CNN based Blockchain Information Protection Model for Emerging Cloud Applications

In the age of mobile internet, the amount of data is growing, and ability to process service data is always getting better. So, protecting data privacy and making sure the service environment is trustworthy have become very important. This paper looks at a trusted privacy service computing model for common uses of convolutional neural networks. The goal is to find data and model calculation methods that support homomorphic encryption to protect data privacy. Build a service process certificate and a method for distributing calculation rights based on blockchain and new contract technology to make sure that service calculations are open, trustworthy, and easy to track. Explore how the new cloud environment resource data service model helps resource providers, model owners, and users work together to make the most of their resources and grow the sharing economy. Lastly, experiments are done to figure out how the model protects privacy

Threonine 150 phosphorylation of keratin 5 is linked to EBS and regulates filament assembly, cell cycle and oxidative stress response

A characteristic feature of the skin blistering disease epidermolysis bullosa simplex is keratin filament (KF) network collapse caused by aggregation of the basal epidermal keratin type II (KtyII) K5 and its type I partner keratin 14 (K14). Here, we examine the role of keratin phosphorylation in KF network rearrangement and cellular functions. We detect phosphorylation of the K5 head domain residue T150 in cytoplasmic epidermolysis bullosa simplex granules containing R125C K14 mutants. Expression of phosphomimetic T150D K5 mutants results in impaired KF formation in keratinocytes. The phenotype is enhanced upon combination with other phosphomimetic K5 head domain mutations. Remarkably, introduction of T150D K5 mutants into KtyII-lacking (KtyII–/–) keratinocytes prevents keratin network formation altogether. In contrast, phosphorylation-deficient T150A K5 leads to KFs with reduced branching and turnover. Assembly of T150D K5 is arrested at the heterotetramer stage coinciding with increased heat shock protein association. Finally, reduced cell viability and elevated response to stressors is noted in T150 mutant cells. Taken together, our findings identify T150 K5 phosphorylation as an important determinant of KF network formation and function with a possible role in epidermolysis bullosa simplex pathogenesis

Generating evidence on antibiotic use across human and animal health sectors using the World Health Organization’s Access, Watch, Reserve (AWaRe) classification: Exploratory pilot study in rural Pune, India

Background and Aim: Human antibiotic formulations in animal feed for therapeutic and non-therapeutic purposes have contributed to antimicrobial resistance worldwide; however, little evidence is available in low- and middle-income countries. We aimed to generate evidence of antibiotic use across the human and animal health sectors by investigating the overlap in antibiotic use in community settings in rural blocks of Pune District, India, following the World Health Organization’s (WHO) Access, Watch, Reserve (AWaRe) classification. Materials and Methods: An exploratory pilot study using a cross-sectional design in two randomly selected rural blocks of the Pune district included 138 interviews with general physicians (GPs, n = 62), pharmacists (n = 60), and veterinary practitioners (n = 16) using semi-structured interview schedules and the WHO AWaRe classification. IBM-Statistical Package for the Social Sciences, Version 21.0 software was used for descriptive statistics and to calculate the proportions of the different antibiotic groups. The WHO AWaRe classification was used to describe antibiotic use by the study participants and to assess the overlap in antibiotic use. Results: Our study provides evidence of an overlap in human and animal antibiotic use in rural community settings across the human and animal health sectors. Amoxicillin (access group), penicillin (access group), and ofloxacin (watch group) were used in both human and animal health. Amoxicillin and penicillin were used to treat common bacterial infections, ofloxacin was used to treat skin infections in humans and animals, and ofloxacin was used to treat pneumonia in animals and urinary bladder infections in humans. In contrast, azithromycin (watch group), cefixime (watch group), and amoxicillin (Access Group), with or without other antibiotics, were the most commonly used antibiotics by GPs in humans. Conclusion: We confirmed the overlap in antibiotic use across the human and animal health sectors in rural community settings, suggesting the need for interventions following the One Health approach. Further, research is required to assess the patterns of this overlap, as well as behavior, knowledge, and potential solutions to help avoid this overlap and prevent the rampant use of antibiotics in the animal and human health sectors in rural community settings

Lentiviral Mediated Transgenesis by In Vivo Manipulation of Spermatogonial Stem Cells

This report describes a technique for the generation of transgenic mice by in vivo manipulation of spermatogonial stem cells with a high rate of success. Spermatogonial stem cells (SSCs) in pre-pubescent animals were infected in vivo with recombinant lentiviruses expressing EGFP-f and mated with normal females. All male pre-founder mice produced transgenic pups with an overall success rate of over 60%. The transgene was heritable and the pre-founder mice could be used in multiple mating experiments. This technology could be used to perform overexpression/knockdown screens in vivo using bar-coded lentiviruses, thus permitting the design of genetic screens in the mouse. Further, this technology could be adapted to other laboratory animals resulting in the generation of model systems that closely approximate human development and disease

Plakophilin3 Loss Leads to an Increase in PRL3 Levels Promoting K8 Dephosphorylation, Which Is Required for Transformation and Metastasis

