Engaging diverse high school students in Missouri through a deliberative climate change forum

Climate change is the most pressing environmental issue in the 21st century. Its effects increase in severity due to human actions that negatively impact natural resources. This produces risks to human health, food security, water supply, and the global economy. In order to address climate change, it is crucial to recognize it as a social-environmental issue. Formal and nonformal education plays an important role in fostering knowledge, attitudes, values, and behavior among students. Thus, it is essential to prioritize education and research that explores differences in knowledge and attitudes toward climate change among diverse high school populations. For that reason, this study aims to engage diverse high school students in Missouri through a deliberative climate change forum. This study was conducted using a mixed-methods approach with students from 2 different Missouri high schools (n=22). The quantitative approach included pre and post-test instruments, while the qualitative procedure was a focus group using the Climate Choices Issue Guide created by the North American Association for Environmental Education (NAAEE). The deliberative climate change forum was divided into five sections: recognition, reduction, adaptation, innovation, and conclusion, with 17 questions in total. Paired-sample tests showed a statistically significant increase in knowledge (t(21)=- 2.806, p=0.005), awareness (t(21)=-6.21, p<0.001), and hope (t(21)=-3.65, p<0.001) after the forum. The students were able to identify what are the causes, and consequences of global warming, and got a better understanding of climate systems. Additionally, participants provided strategies that they considered the most effective ways to address climate change. This suggests that climate change education and deliberative forums can foster awareness about environmental issues and promote positive values and attitudes towards climate change.Includes bibliographical references

Harana

Silhouette of man playing guitarhttps://scholarsjunction.msstate.edu/cht-sheet-music/12590/thumbnail.jp

Porciones 69, 70, 71, 72

From John Closner and Family Collection, contains two typed documents: 1) Affidavit of Francisco Tagle, Sr. as to possession of Porciones No. 71 and 72 (12 March 1906); 2) affidavit describing property purchase options among John Closner, J. P. Withers, James B. Wells (2 May 1902). Porcion 69, 70, 71, 72, 1902-1906, Container: 39, Box: 1, Folder: 8. University of Texas Rio Grande Valley Special Collections and Archives, Edinburg Campus. https://archives.lib.utrgv.edu/repositories/2/archival_objects/80722https://scholarworks.utrgv.edu/hidalgohist/1011/thumbnail.jp

Challenges in Chagas Disease Drug Development.

The protozoan parasite Trypanosoma cruzi causes Chagas disease, an important public health problem throughout Latin America. Current therapeutic options are characterised by limited efficacy, long treatment regimens and frequent toxic side-effects. Advances in this area have been compromised by gaps in our knowledge of disease pathogenesis, parasite biology and drug activity. Nevertheless, several factors have come together to create a more optimistic scenario. Drug-based research has become more systematic, with increased collaborations between the academic and commercial sectors, often within the framework of not-for-profit consortia. High-throughput screening of compound libraries is being widely applied, and new technical advances are helping to streamline the drug development pipeline. In addition, drug repurposing and optimisation of current treatment regimens, informed by laboratory research, are providing a basis for new clinical trials. Here, we will provide an overview of the current status of Chagas disease drug development, highlight those areas where progress can be expected, and describe how fundamental research is helping to underpin the process

Status of Leyte Gulf Fisheries CYs 2001-2011

Leyte Gulf is among the major fishing grounds in the Philippines with a shelf area of 13, 147 km2 covering the islands of Samar and Leyte. For this reason, it was chosen as the study area in Eastern Visayas under the National Stock Assessment Program (NSAP) which aims to assess the status of fisheries resources. This paper presents the fishery stock assessment results from CY 2001-2011. The annual fish catch from 2001-2011 showed a declining trend. The lowest was in 2008 with 12, 483.52 MT while the highest was in 2003 with 26,367.32 MT. The municipal fisheries had a high catch contribution except in 2001 where commercial catch was higher by 30%. Thirty eight (38) types of fishing gears were identified operating in Leyte Gulf. Danish seine (commercial, DSC) had the highest yield in the commercial fisheries sector while for the municipal fisheries sector it was gillnet (GN). The highest catch of DSC was observed in 2004 (4,243.30 MT) and the lowest in 2010 (1,203.05 MT). The highest catch per unit of effort (CPUE) for DSC was in 2004 (288.66 kg/boat landings) and the lowest was in 2010 (167.09 kg/boat landings). For GN, the highest catch and CPUE were in 2004 (3, 010.72 MT) and 2003 (8.27 kg/boat landings) respectively; while the lowest in catch and CPUE were in 2001 (339.37 MT, 4.05 kg/boat landings). The top ten (10) species caught belong to the families Leiognathidae, Carangidae, Nemipteridae, Scombridae, Gerreidae, Engraulidae, Mullidae, Synodontidae, Clupeidae, and Portunidae. The selected five (5) major stocks, which are Rastrelliger kanagurta, Leiognathus bindus, Gazza minuta, Selar crumenophthalmus, and Nemipterus hexodon were mostly abundant in the second half of the year. The percentage of catch at which they were caught before their length at maturity were as follows: 60% for R. kanagurta, 85% for L. bindus, 13% for G. minuta, 45% for S. crumenophthalmus, and 51% for N. hexodon

