Publications by authors named "Alamo D"

One hundred and forty bitches and their offspring (689 puppies) were involved in this study. The influence of different maternal features such as age, breed (brachycephalic/non-brachycephalic), previous births (primiparous/multiparous), health status (complete/incomplete) and litter size over the type of cesarean sections (scheduled/emergency), the neonatal survival, and the incidence of congenital malformations were also examined. Scheduled cesareans were predominant (104/140), of which 90 % were brachycephalic breeds and females were mostly between 2 and 4 years old (54.

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The Amino Acid-Polyamine-Organocation (APC) transporter GadC contributes to the survival of pathogenic bacteria under extreme acid stress by exchanging extracellular glutamate for intracellular γ-aminobutyric acid (GABA). Its structure, determined in an inward-facing conformation at alkaline pH, consists of the canonical LeuT-fold with a conserved five-helix inverted repeat, thereby resembling functionally divergent transporters such as the serotonin transporter SERT and the glucose-sodium symporter SGLT1. However, despite this structural similarity, it is unclear if the conformational dynamics of antiporters such as GadC follow the blueprint of these or other LeuT-fold transporters.

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Article Synopsis
  • LeuT-fold transporters play a crucial role in moving hydrophilic and charged substances like amino acids and sugars across cell membranes, with extensive research on the LeuT transporter providing valuable insights.
  • The review compares different models and mechanisms of transport for LeuT and its relatives, noting both similarities and differences in their function and energy dynamics.
  • It underscores the conservation of structural features in the LeuT fold while also pointing out gaps in understanding that limit the application of current research to practical knowledge about membrane protein transport.
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  • Conformational changes are crucial for the function of many proteins, and their study often requires a comprehensive structural biology approach.
  • The new method, ConfChangeMover (CCM), integrated into the Rosetta modeling suite, effectively models these changes using limited experimental data.
  • Benchmark tests showed CCM outperformed existing Rosetta methods, demonstrating its ability to model various conformational changes and integrate diverse experimental data for better understanding of protein dynamics.
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  • Membrane proteins, like transporters and receptors, undergo conformational changes critical for their functions, which has complicated traditional structure predictions.
  • Recent advancements in AlphaFold2 (AF2) have shown promise in modeling these proteins in multiple conformations, although AF2 was originally designed for static structures.
  • By adjusting the input for the AF2 algorithm, researchers successfully generated multiple accurate conformations of diverse transporters and receptors, indicating a need for future AI tools to better predict a range of functional protein states.
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  • The first issue of the journal was published in January 1982, marking the beginning of its historical journey.
  • Reflecting on its past allows for a deeper understanding of its growth and impact over the years.
  • Upcoming initiatives will be introduced to continue the journal's evolution and relevance in the field.
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Previous work was successful in synthesizing a nickel amine, [Cz(Pyr)(NH-Pyr)], by double C-H activation and functionalization via irradiating a disphenoidal Ni(II) azido complex, [Cz(Pyr)NiN]. The present work seeks to expand upon the earlier research and to substitute the metal with iron or cobalt. Density functional theory (DFT)-B3LYP/6-31+G(d') and APFD/Def2TZVP-was used to simulate the generation of an intermediate with significant nitridyl radical character after the loss of N from the starting azido complex.

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  • The study presents a method for incorporating distance restraints from DEER spectroscopy into Rosetta to model different protein shapes based on experimental data.
  • A multilateration algorithm is utilized to optimize residue rotamer ensembles, ensuring they align with the DEER decay in the time domain.
  • The approach was successfully demonstrated by accurately modeling the transition of the PfMATE protein with minimal deviation from the experimental structure, improving the accuracy and consistency of Rosetta models.
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  • AlphaFold2 created several models of the proton/drug antiporter LmrP for the CASP competition.
  • Previous research using a technique called double electron-electron resonance spectroscopy indicated that one of the less favored AlphaFold2 models might represent a structure that hasn't been captured experimentally yet.
  • This suggests that computational predictions can potentially provide insights into protein structures that are challenging to determine through traditional experimental methods.
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Structure-based antibody and antigen design has advanced greatly in recent years, due not only to the increasing availability of experimentally determined structures but also to improved computational methods for both prediction and design. Constant improvements in performance within the Rosetta software suite for biomolecular modeling have given rise to a greater breadth of structure prediction, including docking and design application cases for antibody and antigen modeling. Here, we present an overview of current protocols for antibody and antigen modeling using Rosetta and exemplify those by detailed tutorials originally developed for a Rosetta workshop at Vanderbilt University.

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construction of loop regions is an important problem in computational structural biology. Compared to regions with well-defined secondary structure, loops tend to exhibit significant conformational heterogeneity. As a result, their structures are often ambiguous when determined using experimental data obtained by crystallography, cryo-EM, or NMR.

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ExoU, a type III secreted phospholipase effector of Pseudomonas aeruginosa, serves as a prototype to model large, dynamic, membrane-associated proteins. ExoU is synergistically activated by interactions with membrane lipids and ubiquitin. To dissect the activation mechanism, structural homology was used to identify an unstructured loop of approximately 20 residues in the ExoU amino acid sequence.

