Failed Species, Innominate Forms, and the Vain Search for Species Limits: Cryptic Diversity in Dusky Salamanders (\u3ci\u3eDesmognathus\u3c/i\u3e) of Eastern Tennessee

Cytochrome B sequences and allozymes reveal complex patterns of molecular variation in dusky salamander (Desmognathus) populations in eastern Tennessee. One group of allozymically distinctive populations, which we refer to as the Sinking Creek form (SCF), combines morphological attributes of Desmognathus fuscus with cytB sequences characteristic of Desmognathus carolinensis. This form is abruptly replaced by D. fuscus just north of Johnson City, TN with no evidence of either sympatry or gene exchange. To the south, allozymic markers indicate a broad zone of admixture with populations characterized by distinct cytB sequences and that may or may not be ultimately referable to Desmognathus conanti. A third distinctive group of populations, which we refer to as the Lemon Gap form (LGF), occurs in the foothills of the Great Smoky and southern Bald Mountains and exchanges genes with Desmognathus santeetlah along the escarpment of the Great Smokies, D. carolinensis in the southern Bald Mountains, and populations of a different haplotype clade in the Ridge and Valley. We treat all these as innominate forms that may represent failed species, recognizing that it may never be possible to reconcile species limits with patterns of phylogeny, morphology, and gene exchange in these salamanders. © 2013 The Authors

Lost Branches on the Tree of Life

Failure to archive published data can impede reproducibility and inhibit downstream synthesis. Alarmingly, we estimate that ∼70% of existing DNA sequence alignments/phylogenetic trees, representing much of the underpinning of modern phylogenetic analysis, are no longer accessible. The evolutionary biology community needs to adopt policies ensuring that data are publicly archived upon publication

Urinary Tract Stones and Osteoporosis: Findings From the Women's Health Initiative

Kidney and bladder stones (urinary tract stones) and osteoporosis are prevalent, serious conditions for postmenopausal women. Men with kidney stones are at increased risk of osteoporosis; however, the relationship of urinary tract stones to osteoporosis in postmenopausal women has not been established. The purpose of this study was to determine whether urinary tract stones are an independent risk factor for changes in bone mineral density (BMD) and incident fractures in women in the Women's Health Initiative (WHI). Data were obtained from 150,689 women in the Observational Study and Clinical Trials of the WHI with information on urinary tract stones status: 9856 of these women reported urinary tract stones at baseline and/or incident urinary tract stones during follow‐up. Cox regression models were used to determine the association of urinary tract stones with incident fractures and linear mixed models were used to investigate the relationship of urinary tract stones with changes in BMD that occurred during WHI. Follow‐up was over an average of 8 years. Models were adjusted for demographic and clinical factors, medication use, and dietary histories. In unadjusted models there was a significant association of urinary tract stones with incident total fractures (HR 1.10; 95% CI, 1.04 to 1.17). However, in covariate adjusted analyses, urinary tract stones were not significantly related to changes in BMD at any skeletal site or to incident fractures. In conclusion, urinary tract stones in postmenopausal women are not an independent risk factor for osteoporosis. © 2015 American Society for Bone and Mineral Research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/115895/1/jbmr2553.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/115895/2/jbmr2553_am.pd

Dietary Patterns and Fractures in Postmenopausal Women: Results From the Women\u27s Health Initiative

