Testing the affiliation hypothesis of homoerotic motivation in humans:the effects of progesterone and priming

The frequency of homoerotic behavior among individuals who do not identify as having an exclusively homosexual sexual orientation suggests that such behavior potentially has adaptive value. Here, we define homoerotic behavior as intimate erotic contact between members of the same sex and affiliation as the motivation to make and maintain social bonds. Among both male and female nonhuman primates, affiliation is one of the main drivers of homoerotic behavior. Correspondingly, in humans, both across cultures and across historical periods, homoerotic behavior appears to play a role in promoting social bonds. However, to date, the affiliation explanation of human homoerotic behavior has not been adequately tested experimentally. We developed a measure of homoerotic motivation with a sample of 244 men and women. Next, we found that, in women (n = 92), homoerotic motivation was positively associated with progesterone, a hormone that has been shown to promote affiliative bonding. Lastly, we explored the effects of affiliative contexts on homoerotic motivation in men (n = 59), finding that men in an affiliative priming condition were more likely to endorse engaging in homoerotic behavior compared to those primed with neutral or sexual concepts, and this effect was more pronounced in men with high progesterone. These findings constitute the first experimental support for the affiliation account of the evolution of homoerotic motivation in humans

The consensus molecular subtypes of colorectal cancer

Colorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression-based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data sharing and analytics across expert groups. We show marked interconnectivity between six independent classification systems coalescing into four consensus molecular subtypes (CMSs) with distinguishing features: CMS1 (microsatellite instability immune, 14%), hypermutated, microsatellite unstable and strong immune activation; CMS2 (canonical, 37%), epithelial, marked WNT and MYC signaling activation; CMS3 (metabolic, 13%), epithelial and evident metabolic dysregulation; and CMS4 (mesenchymal, 23%), prominent transforming growth factor-beta activation, stromal invasion and angiogenesis. Samples with mixed features (13%) possibly represent a transition phenotype or intratumoral heterogeneity. We consider the CMS groups the most robust classification system currently available for CRC-with clear biological interpretability-and the basis for future clinical stratification and subtype-based targeted interventions

The Consensus Molecular Subtypes of Colorectal Cancer

Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use -- https://www.nature.com/authors/policies/license.html#termsColorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression-based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data sharing and analytics across expert groups. We show marked interconnectivity between six independent classification systems coalescing into four consensus molecular subtypes (CMS) with distinguishing features: CMS1 (MSI Immune, 14%), hypermutated, microsatellite unstable, strong immune activation; CMS2 (Canonical, 37%), epithelial, chromosomally unstable, marked WNT and MYC signaling activation; CMS3 (Metabolic, 13%), epithelial, evident metabolic dysregulation; and CMS4 (Mesenchymal, 23%), prominent transforming growth factor β activation, stromal invasion, and angiogenesis. Samples with mixed features (13%) possibly represent a transition phenotype or intra-tumoral heterogeneity. We consider the CMS groups the most robust classification system currently available for CRC - with clear biological interpretability - and the basis for future clinical stratification and subtype-based targeted interventions

Colorectal Cancer Subtypes: Developmental Origin and Microenvironmental Regulation

Cancer is a heterogeneous disease and many cancer types do not represent a single entity, but are composed of biologically and clinically diverse subtypes. The subtype affiliation can influence prognosis and response to therapy. Recently, a multicenter colorectal cancer (CRC) subtyping consortium introduced a consensus molecular classification system for CRC. This will be of great benefit for future basic and clinical research since it enables uniform categorization of CRC specimens across different institutes and studies. The biological conformity observed within each consensus molecular subtype (CMS) holds promise for the design of subtype-specific treatment regimens. Herein, we review the CMSs of CRC with a focus on how multiple parameters, such as the origin, developmental route, and microenvironmental regulation shape distinct subtype

