Hasil untuk "Human anatomy"

Liangyu Yin, Yu Cao, Mengda Tang et al.

ABSTRACT Background While the Global Leadership Initiative on Sarcopenia (GLIS) is promising to standardize sarcopenia diagnosis, its operational implementation remains largely undefined. This study aims to operationalize GLIS and evaluate its feasibility, diagnostic concordance and clinical relevance. Methods This three‐stage, multicenter study enrolled 12 116 participants for cut‐off development (mean age 58.7 years, 48.2% men) and 11 241 participants for outcome analysis (mean age 58.4 years, 49.4% men) from a national survey in China. Another 504 patients with chronic kidney disease were included for validation. We proposed the lower limb skeletal muscle mass to five‐time chair stand test ratio (LFR) to assess muscle‐specific strength (MSS). The GLIS conceptual framework was instantiated into six diagnostic criteria combinations using handgrip strength (HGS), appendicular skeletal muscle mass index (ASMI, estimated using a validated formula) and MSS: (1) all three criteria being low (HAM); (2) low HGS plus low ASMI (HA); (3) low MSS (M); (4) low HGS plus low ASMI, or low MSS (HA/M); (5) low HGS or low MSS (H/M); and (6) low ASMI or low MSS (A/M). Intercriteria concordance of these definitions, relevance with functional outcomes and their concordance with the Asian Working Group for Sarcopenia 2019 (AWGS) criteria were evaluated. Results Low MSS cut‐offs were established as < 0.74 for men and < 0.47 for women. Sarcopenia prevalence varied significantly across different definitions: 1055 (8.7%, AWGS), 405 (3.3%, HAM), 619 (5.1%, HA), 2409 (19.9%, M), 2623 (21.6%, HA/M), 3184 (26.3%, H/M) and 3868 (31.9%, A/M). The HA method showed the highest concordance with the AWGS (accuracy = 0.964, κ = 0.722, sensitivity = 1.000, specificity = 0.962). The H/M method demonstrated the strongest correlation with functional outcomes and optimal diagnostic performance (AUCs range from 0.566 to 0.729), with superior discrimination for impaired activities of daily living (ADL), other functional measures and global functional scores (p < 0.05). All methods independently predicted poor functional outcomes. External validation in CKD showed that the H/M method was either superior or comparable to other methods in identifying disabilities (e.g., predicting functional measures, AUC = 0.627, 95% CI = 0.582–0.672). Conclusions This study establishes an operational framework for GLIS using nationally representative data from China and validates its effectiveness in a clinical setting. LFR proves to be a feasible method for assessing MSS. The H/M method effectively captures functional impairment, which may serve as a useful approach for diagnosing sarcopenia. These findings provide actionable benchmarks for sarcopenia research and clinical practice, potentially informing more refined prevention and intervention strategies.

Alberto Mesa-Lombardo, Nuria García-Magro, Angel Nuñez et al.

The trigeminal system plays a crucial role in processing somatosensory information, and its modulation is essential for maintaining sensory homeostasis. This study investigates the inhibitory modulation of trigeminal somatosensory responses by the locus coeruleus (LC), which is involved in numerous cognitive and physiological functions. Previous electrophysiological investigations have shown a diminished ability of the LC to inhibit somatosensory responses in the caudalis division of the spinal trigeminal nucleus (Sp5C) in diabetic mice. We hypothesize that γ-Amino-butyric acid (GABA)ergic and glycinergic neurons in the Sp5C may also participate in modulatory action from the LC. Using unit recordings in isoflurane anesthetized control and streptozotocin-induced diabetic mice, we examined the effect of LC electrical stimulation on GABAergic and glycinergic neurons, while monitoring trigeminal somatosensory responses to vibrissal stimulation. Local applications of bicuculline or strychnine (antagonists of GABAergic and glycinergic receptors, respectively) demonstrated that GABAergic and glycinergic neurons are under the control of noradrenergic projections from the LC by activation of α1 and α2 noradrenergic receptors, respectively. In diabetic mice, the functionality of these inhibitory circuits was reduced, contributing to the observed deficiency in LC-mediated sensory modulation and likely contributing to generation of neuropathic pain. Immunohistochemical experiments confirmed the presence of α1 and α2 noradrenergic receptors in GABAergic and glycinergic neurons that were altered in diabetic mice. In conclusion, the LC modulation exerted on the somatosensory responses in the Sp5C is not only through noradrenergic receptors on glutamatergic projection neurons but also exerts its control through projections to inhibitory interneurons.

