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TP53 gene mutations are present in more than half of all human cancers. The resulting proteins are mostly full-length with a single amino acid change and are abundantly expressed in cancer cells. Some of the mutant p53 proteins gain oncogenic functions (GOF) through which it actively contribute to the aberrant cell proliferation, increased resistance to apoptotic stimuli and ability to metastasize. Gain of function mutant p53 proteins can transcriptionally regulate the expression of a large plethora of target genes. This mainly occurs through the formation of oncogenic transcriptional competent complexes that include mutant p53 protein, known transcription factors, posttranslational modifiers and scaffold proteins. Mutant p53 protein can also transcriptionally regulate the expression of microRNAs, small non-coding RNAs that regulate gene expression at the posttranscriptional level. Each microRNA can putatively target the expression of hundred mRNAs and consequently impact on many cellular functions. Thus, gain of function mutant p53 proteins can exert their oncogenic activities through the modulation of both non-coding and coding regions of human genome. Over the past 3 decades, the regulation of p53 has been extensively studied. However, the regulation of mutant p53 remained largely unexplored. This snapshot focuses on recent discovery of mutant p53 GOF and regulation.
mouse models --- mutant p53 --- dominant netagive --- therapies --- Oncogenic addiction --- gain of function
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The two most prominent mycobacterial diseases in animals include bovine tuberculosis, caused by Mycobacterium bovis and Johne’s disease, caused by Mycobacterium avium subspecies paratuberculosis. Erradication of both diseases has been hampered by a variety of factors. In many countries, the persistence of tuberculosis in cattle has been attributed to reservoirs of M. bovis in wildlife species. Brushtail possums, deer and badgers are notable examples of wildlife reservoirs for M. bovis. The difficulties in eliminating the wildlife reservoir for M. bovis further suggest the need for vaccination of farmed livestock. Vaccination of wildlife species has also been attempted with mixed results. Delivery of the vaccine to wildlife species appears to be a chief obstacle. Vaccination itself leads to complications for diagnostics. For example, when cattle are vaccinated with both BCG and a commercial Johne’s vaccine there is a biased toward the avian tuberculin skin test reaction. Despite these issues, BCG seems to be the clear standard for vaccination against M. bovis, yet many laboratories are investigating ways to improve on BCG. For Johne’s disease, the available commercial vaccines consist of whole-cell preparations in one form or another. But with the ability to generate directed knockouts of specific genes, a number of defined mutants have been constructed in a few laboratories. These should be tested and directly compared with each other and alongside commercial vaccine formulations to determine not only which vaccine is most protective, but which animal model is best for predicting protection in the target host. To this end, there has been a nation-wide, multi-institutional effort to test the best live, attenuated vaccine against Johne's disease in cattle, sheep and goats. This vaccine trial has spanned six years and was conducted in three phases. The first phase examined attenuation in bovine macrophages, the second phase was colonization of spleen and liver in mice and the third phase was protection from bacterial challenge in goats. Many new ideas and retrospective approaches have emerged from this unprecedented effort. These aspects will be captured in this Research Topic. In this Research Topic, we will seek articles on these above topics, but other issues surrounding vaccination of animals against mycobacteria will also be explored. These include immune parameters, correlates of protection, adjuvants and other vaccine formulations, etc.
Veterinary vaccines. --- Bacterial vaccines. --- Tuberculosis in cattle --- Bacterial Vaccines --- Prevention. --- immunology. --- goat trial --- correlates of protection --- Paratuberculosis --- Johne's disease --- Attenuated mutant --- Vaccine
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The book by M. Imran Kozgar aims to cover the problems of mutation breeding in pulse crops in the light of issues related to food insecurity and malnutrition, which according to FAO are the major threats at the present time. So far the research on induction of mutation in pulse crops is negligible compared to cereal crops, though the pulse crops and especially the chickpea are the largest grown crops in India. The main objective of the book is to reveal and explore the possibility of inducing genetic variability in early generations of mutated chickpea, describe the positive aspects of mutagenic treatments, evaluate the content of mineral elements (iron, manganese, zinc and copper) and physiological parameters of isolated high yielding mutant lines. The author hopes that his book will help to advance studies on pulse crops, and that in the long term it will help to reduce the food insecurity and malnutrition problems presently persisting in various developing countries, including India.