CD133-directed CAR T-cells for MLL Leukemia: On-Target, Off-Tumor Myeloablative Toxicity

Acknowledgements: We thank the Interfant treatment protocol and local physicians for contributing patient samples: Dr. Ronald W Stam (Princess Maxima Centre, Utrech), Dr. Mireia Camos and Dr. Jose Luis Fuster (Spanish Society of Pediatric Hematoncology), Dr. Paola Ballerini (A. Trousseau Hospital, Paris). We also thank Prof. Paresh Vyas (Oxford Univeristy, UK) and Prof. Kajsa Paulsson (Lund University, Sweden) for facilitating access to their RNA-seq database. This work has been supported by the European Research Council (CoG-2014-646903, PoC-2018-811220) to PM, the Spanish Ministry of Economy and Competitiveness (MINECO, SAF-SAF2016-80481-R, BIO2017-85364-R) to PM and EE, the Generalitat de Catalunya (SGR330, SGR102 and PERIS) to PM and EE, the Spanish Association against cancer (AECC-CI-2015) to CB, and the Health Institute Carlos III (ISCIII/FEDER, PI14-01191) to CB. PM also acknowledges financial support from the Obra Social La Caixa-Fundaciò Josep Carreras. SRZ and TV are supported by a Marie Curie fellowships. OM is supported by the Catalan Government through a Beatriu de Pinos fellowship. MB is supported by MINECO through a PhD scholarship. PM is an investigator of the Spanish Cell Therapy cooperative network (TERCEL)

Efficient elimination of primary B-ALL cells in vitro and in vivo using a novel 4-1BB-based CAR targeting a membrane-distal CD22 epitope

Altres ajuts: Funding This work was supported by the Obra Social La Caixa (LCF/PR/HR19/52160011), the Spanish Cancer Association and Leo Messi Foundation to PM.Background There are few therapeutic options available for patients with B-cell acute lymphoblastic leukemia (B-ALL) relapsing as CD19 - either after chemotherapy or CD19-targeted immunotherapies. CD22-chimeric antigen receptor (CAR) T cells represent an attractive addition to CD19-CAR T cell therapy because they will target both CD22 + CD19 - B-ALL relapses and CD19 - preleukemic cells. However, the immune escape mechanisms from CD22-CAR T cells, and the potential contribution of the epitope binding of the anti-CD22 single-chain variable fragment (scFv) remain understudied. Methods Here, we have developed and comprehensively characterized a novel CD22-CAR (clone hCD22.7) targeting a membrane-distal CD22 epitope and tested its cytotoxic effects against B-ALL cells both in in vitro and in vivo assays. Results Conformational epitope mapping, cross-blocking, and molecular docking assays revealed that the hCD22.7 scFv is a high-affinity binding antibody which specifically binds to the ESTKDGKVP sequence, located in the Ig-like V-type domain, the most distal domain of CD22. We observed efficient killing of B-ALL cells in vitro, although the kinetics were dependent on the level of CD22 expression. Importantly, we show an efficient in vivo control of patients with B-ALL derived xenografts with diverse aggressiveness, coupled to long-term hCD22.7-CAR T cell persistence. Remaining leukemic cells at sacrifice maintained full expression of CD22, ruling out CAR pressure-mediated antigen loss. Finally, the immunogenicity capacity of this hCD22.7-scFv was very similar to that of other CD22 scFv previously used in adoptive T cell therapy. Conclusions We report a novel, high-affinity hCD22.7 scFv which targets a membrane-distal epitope of CD22. 4-1BB-based hCD22.7-CAR T cells efficiently eliminate clinically relevant B- CD22 high and CD22 low ALL primary samples in vitro and in vivo. Our study supports the clinical translation of this hCD22.7-CAR as either single or tandem CD22-CD19-CAR for both naive and anti-CD19-resistant patients with B-ALL

The Trypanosoma cruzi vitamin C dependent peroxidase confers protection against oxidative stress but is not a determinant of virulence.

