Spinal muscular atrophy (SMA), a prominent genetic disease of infant mortality, is caused by low levels of survival motor neuron (SMN) protein owing to deletions or mutations of the SMN1 gene. SMN2, ...a nearly identical copy of SMN1 present in humans, cannot compensate for the loss of SMN1 because of predominant skipping of exon 7 during pre-mRNA splicing. With the recent US Food and Drug Administration approval of nusinersen (Spinraza), the potential for correction of SMN2 exon 7 splicing as an SMA therapy has been affirmed. Nusinersen is an antisense oligonucleotide that targets intronic splicing silencer N1 (ISS-N1) discovered in 2004 at the University of Massachusetts Medical School. ISS-N1 has emerged as the model target for testing the therapeutic efficacy of antisense oligonucleotides using different chemistries as well as different mouse models of SMA. Here, we provide a historical account of events that led to the discovery of ISS-N1 and describe the impact of independent validations that raised the profile of ISS-N1 as one of the most potent antisense targets for the treatment of a genetic disease. Recent approval of nusinersen provides a much-needed boost for antisense technology that is just beginning to realize its potential. Beyond treating SMA, the ISS-N1 target offers myriad potentials for perfecting various aspects of the nucleic-acid-based technology for the amelioration of the countless number of pathological conditions.
Nanotechnology is a new and emerging technology with wealth of applications. It involves the synthesis and application of materials having one of the dimensions in the range of 1–100 nm. A wide ...variety of physico–chemical approaches are being used these days for the synthesis of nanoparticles (NPs). However, biogenic reduction of metal precursors to produce corresponding NPs is eco-friendly, less expensive, free of chemical contaminants for medical and biological applications where purity of NPs is of major concern. Biogenic reduction is a “Bottom Up” approach similar to chemical reduction where a reducing agent is replaced by extract of a natural products with inherent stabilizing, growth terminating and capping properties. Furthermore, the nature of biological entities in different concentrations in combination with reducing organic agents influence the size and shape of NPs. Present review focuses on microbes or plants based green synthesis of Ag, Au, Cu, Fe, Pd, Ru, PbS, CdS, CuO, CeO₂, Fe₃O₄, TiO₂, and ZnO NPs and their potential applications.
Physical and cognitive exercise may prevent or delay dementia in later life but the neural mechanisms underlying these therapeutic benefits are largely unknown. We examined structural and functional ...magnetic resonance imaging (MRI) brain changes after 6 months of progressive resistance training (PRT), computerized cognitive training (CCT) or combined intervention. A total of 100 older individuals (68 females, average age=70.1, s.d.±6.7, 55-87 years) with dementia prodrome mild cognitive impairment were recruited in the SMART (Study of Mental Activity and Resistance Training) Trial. Participants were randomly assigned into four intervention groups: PRT+CCT, PRT+SHAM CCT, CCT+SHAM PRT and double SHAM. Multimodal MRI was conducted at baseline and at 6 months of follow-up (immediately after training) to measure structural and spontaneous functional changes in the brain, with a focus on the hippocampus and posterior cingulate regions. Participants' cognitive changes were also assessed before and after training. We found that PRT but not CCT significantly improved global cognition (F(90)=4.1, P<0.05) as well as expanded gray matter in the posterior cingulate (P
<0.05), and these changes were related to each other (r=0.25, P=0.03). PRT also reversed progression of white matter hyperintensities, a biomarker of cerebrovascular disease, in several brain areas. In contrast, CCT but not PRT attenuated decline in overall memory performance (F(90)=5.7, P<0.02), mediated by enhanced functional connectivity between the hippocampus and superior frontal cortex. Our findings indicate that physical and cognitive training depend on discrete neuronal mechanisms for their therapeutic efficacy, information that may help develop targeted lifestyle-based preventative strategies.