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Despite advances in sampling and scoring strategies, Monte Carlo modeling methods still struggle to accurately predict de novo the structures of large proteins, membrane proteins, or proteins of complex topologies. Previous approaches have addressed these shortcomings by leveraging sparse distance data gathered using site-directed spin labeling and electron paramagnetic resonance spectroscopy to improve protein structure prediction and refinement outcomes. However, existing computational implementations entail compromises between coarse-grained models of the spin label that lower the resolution and explicit models that lead to resource-intense simulations.

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The establishment of planar cell polarity (PCP) in the Drosophila eye requires correct specification of the R3/R4 pair of photoreceptor cells, determined by a Frizzled mediated signaling event that specifies R3 and induces Delta to activate Notch signaling in the neighboring cell, specifying it as R4. Here, we investigated the role of the Notch signaling negative regulator Numb in the specification of R3/R4 fates and PCP establishment in the Drosophila eye. We observed that Numb is transiently upregulated in R3 at the time of R3/R4 specification.

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Selective Inhibitor of Nuclear Export (SINE) compounds are a family of small-molecules that inhibit nuclear export through covalent binding to cysteine 528 (Cys528) in the cargo-binding pocket of Exportin 1 (XPO1/CRM1) and promote cancer cell death. Selinexor is the lead SINE compound currently in phase I and II clinical trials for advanced solid and hematological malignancies. In an effort to understand selinexor-XPO1 interaction and to establish whether cancer cell response is a function of drug-target engagement, we developed a quantitative XPO1 occupancy assay.

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This study tried to define neonatal viability after cesarean section in brachycephalic breeds and the efficacy of an adapted Apgar test to assess newborn survival. Data from 44 cesarean sections and 302 puppies were included. Before surgery (59-61 days after ovulation), an ultrasound evaluation defined the fetal biparietal diameter (BPD).

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The aim of this study was to determinate the semen quality of frozen-thawed samples that were chilled for up to 2 days before freezing. The ejaculates (n = 18) from six dogs were collected, pooled and divided into six aliquots. The first aliquot (C, control) was frozen in liquid nitrogen using a conventional protocol to reach a final concentration of 100 × 10(6) spermatozoa/ml, 20% egg yolk and 5% glycerol.

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This study assessed the effects of different incubation temperatures on semen viability and the influence of pooling on semen longevity. In experiment 1, semen samples were collected from five dogs, individually processed (individual semen: IS) and then aliquots from each male were pooled (pooled semen: PS). Semen samples (IS and PS) were diluted in a Tris-glucose-yolk extender and preserved as fresh (37 and 25°C) and chilled semen (4°C).

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This study assessed the efficacy of a dry shipper to preserve canine and caprine semen samples. After equilibration, semen straws from six Majorera bucks and five dogs were frozen and stored in liquid nitrogen (LN). Thirty days after freezing, half of the frozen straws were transferred from LN to a dry shipper (DS).

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This short communication reports the clinical, ultrasonographic and histopathological findings in a cat with atresia of the uterine cervix and mucometra. After 6 months of continuous oestrous behaviour, a remarkable abdominal enlargement was observed in a 14-year-old queen. A presumptive diagnosis of mucometra was concluded after the ultrasound evaluation and based on clinical signs and blood analyses.

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The influence of sexual stimulation and human chorionic gonadotrophin (hCG) administration on plasma testosterone concentrations was assessed in five male Beagles. Each dog was exposed to three experimental treatments: C treatment (Control, no stimulation), hCG treatment (dogs were SC injected with 1000 IU of hCG) and sexually stimulated (SS) treatment where semen was collected from the males. All dogs were exposed to all treatments, one per week for three consecutive weeks, with a 1 week of rest between treatments.

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Bilateral enlargement of both epididymes was observed in a 6-year-old German shepherd dog following a pre-scrotal urethrostomy. Testicular parenchyma showed regular structure, and the spermatogenesis and the steroidogenic functions were not modified. However, macroscopic examination of the tail and the body of both epididymes exhibited multiple white and well-delimited foci.

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This study assessed the efficacy of aglepristone at inducing parturition in pregnant goats. Six experimental groups were defined: group A-5 (n = 12), group A-3.3 (n = 12), group A-2.

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Notch receptors in a given cell are activated by cell surface ligands in neighbouring cells but can also be inhibited by the ligands present within the same cell. This process is known as cis-inhibition of Notch. Additionally, reciprocal cis-inhibition of the ligands by Notch has also been observed, albeit to a limited extent.

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This study assessed the effect of different semen storage temperatures and the influence of semen pooling in semen viability. In experiment 1, semen samples (n = 30) of five Majorera bucks were individually processed [Individual semen (IS)] and after the first dilution (Tris-yolk extender), semen-diluted aliquots from each male were pooled semen (PS). Thereafter, semen samples (IS and PS) were preserved as fresh semen (37 and 20°C), chilled semen (4°C) and frozen semen.

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