Normal contractile algorithm of swallowing related muscles revealed by needle EMG and its comparison to videofluoroscopic swallowing study and high resolution manometry studies: A preliminary study

The purpose of this study was to investigate the function and importance of infrahyoid muscles with the suprahyoid muscles during swallowing, and to investigate swallowing sequences using kinematic analysis, high-resolution manometry (HRM) and electromyography (EMG). As a preliminary study, ten healthy subjects were prospectively enrolled. A needle EMG evaluated the onset latency, peak latency and duration of the suprahyoid and infrahyoid muscles. HRM measured the time intervals among the velopharynx, tongue base, and upper esophageal sphincter. We also evaluated hyoid motion using an automated kinematic analysis software® (AKAS). All of these parameters were synchronized with a tilting motion of the epiglottis. In the EMG analysis, the activations of the suprahyoid muscles developed about 300 ms earlier than that of the infrahyoid muscles. There was a significant relationship between the differences of suprahyoid and infrahyoid muscles’ latency and total duration of the hyoid motion (p < 0.05). The interval time of anterior hyoid motion has a significant correlation in the upper esophageal sphincter (UES) opening time. In conclusions, the functions of the infrahyoid muscles are also as important as that of the suprahyoid muscles for prolonged laryngeal elevation and UES opening. Moreover, kinematic analysis of videofluoroscopic swallowing study (VFSS) and HRM studies could reflect results of needle EMG study and replace EMG study.     

Ecological associations of autopodial osteology in Neotropical geckos

Coevolution of form and function inspires investigation of associations between morphological variation and the exploitation of specific ecological settings. Such relationships, based mostly on traits of external morphology, have been extensively described for vertebrates, and especially so for squamates. External features are, however, composed by both soft tissues and bones, and these likely play different biomechanical roles during locomotion, such as in the autopodia. Therefore, ecological trends identified on the basis of external morphological measurements may not be directly correlated with equivalent variation in osteology. Here, we investigate how refined parameters of autopodial osteology relate to ecology, by contrasting climbing and nonclimbing geckos. Our first step consisted of inferring how external and osteological morphometric traits coevolved in the group. Our results corroborate the hypothesis of coevolution between external and osteological elements in the autopodia of geckos, and provides evidence for associations between specific osteological traits and preferred locomotor habit. Specifically, nonclimbers exhibit longer ultimate and penultimate phalanges of Digit V in the manus and pes and also a longer fifth metatarsal in comparison with climbers, a pattern discussed here in the context of the differential demands made upon locomotion in specific ecological contexts. Our study highlights the relevance of osteological information for discussing the evolution of ecological associations of the tetrapod autopodium. J. Morphol. 278:290–299, 2017. © 2017 Wiley Periodicals, Inc.     

Ontogenic and nutritional modifications in the intestinal fucosylation process at the weaning period. Influence of dietary fibers

In the rat small intestine, the glycosylation changes which normally take place at the weaning period are characterized by a shift from sialylation of fucosylation. The introduction of dietary fibers at weaning is one of the more striking nutritional modification so that some authors have suggested that the presence of fibers and the development of colonic fermentation might be important for the development of the small intestine, as for the colon. In order to define the respective contribution of ontogenic and nutritional factors to the intestinal glycosylation changes at this period, some aspects of the intestinal glycosylation were studied in five groups of rats (16-day-old suckling rats, prolonged nursing 23-day-old rats, 23-day-old rats weaned at day 19 with either a fiber-free, a cellulose or a pectin diet). Intestinal glycoproteins of suckling rats are characterized by a low fucose content and a high proportion of mannose. The amounts of the neutral sugars (fucose, mannose and galactose), expressed either per gram of intestine or for one intestine, are alwars higher in the fiber-fed groups than in the prolonged-nursing group or the group fed the fiber-free diet. Activities which promote fucosylation process (GDP-fucose production and fucosyltransferase activities) and those which are opposed to fucosylation (endogenous inhibitor of fucosyltransferase and GDP-fucose pyrophosphatase) are strongly modified in opposite ways at day 23 as compared to day 16. These modifications depend on the age of the animal (ontogenic factors) with additional modifications induced by the dietary factors. In particular, similar sugar contents and patterns are obtained with cellulose and pectin diests though the enzymatic activities of the fucosylation pathway are very different. No correlation was found between the caecal content of short chain fatty acids and any of the parameters under study. Thus, dietary fibers induce metabolic changes in the small intestine glycosylation in short-term experiments independently of colonic fermentation. Besides, these results point out that the consideration of fucosyl-transferase activities alone are not sufficient to predict glycoprotein fucose content and that other regulatory sites are involved. Dietary manipulations at the weaning period could represent a good model for the study of glycosylation regulation.     

