Psychological and physiological adaptations to sperm competition in humans

Postcopulatory competition between males, in the form of sperm competition, is a widespread phenomenon in many animal species. The extent to which sperm competition has been an important selective pressure during human evolution remains controversial, however. The authors review critically the evidence that human males and females have psychological, behavioral, and physiological adaptations that evolved in response to selection pressures associated with sperm competition. The authors consider, using evidence from contemporary societies, whether sperm competition is likely to have been a significant adaptive problem for ancestral humans and examine the evidence suggesting that human males have physiological and psychological mechanisms that allow for “prudent” sperm allocation in response to variations in the risk of sperm competition

Expression of SARS-CoV-2 receptor ACE2 and the protease TMPRSS2 suggests susceptibility of the human embryo in the first trimester.

While initially recognized as causing respiratory disease, the SARS-CoV-2 virus also affects many other organs leading to other complications. It has emerged that advanced age and obesity are risk factors for complications but questions concerning the potential effects on fetal health and successful pregnancy for those infected with SARS-CoV-2 remain largely unanswered. Here, we examine human pre-gastrulation embryos to determine the expression patterns of the genes ACE2, encoding the SARS-CoV-2 receptor, and TMPRSS2, encoding a protease that cleaves both the viral spike protein and the ACE2 receptor to facilitate infection. We show expression and co-expression of these genes in the trophoblast of the blastocyst and syncytiotrophoblast and hypoblast of the implantation stages, which develop into tissues that interact with the maternal blood supply for nutrient exchange. Expression of ACE2 and TMPRSS2 in these tissues raises the possibility for vertical transmission and indicates that further work is required to understand potential risks to implantation, placental health and fetal health that require further study

An in vitro stem cell model of human epiblast and yolk sac interaction.

Human embryogenesis entails complex signalling interactions between embryonic and extra-embryonic cells. However, how extra-embryonic cells direct morphogenesis within the human embryo remains largely unknown due to a lack of relevant stem cell models. Here, we have established conditions to differentiate human pluripotent stem cells (hPSCs) into yolk sac-like cells (YSLCs) that resemble the post-implantation human hypoblast molecularly and functionally. YSLCs induce the expression of pluripotency and anterior ectoderm markers in human embryonic stem cells (hESCs) at the expense of mesoderm and endoderm markers. This activity is mediated by the release of BMP and WNT signalling pathway inhibitors, and, therefore, resembles the functioning of the anterior visceral endoderm signalling centre of the mouse embryo, which establishes the anterior-posterior axis. Our results implicate the yolk sac in epiblast cell fate specification in the human embryo and propose YSLCs as a tool for studying post-implantation human embryo development in vitro.</i

A questionnaire-based (UM-PDHQ) study of hallucinations in Parkinson's disease

Background: Hallucinations occur in 20-40% of PD patients and have been associated with unfavorable clinical outcomes (i.e., nursing home placement, increased mortality). Hallucinations, like other non-motor features of PD, are not well recognized in routine primary/secondary clinical practice. So far, there has been no instrument for uniform characterization of hallucinations in PD. To this end, we developed the University of Miami Parkinson's disease Hallucinations Questionnaire (UM-PDHQ) that allows comprehensive assessment of hallucinations in clinical or research settings.Methods: The UM-PDHQ is composed of 6 quantitative and 14 qualitative items. For our study PD patients of all ages and in all stages of the disease were recruited over an 18-month period. The UPDRS, MMSE, and Beck Depression and Anxiety Inventories were used for comparisons.Results and Discussion: Seventy consecutive PD patients were included in the analyses. Thirty-one (44.3%) were classified as hallucinators and 39 as non-hallucinators. No significant group differences were observed in terms of demographics, disease characteristics, stage, education, depressive/anxiety scores or cognitive functioning (MMSE) between hallucinators and non-hallucinators. Single mode hallucinations were reported in 20/31 (visual/14, auditory/4, olfactory/2) whereas multiple modalities were reported in 11/31 patients. The most common hallucinatory experience was a whole person followed by small animals, insects and reptiles.Conclusion: Using the UM-PDHQ, we were able to define the key characteristics of hallucinations in PD in our cohort. Future directions include the validation of the quantitative part of the questionnaire than will serve as a rating scale for severity of hallucinations

Aurora-A Mitotic Kinase Induces Endocrine Resistance through Down-Regulation of ERα Expression in Initially ERα+ Breast Cancer Cells

Development of endocrine resistance during tumor progression represents a major challenge in the management of estrogen receptor alpha (ERα) positive breast tumors and is an area under intense investigation. Although the underlying mechanisms are still poorly understood, many studies point towards the ‘cross-talk’ between ERα and MAPK signaling pathways as a key oncogenic axis responsible for the development of estrogen-independent growth of breast cancer cells that are initially ERα+ and hormone sensitive. In this study we employed a metastatic breast cancer xenograft model harboring constitutive activation of Raf-1 oncogenic signaling to investigate the mechanistic linkage between aberrant MAPK activity and development of endocrine resistance through abrogation of the ERα signaling axis. We demonstrate for the first time the causal role of the Aurora-A mitotic kinase in the development of endocrine resistance through activation of SMAD5 nuclear signaling and down-regulation of ERα expression in initially ERα+ breast cancer cells. This contribution is highly significant for the treatment of endocrine refractory breast carcinomas, because it may lead to the development of novel molecular therapies targeting the Aurora-A/SMAD5 oncogenic axis. We postulate such therapy to result in the selective eradication of endocrine resistant ERαlow/− cancer cells from the bulk tumor with consequent benefits for breast cancer patients

