Comparison of Subcutaneous versus Intramuscular Dexmedetomidine-Midazolam-Ketamine-Morphine (DMKM) Mixture as Chemical Restraint for Endoscopic Sex Determination in Aldabra Giant Tortoises (Aldabrachelys gigantea).

Sex identification through coelioscopy is a minimally invasive surgical technique used to determine the sex of chelonians by directly visualizing their internal reproductive organs. An adequate anaesthesiologic plan is essential to guarantee patient immobilization and proper analgesia during the entire surgical procedure. In this study, we evaluated the effects of a combination of dexmedetomidine (0.05 mg/kg), midazolam (1 mg/kg), ketamine (8 mg/kg), and morphine (1 mg/kg) (DMKM) randomly delivered intramuscularly (IM) or subcutaneously (SC) in twenty-one Aldabra giant tortoise (Aldabrachelys gigantea) into the right antebrachium for celioscopic sex identification. Heart rate (HR), respiratory rate (RR), and body temperature (BT) were measured, along with the skeletal muscle tone of the thoracic and pelvic limbs, neck retraction reflex, palpebral reflex, and jaw tone every 15 min. The anaesthesiologic plan was considered to be adequate at the loss of the thoracic and pelvic limb retraction reflexes. After a 45 min interval, if the anaesthetic plan was deemed insufficient for the celioscopic procedure, a 5 mg/kg dose of propofol was administered intravenously into the subcarapacial venous plexus. At the end of the procedure, atipamezole (0.5 mg/kg) and flumazenil (0.05 mg/kg) were administered intramuscularly into the left antebrachium as reversal agents. Both HR and RR decreased from baseline to both 15 and 30 min. Due to the persistence of thoracic and pelvic limb retraction reflexes 45 min after DMKM administration, 6/11 (55%) cases in the SC group required the additional administration of propofol, in contrast to only 1/10 (10%) cases in the IM group (p = 0.05). The recovery times were comparable between the successfully induced animals in the IM and SC groups. In this study, the intramuscular administration of a DMKM combination quickly produced chemical restraint, suitable for celioscopic sex determination.

LEVELNET to visualize, explore, and compare protein-protein interaction networks.

Physical interactions between proteins are central to all biological processes. Yet, the current knowledge of who interacts with whom in the cell and in what manner relies on partial, noisy, and highly heterogeneous data. Thus, there is a need for methods comprehensively describing and organizing such data. LEVELNET is a versatile and interactive tool for visualizing, exploring, and comparing protein-protein interaction (PPI) networks inferred from different types of evidence. LEVELNET helps to break down the complexity of PPI networks by representing them as multi-layered graphs and by facilitating the direct comparison of their subnetworks toward biological interpretation. It focuses primarily on the protein chains whose 3D structures are available in the Protein Data Bank. We showcase some potential applications, such as investigating the structural evidence supporting PPIs associated to specific biological processes, assessing the co-localization of interaction partners, comparing the PPI networks obtained through computational experiments versus homology transfer, and creating PPI benchmarks with desired properties.

Loop extrusion rules: the next generation.

The interphase genome of vertebrates contains roughly 100 000 dynamic loops formed by cohesins. These loops are thought to play important roles in many functions, but their exact contribution in each case remains hotly disputed. The key challenge in studying these loops is the lack of a single experimental technique that could reliably and comprehensively visualize their locations and dynamics. Yet, we can infer them using theoretical models that integrate complementary experimental observations. Modeling proved instrumental in showing that cohesins form loops via extrusion. The loop extrusion model made numerous successful qualitative and quantitative predictions and inspired many experiments. However, it also demonstrated limited accuracy in predicting contact maps. Recent research suggests that the original model did not fully account for the intricate details of the mechanism of loop extrusion and its complex regulation. Here, we review the progress in visualizing extrusion and characterizing the cohesin cofactors. These discoveries can be summarized as 'rules' of cohesin movement along chromosomes and incorporated into the next generation of models. Such improved models will enable more accurate inferences of positions and dynamics of cohesin loops and generate better predictions for designing experiments.

Clinical parameters obtained during tear film examination in domestic rabbits.

BACKGROUND: One of the contributing factors to ocular surface health is a stable precorneal tear film. Considering the increasing interest in rabbits as pets and the limited literature available on domestic rabbit tearing, the aim of this study was to establish normative data for examination of the tear film in domestic rabbits. RESULTS: The study included 75 client-owned domestic Holland Lop rabbits (150 eyes). The following examinations were performed in each eye: Schirmer tear test-1, tear osmometry, interferometry, tear meniscus height measurement and meibography (quantifying meibomian gland loss as a percentage). The resulting median (95% central range) values were 10.0 (5.0-17.3) mm/min for the Schirmer tear test-1, 345.0 (280.5-376.1) mOsm/L for tear osmolarity, grade 2 (1-4) of interferometry, 0.28 (0.20-0.47) mm for tear meniscus height and 0.0 (0.0-67.6) % meibomian gland loss. A significant association was found between tear osmolarity and age, with an estimated decrease of - 4.0 mOsm/L with each additional year of age (p < 0.001). The distributions of interferometry grades were significantly different between males and females (p < 0.001), with grade 1 and grade 2 being the most frequent in females and males, respectively. A weak negative correlation was also observed between interferometry grade and the percentage of meibomian gland loss (r = - 0.22, p = 0.006). CONCLUSIONS: This is an original study that documents extensive tear film parameters in healthy Holland Lop rabbits. The results can be used as normative data for the examination of the tear film in this lagomorph breed.

Multiple protein-DNA interfaces unravelled by evolutionary information, physico-chemical and geometrical properties.

Interactions between proteins and nucleic acids are at the heart of many essential biological processes. Despite increasing structural information about how these interactions may take place, our understanding of the usage made of protein surfaces by nucleic acids is still very limited. This is in part due to the inherent complexity associated to protein surface deformability and evolution. In this work, we present a method that contributes to decipher such complexity by predicting protein-DNA interfaces and characterizing their properties. It relies on three biologically and physically meaningful descriptors, namely evolutionary conservation, physico-chemical properties and surface geometry. We carefully assessed its performance on several hundreds of protein structures and compared it to several machine-learning state-of-the-art methods. Our approach achieves a higher sensitivity compared to the other methods, with a similar precision. Importantly, we show that it is able to unravel 'hidden' binding sites by applying it to unbound protein structures and to proteins binding to DNA via multiple sites and in different conformations. It is also applicable to the detection of RNA-binding sites, without significant loss of performance. This confirms that DNA and RNA-binding sites share similar properties. Our method is implemented as a fully automated tool, [Formula: see text], freely accessible at: http://www.lcqb.upmc.fr/JET2DNA. We also provide a new dataset of 187 protein-DNA complex structures, along with a subset of 82 associated unbound structures. The set represents the largest body of high-resolution crystallographic structures of protein-DNA complexes, use biological protein assemblies as DNA-binding units, and covers all major types of protein-DNA interactions. It is available at: http://www.lcqb.upmc.fr/PDNAbenchmarks.