The desmosome anchors keratin filaments in epithelial cells leading to the formation of a tissue wide IF network. Loss of the desmosomal plaque protein plakophilin3 (PKP3) in HCT116 cells, leads to an increase in neoplastic progression and metastasis, which was accompanied by an increase in K8 levels. The increase in levels was due to an increase in the protein levels of the Phosphatase of Regenerating Liver 3 (PRL3), which results in a decrease in phosphorylation on K8. The increase in PRL3 and K8 protein levels could be reversed by introduction of an shRNA resistant PKP3 cDNA. Inhibition of K8 expression in the PKP3 knockdown clone S10, led to a decrease in cell migration and lamellipodia formation. Further, the K8 PKP3 double knockdown clones showed a decrease in colony formation in soft agar and decreased tumorigenesis and metastasis in nude mice. These results suggest that a stabilisation of K8 filaments leading to an increase in migration and transformation may be one mechanism by which PKP3 loss leads to tumor progression and metastasis

Role of phosphorylation in keratin reorganization

Intermediate filaments, microtubules and microfilaments are major components of the mammalian cytoskeleton. Keratin intermediate filaments, which are strictly composed of a type I and a type II partner, play an important role in maintaining the mechanical integrity of epithelial tissues. Keratin molecules are composed of head (amino-terminal), rod (coiled –coil region) and tail (carboxy-terminal) regions. It was shown that the head region of type II keratin is crucial for keratin filament assembly. Phosphorylation, which is one of the major post-translational modifications of keratins, occurs mainly in the head and tail regions of keratins. This was often accompanied by altered keratin filament rearrangement. Keratin phosphorylation was also linked to fundamental physiological mechanisms such as stress, mitosis and apoptosis. Moreover, several epithelial diseases such as epidermolysis bullosa simplex were associated with abnormal keratin phosphorylation. The aim of this work was to decipher the mechanism of action of phosphorylation on keratin filament network formation and function. To study the effect of phosphorylation on keratin filament network organization, the filament-forming efficiency of a series of phosphomimetic mutants of the type II keratins 5 (K5) and 8 (K8) head regions were examined. Various mutants differing in the number of mutant residues were expressed in human epidermis-derived HaCaT cells. The percentage of cells with keratin filament forming defects correlated with the number of mutated residues. This observation can be taken as an indication of the additive effect of phosphorylation on keratin filament formation irrespective of the keratin isotype. Further, a model system to determine the consequence of phosphorylation on keratin filament organization and function in the absence of endogenous wild type keratins was established. This was achieved by preparing type II keratin knockout murine keratinocyte clones stably re-expressing phosphorylation mutants of the K5 head domain residue T150. T150 K5, which is one of the major phosphorylation sites of K5, was either mutated into a phosphomimetic (T150D K5) or a phosphodeficient (T150A K5) residue. T150D K5-KO keratinocytes showed a diffuse keratin pattern with few granules and small filamentous particles. Further, the T150D K5 mutant was highly soluble, extremely dynamic and mainly composed of tetrameric intermediates most likely arrested during keratin filament assembly. Contrariwise, the T150A K5 mutant was competent in filament formation but exhibited decreased turnover and altered filament topology in the form of increased filament thickness and reduced network branching. Thus, phosphorylation of the T150 K5 residue regulated keratin filament network assembly, dynamics and morphology. Both T150D K5 and T150A K5 mutant clones showed reduced cell viability, upregulated response to oxidative stress and increased association with HSP70 chaperones. T150A K5-KO mutants additionally showed a cell cycle defect marked by a decrease in the G1:G2 phase ratio. Thus, phosphorylation of the T150 K5 residue was linked to cell physiology. Further, immortalized keratinocytes derived from patients with epidermolysis bullosa simplex disease showed colocalization of T150 K5 phospho-epitopes with R125C K14 mutant keratin aggregates, confirming the link between T150 K5 phosphorylation and keratin filament network alteration. In summary, this work showed that mutation at a single phosphorylation site in the keratin molecule could alter keratin filament network formation, keratin dynamics and physiological processes in the cell. Also, a negative correlation between the quantity of phosphorylated residues and keratin filament formation was observed. Thus, phosphorylation was identified as a potent switch in the regulation of keratin structure and function

Primary Non-Hodgkin's Lymphoma of Thyroid Gland -Report of a Rare Case Introduction

Abstract: Goiter is a common presentation of neck swellin

A story of fibers and stress: Matrix-embedded signals for fibroblast activation in the skin

Our skin is continuously exposed to mechanical challenge, including shear, stretch, and compression. The extracellular matrix of the dermis is perfectly suited to resist these challenges and maintain integrity of normal skin even upon large strains. Fibroblasts are the key cells that interpret mechanical and chemical cues in their environment to turnover matrix and maintain homeostasis in the skin of healthy adults. Upon tissue injury, fibroblasts and an exclusive selection of other cells become activated into myofibroblasts with the task to restore skin integrity by forming structurally imperfect but mechanically stable scar tissue. Failure of myofibroblasts to terminate their actions after successful repair or upon chronic inflammation results in dysregulated myofibroblast activities which can lead to hypertrophic scarring and/or skin fibrosis. After providing an overview on the major fibrillar matrix components in normal skin, we will interrogate the various origins of fibroblasts and myofibroblasts in the skin. We then examine the role of the matrix as signaling hub and how fibroblasts respond to mechanical matrix cues to restore order in the confusing environment of a healing wound