Testing prediction accuracy in short-term ecological studies

Applied ecology is based on an assumption that a management action will result in a predicted outcome. Testing the prediction accuracy of ecological models is the most powerful way of evaluating the knowledge implicit in this cause-effect relationship, however, the prevalence of predictive modeling and prediction testing are spreading slowly in ecology. The challenge of prediction testing is particularly acute for small-scale studies, because withholding data for prediction testing (e.g., via k-fold cross validation) can reduce model precision. However, by necessity small-scale studies are common. We use one such study that explored small mammal abundance along an elevational gradient to test prediction accuracy of models with varying degrees of information content. For each of three small mammal species, we conducted 5000 iterations of the following process: (1) randomly selected 75 % of the data to develop generalized linear models of species abundance that used detailed site measurements as covariates, (2) used an information theoretic approach to compare the top model with detailed covariates to habitat type-only and null models constructed with the same data, (3) tested those models’ ability to predict the 25 % of the randomly withheld data, and (4) evaluated prediction accuracy with a quadratic loss function. Detailed models fit the model-evaluation data best but had greater expected prediction error when predicting out-of-sample data relative to the habitat type models. Relationships between species and detailed site variables may be evident only within the framework of explicitly hierarchical analyses. We show that even with a small but relatively typical dataset (n = 28 sampling locations across 125 km over two years), researchers can effectively compare models with different information content and measure models’ predictive power, thus evaluating their own ecological understanding and defining the limits of their inferences. Identifying the appropriate scope of inference through prediction testing is ecologically valuable and is attainable even with small datasets.     

Shear Stress-induced Redistribution of Vascular Endothelial-Protein-tyrosine Phosphatase (VE-PTP) in Endothelial Cells and Its Role in Cell Elongation

Vascular endothelial cells (ECs) are continuously exposed to shear stress (SS) generated by blood flow. Such stress plays a key role in regulation of various aspects of EC function including cell proliferation and motility as well as changes in cell morphology. Vascular endothelial-protein-tyrosine phosphatase (VE-PTP) is an R3-subtype PTP that possesses multiple fibronectin type III-like domains in its extracellular region and is expressed specifically in ECs. The role of VE-PTP in EC responses to SS has remained unknown, however. Here we show that VE-PTP is diffusely localized in ECs maintained under static culture conditions, whereas it undergoes rapid accumulation at the downstream edge of the cells relative to the direction of flow in response to SS. This redistribution of VE-PTP triggered by SS was found to require its extracellular and transmembrane regions and was promoted by integrin engagement of extracellular matrix ligands. Inhibition of actin polymerization or of Cdc42, Rab5, or Arf6 activities attenuated the SS-induced redistribution of VE-PTP. VE-PTP also underwent endocytosis in the static and SS conditions. SS induced the polarized distribution of internalized VE-PTP. Such an effect was promoted by integrin engagement of fibronectin but prevented by inhibition of Cdc42 activity or of actin polymerization. In addition, depletion of VE-PTP by RNA interference in human umbilical vein ECs blocked cell elongation in the direction of flow induced by SS. Our results suggest that the polarized redistribution of VE-PTP in response to SS plays an important role in the regulation of EC function by blood flow.     

