance of IPDGM through a comparison study with a spectral element method (SEM). We show that IPDGM is as accurate as SEM. In addition, we illustrate the efficiency of IPDGM when employed in a seismic imaging process by considering two-dimensional problems involving the Reverse Time Migration.     

Renal failure in pediatric Castleman disease: Four French cases with thrombotic microangiopathy

Pediatric Castleman disease (CD) is an uncommon and poorly understood disorder of the lymph nodes. Renal failure has not been described in pediatric multicentric CD (MCD). We report four cases, who presented with polyadenopathy, organomegaly, edema and fluid accumulations, high blood pressure, and acute renal failure. In all cases, renal biopsy confirmed diffuse thrombotic microangiopathy. Definitive diagnosis of MCD was made by a biopsy of an affected lymph node located by computer tomography before initiation of corticosteroid therapy. Treatment of CD with corticosteroid therapy and rituximab was rapidly effective without relapse to date.     

Ancestral polymorphisms shape the adaptive radiation of Metrosideros across the Hawaiian Islands

Some of the most spectacular adaptive radiations begin with founder populations on remote islands. How genetically limited founder populations give rise to the striking phenotypic and ecological diversity characteristic of adaptive radiations is a paradox of evolutionary biology. We conducted an evolutionary genomics analysis of genus Metrosideros, a landscape-dominant, incipient adaptive radiation of woody plants that spans a striking range of phenotypes and environments across the Hawaiian Islands. Using nanopore-sequencing, we created a chromosome-level genome assembly for Metrosideros polymorpha var. incana and analyzed whole-genome sequences of 131 individuals from 11 taxa sampled across the islands. Demographic modeling and population genomics analyses suggested that Hawaiian Metrosideros originated from a single colonization event and subsequently spread across the archipelago following the formation of new islands. The evolutionary history of Hawaiian Metrosideros shows evidence of extensive reticulation associated with significant sharing of ancestral variation between taxa and secondarily with admixture. Taking advantage of the highly contiguous genome assembly, we investigated the genomic architecture underlying the adaptive radiation and discovered that divergent selection drove the formation of differentiation outliers in paired taxa representing early stages of speciation/divergence. Analysis of the evolutionary origins of the outlier single nucleotide polymorphisms (SNPs) showed enrichment for ancestral variations under divergent selection. Our findings suggest that Hawaiian Metrosideros possesses an unexpectedly rich pool of ancestral genetic variation, and the reassortment of these variations has fueled the island adaptive radiation.

