Mosquito immune responses and compatibility between Plasmodium parasites and anopheline mosquitoes

<p>Abstract</p> <p>Background</p> <p>Functional screens based on dsRNA-mediated gene silencing identified several <it>Anopheles gambiae </it>genes that limit <it>Plasmodium berghei </it>infection. However, some of the genes identified in these screens have no effect on the human malaria parasite <it>Plasmodium falciparum</it>; raising the question of whether different mosquito effector genes mediate anti-parasitic responses to different <it>Plasmodium </it>species.</p> <p>Results</p> <p>Four new <it>An. gambiae </it>(G3) genes were identified that, when silenced, have a different effect on <it>P. berghei </it>(Anka 2.34) and <it>P. falciparum </it>(3D7) infections. Orthologs of these genes, as well as <it>LRIM1 </it>and <it>CTL4</it>, were also silenced in <it>An. stephensi </it>(Nijmegen Sda500) females infected with <it>P. yoelii </it>(17XNL). For five of the six genes tested, silencing had the same effect on infection in the <it>P. falciparum-An. gambiae </it>and <it>P. yoelii-An. stephensi </it>parasite-vector combinations. Although silencing <it>LRIM1 </it>or <it>CTL4 </it>has no effect in <it>An. stephensi </it>females infected with <it>P. yoelii</it>, when <it>An. gambiae </it>is infected with the same parasite, silencing these genes has a dramatic effect. In <it>An. gambiae </it>(G3), TEP1, LRIM1 or LRIM2 silencing reverts lysis and melanization of <it>P. yoelii</it>, while <it>CTL4 </it>silencing enhances melanization.</p> <p>Conclusion</p> <p>There is a broad spectrum of compatibility, the extent to which the mosquito immune system limits infection, between different <it>Plasmodium </it>strains and particular mosquito strains that is mediated by TEP1/LRIM1 activation. The interactions between highly compatible animal models of malaria, such as <it>P. yoelii </it>(17XNL)-<it>An. stephensi </it>(Nijmegen Sda500), is more similar to that of <it>P. falciparum </it>(3D7)-<it>An. gambiae </it>(G3).</p

Prediction of unplanned hospitalizations in older patients treated with chemotherapy

Purpose: To determine the incidence of unplanned hospitalization (UH) and to identify risk factors for UH in elderly patients with cancer who start chemotherapy. Methods: In all, 493 patients over 70 years starting new chemotherapy regimens were prospectively included. A pre-chemotherapy geriatric assessment was performed, and tumor and treatment variables were collected. The association between these factors and UH was examined by using multivariable logistic regression. Score points were assigned to each risk factor. Results: During the first 6 months of treatment, 37% of patients had at least one episode of UH. Risk factors were the use of combination chemotherapy at standard doses, a MAX2 index ≥1, a Charlson comorbidity score ≥2, albumin level &lt;3.5 g/dL, falls in the past 6 months ≥1, and weight loss &gt;5%. Three risk groups for UH were established according to the score in all patients: 0–1: 17.5%; 2: 34%; and 3–7: 57% (p &lt; 0.001). The area under receiver operation characteristic (ROC) curve was 0.72 (95% CI: 0.67–0.77). Conclusion: This simple tool can help to reduce the incidence of UH in elderly patients with cancer who are scheduled to initiate chemotherapy treatmen

Genetic susceptibility to systemic lupus erythematosus protects against cerebral malaria in mice.

Plasmodium falciparum has exerted tremendous selective pressure on genes that improve survival in severe malarial infections. Systemic lupus erythematosus (SLE) is an autoimmune disease that is six to eight times more prevalent in women of African descent than in women of European descent. Here we provide evidence that a genetic susceptibility to SLE protects against cerebral malaria. Mice that are prone to SLE because of a deficiency in FcγRIIB or overexpression of Toll-like receptor 7 are protected from death caused by cerebral malaria. Protection appears to be by immune mechanisms that allow SLE-prone mice better to control their overall inflammatory responses to parasite infections. These findings suggest that the high prevalence of SLE in women of African descent living outside of Africa may result from the inheritance of genes that are beneficial in the immune control of cerebral malaria but that, in the absence of malaria, contribute to autoimmune disease

Prediction of Chemotoxicity, Unplanned Hospitalizations and Early Death in Older Patients with Colorectal Cancer Treated with Chemotherapy

