The tuberous sclerosis complex 1 (TSC1) gene encodes for the growth inhibitory protein, hamartin, and has been clinically implicated in tuberous sclerosis complex (TSC) and associated epilepsy. In this study, we present an induced pluripotent stem cell (iPSC) line derived from a patient with epilepsy and tuberous sclerosis, carrying the TSC1 c.2626-2(IVS20) A > G variant. Peripheral blood mononuclear cells from the patient were successfully reprogrammed into iPSCs, which maintained a normal karyotype, expressed markers of hPSCs, and demonstrated the ability to differentiate into all three germ layers in vivo. This iPSC line serves as a valuable resource for investigating the pathogenic mechanisms underlying epilepsy.
Abstract Aging and regeneration represent complex biological phenomena that have long captivated the scientific community. To fully comprehend these processes, it is essential to investigate molecular dynamics through a lens that encompasses both spatial and temporal dimensions. Conventional omics methodologies, such as genomics and transcriptomics, have been instrumental in identifying critical molecular facets of aging and regeneration. However, these methods are somewhat limited, constrained by their spatial resolution and their lack of capacity to dynamically represent tissue alterations. The advent of emerging spatiotemporal multi-omics approaches, encompassing transcriptomics, proteomics, metabolomics, and epigenomics, furnishes comprehensive insights into these intricate molecular dynamics. These sophisticated techniques facilitate accurate delineation of molecular patterns across an array of cells, tissues, and organs, thereby offering an in-depth understanding of the fundamental mechanisms at play. This review meticulously examines the significance of spatiotemporal multi-omics in the realms of aging and regeneration research. It underscores how these methodologies augment our comprehension of molecular dynamics, cellular interactions, and signaling pathways. Initially, the review delineates the foundational principles underpinning these methods, followed by an evaluation of their recent applications within the field. The review ultimately concludes by addressing the prevailing challenges and projecting future advancements in the field. Indubitably, spatiotemporal multi-omics are instrumental in deciphering the complexities inherent in aging and regeneration, thus charting a course toward potential therapeutic innovations.
Elasmobranchs are common, iconic species in public aquaria; their wild counterparts are key members of marine ecosystems. Post-mortem examination is a critical tool for disease monitoring of wild elasmobranchs and for management of those under human care. Careful necropsy of the head, with a focus on clinically relevant anatomy, can ensure that proper samples are collected, increasing the chance of presumptive diagnoses prior to slower diagnostic workup. Immediate feedback from a thorough head necropsy allows for faster management decisions, often identifying pathogens, routes of pathogen entry, and pathogenesis, which are current shortcomings in published literature. This article proposes a protocol for necropsy of the elasmobranch chondrocranium, emphasizing unique anatomy and careful dissection, evaluation, and sampling of the endolymphatic pores and ducts, inner ears, brain, and olfactory system as part of a complete, whole-body necropsy. Extensive use of cytology and microbiology, along with thorough sample collection for histology and molecular biology, has proven effective in identifying a wide range of pathogens and assisting with characterization of pathogenesis. The cause of mortality is often identified from a head necropsy alone, but does not replace a thorough whole-body dissection. This protocol for necropsy and ancillary diagnostic sample collection and evaluation was developed and implemented in the necropsy of 189 wild and aquarium-housed elasmobranchs across 18 species over 13 years (2011–2023) in California. Using this chondrocranial approach, meningoencephalitis was determined to be the primary cause of mortality in 70% (118/168) of stranded wild and aquarium-housed elasmobranchs. Etiology was largely bacterial or protozoal. Carnobacterium maltaromaticum bacterial meningoencephalitis occurred in salmon sharks (Lamna ditropis), shortfin mako sharks (Isurus oxyrinchus), common thresher sharks (Alopias vulpinus), and one Pacific electric ray (Tetronarce californica). Miamiensis avidus was the most common cause of protozoal meningoencephalitis and found almost exclusively in leopard sharks (Triakis semifasciata) and bat rays (Myliobatis californica) that stranded in San Francisco Bay. Bacterial pathogens were found to use an endolymphatic route of entry, while protozoa entered via the nares and olfactory lamellae. Trauma was the second most common cause of mortality and responsible for 14% (24/168) of wild shark strandings and deaths of aquarium-housed animals.
