The tumour microenvironment links complement system dysregulation and hypoxic signalling.

The complement system is an innate immune pathway typically thought of as part of the first line of defence against "non-self" species. In the context of cancer, complement has been described to have an active role in facilitating cancer-associated processes such as increased proliferation, angiogenesis and migration. Several cellular members of the tumour microenvironment express and/or produce complement proteins locally, including tumour cells. Dysregulation of the complement system has been reported in numerous tumours and increased expression of complement activation fragments in cancer patient specimens correlates with poor patient prognosis. Importantly, genetic or pharmacological targeting of complement has been shown to reduce tumour growth in several cancer preclinical models, suggesting that complement could be an attractive therapeutic target. Hypoxia (low oxygen) is frequently found in solid tumours and has a profound biological impact on cellular and non-cellular components of the tumour microenvironment. In this review, we focus on hypoxia since this is a prevailing feature of the tumour microenvironment that, like increased complement, is typically associated with poor prognosis. Furthermore, interesting links between hypoxia and complement have been recently proposed but never collectively reviewed. Here, we explore how hypoxia alters regulation of complement proteins in different cellular components of the tumour microenvironment, as well as the downstream biological consequences of this regulation

In traditionally male-dominated fields, women are less willing to make sacrifices for their career because discrimination and lower fit with people up the ladder make sacrifices less worthwhile

Women's lower career advancement relative to men is sometimes explained by internal factors such as women's lower willingness to make sacrifices for their career, and sometimes by external barriers such as discrimination. In the current research, positing a dynamic interplay between internal and external factors, we empirically test how external workplace barriers guide individuals' internal decisions to make sacrifices for the advancement of their careers. In two high-powered studies in traditionally male-dominated fields (surgery, N = 1,080; veterinary medicine, N = 1,385), women indicated less willingness than men to make sacrifices for their career. Results of structural equation modeling demonstrated that this difference was explained by women's more frequent experience of gender discrimination and lower perceptible fit with people higher up the professional ladder. These barriers predicted reduced expectations of success in their field (Study 1) and expected success of their sacrifices (Study 2), which in turn predicted lower willingness to make sacrifices. The results explain how external barriers play a role in internal career decision making. Importantly, our findings show that these decision-making processes are similar for men and women, yet, the circumstances under which these decisions are made are gendered. That is, both men and women weigh the odds in deciding whether to sacrifice for their career, but structural conditions may influence these perceived odds in a way that favors men. Overall, this advances our understanding of gender differences, workplace inequalities, and research on the role of “choice” and/or structural discrimination behind such inequalities

Exogenous GDF11, but not GDF8, reduces body weight and improves glucose homeostasis in mice

Insulin resistance is associated with aging in mice and humans. We have previously shown that administration of recombinant GDF11 (rGDF11) to aged mice alters aging phenotypes in the brain, skeletal muscle, and heart. While the closely related protein GDF8 has a role in metabolism, limited data are available on the potential metabolic effects of GDF11 or GDF8 in aging. To determine the metabolic effects of these two ligands, we administered rGDF11 or rGDF8 protein to young or aged mice fed a standard chow diet, short-term high-fat diet (HFD), or long-term HFD. Under nearly all of these diet conditions, administration of exogenous rGDF11 reduced body weight by 3-17% and significantly improved glucose tolerance in aged mice fed a chow (~30% vs. saline) or HF (~50% vs. saline) diet and young mice fed a HFD (~30%). On the other hand, exogenous rGDF8 showed signifcantly lesser effect or no effect at all on glucose tolerance compared to rGDF11, consistent with data demonstrating that GFD11 is a more potent signaling ligand than GDF8. Collectively, our results show that administration of exogenous rGDF11, but not rGDF8, can reduce diet-induced weight gain and improve metabolic homeostasis

One-Component Order Parameter in URu2_2Si2_2 Uncovered by Resonant Ultrasound Spectroscopy and Machine Learning

The unusual correlated state that emerges in URu$_2$Si$_2$ below T$_{HO}$ = 17.5 K is known as "hidden order" because even basic characteristics of the order parameter, such as its dimensionality (whether it has one component or two), are "hidden". We use resonant ultrasound spectroscopy to measure the symmetry-resolved elastic anomalies across T$_{HO}$. We observe no anomalies in the shear elastic moduli, providing strong thermodynamic evidence for a one-component order parameter. We develop a machine learning framework that reaches this conclusion directly from the raw data, even in a crystal that is too small for traditional resonant ultrasound. Our result rules out a broad class of theories of hidden order based on two-component order parameters, and constrains the nature of the fluctuations from which unconventional superconductivity emerges at lower temperature. Our machine learning framework is a powerful new tool for classifying the ubiquitous competing orders in correlated electron systems

An Unusual Case of Bony Styloid Processes That Extend to the Hyoid Bone

The embryological origin of the hyoid bone is a point of uncertainty, with controversy surrounding the relative contribution of the second pharyngeal arch to hyoid development. We encountered a 52-year-old male with bilateral bony styloid extension to the lesser cornu of the hyoid bone during the workup of a patient with laryngeal cancer. This embryological malformation clearly supports the hypothesis that the second pharyngeal arch gives rise to the lesser cornu and demonstrates an unusual clinical finding that may be encountered by otolaryngologists. We demonstrate the imaging findings and surgical management of this unusual anatomical variant and review the embryological basis for this rare malformation

Comparison of Hyperthermal Ground Laboratory Atomic Oxygen Erosion Yields With Those in Low Earth Orbit

The atomic oxygen erosion yields of 26 materials (all polymers except for pyrolytic graphite) were measured in two directed hyperthermal radio frequency (RF) plasma ashers operating at 30 or 35 kHz with air. The hyperthermal asher results were compared with thermal energy asher results and low Earth orbital (LEO) results from the Materials International Space Station Experiment 2 and 7 (MISSE 2 and 7) flight experiments. The hyperthermal testing was conducted to a significant portion of the atomic oxygen fluence similar polymers were exposed to during the MISSE 2 and 7 missions. Comparison of the hyperthermal asher prediction of LEO erosion yields with thermal energy asher erosion yields indicates that except for the fluorocarbon polymers of PTFE and FEP, the hyperthermal energy ashers are a much more reliable predictor of LEO erosion yield than thermal energy asher testing, by a factor of four