Cancer-associated fibroblasts—heroes or villains?

Cancer-associated fibroblasts (CAFs) were originally presumed to represent a homogeneous population uniformly driving tumorigenesis, united by their morphology and peritumoural location. Our understanding of CAFs has since been shaped by sophisticated in vitro and in vivo experiments, pathological association and, more recently, ablation, and it is now widely appreciated that CAFs form a group of highly heterogeneous cells with no single overarching marker. Studies have demonstrated that the CAF population contains different subtypes based on the expression of marker proteins with the capacity to promote or inhibit cancer, with their biological role as accomplices or adversaries dependent on many factors, including the cancer stage. So, while CAFs have been endlessly shown to promote the growth, survival and spread of tumours via improvements in functionality and an altered secretome, they are also capable of retarding tumorigenesis via largely unknown mechanisms. It is important to reconcile these disparate results so that the functions of, or factors produced by, tumour-promoting subtypes can be specifically targeted to improve cancer patient outcomes. This review will dissect out CAF complexity and CAF-directed cancer treatment strategies in order to provide a case for future, rational therapies.Krystyna A. Gieniec, Lisa M. Butler, Daniel L. Worthley and Susan L. Wood

Personality characteristics are independently associated with prospective memory in the laboratory, and in daily life, among older adults

Prospective memory (PM) can deteriorate with age and adversely influence health behaviours. Research suggests that personality is related to PM in healthy young adults, but we know little about the role of personality in the PM amongst older adults. Community-dwelling older adults (N=152) completed the NEO Five-Factor Inventory-3 and PM measures. After adjusting for demographics and general cognition, higher neuroticism and lower levels of openness were independently associated with lower objectively-measured time- and event-based PM. Lower conscientiousness was the only personality predictor of self-reported everyday PM failures. Findings indicate that personality plays a role in PM functioning in the laboratory and daily life

Precise measurements of radio-frequency magnetic susceptibility in (anti)ferromagnetic materials

Dynamic magnetic susceptibility, $\chi$, was studied in several intermetallic materials exhibiting ferromagnetic, antiferromagnetic and metamagnetic transitions. Precise measurements by using a 14 MHz tunnel diode oscillator (TDO) allow detailed insight into the field and temperature dependence of $\chi$. In particular, local moment ferromagnets show a sharp peak in $\chi(T)$ near the Curie temperature, $T_c$. The peak amplitude decreases and shifts to higher temperatures with very small applied dc fields. Anisotropic measurements of CeVSb$_3$ show that this peak is present provided the magnetic easy axis is aligned with the excitation field. In a striking contrast, small moment, itinerant ferromagnets (i.e., ZrZn$_2$) show a broad maximum in $\chi(T)$ that responds differently to applied field. We believe that TDO measurements provide a very sensitive way to distinguish between local and itinerant moment magnetic orders. Local moment antiferromagnets do not show a peak at the N\'eel temperature, $T_N$, but only a sharp decrease of $\chi$ below $T_N$ due to the loss of spin-disorder scattering changing the penetration depth of the ac excitation field. Furthermore, we show that the TDO is capable of detecting changes in spin order as well as metamagnetic transitions. Finally, critical scaling of $\chi(T,H)$ in the vicinity of $T_C$ is discussed in CeVSb$_3$ and CeAgSb$_2$

The effect of feeding different sources and levels of selenium on growth performance and antioxidant status of broilers raised at two different temperatures

1.This study examined the effects of different dietary sources and levels of selenium (Se) on growth performance, hepatic and breast meat Se content, glutathione peroxidase (GSH-Px) activity and total antioxidant status (TAS) in blood, when fed to broilers from 14 to 35 d of age and reared at two different temperatures (20°C and 35 °C). 2. Five hundred and sixty male Ross 308 broilers were reared in a single floor pen and fed the same proprietary starter diet from 0 to 14 d age (229.9 g/kg CP and 12.67 MJ/kg ME, without Se supplementation). 3. The experiment started at 14 d age, and the birds randomly assigned to 112 raised-floor pens (0.36m2 area, 5 birds/pen). Each of the seven experimental diets were offered to birds in 16 pens within four rooms. Two rooms were at 20°C and two rooms were maintained at 35°C. The experimental diets were fed from 14 to 35 d age and contained 214.9 g/kg CP and 13.11 MJ/kg ME. The experimental diets were as follows; control diet containing background Se only (0.189 mg/kg; C); low level sodium selenite (0.376 mg/kg; LSS): high level sodium selenite (0.558 mg/kg; HSS); low level commercial B Traxim® Se (0.244 mg/kg) (LBT); high level B Traxim® Se (0.448 mg/kg; HBT); low level selenised yeast (0.290 mg/kg; LSY); high level selenised yeast (0.487 mg/kg; HSY). 4. Birds consumed more when raised at 20°C compared to birds reared at 35°C (P≤0.05). Birds fed lower Se level reared at 35°C had higher weight gain versus those fed higher Se level (P<0.05). Birds fed SY had the lowest feed intake, weight gain and FCE (P<0.05). The greatest GSH-Px activity was observed in birds fed SS diets (P<0.001). There were interactions between diet x level for TAS, which were highest in birds fed LBT compared to birds fed HBT (P<0.05). Breast Se content was higher in birds fed HSY compared to LSY (P<0.001). The highest hepatic Se was seen in birds fed SY and lowest in C (P<0.001). 5. Birds fed BT diets showed similar levels of Se to those birds fed inorganic Se, and similar levels of GSH-Px to birds fed SY. Further comparative work with broilers fed BT and other Se supplemented diets may elucidate the findings from this report