Chickpea --- Agriculture --- Earth & Environmental Sciences --- Plant Sciences --- Bengal gram --- Chestnut bean --- Chich --- Chich-pea --- Chick-pea --- Cicer arietinum --- Dwarf pea --- Garavance --- Garbanzo --- Gram (Legume) --- Gram pea --- Pea, Chick --- Cicer --- Mutation breeding --- Mutation breeding. --- pulse crops, chickpea, mutation breeding, effectiveness of mutagenic treatments, bioavailability of minerals, physiological parameters of mutant lines.
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The worldwide emergence of antimicrobial-resistant bacteria, specially those resistant to last-resource antibiotics, is now a common problem being defined as one of three priorities for the safeguarding of One Health by the Tripartite Alliance, which includes the World Health Organization (WHO), the Food and Agriculture Organization (FAO) and the Office International des Epizooties (OIE). Bacteria resistance profiles, together with the expression of specific virulence markers, have a major influence on the outcomes of infectious diseases. These bacterial traits are interconnected, since not only the presence of antibiotics may influence bacterial virulence gene expression and consequently infection pathogenesis, but some virulence factors may also contribute to an increased bacterial resistance ability, as observed in biofilm-producing strains. The surveillance of important resistant and virulent clones and associated mobile genetic elements is essential for decision making in terms of mitigation measures to be applied for the prevention of such infections in both human and veterinary medicine. However, the role of natural environments as important components of the dissemination cycle of these strains has not been consider until recently. This Special Issue aims to publish manuscripts that contribute to the understanding of the impact of bacterial antimicrobial resistance and virulence in the three areas of the One Health triad–i.e., animal, human and environmental health.
MRSA --- EMRSA-15 --- MLSB --- bacteremia --- bloodstream infections --- antibiotic resistance --- aquatic contamination --- probabilistic sampling --- San Francisco Estuary --- coast --- Pseudomonas --- Shewanella algae --- Vibrio parahaemolyticus --- biocide --- Listeria monocytogenes --- biofilm --- planktonic culture --- pulsed-field gel electrophoresis --- Escherichia coli --- fosfomycin --- nitrofurantoin --- antimicrobial resistance --- antibiotic susceptibility --- WGS --- phylogenetic analysis --- DNA mismatch repair system --- Salmonella Choleraesuis --- Iberian pig --- wild boar --- phylogenetic relationship --- plasmid replicon typing --- colistin --- carcass --- cfr gene --- fexA gene --- linezolid --- mutation --- pig --- public health --- S. aureus --- avian colibacillosis --- salmonellosis --- MDR --- tetA --- nisin --- mutant prevention concentration --- mutant selection window --- antimicrobial susceptibility testing --- horizontal gene transfer --- Salmonella --- reptiles --- isolation --- biofilms --- chlorhexidine gluconate --- wounds --- Gram-negative bacteria --- colonization --- infection --- clonal lineages --- resistance genes --- virulence factors --- Staphylococcus aureus --- skin and soft-tissue infections --- plasmids --- Panton–Valentine leucocidin
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Oligonucleotides (ON) constitute a new group of molecular agents, the object of significant interest due to their potential value as drugs for diagnostic and therapeutic applications. Their special interest derives from the intrinsic characteristics of ONs: a) ONs are informative agents, a property that derives from the order in which the nucleotides of each particular ON are arranged; b) ONs can act as ligands (ASO, TFO, aptamers, G-quadruplex, etc.) of complementary nucleic acid sequences (DNA or RNA) due to their high capacity to hybridize (by means of Watson and Crick or Hoogsteen links) with other nucleotide sequences, resulting in specific gene modulatory effects. However, nonspecific sequences may also be of interest, as is the case with repetitive nucleotide sequences (CpG) with adjuvant effects of vaccines; c) ONs can also rapidly evolve to achieve specific advantages of utility (targeting, stability, efficacy, toxicity, etc.) or high-sensitivity diagnostic technology (markers, analyzes, biosensors, FISH, microarrays, etc.), by chemical modification of nucleotides in any of their atoms. These properties show that ONs are first-order molecules due to their potential usefulness in practice.In this collection of research articles and review papers, we aim to highlight their therapeutic, but also diagnostic and technological utility as drugs.
