Plasticity of the Muscle Stem Cell Microenvironment

Satellite cells (SCs) are adult muscle stem cells capable of repairing damaged and creating new muscle tissue throughout life. Their functionality is tightly controlled by a microenvironment composed of a wide variety of factors, such as numerous secreted molecules and different cell types, including blood vessels, oxygen, hormones, motor neurons, immune cells, cytokines, fibroblasts, growth factors, myofibers, myofiber metabolism, the extracellular matrix and tissue stiffness. This complex niche controls SC biology-quiescence, activation, proliferation, differentiation or renewal and return to quiescence. In this review, we attempt to give a brief overview of the most important players in the niche and their mutual interaction with SCs. We address the importance of the niche to SC behavior under physiological and pathological conditions, and finally survey the significance of an artificial niche both for basic and translational research purposes

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Chromosome studies in Orchidaceae from Argentina

The center of diversity of Argentinean orchids is in the northeast region of the country. Chromosome numbers and karyotype features of 43 species belonging to 28 genera are presented here. Five chromosome records are the first ones at the genus level; these taxa are Aspidogyne kuckzinskii (2n = 42), Eurystyles actinosophila (2n = 56), Skeptrostachys paraguayensis (2n = 46), Stigmatosema polyaden (2n = 40) and Zygostates alleniana (2n = 54). In addition, a chromosome number is presented for the first time for 15 species: Corymborkis flava (2n = 56), Cyclopogon callophyllus (2n = 28), C. oliganthus (2n = 64), Cyrtopodium hatschbachii (2n = 46), C. palmifrons (2n = 46), Galeandra beyrichii (2n = 54), Habenaria bractescens (2n = 44), Oncidium edwallii (2n = 42), O. fimbriatum (2n = 56), O. pubes (2n = 84), O. riograndense (2n = 56), Pelexia ekmanii (2n = 46), P. lindmanii (2n = 46) and Warrea warreana (2n = 48). For Oncidium longicornu (2n = 42), O. divaricatum (2n = 56) and Sarcoglottis fasciculata (2n = 46+1B?, 46+3B?), a new cytotype was found. Chromosome data support phylogenetic relationships proposed by previous cytological, morphologic and molecular analyses, and in all the cases cover some gaps in the South American literature on orchid chromosomes

Direct Reprogramming of Mouse Fibroblasts into Functional Skeletal Muscle Progenitors

Skeletal muscle harbors quiescent stem cells termed satellite cells and proliferative progenitors termed myoblasts, which play pivotal roles during muscle regeneration. However, current technology does not allow permanent capture of these cell populations in vitro. Here, we show that ectopic expression of the myogenic transcription factor MyoD, combined with exposure to small molecules, reprograms mouse fibroblasts into expandable induced myogenic progenitor cells (iMPCs). iMPCs express key skeletal muscle stem and progenitor cell markers including Pax7 and Myf5 and give rise to dystrophin-expressing myofibers upon transplantation in vivo. Notably, a subset of transplanted iMPCs maintain Pax7 expression and sustain serial regenerative responses. Similar to satellite cells, iMPCs originate from Pax7+ cells and require Pax7 itself for maintenance. Finally, we show that myogenic progenitor cell lines can be established from muscle tissue following small-molecule exposure alone. This study thus reports on a robust approach to derive expandable myogenic stem/progenitor-like cells from multiple cell types

A long non-coding RNA links calreticulin-mediated immunogenic cell removal to RB1 transcription

A subset of promoters bidirectionally expresses long non-coding RNAs (ncRNAs) of unknown function and protein-coding genes (PCGs) in parallel. Here, we define a set of 1107 highly conserved human bidirectional promoters that mediate the linked expression of long ncRNAs and PCGs. Depletion of the long ncRNA expressed from the RB1 promoter, ncRNA-RB1, reveals regulatory effects different from the RB1-controlled transcriptional program. ncRNA-RB1 positively regulates the expression of calreticulin (CALR) that in response to certain therapeutic interventions can translocate from the endoplasmic reticulum to the cell surface, hence activating anticancer immune responses. Knockdown of ncRNA-RB1 in tumor cells reduced expression of CALR, impaired the translocation of the protein to the cell surface upon treatment with anthracylines and consequently inhibited the cellular uptake by macrophages. In conclusion, co-transcription of ncRNA-RB1 and RB1 provides a positive link between the expression of the two tumor suppressors RB1 and the immune-relevant CALR protein. This regulatory interplay exemplifies disease-relevant co-regulation of two distinct gene products, in which loss of expression of one oncosuppressor protein entails the abolition of additional tumor-inhibitory mechanisms