NOTCH3 Expression Is Linked to Breast Cancer Seeding and Distant Metastasis

Background: Development of distant metastases involves a complex multistep biological process termed the invasion-metastasis cascade, which includes dissemination of cancer cells from the primary tumor to secondary organs. NOTCH developmental signaling plays a critical role in promoting epithelial-to-mesenchymal transition, tumor stemness, and metastasis. Although all four NOTCH receptors show oncogenic properties, the unique role of each of these receptors in the sequential stepwise events that typify the invasion-metastasis cascade remains elusive. Methods: We have established metastatic xenografts expressing high endogenous levels of NOTCH3 using estrogen receptor alpha-positive (ERα+) MCF-7 breast cancer cells with constitutive active Raf-1/mitogen-associated protein kinase (MAPK) signaling (vMCF-7Raf-1) and MDA-MB-231 triple-negative breast cancer (TNBC) cells. The critical role of NOTCH3 in inducing an invasive phenotype and poor outcome was corroborated in unique TNBC cells resulting from a patient-derived brain metastasis (TNBC-M25) and in publicly available claudin-low breast tumor specimens collected from participants in the Molecular Taxonomy of Breast Cancer International Consortium database. Results: In this study, we identified an association between NOTCH3 expression and development of metastases in ERα+ and TNBC models. ERα+ breast tumor xenografts with a constitutive active Raf-1/MAPK signaling developed spontaneous lung metastases through the clonal expansion of cancer cells expressing a NOTCH3 reprogramming network. Abrogation of NOTCH3 expression significantly reduced the self-renewal and invasive capacity of ex vivo breast cancer cells, restoring a luminal CD44low/CD24high/ERαhigh phenotype. Forced expression of the mitotic Aurora kinase A (AURKA), which promotes breast cancer metastases, failed to restore the invasive capacity of NOTCH3-null cells, demonstrating that NOTCH3 expression is required for an invasive phenotype. Likewise, pharmacologic inhibition of NOTCH signaling also impaired TNBC cell seeding and metastatic growth. Significantly, the role of aberrant NOTCH3 expression in promoting tumor self-renewal, invasiveness, and poor outcome was corroborated in unique TNBC cells from a patient-derived brain metastasis and in publicly available claudin-low breast tumor specimens. Conclusions: These findings demonstrate the key role of NOTCH3 oncogenic signaling in the genesis of breast cancer metastasis and provide a compelling preclinical rationale for the design of novel therapeutic strategies that will selectively target NOTCH3 to halt metastatic seeding and to improve the clinical outcomes of patients with breast cancer

Feasibility of large-scale deployment of multiple wearable sensors in Parkinson’s disease

Wearable devices can capture objective day-to-day data about Parkinson’s Disease (PD). This study aims to assess the feasibility of implementing wearable technology to collect data from multiple sensors during the daily lives of PD patients. The Parkinson@home study is an observational, two-cohort (North America, NAM; The Netherlands, NL) study. To recruit participants, different strategies were used between sites. Main enrolment criteria were self-reported diagnosis of PD, possession of a smartphone and age ≥18 years. Participants used the Fox Wearable Companion app on a smartwatch and smartphone for a minimum of 6 weeks (NAM) or 13 weeks (NL). Sensor-derived measures estimated information about movement. Additionally, medication intake and symptoms were collected via self-reports in the app. A total of 953 participants were included (NL: 304, NAM: 649). Enrolment rate was 88% in the NL (n = 304) and 51% (n = 649) in NAM. Overall, 84% (n = 805) of participants contributed sensor data. Participants were compliant for 68% (16.3 hours/participant/day) of the study period in NL and for 62% (14.8 hours/participant/day) in NAM. Daily accelerometer data collection decreased 23% in the NL after 13 weeks, and 27% in NAM after 6 weeks. Data contribution was not affected by demographics, clinical characteristics or attitude towards technology, but was by the platform usability score in the NL (χ2 (2) = 32.014, p<0.001), and self-reported depression in NAM (χ2(2) = 6.397, p = .04). The Parkinson@home study shows that it is feasible to collect objective data using multiple wearable sensors in PD during daily life in a large cohort

Transcriptomic Analyses of Sexual Dimorphism of the Zebrafish Liver and the Effect of Sex Hormones

10.1371/journal.pone.0053562PLoS ONE81

The use of airborne laser scanning to develop a pixel-based stratification for a verified carbon offset project

Background The voluntary carbon market is a new and growing market that is increasingly important to consider in managing forestland. Monitoring, reporting, and verifying carbon stocks and fluxes at a project level is the single largest direct cost of a forest carbon offset project. There are now many methods for estimating forest stocks with high accuracy that use both Airborne Laser Scanning (ALS) and high-resolution optical remote sensing data. However, many of these methods are not appropriate for use under existing carbon offset standards and most have not been field tested. Results This paper presents a pixel-based forest stratification method that uses both ALS and optical remote sensing data to optimally partition the variability across an ~10,000 ha forest ownership in Mendocino County, CA, USA. This new stratification approach improved the accuracy of the forest inventory, reduced the cost of field-based inventory, and provides a powerful tool for future management planning. This approach also details a method of determining the optimum pixel size to best partition a forest. Conclusions The use of ALS and optical remote sensing data can help reduce the cost of field inventory and can help to locate areas that need the most intensive inventory effort. This pixel-based stratification method may provide a cost-effective approach to reducing inventory costs over larger areas when the remote sensing data acquisition costs can be kept low on a per acre basis