Doriane Hazart, Brigitte Delhomme, Martin Oheim
et al.
The enteric nervous system (ENS), sometimes referred to as a “second brain” is a quasi-autonomous nervous system, made up of interconnected plexuses organized in a mesh-like network lining the gastrointestinal tract. Originally described as an actor in the regulation of digestion, bowel contraction, and intestinal secretion, the implications of the ENS in various central neuropathologies has recently been demonstrated. However, with a few exceptions, the morphology and pathologic alterations of the ENS have mostly been studied on thin sections of the intestinal wall or, alternatively, in dissected explants. Precious information on the three-dimensional (3-D) architecture and connectivity is hence lost. Here, we propose the fast, label-free 3-D imaging of the ENS, based on intrinsic signals. We used a custom, fast tissue-clearing protocol based on a high refractive-index aqueous solution to increase the imaging depth and allow us the detection of faint signals and we characterized the autofluorescence (AF) from the various cellular and sub-cellular components of the ENS. Validation by immunofluorescence and spectral recordings complete this groundwork. Then, we demonstrate the rapid acquisition of detailed 3-D image stacks from unlabeled mouse ileum and colon, across the whole intestinal wall and including both the myenteric and submucosal enteric nervous plexuses using a new spinning-disk two-photon (2P) microscope. The combination of fast clearing (less than 15 min for 73% transparency), AF detection and rapid volume imaging [less than 1 min for the acquisition of a z-stack of 100 planes (150*150 μm) at sub-300-nm spatial resolution] opens up the possibility for new applications in fundamental and clinical research.
Neurosciences. Biological psychiatry. Neuropsychiatry, Human anatomy
Objective: Before cochlear implantation, accurately identifying the cochlea's morphology is necessary. This study proposes an improved network model based on U-Net, which can realize automatic segmentation of human cochlear anatomy in computed tomography (CT) images. Methods: The CT scan data of 100 patients requiring cochlear implantation diagnosed in our hospital were randomly collected. It was divided into a training set (n = 75) and a test set (n = 25). All data were manually segmented by two clinicians. At the same time, U-Net was used for deep learning of the above data. The cochlea in the test set was compared with the dice similarity coefficient (DSC) and 95% Hausdorff surface distance (HD95%) by manual and automatic segmentation. Results: The DSC and HD95% of manual cochlear image segmentation were 0.761 and 4.343, respectively. The DSC and HD95% were 0.742 and 4.217, respectively, for automatic segmentation of cochlear structure using the U-Net network structure. The difference of DSC and HD95% between the two segmentation methods was not statistically significant (P > 0.05). Conclusions: The cochlea can be thoroughly segmented automatically based on the U-Net neural network, and the precision is close to manual segmentation.
Medical physics. Medical radiology. Nuclear medicine, Nuclear engineering. Atomic power
Background Insertion/deletion polymorphism (InDel), as the third genetic marker, has been given a lot of attention by forensic geneticists since it has the advantages of extensive distributions in the human genome, small amplicon, and low mutation rate. However, the extant InDel panels were only viewed as supplemental tools for kinship analyses. In addition, these panels were not conductive to mixture deconvolution because InDels in these panels mainly displayed two alleles. Aims The purpose of this study is to investigate genetic distributions of a novel panel of InDels and STRs in the Guizhou Han population; assess the forensic application value of the panel; and conduct population genetic analyses of the Guizhou Han and other reference populations based on the overlapping loci. Subjects and methods The bloodstain samples of 209 Guizhou Han were gathered and genotyped by the novel panel. Allelic frequencies and forensic parameters of two miniSTRs and 59 InDels in the panel were estimated. In addition, we assessed phylogenetic relationships among the Guizhou Han and other reference populations by principal component analysis, DA genetic distance, and neighbor-joining tree. Results A total of 139 alleles of 61 loci could be observed in the Guizhou Han population. Polymorphic information content values of 59 InDels were greater than 0.3 in the Guizhou Han population. The cumulative power of discrimination and probability of exclusion of two miniSTRs and 59 InDels in the Guizhou Han population were 0.999999999999999999999999997984 and 0.9999986, respectively. Principal component analysis of 14 populations showed that the Guizhou Han population located closer to Hunan Han and Southern Han Chinese (CHS) populations. Similar results were also discerned from DA genetic distances and the neighbor-joining tree. Conclusion To sum up, the novel panel could be employed for forensic personal identification and paternity testing in the Guizhou Han population as a promising independent tool. Besides, the principal component analysis and phylogenetic tree of the Guizhou Han and other compared populations revealed that the Guizhou Han population possesses close genetic affinities with Hunan Han, CHS, and Han Chinese in Beijing (CHB) populations.