Dan Xie, Yuru Xiao, Xuexin Li et al.

ABSTRACT Background Ventilator‐induced diaphragmatic dysfunction (VIDD) is a major complication in critically ill patients. Prolonged mechanical ventilation (MV) triggers diaphragmatic fibrotic remodelling, but the underlying mechanisms remain unclear. This study investigated the role of the mechanosensitive channel Piezo1 in this process. Methods A rat model of MV was established for 6 or 12 h. Diaphragm structure (atrophy and fibrosis) and function (frequency‐contraction curve and fatigue index) were assessed. The roles of Piezo1 were probed using the inhibitor GsMTx4 (a nonspecific mechanosensitive channel inhibitor) and adeno‐associated virus (AAV)–mediated knockdown. Downstream signalling was identified by RNA sequencing (RNA‐seq) and validated with cytosporone‐B (CsnB, a specific agonist of Nr4a1). Results Compared with controls, MV for 12 h induced significant diaphragm fibrosis, atrophy and dysfunction, alongside increased Piezo1 expression (mRNA: 2.362 ± 0.429 vs. 0.920 ± 0.363, p = 0.0018; protein: 1.098 ± 0.103 vs. 0.676 ± 0.102, p = 0.0007). Both GsMTx4 and Piezo1 knockdown alleviated these effects. Knockdown reduced the collagen deposition area by approximately 21% and downregulated key fibrotic markers including fibronectin (0.749 ± 0.118 vs. 1.081 ± 0.117, p < 0.0001), collagen 1 (0.703 ± 0.087 vs. 1.155 ± 0.131, p < 0.0001), collagen 3 (0.879 ± 0.074 vs. 1.063 ± 0.068, p = 0.022) and α‐SMA (0.872 ± 0.657 vs. 1.108 ± 0.078, p = 0.0031) compared to the MV12 + shCtrl group. RNA‐seq identified Nr4a1 as a downstream factor (p value < 0.009). CsnB treatment increased Nr4a1 expression (1.128 ± 0.113 vs. 0.490 ± 0.084, p < 0.0001), mitigating prolonged MV‐induced diaphragm fibrosis and dysfunction but not atrophy (938.1 ± 116.2 vs. 754.7 ± 155.5, p = 0.1079). Conclusions Piezo1 upregulation is a key mechanism in ventilator‐induced diaphragm fibrosis, potentially mediated through the Akt/Nr4a1 signalling pathway. Targeted inhibition of Piezo1 or activation of Nr4a1 presents a promising therapeutic strategy to prevent fibrosis and preserve diaphragm function.

Rodrigo Terán-Garza, Alejandro Quiroga-Garza, Eduardo A. Rivas-Sánchez et al.