ISSN exercise & sport nutrition review: research & recommendations

Sports nutrition is a constantly evolving field with hundreds of research papers published annually. For this reason, keeping up to date with the literature is often difficult. This paper is a five year update of the sports nutrition review article published as the lead paper to launch the JISSN in 2004 and presents a well-referenced overview of the current state of the science related to how to optimize training and athletic performance through nutrition. More specifically, this paper provides an overview of: 1.) The definitional category of ergogenic aids and dietary supplements; 2.) How dietary supplements are legally regulated; 3.) How to evaluate the scientific merit of nutritional supplements; 4.) General nutritional strategies to optimize performance and enhance recovery; and, 5.) An overview of our current understanding of the ergogenic value of nutrition and dietary supplementation in regards to weight gain, weight loss, and performance enhancement. Our hope is that ISSN members and individuals interested in sports nutrition find this review useful in their daily practice and consultation with their clients

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Gall-inducing insects from Campos de Altitude, Brazil

Insetos indutores de galhas são muito ricos em espécies nas formações vegetais do sudeste do Brasil. O objetivo deste estudo foi descrever a riqueza de morfotipos de galha por meio da caracterização de suas formas externas e os padrões de ocorrência nas plantas hospedeiras. As amostragens foram realizadas em campos rupestres e altitudinais de quatro regiões da Serra da Mantiqueira: 1) campos de altitude do Parque Estadual do Brigadeiro e 2) Parque Nacional do Caparaó, 3) Parque Estadual do Ibitipoca e Parque Nacional do Itatiaia. Foram registradas 93 espécies de galhas induzidas por insetos em 13 famílias, 30 gêneros e 50 espécies de plantas hospedeiras. Sendo 38 a riqueza de insetos indutores de galhas do Parque Estadual do Brigadeiro, 21 do Parque Nacional do Caparaó, 23 do Parque Nacional do Caparaó e 20 do Parque Nacional do Itatiaia. As famílias com maior riqueza foram Asteraceae (33%) e Melastomataceae (17%). A família Cecydomiidae (Diptera) foi a mais frequente (98%). O órgão mais atacado foi o caule (56%) seguido de folha (23%). O fato de apenas 12% das galhas descritas neste estudo já terem sido registradas em trabalhos anteriores, reforça a necessidade em aumentar o esforço amostral na direção de um maior conhecimento sobre a riqueza e história natural dos insetos indutores de galhas no Brasil. ____________________________________________________________________________________ABSTRACT: Gall-inducing insects are very specious in vegetations of southeastern Brazil. Our goal was describe the gall richness by characterizing their external forms and their patterns of occurrence on host plants. Samples were collected from Campos de Altitude at four regions of the Mantiqueira Range: 1) Parque Estadual da Serra do Brigadeiro, 2) Parque Nacional do Caparaó, 3) Parque Estadual do Ibitipoca, 4) Parque Nacional do Itatiaia. We found 93 gall species within 13 families, 30 genera and 50 host plant species. We recorded 38 gall species in Parque Estadual da Serra do Brigadeiro, 21 in Parque Nacional do Caparaó, 23 in Parque Estadual do Ibitipoca and 20 in Parque Nacional do Itatiaia. Asteraceae represented 33% of the species collected, followed by Melastomataceae at 17%; with each one concentrating 56% and 18% of the galling insects, respectively. 98% of galls were Cecydomiidae (Diptera). The most attacked organ was the stem (56%), followed by the leaf (23%). Only 12% of the galls described in our study had been already recorded in previous studies, thus reinforcing the need to increase the sampling effort toward a better understanding of the richness and the natural history of gall-inducing insects from Brazil