DELE1 tracks perturbed protein import and processing in human mitochondria

Protein homeostatic control of mitochondria is key to age-related diseases and organismal decline. However, it is unknown how the diverse types of stress experienced by mitochondria can be integrated and appropriately responded to in human cells. Here we identify perturbations in the ancient conserved processes of mitochondrial protein import and processing as sources of DELE1 activation: DELE1 is continuously sorted across both mitochondrial membranes into the matrix and detects different types of perturbations along the way. DELE1 molecules in transit can become licensed for mitochondrial release and stress signaling through proteolytic removal of N-terminal sorting signals. Import defects that occur at the mitochondrial surface allow DELE1 precursors to bind and activate downstream factor HRI without the need for cleavage. Genome-wide genetics reveal that DELE1 additionally responds to compromised presequence processing by the matrix proteases PITRM1 and MPP, which are mutated in neurodegenerative diseases. These mechanisms rationalize DELE1-dependent mitochondrial stress integration in the human system and may inform future therapies of neuropathies

Endothelial cells induce cancer stem cell features in differentiated glioblastoma cells via bFGF

Glioblastoma multiforme (GBM) is a rapidly growing malignant brain tumor, which has been reported to be organized in a hierarchical fashion with cancer stem cells (CSCs) at the apex. Recent studies demonstrate that this hierarchy does not follow a one-way route but can be reverted with more differentiated cells giving rise to cells possessing CSC features. We investigated the role of tumor microvascular endothelial cells (tMVECs) in reverting differentiated glioblastoma cells to CSC-like cells. We made use of primary GBM lines and tMVECs. To ensure differentiation, CSC-enriched cultures were forced into differentiation using several stimuli and cultures consisting solely of differentiated cells were obtained by sorting on the oligodendrocyte marker O4. Reversion to the CSC state was assessed phenotypically by CSC marker expression and functionally by evaluating clonogenic and multilineage differentiation potential. Conditioned medium of tMVECs was able to replenish the CSC pool by phenotypically and functionally reverting differentiated GBM cells to the CSC state. Basic fibroblast growth factor (bFGF), secreted by tMVECs, recapitulated the effects of the conditioned medium in inducing re-expression of CSC markers and increasing neurosphere formation ability of differentiated GBM cells. Our findings demonstrate that the CSC-based hierarchy displays a high level of plasticity showing that differentiated GBM cells can acquire CSC features when placed in the right environment. These results point to the need to intersect the elaborate network of tMVECs and GBM CSCs for efficient elimination of GBM CSC

Testing the Affiliation Hypothesis of Homoerotic Motivation in Humans: The Effects of Progesterone and Priming.

The frequency of homoerotic behavior among individuals who do not identify as having an exclusively homosexual sexual orientation suggests that such behavior potentially has adaptive value. Here, we define homoerotic behavior as intimate erotic contact between members of the same sex and affiliation as the motivation to make and maintain social bonds. Among both male and female nonhuman primates, affiliation is one of the main drivers of homoerotic behavior. Correspondingly, in humans, both across cultures and across historical periods, homoerotic behavior appears to play a role in promoting social bonds. However, to date, the affiliation explanation of human homoerotic behavior has not been adequately tested experimentally. We developed a measure of homoerotic motivation with a sample of 244 men and women. Next, we found that, in women (n = 92), homoerotic motivation was positively associated with progesterone, a hormone that has been shown to promote affiliative bonding. Lastly, we explored the effects of affiliative contexts on homoerotic motivation in men (n = 59), finding that men in an affiliative priming condition were more likely to endorse engaging in homoerotic behavior compared to those primed with neutral or sexual concepts, and this effect was more pronounced in men with high progesterone. These findings constitute the first experimental support for the affiliation account of the evolution of homoerotic motivation in humans

Cancer heterogeneity--a multifaceted view

Cancers of various organs have been categorized into distinct subtypes after increasingly sophisticated taxonomies. Additionally, within a seemingly homogeneous subclass, individual cancers contain diverse tumour cell populations that vary in important cancer-specific traits such as clonogenicity and invasive potential. Differences that exist between and within a given tumour type have hampered significantly both the proper selection of patients that might benefit from therapy, as well as the development of new targeted agents. In this review, we discuss the differences associated with organ-specific cancer subtypes and the factors that contribute to intra-tumour heterogeneity. It is of utmost importance to understand the biological causes that distinguish tumours as well as distinct tumour cell populations within malignancies, as these will ultimately point the way to more rational anti-cancer treatment