Physiology of acid-base balance in bovines with diarrhea backgrounds from Monteria, Colombia

ABSTRACTObjective. Evaluate the acid-base balance (ABB) in bovines with diarrheic backgrounds in four areas of Montería, Colombia. Materials and methods. From a total of 300 pregnant cows, 60 were selected with their newborns. A direct inspection was performed of vital signs on the calves and the ABB indicators were determined using a gasometric method. Data were processed by means of descriptive statistics and the Duncan test was used to differentiate between the averages. The degree of association was established between the ABB indicators in cows and calves by using the Pearson correlation and a comparison of proportions was performed on the indexes of the newborns. Results. Regarding the cows, the ABB indicators were found within the reference values; however, in the calves the pH, pCO2, HCO3-, the anion gap (AG) and the bases excess (BE) varied. A correlation was found between AG, BE and metabolic hydrogen ions (M*H). The AG in cows and calves showed notable differences (p<0.05) among the farms in the study. According to the numeric classification system, the suction reflect indicated a greater percentage of calves in group one. Conclusions. The ABB analyte measurement in cows was similar to the consulted reference; however, in calves some analytes did not coincide. This suggests metabolic acidosis in newborn calves due to the increase of AG and the decrease of BE. Additionally, its correlation with M*H opens the possibility of new proposals to determine ABB in bovines.RESUMENObjetivo. Evaluar el equilibrio ácido-básico (EAB) en bovinos con antecedentes diarreicos de cuatro zonas de Montería, Colombia. Materiales y métodos. De un total de 300 vacas preñadas se seleccionaron 60 vacas y sus recién nacidos. Se realizó una inspección directa de los signos vitales en terneros y los indicadores del EAB se determinaron mediante técnica gasométrica. Los datos se procesaron mediante estadística descriptiva y para la diferencia entre medias se empleó la prueba de Duncan. El grado de asociación se estableció entre los indicadores del EAB en vacas y terneros mediante la correlación de Pearson y una comparación de proporciones se realizó en los índices del recién nacido. Resultados. En las vacas, los indicadores del EAB se encontraron dentro de los valores de referencia; sin embargo, en los terneros varió el pH, pCO2, HCO3-, la brecha aniónica (AG) y el excesode bases (EB). Se encontró correlación entre AG, EB e hidrogeniones metabólicos (H+M). El AG envacas y terneros indicó diferencias notables (p<0.05) entre las fincas de estudio. De acuerdo con elsistema de calificación numérica, el signo reflejo de succión indicó el mayor porcentaje de terneros enel grupo uno. Conclusiones. La medición de los analitos del EAB en vacas fue similar a la referenciaconsultada; sin embargo, en terneros no coincidió con algunos analitos. Se sugiere acidosis metabólicaen los terneros recién nacidos por el aumento del AG y descenso del EB, además, su correlación conlos H+M abre la posibilidad de nuevas propuestas para la determinación del EAB en bovinos

Plant virus cell-to-cell movement is not dependent on the transmembrane disposition of its movement protein

The cell-to-cell transport of plant viruses depends on one or more virus-encoded movement proteins (MPs). Some MPs are integral membrane proteins that interact with the membrane of the endoplasmic reticulum, but a detailed understanding of the interaction between MPs and biological membranes has been lacking. The cell-to-cell movement of the Prunus necrotic ringspot virus (PNRSV) is facilitated by a single MP of the 30K superfamily. Here, using a myriad of biochemical and biophysical approaches, we show that the PNRSV MP contains only one hydrophobic region (HR) that interacts with the membrane interface, as opposed to being a transmembrane protein. We also show that a proline residue located in the middle of the HR constrains the structural conformation of this region at the membrane interface, and its replacement precludes virus movement

Randomized phase II study of fulvestrant plus palbociclib or placebo in endocrine-sensitive, hormone receptor-positive/HER2–advanced breast cancer: GEICAM/2014–12 (FLIPPER)