Ricardo Jonker, Glen J. Paton, Shahed Nalla

Background: This study investigated the angulation of the odontoid process in a South African skeletal population to establish normative vertical angulation in the sagittal plane and assess variations across population affinity groups, biological sexes, and age categories. The study also investigated standardizing techniques for measuring the angle of the odontoid process. Methods: A cross-sectional study was conducted on 200 cervical axis vertebrae from the Raymond A. Dart Collection. Angulation measurements were taken using digital photographs, ImageJ software and statistical analyses (one-way ANOVA and t-tests). Results: The mean odontoid process angulation (degrees; °) across the sample was 60.45° (±3.10°). No statistically significant differences in angulation were found. Minor variations were observed, with males (60.77° ± 2.94°) showing a slightly higher mean angulation than females (60.08° ± 3.25°). The age groups, “20–40 years” (60.71° ± 3.56°) and “41–55 years” (60.43° ± 3.04°), displayed greater angulation than the 56–70 years age group (60.19° ± 2.68°). Population affinity groups showed that the Black African group had a mean angulation of 60.57° (±3.01°), the White group had 60.06° (±3.04°), and the Coloured group had a slightly higher mean of 60.64° (±3.26°). Conclusions: The study concluded there are statistically insignificant differences in the odontoid process angulation based on population affinity, sex, and age. The findings contribute to a better understanding of cervical spine anatomy and assist in clinical interventions related to the cervical spine.

Gi-Woong Hong, Jovian Wan, Wonseok Choi et al.

Temporal hollowing is a common aesthetic concern addressed with filler injections using an anatomy-based approach. Understanding the complex anatomy of the temporal region, including the superficial temporal artery, temporal branch of the facial nerve, and sentinel vein, is essential for safe and effective treatment. Injection planes—subfascial, within the superficial temporal fat pad, or submuscular—are selected based on individual anatomy and desired outcomes. Techniques like retrograde horizontal fanning with a cannula optimize filler distribution, enhance contour, and minimize complications. Recognizing zones of caution helps prevent vascular and nerve injuries. This approach allows clinicians to achieve natural, youthful fullness in the temples, improving overall facial aesthetics and patient satisfaction.

Shutong Wu, Shutong Wu, Yuchao Yang et al.

Serine protease inhibitors (serpins) are the most numerous and widespread multifunctional protease inhibitor superfamily and are expressed by all eukaryotes. Serpin E2 (serpin peptidase inhibitor, clade E, member 2), a member of the serine protease inhibitor superfamily is a potent endogenous thrombin inhibitor, mainly found in the extracellular matrix and platelets, and expressed in numerous organs and secreted by many cell types. The multiple functions of serpin E2 are mainly mediated through regulating urokinase-type plasminogen activator (uPA, also known as PLAU), tissue-type plasminogen activator (tPA, also known as PLAT), and matrix metalloproteinase activity, and include hemostasis, cell adhesion, and promotion of tumor metastasis. The importance serpin E2 is clear from its involvement in numerous physiological and pathological processes. In this review, we summarize the structural characteristics of the Serpin E2 gene and protein, as well as its roles physiology and disease.

Michael Carl, Kaustubh Lall, Darren Pai et al.

Evaluation of the 3D bone morphology of the glenohumeral joint is necessary for pre-surgical planning. Zero echo time (ZTE) magnetic resonance imaging (MRI) provides excellent bone contrast and can potentially be used in the place of computed tomography. Segmentation of the shoulder anatomy, particularly the humeral head and the acetabulum, is needed for the detailed assessment of each anatomy and for pre-surgical preparation. In this study, we compared the performance of two popular deep learning models based on Google’s DeepLab and U-Net to perform automated segmentation on ZTE MRI of human shoulders. Axial ZTE images of normal shoulders (n = 31) acquired at 3-Tesla were annotated for training with DeepLab and 2D U-Net, and the trained model was validated with testing data (n = 13). While both models showed visually satisfactory results for segmenting the humeral bone, U-Net slightly over-estimated while DeepLab under-estimated the segmented area compared to the ground truth. Testing accuracy quantified by Dice score was significantly higher (<i>p</i> < 0.05) for U-Net (88%) than DeepLab (81%) for the humeral segmentation. We have also implemented the U-Net model onto an MRI console for push-button DL segmentation processing. Although this is an early work with limitations, our approach has the potential to improve shoulder MR evaluation hindered by manual post-processing and may provide clinical benefit for quickly visualizing bones of the glenohumeral joint.

Daniel J. Smit, Konstantin Hoffer, Bettina Bettin et al.

