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The metals pollution in the Sarno River and its environmental impact on the Gulf of Naples (Tyrrhenian Sea, Central Mediterranean Sea) were estimated. Eight selected metals (As, Hg, Cd, Cr, Cu, Ni, Pb and Zn) were determined in the water dissolved phase (DP), suspended particulate matter (SPM) and sediment samples. Selected metals concentrations ranged from 0.32 to 1,680.39 μg l −1 in water DP, from 103.6 to 7,734.6 μg l −1 in SPM and from 90.7 to 2,470.3 mg kg −1 in sediment samples. Contaminant discharges of selected metals into the sea were calculated in about 13,977.6 kg year −1 showing that this river should account as one of the main contribution sources of metals to the Tyrrhenian Sea.

Mutations in the fukutin-related protein (FKRP) have recently been demonstrated to cause limb girdle muscular dystrophy type 2I (LGMD2I), one of the most common forms of the autosomal recessive LGMDs in Europe. We performed a systematic clinical and muscle MRI assessment in 6 LGMD2I patients and compared these findings with those of 14 patients with genetically confirmed diagnosis of other forms of autosomal recessive LGMDs or dystrophinopathies. All LGMD2I patients had a characteristic clinical phenotype with predominant weakness of hip flexion and adduction, knee flexion and ankle dorsiflexion. These findings were also mirrored on MRI of the lower extremities which demonstrated marked signal changes in the adductor muscles, the posterior thigh and posterior calf muscles. This characteristic clinical and MRI phenotype was also seen in LGMD2A. However, in LGMD2A there was a selective involvement of the medial gastrocnemius and soleus muscle in the lower legs which was not seen in LGMD2I. The pattern in LGMD2A and LGMD2I were clearly different from the one seen in alpha-sarcoglycanopathy and dystrophinopathy type Becker which showed marked signal abnormalities in the anterior thigh muscles. Our results indicate that muscular MRI is a powerful tool for differentiating LGMD2I from other forms of autosomal recessive LGMDs and dystrophinopathies.

Background: The limb girdle muscular dystrophies (LGMD) are a heterogeneous group of Mendelian disorders highlighted by weakness of the pelvic and shoulder girdle muscles. Seventeen autosomal loci have been so far identified and genetic tests are mandatory to distinguish among the forms. Mutations at the calpain 3 locus (CAPN3) cause LGMD type 2A. Objective: To obtain unbiased information on the consequences of CAPN3 mutations. Patients: 530 subjects with different grades of symptoms and 300 controls. Methods: High throughput denaturing HPLC analysis of DNA pools. Results: 141 LGMD2A cases were identified, carrying 82 different CAPN3 mutations (45 novel), along with 18 novel polymorphisms/variants. Females had a more favourable course than males. In 94% of the more severely affected patient group, the defect was also discovered in the second allele. This proves the sensitivity of the approach. CAPN3 mutations were found in 35.1% of classical LGMD phenotypes. Mutations were also found in 18.4% of atypical patients and in 12.6% of subjects with high serum creatine kinase levels. Conclusions: A non-invasive and cost–effective strategy, based on the high throughput denaturing HPLC analysis of DNA pools, was used to obtain unbiased information on the consequences of CAPN3 mutations in the largest genetic study ever undertaken. This broadens the spectrum of LGMD2A phenotypes and sets the carrier frequency at 1:103.

Limb girdle muscular dystrophy 2A (LGMD2A), caused by calpain 3 deficiency, is currently diagnosed through the immunodetection of muscle protein by Western blot (WB) analysis . However, WB may provide normal results in patients with LGMD2A. The case of a female (3y 6mo of age) is described. She was found to be affected by asymptomatic hypercreatine-kinaesaemia during routine biochemical analysis at 10 months of age and had developed myopathic signs at the last neurological assessment. The WB of muscle biopsy performed at 28 months of age showed a normal quantity and pattern of bands for calpain 3. Despite this finding, on molecular analysis she was found to be a compound heterozygote for two mutations of the calpain 3 (CAPN3) gene (R110X and G222R). Autocatalytic activity assay showed a loss of function of calpain 3. This is the first genetically confirmed case of very early onset calpainopathy with a normal amount of protein at WB. Molecular analysis is also suggested in very young patients with normal WB.