The aqueous extract of leaf (LE), fruit (FE) and seed (SE) of Moringa oleifera was assessed to examine the ability to inhibit the oxidative DNA damage, antioxidant and anti-quorum sensing (QS) ...potentials. It was found that these extracts could significantly inhibit the OH-dependent damage of pUC18 plasmid DNA and also inhibit synergistically with trolox, with an activity sequence of LE>FE>SE. HPLC and MS/MS analysis was carried out, which showed the presence of gallic acid, chlorogenic acid, ellagic acid, ferulic acid, kaempferol, quercetin and vanillin. The LE was with comparatively higher total phenolics content (105.04mg gallic acid equivalents (GAE)/g), total flavonoids content (31.28mg quercetin equivalents (QE)/g), and ascorbic acid content (106.95mg/100g) and showed better antioxidant activity (85.77%), anti-radical power (74.3), reducing power (1.1 ascorbic acid equivalents (ASE)/ml), inhibition of lipid peroxidation, protein oxidation, OH-induced deoxyribose degradation, and scavenging power of superoxide anion and nitric oxide radicals than did the FE, SE and standard α-tocopherol. Eventually, LE and FE were found to inhibit violacein production, a QS-regulated behavior in Chromobacterium violaceum 12472.
Background
During the last two decades, an increasing number of bariatric surgical procedures have been performed worldwide. There is no consensus regarding optimal perioperative care in bariatric ...surgery. This review aims to present such a consensus and to provide graded recommendations for elements in an evidence-based “enhanced” perioperative protocol.
Methods
The English-language literature between January 1966 and January 2015 was searched, with particular attention paid to meta-analyses, randomised controlled trials and large prospective cohort studies. Selected studies were examined, reviewed and graded. After critical appraisal of these studies, the group of authors reached a consensus recommendation.
Results
Although for some elements, recommendations are extrapolated from non-bariatric settings (mainly colorectal), most recommendations are based on good-quality trials or meta-analyses of good-quality trials.
Conclusions
A comprehensive evidence-based consensus was reached and is presented in this review by the enhanced recovery after surgery (ERAS) Society. The guidelines were endorsed by the International Association for Surgical Metabolism and Nutrition (IASMEN) and based on the evidence available in the literature for each of the elements of the multimodal perioperative care pathway for patients undergoing bariatric surgery.
In order to determine antioxidant activity, the five extracts/fractions of red onion peel were studied for their total content of phenolics (TPC), flavonoids (TFC), antioxidant activity (AOA), free ...radical scavenging activity (FRSA), assayed by DPPH radical in the terms of anti-radical power (ARP) and reducing power (RP), expressed as ascorbic acid equivalents (ASE)/ml. High TPC (384.7±5.0mg GAE/g), TFC (165.2±3.2mg QE/g), AOA (97.4±7.6%), ARP (75.3±4.5) and RP (1.6±0.3 ASE/ml) were found for the ethyl acetate (EA) fraction. EA fraction had markedly higher antioxidant capacity than butylated hydroxytoluene (BHT) in preventive or scavenging capacities against FeCl3-induced lipid peroxidation, protein fragmentation, hydroxyl (site-specific and non-site-specific), superoxide anion and nitric oxide radicals. EA fraction also showed dose dependent antimutagenic activity by following the inhibition of tobacco-induced mutagenicity in Salmonella typhimurium strains (TA102) and hydroxyl radical-induced nicking in plasmid pUC18 DNA. HPLC and MS/MS analysis showed the presence of ferulic, gallic, protocatechuic acids, quercetin and kaempferol. The large amount of polyphenols contained in EA fraction may cause its strong antioxidant and antimutagenic properties. This information shows that EA fraction of red onion peel can be used as natural antioxidant in nutraceutical preparations.
•Marker-assisted backcross improvement of mega varieties of rice.•QTLs for drought, submergence and salt tolerance.•Foreground and recombinant selection.•Background selection using high density 50K ...SNP chip.
