The generation and specificity of cytotoxic T cells raised against syngeneic tumor cells bearing AKR/gross murine leukemia virus antigens

Efforts were made to generate C57BL/6 cytotoxic effector cells to a syngeneic leukemia (E{male}G2) bearing AKR/Gross virus antigens. As we were unable to induce significant cytotoxic activity by immunization with up to 10(8) irradiated E{male}G2 cells, even when cells from such primed animals were subsequently restimulated with E{male}G2 cells in vitro, C57BL/6 mice were immunized with an aliogeneic, virus-producing AKR leukemic cell line (AKR SL3). Peritoneal exudate cells and, to a lesser degree, spleen cells from these mice showed significant lytic activity toward the immunizing allogeneic tumor but not toward E{male}G2. When spleen cells were harvested from animals {approximately equal to}10 d after injection of AKR SL3 and rechallenged in vitro with either E{male}G2 or AKR.H-2(b) SL1, another tumor that displays AKR/Gross virus antigens, then a vigorous cytotoxic response against E{male}G2 and AKR. H-2(b) SL1 was obtained. Effector cells generated by AKR SL3 priming followed by in vitro stimulation with E{male}G2 or AKR.H-2(b) SL1 lysed only cells of H-2(b) haplotype which were strongly positive for the display of serologically detectable AKR/Gross virus antigens. Thus, AKR SL3 cells were not lysed nor were EL4 cells (H-2(b); but only weakly positive for gp70). Cells not bearing the MuLV antigens tested for, such as P815 mastocytoma cells and spleen cell "blasts" from C57BL/6 and CBA (H-2(k)) mice, were also insusceptible to attack. The cytotoxic effector cells induced bore Thy 1.2 alloantigen and were of the Lyt 1+2+ phenotype. Collectively, these findings are consistent with the conclusion that the cytotoxic T cells raised against E{male}G2 are directed against AKR/Gross virus-associated antigens and are H-2 restricted. It will be of interest to determine the relevance of such effector cells to the known resistance of the C57BL/6 mouse to AKR/Gross virus-induced leukemia

Optimizing the colour and fabric of targets for the control of the tsetse fly Glossina fuscipes fuscipes

Background: Most cases of human African trypanosomiasis (HAT) start with a bite from one of the subspecies of Glossina fuscipes. Tsetse use a range of olfactory and visual stimuli to locate their hosts and this response can be exploited to lure tsetse to insecticide-treated targets thereby reducing transmission. To provide a rational basis for cost-effective designs of target, we undertook studies to identify the optimal target colour. Methodology/Principal Findings: On the Chamaunga islands of Lake Victoria , Kenya, studies were made of the numbers of G. fuscipes fuscipes attracted to targets consisting of a panel (25 cm square) of various coloured fabrics flanked by a panel (also 25 cm square) of fine black netting. Both panels were covered with an electrocuting grid to catch tsetse as they contacted the target. The reflectances of the 37 different-coloured cloth panels utilised in the study were measured spectrophotometrically. Catch was positively correlated with percentage reflectance at the blue (460 nm) wavelength and negatively correlated with reflectance at UV (360 nm) and green (520 nm) wavelengths. The best target was subjectively blue, with percentage reflectances of 3%, 29%, and 20% at 360 nm, 460 nm and 520 nm respectively. The worst target was also, subjectively, blue, but with high reflectances at UV (35% reflectance at 360 nm) wavelengths as well as blue (36% reflectance at 460 nm); the best low UV-reflecting blue caught 3× more tsetse than the high UV-reflecting blue. Conclusions/Significance: Insecticide-treated targets to control G. f. fuscipes should be blue with low reflectance in both the UV and green bands of the spectrum. Targets that are subjectively blue will perform poorly if they also reflect UV strongly. The selection of fabrics for targets should be guided by spectral analysis of the cloth across both the spectrum visible to humans and the UV region

In an in vitro model of human tuberculosis, monocyte-microglial networks regulate matrix metalloproteinase-1 and -3 gene expression and secretion via a p38 mitogen activated protein kinase-dependent pathway.

