Lamin-Related Congenital Muscular Dystrophy Alters Mechanical Signaling and Skeletal Muscle Growth

Laminopathies are a clinically heterogeneous group of disorders caused by mutations in the LMNA gene, which encodes the nuclear envelope proteins lamins A and C. The most frequent diseases associated with LMNA mutations are characterized by skeletal and cardiac involvement, and include autosomal dominant Emery–Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy type 1B, and LMNA-related congenital muscular dystrophy (LMNA-CMD). Although the exact pathophysiological mechanisms responsible for LMNA-CMD are not yet understood, severe contracture and muscle atrophy suggest that mutations may impair skeletal muscle growth. Using human muscle stem cells (MuSCs) carrying LMNA-CMD mutations, we observe impaired myogenic fusion with disorganized cadherin/β catenin adhesion complexes. We show that skeletal muscle from Lmna-CMD mice is unable to hypertrophy in response to functional overload, due to defective fusion of activated MuSCs, defective protein synthesis and defective remodeling of the neuromuscular junction. Moreover, stretched myotubes and overloaded muscle fibers with LMNA-CMD mutations display aberrant mechanical regulation of the yes-associated protein (YAP). We also observe defects in MuSC activation and YAP signaling in muscle biopsies from LMNA-CMD patients. These phenotypes are not recapitulated in closely related but less severe EDMD models. In conclusion, combining studies in vitro, in vivo, and patient samples, we find that LMNA-CMD mutations interfere with mechanosignaling pathways in skeletal muscle, implicating A-type lamins in the regulation of skeletal muscle growth.     

Eugenol,citral, and hexanal,alone or in combination with heat,affect viability,biofilm formation,and swarming on Shiga-toxin-producing Escherichia coli

Shiga-toxin-producing Escherichia coli strains are pathogenic for humans and cause mild to severe illnesses. In this study, the antimicrobial effect of citral, eugenol, and hexanal in combination with heat shock (HS) was evaluated in terms of the growth, biofilm formation, swarming, and expression of virulence genes of STEC serotypes (O157:H7, O103, O111, and O26). Eugenol was the most effective compound against the growth of E. coli strains (MBC = 0.58 to 0.73 mg/mL), followed by citral (MBC = 0.86 to 1.26 mg/mL) and hexanal (MBC = 2.24 to 2.52 mg/mL). Biofilm formation and swarming motility have great variability between STEC strains. Natural compounds—alone or combined with HS—inhibited biofilm formation; however, swarming motility was induced by most treatments. The expression of the studied genes during biofilm formation and swarming under natural antimicrobials was affected but not in a uniform pattern. These treatments could be used to control contamination of STEC and inhibit biofilm formation.     

Nutritional and functional characterisation of hydrolysates from quinoa flour (Chenopodium quinoa) using two proteases

The objective was to study the nutritional and functional properties of hydrolysates from quinoa (Chenopodium quinoa) obtained by enzymatic hydrolysis of defatted quinoa flour (DQF). The commercial enzymes alcalase and flavourzyme were used to obtain the hydrolysates defatted quinoa flour hydrolysate with alcalase (DQFA) and defatted quinoa flour hydrolysate with flavourzyme (DQFF), respectively, after 3 h of digestion at 50°C and pH 8. The degree of hydrolysis (47.32%), yield (31.05%) and protein recovery (88.80%) values were higher in DQFA; however, its protein content (48.34%) was lower compared to that of DQFF (55.06%). Also, DQFA had a solubility greater than 57% over a wide pH range (2–10) and good foam stability (70–90%). On the other hand, DQFF presented adequate emulsifying activity (61.30 m²/g), emulsifying stability (158.62 min) and foaming capacity (131%). Due to the high content of macro- and micronutrients and adequate emulsifying and foaming properties, DQFA and DQFF could be used as ingredients in various processed food products and protein supplements.     

