Evolution of protamine genes and changes in sperm head phenotype in rodents

Little is known about the genetic basis of evolutionary changes in sperm phenotype. Postcopulatory sexual selection is associated with differences in protamine gene sequences and promoters and is a powerful force acting on sperm form and function, although links between protamine evolution and sperm phenotype are scarce. Protamines are involved in sperm chromatin condensation, and protamine deficiency negatively affects sperm morphology and male fertility, thus suggesting that they are important for sperm design and function. We examined changes in protamine genes and sperm phenotype in rodents to understand the role of sexual selection on protamine evolution and sperm design. We performed a genotype-phenotype association study using root-to-tip dN/dS (nonsynonymous/ synonymous substitutions rate ratio) to account for evolutionary rates and phylogenetic generalized least squares analyses to compare genetic and morphometric data. Evolutionary rates of protamine 1 and the protamine 2 domain cleaved off during chromatin condensation correlated with head size and elongation. Protamine 1 exhibited restricted positive selection on some functional sites, which seemed sufficient to preserve its role in head design. The cleaved-protamine 2, whose relaxation is halted by sexual selection, seems to ensure small, elongated heads that would make sperm more competitive. No association existed between mature-protamine 2 and head phenotype, suggesting little involvement during chromatin condensation and a likely role maintaining the condensed state. Our results suggest that evolutionary changes in protamines could be related to complex developmental modifications in the sperm head. This represents an important step toward understanding the role of changes in gene coding sequences in the divergence of germ cell phenotype. © 2014 by the Society for the Study of Reproduction, Inc.Peer Reviewe

Coevolution of positively selected IZUMO1 and CD9 in rodents: Evidence of interaction between gamete fusion proteins?

Proteins involved in sexual reproduction are known to evolve rapidly, often as the result of positive Darwinian selection, although the selective forces driving such adaptive changes are poorly understood. A process of coevolution between proteins in male and female gametes may promote rapid divergence of fertilization proteins. In the mouse, only two proteins have been shown so far to be essential for sperm-egg fusion, IZUMO1 in the sperm cell and CD9 in the egg. The role of these proteins has not been fully elucidated, and it has been suggested that they may act as fusogens, interacting in trans with proteins on the other cell, or regulators of fusogens through cis interactions. Here we analyze the evolution of IZUMO1 and CD9 in a group of rodent species. To assess possible protein interactions between IZUMO1 and CD9, we examined potential coevolution based on analyses of correlated evolutionary rates. We found evidence that both proteins evolve adaptively, with a more intense signal of positive selection in IZUMO1. In addition, our findings suggest that these proteins may have some form of interaction, although they have not been regarded as fusogens interacting directly with each other. The adaptive divergence of IZUMO1 and CD9 could influence reproductive compatibility, and, thus, these proteins may participate in the establishment of specific sperm-egg recognition systems. Further studies are required to uncover the role of IZUMO1 and CD9 during gamete fusion in order to understand the molecular basis of their coevolution, as other selective forces could also lead to general signatures of coevolution. © 2014 by the Society for the Study of Reproduction, Inc.Peer Reviewe

Statics and dynamics of domain patterns in hexagonal-orthorhombic ferroelastics

We study the statics and the dynamics of domain patterns in proper hexagonal-orthorhombic ferroelastics; these patterns are of particular interest because they provide a rare physical realization of disclinations in crystals. Both our static and dynamical theories are based entirely on classical, nonlinear elasticity theory; we use the minimal theory consistent with stability, symmetry and ability to explain qualitatively the observed patterns. After scaling, the only parameters of the static theory are a temperature variable and a stiffness variable. For moderate to large stiffness, our static results show nested stars, unnested stars, fans and other nodes, triangular and trapezoidal regions of trapped hexagonal phase, etc observed in electron microscopy of Ta4N and Mg-Cd alloys, and also in lead orthovanadate (which is trigonal-monoclinic); we even find imperfections in some nodes, like those observed. For small stiffness, we find patterns like those observed in the mineral Mg-cordierite. Our dynamical studies of growth and relaxation show the formation of these static patterns, and also transitory structures such as 12-armed bursts, streamers and striations which are also seen experimentally. The major aspects of the growth-relaxation process are quite unlike those in systems with conventional order parameters, for it is inherently nonlocal; for example, the changes from one snapshot to the next are not predictable by inspection.Comment: 9 pages, 3 figures (1 b&w, 2 colour); animations may be viewed at http://huron.physics.utoronto.ca/~curnoe/sim.htm

Spatial encoding in spinal sensorimotor circuits differs in different wild type mice strains

<p>Abstract</p> <p>Background</p> <p>Previous studies in the rat have shown that the spatial organisation of the receptive fields of nociceptive withdrawal reflex (NWR) system are functionally adapted through experience dependent mechanisms, termed somatosensory imprinting, during postnatal development. Here we wanted to clarify 1) if mice exhibit a similar spatial encoding of sensory input to NWR as previously found in the rat and 2) if mice strains with a poor learning capacity in various behavioural tests, associated with deficient long term potention, also exhibit poor adaptation of NWR.</p> <p>The organisation of the NWR system in two adult wild type mouse strains with normal long term potentiation (LTP) in hippocampus and two adult wild type mouse strains exhibiting deficiencies in corresponding LTP were used and compared to previous results in the rat. Receptive fields of reflexes in single hindlimb muscles were mapped with CO₂laser heat pulses.</p> <p>Results</p> <p>While the spatial organisation of the nociceptive receptive fields in mice with normal LTP were very similar to those in rats, the LTP impaired strains exhibited receptive fields of NWRs with aberrant sensitivity distributions. However, no difference was found in NWR thresholds or onset C-fibre latencies suggesting that the mechanisms determining general reflex sensitivity and somatosensory imprinting are different.</p> <p>Conclusion</p> <p>Our results thus confirm that sensory encoding in mice and rat NWR is similar, provided that mice strains with a good learning capability are studied and raise the possibility that LTP like mechanisms are involved in somatosensory imprinting.</p

Effectiveness of a telephone-based intervention for smoking cessation in patients with severe mental disorders : Study protocol for a randomized controlled trial

Background: Up to 75% of inpatients with mental disorders smoke, and their life expectancy is decreased by up to 25 years compared to the general population. Hospitalized patients without monitoring after discharge quickly return to prehospitalization levels of tobacco use. The aim of the 061 QuitMental study is to assess the effectiveness of a multicomponent and motivational telephone-based intervention to stop smoking through a quitline addressed to smokers discharged from mental health hospital wards. Methods: A pragmatic randomized controlled trial, single blinded, will include 2:1 allocation to the intervention group (IG) and the control group (CG). The IG will receive telephone assistance to quit smoking (including psychological and psychoeducational support, and pharmacological treatment advice if required) proactively for 12 months, and the CG will receive only brief advice after discharge. The sample size, calculated with an expected difference of 15 points on smoking abstinence between groups (IG, 20% and CG, 5%), α = 0.05, β = 0.10, and 20% loss, will be 334 participants (IG) and 176 participants (CG). Participants are adult smokers discharged from psychiatric units of five acute hospitals. Measurements include dependent variables (self-reported 7-day point prevalence smoking abstinence (carbon monoxide verified), duration of abstinence, number of quit attempts, motivation, and self-efficacy to quit) and independent variables (age, sex, and psychiatric diagnoses). In data analysis, IG and CG data will be compared at 48 h and 1, 6, and 12 months post discharge. Multivariate logistic regression (odds ratio; 95% confidence interval) of dependent variables adjusted for potential confounding variables will be performed. The number needed to treat to achieve one abstinence outcome will be calculated. We will compare the abstinence rate of enrolled patients between groups. Discussion: This trial evaluates an innovative format of a quitline for smokers with severe mental disorders regardless of their motivation to quit. If effective, the pragmatic nature of the study will permit transfer to routine clinical practice in the National Health System. Trial registration: ClinicalTrials.gov, NCT03230955. Registered on 24 July 2017

Effectiveness of a telephone-based intervention for smoking cessation in patients with severe mental disorders: study protocol for a randomized controlled trial

Background: up to 75% of inpatients with mental disorders smoke, and their life expectancy is decreased by up to 25 years compared to the general population. Hospitalized patients without monitoring after discharge quickly return to prehospitalization levels of tobacco use. The aim of the 061 QuitMental study is to assess the effectiveness of a multicomponent and motivational telephone-based intervention to stop smoking through a quitline addressed to smokers discharged from mental health hospital wards. Methods: a pragmatic randomized controlled trial, single blinded, will include 2:1 allocation to the intervention group (IG) and the control group (CG). The IG will receive telephone assistance to quit smoking (including psychological and psychoeducational support, and pharmacological treatment advice if required) proactively for 12 months, and the CG will receive only brief advice after discharge. The sample size, calculated with an expected difference of 15 points on smoking abstinence between groups (IG, 20% and CG, 5%), α = 0.05, β = 0.10, and 20% loss, will be 334 participants (IG) and 176 participants (CG). Participants are adult smokers discharged from psychiatric units of five acute hospitals. Measurements include dependent variables (self-reported 7-day point prevalence smoking abstinence (carbon monoxide verified), duration of abstinence, number of quit attempts, motivation, and self-efficacy to quit) and independent variables (age, sex, and psychiatric diagnoses). In data analysis, IG and CG data will be compared at 48 h and 1, 6, and 12 months post discharge. Multivariate logistic regression (odds ratio; 95% confidence interval) of dependent variables adjusted for potential confounding variables will be performed. The number needed to treat to achieve one abstinence outcome will be calculated. We will compare the abstinence rate of enrolled patients between groups. Discussion: this trial evaluates an innovative format of a quitline for smokers with severe mental disorders regardless of their motivation to quit. If effective, the pragmatic nature of the study will permit transfer to routine clinical practice in the National Health System

