Triply Threaded [4]Rotaxanes

[4]Rotaxanes featuring three axles threaded through a single ring have been prepared through active metal template synthesis. Nickel-catalyzed sp3-sp3 homocouplings of alkyl bromide ‘half threads’ through 37- and 38-membered 2,2':6',2"-terpyridyl macrocycles generates triply-threaded [4]rotaxanes in up to 11 % yield. An analogous 39-membered macrocycle produced no rotaxane products under similar conditions. The constitutions of the [4]rotaxanes were determined by NMR spectroscopy and mass spectrometry. Doubly-threaded [3]rotaxanes were also obtained from the reactions but no [2]rotaxanes were isolated, suggesting that upon demetallation the axle of a singly-threaded rotaxane can slip through a macrocycle that is sufficiently large to accommodate three threads

The era of cryptic exons: implications for ALS-FTD

TDP-43 is an RNA-binding protein with a crucial nuclear role in splicing, and mislocalises from the nucleus to the cytoplasm in a range of neurodegenerative disorders. TDP-43 proteinopathy spans a spectrum of incurable, heterogeneous, and increasingly prevalent neurodegenerative diseases, including the amyotrophic lateral sclerosis and frontotemporal dementia disease spectrum and a significant fraction of Alzheimer's disease. There are currently no directed disease-modifying therapies for TDP-43 proteinopathies, and no way to distinguish who is affected before death. It is now clear that TDP-43 proteinopathy leads to a number of molecular changes, including the de-repression and inclusion of cryptic exons. Importantly, some of these cryptic exons lead to the loss of crucial neuronal proteins and have been shown to be key pathogenic players in disease pathogenesis (e.g., STMN2), as well as being able to modify disease progression (e.g., UNC13A). Thus, these aberrant splicing events make promising novel therapeutic targets to restore functional gene expression. Moreover, presence of these cryptic exons is highly specific to patients and areas of the brain affected by TDP-43 proteinopathy, offering the potential to develop biomarkers for early detection and stratification of patients. In summary, the discovery of cryptic exons gives hope for novel diagnostics and therapeutics on the horizon for TDP-43 proteinopathies

Minoritized Scientists in the United States: An Identity Perspective to Science Communication

This study investigates how tenure-track faculty from historically marginalized groups in the environmental sciences approach science communication based on their self-identities. A thematic analysis of 28 in-depth interviews with U.S.-based participants using the Communication Theory of Identity and Border-Crossing Theory was conducted to explore the interrelation of layers of identity, the identity gaps participants experience, and their communication practices. The results show that communication merges fragments of identity not to form a fixed identity, but to create an evolving consciousness about who you are and how you communicate. Implications for science communication training are discussed

Variation in Sex Allocation and Floral Morphology in an Expanding Distylous Plant Hybrid Complex

Premise of research. Sex allocation, the relative energy devoted to producing pollen, ovules, and floral displays, can significantly affect reproductive output and population dynamics. In this study, we investigated floral morphology and gamete production in bisexual, distylous plants from a self-incompatible hybrid complex (Piriqueta cistoides ssp. caroliniana Walter [Arbo]; Turneraceae). Sampling focused on two parent types (C, V) and their stable hybrid derivative (H). Since H morphotypes are heterotic for growth and fruit production, we hypothesized that they would produce larger flowers with more gametes. We also anticipated that plants with long styles (long morphs) would produce less pollen than short morphs, since long-morph pollen is larger. Methodology. Over two consecutive summers, flowers were collected from 1465 individual plants in 28 field populations. Floral parameters were measured digitally, and each flower’s pollen number, ovule number, and stigma-anther separation was quantified under a dissecting microscope. Gamete production (n = 332) and stigma-anther separation (n = 119) were also quantified for plants from a greenhouse accession. Pivotal results. Floral display differed among morphotypes, with H plants producing the largest flowers and C plants displaying the least petal separation. Hybrid morphotypes produced significantly more pollen than parental morphotypes, and pollen quantity was significantly greater for long morphs. Ovule production, however, was greatest for V flowers. Stigma-anther separation differed between years and style morphs (greater for short morphs) but not among morphotypes or within a single season. Conclusions. Differences in pollen production between morphs were not consistent with trade-offs in pollen size and number or selection for increased male function in short morphs. Greater stigma-anther separation in short morphs supported the hypothesis of selection to reduce pollen interference. Enhanced floral display and pollen production followed other heterotic traits observed in H morphotypes. The superior ability of H morphotypes to attract pollinators and sire seeds might partially explain this hybrid zone’s continuing expansion

Estimating the rate of intersubtype recombination in early HIV-1 group M strains

West Central Africa has been implicated as the epicenter of the HIV-1 epidemic, and almost all group M subtypes can be found there. Previous analysis of early HIV-1 group M sequences from Kinshasa in the Democratic Republic of Congo, formerly Zaire, revealed that isolates from a number of individuals fall in different positions in phylogenetic trees constructed from sequences from opposite ends of the genome as a result of recombination between viruses of different subtypes. Here, we use discrete ancestral trait mapping to develop a procedure for quantifying HIV-1 group M intersubtype recombination across phylogenies, using individuals' gag (p17) and env (gp41) subtypes. The method was applied to previously described HIV-1 group M sequences from samples obtained in Kinshasa early in the global radiation of HIV. Nine different p17 and gp41 intersubtype recombinant combinations were present in the data set. The mean number of excess ancestral subtype transitions (NEST) required to map individuals' p17 subtypes onto the gp14 phylogeny samples, compared to the number required to map them onto the p17 phylogenies, and vice versa, indicated that excess subtype transitions occurred at a rate of approximately 7 × 10(−3) to 8 × 10(−3) per lineage per year as a result of intersubtype recombination. Our results imply that intersubtype recombination may have occurred in approximately 20% of lineages evolving over a period of 30 years and confirm intersubtype recombination as a substantial force in generating HIV-1 group M diversity