Autosomal recessive limb-girdle muscular dystrophies (LGMD2s) are a clinically and genetically heterogeneous group of disorders, characterized by progressive involvement of the proximal limb girdle muscles; the group includes at least 10 different genetic entities. The calpainopathies (LGMD2A), a subgroup of LGMD2s, are estimated to be the most common forms of LGMD2 in all populations so far investigated. LGMD2A is usually characterized by symmetrical and selective atrophy of pelvic, scapular and trunk muscles and a moderate to gross elevation of serum CK. However, the course is highly variable. It is caused by mutations in the CAPN3 gene, which encodes for the calpain-3 protein. Until now, 161 pathogenic mutations have been found in the CAPN3 gene. In the present study, through screening of 93 unrelated LGMD2 families, we identified 29 families with LGMD2A, 21 (22.6%) of which were identified as having CAPN3 gene mutations. We detected six novel (p.K211N, p.D230G, p.Y322H, p.R698S, p.Q738X, c.2257delGinsAA) and nine previously reported mutations (c.550delA, c.19_23del, c.1746-20C>G, p.R49H, p.R490Q, p.Y336N, p.A702V, p.Y537X, p.R541Q) in the CAPN3 gene. There may be a wide variety of mutations, but clustering of specific mutations (c.550delA: 40%, p.R490Q: 10%) could be used in the diagnostic scheme in Turkey.

Background: Malignant hyperthermia (MH) is a fatal autosomal dominant pharmacogenetic disorder characterized by skeletal muscle hypertonicity that causes a sudden increase in body temperature after exposure to common anesthetic agents. The disease is genetically heterogeneous, with mutations in the gene encoding the skeletal muscle ryanodine receptor (RYR1) at 19q13.1 accounting for up to 80% of the cases. To date, at least 42 RYR1 mutations have been described that cause MH and/or central core disease. Because the RYR1 gene is huge, containing 106 exons, molecular tests have focused on the regions that are more frequently mutated. Thus the causative defect has been identified in only a fraction of families as linked to chromosome 19q, whereas in others it remains undetected. Methods: We used denaturing HPLC (DHPLC) to analyze the RYR1 gene. We set up conditions to scan the 27 exons to identify both known and unknown mutations in critical regions of the protein. For each exon, we analyzed members from 52 families with positive in vitro contracture test results, but without preliminary selection by linkage analysis. Results: We identified seven different mutations in 11 MH families. Among them, three were novel MH alleles: Arg44Cys, Arg533Cys, and Val2117Leu. Conclusion: Because of its sensitivity and speed, DHPLC could be the method of choice for the detection of unknown mutations in the RYR1 gene.

The burden of food insecurity is large in Sub-Saharan Africa, yet the evidence-base on the relation between household food insecurity and early child development is extremely limited. Furthermore, available research mostly relies on cross-sectional data, limiting the quality of existing evidence. We use longitudinal data on preschool-aged children and their households in Ghana to investigate how being in a food insecure household was associated with early child development outcomes across three years. Household food insecurity was measured over three years using the Household Hunger Score. Households were first classified as \"ever food insecure\" if they were food insecure at any round. We also assessed persistence of household food insecurity by classifying households into three categories: (i) never food insecure; (ii) transitory food insecurity, if the household was food insecure only in one wave; and (iii) persistent food insecurity, if the household was food insecure in two or all waves. Child development was assessed across literacy, numeracy, social-emotional, short-term memory, and self-regulation domains. Controlling for baseline values of each respective outcome and child and household characteristics, children from ever food insecure households had lower literacy, numeracy and short-term memory. When we distinguished between transitory and persistent food insecurity, transitory spells of food insecurity predicted decreased numeracy (β = -0.176, 95% CI: -0.317; -0.035), short-term memory (β = -0.237, 95% CI: -0.382; -0.092), and self-regulation (β = -0.154, 95% CI: -0.326; 0.017) compared with children from never food insecure households. By contrast, children residing in persistently food insecure households had lower literacy scores (β = -0.243, 95% CI: -0.496; 0.009). No gender differences were detected. Results were broadly robust to the inclusion of additional controls. This novel evidence from a Sub-Saharan African country highlights the need for multi-sectoral approaches including social protection and nutrition to support early child development.

