Medical imaging for the tracking of micromotors

Micro/nanomotors are useful tools for several biomedical applications, including targeted drug delivery and minimally invasive microsurgeries. However, major challenges such as in vivo imaging need to be addressed before they can be safely applied on a living body. Here, we show that positron emission tomography (PET), a molecular imaging technique widely used in medical imaging, can also be used to track a large population of tubular Au/PEDOT/Pt micromotors. Chemisorption of an iodine isotope onto the micromotor’s Au surface rendered them detectable by PET, and we could track their movements in a tubular phantom over time frames of up to 15 min. In a second set of experiments, micromotors and the bubbles released during self-propulsion were optically tracked by video imaging and bright-field microscopy. The results from direct optical tracking agreed with those from PET tracking, demonstrating that PET is a suitable technique for the imaging of large populations of active micromotors in opaque environments, thus opening opportunities for the use of this mature imaging technology for the in vivo localization of artificial swimmers

The second-generation antipsychotic drug aripiprazole modulates the serotonergic system in pancreatic islets and induces beta cell dysfunction in female mice

[Aims/hypothesis]: Second-generation antipsychotic (SGA) drugs have been associated with the development of type 2 diabetes and the metabolic syndrome in patients with schizophrenia. In this study, we aimed to investigate the effects of two different SGA drugs, olanzapine and aripiprazole, on metabolic state and islet function and plasticity. [Methods]: We analysed the functional adaptation of beta cells in 12-week-old B6;129 female mice fed an olanzapine- or aripiprazole-supplemented diet (5.5–6.0 mg kg−1 day−1) for 6 months. Glucose and insulin tolerance tests, in vivo glucose-stimulated insulin secretion and indirect calorimetry were performed at the end of the study. The effects of SGAs on beta cell plasticity and islet serotonin levels were assessed by transcriptomic analysis and immunofluorescence. Insulin secretion was assessed by static incubations and Ca2+ fluxes by imaging techniques. [Results]: Treatment of female mice with olanzapine or aripiprazole for 6 months induced weight gain (p<0.01 and p<0.05, respectively), glucose intolerance (p<0.01) and impaired insulin secretion (p<0.05) vs mice fed a control chow diet. Aripiprazole, but not olanzapine, induced serotonin production in beta cells vs controls, likely by increasing tryptophan hydroxylase 1 (TPH1) expression, and inhibited Ca2+ flux. Of note, aripiprazole increased beta cell size (p<0.05) and mass (p<0.01) vs mice fed a control chow diet, along with activation of mechanistic target of rapamycin complex 1 (mTORC1)/S6 signalling, without preventing beta cell dysfunction. [Conclusions/interpretation]: Both SGAs induced weight gain and beta cell dysfunction, leading to glucose intolerance; however, aripiprazole had a more potent effect in terms of metabolic alterations, which was likely a result of its ability to modulate the serotonergic system. The deleterious metabolic effects of SGAs on islet function should be considered while treating patients as these drugs may increase the risk for development of the metabolic syndrome and diabetes.This work was funded by H2020 Marie Sklodowska-Curie ITN-TREATMENT (Grant Agreement 721236, European Commission). We also acknowledge grants RTI2018-094052-B-100/ AEI/10.13039/501100011033 (Ministerio de Ciencia e Innovación y Fondo Europeo de Desarrollo Regional [FEDER]) and S2017/BMD-3684 (Comunidad de Madrid, Spain), and grants from Fundación Ramón Areces (Spain) and CIBERDEM (ISCIII, Spain)

A neurodegenerative disease landscape of rare mutations in Colombia due to founder effects