quantum dots (QDs) --- DNAzyme --- ROS --- Amplex Red --- light-induced activity --- DNA methylation --- histone code --- microRNA --- nanoparticles --- noncoding RNA --- pulmonary arterial hypertension --- aptamer --- aptasensor --- influenza --- SERS --- virus detection --- α-synuclein --- antisense oligonucleotide --- dopamine neurotransmission --- double mutant A30P*A53T* --- motor deficits --- Parkinson’s disease --- transgenic mouse model --- G-quadruplexes --- covalent dimer construct --- anti-proliferative activity --- primary cell culture of human glioma --- antisensense oligonucleotide --- Foxp3 --- regulatory T cells --- vaccine immunogenicity --- Sporothrix schenckii --- Marfan syndrome --- fibrillin-1 --- antisense oligonucleotides --- exon skipping --- splice-switching
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The Special Issue “Juvenile Onset Huntington’s Disease” highlights the growing interest in understanding the unique aspects of this ultra-rare disorder. After decades of research, gene therapy trials are underway for Adult Onset Huntington’s Disease (AOHD). However, patients with Juvenile Onset Huntington’s Disease (JOHD) are often excluded from these efforts, leaving many questions regarding its phenomenology. The current issue includes seven articles spanning work on the difficult emotional experiences of parents of children with JOHD; a review of the clinical manifestations of JOHD; behavioral issues in JOHD; CAG repeat and age of motor onset; autonomic nervous system dysfunction; and abnormality in MRI metabolic markers. Finally, a review of the therapeutic advances is included, highlighting future possibilities of clinical trials in JOHD subjects. The HD community—patients, family members at-risk for HD, caregivers, health-care professionals and scientists—is keen on expanding our understanding of JOHD. In the flurry of research on AOHD, those with JOHD were seemingly ‘left behind.’ The study of patients who are afflicted early in life with HD has become imperative, with this Special Issue representing just the beginning of the required effort to address this urgent need.
Huntington’s disease --- CAG repeat --- mutant huntingtin (mHTT) --- therapeutics --- neurodegeneration --- juvenile Huntington’s disease --- pediatric Huntington’s disease --- early-onset Huntington’s disease --- personal experiences --- caregivers --- case series --- juvenile-onset Huntington’s disease --- T1-Rho --- neuroimaging --- behavioral regulation --- executive function --- trinucleotide repeat disorder --- CAG --- motor onset --- juvenile-onset Huntington’s Disease --- autonomic --- n/a --- Huntington's disease --- juvenile Huntington's disease --- pediatric Huntington's disease --- early-onset Huntington's disease --- juvenile-onset Huntington's disease --- juvenile-onset Huntington's Disease
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The papers included in this Special Issue address a variety of important aspects of Genetics, Genomics and Biotechnology of Plant Cytoplasmic Organelles, including new advances in the sequencing of both mitochondria and chloroplasts’ genomes using Next-Generation Sequencing technology in plant species and algae including important crop and tree species, in vitro culture protocol, and identification of a core module of genes involved in plastid development. In particular, the published studies focus on the description of adaptive evolution, elucidate mitochondrial mRNA processing, highlight the effect of domestication process on plastome variability and report the development of molecular markers. A meta-analysis of recently published genome-wide expression studies allowed the identification of novel nuclear genes, involved in the complex and still unrevealed mechanisms at the basis of communication between chloroplast and nucleus (retrograde signalling) during plastid development (biogenic control). Finally, an optimized regeneration protocol useful in plastid transformation of recalcitrant species, such as sugarcane, has been reported.
mitochondrial genome --- buckwheat --- plastid genome --- genetic diversity --- long reads --- targeted assembly --- genome assembly --- Fagus --- Fagaceae --- Fagales --- molecular marker --- mitochondrial marker --- taxon assignment --- CAPS marker --- SNP --- next-generation sequencing --- Solanum --- Italian landraces --- plastome --- molecular markers --- phylogenetic analysis --- plastid transformation --- sugarcane --- unfurled leaves --- streptomycin --- heteroplasmy --- mesophyll and bundle sheath cells --- plastids --- photomorphogenesis --- retrograde control --- biogenic signals --- lincomycin --- norflurazon --- pap7-1 mutant --- mitochondria --- RNA processing --- algal evolution --- circular RNA --- polycytidylation --- PacBio Iso-Seq --- Capparaceae --- chloroplast genome --- Cadaba --- Maerua --- phylogenetic relationships
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The mechanistic/mammalian target of rapamycin (mTOR), a serine/threonine kinase, is a central regulator for human physiological activity. Deregulated mTOR signaling is implicated in a variety of disorders, such as cancer, obesity, diabetes, and neurodegenerative diseases. The papers published in this Special Issue summarize the current understanding of the mTOR pathway and its role in the regulation of tissue regeneration, regulatory T cell differentiation and function, and different types of cancer including hematologic malignancies, skin, prostate, breast, and head and neck cancer. The findings highlight that targeting mTOR pathway is a promising strategy to fight against certain human diseases.