Simple Summary Chemotoxicity, unplanned hospitalizations (Uhs) and early death (ED) are common among older patients with cancer who receive chemotherapy. Our objective was to determine factors predicting these complications. A predictive score for these three complications based on geriatric, tumor and laboratory variables was developed in a series of 215 older patients with colorectal carcinoma receiving chemotherapy. The use of this score may reliably identify patients at risk to have excessive toxicity with chemotherapy, UH or ED, thus helping to plan treatment, implement adaptive measures, and intensify follow-up. Purpose: To identify risk factors for toxicity, unplanned hospitalization (UH) and early death (ED) in older patients with colorectal carcinoma (CRC) initiating chemotherapy. Methods: 215 patients over 70 years were prospectively included. Geriatric assessment was performed before treatment, and tumor and treatment variables were collected. The association between these factors and grade 3-5 toxicity, UH and ED (<6 months) was examined by using multivariable logistic regression. Score points were assigned to each risk factor. Results: During the first 6 months of treatment, 33% of patients developed grade 3-5 toxicity, 31% had UH and 23% died. Risk factors were, for toxicity, instrumental activities of daily living, creatinine clearance, weight loss and MAX2 index; for UH, Charlson Comorbidity Score, creatinine clearance, weight loss, serum albumin, and metastatic disease; and for ED, basic activities in daily living, weight loss, metastatic disease, and hemoglobin levels. Predictive scores were built with these variables. The areas under receiver operation characteristic (ROC) curves for toxicity, UH and ED were 0.70 (95% CI: 0.64-0.766), 0.726 (95% IC: 0.661-0.799) and 0.74 (95% IC: 0.678-0.809), respectively. Conclusion: Simple scores based on geriatric, tumor and laboratory characteristics predict severe toxicity, UH and ED, and may help in treatment planning

The Anopheles gambiae Oxidation Resistance 1 (OXR1) Gene Regulates Expression of Enzymes That Detoxify Reactive Oxygen Species

OXR1 is an ancient gene, present in all eukaryotes examined so far that confers protection from oxidative stress by an unknown mechanism. The most highly conserved region of the gene is the carboxyl-terminal TLDc domain, which has been shown to be sufficient to prevent oxidative damage.OXR1 has a complex genomic structure in the mosquito A. gambiae, and we confirm that multiple splice forms are expressed in adult females. Our studies revealed that OXR1 regulates the basal levels of catalase (CAT) and glutathione peroxidase (Gpx) expression, two enzymes involved in detoxification of hydrogen peroxide, giving new insight into the mechanism of action of OXR1. Gene silencing experiments indicate that the Jun Kinase (JNK) gene acts upstream of OXR1 and also regulates expression of CAT and GPx. Both OXR1 and JNK genes are required for adult female mosquitoes to survive chronic oxidative stress. OXR1 silencing decreases P. berghei oocyst formation. Unexpectedly, JNK silencing has the opposite effect and enhances Plasmodium infection in the mosquito, suggesting that JNK may also mediate some, yet to be defined, antiparasitic response.The JNK pathway regulates OXR1 expression and OXR1, in turn, regulates expression of enzymes that detoxify reactive oxygen species (ROS) in Anopheles gambiae. OXR1 silencing decreases Plasmodium infection in the mosquito, while JNK silencing has the opposite effect and enhances infection

Development and Validation of an Early Mortality Risk Score for Older Patients Treated with Chemotherapy for Cancer

Background: Estimation of life expectancy in older patients is relevant to select the best treatment strategy. We aimed to develop and validate a score to predict early mortality in older patients with cancer. Patients and Methods: A total of 749 patients over 70 years starting new chemotherapy regimens were prospectively included. A prechemotherapy assessment that included sociodemographic variables, tumor/treatment variables, and geriatric assessment variables was performed. Association between these factors and early death was examined using multivariable logistic regression. Score points were assigned to each risk factor. External validation was performed on an independent cohort. Results: In the training cohort, the independent predictors of 6-month mortality were metastatic stage (OR 4.8, 95% CI [2.4-9.6]), ECOG-PS 2 (OR 2.3, 95% CI [1.1-5.2]), ADL ≤ 5 (OR 1.7, 95% CI [1.1-3.5]), serum albumin levels ≤ 3.5 g/dL (OR 3.4, 95% CI [1.7-6.6]), BMI < 23 kg/m2 (OR 2.5, 95% CI [1.3-4.9]), and hemoglobin levels < 11 g/dL (OR 2.4, 95% CI (1.2-4.7)). With these results, we built a prognostic score. The area under the ROC curve was 0.78 (95% CI, 0.73 to 0.84), and in the validation set, it was 0.73 (95% CI: 0.67-0.79). Conclusions: This simple and highly accurate tool can help physicians making decisions in elderly patients with cancer who are planned to initiate chemotherapy treatment

