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1.
Nat Cell Biol ; 23(9): 939-952, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34475533

RESUMO

Regeneration requires the coordination of stem cells, their progeny and distant differentiated tissues. Here, we present a comprehensive atlas of whole-body regeneration in Schmidtea mediterranea and identify wound-induced cell states. An analysis of 299,998 single-cell transcriptomes captured from regeneration-competent and regeneration-incompetent fragments identified transient regeneration-activated cell states (TRACS) in the muscle, epidermis and intestine. TRACS were independent of stem cell division with distinct spatiotemporal distributions, and RNAi depletion of TRACS-enriched genes produced regeneration defects. Muscle expression of notum, follistatin, evi/wls, glypican-1 and junctophilin-1 was required for tissue polarity. Epidermal expression of agat-1/2/3, cyp3142a1, zfhx3 and atp1a1 was important for stem cell proliferation. Finally, expression of spectrinß and atp12a in intestinal basal cells, and lrrk2, cathepsinB, myosin1e, polybromo-1 and talin-1 in intestinal enterocytes regulated stem cell proliferation and tissue remodelling, respectively. Our results identify cell types and molecules that are important for regeneration, indicating that regenerative ability can emerge from coordinated transcriptional plasticity across all three germ layers.


Assuntos
Células Epidérmicas/citologia , Regeneração/fisiologia , Células-Tronco/metabolismo , Animais , Mediterranea/metabolismo , Interferência de RNA/fisiologia , Transcriptoma/fisiologia
3.
J Cardiovasc Electrophysiol ; 32(8): 2107-2115, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34216076

RESUMO

BACKGROUND: Outcomes of catheter ablation (CA) among patients with nonparoxysmal atrial fibrillation (AF) are largely disappointing. OBJECTIVE: We sought to evaluate the feasibility, effectiveness, and safety of a single-stage stepwise endo-/epicardial approach in patients with persistent/longstanding-persistent AF. METHODS: We enrolled 25 consecutive patients with symptomatic persistent (n = 4) or longstanding-persistent (n = 21) AF and at least one prior endocardial procedure, who underwent CA using an endo-/epicardial approach. Our anatomical stepwise protocol included multiple endocardial as well as epicardial (Bachmann's bundle [BB] and ligament of Marshall ablations) components, and entailed ablation of atrial tachycardias emerging during the procedure. The primary outcome was freedom from any AF/atrial tachycardia episode after a 3-month blanking period. The secondary outcome was patients' symptom status during follow-up. RESULTS: The stepwise endo-/epicardial approach allowed sinus rhythm restoration in 72% of patients, either directly (n = 6, 24%) or after AF organization into atrial tachycardia (n = 12, 48%). BB's ablation was commonly implicated in arrhythmia termination. After a median follow-up of 266 days (interquartile range, 96 days), survival free from AF/atrial tachycardia was 88%. Antiarrhythmic drugs could be discontinued in 22 patients (88%). As compared to baseline, more patients were asymptomatic at 9-month follow-up (0% vs. 56%, p = .02). Five patients (20%) developed mild medical complications, whereas one subject (4%) had severe kidney injury requiring dialysis. CONCLUSION: A single-stage endo-/epicardial CA resulted in favorable rhythm and symptom outcomes in a cohort of patients with symptomatic persistent/longstanding-persistent AF and one or more prior endocardial procedures. Epicardial ablation of BB was commonly implicated in procedural success.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Humanos , Mediterranea , Recidiva , Resultado do Tratamento
4.
Sci Rep ; 11(1): 11002, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34040129

RESUMO

Marseille-P9602T is a Chryseobacterium-like strain that we isolated from planarian Schmidtea mediterranea and characterized by taxono-genomic approach. We found that Marseille-P9602T strain exhibits a 16S rRNA gene sequence similarity of 98.76% with Chryseobacterium scophthalmum LMG 13028T strain, the closest phylogenetic neighbor. Marseille-P9602T strain was observed to be a yellowish-pigmented, Gram-negative, rod-shaped bacterium, growing in aerobic conditions and belonging to the Flavobacteriaceae family. The major fatty acids detected are 13-methyl-tetradecanoic acid (57%), 15-methylhexadecenoic acid (18%) and 12-methyl-tetradecanoic acid (8%). Marseille-P9602 strain size was found from genome assembly to be of 4,271,905 bp, with a 35.5% G + C content. The highest values obtained for Ortho-ANI and dDDH were 91.67% and 44.60%, respectively. Thus, hereby we unravel that Marseille-P9602 strain is sufficiently different from other closed related species and can be classified as a novel bacterial species, for which we propose the name of Chryseobacterium schmidteae sp. nov. Type strain is Marseille-P9602T (= CSUR P9602T = CECT 30295T).