Background The potential benefit of adding palbociclib to fulvestrant as first-line treatment in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative endocrine-sensitive advanced breast cancer (ABC) patients remains uncharacterized. Patients and methods In this randomized (1:1), double-blind, phase II study, postmenopausal women with HR-positive, HER2-negative ABC with de novo metastatic disease or those who relapsed after >12 months of adjuvant endocrine therapy received palbociclib/fulvestrant or placebo/fulvestrant. Stratification was based on recurrent versus de novo metastatic disease and visceral involvement. The primary objective was one-year progression-free survival (PFS-1y) rate. The sample size was 190 patients. The two-sided alpha of 0.2, 80% of power to detect a difference between the arms, assuming PFS rates of 0.695 and 0.545 for palbociclib/fulvestrant and placebo/fulvestrant, respectively. Results In total, 189 patients were randomized to palbociclib/fulvestrant ([n = 94] or placebo/fulvestrant [n = 95]). 45.5% and 60.3% of patients had de novo metastatic disease and visceral involvement, respectively. PFS-1y rates were 83.5% and 71.9% in the palbociclib/fulvestrant and placebo/fulvestrant arms, (HR 0.55, 80% CI 0.36–0.83, P = 0.064). The median PFS were 31.8 and 22.0 months for the palbociclib/fulvestrant and placebo/fulvestrant arms (aHR 0.48, 80% CI 0.37–0.64, P = 0.001). The most frequent grade 3–4 adverse events were neutropenia (68.1% vs. 0%), leucopenia (26.6% vs. 0%), anemia (3.2% vs. 0%), and lymphopenia (14.9% vs. 2.1%) for the palbociclib/fulvestrant and placebo/fulvestrant, respectively. The most frequent non-hematologic grade 3–4 adverse event was fatigue (4.3% vs. 0%). Conclusions Palbociclib/fulvestrant demonstrated better PFS-1y rates and median PFS than placebo/fulvestrant in HR-positive/HER2-negative endocrine-sensitive ABC patients

The O-mannosylation and production of recombinant APA (45/47 KDa) protein from Mycobacterium tuberculosis in Streptomyces lividans is affected by culture conditions in shake flasks

<p>Abstract</p> <p>Background</p> <p>The Ala-Pro-rich <it>O</it>-glycoprotein known as the 45/47 kDa or APA antigen from <it>Mycobacterium tuberculosis </it>is an immunodominant adhesin restricted to mycobacterium genus and has been proposed as an alternative candidate to generate a new vaccine against tuberculosis or for diagnosis kits. In this work, the recombinant <it>O</it>-glycoprotein APA was produced by the non-pathogenic filamentous bacteria <it>Streptomyces lividans</it>, evaluating three different culture conditions. This strain is known for its ability to produce heterologous proteins in a shorter time compared to <it>M. tuberculosis</it>.</p> <p>Results</p> <p>Three different shake flask geometries were used to provide different shear and oxygenation conditions; and the impact of those conditions on the morphology of <it>S. lividans </it>and the production of rAPA was characterized and evaluated. Small unbranched free filaments and mycelial clumps were found in baffled and coiled shake flasks, but one order of magnitude larger pellets were found in conventional shake flasks. The production of rAPA is around 3 times higher in small mycelia than in larger pellets, most probably due to difficulties in mass transfer inside pellets. Moreover, there are four putative sites of <it>O</it>-mannosylation in native APA, one of which is located at the carboxy-terminal region. The carbohydrate composition of this site was determined for rAPA by mass spectrometry analysis, and was found to contain different glycoforms depending on culture conditions. Up to two mannoses residues were found in cultures carried out in conventional shake flasks, and up to five mannoses residues were determined in coiled and baffled shake flasks.</p> <p>Conclusions</p> <p>The shear and/or oxygenation parameters determine the bacterial morphology, the productivity, and the <it>O</it>-mannosylation of rAPA in <it>S. lividans</it>. As demonstrated here, culture conditions have to be carefully controlled in order to obtain recombinant <it>O</it>-glycosylated proteins with similar "quality" in bacteria, particularly, if the protein activity depends on the glycosylation pattern. Furthermore, it will be an interesting exercise to determine the effect of shear and oxygen in shake flasks, to obtain evidences that may be useful in scaling-up these processes to bioreactors. Another approach will be using lab-scale bioreactors under well-controlled conditions, and study the impact of those on rAPA productivity and quality.</p