An Epithelial Serine Protease, AgESP, Is Required for Plasmodium Invasion in the Mosquito Anopheles gambiae

Background: Plasmodium parasites need to cross the midgut and salivary gland epithelia to complete their life cycle in the mosquito. However, our understanding of the molecular mechanism and the mosquito genes that participate in this process is still very limited. Methodology/Principal Findings: We identified an Anopheles gambiae epithelial serine protease (AgESP) that is constitutively expressed in the submicrovillar region of mosquito midgut epithelial cells and in the basal side of the salivary glands that is critical for Plasmodium parasites to cross these two epithelial barriers. AgESP silencing greatly reduces Plasmodium berghei and Plasmodium falciparum midgut invasion and prevents the transcriptional activation of gelsolin, a key regulator of actin remodeling and a reported Plasmodium agonist. AgESP expression is highly induced in midgut cells invaded by Plasmodium, suggesting that this protease also participates in the apoptotic response to invasion. In salivary gland epithelial cells, AgESP is localized on the basal side–the surface with which sporozoites interact. AgESP expression in the salivary gland is also induced in response to P. berghei and P. falciparum sporozoite invasion, and AgESP silencing significantly reduces the number of sporozoites that invade this organ. Conclusion: Our findings indicate that AgESP is required for Plasmodium parasites to effectively traverse the midgut and salivary gland epithelial barriers. Plasmodium parasites need to modify the actin cytoskeleton of mosquito epithelial cells t

