Old name, new face: A systematic analysis of flexor digitorum superficialis muscle with "chiasma antebrachii".

The gross anatomy of the forearm flexors, particularly that of the flexor digitorum superficialis (FDS) muscle, has been described and graphically illustrated in several anatomical books and atlases starting in the middle of the century before last. However, in anatomical dissection studies as well as in clinical-anatomical courses training muscle-specific targeted injections due to movement disorders such as dystonia or spasticity, it has become apparent that there is a need for a closer investigation of the complex construction of the FDS muscle. To this end, we studied the structure of the muscle bellies and tendons of FDS on 46 human body donates that have been used either in our dissection or clinical-anatomical training courses. With this, we demonstrate here the topographical configuration of the individual muscle belly for each of digits 2 through 5 and the exact paths of their tendons until their passing through the carpal tunnel. Furthermore, we demonstrate the presence of a chiasm of the FDS tendons for the digits 2 and 3, approximately 3-4 cm proximal of the carpal tunnel. Thus, we introduce herewith the terminology "chiasma antebrachii". These findings were confirmed in situ by imaging of fixed human body donates via MRI and corroborated by MRI and ultrasound imaging in two volunteers. Taken together, the present findings enable an updated understanding of the complex organization of the heads, bellies, and tendons of FDS that is relevant not only for anatomical teaching but also clinical interventions.

Plakophilin 2 regulates intestinal barrier function by modulating protein kinase C activity in vitro.

Previous data provided evidence for a critical role of desmosomes to stabilize intestinal epithelial barrier (IEB) function. These studies suggest that desmosomes not only contribute to intercellular adhesion but also play a role as signaling hubs. The contribution of desmosomal plaque proteins plakophilins (PKP) in the intestinal epithelium remains unexplored. The intestinal expression of PKP2 and PKP3 was verified in human gut specimens, human intestinal organoids as well as in Caco2 cells whereas PKP1 was not detected. Knock-down of PKP2 using siRNA in Caco2 cells resulted in loss of intercellular adhesion and attenuated epithelial barrier. This was paralleled by changes of the whole desmosomal complex, including loss of desmoglein2, desmocollin2, plakoglobin and desmoplakin. In addition, tight junction proteins claudin1 and claudin4 were reduced following the loss of PKP2. Interestingly, siRNA-induced loss of PKP3 did not change intercellular adhesion and barrier function in Caco2 cells, while siRNA-induced loss of both PKP2 and PKP3 augmented the changes observed for reduced PKP2 alone. Moreover, loss of PKP2 and PKP2/3, but not PKP3, resulted in reduced activity levels of protein kinase C (PKC). Restoration of PKC activity using Phorbol 12-myristate 13-acetate (PMA) rescued loss of intestinal barrier function and attenuated the reduced expression patterns of claudin1 and claudin4. Immunostaining, proximity ligation assays and co-immunoprecipitation revealed a direct interaction between PKP2 and PKC. In summary, our in vitro data suggest that PKP2 plays a critical role for intestinal barrier function by providing a signaling hub for PKC-mediated expression of tight junction proteins claudin1 and claudin4.

Intestinal Epithelial Barrier Maturation by Enteric Glial Cells Is GDNF-Dependent.

Enteric glial cells (EGCs) of the enteric nervous system are critically involved in the maintenance of intestinal epithelial barrier function (IEB). The underlying mechanisms remain undefined. Glial cell line-derived neurotrophic factor (GDNF) contributes to IEB maturation and may therefore be the predominant mediator of this process by EGCs. Using GFAPcre x Ai14floxed mice to isolate EGCs by Fluorescence-activated cell sorting (FACS), we confirmed that they synthesize GDNF in vivo as well as in primary cultures demonstrating that EGCs are a rich source of GDNF in vivo and in vitro. Co-culture of EGCs with Caco2 cells resulted in IEB maturation which was abrogated when GDNF was either depleted from EGC supernatants, or knocked down in EGCs or when the GDNF receptor RET was blocked. Further, TNFα-induced loss of IEB function in Caco2 cells and in organoids was attenuated by EGC supernatants or by recombinant GDNF. These barrier-protective effects were blunted when using supernatants from GDNF-deficient EGCs or by RET receptor blockade. Together, our data show that EGCs produce GDNF to maintain IEB function in vitro through the RET receptor.

Simulating the Post-gastric Bypass Intestinal Microenvironment Uncovers a Barrier-Stabilizing Role for FXR.

Regional changes to the intestinal microenvironment brought about by Roux-en-Y gastric bypass (RYGB) surgery may contribute to some of its potent systemic metabolic benefits through favorably regulating various local cellular processes. Here, we show that the intestinal contents of RYGB-operated compared with sham-operated rats region-dependently confer superior glycemic control to recipient germ-free mice in association with suppression of endotoxemia. Correspondingly, they had direct barrier-stabilizing effects on an intestinal epithelial cell line which, bile-exposed intestinal contents, were partly farnesoid X receptor (FXR)-dependent. Further, circulating fibroblast growth factor 19 levels, a readout of intestinal FXR activation, negatively correlated with endotoxemia severity in longitudinal cohort of RYGB patients. These findings suggest that various host- and/or microbiota-derived luminal factors region-specifically and synergistically stabilize the intestinal epithelial barrier following RYGB through FXR signaling, which could potentially be leveraged to better treat endotoxemia-induced insulin resistance in obesity in a non-invasive and more targeted manner.

Rapid Attentional Selection of Non-native Stimuli despite Perceptual Narrowing.

Visual experiences increase our ability to discriminate environmentally relevant stimuli (native stimuli, e.g., human faces) at the cost of a reduced sensitivity to irrelevant or infrequent stimuli (non-native stimuli, e.g., monkey/ape faces)-a developmental progression known as perceptual narrowing. One possible source of the reduced sensitivity in distinguishing non-native stimuli (e.g., one ape face vs. another ape face) could be underspecified attentional search templates (i.e., working memory representations). To determine whether perceptual narrowing stems from underspecified attentional templates for non-native exemplars, this study used ERP (the N2pc component) and behavioral measures in a visual search task, where the target was either an exemplar (e.g., a specific ape face) or a category (e.g., any ape face). The N2pc component, an ERP marker of early attentional selection emerging at 200 msec poststimulus, is typically modulated by the specificity of the target and, therefore, by the attentional template-the N2pc is larger for specific items versus categories. In two experiments using both human and ape faces (i.e., native and non-native stimuli), we found that perceptual narrowing affects later response selection (i.e., manual RT and accuracy), but not early attentional selection relying on attentional templates (i.e., the N2pc component). Our ERP results show that adults deploy exemplar level attentional templates for non-native stimuli (as well as native stimuli), despite poor downstream behavioral performance. Our findings suggest that long-term previous experience with reduced exemplar level judgments (i.e., perceptual narrowing) does not appear to eliminate early attentional selection of non-native exemplars.