Response in blood and urinary parameters of dairy cows to the increase in dietary cation-anion balance

Estudou-se efeito de quatro níveis de dietas catiônicas sobre os parâmetros ácido-base do sangue e o pH urinário de vacas em lactação. Para a manipulação dos níveis do balanço cátion-amônico da dieta (BCAD), foram adicionadas diferentes concentrações de bicarbonato de sódio às dietas, obtendo-se os seguintes tratamentos: +150, +250, +400 e +500mEq/kg de matéria seca. O experimento foi realizado durante o verão, por um período total de 72 dias, utilizando-se oito vacas da raça Holandesa após o pico de lactação, distribuídas em quadrado latino (4x4), replicado, em que cada período teve duração de 18 dias. O pH urinário e o bicarbonato, o pH, o CO2 total e a pCO2 do sangue aumentaram linearmente (P<0,01) com o aumento do BCAD. As concentrações de sódio e potássio do sangue não foram modificadas (P>0,05) pelo BCAD. A concentração de cloro no sangue diminuiu linearmente (P<0,01) com o aumento do BCAD. O aumento do BCAD afetou o equilíbrio ácido-base das vacas, promovendo efeito alcalinogênico, o que poderia levar a diferenças significativas no desempenho do animal.The effect of four levels of cationic diets on acid-basic parameters of blood and the urinary pH were studied in dairy cattle. In order tomanage the dietary cation-anion balance (DCAB) different concentrations of sodium bicarbonate were added to diets, obtaining the following treatments: +150, +250, +400, and +500mEq/kg dry matter. The experiment was performed during the summer, totalizing 72 days, using eight Holstein cows after the lactating peak, distributed in 4 x 4 replicated latin square, with 18 days in each period. The urinary pH and the blood parameters (bicarbonate, pH, total CO2, and pCO2) linearly increased (P<0.01) with the DCAB increase. The sodium and potassium concentrations in blood were not modified (P>0.05) by DCAB. The chloride concentration in blood linearly decreased (P<0.01) with the DCAB increase. The DCAB increase affected the acid-base status of cows, promoting an alkalinogenic effect, what could lead to significant differences on animal performance

PP-waves from BPS supergravity monopoles

We discuss the Penrose limit of the Chamseddine-Volkov BPS selfgravitating monopole in four dimensional N=4 supergravity theory with non-abelian gauge multiplets. We analyze the properties of the resulting supersymmetric pp-wave solutions when various Penrose limits are considered. Apart from the usual rescaling of coordinates and fields we find that a rescaling of the gauge coupling constant to zero is required, rendering the theory abelian. We also study the Killing spinor equations showing an enhancement of the supersymmetries preserved by the solutions and discuss the embedding of the pp-wave solution in $d=10$ dimensions.Comment: 14 pages, no figures. Minor changes, to appear in Phys. Lett.

A Comparison of Priority Rules for Non-passing Automated Stacking Cranes

A recent trend in container ports is to operate dual non-passing Automated Storage Cranes (ASCs) that collaborate to serve storage and retrieval requests from opposite ends of a storage block. Since the ASCs are unable to pass each other, there is an exchange zone that serves as a temporary storage location so that one crane can start a request and leave it to the other crane to complete it. In this study, twelve priority rules are introduced and evaluated to determine which rule minimizes the total makespan for serving all requests, given the sequence in which each ASC will serve the requests. Preliminary results from 12 randomly generated experiments indicate that the priority rules favoring the crane furthest away from the origin of the next request (LonOri) and the longest individual completion times (LonTot) outperformed all other rules in terms of the average percent difference with the best found solution and in terms of the percent of times the priority rule yield the best found solution. Also, combining priority rules AdvFun and LonRem yields the best makespan in 11 of the 12 (91.67%) problem instances tested. Results of this study transcend container ports as it is applicable to any material handling system composed of non-passing MHE and that has pickup/deposit points at the ends of the system

Comments on the U(2) Noncommutative Instanton

We discuss the 't Hoof ansatz for instanton solutions in noncommutative U(2) Yang-Mills theory. We show that the extension of the ansatz leading to singular solutions in the commutative case, yields to non self-dual (or self-antidual) configurations in noncommutative space-time. A proposal leading to selfdual solutions with Q=1 topological charge (the equivalent of the regular BPST ansatz) can be engineered, but in that case the gauge field and the curvature are not Hermitian (although the resulting Lagrangian is real).Comment: Latex file, no figure