IMPORTANCE: Considerable efforts have been undertaken to relate single nutrients to bone health. To this point, results are inconsistent. Suboptimal single nutrient intake does not occur in isolation but rather reflects a poor diet quality. OBJECTIVE: To assess the association between adherence to a diet quality index constructed on the basis of dietary recommendations or existing healthy dietary patterns and fractures in postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: Post hoc analysis was conducted of longitudinal data from 40 clinical centers throughout the United States included in the Women\u27s Health Initiative (WHI) observational study. Participants in the prospective cohort included 93676 women who were eligible for the WHI if they were aged 50 to 79 years. Recruitment was conducted from October 1, 1993, to December 31, 1998, with the study ending August 29, 2014. The WHI food frequency questionnaire was used to derive nutrient and food intake at baseline. Diet quality and adherence were assessed by scores on the alternate Mediterranean Diet (aMED), a 9-category measure of adherence to a Mediterranean dietary pattern; the Healthy Eating Index 2010 (HEI-2010), a 100-point measure of 12 food components; the 11-item Alternate Healthy Eating Index 2010 (AHEI-2010); or the 8-component Dietary Approaches to Stop Hypertension (DASH) diet score. MAIN OUTCOMES AND MEASURES: Outcome measures included incident total and hip fractures. Hazard ratios (HRs) by quintiles of dietary index scores were estimated using Cox proportional hazards regression analyses. RESULTS: Of the 93676 participants, 90014 were included in the analysis (mean [SD] age, 63.6 [7.4]) years. During a median follow-up time of 15.9 years, there were 2121 cases of hip fractures and 28718 cases of total fractures. Women scoring in the highest quintile (Q5) of the aMED index had a lower risk for hip fractures (HR, 0.80; 95% CI, 0.66-0.97), with an absolute risk reduction of 0.29% and a number needed to treat of 342 (95% CI, 249-502). No association between the aMED score and total fractures was observed (Q5 HR, 1.01; 95% CI, 0.95-1.07). Higher HEI-2010 or DASH scores tended to be inversely related to hip fracture risk, but the results were nonsignificant (Q5 HR, 0.87; 95% CI, 0.75-1.02; and Q5 HR, 0.89; 95% CI, 0.75-1.06, respectively). The AHEI-2010 score was associated with neither hip nor total fractures. CONCLUSIONS AND RELEVANCE: Higher adherence to a Mediterranean diet is associated with a lower risk for hip fractures. These results support that a healthy dietary pattern may play a role in maintaining bone health in postmenopausal women

Lipoprotein(a) plasma levels, bone mineral density and risk of hip fracture: a post hoc analysis of the Women\u27s Health Initiative, USA

OBJECTIVES: Elevated Lipoprotein(a) (Lp[a]) is a well-known risk factor for cardiovascular disease. However, its roles in bone metabolism and fracture risk are unclear. We therefore investigated whether plasma Lp(a) levels were associated with bone mineral density (BMD) and incident hip fractures in a large cohort of postmenopausal women. DESIGN: Post hoc analysis of data from the Women\u27s Health Initiative (WHI), USA. SETTING: 40 clinical centres in the USA. PARTICIPANTS: The current analytical cohort consisted of 9698 white, postmenopausal women enrolled in the WHI, a national prospective study investigating determinants of chronic diseases including heart disease, breast and colorectal cancers and osteoporotic fractures among postmenopausal women. Recruitment for WHI took place from 1 October 1993 to 31 December 1998. EXPOSURES: Plasma Lp(a) levels were measured at baseline. OUTCOME MEASURES: Incident hip fractures were ascertained annually and confirmed by medical records with follow-up through 29 August 2014. BMD at the femoral neck was measured by dual X-ray absorptiometry in a subset of participants at baseline. STATISTICAL ANALYSES: Cox proportional hazards and logistic regression models were used to evaluate associations of quartiles of plasma Lp(a) levels with hip fracture events and hip BMD T-score, respectively. RESULTS: During a mean follow-up of 13.8 years, 454 incident cases of hip fracture were observed. In analyses adjusting for confounding variables including age, body mass index, history of hysterectomy, smoking, physical activity, diabetes mellitus, general health status, cardiovascular disease, use of menopausal hormone therapy, use of bisphosphonates, calcitonin or selective-oestrogen receptor modulators, baseline dietary and supplemental calcium and vitamin D intake and history of fracture, no significant association of plasma Lp(a) levels with low hip BMD T-score or hip fracture risk was detected. CONCLUSIONS: These findings suggest that plasma Lp(a) levels are not related to hip BMD T-score or hip fracture events in postmenopausal women. TRIAL REGISTRATION NUMBER: NCT00000611; Post-results

Divergence times and the evolution of morphological complexity in an early land plant lineage (Marchantiopsida) with a slow molecular rate

Summary We present a complete generic-level phylogeny of the complex thalloid liverworts, a lineage that includes the model system Marchantia polymorpha. The complex thalloids are remarkable for their slow rate of molecular evolution and for being the only extant plant lineage to differentiate gas exchange tissues in the gametophyte generation. We estimated the divergence times and analyzed the evolutionary trends of morphological traits, including air chambers, rhizoids and specialized reproductive structures. A multilocus dataset was analyzed using maximum likelihood and Bayesian approaches. Relative rates were estimated using local clocks. Our phylogeny cements the early branching in complex thalloids. Marchantia is supported in one of the earliest divergent lineages. The rate of evolution in organellar loci is slower than for other liverwort lineages, except for two annual lineages. Most genera diverged in the Cretaceous. Marchantia polymorpha diversified in the Late Miocene, giving a minimum age estimate for the evolution of its sex chromosomes. The complex thalloid ancestor, excluding Blasiales, is reconstructed as a plant with a carpocephalum, with filament-less air chambers opening via compound pores, and without pegged rhizoids. Our comprehensive study of the group provides a temporal framework for the analysis of the evolution of critical traits essential for plants during land colonization

