LemurFaceID: a face recognition system to facilitate individual identification of lemurs

Background: Long-term research of known individuals is critical for understanding the demographic and evolutionary processes that influence natural populations. Current methods for individual identification of many animals include capture and tagging techniques and/or researcher knowledge of natural variation in individual phenotypes. These methods can be costly, time-consuming, and may be impractical for larger-scale, populationlevel studies. Accordingly, for many animal lineages, long-term research projects are often limited to only a few taxa. Lemurs, a mammalian lineage endemic to Madagascar, are no exception. Long-term data needed to address evolutionary questions are lacking for many species. This is, at least in part, due to difficulties collecting consistent data on known individuals over long periods of time. Here, we present a new method for individual identification of lemurs (LemurFaceID). LemurFaceID is a computer-assisted facial recognition system that can be used to identify individual lemurs based on photographs. Results: LemurFaceID was developed using patch-wise Multiscale Local Binary Pattern features and modified facial image normalization techniques to reduce the effects of facial hair and variation in ambient lighting on identification. We trained and tested our system using images from wild red-bellied lemurs (Eulemur rubriventer) collected in Ranomafana National Park, Madagascar. Across 100 trials, with different partitions of training and test sets, we demonstrate that the LemurFaceID can achieve 98.7% ± 1.81% accuracy (using 2-query image fusion) in correctly identifying individual lemurs. Conclusions: Our results suggest that human facial recognition techniques can be modified for identification of individual lemurs based on variation in facial patterns. LemurFaceID was able to identify individual lemurs based on photographs of wild individuals with a relatively high degree of accuracy. This technology would remove many limitations of traditional methods for individual identification. Once optimized, our system can facilitate long-term research of known individuals by providing a rapid, cost-effective, and accurate method for individual identification

The Transcription Factor REST Is Lost in Aggressive Breast Cancer

The function of the tumor suppressor RE1 silencing transcription factor (REST) is lost in colon and small cell lung cancers and is known to induce anchorage-independent growth in human mammary epithelial cells. However, nothing is currently known about the role of this tumor suppressor in breast cancer. Here, we test the hypothesis that loss of REST function plays a role in breast cancer. To assay breast tumors for REST function, we developed a 24-gene signature composed of direct targets of the transcriptional repressor. Using the 24- gene signature, we identified a previously undefined RESTless breast tumor subtype. Using gene set enrichment analysis, we confirmed the aberrant expression of REST target genes in the REST–less tumors, including neuronal gene targets of REST that are normally not expressed outside the nervous system. Examination of REST mRNA identified a truncated splice variant of REST present in the REST–less tumor population, but not other tumors. Histological analysis of 182 outcome-associated breast tumor tissues also identified a subpopulation of tumors that lack full-length, functional REST and over-express the neuroendocrine marker and REST target gene Chromogranin A. Importantly, patients whose tumors were found to be REST–less using either the 24-gene signature or histology had significantly poorer prognosis and were more than twice as likely to undergo disease recurrence within the first 3 years after diagnosis. We show here that REST function is lost in breast cancer, at least in part via an alternative splicing mechanism. Patients with REST–less breast cancer undergo significantly more early disease recurrence than those with fully functional REST, regardless of estrogen receptor or HER2 status. Importantly, REST status may serve as a predictor of poor prognosis, helping to untangle the heterogeneity inherent in disease course and response to treatment. Additionally, the alternative splicing observed in REST–less breast cancer is an attractive therapeutic target

Should a Sentinel Node Biopsy Be Performed in Patients with High-Risk Breast Cancer?

A negative sentinel lymph node (SLN) biopsy spares many breast cancer patients the complications associated with lymph node irradiation or additional surgery. However, patients at high risk for nodal involvement based on clinical characteristics may remain at unacceptably high risk of axillary disease even after a negative SLN biopsy result. A Bayesian nomogram was designed to combine the probability of axillary disease prior to nodal biopsy with customized test characteristics for an SLN biopsy and provides the probability of axillary disease despite a negative SLN biopsy. Users may individualize the sensitivity of an SLN biopsy based on factors known to modify the sensitivity of the procedure. This tool may be useful in identifying patients who should have expanded upfront exploration of the axilla or comprehensive axillary irradiation

Potent and Broad Inhibition of HIV-1 by a Peptide from the gp41 Heptad Repeat-2 Domain Conjugated to the CXCR4 Amino Terminus.