Racial/ethnic disparities in annual mammogram compliance among households in Little Haiti, Miami-Dade County, Florida

Abstract Introduction Breast cancer is the most commonly diagnosed cancer and the 2nd leading cause of cancer-related deaths among women in the U.S. Although routine screening via mammogram has been shown to increase survival through early detection and treatment of breast cancer, only 3 out of 5 women age ?40 are compliant with annual mammogram within the U.S. and the state of Florida. A breadth of literature exists on racial/ethnic disparities in compliance with mammogram; however, few such studies include data on individual Black subgroups, such as Haitians. This study assessed the association between race/ethnicity and annual mammogram compliance among randomly selected households residing in the largely Haitian community of Little Haiti, Miami-Dade County (MDC), Florida. Methods This study used cross-sectional, health data from a random-sample, population-based survey conducted within households residing in Little Haiti between November 2011 and December 2012 (n = 951). Mammogram compliance was defined as completion of mammogram by all female household members within the 12 months prior to the survey. The association between mammogram compliance and race/ethnicity was assessed using binary logistic regression models. Potential confounders were identified as factors that were conservatively associated with both compliance and race/ethnicity (P???0.20). Analyses were restricted to households containing at least 1 female member age ?40 (n = 697). Results Overall compliance with annual mammogram was 62%. Race/ethnicity was significantly associated with mammogram compliance (P = 0.030). Compliance was highest among non-Hispanic Black (NHB) households (75%), followed by Hispanic (62%), Haitian (59%), and non-Hispanic White (NHW) households (51%). After controlling for educational level, marital status, employment status, the presence of young children within the household, health insurance status, and regular doctor visits, a borderline significant disparity in mammogram compliance was observed between Haitian and NHB households (adjusted odds ratio = 1.63, P = 0.11). No other racial/ethnic disparities were observed. Discussion Compliance with annual mammogram was low among the surveyed households in Little Haiti. Haitian households underutilized screening by means of annual mammogram compared with NHB households, although this disparity was not significant. Compliance rates could be enhanced by conducting individualized, mammogram screening-based studies to identify the reasons behind low rate of compliance among households in this underserved, minority population

Vru (Sub0144) controls expression of proven and putative virulence determinants and alters the ability of Streptococcus uberis to cause disease in dairy cattle

The regulation and control of gene expression in response to differing environmental stimuli is crucial for successful pathogen adaptation and persistence. The regulatory gene vru of Streptococcus uberis encodes a stand-alone response regulator with similarity to the Mga of group A Streptococcus. Mga controls expression of a number of important virulence determinants. Experimental intramammary challenge of dairy cattle with a mutant of S. uberis carrying an inactivating lesion in vru showed reduced ability to colonize the mammary gland and an inability to induce clinical signs of mastitis compared with the wild-type strain. Analysis of transcriptional differences of gene expression in the mutant, determined by microarray analysis, identified a number of coding sequences with altered expression in the absence of Vru. These consisted of known and putative virulence determinants, including Lbp (Sub0145), SclB (Sub1095), PauA (Sub1785) and hasA (Sub1696)

Inulin oligofructose attenuates metabolic syndrome in high-carbohydrate, high-fat diet-fed rats

Prebiotics alter bacterial content in the colon, and therefore could be useful for obesity management. We investigated the changes following addition of inulin oligofructose (IO) in the food of rats fed either a corn starch (C) diet or a high-carbohydrate, high-fat (H) diet as a model of diet-induced metabolic syndrome. IO did not affect food intake, but reduced body weight gain by 5·3 and 12·3 % in corn starch+inulin oligofructose (CIO) and high-carbohydrate, high-fat with inulin oligofructose (HIO) rats, respectively. IO reduced plasma concentrations of free fatty acids by 26·2 % and TAG by 75·8 % in HIO rats. IO increased faecal output by 93·2 %, faecal lipid excretion by 37·9 % and weight of caecum by 23·4 % and colon by 41·5 % in HIO rats. IO improved ileal morphology by reducing inflammation and improving the density of crypt cells in HIO rats. IO attenuated H diet-induced increases in abdominal fat pads (C 275 (sem 19), CIO 264 (sem 40), H 688 (sem 55), HIO 419 (sem 32) mg/mm tibial length), fasting blood glucose concentrations (C 4·5 (sem 0·1), CIO 4·2 (sem 0·1), H 5·2 (sem 0·1), HIO 4·3 (sem 0·1) mmol/l), systolic blood pressure (C 124 (sem 2), CIO 118 (sem 2), H 152 (sem 2), HIO 123 (sem 3) mmHg), left ventricular diastolic stiffness (C 22·9 (sem 0·6), CIO 22·9 (sem 0·5), H 27·8 (sem 0·5), HIO 22·6 (sem 1·2)) and plasma alanine transaminase (C 29·6 (sem 2·8), CIO 32·1 (sem 3·0), H 43·9 (sem 2·6), HIO 33·6 (sem 2·0) U/l). IO attenuated H-induced increases in inflammatory cell infiltration in the heart and liver, lipid droplets in the liver and plasma lipids as well as impaired glucose and insulin tolerance. These results suggest that increasing soluble fibre intake with IO improves signs of the metabolic syndrome by decreasing gastrointestinal carbohydrate and lipid uptake