Rice is a staple cereal of India cultivated in about 43.5Mha area but with relatively low average productivity. Abiotic factors like drought, flood and salinity affect rice production adversely in more than 50% of this area. Breeding rice varieties with inbuilt tolerance to these stresses offers an economically viable and sustainable option to improve rice productivity. Availability of high quality reference genome sequence of rice, knowledge of exact position of genes/QTLs governing tolerance to abiotic stresses and availability of DNA markers linked to these traits has opened up opportunities for breeders to transfer the favorable alleles into widely grown rice varieties through marker-assisted backcross breeding (MABB). A large multi-institutional project, “From QTL to variety: marker-assisted breeding of abiotic stress tolerant rice varieties with major QTLs for drought, submergence and salt tolerance” was initiated in 2010 with funding support from Department of Biotechnology, Government of India, in collaboration with International Rice Research Institute, Philippines. The main focus of this project is to improve rice productivity in the fragile ecosystems of eastern, northeastern and southern part of the country, which bear the brunt of one or the other abiotic stresses frequently. Seven consistent QTLs for grain yield under drought, namely, qDTY1.1, qDTY2.1, qDTY2.2, qDTY3.1, qDTY3.2, qDTY9.1 and qDTY12.1 are being transferred into submergence tolerant versions of three high yielding mega rice varieties, Swarna-Sub1, Samba Mahsuri-Sub1 and IR 64-Sub1. To address the problem of complete submergence due to flash floods in the major river basins, the Sub1 gene is being transferred into ten highly popular locally adapted rice varieties namely, ADT 39, ADT 46, Bahadur, HUR 105, MTU 1075, Pooja, Pratikshya, Rajendra Mahsuri, Ranjit, and Sarjoo 52. Further, to address the problem of soil salinity, Saltol, a major QTL for salt tolerance is being transferred into seven popular locally adapted rice varieties, namely, ADT 45, CR 1009, Gayatri, MTU 1010, PR 114, Pusa 44 and Sarjoo 52. Genotypic background selection is being done after BC2F2 stage using an in-house designed 50K SNP chip on a set of twenty lines for each combination, identified with phenotypic similarity in the field to the recipient parent. Near-isogenic lines with more than 90% similarity to the recipient parent are now in advanced generation field trials. These climate smart varieties are expected to improve rice productivity in the adverse ecologies and contribute to the farmer’s livelihood.
The North-Eastern region (NER) of India, comprising of Arunachal Pradesh, Assam, Manipur, Meghalaya, Mizoram, Nagaland and Tripura, is a hot spot for genetic diversity and the most probable origin of ...rice. North-east rice collections are known to possess various agronomically important traits like biotic and abiotic stress tolerance, unique grain and cooking quality. The genetic diversity and associated population structure of 6,984 rice accessions, originating from NER, were assessed using 36 genome wide unlinked single nucleotide polymorphism (SNP) markers distributed across the 12 rice chromosomes. All of the 36 SNP loci were polymorphic and bi-allelic, contained five types of base substitutions and together produced nine types of alleles. The polymorphic information content (PIC) ranged from 0.004 for Tripura to 0.375 for Manipur and major allele frequency ranged from 0.50 for Assam to 0.99 for Tripura. Heterozygosity ranged from 0.002 in Nagaland to 0.42 in Mizoram and gene diversity ranged from 0.006 in Arunachal Pradesh to 0.50 in Manipur. The genetic relatedness among the rice accessions was evaluated using an unrooted phylogenetic tree analysis, which grouped all accessions into three major clusters. For determining population structure, populations K = 1 to K = 20 were tested and population K = 3 was present in all the states, with the exception of Meghalaya and Manipur where, K = 5 and K = 4 populations were present, respectively. Principal Coordinate Analysis (PCoA) showed that accessions were distributed according to their population structure. AMOVA analysis showed that, maximum diversity was partitioned at the individual accession level (73% for Nagaland, 58% for Arunachal Pradesh and 57% for Tripura). Using POWERCORE software, a core set of 701 accessions was obtained, which accounted for approximately 10% of the total NE India collections, representing 99.9% of the allelic diversity. The rice core set developed will be a valuable resource for future genomic studies and crop improvement strategies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Constructed wetland (CW) efficiently decreased up to 90% BOD from sewage in 24h.•P. australis, T. latifolia and C. esculenta (HGR) were main components of CW.•CW efficiently removed nutrients and ...metals from sewage.
With aim to develop an efficient and ecofriendly approach for on-site treatment of sewage, a sub-surface flow constructed wetland (CW) has been developed by raising potential aquatic macrophytes; Typha latifolia, Phragmites australis, Colocasia esculenta, Polygonum hydropiper, Alternanthera sessilis and Pistia stratoites in gravel as medium. Sewage treatment potential of CW was evaluated by varying retention time at three different stages of plant growth and stabilization. After 6months, monitoring of fully established CW indicated reduction of 90%, 65%, 78%, 84%, 76% and 86% of BOD, TSS, TDS, NO3–N, PO4–P and NH4–N, respectively in comparison to inlet after 36h of retention time. Sewage treatment through CW also resulted in reduction of heavy metal contents. Thus, CW proved an effective method for treatment of wastewater and may be developed along river Ganga stretch as an alternative technology. Treated water may be drained into river to check further deterioration of Ganga water quality.
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