Some Noncommutative Multi-instantons from Vortices in Curved Space

We construct U(2) noncommutative multi-instanton solutions by extending Witten's ansatz [1] which reduces the problem of cylindrical symmetry in four dimensions to that of a set of Bogomol'nyi equations for an Abelian Higgsmodel in two dimensional curved space. Using the Fock space approach, we give explicit vortex solutions to the Bogomol'nyi equations and, from them, we present multi-instanton solutions.Comment: 10 pages. LaTe

A drug repurposing screen for whipworms informed by comparative genomics.

Hundreds of millions of people worldwide are infected with the whipworm Trichuris trichiura. Novel treatments are urgently needed as current drugs, such as albendazole, have relatively low efficacy. We have investigated whether drugs approved for other human diseases could be repurposed as novel anti-whipworm drugs. In a previous comparative genomics analysis, we identified 409 drugs approved for human use that we predicted to target parasitic worm proteins. Here we tested these ex vivo by assessing motility of adult worms of Trichuris muris, the murine whipworm, an established model for human whipworm research. We identified 14 compounds with EC50 values of ≤50 μM against T. muris ex vivo, and selected nine for testing in vivo. However, the best worm burden reduction seen in mice was just 19%. The high number of ex vivo hits against T. muris shows that we were successful at predicting parasite proteins that could be targeted by approved drugs. In contrast, the low efficacy of these compounds in mice suggest challenges due to their chemical properties (e.g. lipophilicity, polarity, molecular weight) and pharmacokinetics (e.g. absorption, distribution, metabolism, and excretion) that may (i) promote absorption by the host gastrointestinal tract, thereby reducing availability to the worms embedded in the large intestine, and/or (ii) restrict drug uptake by the worms. This indicates that identifying structural analogues that have reduced absorption by the host, and increased uptake by worms, may be necessary for successful drug development against whipworms

Micro-Hall Magnetometry Studies of Thermally Assisted and Pure Quantum Tunneling in Single Molecule Magnet Mn12-Acetate

We have studied the crossover between thermally assisted and pure quantum tunneling in single crystals of high spin (S=10) uniaxial single molecule magnet Mn12-acetate using micro-Hall effect magnetometry. Magnetic hysteresis experiments have been used toinvestigate the energy levels that determine the magnetization reversal as a function of magnetic field and temperature. These experiments demonstrate that the crossover occurs in a narrow (~0.1 K) or broad (~1 K) temperature interval depending on the magnitude and direction of the applied field. For low external fields applied parallel to the easy axis, the energy levels that dominate the tunneling shift abruptly with temperature. In the presence of a transverse field and/or large longitudinal field these energy levels change with temperature more gradually. A comparison of our experimental results with model calculations of this crossover suggest that there are additional mechanisms that enhance the tunneling rate of low lying energy levels and broaden the crossover for small transverse fields.Comment: 5 pages, 5 figure

Development of COVID-19 monoclonal antibodies and recombinant proteins as reagents for biomedical research and diagnostic test