The Neandertal nature of the Atapuerca Sima de los Huesos mandibles

The recovery of additional mandibular fossils from the Atapuerca Sima de los Huesos (SH) site provides new insights into the evolutionary significance of this sample. In particular, morphological descriptions of the new adult specimens are provided, along with standardized metric data and phylogenetically relevant morphological features for the expanded adult sample. The new and more complete specimens extend the known range of variation in the Atapuerca (SH) mandibles in some metric and morphological details. In other aspects, the addition of new specimens has made it possible to confirm previous observations based on more limited evidence. Pairwise comparisons of individual metric variables revealed the only significant difference between the Atapuerca (SH) hominins and Neandertals was a more vertical symphysis in the latter. Similarly, principal components analysis of size-adjusted variables showed a strong similarity between the Atapuerca (SH) hominins and Neandertals. Morphologically, the Atapuerca (SH) mandibles show nearly the full complement of Neandertal-derived features. Nevertheless, the Neandertals differ from the Atapuerca (SH) mandibles in showing a high frequency of the H/O mandibular foramen, a truncated, thinned and inverted gonial margin, a high placement of the mylohyoid line at the level of the M3, a more vertical symphysis and somewhat more pronounced expression of the chin structures. Size-related morphological variation in the SH hominins includes larger retromolar spaces, more posterior placement of the lateral corpus structures, and stronger markings associated with the muscles of mastication in larger specimens. However, phylogenetically relevant features in the SH sample are fairly stable and do not vary with the overall size of the mandible. Direct comparison of the enlarged mandibular sample from Atapuerca (SH) with the Mauer mandible, the type specimen of H. heidelbergensis, reveals important differences from the SH hominins, and there is no morphological counterpart of Mauer within the SH sample, suggesting the SH fossils should not be assigned to this taxon. The Atapuerca (SH) mandibles show a greater number of derived Neandertal features, particularly those related to midfacial prognathism and in the configuration of the superior ramus, than other European middle Pleistocene specimens. This suggests that more than one evolutionary lineage co-existed in the middle Pleistocene, and, broadly speaking, it appears possible to separate the European middle Pleistocene mandibular remains into two distinct groupings. One group shows a suite of derived Neandertal features and includes specimens from the sites of Atapuerca (SH), Payre, l'Aubesier and Ehringsdorf. The other group includes specimens that generally lack derived Neandertal features and includes the mandibles from the sites of Mauer, Mala Balanica, Montmaurin and (probably) Visogliano. The two published Arago mandibles differ strongly from one another, with Arago 2 probably belonging to this former group, and Neandertal affinities being more difficult to identify in Arago 13. Outside of the SH sample, derived Neandertal features in the mandible only become more common during the second half of the middle Pleistocene. Acceptance of a cladogenetic pattern of evolution during the European middle Pleistocene has the potential to reconcile the predictions of the accretion model and the two phases model for the appearance of Neandertal morphology. The precise taxonomic classification of the SH hominins must contemplate features from the dentition, cranium, mandible and postcranial skeleton, all of which are preserved at the SH site. Nevertheless, the origin of the Neandertal clade may be tied to a speciation event reflected in the appearance of a suite of derived Neandertal features in the face, dentition and mandible, all of which are present in the Atapuerca (SH) hominins. This same suite of features also provides a useful anatomical basis to include other European middle Pleistocene mandibles and crania within the Neandertal clade.Depto. de Geodinámica, Estratigrafía y PaleontologíaFac. de Ciencias GeológicasTRUEBinghamton UniversityMinisterio de Ciencia e Innovación y UniversidadesJunta de Castilla y Leónpu

Yb-doped strictly all-fiber laser actively Q-switched by intermodal acousto-optic modulation

We show an actively Q-switched ytterbium-doped strictly all-fiber laser. Cavity loss modulation is achieved in a tapered optical fiber by core-to-cladding mode-coupling induced by travelling flexural acoustic waves. When the acoustical signal is switched-off, the optical power losses within the cavity are reduced, and then a laser pulse is emitted. Trains of Q-switched pulses were successfully obtained at repetition rates in the range 1-10 kHz, with pump powers between 59 and 88 mW, at the optical wavelength of 1064.1 nm. Best results were for laser pulses of 118 mW peak power, 1.8 μs of time width, with a pump power of 79 mW, at 7 kHz repetition rate.Fil: Villegas García, Irma Lorena. Universidad de Valencia; España. Centro de Investigaciones en Optica; MéxicoFil: Cuadrado Laborde, Christian Ariel. Universidad de Valencia; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Ópticas. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones Ópticas. Universidad Nacional de La Plata. Centro de Investigaciones Ópticas; ArgentinaFil: Díez, Antonio. Universidad de Valencia; EspañaFil: Cruz, Jose Luis. Universidad de Valencia; EspañaFil: Martínez Gámez, M. A.. Centro de Investigaciones en Óptica; MéxicoFil: Andrés Bou, Miguel Vicente. Universidad de Valencia; Españ

Magneto-Fluorescent Mesoporous Nanocarriers for the Dual-Delivery of Ofloxacin and Doxorubicin to Tackle Opportunistic Bacterial Infections in Colorectal Cancer