Background The Colombian population, as well as those in other Latin American regions, arose from a recent tri-continental admixture among Native Americans, Spanish invaders, and enslaved Africans, all of whom passed through a population bottleneck due to widespread infectious diseases that left small isolated local settlements. As a result, the current population reflects multiple founder effects derived from diverse ancestries. Methods We characterized the role of admixture and founder effects on the origination of the mutational landscape that led to neurodegenerative disorders under these historical circumstances. Genomes from 900 Colombian individuals with Alzheimer’s disease (AD) [n = 376], frontotemporal lobar degeneration-motor neuron disease continuum (FTLD-MND) [n = 197], early-onset dementia not otherwise specified (EOD) [n = 73], and healthy participants [n = 254] were analyzed. We examined their global and local ancestry proportions and screened this cohort for deleterious variants in disease-causing and risk-conferring genes. Results We identified 21 pathogenic variants in AD-FTLD related genes, and PSEN1 harbored the majority (11 pathogenic variants). Variants were identified from all three continental ancestries. TREM2 heterozygous and homozygous variants were the most common among AD risk genes (102 carriers), a point of interest because the disease risk conferred by these variants differed according to ancestry. Several gene variants that have a known association with MND in European populations had FTLD phenotypes on a Native American haplotype. Consistent with founder effects, identity by descent among carriers of the same variant was frequent. Conclusions Colombian demography with multiple mini-bottlenecks probably enhanced the detection of founder events and left a proportionally higher frequency of rare variants derived from the ancestral populations. These findings demonstrate the role of genomically defined ancestry in phenotypic disease expression, a phenotypic range of different rare mutations in the same gene, and further emphasize the importance of inclusiveness in genetic studies.Q2Q2Antecedentes La población colombiana, así como la de otras regiones latinoamericanas, surgió de una mezcla tricontinental reciente entre los nativos americanos, los invasores españoles y los africanos esclavizados, todos los cuales pasaron por un cuello de botella poblacional debido a enfermedades infecciosas generalizadas que dejaron a pequeños aislados. asentamientos locales. Como resultado, la población actual refleja múltiples efectos fundadores derivados de diversas ascendencias. Métodos Caracterizamos el papel de la mezcla y los efectos fundadores en el origen del paisaje mutacional que condujo a trastornos neurodegenerativos en estas circunstancias históricas. Genomas de 900 individuos colombianos con enfermedad de Alzheimer (EA) [n = 376], continuo degeneración lobar frontotemporal-enfermedad de la motoneurona (FTLD-MND) [n = 197], demencia de inicio temprano no especificada (EOD) [n = 73 ], y participantes sanos [n = 254] fueron analizados. Examinamos sus proporciones de ascendencia global y local y examinamos esta cohorte en busca de variantes nocivas en los genes que causan enfermedades y confieren riesgos. Resultados Identificamos 21 variantes patogénicas en genes relacionados con AD-FTLD, y PSEN1 albergaba la mayoría (11 variantes patogénicas). Se identificaron variantes de las tres ascendencias continentales. Las variantes heterocigotas y homocigotas de TREM2 fueron las más comunes entre los genes de riesgo de EA (102 portadores), un punto de interés porque el riesgo de enfermedad conferido por estas variantes difería según la ascendencia. Varias variantes genéticas que tienen una asociación conocida con MND en poblaciones europeas tenían fenotipos FTLD en un haplotipo nativo americano. De acuerdo con los efectos del fundador, la identidad por descendencia entre portadores de la misma variante fue frecuente. Conclusiones La demografía colombiana con múltiples mini-cuellos de botella probablemente mejoró la detección de eventos fundadores y dejó una frecuencia proporcionalmente más alta de variantes raras derivadas de las poblaciones ancestrales. Estos hallazgos demuestran el papel de la ascendencia definida genómicamente en la expresión fenotípica de la enfermedad, un rango fenotípico de diferentes mutaciones raras en el mismo gen, y enfatizan aún más la importancia de la inclusión en los estudios genéticos.https://orcid.org/0000-0001-6529-7077https://scholar.google.com/citations?hl=es&user=kaGongoAAAAJ&view_op=list_works&sortby=pubdatehttps://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0000055000&lang=esRevista Internacional - Indexad

A neurodegenerative disease landscape of rare mutations in Colombia due to founder effects.