The loss of a fellow service member: Complicated grief in postâ 9/11 service members and veterans with combatâ related posttraumatic stress disorder

Bereavement is a potent and highly prevalent stressor among service members and veterans. However, the psychological consequences of bereavement, including complicated grief (CG), have been minimally examined. Loss was assessed in 204 postâ 9/11, when service members and veterans with combatâ related posttraumatic stress disorder (PTSD) took part in a multicenter treatment study. Those who reported the loss of an important person completed the inventory of complicated grief (ICG; nâ =â 160). Over three quarters (79.41%) of the sample reported an important lifetime loss, with close to half (47.06%) reporting the loss of a fellow service member (FSM). The prevalence of CG was 24.75% overall, and nearly one third (31.25%) among the bereaved. CG was more prevalent among veterans who lost a fellow service member (FSM) (41.05%, nâ =â 39) compared to those bereaved who did not (16.92%, nâ =â 11; ORâ =â 3.41, 95% CI: 1.59, 7.36). CG was associated with significantly greater PTSD severity, functional impairment, traumaâ related guilt, and lifetime suicide attempts. Complicated grief was prevalent and associated with adverse psychosocial outcomes in veterans and service members with combatâ related PTSD. Clinicians working with this population should inquire about bereavement, including loss of a FSM, and screen for CG. Additional research examining CG in this population is needed.The loss of a fellow service member occurs commonly and is associated with complicated grief (CG) amongst service members and veterans with combatâ related posttraumatic stress disorder (PTSD). The presence of CG in this study was associated with more severe PTSD, guilt, and lifetime suicide attempts, as well as poorer functioning.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139942/1/jnr24094_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139942/2/jnr24094.pd

Contrasting patterns of evolutionary constraint and novelty revealed by comparative sperm proteomic analysis in Lepidoptera

Background: Rapid evolution is a hallmark of reproductive genetic systems and arises through the combined processes of sequence divergence, gene gain and loss, and changes in gene and protein expression. While studies aiming to disentangle the molecular ramifications of these processes are progressing, we still know little about the genetic basis of evolutionary transitions in reproductive systems. Here we conduct the first comparative analysis of sperm proteomes in Lepidoptera, a group that exhibits dichotomous spermatogenesis, in which males produce a functional fertilization-competent sperm (eupyrene) and an incompetent sperm morph lacking nuclear DNA (apyrene). Through the integrated application of evolutionary proteomics and genomics, we characterize the genomic patterns potentially associated with the origination and evolution of this unique spermatogenic process and assess the importance of genetic novelty in Lepidopteran sperm biology. Results: Comparison of the newly characterized Monarch butterfly (Danaus plexippus) sperm proteome to those of the Carolina sphinx moth (Manduca sexta) and the fruit fly (Drosophila melanogaster) demonstrated conservation at the level of protein abundance and post-translational modification within Lepidoptera. In contrast, comparative genomic analyses across insects reveals significant divergence at two levels that differentiate the genetic architecture of sperm in Lepidoptera from other insects. First, a significant reduction in orthology among Monarch sperm genes relative to the remainder of the genome in non-Lepidopteran insect species was observed. Second, a substantial number of sperm proteins were found to be specific to Lepidoptera, in that they lack detectable homology to the genomes of more distantly related insects. Lastly, the functional importance of Lepidoptera specific sperm proteins is broadly supported by their increased abundance relative to proteins conserved across insects. Conclusions: Our results identify a burst of genetic novelty amongst sperm proteins that may be associated with the origin of heteromorphic spermatogenesis in ancestral Lepidoptera and/or the subsequent evolution of this system. This pattern of genomic diversification is distinct from the remainder of the genome and thus suggests that this transition has had a marked impact on lepidopteran genome evolution. The identification of abundant sperm proteins unique to Lepidoptera, including proteins distinct between specific lineages, will accelerate future functional studies aiming to understand the developmental origin of dichotomous spermatogenesis and the functional diversification of the fertilization incompetent apyrene sperm morph