BACKGROUND: The neglected parasitic infection Chagas disease is rapidly becoming a globalised public health issue due to migration. There are only two anti-parasitic drugs available to treat this disease, benznidazole and nifurtimox. Thus it is important to identify and validate new drug targets in Trypanosoma cruzi, the causative agent. T. cruzi expresses an ER-localised ascorbate-dependent peroxidase (TcAPx). This parasite-specific enzyme has attracted interest from the perspective of targeted chemotherapy. METHODOLOGY/PRINCIPAL FINDINGS: To assess the importance of TcAPx in protecting T. cruzi from oxidative stress and to determine if it is essential for virulence, we generated null mutants by targeted gene disruption. Loss of activity was associated with increased sensitivity to exogenous hydrogen peroxide, but had no effect on susceptibility to the front-line Chagas disease drug benznidazole. This suggests that increased oxidative stress in the ER does not play a significant role in its mechanism of action. Homozygous knockouts could proceed through the entire life-cycle in vitro, although they exhibited a significant decrease in their ability to infect mammalian cells. To investigate virulence, we exploited a highly sensitive bioluminescence imaging system which allows parasites to be monitored in real-time in the chronic stage of murine infections. This showed that depletion of enzyme activity had no effect on T. cruzi replication, dissemination or tissue tropism in vivo. CONCLUSIONS/SIGNIFICANCE: TcAPx is not essential for parasite viability within the mammalian host, does not have a significant role in establishment or maintenance of chronic infections, and should therefore not be considered a priority for drug design

Nitroheterocyclic drugs cure experimental <i>Trypanosoma cruzi</i> infections more effectively in the chronic stage than in the acute stage

The insect-transmitted protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease, and infects 5-8 million people in Latin America. Chagas disease is characterised by an acute phase, which is partially resolved by the immune system, but then develops as a chronic life-long infection. There is a consensus that the front-line drugs benznidazole and nifurtimox are more effective against the acute stage in both clinical and experimental settings. However, confirmative studies have been restricted by difficulties in demonstrating sterile parasitological cure. Here, we describe a systematic study of nitroheterocyclic drug efficacy using highly sensitive bioluminescence imaging of murine infections. Unexpectedly, we find both drugs are more effective at curing chronic infections, judged by treatment duration and therapeutic dose. This was not associated with factors that differentially influence plasma drug concentrations in the two disease stages. We also observed that fexinidazole and fexinidazole sulfone are more effective than benznidazole and nifurtimox as curative treatments, particularly for acute stage infections, most likely as a result of the higher and more prolonged exposure of the sulfone derivative. If these findings are translatable to human patients, they will have important implications for treatment strategies

Effective Lagrangian approach to neutrinoless double beta decay and neutrino masses

Neutrinoless double beta ($0\nu\beta\beta$) decay can in general produce electrons of either chirality, in contrast with the minimal Standard Model (SM) extension with only the addition of the Weinberg operator, which predicts two left-handed electrons in the final state. We classify the lepton number violating (LNV) effective operators with two leptons of either chirality but no quarks, ordered according to the magnitude of their contribution to \znbb decay. We point out that, for each of the three chirality assignments, $e_Le_L, e_Le_R$ and $e_Re_R$, there is only one LNV operator of the corresponding type to lowest order, and these have dimensions 5, 7 and 9, respectively. Neutrino masses are always induced by these extra operators but can be delayed to one or two loops, depending on the number of RH leptons entering in the operator. Then, the comparison of the $0\nu\beta\beta$ decay rate and neutrino masses should indicate the effective scenario at work, which confronted with the LHC searches should also eventually decide on the specific model elected by nature. We also list the SM additions generating these operators upon integration of the heavy modes, and discuss simple realistic examples of renormalizable theories for each case.Comment: Accepted for publication. Few misprints corrected and new references adde