Color evolution during a coating process of pharmaceutical tablet cores by random spraying

Placebo white tablet cores (lactose anhydrous [47.6%], corn starch [23.8%], microcrystalline cellulose [19.1%], polyvinylpyrrolidone [7.9%], magnesium stearate [0.8%], and talcum powder [0.8%]) were coated with a colorant (hydroxypropyl methylcellulose [8% w/v], titanium dioxide [0.2% w/v], FD&C yellow No. 6 with aluminum lacquer [0.8% w/v], polyethylene glycol 4000 [0.4% w/v], and purified water [q.s.p. 100 mL]) using a random spraying method during 130 minutes. During the coating process, batches of 21 samples were extracted every 10 minutes and measured with a DigiEye imaging system. The initial cores showed very similar and uniform colors (Mean Color Difference from the Mean [MCDM] of 0.8 CIELAB units), but partially coated tablets showed lower uniformity (MCDM below 2.0 CIELAB units). There was a high color variability (MCDM about 4.0 CIELAB units) among tablets of the same batch in the period between 10 and 30 minutes, which decreased as the coating process progressed, until achieving a final acceptable value (MCDM below 2.0 CIELAB units). During the coating process, L^* decreased, C^*_ab strongly increased, and h _ab remained nearly constant (disregarding results at 0 and 10 minutes). CIELAB and CIEDE2000 color differences (mainly chroma differences) with respect to the initial color of the tablets were modeled as a function of time by exponential functions with three coefficients. The color change in the interval from 90 to 130 minutes (4.3 CIELAB units, or 2.6 CIEDE2000 units), may be considered negligible bearing in mind the color variability in the batches of 21 samples and typical values of visual color thresholds.     

Content Management Systems: Enriched learning opportunities for all?

This article examines the popular claim of Content Management Systems (CMSs) that providing a rich toolset and leaving the use under learner control is beneficial to learning. By means of a literature review, the current contribution examines whether all students are capable of using CMS tools so that their learning is enhanced. In contrast to what is assumed, the study conceptualizes tool use as a complex self-regulation strategy that cannot be taken for granted. Specifically, the article reviews empirical studies in relation to three topics: (a) personal agency in tool use, (b) performance effects of tool use and (c) influencing tool use variables. Findings reveal that not every student profited from the CMS learning opportunities; in multiple studies students differed in their tool use, and these differences had significant performance effects. Hence, these findings suggest that the pedagogical claim CMSs make is problematic. Besides this accumulated corpus of knowledge, the review revealed serious limitations in the retrieved studies which could hamper our findings. As a consequence, the review establishes a need for further research into students’ CMS tool use from an instructional design perspective. In addition to the theoretical framework, several directions for future research are given.     

Synergistic action between Caryocar coriaceum Wittm. fixed oil with aminoglycosides in vitro

The oil obtained from the Caryocar coriaceum Wittm. (pequi) fruit pulp (C. coriaceum fixed oil – CCFO), rich in fatty acids, has been secularly employed by traditional medicine in the treatment of respiratory affections, skin inflammation, and wounds. These observations encouraged us to investigate the antimicrobial activity of CCFO and to investigate its effect in combination with aminoglycosides. The minimum inhibitory concentration (MIC) of CCFO alone and associated with aminoglycosides against Escherichia coli and Staphylococcus aureus strains were determined using microdilution assay. CCFO alone had a MIC of 512 µg/mL against E. coli and S. aureus resistant strains. Combining the CCFO with aminoglycosides reduced the MIC of aminoglycosides against the resistant strains of E. coli and S. aureus. The results obtained indicate that CCFO displays a significant synergistic antibiotic effect when combined with aminoglycosides, demonstrating that the oil constituents (fatty acids) may act as potentiators of the antibiotic activity of aminoglycosides. These properties make CCFO oil an interesting alternative as a remedy or nutraceutical against multiresistant bacteria, preventing the development of resistance by these microorganisms. Practical applications: This article demonstrates the capacity of the C. coriaceum oil to enhance the antibiotic activity of aminoglycosides. This activity could represent a new way to combat the growing bacterial resistance to antibiotics, an important problem of public health.     

Electrochemically Stimulated Release from Liposomes Embedded in a Polyelectrolyte Multilayer

Triggered release of an entrapped dye from vesicles embedded in a polyelectrolyte multilayer (PEM), as a consequence of the electrochemically induced local pH change in the vicinity of the electrode, is reported. The PEM was deposited on an indium tin oxide (ITO) electrode wherein lipid vesicles filled with a fluorescent dye were embedded. The use of vesicles with a strong negative charge and the polyelectrolyte species of the PEM matrix with a polycation as topmost layer enabled the generation of a stable layer of liposomes in the PEM.