Guided accumulation of active particles by topological design of a second-order skin effect

Collective guidance of out-of-equilibrium systems without using external fields is a challenge of paramount importance in active matter, ranging from bacterial colonies to swarms of self-propelled particles. Designing strategies to guide active matter and exploiting enhanced diffusion associated to its motion will provide insights for application from sensing, drug delivery to water remediation. However, achieving directed motion without breaking detailed balance, for example by asymmetric topographical patterning, is challenging. Here we engineer a two-dimensional periodic topographical design with detailed balance in its unit cell where we observe spontaneous particle edge guidance and corner accumulation of self-propelled particles. This emergent behaviour is guaranteed by a second-order non-Hermitian skin effect, a topologically robust non-equilibrium phenomenon, that we use to dynamically break detailed balance. Our stochastic circuit model predicts, without fitting parameters, how guidance and accumulation can be controlled and enhanced by design: a device guides particles more efficiently if the topological invariant characterizing it is non-zero. Our work establishes a fruitful bridge between active and topological matter, and our design principles offer a blueprint to design devices that display spontaneous, robust and predictable guided motion and accumulation, guaranteed by out-of-equilibrium topology

Pattern of humoral immune response to Plasmodium falciparum blood stages in individuals presenting different clinical expressions of malaria

Abstract\ud \ud \ud \ud Background\ud \ud The development of protective immunity against malaria is slow and to be maintained, it requires exposure to multiple antigenic variants of malaria parasites and age-associated maturation of the immune system. Evidence that the protective immunity is associated with different classes and subclasses of antibodies reveals the importance of considering the quality of the response. In this study, we have evaluated the humoral immune response against Plasmodium falciparum blood stages of individuals naturally exposed to malaria who live in endemic areas of Brazil in order to assess the prevalence of different specific isotypes and their association with different malaria clinical expressions.\ud \ud \ud \ud Methods\ud \ud Different isotypes against P. falciparum blood stages, IgG, IgG1, IgG2, IgG3, IgG4, IgM, IgE and IgA, were determined by ELISA. The results were based on the analysis of different clinical expressions of malaria (complicated, uncomplicated and asymptomatic) and factors related to prior malaria exposure such as age and the number of previous clinical malaria attacks. The occurrence of the H131 polymorphism of the FcγIIA receptor was also investigated in part of the studied population.\ud \ud \ud \ud Results\ud \ud The highest levels of IgG, IgG1, IgG2 and IgG3 antibodies were observed in individuals with asymptomatic and uncomplicated malaria, while highest levels of IgG4, IgE and IgM antibodies were predominant among individuals with complicated malaria. Individuals reporting more than five previous clinical malaria attacks presented a predominance of IgG1, IgG2 and IgG3 antibodies, while IgM, IgA and IgE antibodies predominated among individuals reporting five or less previous clinical malaria attacks. Among individuals with uncomplicated and asymptomatic malaria, there was a predominance of high-avidity IgG, IgG1, IgG2 antibodies and low-avidity IgG3 antibodies. The H131 polymorphism was found in 44.4% of the individuals, and the highest IgG2 levels were observed among asymptomatic individuals with this allele, suggesting the protective role of IgG2 in this population.\ud \ud \ud \ud Conclusion\ud \ud Together, the results suggest a differential regulation in the anti-P. falciparum antibody pattern in different clinical expressions of malaria and showed that even in unstable transmission areas, protective immunity against malaria can be observed, when the appropriated antibodies are produced.We would like to especially thank Dr. Cristóvão Luis Pitangueira Mangueira, Flávia Cristina Kinskowski and Milca Geane de Lamos Valim at the Central Laboratory of the Clinical Hospital for participating in the determination of the total IgE and IgA levels. This work was supported by FAPESP (process number 2001/04073-5) and Laboratório de Investigações Médicas do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (LIM-48/HCFMUSP)We would like to especially thank Dr. Cristóvão Luis Pitangueira Mangueira, Flávia Cristina Kinskowski and Milca Geane de Lamos Valim at the Central Laboratory of the Clinical Hospital for participating in the determination of the total IgE and IgA levels. This work was supported by FAPESP (process number 2001/040735) and Laboratório de Investigações Médicas do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (LIM48/HCFMUSP