BACKGROUND: Tuberculosis (TB) of the central nervous system (CNS) is characterized by extensive tissue inflammation, driven by molecules that cleave extracellular matrix such as matrix metalloproteinase (MMP)-1 and MMP-3. However, relatively little is known about the regulation of these MMPs in the CNS. METHODS: Using a cellular model of CNS TB, we stimulated a human microglial cell line (CHME3) with conditioned medium from Mycobacterium tuberculosis-infected primary human monocytes (CoMTb). MMP-1 and MMP-3 secretion was detected using ELISAs confirmed with casein zymography or western blotting. Key results of a phospho-array profile that detects a wide range of kinase activity were confirmed with phospho-Western blotting. Chemical inhibition (SB203580) of microglial cells allowed investigation of expression and secretion of MMP-1 and MMP-3. Finally we used promoter reporter assays employing full length and MMP-3 promoter deletion constructs. Student's t-test was used for comparison of continuous variables and multiple intervention experiments were compared by one-way ANOVA with Tukey's correction for multiple pairwise comparisons. RESULTS: CoMTb up-regulated microglial MMP-1 and MMP-3 secretion in a dose- and time-dependent manner. The phospho-array profiling showed that the major increase in kinase activity due to CoMTb stimulation was in p38 mitogen activated protein kinase (MAPK), principally the α and γ subunits. p38 phosphorylation was detected at 15 minutes, with a second peak of activity at 120 minutes. High basal extracellular signal-regulated kinase activity was further increased by CoMTb. Secretion and expression of MMP-1 and MMP-3 were both p38 dependent. CoMTb stimulation of full length and MMP-3 promoter deletion constructs demonstrated up-regulation of activity in the wild type but a suppression site between -2183 and -1612 bp. CONCLUSIONS: Monocyte-microglial network-dependent MMP-1 and MMP-3 gene expression and secretion are dependent upon p38 MAPK in tuberculosis. p38 is therefore a potential target for adjuvant therapy in CNS TB

The group structure of non-Abelian NS-NS transformations

We study the transformations of the worldvolume fields of a system of multiple coinciding D-branes under gauge transformations of the supergravity Kalb-Ramond field. We find that the pure gauge part of these NS-NS transformations can be written as a U(N) symmetry of the underlying Yang-Mills group, but that in general the full NS-NS variations get mixed up non-trivially with the U(N). We compute the commutation relations and the Jacobi identities of the bigger group formed by the NS-NS and U(N) transformations.Comment: Latex, 11 pages. v2: Typos corrected; version to appear in JHEP

Tuberculosis/HIV/AIDS coinfection in Porto Alegre, RS/Brazil - invisibility and silencing of the most affected groups

OBJECTIVE: To analyze how belonging to certain social groups contributes to constituting the vulnerabilities associated with illnesses due to tuberculosis/HIV/AIDS coinfection. METHODOLOGYThis is a qualitative study carried out in the city of Porto Alegre, state of Rio Grande do Sul, in regions of high social vulnerability. Twenty coinfected people were interviewed in specialized health services between August and December 2016. The analysis was based on the frameworks The Sound of Silence and Vulnerability and Human Rights. RESULTS: Socioeconomic conditions were decisive for the constitution of the vulnerability conditions. Processes of people invisibilization, and the silencing of their voices, in a scenario marked by economic, racial and gender inequalities, contributed for their health needs not to be understood and effectively taken into account in the services actions. FINAL CONSIDERATIONS: The more effective strategies are to legitimize voices and to understand the needs of those affected by coinfection, the greater the chances that programmatic responses to the problem will be successful

Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22

A substantial proportion of familial colorectal cancer (CRC) is not a consequence of known susceptibility loci, such as mismatch repair (MMR) genes, supporting the existence of additional loci. To identify novel CRC loci, we conducted a genome-wide linkage scan in 356 white families with no evidence of defective MMR (i.e., no loss of tumor expression of MMR proteins, no microsatellite instability (MSI)-high tumors, or no evidence of linkage to MMR genes). Families were ascertained via the Colon Cancer Family Registry multi-site NCI-supported consortium (Colon CFR), the City of Hope Comprehensive Cancer Center, and Memorial University of Newfoundland. A total of 1,612 individuals (average 5.0 per family including 2.2 affected) were genotyped using genome-wide single nucleotide polymorphism linkage arrays; parametric and non-parametric linkage analysis used MERLIN in a priori-defined family groups. Five lod scores greater than 3.0 were observed assuming heterogeneity. The greatest were among families with mean age of diagnosis less than 50 years at 4q21.1 (dominant HLOD = 4.51, α = 0.84, 145.40 cM, rs10518142) and among all families at 12q24.32 (dominant HLOD = 3.60, α = 0.48, 285.15 cM, rs952093). Among families with four or more affected individuals and among clinic-based families, a common peak was observed at 15q22.31 (101.40 cM, rs1477798; dominant HLOD = 3.07, α = 0.29; dominant HLOD = 3.03, α = 0.32, respectively). Analysis of families with only two affected individuals yielded a peak at 8q13.2 (recessive HLOD = 3.02, α = 0.51, 132.52 cM, rs1319036). These previously unreported linkage peaks demonstrate the continued utility of family-based data in complex traits and suggest that new CRC risk alleles remain to be elucidated. © 2012 Cicek et al