ABSTRACT Background Research on circulating tumor cells (CTCs) offers the opportunity to better understand the initial steps of blood‐borne metastasis as main cause of cancer‐related deaths. Here, we have used the colon cancer CTC‐MCC‐41 and breast cancer CTC‐ITB‐01 lines, which were both established from human CTCs as permanent cell lines as models to further study CTC biology with special emphasis on anchorage‐independent survival and growth. Methods and Results Both cell lines showed a marked intrinsic plasticity to switch between suspension and adherent in vitro growth, in 2D adherent culture conditions, and established an equilibrium of both growth patterns with predominant adherent cells in the CTC‐MCC‐41 line (77%) and suspension cells in the CTC‐ITB‐01 line (85%). Western blot analysis revealed a higher expression of pERK1/2 in CTC‐ITB‐01 adherent cells compared to the suspension counterpart that suggested the involvement of kinases in this process. Subsequent functional kinome profiling identified several serine/threonine as well as tyrosine kinases that were differentially regulated in adherent and suspension CTCs. In the adherent cells of the breast cancer line CTC‐ITB‐01 the activity of MSK1, Src family kinases and the PKG family was increased compared to the suspension counterpart. In adherent cells of the colorectal CTC‐MCC‐41 line, an increased activity of TYRO3 and JAK2 was detected, whereas p38 MAPK was strongly impaired in the suspension CTC‐MCC‐41 cells. Some of the regulated kinases, which include the Src family, TYRO3, MSK1, JAK2 and p38 MAPK, have been associated with crucial cellular processes including proliferation, migration and dormancy in the past. Conclusions The investigated CTC lines exhibit a high plasticity, similar to the concept of ‘adherent‐to‐suspension transition (AST)’ that was recently suggested as a new hallmark of tumor biology by Huh et al. Moreover, we identified differentially regulated kinome profiles that may represent potential targets for future studies on therapeutic interventions.

Andrea E. Dillinger, Sabrina Kuespert, Amin A. Seleem et al.

TGF-β2 is the predominant TGF-β isoform within the eye. One function of TGF-β2 is to provide the eye with immune protection against intraocular inflammation. The beneficial function of TGF-β2 within the eye must be under tight control of a network of different factors. A disbalance of the network can result in different eye diseases. In Primary Open-Angle Glaucoma (POAG), one of the leading causes of irreversible blindness worldwide, TGF-β2 is significantly elevated in the aqueous humor and antagonistic molecules like BMPs are reduced. The changes provoke an altering of the quantity and quality of the extracellular matrix and the actin cytoskeleton in the outflow tissues, leading to an increased outflow resistance and thereby to an increased intraocular pressure (IOP), the major risk factor for primary open-angle glaucoma. The pathologic effect of TGF-β2 in primary open-angle glaucoma is mainly meditated by CCN2/CTGF. CCN2/CTGF can modulate TGF-β and BMP signaling by direct binding. The eye specific overexpression of CCN2/CTGF caused an increase in IOP and led to a loss of axons, the hallmark of primary open-angle glaucoma. CCN2/CTGF appears to play a critical role in the homeostatic balance of the eye, so we investigated if CCN2/CTGF can modulate BMP and TGF-β signaling pathways in the outflow tissues. To this end, we analyzed the direct effect of CCN2/CTGF on both signaling pathways in two transgenic mouse models with a moderate (βB1-CTGF1) and a high CCN2/CTGF (βB1-CTGF6) overexpression and in immortalized human trabecular meshwork (HTM) cells. Additionally, we investigate whether CCN2/CTGF mediates TGF-β effects via different pathways. We observed developmental malformations in the ciliary body in βB1-CTGF6 caused by an inhibition of the BMP signaling pathway. In βB1-CTGF1, we detected a dysregulation of the BMP and TGF-β signaling pathways, with reduced BMP activity and increased TGF-β signaling. A direct CCN2/CTGF effect on BMP and TGF-β signaling was shown in immortalized HTM cells. Finally, CCN2/CTGF mediated its effects on TGF-β via the RhoA/ROCK and ERK signaling in immortalized HTM cells. We conclude that CCN2/CTGF functions as a modulator of the homeostatic balance of BMP and TGF-β signaling pathways, which is shifted in primary open-angle glaucoma.