Inflammation, hypertension, and negative heart health outcomes including cardiovascular disease are closely linked but the mechanisms by which inflammation can cause high blood pressure are not yet fully elucidated. Cyclooxygenase (COX) enzymes play a role in pain, inflammation, and hypertension development, and inhibition of these enzymes is currently of great interest to researchers and pharmaceutical companies. Non-steroidal anti-inflammatory drugs are the drug of choice in terms of COX inhibition but can have negative side effects for consumers. Functional food ingredients containing cyclooxygenase inhibitors offer a strategy to inhibit cyclooxygenases without negative side effects. Several COX inhibitors have been discovered, to date, from marine and other resources. We describe here, for the first time, the generation and characterization of a bioactive hydrolysate generated using Viscozyme® and Alcalase from the red microalga Porphyridium sp. The hydrolysate demonstrates in vitro COX-1 inhibitory activity and antihypertensive activity in vivo, assessed using spontaneously hypertensive rats (SHRs). Peptides were identified and sequenced using MS and assessed using an in silico computational approach for potential bioactivities. The peptides predicted to be bioactive, including GVDYVRFF, AIPAAPAAPAGPKLY, and LIHADPPGVGL were chemically synthesized and cyclooxygenase inhibition was confirmed. Peptides AIPAAPAAPAGPKLY and LIHADPPGVGL had COX-1 IC50 values of 0.2349 mg/mL (0.16 µM) and 0.2193 mg/mL (0.2 µM), respectively. The hydrolysate was included in a food carrier (jelly candies) and an antihypertensive effect was observed in SHRs.

BIOPEP-UWM, a peptide database, contains 5128 peptides from a myriad of resources. Five listed peptides are Angiotensin-I-converting enzyme (ACE-1; EC3.4.15.1) inhibitory peptides derived from a red alga, while two from Chlorella vulgaris have anti-cancer and antioxidative bioactivities. Herein, we describe a process combining hydrolysis with two enzymes, Alcalase and Viscozyme, and filtration to generate protein-rich, bioactive peptide-containing hydrolysates from mixed species of Chlorella sp. and Scenedesmus sp. The potential of generated algal hydrolysates to act as food ingredients was determined by assessment of their techno-functional (foaming, emulsification, solubility, water holding, and oil holding capacity) properties. Bioactive screening of hydrolysates in vitro combined with mass spectrometry (MS) and in silico predictions identified bioactive and functional hydrolysates and six novel peptides. Peptides derived from Chlorella mix have the sequences YDYIGNNPAKGGLF and YIGNNPAKGGLF with predicted anti-inflammatory (medium confidence) and umami potential. Peptides from Scenedesmus mix have sequences IEWYGPDRPKFL, RSPTGEIIFGGETM, TVQIPGGERVPFLF, and IEWYGPDRPKFLGPF with predicted anti-inflammatory, anti-diabetic, and umami attributes. Such microalgal hydrolysates could provide essential amino acids to consumers as well as tertiary health benefits to improve human global health.

Obesity and type 2 diabetes are strongly associated with adipose tissue dysfunction and impaired adipogenesis. Understanding the molecular underpinnings that control adipogenesis is thus of fundamental importance for the development of novel therapeutics against metabolic disorders. However, translational approaches are hampered as current models do not accurately recapitulate adipogenesis. Here, a scaffold‐free versatile 3D adipocyte culture platform with chemically defined conditions is presented in which primary human preadipocytes accurately recapitulate adipogenesis. Following differentiation, multi‐omics profiling and functional tests demonstrate that 3D adipocyte cultures feature mature molecular and cellular phenotypes similar to freshly isolated mature adipocytes. Spheroids exhibit physiologically relevant gene expression signatures with 4704 differentially expressed genes compared to conventional 2D cultures (false discovery rate < 0.05), including the concerted expression of factors shaping the adipogenic niche. Furthermore, lipid profiles of >1000 lipid species closely resemble patterns of the corresponding isogenic mature adipocytes in vivo (R2 = 0.97). Integration of multi‐omics signatures with analyses of the activity profiles of 503 transcription factors using global promoter motif inference reveals a complex signaling network, involving YAP, Hedgehog, and TGFβ signaling, that links the organotypic microenvironment in 3D culture to the activation and reinforcement of PPARγ and CEBP activity resulting in improved adipogenesis. A scaffold‐free high‐throughput compatible 3D human adipocyte culture platform in chemically defined media is presented. The model is long‐term stable and closely resembles human adipocytes in vivo on transcriptomic, lipidomic, and functional level. Furthermore, transcription factor activity analysis reveals a complex signaling network that links the organotypic microenvironment to improved adipogenesis.