Background: The Colombian population, as well as those in other Latin American regions, arose from a recent tri-continental admixture among Native Americans, Spanish invaders, and enslaved Africans, all of whom passed through a population bottleneck due to widespread infectious diseases that left small isolated local settlements. As a result, the current population reflects multiple founder effects derived from diverse ancestries. Methods: We characterized the role of admixture and founder effects on the origination of the mutational landscape that led to neurodegenerative disorders under these historical circumstances. Genomes from 900 Colombian individuals with Alzheimer's disease (AD) [n = 376], frontotemporal lobar degeneration-motor neuron disease continuum (FTLD-MND) [n = 197], early-onset dementia not otherwise specified (EOD) [n = 73], and healthy participants [n = 254] were analyzed. We examined their global and local ancestry proportions and screened this cohort for deleterious variants in disease-causing and risk-conferring genes. Results: We identified 21 pathogenic variants in AD-FTLD related genes, and PSEN1 harbored the majority (11 pathogenic variants). Variants were identified from all three continental ancestries. TREM2 heterozygous and homozygous variants were the most common among AD risk genes (102 carriers), a point of interest because the disease risk conferred by these variants differed according to ancestry. Several gene variants that have a known association with MND in European populations had FTLD phenotypes on a Native American haplotype. Consistent with founder effects, identity by descent among carriers of the same variant was frequent. Conclusions: Colombian demography with multiple mini-bottlenecks probably enhanced the detection of founder events and left a proportionally higher frequency of rare variants derived from the ancestral populations. These findings demonstrate the role of genomically defined ancestry in phenotypic disease expression, a phenotypic range of different rare mutations in the same gene, and further emphasize the importance of inclusiveness in genetic studies

Variación en los niveles séricos de Calcio, Fósforo, Magnesio, Cobre y Zinc durante las distintas etapas productivas en cabras de leche en un tambo caprino del noroeste argentino

El objetivo de este trabajo fue evaluar los niveles séricos de calcio (Ca), fósforo (P), magnesio (Mg), cobre (Cu), y zinc (Zn) en cabras lecheras en diferentes etapas productivas. Se seleccionaron 20 cabras de raza Saanen en diferentes estadios productivos: preparto (1 a 2 semanas previas al parto), posparto (1 a 2 semanas de lactancia), pico de lactancia (6 a 8 semanas de lactancia posparto) y período de seca (15 a 30 días de finalizada la lactancia) de un establecimiento lechero del valle de Lerma, Salta. Se colectaron muestras de sangre y se midieron los niveles séricos de Ca, Mg, Cu, y Zn empleando espectrofotometría de absorción atómica y P por colorimetría. Se identificó hipocalcemia (7,7±0,2 mg/dL) e hipofosfatemia (3,4±0,4 mg/dL) durante todas las etapas productivas. El Mg, por el contrario, presentó niveles adecuados durante todo el ensayo (2,5±0,06 mg/dL). Con respecto a los microminerales evaluados, solo los niveles séricos de Zn fueron inferiores a los recomendaros en todos los periodos productivos (53±4 µg/dL). Los niveles de Cu estuvieron dentro de los límites normales (53±4 µg/dL). Estos resultados permitieron identificar anormalidades en los niveles de Ca, P y Zn durante los periodos productivos evaluados. La información sobre deficiencias minerales en cabras es escasa y debe estudiarse más al respecto.The aim of this study was to evaluate the serum levels of calcium (Ca), phosphorus (P), magnesium (Mg), copper (Cu), and zinc (Zn) in dairy goats in different productive periods. Twenty Saanen breed goats were selected at different productive stages: prepartum (1 to 2 weeks before partum), postpartum (1 to 2 weeks of lactation), peak of lactation (6 to 8 weeks postpartum) and dry period (15 to 30 days of the final lactation) of a dairy farm in the Valle de Lerma, in the province of Salta. Blood samples werecollected and then, Ca, Mg, Cu and Zn levels were measured using atomic absorption spectrophotometry, and P was measured by colorimetric. Hypocalcaemia (7,7±0,2 mg/dL) and hypophosphatemia (3,4±0,4 mg/dL) were found in all production stages.In contrast, Mg levels didnot present variation during all the samplings (2.5 ± 0.06 mg / dL).In evaluated micro-minerals, only the serum levels of Zn were lower than those recommended in all the productive periods (53 ± 4 μg / dL). Serum cupper levels were within normal limits (53 ± 4 μg / dL). The obtained results allowed identifying abnormalities in Ca, P and Zn levels during the evaluated productive periods. Information about mineral deficiency in goats is restricted and it is needed to study more about it.EEA SaltaFil: Vitulli Moya, Gabriel. Universidad Católica de Salta. Facultad de Ciencias Agrarias y Veterinarias; ArgentinaFil: Vázquez, Victoria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Investigación Animal Chaco Semiarido. Área de Investigación en Salud Animal; Argentina.Fil: Martinez, Gabriela Marcela. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta; ArgentinaFil: Colque Caro, Luis Adrián. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Investigación Animal Chaco Semiarido. Área de Investigación en Salud Animal; Argentina.Fil: Medina Vallejo, Diego M. Universidad Católica de Salta. Facultad de Ciencias Agrarias y Veterinarias; ArgentinaFil: Suarez, Victor Humberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Investigación Animal Chaco Semiarido. Área de Investigación en Salud Animal; Argentina.Fil: Mattioli, Guillermo A. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Laboratorio de Nutrición Mineral; ArgentinaFil: Rosa, Diana E. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Laboratorio de Nutrición Mineral; ArgentinaFil: Micheloud, Juan Francisco. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Investigación Animal Chaco Semiarido. Grupo de Patología, Epidemiología e Investigación Diagnóstica-Área de Sanidad Animal; Argentina. Universidad Católica de Salta. Facultad de Ciencias Agrarias y Veterinarias; Argentin