Cholestasis associated to inborn errors in bile acid synthesis

Several metabolic pathways are involved in the biotransformation of C27 neutral cholesterol to C24 primary bile acids (BAs), mainly cholic acid (CA) and chenodeoxycholic acid (CDCA), which are then conjugated with glycine or taurine. This process can start with the modification of the steroid ring or the shortening of the side chain and involves enzymes present in different subcellular compartments. Inborn errors affecting the biogenesis of organelles, such as peroxisomes, or the expression or function of specific enzymes of these convergent routes result in: i) the lack of mature C24-BAs, with the subsequent impairment in digestion and absorption of dietary fat and liposoluble vitamins, such as vitamin K, which may account for a deficient hepatic synthesis of several coagulation factors; ii) the accumulation of intermediate metabolites, which may affect hepatocyte physiology, causing cholestasis as a commonly shared alteration besides other deleterious hepatic events; and iii) extrahepatic clinical manifestations due to accumulation of toxic metabolites in other territories, such as the nervous system, causing neurological disorders. In general, diseases whose primary alteration is a genetic defect in BA synthesis are diagnosed in children or young individuals with a very low incidence. The symptomatology can markedly vary among individuals, ranging from mild to severe conditions. Oral therapy, based on the enrichment of the BA pool with natural C24-BAs, such as CA, CDCA, glyco-CA, or ursodeoxycholic acid (UDCA), depending on the exact deficiency causing the disease, may be beneficial in preventing life-threatening situations. In contrast, in other cases, a liver transplant is the only option for these patients. This review describes the updated information on the genetic and molecular bases of these diseases and the current approaches to achieve a selective diagnosis and specific treatment

Efecto del entomopatógeno Metathizium anisopliae, (Metch) Sorokin en larvas de los géneros Plectris, Serica y Macrodactylus, presentes en el cultivo de la arracacha (Arracacia xanthorriza)

El municipio de Cajamarca es el primer productor de arracacha en Colombia, con 5.000 has sembradas al año, cultivo que es el eje del sistema de producción y la principal fuente de ingresos de los agricultores. El principal problema del sistema es el ataque de plagas del suelo (chisas), que causan daños de tipo directo, al afectar el desarrollo del cultivo y la formación de raíces tuberosas e indirectos al disminuir el tiempo de ocupación del suelo e incrementar las áreas improductivas dentro del mismo, ocasionando el 30% de pérdidas de la producción e incrementando los costos en un 22%. El objeto del presente trabajo fue evaluar un agente causante de mortalidad que fuera económico, práctico, efectivo y de fácil multiplicación como Metarhizium anisopliae, utilizado como controlador de insectos dañinos en diversos cultivos comerciales. Para la multiplicación del entomopatógeno se utilizó una cepa nativa de la zona de Cajamarca. Las chisas, recolectadas en fincas de Cajamarca, se cuarentenaron por 30 días; para la determinación de la CL-50 y el TL-50 del entomopatógeno, se evaluaron seis concentraciones (100, 102, 104, 106, 108, 1010); se trataron larvas de tres géneros de la familia Meiolonthidae Serica, Plectris y Macrodactylus por medio del método de la vía húmeda sumergiéndolas en una suspensión homogenizada de concentración conocida, por espacio de 10 segundos. Se empleó un diseño completamente al azar con 6 tratamientos y 3 repeticiones. La sintomatología presentada por las larvas afectadas fue similar en los 3 géneros, caracterizándose por puntos de entrada de color café y negro localizados cerca o en sus aberturas naturales. El análisis de Probit reportó para el género Serica una CL 50 de 2.07* 104 conidias/ml y una TL 50 de 22 días; para el género Plectris una CL 50 de 8.6 * 103 conidias/ml y una TL 50 de 46.86 días; para Macrodactylus la CL 50 fue de 4.16 * 1013 conidias/ml y una TL 50 de 207 días. Según la mortalidad observada en los 3 géneros, Serica y Plectris son más susceptibles al hongo que Macrodactylus.Cajamarca is the first producer of Arracacia in Colombia, this crop is the main source of incomes of the region. The main problem of the Arracacia production system is the "chisa" which causes either direct damages (affecting crop development and root formation) or indirect damages (increasing improductive areas); as a consequence of this pest production is reduced in about 300 and the production costs are raised in 22%. The objective of this research was to evaluate an economic practice and effective agent of mortality of easy multiplication such as Metarhizium which has been used as a controler of pest insects in different commercial crops. To multiplicate the entomopatogenic a native stump of the Cajamarca zone was used. Chisas were collected from several farms of the zone and quarantined curing 30 days; to determine the CL 50 and TL 50 of the entomopatogenic there were evaluated six concentrations (100, 102, 101, 100, 100 and 100); larvae of 3 genus of the Melolonthidae family Serica, Plectris and Macrodactylus were treated by using the moisture way method, summering them in homogeneous suspension of known concentration during 10 seconds. A completely randomized experimental design with 6 treatments and 3 replications was used. Sintomatology presented for the affected larvae was similar in the 3 genus and was characterized by entrance points of brown and black color, localized near the natural openings of these. Probit analysis reported for Serica, a CL 50 of 2.0710 conidias/mI and a TL 50 of 22 days; for Plectris genera Cl 50 was 8.6*103 conidias!ml and TL 50 46.86 days, and for Macrodactylus genera CL 50 of 4.1610113 conidias/mI and TL 50 of 207 days. According to the mortality observed, Serica and Plectris genus are more susceptible to the fungus than Macrodactylus.Arracacha-Arracacia xanthorrhiza - Arracacia xanthorrhiza Bancr