HIV-1 entry can be inhibited by soluble peptides from the gp41 heptad repeat-2 (HR2) domain that interfere with formation of the 6-helix bundle during fusion. Inhibition has also been seen when these peptides are conjugated to anchoring molecules and over-expressed on the cell surface. We hypothesized that potent anti-HIV activity could be achieved if a 34 amino acid peptide from HR2 (C34) were brought to the site of virus-cell interactions by conjugation to the amino termini of HIV-1 coreceptors CCR5 or CXCR4. C34-conjugated coreceptors were expressed on the surface of T cell lines and primary CD4 T cells, retained the ability to mediate chemotaxis in response to cognate chemokines, and were highly resistant to HIV-1 utilization for entry. Notably, C34-conjugated CCR5 and CXCR4 each exhibited potent and broad inhibition of HIV-1 isolates from diverse clades irrespective of tropism (i.e., each could inhibit R5, X4 and dual-tropic isolates). This inhibition was highly specific and dependent on positioning of the peptide, as HIV-1 infection was poorly inhibited when C34 was conjugated to the amino terminus of CD4. C34-conjugated coreceptors could also inhibit HIV-1 isolates that were resistant to the soluble HR2 peptide inhibitor, enfuvirtide. When introduced into primary cells, CD4 T cells expressing C34-conjugated coreceptors exhibited physiologic responses to T cell activation while inhibiting diverse HIV-1 isolates, and cells containing C34-conjugated CXCR4 expanded during HIV-1 infection in vitro and in a humanized mouse model. Notably, the C34-conjugated peptide exerted greater HIV-1 inhibition when conjugated to CXCR4 than to CCR5. Thus, antiviral effects of HR2 peptides can be specifically directed to the site of viral entry where they provide potent and broad inhibition of HIV-1. This approach to engineer HIV-1 resistance in functional CD4 T cells may provide a novel cell-based therapeutic for controlling HIV infection in humans

Objectively measured physical activity of USA adults by sex, age, and racial/ethnic groups: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Accelerometers were incorporated in the 2003–2004 National Health and Nutritional Examination Survey (NHANES) study cycle for objective assessment of physical activity. This is the first time that objective physical activity data are available on a nationally representative sample of U.S. residents. The use of accelerometers allows researchers to measure total physical activity, including light intensity and unstructured activities, which may be a better predictor of health outcomes than structured activity alone. The aim of this study was to examine objectively determined physical activity levels by sex, age and racial/ethnic groups in a national sample of U.S. adults.</p> <p>Methods</p> <p>Data were obtained from the 2003–2004 NHANES, a cross-sectional study of a complex, multistage probability sample of the U.S. population. Physical activity was assessed with the Actigraph AM-7164 accelerometer for seven days following an examination. 2,688 U.S. adults with valid accelerometer data (i.e. at least four days with at least 10 hours of wear-time) were included in the analysis. Mean daily total physical activity counts, as well as counts accumulated in minutes of light, and moderate-vigorous intensity physical activity are presented by sex across age and racial/ethnic groups. Generalized linear modeling using the log link function was performed to compare physical activity in sex and racial/ethnic groups adjusting for age.</p> <p>Results</p> <p>Physical activity decreases with age for both men and women across all racial/ethnic groups with men being more active than women, with the exception of Hispanic women. Hispanic women are more active at middle age (40–59 years) compared to younger or older age and not significantly less active than men in middle or older age groups (i.e. age 40–59 or age 60 and older). Hispanic men accumulate more total and light intensity physical activity counts than their white and black counterparts for all age groups.</p> <p>Conclusion</p> <p>Physical activity levels measured objectively by accelerometer demonstrated that Hispanic men are, in general, more active than their white and black counterparts. This appears to be in contrast to self-reported physical activity previously reported in the literature and identifies the need to use objective measures in situations where the contribution of light intensity and/or unstructured physical activity cannot be assumed homogenous across the populations of interest.</p

Results from a natural experiment: initial neighbourhood investments do not change objectively-assessed physical activity, psychological distress or perceptions of the neighbourhood