Heat storage in upper and lower body during high-intensity exercise in athletes with spinal cord injuries

Background: The thermophysiology of athletes with spinal cord injuries (SCI) is not well understood. Spinal cord lesions impact muscle mass, thermoregulatory neural signals and circulatory function. Understanding SCI thermoregulation physiology would benefit exercise function. Therefore, this study was designed to describe heat storage in the upper and lower bodies of SCI and able-bodied (AB) athletes. Procedure: Seven SCI and 8 AB athletes (matched for arm-crank VO2 peak) performed a ramp protocol in an environment similar to an indoor competitive environment (21˚C±1.5˚C, 55±3% relative humidity).Results: SCI athletes experienced similar upper-body heat storage of 0.82±0.59 J.g-1 and lower-body heat storage of 0.47±0.33 J.g-1 compared with that of AB athletes at 0.80±0.61 J.g-1 and 0.27±0.22 J.g-1 for upper and lower body, respectively. There were no significant differences between groups for rectal temperature (Trec) or oesophageal temperature (Tes). However, mean skin temperature (Msk) was significantly higher for SCI throughout the exercise bout (p=0.006). Conclusions: The results of this study suggest that SCI and AB athletes appear to thermoregulate in a similar manner, though SCI tend to store slightly more heat

Exposure to microplastics reduces attachment strength and alters the haemolymph proteome of blue mussels (Mytilus edulis)

The contamination of marine ecosystems with microplastics, such as the polymer polyethylene, a commonly used component of single-use packaging, is of global concern. Although it has been suggested that biodegradable polymers, such as polylactic acid, may be used to replace some polyethylene packaging, little is known about their effects on marine organisms. Blue mussels, Mytilus edulis, have become a “model organism” for investigating the effects of microplastics in marine ecosystems. We show here that repeated exposure, over a period of 52 days in an outdoor mesocosm setting, of M. edulis to polyethylene microplastics reduced the number of byssal threads produced and the attachment strength (tenacity) by ∼50%. Exposure to either type of microplastic altered the haemolymph proteome and, although a conserved response to microplastic exposure was observed, overall polyethylene resulted in more changes to protein abundances than polylactic acid. Many of the proteins affected are involved in vital biological processes, such as immune regulation, detoxification, metabolism and structural development. Our study highlights the utility of mass spectrometry-based proteomics to assess the health of key marine organisms and identifies the potential mechanisms by which microplastics, both conventional and biodegradable, could affect their ability to form and maintain reefs

Acute and session RPE responses during resistance training: Bouts to failure at 60% and 90% of 1RM

Objective. To compare resistance bouts performed to failure atlow (60% 1RM) and high (90% 1RM) workloads for acute rate of perceived exertion (RPE) (per exercise), session RPE (S-RPE) (30 min post), HR (per exercise) and total work (per session, and per exercise).Background. RPE is a convenient method for quantifying intensityin aerobic exercise. However, RPE has recently been extended to exercise modalities dominated by anaerobic pathways such as resistance training (RT). Method. Subjects (N=12) were assessed using an exercise-specific1 repetition maximum (1RM) for 6 exercises. On separate days in a counterbalanced order, subjects performed 3 sets of each exercise to volitional failure at a low intensity (LI) and a high intensity (HI) with 2 minutes rest between sets and exercises. At the end of each set, subjects estimated acute RPE for that set using a 10-point numerical scale. Thirty minutes after the end of the exercise session subjects estimated their S-RPE for the entire workout. HR, total work, and acute RPE were compared (HI v. LI) using repeated measures ANOVA.Results. A paired samples t-test showed LI was significantly higher(p=0.039) than HI for session RPE (LI=8.8±0.8, HI=6.3±1.2) andtotal work (LI=17461±4419, HI=8659±2256) (p=0.043). Per exercise,total work and acute RPE were significantly greater (p=0.01) for LI for all exercises. Peak HR was significantly higher per exercise during LI for leg press (p=0.041), bench press (p=0.031), lat pull-down (p=0.037) and shoulder press (p=0.046)