The status of the world's land and marine mammals: diversity, threat, and knowledge

Knowledge of mammalian diversity is still surprisingly disparate, both regionally and taxonomically. Here, we present a comprehensive assessment of the conservation status and distribution of the world's mammals. Data, compiled by 1700+ experts, cover all 5487 species, including marine mammals. Global macroecological patterns are very different for land and marine species but suggest common mechanisms driving diversity and endemism across systems. Compared with land species, threat levels are higher among marine mammals, driven by different processes (accidental mortality and pollution, rather than habitat loss), and are spatially distinct (peaking in northern oceans, rather than in Southeast Asia). Marine mammals are also disproportionately poorly known. These data are made freely available to support further scientific developments and conservation action

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Spatiotemporal expression and localization of matrix metalloproteinas-9 in a murine model of thoracic aortic aneurysm

ObjectiveMatrix metalloproteinase-9 (MMP-9) has been widely described to play a critical role in aneurysm development. The goal of this study was to determine the spatiotemporal changes in MMP-9 expression and abundance in the early stages of aortic dilatation during the course of thoracic aortic aneurysm (TAA) formation in a mouse model.MethodsIn this study, TAAs were surgically induced in a transgenic reporter mouse strain expressing the β-galactosidase (β-gal) gene under control of the MMP-9 promoter. Terminal studies were performed during the early stages of TAA development at 1 week (n = 6), 2 weeks (n = 6), and 4 weeks (n = 6) post-TAA induction surgery. Changes in aortic outer diameter were determined in vivo by video micrometry. MMP-9 transcriptional activity (β-gal staining) and protein content (immunohistochemistry) were quantified at each time point and expressed as a percentage of unoperated reference control mice (n = 6).ResultsAortic dilatation was evident at 1 week and reached maximal size at 2 weeks (21% ± 6% increase from baseline, P < .05). MMP-9 transcriptional activity was detected at 1 week post-TAA induction (722% ± 323%, P = .19), reached a maximum within the adventitia at 2 weeks (1770% ± 505%, P < .05), and returned to baseline by 4 weeks (167% ± 47%, P = .21). MMP-9 transcription at 2 weeks colocalized with fibroblasts and smooth muscle cells. MMP-9 protein content within the aortic adventitia was increased at 2 weeks post-TAA induction (413% ± 124%, P < .05) and remained elevated at 4 weeks (222% ± 41%, P < .05). MMP-9 staining was most intense at the adventitial–medial border and could be detected throughout the elastic media.ConclusionsThese findings demonstrate a unique spatiotemporal pattern of MMP-9 transcriptional activation and protein content in the developing TAA. Colocalization studies suggest that early dilatation may be driven in part by MMP-9 produced by endogenous cells residing within the aortic vascular wall.Clinical RelevanceThe detection of thoracic abdominal aneurysm (TAA) formation and progression remains clinically difficult to manage. TAA development is a multifactorial process influenced by both cellular and extracellular mechanisms that converge on common maladaptive signaling pathways that alter the vascular environment. Active remodeling of the vascular extracellular matrix has been directly implicated in aortic dilatation and aneurysm development, and multiple studies have shown that matrix metalloproteinase-9 (MMP-9) has a critical role in this process. Thus, the goal of this study was to define the spatiotemporal relationship between MMP-9 expression/abundance and the initiation of aortic dilatation in the developing TAA. Understanding when and where MMP-9 is expressed locally defines a therapeutic window during which disruption of MMP-9 activity may aid in attenuating TAA progression

Concordance Between Life Satisfaction and Six Elements of Well-Being Among Respondents to a Health Assessment Survey, HealthPartners Employees, Minnesota, 2011

Introduction: We assessed and tracked perceptions of well-being among employees of member companies of HealthPartners, a nonprofit health care provider and health insurance company in Bloomington, Minnesota. The objective of our study was to determine the concordance between self-reported life satisfaction and a construct of subjective well-being that comprised 6 elements of well-being: emotional and mental health, social and interpersonal status, financial status, career status, physical health, and community support. Methods: We analyzed responses of 23,268 employees (of 37,982 invitees) from 6 HealthPartners companies who completed a health assessment in 2011. We compared respondents’ answers to the question, “How satisfied are you with your life?” with their indicators of well-being where “high life satisfaction” was defined as a rating of 9 or 10 on a scale of 0 (lowest) to 10 (highest) and “high level of well-being” was defined as a rating of 9 or 10 for 5 or 6 of the 6 indicators of well-being. Result We found a correlation between self-reported life satisfaction and the number of well-being elements scored as high (9 or 10) (r = 0.62, P < .001); 73.6% of the respondents were concordant (high on both or high on neither). Although 82.9% of respondents with high overall well-being indicated high life satisfaction, only 34.7% of those indicating high life satisfaction reported high overall well-being. Conclusion: The correlation between self-reported life satisfaction and our well-being measure was strong, and members who met our criterion of high overall well-being were likely to report high life satisfaction. However, many respondents who reported high life satisfaction did not meet our criterion for high overall well-being, which suggests that either they adapted to negative life circumstances or that our well-being measure did not identify their sources of life satisfaction

Lactate dehydrogenase activity drives hair follicle stem cell activation.

Although normally dormant, hair follicle stem cells (HFSCs) quickly become activated to divide during a new hair cycle. The quiescence of HFSCs is known to be regulated by a number of intrinsic and extrinsic mechanisms. Here we provide several lines of evidence to demonstrate that HFSCs utilize glycolytic metabolism and produce significantly more lactate than other cells in the epidermis. Furthermore, lactate generation appears to be critical for the activation of HFSCs as deletion of lactate dehydrogenase (Ldha) prevented their activation. Conversely, genetically promoting lactate production in HFSCs through mitochondrial pyruvate carrier 1 (Mpc1) deletion accelerated their activation and the hair cycle. Finally, we identify small molecules that increase lactate production by stimulating Myc levels or inhibiting Mpc1 carrier activity and can topically induce the hair cycle. These data suggest that HFSCs maintain a metabolic state that allows them to remain dormant and yet quickly respond to appropriate proliferative stimuli