X-ray analyses of macaque vocal tract movements show that monkeys’ inability to speak is not due to limitations of peripheral anatomy. For four decades, the inability of nonhuman primates to produce human speech sounds has been claimed to stem from limitations in their vocal tract anatomy, a conclusion based on plaster casts made from the vocal tract of a monkey cadaver. We used x-ray videos to quantify vocal tract dynamics in living macaques during vocalization, facial displays, and feeding. We demonstrate that the macaque vocal tract could easily produce an adequate range of speech sounds to support spoken language, showing that previous techniques based on postmortem samples drastically underestimated primate vocal capabilities. Our findings imply that the evolution of human speech capabilities required neural changes rather than modifications of vocal anatomy. Macaques have a speech-ready vocal tract but lack a speech-ready brain to control it.
AbstractLearning objectives typically indicate subject matter judged to be important or that represents essential material to be learned during a course. We report here on our efforts to identify essential course content and determine our effectiveness teaching and assessing this content in our preclinical human anatomy course. Using a consensus driven approach, we identified anatomical structures, relationships, and functional concepts judged to represent essential material in our unit on the thorax that students were expected to be familiar with. We then determined performance on specific examination questions that focused directly on the essential material. Thirty‐seven of 48 students (77%) correctly answered all 34 of 51 questions that directly focused on content we defined as essential. The remaining 11 students answered the majority of these questions correctly. The overall mean score was 86% (range 61%–98%). Our review of student performance on the End of Block thorax examination confirmed our belief that we were successful in helping students learn material we defined as essential. We found the process described here to be helpful in defining essential content and for helping focus and improve medical education and learning assessment based on that material. We believe the idea of defining essential content that can be efficiently taught and effectively learned within a proscribed period of time is an important and necessary objective. We believe the approach used here might be successfully utilized in other programs in efforts aimed at quality improvement.
Michael Hermanussen, Christiane Scheffler, Liza Wilke
et al.
Seventeen scientists met for this year’s conference on Auxology held at Krobielowice castle, Poland, to discuss growth and public health concerns. The regulation of growth is complex and besides metabolic and endocrine components including hypothalamic releasing factors, growth hormone and multiple downstream effectors, comprises the full spectrum of the psychosocial, economic and emotional environment including signaling dominance, competence, prestige, or subordination and indulgence, all of this being sensitive to urban or rural lifestyle, the political climate and with marked plasticity throughout history. New statistical techniques (St. Nicolas House Analysis) are presented for analyzing anthropometric variables for public health concerns. The impact of spatial differences on developmental tempo, growth in height, and the prevalence of childhood obesity are discussed as well as the impact of social mobility on obesity, and the benefits of the biopsychosocial status when getting along with socio-economic disasters and the COVID-19 pandemic.
Abstract Background In 2016, the International Commission on Radiological Protection (ICRP) published the results of Monte Carlo simulations performed using updated and anatomically realistic voxelized phantoms. The resulting specific absorbed fractions are based on more realistic human anatomy than those computed in the stylized, geometrical Cristy–Eckerman (CE) phantom. Despite this development, the ICRP-absorbed fractions have not been widely adopted for radiopharmaceutical dosimetry. To help make the transition, we have established a correspondence between source and target tissues defined in the CE phantom and those defined in the ICRP phantoms. Results The ICRP phantom has 79 source regions and 43 target regions in comparison with the 23 source and 18 target tissue regions defined in the CE phantom. The ICRP phantom provides tissue regions with greater anatomical detail. Some of this additional detail is focused on radiation protection and dosimetry of inhaled/ingested radioactivity. Some, but not all, of this detail is useful and appropriate for radiopharmaceutical therapy. We have established the correspondence between CE and ICRP phantom source and target regions and attempted to highlight the ICRP source tissues relevant to radiopharmaceutical therapy (RPT). This paper provides tables and figures highlighting the correspondences established. Conclusion The results provide assistance in transitioning from CE-stylized phantoms to the anatomically accurate voxelized ICRP phantoms. It provides specific guidance for porting the total absorbed activity for regions as defined in the CE phantom to regions within the ICRP phantoms.
