In contrast to antigen-specific αβ-T cells (adaptive immune system), γδ-T cells can recognize and lyse malignantly transformed cells almost immediately upon encounter in a manner that does not require the recognition of tumor-specific antigens (innate immune system). Given the welldocumented capacity of γδ-T cells to innately kill a variety of malignant cells, efforts are now actively underway to exploit the antitumor properties of γδ-T cells for clinical purposes. Here, we present for the first time preclinical in vivo mouse models of γδ-T cell-based immunotherapy directed against breast cancer. These studies were explicitly designed to approximate clinical situations in which adoptively-transferred γδ-T cells would be employed therapeutically against breast cancer. Using radioisotope-labeled γδ-T cells, we first show that adoptively-transferred γδ-T cells localize to breast tumors in a mouse model (4T1 mammary adenocarcinoma) of human breast cancer. Moreover, by using an antibody directed against the γδ-T cell receptor (TCR) we determined that localization of adoptively-transferred γδ-T cells to tumor is a TCR-dependant process. Additionally, biodistribution studies revealed that adoptively-transferred γδ-T cells traffic differently in tumor-bearing mice compared to healthy with fewer γδ-T cells localizing into the spleens of tumor-bearing mice. Finally, in both syngeneic (4T1) and xenogeneic (2Lmp) models of breast cancer, we demonstrate that adoptively-transferred γδ-T cells are both effective against breast cancer and are otherwise welltolerated by treated animals. These findings provide a strong preclinical rationale for using ex vivo expanded adoptively-transferred γδ-T cells as a form of cell-based immunotherapy for the treatment of breast cancer. Additionally, these studies establish that clinically-applicable methods for radiolabeling γδ-T cells allows for the tracking of adoptively-transferred γδ-T cells in tumor-bearing hosts.

Background Approximately 20.5 million infants were born weighing <2500 g (defined as low birthweight or LBW) in 2015, primarily in low- and middle-income countries (LMICs). Infants born LBW, including those born preterm (<37 weeks gestation), are at increased risk for numerous consequences, including neonatal mortality and morbidity as well as suboptimal health and nutritional status later in life. The objective of this study was to identify predictors of LBW and preterm birth among infants in rural Uganda. Methods Data were derived from a prospective birth cohort study conducted from 2014–2016 in 12 districts across northern and southwestern Uganda. Birth weights were measured in triplicate to the nearest 0.1 kg by trained enumerators within 72 hours of delivery. Gestational age was calculated from the first day of last menstrual period (LMP). Associations between household, maternal, and infant characteristics and birth outcomes (LBW and preterm birth) were assessed using bivariate and multivariable logistic regression with stepwise, backward selection analyses. Results Among infants in the study, 4.3% were born LBW (143/3,337), and 19.4% were born preterm (744/3,841). In multivariable analysis, mothers who were taller (>150 cm) (adjusted Odds Ratio (aOR) = 0.42 (95% CI = 0.24, 0.72)), multigravida (aOR = 0.62 (95% CI = 0.39, 0.97)), or with adequate birth spacing (>24 months) (aOR = 0.60 (95% CI = 0.39, 0.92)) had lower odds of delivering a LBW infant Mothers with severe household food insecurity (aOR = 1.84 (95% CI = 1.22, 2.79)) or who tested positive for malaria during pregnancy (aOR = 2.06 (95% CI = 1.10, 3.85)) had higher odds of delivering a LBW infant. In addition, in multivariable analysis, mothers who resided in the Southwest (aOR = 0.64 (95% CI = 0.54, 0.76)), were ≥20 years old (aOR = 0.76 (95% CI = 0.61, 0.94)), with adequate birth spacing (aOR = 0.76 (95% CI = 0.63, 0.93)), or attended ≥4 antenatal care (ANC) visits (aOR = 0.56 (95% CI = 0.47, 0.67)) had lower odds of delivering a preterm infant; mothers who were neither married nor cohabitating (aOR = 1.42 (95% CI = 1.00, 2.00)) or delivered at home (aOR = 1.25 (95% CI = 1.04, 1.51)) had higher odds. Conclusions In rural Uganda, severe household food insecurity, adolescent pregnancy, inadequate birth spacing, malaria infection, suboptimal ANC attendance, and home delivery represent modifiable risk factors associated with higher rates of LBW and/or preterm birth. Future studies on interventions to address these risk factors may be warranted.

