Functionally heterogeneous human satellite cells identified by single cell RNA sequencing.

Although heterogeneity is recognized within the murine satellite cell pool, a comprehensive understanding of distinct subpopulations and their functional relevance in human satellite cells is lacking. We used a combination of single cell RNA sequencing and flow cytometry to identify, distinguish, and physically separate novel subpopulations of human PAX7+ satellite cells (Hu-MuSCs) from normal muscles. We found that, although relatively homogeneous compared to activated satellite cells and committed progenitors, the Hu-MuSC pool contains clusters of transcriptionally distinct cells with consistency across human individuals. New surface marker combinations were enriched in transcriptional subclusters, including a subpopulation of Hu-MuSCs marked by CXCR4/CD29/CD56/CAV1 (CAV1+). In vitro, CAV1+ Hu-MuSCs are morphologically distinct, and characterized by resistance to activation compared to CAV1- Hu-MuSCs. In vivo, CAV1+ Hu-MuSCs demonstrated increased engraftment after transplantation. Our findings provide a comprehensive transcriptional view of normal Hu-MuSCs and describe new heterogeneity, enabling separation of functionally distinct human satellite cell subpopulations

Obesity is not associated with disease-free interval, melanoma-specific survival, or overall survival in patients with clinical stage IB-II melanoma after SLNB

BACKGROUND AND OBJECTIVES: Clinicopathologic characteristics have prognostic value in clinical stage IB‐II patients with melanoma. Little is known about the prognostic value of obesity that has been associated with an increased risk for several cancer types and worsened prognosis after diagnosis. This study aims to examine effects of obesity on outcome in patients with clinical stage IB‐II melanoma. METHODS: Prospectively recorded data of patients with clinical stage IB‐II melanoma who underwent sentinel lymph node biopsy (SLNB) between 1995 and 2018 at the University Medical Center of Groningen were collected from medical files and retrospectively analyzed. Cox‐regression analyses were used to determine associations between obesity (body mass index> 30), tumor (location, histology, Breslow‐thickness, ulceration, mitotic rate, SLN‐status) and patient‐related variables (gender, age, and social‐economic‐status [SES]) and disease‐free interval (DFI), melanoma‐specific survival (MSS), and overall survival (OS). RESULTS: Of the 715 patients, 355 (49.7%) were women, median age was 55 (range 18.6‐89) years, 149 (20.8%) were obese. Obesity did not significantly affect DFI (adjusted hazard ratio [HR] = 1.40; 95% confidence interval [CI] = 0.98–2.00; p = 0.06), MSS (adjusted HR = 1.48;95%CI = 0.97–2.25; p = 0.07), and OS (adjusted HR = 1.25; 95% CI = 0.85–1.85; p = 0.25). Increased age, arm location, increased Breslow‐thickness, ulceration, increased mitotic rate, and positive SLN‐status were significantly associated with decreased DFI, MSS, and OS. Histology, sex, and SES were not associated. CONCLUSION: Obesity was not associated with DFI, MSS, or OS in patients with clinical stage IB‐II melanoma who underwent SLNB

The Relationship of Anatomic Variation of Pancreatic Ductal System and Pancreaticobiliary Diseases

The aims of this study were to identify the morphological diversities and anatomical variations of pancreatic ductal system and to define the relationships between pancreatic ductal systems, pancreaticobiliary diseases, and procedure-related complications, including post-ERCP pancreatitis. This study included 582 patients in whom both pancreatic duct (PD) and common bile duct were clearly visible by ERCP. PD systems were categorized into four types according to the relationship between common bile duct and PD. In types A and B, Wirsung duct formed the main PD. In type C, Wirsung duct did not form the main PD. If PD system did not fall into any of these three types, it was categorized as type D. The distribution of types among pancreatic ducts examined was as follows: type A: 491 cases (84.4%), type B: 56 cases (9.6%), type C: 20 cases (3.4%), and type D: 15 cases (2.6%). The anomalous anatomic variations of PD systems were divided into migration, fusion, and duplication anomalies. PD anomalies were noted in 51 patients, of which 19 (3.3%) were fusion anomalies (12 complete pancreas divisum, 7 incomplete pancreas divisum), and 32 (5.5%) were duplication anomalies (5 number variations, 27 form variations). No significant relationships between various PD morphologies and pancreaticobiliary diseases were found. However, post-ERCP hyperamylasemia was more frequently found in types C (41.7%), D (50%) and A (19.8%) than in type B (9.4%). In summary, whether Wirsung duct forms the main PD and the presence or absence of the opening of the Santorini duct are both important factors in determining the development of pancreatitis and hyperamylasemia after ERCP

Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics

Bio-signal based control in assistive robots: a survey

Recently, bio-signal based control has been gradually deployed in biomedical devices and assistive robots for improving the quality of life of disabled and elderly people, among which electromyography (EMG) and electroencephalography (EEG) bio-signals are being used widely. This paper reviews the deployment of these bio-signals in the state of art of control systems. The main aim of this paper is to describe the techniques used for (i) collecting EMG and EEG signals and diving these signals into segments (data acquisition and data segmentation stage), (ii) dividing the important data and removing redundant data from the EMG and EEG segments (feature extraction stage), and (iii) identifying categories from the relevant data obtained in the previous stage (classification stage). Furthermore, this paper presents a summary of applications controlled through these two bio-signals and some research challenges in the creation of these control systems. Finally, a brief conclusion is summarized

Oncogenic HER2Δ16 suppresses miR-15a/16 and deregulates BCL-2 to promote endocrine resistance of breast tumors

Tamoxifen is the most commonly prescribed therapy for patients with estrogen receptor (ER)α-positive breast tumors. Tumor resistance to tamoxifen remains a serious clinical problem especially in patients with tumors that also overexpress human epidermal growth factor receptor 2 (HER2). Current preclinical models of HER2 overexpression fail to recapitulate the clinical spectrum of endocrine resistance associated with HER2/ER-positive tumors. Here, we show that ectopic expression of a clinically important oncogenic isoform of HER2, HER2Δ16, which is expressed in >30% of ER-positive breast tumors, promotes tamoxifen resistance and estrogen independence of MCF-7 xenografts. MCF-7/HER2Δ16 cells evade tamoxifen through upregulation of BCL-2, whereas mediated suppression of BCL-2 expression or treatment of MCF-7/HER2Δ16 cells with the BCL-2 family pharmacological inhibitor ABT-737 restores tamoxifen sensitivity. Tamoxifen-resistant MCF-7/HER2Δ16 cells upregulate BCL-2 protein levels in response to suppressed ERα signaling mediated by estrogen withdrawal, tamoxifen treatment or fulvestrant treatment. In addition, HER2Δ16 expression results in suppression of BCL-2-targeting microRNAs miR-15a and miR-16. Reintroduction of miR-15a/16 reduced tamoxifen-induced BCL-2 expression and sensitized MCF-7/HER2Δ16 to tamoxifen. Conversely, inhibition of miR-15a/16 in tamoxifen-sensitive cells activated BCL-2 expression and promoted tamoxifen resistance. Our results suggest that HER2Δ16 expression promotes endocrine-resistant HER2/ERα-positive breast tumors and in contrast to wild-type HER2, preclinical models of HER2Δ16 overexpression recapitulate multiple phenotypes of endocrine-resistant human breast tumors. The mechanism of HER2Δ16 therapeutic evasion, involving tamoxifen-induced upregulation of BCL-2 and suppression of miR-15a/16, provides a template for unique therapeutic interventions combining tamoxifen with modulation of microRNAs and/or ABT-737-mediated BCL-2 inhibition and apoptosis