Adaptive radiations exhibit extraordinary levels of morphological and ecological diversity (1). Although definitions of adaptive radiation vary (2–7), all center on ecological opportunity as a driver of adaptation and, ultimately, diversification (2, 8–10). Divergent selection, the primary mechanism underlying adaptive radiations, favors extreme phenotypes (11) and selects alleles that confer adaptation to unoccupied or under-utilized ecological niches. Differential adaptation results in divergence and, ultimately, reproductive isolation between populations (12). Adaptive radiations demonstrate the remarkable power of natural selection as a driver of biological diversity and provide excellent systems for studying evolutionary processes involved in diversification and speciation (13).Adaptive radiations on remote oceanic islands are especially interesting, as colonization of remote islands is expected to involve population bottlenecks that restrict genetic variation (14). Adaptive radiations in such settings are especially impressive and even paradoxical, given the generation of high species richness from an initially limited gene pool (15). Several classic examples of adaptive radiation occur on oceanic islands, such as Darwin’s finches from the Galapagos islands (16), anole lizards from the Caribbean islands (9), Hawaiian Drosophilids (17), and Hawaiian silverswords (18), to name a few.Recent advances in genome sequencing and analyses have greatly improved our ability to examine the genetics of speciation and adaptive radiation. By examining sequences of multiple individuals from their natural environment, it has become possible to “catch in the act” the speciation processes between incipient lineages (19). Genomic studies of early stage speciation show that differentiation accumulates in genomic regions that restrict the homogenizing effects of gene flow between incipient species (20). The number, size, and distribution of these genomic regions can shed light on evolutionary factors involved in speciation (19). Regions of high genomic differentiation can also form from evolutionary factors unrelated to speciation, such as linkage associated with recurrent background selection or selective sweeps on shared genomic features (21, 22).Genomic studies of lineages undergoing rapid ecological diversification have begun to reveal the evolutionary mechanisms underlying adaptive radiations. Importantly, these studies highlight the pivotal role of hybridization between populations and the consequent exchange of adaptive alleles that facilitates rapid speciation and the colonization of diverse niches (23–25). Most genomic studies of adaptive radiation involve animal systems, however, in particular, birds and fishes. In plants, genomic studies of adaptive radiation are sparse (26–28), and all examine continent-wide radiations. There are no genomics studies of plant adaptive radiations in geographically restricted systems such as remote islands. Because the eco-evolutionary scenarios associated with adaptive radiations are diverse (5, 29), whether commonalities identified in adaptive radiations in animals (23, 30) are applicable to plants is an open question. For example, the genetic architecture of animal adaptive radiations typically involves differentiation at a small number of genomic regions (31–33). In contrast, the limited insights available for plants suggest a more complex genetic architecture (26).We investigated the evolutionary genomics of adaptive radiation in Metrosideros Banks ex Gaertn. (Myrtaceae) across the Hawaiian Islands. Hawaiian Metrosideros is a landscape-dominant, hypervariable, and highly dispersible group of long-lived (possibly >650 y) (34) woody taxa that are nonrandomly distributed across Hawaii’s heterogeneous landscape, including cooled lava flows, wet forests and bogs, subalpine zones, and riparian zones (35, 36). About 25 taxa or morphotypes are distinguished by vegetative characters ranging from prostate plants that flower a few centimeters above ground to 30-m-tall trees, and leaves range dramatically in size, shape, pubescence, color, and rugosity (35, 37, 38); a majority of these forms are intraspecific varieties or races (provisional varieties) of the abundant species, Metrosideros polymorpha (35, 36, 38). Variation in leaf mass per area within the four Metrosideros taxa on Hawaii Island alone matches that observed for woody species globally (39). Common garden experiments (38, 40–44) and parent–offspring analysis (45) demonstrate heritability of taxon-diagnostic vegetative traits, indicating that taxa are distinct genetic groups and not the result of phenotypic plasticity. Metrosideros taxa display evidence of local adaptation to contrasting environments (46, 47), suggesting ecological divergent selection is responsible for diversification within the group (48). This diversification, which spans the past ∼3.1 to 3.9 million years (49, 50), has occurred despite the group’s high capacity for gene flow by way of showy bird-pollinated flowers and tiny wind-dispersed seeds (36, 51). Lastly, the presence of partial reproductive isolating barriers between taxa is consistent with the early stages of speciation (52). Here, we generated several genomic resources for Hawaiian Metrosideros and used these in population genomics analyses to gain deeper insights into the genomic architecture and evolutionary processes underlying this island adaptive radiation.     

Correlations between corneal hysteresis, intraocular pressure, and corneal central pachymetry

PURPOSE: To analyze the correlation between corneal hysteresis (CH) measured with the Ocular Response Analyzer (ORA, Reichert) and ultrasonic corneal central thickness (CCT US) and intraocular pressure measured with Goldmann applanation tonometry (IOP GA). SETTING: Bordeaux 2 University, Ophthalmology Department, Bordeaux, France. METHODS: This study comprised 498 eyes of 258 patients. Corneal hysteresis, corneal resistance factor (CRF), and IOP corneal-compensated (IOPcc) were provided by the ORA device; CCT US and IOP GA were also measured in each eye. The study population was divided into 5 groups: normal (n = 122), glaucoma (n = 159), keratoconus (n = 88), laser in situ keratomileusis (LASIK) (n = 78), and photorefractive keratectomy (n = 39). The Pearson correlation was used for statistical analysis. RESULTS: Corneal hysteresis was not strongly correlated with IOP or CCT US. The mean CH in the LASIK (8.87 mm Hg) and keratoconus (8.34 mm Hg) groups was lower than in the glaucoma (9.48 mm Hg) and normal (10.26 mm Hg) groups. The lower the CH, the lower its correlation with IOPcc and IOP GA. A CH higher than the CRF was significantly associated with the keratoconus and post-LASIK groups. CONCLUSIONS: Corneal hysteresis, a new corneal parameter, had a moderate dependence on IOP and CCT US. Weaker corneas could be screened with ORA parameters, and low CH could be considered a risk factor for underestimation of IOP. The CCT US should continue to be considered a useful parameter.