Medical physics. Medical radiology. Nuclear medicine
The cumulative knowledge of retina development has been instrumental in the generation of retinal organoid systems from pluripotent stem cells; and these three-dimensional organoid models, in turn, have provided unprecedented opportunities for retinal research and translational applications, including the ability to model disease in a human setting and to apply these models to the development and validation of therapeutic drugs. In this review article, we examine how retinal organoids can also contribute to our understanding of retinal developmental mechanisms, how this knowledge can be applied to modeling developmental abnormalities, and highlight some of the avenues that remain to be explored.
The molecular network features of spinal cord development that are integral to tissue engineering remain poorly understood in placental mammals, especially in terms of their relationships with vital biological processes such as regeneration. Here, using a large-scale temporal transcriptomic analysis of rat spinal cord from the embryonic stage to adulthood, we show that fluctuating RNA expression levels reflect highly active transcriptional regulation, which may initiate spinal cord patterning. We also demonstrate that microRNAs (miRNAs) and transcriptional factors exhibit a mosaic profile based on their expression patterns, while differential alternative splicing events reveal that alternative splicing may be a driving force for the development of the node of Ranvier. Our study also supports the existence of a negative correlation between innate immunity and intrinsic growth capacity. Epigenetic modifications appear to perform their respective regulatory functions at different stages of development, while guanine nucleotide-binding protein (G protein)-coupled receptors (including olfactory receptors (ORs)) may perform pleiotropic roles in axonal growth. This study provides a valuable resource for investigating spinal cord development and complements the increasing number of single-cell datasets. These findings also provide a genetic basis for the development of novel tissue engineering strategies.
Increasing evidence indicates that lymphocyte cytosolic protein 1 (LCP1) overexpression contributes to tumor progression; however, its role in osteosarcoma (OS) remains unclear. We aimed to investigate the potential effect of LCP1 in OS and the underlying mechanisms. We first demonstrated that LCP1 is upregulated in OS cell lines and tissues. Then, we found that aberrant expression of LCP1 could induce the proliferation and metastasis of OS cells in vitro and in vivo by destabilizing neuregulin receptor degradation protein-1 (Nrdp1) and subsequently activating the JAK2/STAT3 signaling pathway. When coculturing OS cells with bone marrow-derived mesenchymal stem cells (BMSCs) in vitro, we validated that oncogenic LCP1 in OS was transferred from BMSCs via exosomes. Moreover, microRNA (miR)-135a-5p, a tumor suppressor, was found to interact upstream of LCP1 to counteract the pro-tumorigenesis effects of LCP1 in OS. In conclusion, BMSC-derived exosomal LCP1 promotes OS proliferation and metastasis via the JAK2/STAT3 pathway. Targeting the miR-135a-5p/LCP1 axis may have potential in treating OS.
Aakanksha Shukla, Pradeep Bokariya, Ruchi Kothari
et al.
Introduction
Anthropometry is the scientific study of the measurements and proportions of the human body. Anthropometric studies are an integral part of craniofacial surgery and syndromology. Each orbital cavity is essentially intended as a socket for the eyeball. Assessment of orbital dimensions is important for knowing the anatomy of orbital structures and surgical management of orbital pathologies.
Aim
To estimate the orbital index and length of superior orbital fissure using dry skulls.
Methods
The study was conducted in the Anatomy department after ethics clearance. Forty dried skulls were utilised for study. The measurements for the dimensions of the orbital cavities were taken directly using a digital Vernier Calliper calibrated in millimetres except inter distance between lateral walls which was estimated by spreading calliper. The parameters investigated in our study were Orbital height, Orbital breadth, Length of superior Orbital fissure, Inter-distance between medial wall and Inter - distance between lateral walls of Orbit. Orbital index was calculated using formula: OI = orbital height/orbital breadth×100.