Chantal E. Holtkamp, Dawid Warmus, Klaudia Bonowicz et al.

Melatonin (<i>N</i>-acetyl-5-methoxytryptamine) is recognized as an effective antioxidant produced by the pineal gland, brain and peripheral organs, which also has anti-inflammatory, immunomodulatory, and anti-tumour capacities. Melatonin has been reported as a substance that counteracts ultraviolet radiation B (UVB)-induced intracellular disturbances. Nevertheless, the mechanistic actions of related molecules including its kynurenic derivatives (<i>N</i>¹-acetyl-<i>N</i>²-formyl-5-methoxykynurenine (AFMK)), its indolic derivatives (6-hydroxymelatonin (6(OH)MEL) and 5-methoxytryptamine (5-MT)) and its precursor <i>N</i>-acetylserotonin (NAS) are only poorly understood. Herein, we treated human epidermal keratinocytes with UVB and assessed the protective effect of the studied substances in terms of the maintenance of mitochondrial function or their radical scavenging capacity. Our results show that UVB caused the significant elevation of catalase (CAT) and superoxide dismutase (Mn-SOD), the dissipation of mitochondrial transmembrane potential (mtΔΨ), a reduction in ATP synthesis, and the enhanced release of cytochrome <i>c</i> into cytosol, leading subsequently to UVB-mediated activation of the caspases and apoptosis (appearance of sub-G₁ population). Our findings, combined with data reported so far, indicate the counteracting and beneficial actions of melatonin and its molecular derivatives against these deleterious changes within mitochondria. Therefore, they define a path to the development of novel strategies delaying mitochondrial aging and promoting the well-being of human skin.

Antoine Micheau, Denis Hoa

Ningjian Wang, Ying Sun, Haojie Zhang et al.

Abstract Background The fat‐to‐muscle mass ratio (FMR) might be an indicator to assess type 2 diabetes risk independent of general obesity. However, no longitudinal studies have explored the extent to which total and regional FMRs may confer risks. We aimed to measure the sex‐specific associations between FMRs of the arm, leg, trunk and whole body and incident type 2 diabetes. Methods A total of 464 817 participants (207 286 men and 257 531 women, mean age 56.5 ± 8.2 and 56.2 ± 8.0 years old, respectively) free of diabetes at baseline were included in this prospective cohort study with UK Biobank data. Fat mass and muscle mass were estimated using a bioelectrical impedance assessment device (Tanita BC 418MA). FMR was calculated as fat mass divided by muscle mass in corresponding body parts (total body, arm, leg and trunk). Cox proportional hazard models were used to estimate the aforementioned associations among men and women. Interaction analyses were performed between FMRs and body mass index (BMI) categories (BMI < 25 kg/m2 and BMI ≥ 25 kg/m2). Results Over the median 11.0 years (5 057 534 person‐years) of follow‐up, we documented 11 618 cases of type 2 diabetes. There was a significantly positive association between total and regional FMR and incident type 2 diabetes, even after adjusting for BMI and other covariates. Compared with other body parts, FMRs of the whole body and leg showed the strongest relationship among men and women, respectively (hazard ratio per 1 SD, 95% confidence interval: 1.67, 1.55–1.80; 1.45, 1.39–1.53). A significant interaction (P for interaction < 0.001) between BMI category and FMRs of different body parts was observed. In the stratified analysis by BMI category and tertiles of FMRs, overweight/obese individuals with a high FMR tertile tended to have the highest hazard ratio, ranging from 5.91 to 7.94 in whole body and regional areas. Conclusions In this large prospective study, higher total and regional FMRs were associated with a higher risk of developing type 2 diabetes, independent of BMI. This association was markedly strengthened in participants with BMI ≥ 25 kg/m2.