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

Knowledge to Serve the City: Insights from an Emerging Knowledge-Action Network to Address Vulnerability and Sustainability in San Juan, Puerto Rico

This paper presents initial efforts to establish the San Juan Urban Long-Term Research Area Exploratory (ULTRA-Ex), a long-term program aimed at developing transdisciplinary social-ecological system (SES) research to address vulnerability and sustainability for the municipality of San Juan. Transdisciplinary approaches involve the collaborations between researchers, stakeholders, and citizens to produce socially-relevant knowledge and support decision-making. We characterize the transdisciplinary arrangement emerging in San Juan ULTRA-Ex as a knowledge-action network composed of multiple formal and informal actors (e.g., scientists, policymakers, civic organizations and other stakeholders) where knowledge, ideas, and strategies for sustainability are being produced, evaluated, and validated. We describe in this paper the on-the-ground social practices and dynamics that emerged from developing a knowledge-action network in our local context. Specifically, we present six social practices that were crucial to the development of our knowledge-action network: 1) understanding local framings; 2) analyzing existing knowledge-action systems in the city; 3) framing the social-ecological research agenda; 4) collaborative knowledge production and integration; 5) boundary objects and practices; and 6) synthesis, application, and adaptation. We discuss key challenges and ways to move forward in building knowledge-action networks for sustainability. Our hope is that the insights learned from this process will stimulate broader discussions on how to develop knowledge for urban sustainability, especially in tropical cities where these issues are under-explored

Cyanomethylene-bis(phosphonate)-Based Lanthanide Complexes: Structural, Photophysical, and Magnetic Investigations

10 pagesInternational audienceThe syntheses, structural investigations, magnetic and photophysical properties of a series of 10 lanthanide mononuclear complexes, containing the heteroditopic ligand cyanomethylene-bis(5,5-dimethyl-2-oxo-1,3,2λ5-dioxa-phosphorinane) (L), are described. The crystallographic analyses indicate two structural types: in the first one, [LnIII(L)3(H2O)2]*H2O (Ln = La, Pr, Nd), the metal ions are eight-coordinated within a square antiprism geometry, while the second one, [LnIII(L)3(H2O)]*8H2O (Ln = Sm, Eu, Gd, Tb, Dy, Ho, Er), contains seven-coordinated LnIII ions within distorted monocapped trigonal prisms...

Body-fat sensor triggers ribosome maturation in the steroidogenic gland to initiate sexual maturation in Drosophila

Fat stores are critical for reproductive success and may govern maturation initiation. Here, we report that signaling and sensing fat sufficiency for sexual maturation commitment requires the lipid carrier apolipophorin in fat cells and Sema1a in the neuroendocrine prothoracic gland (PG). Larvae lacking apolpp or Sema1a fail to initiate maturation despite accruing sufficient fat stores, and they continue gaining weight until death. Mechanistically, sensing peripheral body-fat levels via the apolipophorin/Sema1a axis regulates endocytosis, endoplasmic reticulum remodeling, and ribosomal maturation for the acquisition of the PG cells' high biosynthetic and secretory capacity. Downstream of apolipophorin/Sema1a, leptin-like upd2 triggers the cessation of feeding and initiates sexual maturation. Human Leptin in the insect PG substitutes for upd2, preventing obesity and triggering maturation downstream of Sema1a. These data show how peripheral fat levels regulate the control of the maturation decision-making process via remodeling of endomembranes and ribosomal biogenesis in gland cells