Result:
Mean orbital height of right orbit of the dry skulls was 31.94±2.91mm and Left orbit was 31.85±3.34mm. Mean Orbital breadth of right orbit was 39.6±1.88mm and Left orbit was 39.91±2.65mm. The mean inter-distance between medial walls of orbits was 21.62±1.08mm. The mean inter-distance between lateral walls of orbits was 94.28±4.45mm. Mean length of right superior orbital fissure of the dry skulls was 1.39±0.21cm and Left orbital fissure was 1.4 ±0.24cm. The mean Orbital index of Right orbit was 80.9 and Left Orbit was 80.2. Paired t test demonstrated no significant statistical difference between the right and left orbits (p>0.05).
Conclusion:
Normative Data for Indian skulls was reported. No significant difference was reported in the right and left orbits.
Background: The styloid process (SP) refers to a cylindrical piece projecting from the inferior of the temporal bone, situated anterior to the stylomastoid foramen. It is an anatomic formation close to major vessels and nerves, and its excessive elongation results in pathologies leading to anatomical disorders, such as Eagle’s syndrome. Several studies have been conducted on SP in relation to its close proximity to vessels and nerves, but there is no study that reveals its distance to important anatomical formations, such as the internal auditory meatus (IAM), carotid canal (CC), cochlea, tegmen tympani (TT) and tragus. In the current study, we aimed to investigate the incidence of Eagle’s syndrome based on morphometric measurements of SP. Materials and methods: The patient files archived in the Radiology Department of Adiyaman University Training and Research Hospital were retrospectively examined. The study was carried out on the data of patients for whom specialist radiologists found no pathology findings on the computed tomography images. A total of 77 individuals (36 females and 41 males) aged 22 to 54 years were included in the study. The length of SP and its distances to IAM, cochlea, CC, TT and tragus were obtained using computed tomography radiological measurements. Results: When the individual measurements performed on computed tomography images were evaluated in men and women, no significant difference was found concerning the distance between SP and various anatomic structures in close proximity to SP (p > 0.05). However, there was a statistically significant difference between the genders in length of the right SP (p = 0.003) and left SP (p = 0.006). Conclusions: This anthropometric study revealed the standard morphometric measurements of SP. We believe that the data obtained will help clinicians to identify and diagnose pathologies more easily.
Objective: Since decreased brain-derived neurotrophic factor (BDNF) and increased dipeptidyl peptidase-4 (DPP4) activity have both been implicated in the pathogenesis of mild cognitive impairment (MCI), the aim of our study was to evaluate the association of MCI with plasma DPP4 activity to BDNF ratio (DBR) in an elderly population with normal glucose tolerance.Methods: We cross-sectionally measured C-reactive protein, interleukin-6, nitrotyrosine, 8-iso-PGF2a, DPP4 activity BDNF and calculated the DBR in a total of 1,066 elderly participants in China. MCI was determined by the Montreal Cognitive Assessment and finally confirmed by neurologists.Results: An inverse correlation was found between DPP4 activity and BDNF (r = -0.456, P < 0.001) and this inverse correlation was partly mediated by nitrotyrosine and 8-iso-PGF2a. Across rising quartiles of DBR, nitrotyrosine, 8-iso-PGF2a, C-reactive protein and interleukin-6 progressively increased, whereas the Montreal Cognitive Assessment score progressively decreased. Subjects in the lowest quartile of BDNF and highest quartiles of DBR and DPP4 activity, had higher MCI risk compared with subjects in the highest quartile of the BDNF and lowest quartiles of DBR and DPP4 activity, respectively (all P < 0.05). The odds ratio for MCI became more pronounced with decreased BDNF and increased DPP4.Conclusion: In conclusion, a negative correlation was found between DPP4 activity and BDNF, and this negative correlation was partly mediated by oxidative stress, not inflammation. The DBR was positively associated with MCI and thus may be used as a novel risk biomarker for MCI in an elderly population with normal glucose tolerance.