Abstract Background Few studies have assessed objectively measured physical activity (PA), active transportation, psychological distress and neighborhood perceptions among residents of a neighborhood before and after substantial improvements in its physical environment. Also, most research-to-date has employed study designs subject to neighborhood selection, which may introduce bias in reported findings. We built upon a previously enrolled cohort of households from two low-income predominantly African American Pittsburgh neighborhoods, matched on socio-demographic composition including race/ethnicity, income and education. One of the two neighborhoods received substantial neighborhood investments over the course of this study including, but not limited to public housing development and greenspace/landscaping. We implemented a natural experiment using matched intervention and control neighborhoods and conducted pre-post assessments among the cohort. Our comprehensive assessments included accelerometry-based PA, active transportation, psychological distress and perceptions of the neighborhood, with assessments conducted both prior to and following the neighborhood changes. In 2013, we collected data from 1003 neighborhood participants and in 2016, we re-interviewed 676 of those participants. We conducted an intent to treat analysis, with a difference-in-difference estimator using attrition weighting to account for nonresponse between 2013 and 2016. In addition, we derived an individual-level indicator of exposure to neighbourhood investment and estimated effect of exposure to investment on the same set of outcomes using covariate-adjusted models. Results We observed no statistically significant differences in activity, psychological distress, satisfaction with one’s neighborhood as a place to live or any of the other measures we observed prior to and after the neighborhood investments between the intervention and control neighborhoods or those exposed vs not exposed to investments. Conclusions Using this rigorous study design, we observed no significant changes in the intervention neighborhood above and beyond secular trends present in the control neighborhood. Although neighborhood investment may have other benefits, we failed to see improvement in PA, psychological distress or related outcomes in the low-income African American neighborhoods in our study. This may be an indication that improvements in the physical environment may not directly translate into improvements in residents’ physical activity or health outcomes without additional individual-level interventions. It is also possible that these investments were not dramatic enough to spur change within the three year period. Additional studies employing similar design with other cohorts in other settings are needed to confirm these results. Trial registration Trial Registration is not applicable since we did not prospectively assign individuals to a health-related intervention.https://deepblue.lib.umich.edu/bitstream/2027.42/148333/1/12966_2019_Article_793.pd

A Pleiotropically Acting MicroRNA, miR-31, Inhibits Breast Cancer Metastasis

MicroRNAs are well suited to regulate tumor metastasis because of their capacity to coordinately repress numerous target genes, thereby potentially enabling their intervention at multiple steps of the invasion-metastasis cascade. We identify a microRNA exemplifying these attributes, miR-31, whose expression correlates inversely with metastasis in human breast cancer patients. Overexpression of miR-31 in otherwise-aggressive breast tumor cells suppresses metastasis. We deploy a stable microRNA sponge strategy to inhibit miR-31 in vivo; this allows otherwise-nonaggressive breast cancer cells to metastasize. These phenotypes do not involve confounding influences on primary tumor development and are specifically attributable to miR-31-mediated inhibition of several steps of metastasis, including local invasion, extravasation or initial survival at a distant site, and metastatic colonization. Such pleiotropy is achieved via coordinate repression of a cohort of metastasis-promoting genes, including RhoA. Indeed, RhoA re-expression partially reverses miR-31-imposed metastasis suppression. These findings indicate that miR-31 uses multiple mechanisms to oppose metastasis.Massachusetts Institute of Technology (Daniel K. Ludwig Foundation Cancer Research Professor)American Cancer Society (ACS Research Professor)United States. Dept. of Defense (Breast Cancer Research Program Predoctoral Fellow)United States. Dept. of Defense (Breast Cancer Research Program, DoD BCRP Idea Award))Harvard University (Harvard Breast Cancer SPORE)National Institutes of Health (U.S.) (RO1 CA078461)National Institutes of Health (U.S.) (PO1 CA080111

X chromosomal abnormalities in basal-like human breast cancer

SummarySporadic basal-like cancers (BLC) are a distinct class of human breast cancers that are phenotypically similar to BRCA1-associated cancers. Like BRCA1-deficient tumors, most BLC lack markers of a normal inactive X chromosome (Xi). Duplication of the active X chromosome and loss of Xi characterized almost half of BLC cases tested. Others contained biparental but nonheterochromatinized X chromosomes or gains of X chromosomal DNA. These abnormalities did not lead to a global increase in X chromosome transcription but were associated with overexpression of a small subset of X chromosomal genes. Other, equally aneuploid, but non-BLC rarely displayed these X chromosome abnormalities. These results suggest that X chromosome abnormalities contribute to the pathogenesis of BLC, both inherited and sporadic