Probing Bogoliubov Quasiparticles in Superfluid 3He with a ‘Vibrating-Wire Like’ MEMS Device

International audienceWe have measured the interaction between superfluid 3 He-B and a micro-machined goalpost-shaped device at temperatures below 0.2 T c. The measured damping follows well the theory developed for vibrating wires, in which the An-dreev reflection of quasiparticles in the flow field around the moving structure leads to a nonlinear frictional force. At low velocities the damping force is proportional to velocity while it tends to saturate for larger excitations. Above a velocity of 2.6 mms −1 the damping abruptly increases, which is interpreted in terms of Cooper-pair breaking. Interestingly, this critical velocity is significantly lower than reported with other mechanical probes immersed in superfluid 3 He. Furthermore , we report on a nonlinear resonance shape for large motion amplitudes that we interpret as an inertial effect due to quasiparticle friction, but other mechanisms could possibly be invoked as well. PACS numbers: 85.85.+j, 67.30.H-, 67.30.e

Changes in the immune landscape of TNBC after neoadjuvant chemotherapy: correlation with relapse

Introduction: Patients with high-risk, triple negative breast cancer (TNBC) often receive neoadjuvant chemotherapy (NAC) alone or with immunotherapy. Various single-cell and spatially resolved techniques have demonstrated heterogeneity in the phenotype and distribution of macrophages and T cells in this form of breast cancer. Furthermore, recent studies in mice have implicated immune cells in perivascular (PV) areas of tumors in the regulation of metastasis and anti-tumor immunity. However, little is known of how the latter change during NAC in human TNBC or their impact on subsequent relapse, or the likely efficacy of immunotherapy given with or after NAC. Methods: We have used multiplex immunofluorescence and AI-based image analysis to compare the immune landscape in untreated and NAC-treated human TNBCs. We quantified changes in the phenotype, distribution and intercellular contacts of subsets of tumor-associated macrophages (TAMs), CD4+ and CD8+ T cells, and regulatory T cells (Tregs) in PV and non-PV various areas of the stroma and tumor cell islands. These were compared in tumors from patients who had either developed metastases or were disease-free (DF) after a three-year follow up period. Results: In tumors from patients who remained DF after NAC, there was a marked increase in stromal CD163+ TAMs, especially those expressing the negative checkpoint regulator, T-cell immunoglobulin and mucin domain 3 (TIM-3). Whereas CD4+ T cells preferentially located to PV areas in the stroma of both untreated and NAC-treated tumors, specific subsets of TAMs and Tregs only did so only after NAC. Distinct subsets of CD4+ and CD8+ T cells formed PV clusters with CD163+ TAMs and Tregs. These were retained after NAC. Discussion: Quantification of stromal TIM-3+CD163+ TAMs in tumor residues after NAC may represent a new way of identifying patients at high risk of relapse. PV clustering of immune cells is highly likely to regulate the activation and function of T cells, and thus the efficacy of T cell-based immunotherapies administered with or after NAC

Effect of feeding different sources of selenium on growth performance and antioxidant status of broilers

