Ancient Yersinia pestis and Salmonella enterica genomes from Bronze Age Crete

During the late 3rd millennium BCE, the Eastern Mediterranean and Near East witnessed societal changes in many regions, which are usually explained with a combination of social and climatic factors.1, 2, 3, 4 However, recent archaeogenetic research forces us to rethink models regarding the role of infectious diseases in past societal trajectories.5 The plague bacterium Yersinia pestis, which was involved in some of the most destructive historical pandemics,5, 6, 7, 8 circulated across Eurasia at least from the onset of the 3rd millennium BCE,9, 10, 11, 12, 13 but the challenging preservation of ancient DNA in warmer climates has restricted the identification of Y. pestis from this period to temperate climatic regions. As such, evidence from culturally prominent regions such as the Eastern Mediterranean is currently lacking. Here, we present genetic evidence for the presence of Y. pestis and Salmonella enterica, the causative agent of typhoid/enteric fever, from this period of transformation in Crete, detected at the cave site Hagios Charalambos. We reconstructed one Y. pestis genome that forms part of a now-extinct lineage of Y. pestis strains from the Late Neolithic and Bronze Age that were likely not yet adapted for transmission via fleas. Furthermore, we reconstructed two ancient S. enterica genomes from the Para C lineage, which cluster with contemporary strains that were likely not yet fully host adapted to humans. The occurrence of these two virulent pathogens at the end of the Early Minoan period in Crete emphasizes the necessity to re-introduce infectious diseases as an additional factor possibly contributing to the transformation of early complex societies in the Aegean and beyond.Results and discussion STAR★Method

Distributed and self-adaptive microfluidic cell cooling for CPV dense array receivers

Temperature non uniformities of the CPV receivers lead to mismatch losses. In order to deal with this issue, a cooling device, formed by a matrix of microfluidic cells with individually variable coolant flow rate, has been developed. This device tailors the distribution of the heat extraction capacity over the CPV receiver to the local cooling needs in order to reduce the temperature non uniformities with respect to microchannel devices when submitted to uniform or non-uniform illumination profiles. At equal average temperature of the CPV receiver, power generation applying the matrix of microfluidic cells with individually variable coolant flow rate is 9.7% higher than the one with conventional microchannel technology.The research leading to these results has been performed within the STREAMS project and received funding from the European Community's Horizon 2020 program under Grant Agreement n° 68856

Aceptabilidad por el conejo de la harina de coco desgrasada entre diferentes fuentes de alimento

To determine the acceptability of defatted coconut flour supplied as the sole feed and incorporated at different levels in the rabbit diet, two experiments were performed in which random block designs were used. In the first experiment the treatments were: T1 corn flour, T2 alfalfa flour, and T3 defatted coconut flour. In the second, the treatments consisted of supplying the diets with the inclusion of defatted coconut flour in growing percentage (0, 10, 20, 30 and 40 %). In both studies Chinchilla breed male rabbits of 80 days old were used, weighting an average of 2,150 ± 103 g, 21 and 35 rabbits respectively. Variables attempt to consume and food consume showed similar results, both in defatted coconut flour supplied as the sole feed and when mixed with other ingredients. Animals made consumption attempts for nearly 24 hours and the highest consumption attempts were observed at night. Animals showed the highest acceptance for diets of 10% defatted coconut flour inclusion. The results suggest defatted coconut flour is an agro-industrial by-product with potentiality to be included in rabbit diets and to substitute traditional feed used for this specie.Con el propósito de determinar el grado de aceptabilidad de la harina de coco desgrasada suministrada como alimento único e incorporado en diferentes niveles en la dieta para conejos, fueron realizados dos experimentos en los que se emplearon diseños bloques al azar. En el primer experimento los tratamientos fueron: T1 harina de maíz, T2 harina de alfalfa y T3 harina de coco desgrasada; para el segundo, los tratamientos consistieron en el suministro de las dietas con la inclusión de 0, 10, 20, 30 y 40 % de harina de coco desgrasada.  En los dos estudios se utilizaron conejos machos de la raza chinchilla de 80 días de edad, con un peso promedio de 2150 ±103 g, 21 y 35 animales respectivamente. Se observó una conducta similar en las variables intento de consumo y consumo de alimentos, tanto cuando se suministró la harina de coco desgrasada como alimento único como cuando se mezcló con otros ingredientes. Los animales realizaron intentos de consumo durante casi las 24 h, con los mayores intentos de consumo en el horario nocturno. Los animales muestran la mayor aceptación por las dietas del 10 % de inclusión de harina de coco desgrasada. Los resultados sugieren que la harina de coco desgrasada es un subproducto agroindustrial con potencialidades para ser incorporada en las dietas de conejos y sustituir alimentos convencionales tradicionalmente empleados en los piensos elaborados para esta especie

Análisis nutricional de la harina de copra de coco desgrasada para su uso en la alimentación del conejo (Oryctolagus cuniculus)

Defatted coconut meal is an agro-industrial by-product that is produced in the municipality of Baracoa, province of Guantánamo, Cuba, in considerable quantities and available for its use as animal feed. The present study evaluated the nutritional quality of defatted coconut flour. A 60 kg sample was taken from one day of production and its composition was determined: dry matter, crude protein, crude fibre, acid detergent fibre, neutral detergent fibre, cellulose, lignin, ashes, minerals (Ca, P, K, Mg) and the fatty acid profile. The results show that the average values for all the nutrients present in defatted coconut meal present an adequate balance of nutrients to be used as raw material in the formulation of diets for animal feed, especially for rabbits. It had a high percentage of crude fibre and crude protein and adequate fatty acid profile.La harina de coco desgrasada es un subproducto agroindustrial que se produce en el municipio de Baracoa. provincia de Guantánamo, Cuba en cantidades considerables y disponibles para ser utilizado en la alimentación animal. El presente estudio evaluó la calidad nutricional de la harina de coco desgrasada. Se tomó una muestra de 60 kg de un día de producción y se determinó materia seca, proteína bruta, fibra bruta, fibra ácida detergente, fibra neutro detergente, celulosa, lignina, cenizas, minerales (Ca, P, K, Mg) y el perfil de los ácidos grasos. Los resultados demuestran que los valores promedios para todos los nutrientes que presenta la harina de coco desgrasada presentan un adecuado balance de nutrientes para ser utilizado como materia prima en la formulación de dietas para la alimentación animal, en especial para el conejo. Se destaca su alto porcentaje de fibra bruta. proteína bruta y perfil de ácidos grasos

Efecto de la harina de coco desgrasada en el crecimiento del conejo

To evaluate the influence of defatted coconut flour (HCD) on the productive performance and yield to the carcass for growing rabbits, five diets were elaborated with increasing levels of this (0, 10, 20, 30 and 40 %), which were supplied to 130 animals of the Chinchilla breed, with a completely randomized design. The initial and final live weights, average daily gain, feed consumption, feed conversion, yield to the carcass and its valuable cuts were determined. The experimental period was 78 days. The final live weight of the animals during the fattening cycle was between 2060 and 2242 g/animal, in all cases above 2000 g which is the one established for the slaughter of the animals, the mean weight gain oscillated between 25.4 and 28.4. The inclusion of defatted coconut meal in the diet up to 40 % did not affect the yield to the carcass, its average values ​​ranged between 49.72 and 53.5 %. The results indicate that the rabbits made an adequate absorption of the nutrients when using defatted coconut flour for their growth, in addition the economic performance of the production system is improved.Para evaluar la influencia de la harina de coco desgrasada (HCD) en el comportamiento productivo y el rendimiento a la canal para conejos en crecimiento, fueron elaboradas cinco dietas con niveles crecientes de esta (0, 10, 20, 30 y 40 %), las cuales fueron suministradas a 130 animales de la raza chinchilla, con un diseño completamente aleatorizado. Fueron determinados los pesos vivo inicial y final, ganancia media diaria, consumo de alimento, conversión alimenticia, rendimiento a la canal y sus cortes valiosos. El período experimental fue de 78 días.  El peso vivo final de los animales durante el ciclo de ceba estuvo entre 2060 y 2242 g/animal, en todos los casos por encima de los 2000 g, que es el establecido para el sacrificio de los animales. La ganancia media de peso osciló entre 25.4 y 28.4. La inclusión de la harina de coco desgrasada en la dieta hasta un 40 % no afectó el rendimiento a la canal, sus valores promedios oscilaron entre 49.72 y 53.5%. Los resultados indican que los conejos realizaron una adecuada absorción de los nutrientes al utilizar harina de coco desgrasada para su crecimiento, además se mejora el rendimiento económico del sistema de producción

Effect of defatted coconut flour on rabbit growth

1 recurso en línea (páginas 47-59).To evaluate the influence of defatted coconut flour (HCD) on the productive performance and yield to the carcass for growing rabbits, five diets were elaborated with increasing levels of this (0, 10, 20, 30 and 40 %), which were supplied to 130 animals of the Chinchilla breed, with a completely randomized design. The initial and final live weights, average daily gain, feed consumption, feed conversion, yield to the carcass and its valuable cuts were determined. The experimental period was 78 days. The final live weight of the animals during the fattening cycle was between 2060 and 2242 g/animal, in all cases above 2000 g which is the one established for the slaughter of the animals, the mean weight gain oscillated between 25.4 and 28.4. The inclusion of defatted coconut meal in the diet up to 40 % did not affect the yield to the carcass, its average values ranged between 49.72 and 53.5 %. The results indicate that the rabbits made an adequate absorption of the nutrients when using defatted coconut flour for their growth, in addition the economic performance of the production system is improved.Para evaluar la influencia de la harina de coco desgrasada (HCD) en el comportamiento productivo y el rendimiento a la canal para conejos en crecimiento, fueron elaboradas cinco dietas con niveles crecientes de esta (0, 10, 20, 30 y 40 %), las cuales fueron suministradas a 130 animales de la raza chinchilla, con un diseño completamente aleatorizado. Fueron determinados los pesos vivo inicial y final, ganancia media diaria, consumo de alimento, conversión alimenticia, rendimiento a la canal y sus cortes valiosos. El período experimental fue de 78 días. El peso vivo final de los animales durante el ciclo de ceba estuvo entre 2060 y 2242 g/animal, en todos los casos por encima de los 2000 g, que es el establecido para el sacrificio de los animales. La ganancia media de peso osciló entre 25.4 y 28.4. La inclusión de la harina de coco desgrasada en la dieta hasta un 40 % no afectó el rendimiento a la canal, sus valores promedios oscilaron entre 49.72 y 53.5%. Los resultados indican que los conejos realizaron una adecuada absorción de los nutrientes al utilizar harina de coco desgrasada para su crecimiento, además se mejora el rendimiento económico del sistema de producción.Bibliografía y webgrafía: páginas 56-59

Effect of defatted coconut flour on rabbit growth

1 recurso en línea (páginas 47-59).To evaluate the influence of defatted coconut flour (HCD) on the productive performance and yield to the carcass for growing rabbits, five diets were elaborated with increasing levels of this (0, 10, 20, 30 and 40 %), which were supplied to 130 animals of the Chinchilla breed, with a completely randomized design. The initial and final live weights, average daily gain, feed consumption, feed conversion, yield to the carcass and its valuable cuts were determined. The experimental period was 78 days. The final live weight of the animals during the fattening cycle was between 2060 and 2242 g/animal, in all cases above 2000 g which is the one established for the slaughter of the animals, the mean weight gain oscillated between 25.4 and 28.4. The inclusion of defatted coconut meal in the diet up to 40 % did not affect the yield to the carcass, its average values ranged between 49.72 and 53.5 %. The results indicate that the rabbits made an adequate absorption of the nutrients when using defatted coconut flour for their growth, in addition the economic performance of the production system is improved.Para evaluar la influencia de la harina de coco desgrasada (HCD) en el comportamiento productivo y el rendimiento a la canal para conejos en crecimiento, fueron elaboradas cinco dietas con niveles crecientes de esta (0, 10, 20, 30 y 40 %), las cuales fueron suministradas a 130 animales de la raza chinchilla, con un diseño completamente aleatorizado. Fueron determinados los pesos vivo inicial y final, ganancia media diaria, consumo de alimento, conversión alimenticia, rendimiento a la canal y sus cortes valiosos. El período experimental fue de 78 días. El peso vivo final de los animales durante el ciclo de ceba estuvo entre 2060 y 2242 g/animal, en todos los casos por encima de los 2000 g, que es el establecido para el sacrificio de los animales. La ganancia media de peso osciló entre 25.4 y 28.4. La inclusión de la harina de coco desgrasada en la dieta hasta un 40 % no afectó el rendimiento a la canal, sus valores promedios oscilaron entre 49.72 y 53.5%. Los resultados indican que los conejos realizaron una adecuada absorción de los nutrientes al utilizar harina de coco desgrasada para su crecimiento, además se mejora el rendimiento económico del sistema de producción.Bibliografía y webgrafía: páginas 56-59