Leucine zipper/EF-hand-containing transmembrane protein 1 (LETM1) has been identified as the gene responsible for Wolf-Hirschhorn syndrome (WHS), which is characterized by intellectual disability, epilepsy, growth delay and craniofacial dysgenesis. LETM1 is a mitochondrial inner membrane protein that encodes a homolog of the yeast protein Mdm38, which is involved in mitochondrial morphology. In the present review, the importance of LETM1 in WHS and its role within the mitochondrion was explored. LETM1 governs the mitochondrion ion channel and is involved in mitochondrial respiration. Recent studies have reported that LETM1 acts as a mitochondrial Ca 2+ /H + antiporter. LETM1 has also been identified as a K + /H + exchanger, and serves a role in Mg 2+ homeostasis. The function of LETM1 in mitochondria regulation is regulated by its binding partners, carboxyl-terminal modulator protein and mitochondrial ribosomal protein L36. Therefore, we describe the remarkable role of LETM1 in mitochondrial network physiology and its function in mitochondrion-mediated cell death. In the context of these findings, we suggest that the participation of LETM1 in tumorigenesis through the alteration of cancer metabolism should be investigated. This review provides a comprehensive description of LETM1 function, which is required for mitochondrial homeostasis and cellular viability.

Antipsychotic drugs are regularly used for the treatment of many types of psychiatric disorders. The administration of second-generation antipsychotics is often associated with weight gain and the development of diabetes mellitus; however, the molecular mechanisms underlying the effects of these drugs remain poorly understood. Leptin and insulin play key roles in the regulation of energy balance and glucose homeostasis, and resistance to the actions of these hormones can occur with obesity and inflammation, resulting in the pathogenesis of obesity and type 2 diabetes. In this study, the effects of risperidone on the insulin-induced protein kinase B (PKB) phosphorylation and leptin-stimulated signal transducer and activator of transcription 3 (STAT3) phosphorylation were investigated in the human SH-SY5Y neuroblastoma cell line. The treatment of these cells with risperidone induced the activation of extracellular signal-related kinase (ERK) by cellular cyclic adenosine 3-monophosphate (cAMP)-dependent protein kinase (also known as protein kinase A; PKA) and the mechanisms involved include the induction of suppressor of cytokine signaling 3 (SOCS3) and suppressor of cytokine signaling 6 (SOCS6) expression. The risperidone-induced ERK activation induced an upregulation of SOCS3 and SOCS6 mRNA expression levels. Taken together, these results suggest that risperidone modulates SOCS3 and SOCS6 expression through adenylate cyclase-mediated ERK activation, which, in turn, leads to an inhibition of insulin-induced PKB phosphorylation and leptin-stimulated STAT3 phosphorylation. Eventually, these effects result in excessive body weight gain due to the inhibition of both the leptin and insulin signaling pathways.

The present study is in response to increased interest towards assessing the feasibility of a small-scale autonomous helicopter (gross weight less than 1 kg) for Martian exploration. An autonomous rotorcraft may be ideally suited for such an application because of its unique advantages, which include the ability to take off/land vertically on harsh terrain, and greater speed, range, and field of view, when compared to a traditional surface rover. The atmospheric conditions on Mars present a unique set of design challenges. Even though the Martian gravity is only about 38% of Earth's gravity, the Martian average atmospheric density is about 70 times lower than Earth's atmospheric density. Therefore, the rotors would be operating at extremely low Reynolds numbers, even lower than 5000 for a small-scale helicopter. However, the Mach number will be significantly higher (M > 0.4) because of the higher tip speed required (due to lower density) and because of the fact that the speed of sound on Mars is only about 72% of the speed of sound on Earth. This low-Reynolds-number, high-Mach-number flow condition on the blade imposes severe constraints on the rotor design. The solution proposed in the present study involves scaling up the rotor size to produce the required thrust at acceptable Mach and Reynolds numbers. The hover performance of a full-scale rotor for a 200 g Martian coaxial helicopter was experimentally evaluated in an evacuation chamber, where the exact Martian air density was simulated. The maximum figure of merit obtained for the baseline rotor was less than 0.4 at an operating Reynolds number of 3300 and Mach number of 0.34. Increasing the Reynolds number at a constant Mach number by changing the air density increased the figure of merit of the same rotor to over 0.6 at a Reynolds number of 35,000. As the Reynolds numbers was decreased to ultralow values (Re < 5000), the blade collective pitch angle for maximum figure of merit increased even up to 30 deg. A key conclusion from this study is the feasibility of small-scale hovering flight on Mars with a realistic endurance (12-13 min). Nomenclature= blade chord DL = T∕A, disk loading FM = figure of merit P = mechanical power required PL = T∕P, power loading R = radius of the rotor T = thrust κ = induced power factor ρ = air density σ = solidity (total blade area/rotor disk area) Ω = rotational speed