Funding Resilient Infrastructure in New Jersey: Attitudes Following a Natural Disaster

Recent major natural disasters in New Jersey have demonstrated the need to increase the resilience of transportation infrastructure. This research examines public attitudes toward revenue sources that can be dedicated to protecting vulnerable areas, most notably the transportation linkages on which the state depends. A statewide survey was conducted to gather data approximately four months following Superstorm Sandy, the costliest natural disaster in the state’s history. The authors’ objective was to sample public attitudes while the impacts of the disaster were still fresh. They found little support for temporary tax increases to improve resiliency, with the most positive support for taxing visitors (i.e., a hotel and recreational tax) and for a 30-year bond measure (i.e., taxing the future). This observation seemingly contradicts broad support for investing in new infrastructure, as well as maintaining and protecting existing infrastructure. Multivariate analysis to understand the underlying attitudes toward raising revenue found that more left-leaning or communitarian attitudes are associated with more support for gasoline, income, or sales taxes devoted to mitigating vulnerability. Those who supported investment in transit and protecting infrastructure also were more likely to support these taxes. There was no parallel finding of factors associated with taxing visitors or issuing bonds

Conformational distributions of isolated myosin motor domains encode their mechanochemical properties

Myosin motor domains perform an extraordinary diversity of biological functions despite sharing a common mechanochemical cycle. Motors are adapted to their function, in part, by tuning the thermodynamics and kinetics of steps in this cycle. However, it remains unclear how sequence encodes these differences, since biochemically distinct motors often have nearly indistinguishable crystal structures. We hypothesized that sequences produce distinct biochemical phenotypes by modulating the relative probabilities of an ensemble of conformations primed for different functional roles. To test this hypothesis, we modeled the distribution of conformations for 12 myosin motor domains by building Markov state models (MSMs) from an unprecedented two milliseconds of all-atom, explicit-solvent molecular dynamics simulations. Comparing motors reveals shifts in the balance between nucleotide-favorable and nucleotide-unfavorable P-loop conformations that predict experimentally measured duty ratios and ADP release rates better than sequence or individual structures. This result demonstrates the power of an ensemble perspective for interrogating sequence-function relationships

Genital Pain and Numbness and Female Sexual Dysfunction in Adult Bicyclists.

IntroductionBicycle seat pressure on the perineum may impair arousal and clitoral erection, likely contributing to genital pain and numbness experienced by female cyclists.AimWe aimed to identify the association between genital pain and numbness experienced by female cyclists and female sexual dysfunction (FSD).MethodsFemale cyclists were recruited to complete an online survey using the Female Sexual Function Index (FSFI), a validated questionnaire to assess FSD. Cyclist demographics, experience, preferred riding style, use of ergonomic cycle modifications, and genital discomfort while riding were also queried. Multivariate logistic regression analysis was used to evaluate risk factors of FSD.Main outcome measuresThe main outcome was FSFI score, which is used to diagnose FSD when the FSFI score is <26.55.ResultsOf the survey respondents, 178 (53.1%) completed the survey and FSFI questionnaire. Mean age was 48.1 years (±0.8 standard error [SE]), and the average riding experience was 17.1 years (±0.9 SE). Overall, 53.9% of female cyclists had FSD, 58.1% reported genital numbness, and 69.1% reported genital pain. After adjusting for age, body mass index, relationship status, smoking history, comorbidities, and average time spent cycling per week, females who reported experiencing genital numbness half the time or more were more likely to have FSD (adjusted odds ratio [aOR], 6.0; 95% CI, 1.5-23.6; P = .01), especially if localized to the clitoris (aOR, 2.5; 95% CI, 1.2-5.5; P = .02). Females that reported genital pain half the time or more while cycling also were more likely to have FSD (aOR, 3.6; 95% CI, 1.2-11.1; P = .02). Cyclists experiencing genital pain within the first hour of their ride were more likely to have FSD (aOR, 12.6; 95% CI, 2.5-63.1; P = .002). Frequency and duration of cycling were not associated with FSD. Analysis of FSFI domains found that the frequency of numbness was correlated with decreased arousal, orgasm, and satisfaction during intercourse, whereas the frequency of pain significantly reduced arousal, orgasm, and genital lubrication.Clinical implicationsFemale cyclists that experience numbness and/or pain have higher odds of reporting FSD.Strengths & limitationsOur study includes a validated questionnaire to assess FSD and queries specific characteristics and symptoms of genital pain and genital numbness; however, the study is limited by its cross-sectional survey design.ConclusionThis study highlights the need for cyclists to address genital pain and numbness experienced while cycling, and future studies are required to determine if alleviating these symptoms can reduce the impact of cycling on female sexual function. Greenberg GR, Khandwala YS, Breyer BN, et al. Genital Pain and Numbness and Female Sexual Dysfunction in Adult Bicyclists. J Sex Med 2019; 16:1381-1389

Mechanical dysfunction of the sarcomere induced by a pathogenic mutation in troponin T drives cellular adaptation

Familial hypertrophic cardiomyopathy (HCM), a leading cause of sudden cardiac death, is primarily caused by mutations in sarcomeric proteins. The pathogenesis of HCM is complex, with functional changes that span scales, from molecules to tissues. This makes it challenging to deconvolve the biophysical molecular defect that drives the disease pathogenesis from downstream changes in cellular function. In this study, we examine an HCM mutation in troponin T, R92Q, for which several models explaining its effects in disease have been put forward. We demonstrate that the primary molecular insult driving disease pathogenesis is mutation-induced alterations in tropomyosin positioning, which causes increased molecular and cellular force generation during calcium-based activation. Computational modeling shows that the increased cellular force is consistent with the molecular mechanism. These changes in cellular contractility cause downstream alterations in gene expression, calcium handling, and electrophysiology. Taken together, our results demonstrate that molecularly driven changes in mechanical tension drive the early disease pathogenesis of familial HCM, leading to activation of adaptive mechanobiological signaling pathways