Luis Fernandez de Castro, Brian J. Sworder, Byron Mui et al.

Abstract In a previous transcriptomic study of human bone marrow stromal cells (BMSCs, also known as bone marrow-derived “mesenchymal stem cells”), SFRP2 was highly over-represented in a subset of multipotent BMSCs (skeletal stem cells, SSCs), which recreate a bone/marrow organ in an in vivo ectopic bone formation assay. SFRPs modulate WNT signaling, which is essential to maintain skeletal homeostasis, but the specific role of SFRP2 in BMSCs/SSCs is unclear. Here, we evaluated Sfrp2 deficiency on BMSC/SSC function in models of skeletal organogenesis and regeneration. The skeleton of Sfrp2-deficient (KO) mice is overtly normal; but their BMSCs/SSCs exhibit reduced colony-forming efficiency, reflecting low SSC self-renewal/abundancy. Sfrp2 KO BMSCs/SSCs formed less trabecular bone than those from WT littermates in the ectopic bone formation assay. Moreover, regeneration of a cortical drilled hole defect was dramatically impaired in Sfrp2 KO mice. Sfrp2-deficient BMSCs/SSCs exhibited poor in vitro osteogenic differentiation as measured by Runx2 and Osterix expression and calcium accumulation. Interestingly, activation of the Wnt co-receptor, Lrp6, and expression of Wnt target genes, Axin2, C-myc and Cyclin D1, were reduced in Sfrp2-deficient BMSCs/SSCs. Addition of recombinant Sfrp2 restored most of these activities, suggesting that Sfrp2 acts as a Wnt agonist. We demonstrate that Sfrp2 plays a role in self-renewal of SSCs and in the recruitment and differentiation of adult SSCs during bone healing. SFRP2 is also a useful marker of BMSC/SSC multipotency, and a factor to potentially improve the quality of ex vivo expanded BMSC/SSC products.

Flurin Pfiffner, Lukas Prochazka, Ivo Dobrev et al.

(1) Background: The measurement of intracochlear sound pressure (ICSP) is relevant to obtain better understanding of the biomechanics of hearing. The goal of this work was a proof of concept of a partially implantable intracochlear acoustic receiver (ICAR) fulfilling all requirements for acute ICSP measurements in a large animal. The ICAR was designed not only to be used in chronic animal experiments but also as a microphone for totally implantable cochlear implants (TICI). (2) Methods: The ICAR concept was based on a commercial MEMS condenser microphone customized with a protective diaphragm that provided a seal and optimized geometry for accessing the cochlea. The ICAR was validated under laboratory conditions and using in-vivo experiments in sheep. (3) Results: For the first time acute ICSP measurements were successfully performed in a live specimen that is representative of the anatomy and physiology of the human. Data obtained are in agreement with published data from cadavers. The surgeons reported high levels of ease of use and satisfaction with the system design. (4) Conclusions: Our results confirm that the developed ICAR can be used to measure ICSP in acute experiments. The next generation of the ICAR will be used in chronic sheep experiments and in TICI.

Sebastian Römer, Hannah Bender, Wolfgang Knabe et al.