This study was conducted to determine the effect of different sources of selenium (Se) on breast and liver tissue deposition, apparent metabolisable energy (AME), growth performance and antioxidant status of broilers, measured as Se content in liver and breast tissues and glutathione peroxidase (GSH-Px) in blood, when used in 0–35 d broiler chicken diets. 2. A total of 200 male Ross 308 broilers were used in the feeding trial, which comprised two dietary phases, a starter from 0 to 21 d and finisher from 21 to 35 d of age. Four treatments with 10 replications each were used. A control diet (C) was formulated that was sufficient in protein and energy (230 and 215 g/kg of crude protein and 12.67 and 13.11 MJ/kg of metabolisable energy, respectively), for both phases, but contained background Se only from the feed ingredients. The first treatment diet (IS) was made from the C diet supplemented with 10.35 g/t inorganic source of elemental Se in both feed phases. The third treatment (SY) was the control diet supplemented with 136.36 g/t selenised yeast (Sacchromyces cerevisiae) in both feed phases. A fourth treatment (SS) was the C diet supplemented with 0.666 g/t sodium selenite an inorganic source of Se in both starter and finisher diets. 3. Birds fed the SY diet consumed less and weighed less than those fed IS or C (P < 0.05; 0–35 d of age), but there was no difference compared to birds fed SS diets. There were no differences in FCR or dietary AME between broilers fed different Se sources. All diets containing supplementary Se increased concentrations in the liver and breast muscle, and for GSH-Px levels in blood compared to birds fed the C diet (P < 0.001). Birds fed SY diets had greater Se levels in liver and breast tissues compared to birds fed any of the other diets (P < 0.001). 4. Diets supplemented with Se had variable effects on broiler growth performances and antioxidant status. Feeding Se from a yeast source has higher transfer into breast tissues. Feeding different sources and levels of Se to birds in a more challenging situation to induce oxidative stress may bring more conclusive results

Electron Dynamics in Nd1.85_{1.85}Ce.15_{.15}CuO4+δ_{4+\delta}: Evidence for the Pseudogap State and Unconventional c-axis Response

Infrared reflectance measurements were made with light polarized along the a- and c-axis of both superconducting and antiferromagnetic phases of electron doped Nd$_{1.85}$Ce$_{.15}$CuO$_{4+\delta}$. The results are compared to characteristic features of the electromagnetic response in hole doped cuprates. Within the CuO$_2$ planes the frequency dependent scattering rate, 1/$\tau(\omega)$, is depressed below $\sim$ 650 cm$^{-1}$; this behavior is a hallmark of the pseudogap state. While in several hole doped compounds the energy scales associated with the pseudogap and superconducting states are quite close, we are able to show that in Nd$_{1.85}$Ce$_{.15}$CuO$_{4+\delta}$ the two scales differ by more than one order of magnitude. Another feature of the in-plane charge response is a peak in the real part of the conductivity, $\sigma_1(\omega)$, at 50-110 cm$^{-1}$ which is in sharp contrast with the Drude-like response where $\sigma_1(\omega)$ is centered at $\omega=0$. This latter effect is similar to what is found in disordered hole doped cuprates and is discussed in the context of carrier localization. Examination of the c-axis conductivity gives evidence for an anomalously broad frequency range from which the interlayer superfluid is accumulated. Compelling evidence for the pseudogap state as well as other characteristics of the charge dynamics in Nd$_{1.85}$Ce$_{.15}$CuO$_{4+\delta}$ signal global similarities of the cuprate phase diagram with respect to electron and hole doping.Comment: Submitted to PR

Feeding dihydroquercetin and vitamin E to broiler chickens reared at standard and high ambient temperatures

The use of natural antioxidants, in particular polyphenols such as dihydroquercetin (DHQ), in animal nutrition has recently increased in popularity. This may partly be due to the risk of increased incidences of heat stress associated with raising livestock in warmer ambient temperatures, facilitated by global warming, reducing antioxidant capacity. The current research demonstrates the effect of dietary DHQ, vitaminEand standard or high ambient temperatures on growth performance, energy and nutrient metabolism, gastrointestinal tract (GIT) development, jejunal villus morphometry and antioxidant status in broiler chickens. Each of the four experimental diets was fed to 16 pens of five birds, which were allocated to four rooms (four pens in each room). The temperature in two rooms was maintained at aconstant 35°C (high temperature; HT), and the temperature in the other two rooms was gradually reduced from 27°C at 7 dof age to 22°C at 20 dof age (standard temperature; ST). Rearing birds at HT reduced feed intake, weight gain, weight of small intestine, total GIT, liver, spleen, heart, villus height, villus surface area and lowered blood glutationperoxidase (GSH-Px). Dietary DHQ increased blood GSH-Px and total antioxidant status, increased heart weight and reduced caecal size. When fed separately, DHQ and vitamin E improved hepatic vitamin E concentration. Feeding vitamin Eincreased spleen and liver weights. When fed together, DHQ and vitamin Ereduced villus height, villus height to crypt depth ratio and villus surface area. Temperature and antioxidants did not affect energy and nutrient metabolism. There were no effects of dietary antioxidants on growth performance of broiler chickens and there were no mortalities. At present, it is unclear if feeding antioxidants (in particular DHQ) at different levels, using different dietary formulations, and rearing birds under arange of environmental conditions may be effective at enhancing production performance and bird health in hot ambient climates