Since SARS-COV-2 virus spread worldwide and COVID-19 turned rapidly into a pandemic illness, the necessity for vaccines and diagnostic tests became crucial. The viral surface is decorated with Spike, the major antigenic determinant and main target for vaccine development. Within Spike, the receptor binding domain (RBD), constitutes the main target of highly neutralizing antibodies found in COVID-19 convalescent plasma. Besides vaccination, another important aspect of Spike (and RBD) is their use as immunogen for the development of poli- and monoclonal antibodies (mAbs) for therapeutic and diagnostic purposes. Here we report the development and preliminary biochemical characterization of a set of monoclonal antibodies against the Spike RBD domain along with the recombinant expression of two mayor COVID-19 protein reagents: the viral Spike RBD domain and the extracellular domain of the human receptor ACE2. RBD and the extracellular domain of ACE2 (aa 1-740) were obtained through transient gene transfection (TGE) in two different mammalian cell culture systems: HEK293T adherent monolayers and Expi293 suspension cultures. Due to its low cost and ease scale-up, all transfections were carried with polyethyleneimine (PEI). Expressed proteins were purified from culture supernatants by immobilized metal affinity chromatography. Anti-RBD mAbs were developed from two different immunization schemes: one aimed to elicit antibodies with viral neutralizing potential, and the other with the ability to recognize denatured RBD for routinary lab immunoassays. To achieve this, the first group of mice was immunized with RBD in aluminium salts (RBD/Al) and the other with RBD emulsified in Freunds adyuvant (RBD/FA). Polyclonal and monoclonal antibody reactivities against native or denatured RBD forms were then assessed by ELISA. Complete RBD denaturation was followed by intrinsic fluorescence spectral changes upon different physicochemical stress treatments. As expected, RBD/Al immunized mice developed an antibody response shifted to native RBD while those immunized with RBD/FA showed a high response against both forms of the protein. In accordance with the observed polyclonal response, RBD/FA derived mAbs recognize both, native and denatured RBD. On the contrary, hybridomas generated from the RBD/Al protocol mostly recognize RBD in its native state. Further ELISA binding assays revealed that all RBD/FA derived mAbs can form a trimeric complex with ACE2 and RBD, denoting they would not have viral neutralizing activity. ELISA competition assays with the RBD/ACE2 complex aimed to determine the neutralization potential of the RBD/Al derived mAbs are under way. Overall, the anti-Spike RBD mAbs and the recombinant RBD and ACE2 proteins presented here constitute valuable tools for diverse COVID-19 academic research projects and local immunity surveillance testing.Fil: Acuña Intrieri, M. E. Universidad Nacional de San Martin. Centro de Rediseño E Ingenieria de Proteinas.; ArgentinaFil: Deriane, M.A. Universidad Nacional de San Martin. Centro de Rediseño E Ingenieria de Proteinas.; ArgentinaFil: Miller, C.. Universidad Nacional de San Martin. Centro de Rediseño E Ingenieria de Proteinas.; ArgentinaFil: Czibener, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Correa, E.. No especifíca;Fil: Cragnaz, L.. No especifíca;Fil: Guerra, L.. No especifíca;Fil: Rodriguez, S.. No especifíca;Fil: Goldbaum, F.A.. Universidad Nacional de San Martin. Centro de Rediseño E Ingenieria de Proteinas.; ArgentinaFil: Seigelchifer, M.. No especifíca;Fil: Comerci, Diego José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Montagna, Georgina Nuri. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Cerutti, Maria Laura. Universidad Nacional de San Martin. Centro de Rediseño E Ingenieria de Proteinas.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaLVII Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research y XVI Annual Meeting of the Argentinean Society for General MicrobiologyVirtualArgentinaSociedad Argentina de Investigación Bioquímica y Biología MolecularAsociación Civil de Microbiología Genera

FGFR1 and PROKR2 rare variants found in patients with combined pituitary hormone deficiencies.

The genetic aetiology of congenital hypopituitarism (CH) is not entirely elucidated. FGFR1 and PROKR2 loss-of-function mutations are classically involved in hypogonadotrophic hypogonadism (HH), however, due to the clinical and genetic overlap of HH and CH; these genes may also be involved in the pathogenesis of CH. Using a candidate gene approach, we screened 156 Brazilian patients with combined pituitary hormone deficiencies (CPHD) for loss-of-function mutations in FGFR1 and PROKR2. We identified three FGFR1 variants (p.Arg448Trp, p.Ser107Leu and p.Pro772Ser) in four unrelated patients (two males) and two PROKR2 variants (p.Arg85Cys and p.Arg248Glu) in two unrelated female patients. Five of the six patients harbouring the variants had a first-degree relative that was an unaffected carrier of it. Results of functional studies indicated that the new FGFR1 variant p.Arg448Trp is a loss-of-function variant, while p.Ser107Leu and p.Pro772Ser present signalling activity similar to the wild-type form. Regarding PROKR2 variants, results from previous functional studies indicated that p.Arg85Cys moderately compromises receptor signalling through both MAPK and Ca(2) (+) pathways while p.Arg248Glu decreases calcium mobilization but has normal MAPK activity. The presence of loss-of-function variants of FGFR1 and PROKR2 in our patients with CPHD is indicative of an adjuvant and/or modifier effect of these rare variants on the phenotype. The presence of the same variants in unaffected relatives implies that they cannot solely cause the phenotype. Other associated genetic and/or environmental modifiers may play a role in the aetiology of this condition