World checklist of hornworts and liverworts

A working checklist of accepted taxa worldwide is vital in achieving the goal of developing an online flora of all known plants by 2020 as part of the Global Strategy for Plant Conservation. We here present the first-ever worldwide checklist for liverworts (Marchantiophyta) and hornworts (Anthocerotophyta) that includes 7486 species in 398 genera representing 92 families from the two phyla. The checklist has far reaching implications and applications, including providing a valuable tool for taxonomists and systematists, analyzing phytogeographic and diversity patterns, aiding in the assessment of floristic and taxonomic knowledge, and identifying geographical gaps in our understanding of the global liverwort and hornwort flora. The checklist is derived from a working data set centralizing nomenclature, taxonomy and geography on a global scale. Prior to this effort a lack of centralization has been a major impediment for the study and analysis of species richness, conservation and systematic research at both regional and global scales. The success of this checklist, initiated in 2008, has been underpinned by its community approach involving taxonomic specialists working towards a consensus on taxonomy, nomenclature and distribution

recommendations by the Conect4Children expert advice group

Funding Information: Competing interests: A.V.R. has received Speaker fees/Consultant for Abbvie, Novartis, UCB, SOBI, Eli Lilly and Roche. N.M. reports grants outside the submitted work in the last five years from the Medical Research Council, National Institute of Health Research, March of Dimes, British Heart Foundation, HCA international, Health Data Research UK, Shire Pharmaceuticals, Chiesi Pharmaceuticals, Prolacta Life Sciences, and Westminster Children’s Research Fund; N.M. is a member of the Nestle Scientific Advisory Board and accepts no personal remuneration for this role. N.M. reports travel and accommodation reimbursements from Chiesi, Nestle and Shire. N.M. is a member of C4C, International Neonatal Collaboration (INC), UK National Research Ethics Advisory Service and MHRA advisory groups and/or working parties. S.W. has received compensation as a member of the scientific advisory board of AM Pharma, Novartis and Khondrion and receives research funding from IMI2 for the Conect4children project. B.A. has worked for GlaxoSmithKline between October 2006 and September 2009 and holds company shares. Between October 2009 and May 2015, she has worked for Novartis. M.S. has recieved research grant and honoraria for meetings and Advisory Boards from Alexion, Sanofi/Genzyme, Takeda, CHIESI, Ultragenix, Orchard, Orphazyme. P.I. is a permanent employee of Bayer AG, Germany. M.V. has received compensation for Advisory boards or Steering committes from Roche, Novartis, Achillion, Apellis, Retrophin/Travere, Alexion pharmaceuticals. C.M. has been a consultant to or has received honoraria from Janssen, Angelini, Servier, Nuvelution, Otsuka, Lundbeck, Pfizer, Neuraxpharm and Esteve outside the submitted work. She declares conflicts of interest unrelated to the present work. M.C. had advisory roles for AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Lilly, and Roche in the last 2 years (outside the topic of the submitted work, for oncology drugs). M.J. has received research grants from Shire and has been engaged as a speaker or consultant by Shire, Ginsana, PCM Scientific Evolan, and New Nordic, all unrelated to the present work. P.S. has received speaker fees and participated at advisory boards for Biomarin, Zogenyx, GW Pharmaceuticals, and has received research funding by ENECTA BV, GW Pharmaceuticals, Kolfarma srl., Eisai. E.R. has received speaker fees and participated at advisory boards for Eisai and has received research funding by GW Pharmaceuticals, Pfizer, Italian Ministry of Health (MoH) and the Italian Medicine Agency (AIFA). This work was developed within the framework of the DINOGMI Department of Excellence of MIUR 2018-2022 (legge 232 del 2016). M.A.R. is a member of the c4c Ethics Expert Group and received compensation for ethical consulting activities from Bayer AG Wallace Crandall is employee of Eli Lilly and Co. P.C. is an employee of UCB, and owns stock in the company. She was previously an employee of GSK and owns stock in the company. N.R. has received honoraria for consultancies or speaker bureaus from the following pharmaceutical companies in the past 3 years: Ablynx, Amgen, Astrazeneca-Medimmune, Aurinia, Bayer, Bristol Myers and Squibb, Cambridge Healthcare Research (CHR), Celgene, Domain therapeutic, Eli-Lilly, EMD Serono, Glaxo Smith and Kline, Idorsia, Janssen, Novartis, Pfizer, Sobi, UCB. The IRCCS Istituto Giannina Gaslini (IGG), where NR works as full-time public employee has received contributions from the following industries in the last 3 years: Bristol Myers and Squibb, Eli-Lilly, F Hoffmann-La Roche, Novartis, Pfizer, Sobi. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties. M.L. receives/has received consultation fees from CSL Behring, Novartis, Roche and Octopharma, travel grants from Merck Serono, and been awarded educational grants to organise meetings by Novartis, Biogen Idec, Merck Serono and Bayer. All other authors have no disclosures. Funding Information: Conect4children has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777389. The Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. The views expressed in this article are the personal views of the author(s) and should not be interpreted as made on behalf of, or reflecting the position of, the regulatory agency/agencies or organisations with which the author(s) is/are employed/affiliated . Publisher Copyright: © 2021, The Author(s).Background: The COVID-19 pandemic has had a devastating impact on multiple aspects of healthcare, but has also triggered new ways of working, stimulated novel approaches in clinical research and reinforced the value of previous innovations. Conect4children (c4c, www.conect4children.org) is a large collaborative European network to facilitate the development of new medicines for paediatric populations, and is made up of 35 academic and 10 industry partners from 20 European countries, more than 50 third parties, and around 500 affiliated partners. Methods: We summarise aspects of clinical research in paediatrics stimulated and reinforced by COVID-19 that the Conect4children group recommends regulators, sponsors, and investigators retain for the future, to enhance the efficiency, reduce the cost and burden of medicines and non-interventional studies, and deliver research-equity. Findings: We summarise aspects of clinical research in paediatrics stimulated and reinforced by COVID-19 that the Conect4children group recommends regulators, sponsors, and investigators retain for the future, to enhance the efficiency, reduce the cost and burden of medicines and non-interventional studies, and deliver research-equityWe provide examples of research innovation, and follow this with recommendations to improve the efficiency of future trials, drawing on industry perspectives, regulatory considerations, infrastructure requirements and parent–patient–public involvement. We end with a comment on progress made towards greater international harmonisation of paediatric research and how lessons learned from COVID-19 studies might assist in further improvements in this important area.publishersversionepub_ahead_of_prin