The neocortex is the most complex part of the mammalian brain and as such it has undergone tremendous expansion during evolution, especially in primates. The majority of neocortical neurons originate from distinct neural stem and progenitor cells (NPCs) located in the ventricular and subventricular zone (SVZ). Previous studies revealed that the SVZ thickness as well as the abundance and distribution of NPCs, especially that of basal radial glia (bRG), differ markedly between the lissencephalic rodent and gyrencephalic primate neocortex. The northern tree shrew (Tupaia belangeri) is a rat-sized mammal with a high brain to body mass ratio, which stands phylogenetically mid-way between rodents and primates. Our study provides – for the first time – detailed data on the presence, abundance and distribution of bRG and other distinct NPCs in the developing neocortex of the northern tree shrew (Tupaia belangeri). We show that the developing tree shrew neocortex is characterized by an expanded SVZ, a high abundance of Pax6+ NPCs in the SVZ, and a relatively high percentage of bRG at peak of upper-layer neurogenesis. We further demonstrate that key features of tree shrew neocortex development, e.g., the presence, abundance and distribution of distinct NPCs, are closer related to those of gyrencephalic primates than to those of ferret and lissencephalic rodents. Together, our study provides novel insight into the evolution of bRG and other distinct NPCs in the neocortex development of Euarchontoglires and introduces the tree shrew as a potential novel model organism in the area of human brain development and developmental disorders.

Constantin CIORBĂ

In recent years the Republic of Moldova has taken a number of measures related to the modernization of education system at all levels, but the highest claims have taken place at the level of higher education. Since 2008, our country has joined the Bologna Process, viz. it has been part of the European system of training specialists in various fields in higher education institutions, including physical education and sports. One of the main components of the quality of training of physical education and sports specialists in higher education institutions is the motivational one, which ultimately determines quality of training of the future specialist in the field. In this context, some concrete ways of forming the motivational component are proposed, which in the last instance will contribute to the improvement of the quality level of the students of higher education institutions of physical education and sports.

Houman Qadir, Samuel R. Krimmel, Chaoqi Mu et al.

The claustrum is a narrow subcortical brain structure that resides between the striatum and insular cortex. The function of the claustrum is not fully described, and while our previous work supports a role for the claustrum in top-down cognitive control of action, other evidence suggests the claustrum may be involved in detecting salient changes in the external environment. The anterior cingulate cortex (ACC) and the anterior insular (aINS) are the two major participants in the salience network of human brain regions that activate in response to salient stimuli. While bidirectional connections between the ACC and the claustrum exist from mouse to non-human primate, the aINS connectivity with claustrum remains unclear, particularly in mouse. Here, we explored structural connections of the aINS with the claustrum and ACC through adeno-associated virus neuronal tract tracer injections into the ACC and aINS of the mouse. We detected sparse projections from the claustrum to the aINS and diffuse projections from the aINS to the borders of the claustrum were observed in some cases. In contrast, the insular cortex and endopiriform nucleus surrounding the claustrum had rich interconnectivity with aINS. Additionally, we observed a modest interconnectivity between ACC and the aINS. These data support the idea that claustrum neuron responses to salient stimuli may be driven by the ACC rather than the aINS.

Montserrat Samsó

Excitation contraction coupling, the rapid and massive Ca2+ release under control of an action potential that triggers muscle contraction, takes places at specialized regions of the cell called triad junctions. There, a highly ordered supramolecular complex between the dihydropyridine receptor (DHPR) and the ryanodine receptor (RyR1) mediates the quasi‐instantaneous conversion from T‐tubule depolarization into Ca2+ release from the sarcoplasmic reticulum (SR). The DHPR has several key modules required for EC coupling: the voltage sensors and II‐III loop in the alpha1s subunit, and the beta subunit. To gain insight into their molecular organization, this review examines the most updated 3D structure of the DHPR as obtained by transmission electron microscopy and image reconstruction. Although structure determination of a heteromeric membrane protein such as the DHPR is challenging, novel technical advances in protein expression and 3D labeling facilitated this task. The 3D structure of the DHPR complex consists of a main body with five irregular corners around its perimeter encompassing the transmembrane alpha 1s subunit besides the intracellular beta subunit, an extended extracellular alpha 2 subunit, and a bulky intracellular II‐III loop. The structural definition attained at 19 Å resolution enabled docking of the atomic coordinates of structural homologs of the alpha1s and beta subunits. These structural features, together with their relative location with respect to the RyR1, are discussed in the context of the functional data.

Antoine Micheau, Denis Hoa