Microrna-221 and Microrna-222 Modulate Differentiation and Maturation of Skeletal Muscle Cells

BACKGROUND:MicroRNAs (miRNAs) are a class of small non-coding RNAs that have recently emerged as important regulators of gene expression. They negatively regulate gene expression post-transcriptionally by translational repression and target mRNA degradation. miRNAs have been shown to play crucial roles in muscle development and in regulation of muscle cell proliferation and differentiation. METHODOLOGY/PRINCIPAL FINDINGS:By comparing miRNA expression profiling of proliferating myoblasts versus differentiated myotubes, a number of modulated miRNAs, not previously implicated in regulation of myogenic differentiation, were identified. Among these, miR-221 and miR-222 were strongly down-regulated upon differentiation of both primary and established myogenic cells. Conversely, miR-221 and miR-222 expression was restored in post-mitotic, terminally differentiated myotubes subjected to Src tyrosine kinase activation. By the use of specific inhibitors we provide evidence that expression of miR-221 and miR-222 is under the control of the Ras-MAPK pathway. Both in myoblasts and in myotubes, levels of the cell cycle inhibitor p27 inversely correlated with miR-221 and miR-222 expression, and indeed we show that p27 mRNA is a direct target of these miRNAs in myogenic cells. Ectopic expression of miR-221 and miR-222 in myoblasts undergoing differentiation induced a delay in withdrawal from the cell cycle and in myogenin expression, followed by inhibition of sarcomeric protein accumulation. When miR-221 and miR-222 were expressed in myotubes undergoing maturation, a profound alteration of myofibrillar organization was observed. CONCLUSIONS/SIGNIFICANCE:miR-221 and miR-222 have been found to be modulated during myogenesis and to play a role both in the progression from myoblasts to myocytes and in the achievement of the fully differentiated phenotype. Identification of miRNAs modulating muscle gene expression is crucial for the understanding of the circuits controlling skeletal muscle differentiation and maintenance

Whole mitochondrial genomes unveil the impact of domestication on goat matrilineal variability

Background: The current extensive use of the domestic goat (Capra hircus) is the result of its medium size and high adaptability as multiple breeds. The extent to which its genetic variability was influenced by early domestication practices is largely unknown. A common standard by which to analyze maternally-inherited variability of livestock species is through complete sequencing of the entire mitogenome (mitochondrial DNA, mtDNA). Results: We present the first extensive survey of goat mitogenomic variability based on 84 complete sequences selected from an initial collection of 758 samples that represent 60 different breeds of C. hircus, as well as its wild sister species, bezoar (Capra aegagrus) from Iran. Our phylogenetic analyses dated the most recent common ancestor of C. hircus to ~460,000 years (ka) ago and identified five distinctive domestic haplogroups (A, B1, C1a, D1 and G). More than 90 % of goats examined were in haplogroup A. These domestic lineages are predominantly nested within C. aegagrus branches, diverged concomitantly at the interface between the Epipaleolithic and early Neolithic periods, and underwent a dramatic expansion starting from ~12–10 ka ago. Conclusions: Domestic goat mitogenomes descended from a small number of founding haplotypes that underwent domestication after surviving the last glacial maximum in the Near Eastern refuges. All modern haplotypes A probably descended from a single (or at most a few closely related) female C. aegagrus. Zooarchaelogical data indicate that domestication first occurred in Southeastern Anatolia. Goats accompanying the first Neolithic migration waves into the Mediterranean were already characterized by two ancestral A and C variants. The ancient separation of the C branch (~130 ka ago) suggests a genetically distinct population that could have been involved in a second event of domestication. The novel diagnostic mutational motifs defined here, which distinguish wild and domestic haplogroups, could be used to understand phylogenetic relationships among modern breeds and ancient remains and to evaluate whether selection differentially affected mitochondrial genome variants during the development of economically important breeds

Group psychological counseling to contrast academic burnout: a research protocol for a randomized controlled trial

Academic burnout is a condition characterized by exhaustion, cynicism, a distant attitude toward studying, and diminished self-efficacy in academic activities. Preliminary scientific findings indicate that interventions designed to alleviate work burnout also hold promise for mitigating academic burnout, however clear evidence based on randomized controlled trials is still missing. This research protocol describes a randomized controlled trial aimed at evaluating the efficacy of an online group psychological intervention to contrast academic burnout. Participants with high levels of burnout will be assigned to a psychological counseling group or a waiting list control group. The research comprises several phases: (T0) Screening, Recruitment, and Randomization; (T1) Baseline assessment (pre-intervention); (T2) Outcome Assessment (post-intervention); and (T3) Follow-up Assessment (3 months post-intervention). The primary outcomes include burnout symptoms, general wellbeing, and academic achievement. Additionally, secondary variables such as effort-reward imbalances, satisfaction/frustration of basic psychological needs, intrapersonal and interpersonal emotion regulation, coping strategies, and social support will be examined. The psychological intervention strategies will encompass psychoeducation, self-awareness enhancement, cognitive restructuring, and promotion of social support. This research protocol is an initial step toward evidence-based psychological interventions to treat academic burnout

Helena’s Many Daughters: More Mitogenome Diversity behind the Most Common West Eurasian mtDNA Control Region Haplotype in an Extended Italian Population Sample