Tigers of Sundarbans in India: Is the Population a Separate Conservation Unit?

The Sundarbans tiger inhabits a unique mangrove habitat and are morphologically distinct from the recognized tiger subspecies in terms of skull morphometrics and body size. Thus, there is an urgent need to assess their ecological and genetic distinctiveness and determine if Sundarbans tigers should be defined and managed as separate conservation unit. We utilized nine microsatellites and 3 kb from four mitochondrial DNA (mtDNA) genes to estimate genetic variability, population structure, demographic parameters and visualize historic and contemporary connectivity among tiger populations from Sundarbans and mainland India. We also evaluated the traits that determine exchangeability or adaptive differences among tiger populations. Data from both markers suggest that Sundarbans tiger is not a separate tiger subspecies and should be regarded as Bengal tiger (P. t. tigris) subspecies. Maximum likelihood phylogenetic analyses of the mtDNA data revealed reciprocal monophyly. Genetic differentiation was found stronger for mtDNA than nuclear DNA. Microsatellite markers indicated low genetic variation in Sundarbans tigers (He= 0.58) as compared to other mainland populations, such as northern and Peninsular (Hebetween 0.67- 0.70). Molecular data supports migration between mainland and Sundarbans populations until very recent times. We attribute this reduction in gene flow to accelerated fragmentation and habitat alteration in the landscape over the past few centuries. Demographic analyses suggest that Sundarbans tigers have diverged recently from peninsular tiger population within last 2000 years. Sundarbans tigers are the most divergent group of Bengal tigers, and ecologically non-exchangeable with other tiger populations, and thus should be managed as a separate "evolutionarily significant unit" (ESU) following the adaptive evolutionary conservation (AEC) concept.Wildlife Institute of India, Dehra Dun (India)