mTOR --- histone deacetylase --- prostate cancer --- integrins --- adhesion --- invasion --- cell metabolism --- T cells --- Foxp3 --- Acute Lymphoblastic leukemia --- targeted therapy --- metabolism --- cell signalling --- mTOR signalling --- head and neck cancer --- mutant genes --- biomarkers --- targeted therapies --- clinical trials --- cancers --- inhibitors --- photodynamic therapy --- PI3K --- Akt --- skin cancers --- phytochemicals --- melanoma --- basal cell carcinoma --- squamous cell carcinoma --- Merkel cell carcinoma --- TNBC --- eribulin --- PI3K/AKT/mTOR --- everolimus --- combination --- synergy --- mTOR signaling --- tissue regeneration --- neuron --- muscle --- liver --- intestine --- hematologic malignancies --- regulatory T cells --- tumor
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Some terms, such as eco-friendly, circular economy and green technologies, have remained in our vocabulary, because the truth is that mankind is altering the planet to put its own subsistence at risk. Besides, for rationalization in the consumption of raw materials and energy, the recycling of waste through efficient and sustainable processes forms the backbone of the paradigm of a sustainable industry. One of the most relevant technologies for the new productive model is anaerobic digestion. Historically, anaerobic digestion has been developed in the field of urban wastes and wastewater treatments, but in the new challenge, its role is more relevant. Anaerobic digestion is a technologically mature biological treatment, which joins bioenergy production with the efficient removal of contaminants. This issue provides a specialized, but broad in scope, overview of the possibilities of the anaerobic digestion of lignocellulosic biomass (mainly forestry and agricultural wastes), which is expected to be a more promising substrate for the development of biorefineries. Its conversion to bioenergy through anaerobic digestion must solve some troubles: the complex lignocellulosic structure needs to be deconstructed by pretreatments and a co-substrate may need to be added to improve the biological process. Ten selected works advance this proposal into the future.
exhausted sugar beet pulp --- pig manure --- anaerobic co-digestion --- thermophilic --- lignocellulosic waste --- anaerobic digestion --- biogas --- optimization --- operating parameters --- review --- particle-rich substrate --- suspended solids disintegration --- disintegration kinetics --- cellulase --- lignocellulosic biomass --- pretreatment methods --- limitations --- hydro-thermal pretreatment --- biofuels --- feedstock and degradation pathway --- AD systems --- pretreatment technologies --- process stability --- codigestion --- rice straw --- nutrients --- recycling --- digestate --- methane --- corn residue --- organosolv pretreatment --- sugar beet by-products --- manure --- semi-continuous feeding mode --- methane improvement --- non-classical parameters --- sorghum mutant --- biomass --- soluble sugars --- dilute acid pretreatment --- one-pot process --- n/a
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Polyamines are small organic compounds found in all living organisms. In recent years, there have been many exciting advances in our understanding of plant polyamines, such as the determination of the biosynthetic and catabolic pathways of plant polyamines and the identification of the roles that plant polyamines play in cellular processes. This Special Issue contains six original research papers and three review articles, providing valuable insights and information for future polyamine-related research.
polyamine oxidase --- norspermidine --- thermospermine --- Selaginella lepidophylla --- Arabidopsis thaliana mutant --- polyamines --- spermidine --- nonsense-mediated decay --- no-go decay --- non-stop decay --- quality control --- translation --- copper amine oxidases --- H2O2 --- ROS --- ABA --- stomatal closure --- back conversion pathway --- polyamine catabolism --- stress response --- terminal catabolism pathway --- Ranunculus biternatus --- Ranunculus pseudotrullifolius --- Ranunculus moseleyi --- secondary metabolite variation --- amines --- quercetins --- natural populations --- environment --- redundancy --- sub-Antarctic plants --- Arabidopsis --- phloem --- rice --- spermine --- xylem --- nitrogen metabolism --- abiotic and biotic stress --- hydrogen peroxide --- antioxidant machinery --- heat shock proteins --- heat stress --- polyamine oxidases --- PA acetylation --- PA oxidation --- PA back-conversion --- putrescine --- tomato --- spermidine synthase --- fruit shape --- cell division --- cell expansion --- copper amine oxidase
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