The high number of matching haplotypes of the most common mitochondrial (mt)DNA lineages are considered to be the greatest limitation for forensic applications. This study investigates the potential to solve this constraint by massively parallel sequencing a large number of mitogenomes that share the most common West Eurasian mtDNA control region (CR) haplotype motif (263G 315.1C 16519C). We augmented a pilot study on 29 to a total of 216 Italian mitogenomes that represents the largest set of the most common CR haplotype compiled from a single country. The extended population sample confirmed and extended the huge coding region diversity behind the most common CR motif. Complete mitogenome sequencing allowed for the detection of 163 distinct haplotypes, raising the power of discrimination from 0 (CR) to 99.6% (mitogenome). The mtDNAs were clustered into 61 named clades of haplogroup H and did not reveal phylogeographic trends within Italy. Rapid individualization approaches for investigative purposes are limited to the most frequent H clades of the dataset, viz. H1, H3, and H7

Onopordum platylepis (Murb.) Murb. as a novel source of thistle rennet: First application to the manufacture of traditional Italian raw ewe’s milk cheese

In this study, for the very first time, aqueous extracts obtained from flowers of spontaneously grown or cultivated Onopordum platylepis (Murb.) Murb. thistles were used as coagulating agents for the pilot-scale manufacture of Caciofiore, a traditional Italian raw ewe’s milk cheese. Cheese prototypes were compared to control cheeses curdled with a commercial thistle rennet obtained from flowers of Cynara cardunculus L. After 45 days of ripening under controlled conditions, both the experimental and control cheese prototypes were analyzed for: cheese yield, physico-chemical (pH, titratable acidity, aw, proximate composition), morpho-textural (color and texture), and microbiological parameters (viable cell counts and species composition assessed by Illumina sequencing), as well as volatile profile by SPME-GC–MS. Slight variations in titratable acidity, color, and texture were observed among samples. Based on the results overall collected, neither the yield nor the proximate composition was apparently affected by the type of thistle coagulant. However, the experimental cheese prototypes curdled with extracts from flowers of both spontaneous or cultivated thistles showed 10 % higher values of water-soluble nitrogen compared to the control prototypes. On the other hand, these latter showed slightly higher loads of presumptive lactococci, thermophilic cocci, coliforms, and eumycetes, but lower counts of Escherichia coli. No statistically significant differences were revealed by the metataxonomic analysis of the bacterial and fungal biota. Though most volatile organic compounds (VOCs) were consistent among the prototypes, significant variability was observed in the abundance of some key aroma compounds, such as butanoic, hexanoic, and octanoic acids, ethanol, propan-2-ol, isobutyl acetate, 2-methyl butanoic acid, and 3-methyl butanal. However, further investigations are required to attribute these differences to either the type of coagulant or the metabolic activity of the microorganisms occurring in the analyzed cheese samples. The results overall collected support the potential exploitation of O. platylepis as a novel source of thistle coagulant to produce ewe’s milk cheeses.Ciencias de la AlimentaciónFarmacia y Nutrició

Ponatinib alone or with chemo-immunotherapy in heavily pre-treated Philadelphia-like acute lymphoblastic leukemia: a CAMPUS ALL real-life study

Not available

Abdominal drainage after elective colorectal surgery: propensity score-matched retrospective analysis of an Italian cohort

background: In italy, surgeons continue to drain the abdominal cavity in more than 50 per cent of patients after colorectal resection. the aim of this study was to evaluate the impact of abdominal drain placement on early adverse events in patients undergoing elective colorectal surgery. methods: a database was retrospectively analysed through a 1:1 propensity score-matching model including 21 covariates. the primary endpoint was the postoperative duration of stay, and the secondary endpoints were surgical site infections, infectious morbidity rate defined as surgical site infections plus pulmonary infections plus urinary infections, anastomotic leakage, overall morbidity rate, major morbidity rate, reoperation and mortality rates. the results of multiple logistic regression analyses were presented as odds ratios (OR) and 95 per cent c.i. results: a total of 6157 patients were analysed to produce two well-balanced groups of 1802 patients: group (A), no abdominal drain(s) and group (B), abdominal drain(s). group a versus group B showed a significantly lower risk of postoperative duration of stay >6 days (OR 0.60; 95 per cent c.i. 0.51-0.70; P < 0.001). a mean postoperative duration of stay difference of 0.86 days was detected between groups. no difference was recorded between the two groups for all the other endpoints. conclusion: this study confirms that placement of abdominal drain(s) after elective colorectal surgery is associated with a non-clinically significant longer (0.86 days) postoperative duration of stay but has no impact on any other secondary outcomes, confirming that abdominal drains should not be used routinely in colorectal surgery

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Association of variants in the SPTLC1 gene with juvenile amyotrophic lateral sclerosis

Importance Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation. Objective To identify the genetic variants associated with juvenile ALS. Design, Setting, and Participants In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism. Main Outcomes and Measures De novo variants present only in the index case and not in unaffected family members. Results Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway. Conclusions and Relevance These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene

Being a Dog: A Review of the Domestication Process

The process of canine domestication represents certainly one of the most interesting questions that evolutionary biology aims to address. A “multiphase” view of this process is now accepted, with a first phase during which different groups of wolves were attracted by the anthropogenic niche and a second phase characterized by the gradual establishment of mutual relationships between wolves and humans. Here, we provide a review of dog (Canis familiaris) domestication, highlighting the ecological differences between dogs and wolves, analyzing the molecular mechanisms which seem to have influenced the affiliative behaviors first observed in Belyaev’s foxes, and describing the genetics of ancient European dogs. Then, we focus on three Mediterranean peninsulas (Balkan, Iberian and Italian), which together represent the main geographic area for studying canine domestication dynamics, as it has shaped the current genetic variability of dog populations, and where a well-defined European genetic structure was pinpointed through the analysis of uniparental genetic markers and their phylogeny