The Research Journey as a Challenge Towards New Trends

The academic community of the department of Risaralda, in its permanent interest in evidencing the results of the research processes that are carried out from the Higher Education Institutions and as a product of the VI meeting of researchers of the department of Risaralda held in November 2021 presents its work: “The journey of research as a challenge towards new trends”, which reflects the result of the latest research and advances in different lines of knowledge in Agricultural Sciences, Health Sciences, Social Sciences and Technology and Information Sciences, which seek to solve and meet the demands of the different sectors. This work would not have been possible without the help of each of the teachers, researchers and authors who presented their articles that make up each of the chapters of the book, to them our gratitude for their commitment, dedication and commitment, since their sole purpose is to contribute from the academy and science to scientific and technological development in the search for the solution of problems and thus contribute to transform the reality of our society and communities. We also wish to extend our gratitude to the institutions of the Network that made this publication possible: UTP, UCP, UNAD, UNIREMINGTON; UNISARC, CIAF, Universidad Libre, Uniclaretiana, Fundación Universitaria Comfamiliar and UNIMINUTO, institutions that in one way or another allowed this work to become a reality, which we hope will be of interest to you.Preface............................................................................................................................7 Chapter 1. Technologies and Engineering Towards a humanization in Engineering using soft skills in training in Engineers.............................................................................................................11 Omar Iván Trejos Buriticá1, Luis Eduardo Muñoz Guerrero Innovative materials in construction: review from a bibliometric analysis....................................................................................................................27 Cristian Osorio Gómez, Daniel Aristizábal Torres, Alejandro Alzate Buitrago, Cristhian Camilo Amariles López Bibliometric review of disaster risk management: progress, trends, and challenges.........................................................................................................51 Alejandro Alzate Buitrago, Gloria Milena Molina Vinasco. Incidence of land coverage and geology, in the unstability of lands of the micro-basin of the Combia creek, Pereira, Risaralda....................................73 Alejandro Alzate Buitrago, Daniel Aristizábal Torres. Chapter 2. Arts, Humanities, and Social Sciences Training experience with teachers teaching mathematics using the inquiry methodology ...............................................................................................95 Vivian Libeth Uzuriaga López, Héctor Gerardo Sánchez Bedoya. Interpretation of the multiple representations of the fears associated to the boarding of limited visual patients in the elective I students’ written productions and low vision ...................................................................................113 Eliana Bermúdez Cardona, Ana María Agudelo Guevara, Caterine Villamarín Acosta. The relevance of local knowledge in social sciences............................................131 Alberto Antonio Berón Ospina, Isabel Cristina Castillo Quintero. Basic education students’ conceptions of conflict a view from the peace for the education....................................................................................................143 Astrid Milena Calderón Cárdenas,Carolina Aguirre Arias, Carolina Franco Ossa, Martha Cecilia Gutiérrez Giraldo, Orfa Buitrago. Comprehensive risk prevention in educational settings: an interdisciplinary and socio-educational approach ............................................................................163 Olga María Henao Trujillo, Claudia María López Ortiz. Chapter 3. Natural and Agricultural Sciences Physicochemical characterization of three substrates used in the deep bedding system in swine .......................................................................................175 Juan Manuel Sánchez Rubio, Andrés Felipe Arias Roldan, Jesús Arturo Rincón Sanz, Jaime Andrés Betancourt Vásquez. Periodic solutions in AFM models........................................................................187 Daniel Cortés Zapata, Alexander Gutiérrez Gutiérrez. Phenology in flower and fruit of Rubus glaucus benth. Cv. Thornless in Risaralda: elements for phytosanitary management .........................................199 Shirley Palacios Castro, Andrés Alfonso Patiño Martínez, James Montoya Lerma, Ricardo Flórez, Harry Josué Pérez. Socio-economic and technical characterization of the cultivation of avocado (Persea americana) in Risaralda..............................................................217 Andrés Alfonso Patiño Martínez, Kelly Saudith Castañez Poveda, Eliana Gómez Correa. Biosecurity management in backyard systems in Santa Rosa de Cabal, Risaralda................................................................................................................227 Julia Victoria Arredondo Botero, Jaiver Estiben Ocampo Jaramillo, Juan Sebastián Mera Vallejo, Álvaro de Jesús Aranzazu Hernández. CONTENTS Physical-chemical diagnosis of soils in hillside areas with predominance of Lulo CV. La Selva production system in the department of Risaralda.............241 Adriana Patricia Restrepo Gallón, María Paula Landinez Montes, Jimena Tobón López. Digestibility of three concentrates used in canine feeding....................................271 María Fernanda Mejía Silva, Valentina Noreña Sánchez, Gastón Adolfo Castaño Jiménez. Chapter 4. Economic, Administrative, and Accounting Sciences Financial inclusion in households from socioeconomic strata 1 and 2 in the city of Pereira ..................................................................................................285 Lindy Neth Perea Mosquera, Marlen Isabel Redondo Ramírez, Angélica Viviana Morales. Internal marketing strategies as a competitive advantage for the company Mobilautos SAS de Dosquebradas........................................................................303 Inés Montoya Sánchez, Sandra Patricia Viana Bolaños, Ana María Barrera Rodríguez. Uses of tourist marketing in the tourist sector of the municipality of Belén de Umbría, Risaralda.............................................................................................319 Ana María Barrera Rodríguez, Paola Andrea Echeverri Gutiérrez, María Camila Parra Buitrago, Paola Andrea Martín Muñoz, Angy Paola Ángel Vélez, Luisa Natalia Trejos Ospina. Territorial prospective of Risaralda department (Colombia), based on the SDGS...............................................................................................................333 Juan Guillermo Gil García, Samanta Londoño Velásquez. Chapter 5. Health and Sports Sciences Performance evaluation in times of pandemic. What do medical students think?.......................................................................................................353 Samuel Eduardo Trujillo Henao, Rodolfo A. Cabrales Vega, Germán Alberto Moreno Gómez. The relevance of the therapist’s self and self-reference in the training of psychologists.....................................................................................................371 Maria Paula Marmolejo Lozano, Mireya Ospina Botero. Habits related to oral health which influence lifestyle of elder people in a wellness center for the elderly in Pereira 2020. .............................................387 Isadora Blanco Pérez, Olga Patricia Ramírez Rodríguez, Ángela María Rincón Hurtado. Analysis of the suicide trend in the Coffee Region in Colombia during the years 2012-2018 ..............................................................................................405 Germán Alberto Moreno Gómez, Jennifer Nessim Salazar, Jairo Franco Londoño, Juan Carlos Medina Osorio. Hind limb long bone fractures in canines and felines...........................................419 María Camila Cruz Vélez, Valentina Herrera Morales, Alba Nydia Restrepo Jiménez, Lina Marcela Palomino, Gabriel Rodolfo Izquierdo Bravo. Prevalence of overweight and obesity in children in the rural and urban area of Risaralda....................................................................................................439 Angela María Álvarez López, Angela Liceth Pérez Rendón, Alejandro Gómez Rodas, Luis Enrique Isaza Velásquez. Chapter 6. Architecture, Design and Advertising The artisan crafts of Risaralda, characteristics, importance, and risks within the Colombian Coffee Cultural Landscape, CCCL....................................457 Yaffa Nahir Ivette Gómez Barrera, Javier Alfonso López Morales

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality