Comparing serial X-ray crystallography and microcrystal electron diffraction (MicroED) as methods for routine structure determination from small macromolecular crystals.

Innovative new crystallographic methods are facilitating structural studies from ever smaller crystals of biological macromolecules. In particular, serial X-ray crystallography and microcrystal electron diffraction (MicroED) have emerged as useful methods for obtaining structural information from crystals on the nanometre to micrometre scale. Despite the utility of these methods, their implementation can often be difficult, as they present many challenges that are not encountered in traditional macromolecular crystallography experiments. Here, XFEL serial crystallography experiments and MicroED experiments using batch-grown microcrystals of the enzyme cyclophilin A are described. The results provide a roadmap for researchers hoping to design macromolecular microcrystallography experiments, and they highlight the strengths and weaknesses of the two methods. Specifically, we focus on how the different physical conditions imposed by the sample-preparation and delivery methods required for each type of experiment affect the crystal structure of the enzyme

Layer-by-Layer Assembled Antisense DNA Microsponge Particles for Efficient Delivery of Cancer Therapeutics

Antisense oligonucleotides can be employed as a potential approach to effectively treat cancer. However, the inherent instability and inefficient systemic delivery methods for antisense therapeutics remain major challenges to their clinical application. Here, we present a polymerized oligonucleotides (ODNs) that self-assemble during their formation through an enzymatic elongation method (rolling circle replication) to generate a composite nucleic acid/magnesium pyrophosphate sponge-like microstructure, or DNA microsponge, yielding high molecular weight nucleic acid product. In addition, this densely packed ODN microsponge structure can be further condensed to generate polyelectrolyte complexes with a favorable size for cellular uptake by displacing magnesium pyrophosphate crystals from the microsponge structure. Additional layers are applied to generate a blood-stable and multifunctional nanoparticle via the layer-by-layer (LbL) assembly technique. By taking advantage of DNA nanotechnology and LbL assembly, functionalized DNA nanostructures were utilized to provide extremely high numbers of repeated ODN copies for efficient antisense therapy. Moreover, we show that this formulation significantly improves nucleic acid drug/carrier stability during in vivo biodistribution. These polymeric ODN systems can be designed to serve as a potent means of delivering stable and large quantities of ODN therapeutics systemically for cancer treatment to tumor cells at significantly lower toxicity than traditional synthetic vectors, thus enabling a therapeutic window suitable for clinical translation.United States. Dept. of Defense. Ovarian Cancer Research Program (Teal Innovator Award Grant OC120504)Natural Sciences and Engineering Research Council of Canada (Postdoctoral Fellowship)National Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award 1F32EB017614-01)National Science Foundation (U.S.). Graduate Research Fellowshi

Comunicación organizacional en Inversiones Antoley E.I.R.L, Cercado de Lima, 2022

La presente investigación tuvo como objetivo general conocer la característica de la comunicación organizacional en Inversiones Antoley E.I.R.L, Cercado de Lima, 2022. En la cual logró conocer que existen tipos de comunicación; ascendente, descendente y horizontal. De esta manera, permita que podamos identificar problemas, hacer mejoras y tomar buenas decisiones. La metodología empleada fue de tipo básica, no aplicada, con diseño no experimental y con un enfoque cualitativo. En la cual se pudo aplicar como instrumento un cuestionario de preguntas para la entrevista a profundidad. Los resultados evidenciaron mediante la entrevista que la empresa si cuenta con una comunicación estable, que la comunicación entre colaboradores es deficiente pero manejable, así mismo, el jefe es el encargado de la supervisión de las ventas, del almacenaje, entrada y salida del producto. Si cuenta con una comunicación ascendente, el jefe está informado de todos los movimientos. También cumple con una comunicación descendente, ya que los trabajadores están informados antes de tomar una decisión. Por lo tanto, se concluyó que la comunicación organizacional es apropiada y aporta en el crecimiento empresarial de Inversiones Antoley

Proyecto transnacionalizador: Tisa y su impacto en los procesos históricos, políticos, económicos, sociales y humanos

El TISA (Trade in Services Agreement) es un acuerdo comercial desconocido, del que nadie habla, negociado con gran hermetismo; entre sus promotores encontramos aquellos que abogan por la apertura del “mercado de servicios” a la lógica del capital internacional. No escapa la educación, la salud, el transporte, las telecomunicaciones, servicios financieros, el agua potable, la protección de los datos de la ciudadanía; en síntesis, la democracia y las políticas públicas. El Acuerdo sobre el Comercio de Servicios (ACS) dentro del Trade in Services Agreement (TISA) integrado, por 50 países: E.E.U.U, la U.E. América Latina, Asia y otros; sin que sus poblaciones ni sus parlamentos expresen su punto de vista. Las fuertes presiones internacionales amenazan gravemente la existencia de los servicios públicos, esenciales y no esenciales y agudiza las tentativas de regulación del sector financiero, en detrimento de más del 70% de la población mundia

Digestibilidade dos nutrientes de rações com diferentes níveis de proteína degradável no rúmen e fonte de amido de alta degradabilidade ruminal em ovinos - DOI: 10.4025/actascianimsci.v26i4.1742

Nutrients apparent digestibility coefficients were evaluated in four diets with diferent levels of Ruminal Degradable Protein (RDP): 47%, 52%, 57%, 62%, using the cassava by- product flour (high ruminal degradability source). Four ovines were used (live weight 61,35kg) ± in a 4X4 Latin square design with four periods of 21 days each. Total collect of feces was used. The animals were accomodated in metabolic cages with dispositives to collect urine and feces. The dates were analysed on SAEG system. There were no effects on intake of: dry matter (DM), organic matter (OM), crude protein (CP), neutral detergent fibre (NDF). A linear effect was observed to the apparent digestibility coeficient (ADC) of DM, equation: ADC MS = 68.6 + 0.022 RDP. There were no observed diferences in the coefficients of digestibility of OM, CP, NDF for the levels of RDP.Avaliou-se o coeficiente de digestibilidade aparente dos nutrientes de quatro rações experimentais contendo diferentes níveis de Proteína Degradável no Rúmen (PDR): 47%, 52%, 57% e 62%, usando-se a farinha de varredura de mandioca (amido de alta degradabilidade ruminal). Utilizou-se quatro ovinos com peso médio de 61,35kg em delineamento em quadrado latino 4X4 em quatro períodos de 21 dias. Adotou-se o método de coleta total de fezes. Os animais foram colocados em gaiolas metabólicas com dispositivos para coletas de urina e de fezes. Os dados foram analisados no sistema SAEG. Não houve efeito para os consumos dos nutrientes avaliados: matéria seca (MS), matéria orgânica (MO), proteína bruta (PB) e fibra em detergente neutro (FDN). Observou-se efeito linear para o coeficiente de digestibilidade aparente (CDA) da matéria seca (CDA MS = 68,6 + 0,022 PDR). Não foi observado diferença nos CDA da MO, PB, FDN entre os tratamentos com diferentes níveis de PDR

AllergoOncology:Opposite Outcomes of Immune Tolerance in Allergy and Cancer

While desired for the cure of allergy, regulatory immune cell subsets and nonclassical Th2-biased inflammatory mediators in the tumour microenvironment can contribute to immune suppression and escape of tumours from immunological detection and clearance. A key aim in the cancer field is therefore to design interventions that can break immunological tolerance and halt cancer progression, whereas on the contrary allergen immunotherapy exactly aims to induce tolerance. In this position paper, we review insights on immune tolerance derived from allergy and from cancer inflammation, focusing on what is known about the roles of key immune cells and mediators. We propose that research in the field of AllergoOncology that aims to delineate these immunological mechanisms with juxtaposed clinical consequences in allergy and cancer may point to novel avenues for therapeutic interventions that stand to benefit both disciplines

Proteína degradável no rúmen associada a fontes de amido de alta ou baixa degradabilidade: digestibilidade in vitro e desempenho de novilhos em crescimento Rumen degradable protein associated to starch sources of different ruminal degradability: in vitro digestibility and performance of growing steers

Objetivou-se avaliar os efeitos de teores crescentes de proteína degradável no rúmen (PDR = 47, 52, 57 e 62%) associados a fontes de amido de baixa (milho) ou de alta (farinha de varredura de mandioca - FVM) degradabilidade ruminal em rações com 50:50% volumoso:concentrado sobre a digestibilidade in vitro da MS (DIVMS) e o ganho de peso de novilhos em crescimento. Para determinação da DIVMS, foi utilizada a técnica de dois estádios de Tilley & Terry (1963). As médias obtidas para a DIVMS foram submetidas às análises de variância e regressão em função do teor de PDR da ração. Para o ensaio de desempenho animal, foram utilizados 32 novilhos mestiços (Nelore x Red Angus), não-castrados (275 kg de PV), alojados em duplas, em delineamento experimental inteiramente casualizado. Não foi observado efeito do teor de PDR de dietas contendo milho sobre a DIVMS, indicando que não houve deficiência de nitrogênio e que, possivelmente, a digestibilidade da fonte de amido (milho) foi o fator limitante. Observou-se efeito quadrático do teor de PDR sobre a DIVMS para as dietas contendo FVM, o que indica a ocorrência do efeito de sincronização entre a disponibilidade de energia e nitrogênio, permitindo aumento da atividade microbiana nos níveis mais elevados de PDR na ração e melhor utilização da energia proveniente da fonte de amido de alta degradabilidade ruminal. Não foi observado efeito dos diferentes teores de PDR e da fonte de amido de alta degradabilidade ruminal sobre o consumo de MS, o ganho de peso médio e a conversão alimentar dos animais.<br>The objective of this study was to evaluate the effects of increasing levels of rumen-degradable protein (RDP = 47, 52, 57 and 62%) associated to starch sources of low (corn) and high (cassava by-product (CBP) ruminal degradability on in vitro DM digestibility (IVDMD) and average daily gain of growing steers. In vitro DM digestibility was determined by using the Tilley and Terry (1963) technique. The in vitro data was submitted to analysis of variance and regression analysis in function of dietary RDP levels. The in vivo trial was conducted using 32 crossbred steers (Nellore x Red Angus) averaging 275 kg of body weight and fed diets with 50:50 forage:concentrate ratio. Animals were housed in pairs and assigned to treatments according to a completely randomized design. No effect of increasing RDP levels was observed on IVDMD on diets supplemented with corn indicating no lack of nitrogen. Thus, corn digestibility appeared to be the limiting factor on IVDMD. A significant quadratic effect was found for IVDMD by increasing the RDP levels on diets supplemented with CBP suggesting that a better synchronization between energy availability and ammonia release improved microbial growth, which increased the efficiency of energy and RDP utilization on diets with high RDP. It was not observed effect of different RDP levels associated to a starch source rapidly degraded in the rumen on DM intake, average daily gain, and feed conversion on feedlot steers