A Comprehensive Resource for Induced Pluripotent Stem Cells from Patients with Primary Tauopathies.

Primary tauopathies are characterized neuropathologically by inclusions containing abnormal forms of the microtubule-associated protein tau (MAPT) and clinically by diverse neuropsychiatric, cognitive, and motor impairments. Autosomal dominant mutations in the MAPT gene cause heterogeneous forms of frontotemporal lobar degeneration with tauopathy (FTLD-Tau). Common and rare variants in the MAPT gene increase the risk for sporadic FTLD-Tau, including progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). We generated a collection of fibroblasts from 140 MAPT mutation/risk variant carriers, PSP, CBD, and cognitively normal controls; 31 induced pluripotent stem cell (iPSC) lines from MAPT mutation carriers, non-carrier family members, and autopsy-confirmed PSP patients; 33 genome engineered iPSCs that were corrected or mutagenized; and forebrain neural progenitor cells (NPCs). Here, we present a resource of fibroblasts, iPSCs, and NPCs with comprehensive clinical histories that can be accessed by the scientific community for disease modeling and development of novel therapeutics for tauopathies

Why Don't We Ask? A Complementary Method for Assessing the Status of Great Apes

Species conservation is difficult. Threats to species are typically high and immediate. Effective solutions for counteracting these threats, however, require synthesis of high quality evidence, appropriately targeted activities, typically costly implementation, and rapid re-evaluation and adaptation. Conservation management can be ineffective if there is insufficient understanding of the complex ecological, political, socio-cultural, and economic factors that underlie conservation threats. When information about these factors is incomplete, conservation managers may be unaware of the most urgent threats or unable to envision all consequences of potential management strategies. Conservation research aims to address the gap between what is known and what knowledge is needed for effective conservation. Such research, however, generally addresses a subset of the factors that underlie conservation threats, producing a limited, simplistic, and often biased view of complex, real world situations. A combination of approaches is required to provide the complete picture necessary to engage in effective conservation. Orangutan conservation (Pongo spp.) offers an example: standard conservation assessments employ survey methods that focus on ecological variables, but do not usually address the socio-cultural factors that underlie threats. Here, we evaluate a complementary survey method based on interviews of nearly 7,000 people in 687 villages in Kalimantan, Indonesia. We address areas of potential methodological weakness in such surveys, including sampling and questionnaire design, respondent biases, statistical analyses, and sensitivity of resultant inferences. We show that interview-based surveys can provide cost-effective and statistically robust methods to better understand poorly known populations of species that are relatively easily identified by local people. Such surveys provide reasonably reliable estimates of relative presence and relative encounter rates of such species, as well as quantifying the main factors that threaten them. We recommend more extensive use of carefully designed and implemented interview surveys, in conjunction with more traditional field methods

Interlaboratory study on quantitative methods of analysis of C10- C13 polychloro-n-alkanes

Seven laboratories participated in an international interlaboratory comparison exercise to compare the quantitative methods used for measuring C10-C13 polychloro-n-alkanes (PCAs). Participants were supplied with two solutions (PCA-1, PCA-70) containing PCAs of \u27known\u27 but unstated concentrations, and two real world samples (fish extracts FE1 and FE2) each consisting of a cleaned up extract (lipid-free) of a fish tissue known to contain PCAs. A well-characterized commercial formulation, PCA-60, of stated concentration was also supplied and was used as the external standard for the exercise. Participants having other commercially available C10-C13 PCA mixtures were encouraged to use them as external standards for the study, and the choice of the quantitative method employed was left to participants, though all were based on high-resolution gas chromatography with detection by electron capture negative ion mass spectrometry (plus electron capture detection in one case). The results of the study met with mixed success. For measurements on the PCA-1 sample, whose composition and gas chromatographic profile were quite different from the PCA-60 sample, the determined concentration was 99.3 ± 19.5 ng/μL (mean ± the standard deviation of the laboratory means); the true concentration of this mixture was 74 ng/μL. For the PCA-70 sample, which has a composition and gas chromatographic profile similar to that of PCA-60, the result was 297 ± 132 ng/μL, compared to the true concentration of i 18 ng/μL. It is still unclear why the larger discrepancy arises for the latter sample; this observation implies that different commercial formulations used as standards would provide quite different estimates of PCA concentrations. The interlaboratory precision for measurements on the FE1 sample (coefficient of variation (CV) of 27%) was better than that for the FE2 sample (CV of 47%). An explanation for the larger variation is that some of the quantitative procedures used in measuring PCA levels in the FE2 sample did not take into account the effects of coeluting interferences, which are observed at nominal mass spectral resolution, thus making some of the values too high