Funding Information: This work was funded by the Associate Laboratory for Green Chemistry—LAQV which is financed by national funds from FCT/MCTES (UIDB/50006/2020 and UIDP/50006/2020) as well as the Scientific Society PROTEOMASS (Portugal) for funding support (General Funding Grant 2021). G.M thanks to FCT/MEC (Portugal) for his doctoral grant PD/BD/142865/2018. E.O thanks FCT/MEC (Portugal) for the individual contract, CEECIND/00648/2017. This work was also funded by FCT—Foundation for Science and Technology, I.P., through projects UIDB/04077/2020, UIDP/04077/2020, OrMagNa—PTDC/NAN-MAT/28785/2017, BioISI—UID/Multi/04046/2019, UIDB/04046/2020 and UIDP/04046/2020 Centre grants (BioISI) and NECL infrastructure. Publisher Copyright: © 2022 by the authors.Cancer-related opportunistic bacterial infections are one major barrier for successful clinical therapies, often correlated to the production of genotoxic factors and higher cancer incidence. Although dual anticancer and antimicrobial therapies are a growing therapeutic fashion, they still fall short when it comes to specific delivery and local action in in vivo systems. Nanoparticles are seen as potential therapeutic vectors, be it by means of their intrinsic antibacterial properties and effective delivery capacity, or by means of their repeatedly reported modulation and maneuverability. Herein we report on the production of a biocompatible, antimicrobial magneto-fluorescent nanosystem (NANO3) for the delivery of a dual doxorubicin–ofloxacin formulation against cancer-related bacterial infections. The drug delivery capacity, rendered by its mesoporous silica matrix, is confirmed by the high loading capacity and stimuli-driven release of both drugs, with preference for tumor-like acidic media. The pH-dependent emission of its surface fluorescent SiQDs, provides an insight into NANO3 surface behavior and pore availability, with the SiQDs working as pore gates. Hyperthermia induces heat generation to febrile temperatures, doubling drug release. NANO3-loaded systems demonstrate significant antimicrobial activity, specifically after the application of hyperthermia conditions. NANO3 structure and antimicrobial properties confirm their potential use in a future dual anticancer and antimicrobial therapeutical vector, due to their drug loading capacity and their surface availability for further modification with bioactive, targeting species.publishersversionpublishe

COPLA, a taxonomic classifier of plasmids

Background: Plasmids are mobile genetic elements, key in the dissemination of antibiotic resistance, virulence determinants and other adaptive traits in bacteria. Obtaining a robust method for plasmid classification is necessary to better understand the genetics and epidemiology of many pathogens. Until now, plasmid classification systems focused on specific traits, which limited their precision and universality. The definition of plasmid taxonomic units (PTUs), based on average nucleotide identity metrics, allows the generation of a universal plasmid classification scheme, applicable to all bacterial taxa. Here we present COPLA, a software able to assign plasmids to known and novel PTUs, based on their genomic sequence. Results: We implemented an automated pipeline able to assign a given plasmid DNA sequence to its cognate PTU, and assessed its performance using a sample of 1000 unclassified plasmids. Overall, 41% of the samples could be assigned to a previously defined PTU, a number that reached 63% in well-known taxa such as the Enterobacterales order. The remaining plasmids represent novel PTUs, indicating that a large fraction of plasmid backbones is still uncharacterized. Conclusions: COPLA is a bioinformatic tool for universal, species-independent, plasmid classification. Offered both as an automatable pipeline and an open web service, COPLA will help bacterial geneticists and clinical microbiologists to quickly classify plasmids.This work was supported by the Spanish Ministry of Science and Innovation [PID2020-117923GB-I00 to FdlC]; the Spanish Ministry of Economy, Industry and Competitiveness [DI-17-09164 to SR-S]; and USA Centers for Disease Control and Prevention [200-2019-06679 to FdlC]. The funders had no role in the design of the study, nor in the collection, analysis, and interpretation of data, nor in writing the manuscript included in this submission

Formulation and optimization of polymeric nanoparticles loaded with riolozatrione: a promising nanoformulation with potential anti-herpetic activity

Riolozatrione (RZ) is a diterpenoid compound isolated from a dichloromethane extract of the Jatropha dioica root. This compound has been shown to possess moderate anti-herpetic activity in vitro. However, because of the poor solubility of this compound in aqueous vehicles, generating a stable formulation for potential use in the treatment of infection is challenging. The aim of this work was to optimize and physiochemically characterize Eudragit® L100-55-based polymeric nanoparticles (NPs) loaded with RZ (NPR) for in vitro anti-herpetic application. The NPs formulation was initially optimized using the dichloromethane extract of J. dioica, the major component of which was RZ. The optimized NPR formulation was stable, with a size of 263 nm, polydispersity index < 0.2, the zeta potential of –37 mV, and RZ encapsulation efficiency of 89 %. The NPR showed sustained release of RZ for 48 h with release percentages of 95 and 97 % at neutral and slightly acidic pH, respectively. Regarding in vitro anti-herpetic activity, the optimized NPR showed a selectivity index for HSV-1 of ≈16 and for HSV-2 of 13