2-(Trimethylammonium) Ethyl (R)-3-Methoxy-3-oxo-2-Stearamidopropyl Phosphate Suppresses Osteoclast Maturation and Bone Resorption by Targeting Macrophage-Colony Stimulating Factor Signaling

2-(Trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient megakaryopoiesis. Here, we show that (R)-TEMOSPho blocks osteoclast maturation from progenitor cells of hematopoietic origin, as well as blocking the resorptive function of mature osteoclasts. The inhibitory effect of (R)-TEMOSPho on osteoclasts was due to a disruption of the actin cytoskeleton, resulting from impaired downstream signaling of c-Fms, a receptor for macrophage-colony stimulating factor linked to c-Cbl, phosphoinositol-3-kinase (PI3K), Vav3, and Rac1. In addition, (R)-TEMOSPho blocked inflammation-induced bone destruction by reducing the numbers of osteoclasts produced in mice. Thus, (R)-TEMOSPho may represent a promising new class of antiresorptive drugs for the treatment of bone loss associated with increased osteoclast maturation and activity.     

Alternative rib bone biopsy measurements to estimate changes in skeletal mineral reserves in cattle

Rib bone biopsy samples are often used to estimate changes in skeletal mineral reserves in cattle but differences in sampling procedures and the bone measurements reported often make interpretation and comparisons among experiments difficult. ‘Full-core’ rib bone biopsy samples, which included the external cortical bone, internal cortical bone and trabecular bone (CB_ext, CB_int and Trab, respectively), were obtained from cattle known to be in phosphorus (P) adequate (P_adeq) or severely P-deficient (P_defic) status. Experiments 1 and 2 examined growing steers and Experiment 3 mature breeder cows. The thickness of cortical bone, specific gravity (SG), and the amount and concentration of ash and P per unit fresh bone volume, differed among CB_ext, CB_int and Trab bone. P concentration (mg/cc) was closely correlated with both SG and ash concentrations (pooled data, r=0.99). Thickness of external cortical bone (CBT_ext) was correlated with full-core P concentration (FC-P_conc) (pooled data, r=0.87). However, an index, the amount of P in CB_ext per unit surface area of CB_ext (PSACB; mg P/mm²), was more closely correlated with the FC-P_conc (pooled data, FC-P_conc=37.0+146×PSACB; n=42, r=0.94, RSD=7.7). Results for measured or estimated FC-P_conc in 10 published studies with cattle in various physiological states and expected to be P_adeq or in various degrees of P_defic status were collated and the ranges of FC-P_conc indicative of P adequacy and P deficiency for various classes of cattle were evaluated. FC-P_conc was generally in the range 130 to 170 and 100 to 120 mg/cc fresh bone in P_adeq mature cows and young growing cattle, respectively. In conclusion, the FC-P_conc could be estimated accurately from biopsy samples of CB_ext. This allows comparisons between studies where full-core or only CB_ext biopsy samples of rib bone have been obtained to estimate changes in the skeletal P status of cattle and facilitates evaluation of the P status of cattle.     

Baicalin positively regulates osteoclast function by activating MAPK/Mitf signalling

Activation of osteoblasts in bone formation and osteoclasts in bone resorption is important during the bone fracture healing process. There has been a long interest in identifying and developing a natural therapy for bone fracture healing. In this study, we investigated the regulation of osteoclast differentiation by baicalin, which is a natural molecule extracted from Eucommiaulmoides (small tree native to China). It was determined that baicalin enhanced osteoclast maturation and bone resorption activity in a dose‐dependent manner. Moreover, this involves the activation of MAPK, increased Mitf nuclear translocation and up‐regulation of downstream osteoclast‐related target genes expression. The baicalin‐induced effect on osteoclast differentiation can be mimicked by specific inhibitors of p‐ERK (U0126) and the Mitf‐specific siRNA, respectively. Protein–ligand docking prediction identified that baicalin might bind to RANK, which is the upstream receptor of p‐ERK/Mitf signalling in osteoclasts. This indicated that RANK might be the binding target of baicalin. In sum, our findings revealed baicalin increased osteoclast maturation and function via p‐ERK/Mitf signalling. In addition, the results suggest that baicalin can potentially be used as a natural product for the treatment of bone fracture.