Assuntos
Chryseobacterium , Mediterranea , Filogenia , RNA Ribossômico 16S
5.
Molecules ; 26(4)2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33672591

RESUMO

The present study provides new data concerning the chemical characterisation of Physcia mediterranea Nimis, a rare Mediterranean species belonging to the family Physciaceae. The phytochemical screening was carried out using GC-MS, HPLC-ESI-MS-MS, and NMR techniques. Hot extraction of n-hexane was carried out, followed by separation of the part insoluble in methanol: wax (WA-hex), from the part soluble in methanol (ME-hex). GC-MS analysis of the ME-hex part revealed the presence of methylbenzoic acids such as sparassol and atraric acid and a diterpene with a kaurene skeleton which has never been detected before in lichen species. Out of all the compounds identified by HPLC-ESI-MS-MS, sixteen compounds are common between WA-hex and ME-hex. Most are aliphatic fatty acids, phenolic compounds and depsides. The wax part is characterised by the presence of atranorin, a depside of high biological value. Proton 1H and carbon 13C NMR have confirmed its identification. Atranol, chloroatranol (depsides compound), Ffukinanolide (sesquiterpene lactones), leprolomin (diphenyl ether), muronic acid (triterpenes), and ursolic acid (triterpenes) have also been identified in ME-hex. The results suggested that Physcia mediterranea Nimis is a valuable source of bioactive compounds that could be useful for several applications as functional foods, cosmetics, and pharmaceuticals.


Assuntos
Líquens/química , Mediterranea/química , Compostos Fitoquímicos/análise , Estrutura Molecular , Especificidade da Espécie
6.
Diabetes Res Clin Pract ; 171: 108616, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33310172

RESUMO

AIM: To compare the changes in HbA1c, the effect on body weight or both combined after the addition of a DPP-4i, SGLT-2i, or sulfonylureas (SU) to metformin in real-world condition. METHODS: We used a primary care SIDIAP database. The included subjects were matched by propensity score according to baseline age, sex, HbA1c, weight, inclusion date, diabetes duration, and kidney function. RESULTS: Mean absolute HbA1c reduction was: 1.28% for DPP4i, 1.29% for SGLT2i and 1.26% for SU. Mean weight reduction was: 1.21 kg for DPP4i, 3.47 kg for SGLT2i and 0.04 kg for SU. The proportion of patients who achieved combined target HbA1c (≥0.5%) and weight (≥3%) reductions after the addition of DPP-4i, SGLT-2i or SU, was: 24.2%, 41.3%, and 15.2%, respectively. Small differences in systolic blood pressure reduction (1.07, 3.10 and 0.96 mmHg, respectively) were observed in favour of SGLT-2i. Concerning the lipids, we observed small differences, with an HDL-cholesterol increase with SGLT-2i. CONCLUSION: Our real-world study showed that the addition of SGLT-2i to metformin was associated with greater reductions in weight and the combination target of weight-HbA1c compared to SU and DPP4 inhibitors. However, similar hypoglycaemic effectiveness was observed among the three-drug classes.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Quimioterapia Combinada/métodos , Administração Oral , Feminino , Humanos , Masculino , Mediterranea , Pessoa de Meia-Idade , Estudos Retrospectivos
7.
PLoS One ; 15(11): e0240414, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33237902

RESUMO

The availability of reliable commercial information is considered a key feature of inter-regional trade if the Roman economy was highly integrated. However, the extent to which archaeological and historical sources of inter-regional trade reflect the degree of economic integration is still not fully understood, a question which lies at the heart of current debates in Roman Studies. Ceramic tableware offers one of the only comparable and quantifiable sources of information for Roman inter-regional trade over centuries-long time periods. The distribution patterns and stylistic features of tablewares from the East Mediterranean dated between 200 BC and AD 300 suggest a competitive market where buying decisions might have been influenced by access to reliable commercial information. We contribute to this debate by representing three competing hypotheses in an agent-based model: success-biased social learning of tableware buying strategies (requiring access to reliable commercial information from all traders), unbiased social learning (requiring limited access), and independent learning (requiring no access). We use approximate Bayesian computation (ABC) to evaluate which hypothesis best describes archaeologically observed tableware distribution patterns. Our results revealed success-bias is not a viable theory and we demonstrate instead that local innovation (independent learning) is a plausible driving factor in inter-regional tableware trade. We also suggest that tableware distribution should instead be explored as a small component of long-distance trade cargoes dominated by foodstuffs, metals, and building materials.


Assuntos
Cerâmica/economia , Comércio/história , Arqueologia , Teorema de Bayes , História Antiga , Humanos , Mediterranea , Mundo Romano , Análise de Sistemas
8.
J Cell Sci ; 133(8)2020 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-32107291

RESUMO

Pluripotent stem cells hold great potential for regenerative medicine. Increased replication and division, such is the case during regeneration, concomitantly increases the risk of adverse outcomes through the acquisition of mutations. Seeking for driving mechanisms of such outcomes, we challenged a pluripotent stem cell system during the tightly controlled regeneration process in the planarian Schmidtea mediterranea Exposure to the genotoxic compound methyl methanesulfonate (MMS) revealed that despite a similar DNA-damaging effect along the anteroposterior axis of intact animals, responses differed between anterior and posterior fragments after amputation. Stem cell proliferation and differentiation proceeded successfully in the amputated heads, leading to regeneration of missing tissues. Stem cells in the amputated tails showed decreased proliferation and differentiation capacity. As a result, tails could not regenerate. Interference with the body-axis-associated component ß-catenin-1 increased regenerative success in tail fragments by stimulating proliferation at an early time point. Our results suggest that differences in the Wnt signalling gradient along the body axis modulate stem cell responses to MMS.


Assuntos
Planárias , Animais , Dano ao DNA/genética , Cabeça , Mediterranea , Planárias/genética , Planárias/metabolismo , Via de Sinalização Wnt , beta Catenina/genética , beta Catenina/metabolismo
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