Infiltration of Proinflammatory M1 Macrophages into the Outer Retina Precedes Damage in a Mouse Model of Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a major cause of blindness in the developed world. Oxidative stress and inflammation are implicated in AMD, but precise mechanisms remain poorly defined. Carboxyethylpyrrole (CEP) is an AMD-associated lipid peroxidation product. We previously demonstrated that mice immunized with CEP-modified albumin developed AMD-like degenerative changes in the outer retina. Here, we examined the kinetics of lesion development in immunized mice and the presence of macrophages within the interphotoreceptor matrix (IPM), between the retinal pigment epithelium and photoreceptor outer segments. We observed a significant and time-dependent increase in the number of macrophages in immunized mice relative to young age-matched controls prior to overt pathology. These changes were more pronounced in BALB/c mice than in C57BL/6 mice. Importantly, IPM-infiltrating macrophages were polarized toward the M1 phenotype but only in immunized mice. Moreover, when Ccr2-deficient mice were immunized, macrophages were not present in the IPM and no retinal lesions were observed, suggesting a deleterious role for these cells in our model. This work provides mechanistic evidence linking immune responses against oxidative damage with the presence of proinflammatory macrophages at sites of future AMD and experimentally demonstrates that manipulating immunity may be a target for modulating the development of AMD

Pre-Clinical Evaluation of a Novel Nanoemulsion-Based Hepatitis B Mucosal Vaccine

Hepatitis B virus infection remains an important global health concern despite the availability of safe and effective prophylactic vaccines. Limitations to these vaccines include requirement for refrigeration and three immunizations thereby restricting use in the developing world. A new nasal hepatitis B vaccine composed of recombinant hepatitis B surface antigen (HBsAg) in a novel nanoemulsion (NE) adjuvant (HBsAg-NE) could be effective with fewer administrations.Physical characterization indicated that HBsAg-NE consists of uniform lipid droplets (349+/-17 nm) associated with HBsAg through electrostatic and hydrophobic interactions. Immunogenicity of HBsAg-NE vaccine was evaluated in mice, rats and guinea pigs. Animals immunized intranasally developed robust and sustained systemic IgG, mucosal IgA and strong antigen-specific cellular immune responses. Serum IgG reached > or = 10(6) titers and was comparable to intramuscular vaccination with alum-adjuvanted vaccine (HBsAg-Alu). Normalization showed that HBsAg-NE vaccination correlates with a protective immunity equivalent or greater than 1000 IU/ml. Th1 polarized immune response was indicated by IFN-gamma and TNF-alpha cytokine production and elevated levels of IgG(2) subclass of HBsAg-specific antibodies. The vaccine retains full immunogenicity for a year at 4 degrees C, 6 months at 25 degrees C and 6 weeks at 40 degrees C. Comprehensive pre-clinical toxicology evaluation demonstrated that HBsAg-NE vaccine is safe and well tolerated in multiple animal models.Our results suggest that needle-free nasal immunization with HBsAg-NE could be a safe and effective hepatitis B vaccine, or provide an alternative booster administration for the parenteral hepatitis B vaccines. This vaccine induces a Th1 associated cellular immunity and also may provide therapeutic benefit to patients with chronic hepatitis B infection who lack cellular immune responses to adequately control viral replication. Long-term stability of this vaccine formulation at elevated temperatures suggests a direct advantage in the field, since potential excursions from cold chain maintenance could be tolerated without a loss in therapeutic efficacy

Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild disease

The kinetics of the immune changes in COVID-19 across severity groups have not been rigorously assessed. Using immunophenotyping, RNA sequencing, and serum cytokine analysis, we analyzed serial samples from 207 SARS-CoV2-infected individuals with a range of disease severities over 12 weeks from symptom onset. An early robust bystander CD8+ T cell immune response, without systemic inflammation, characterized asymptomatic or mild disease. Hospitalized individuals had delayed bystander responses and systemic inflammation that was already evident near symptom onset, indicating that immunopathology may be inevitable in some individuals. Viral load did not correlate with this early pathological response but did correlate with subsequent disease severity. Immune recovery is complex, with profound persistent cellular abnormalities in severe disease correlating with altered inflammatory responses, with signatures associated with increased oxidative phosphorylation replacing those driven by cytokines tumor necrosis factor (TNF) and interleukin (IL)-6. These late immunometabolic and immune defects may have clinical implications