Deubiquitylating enzymes and disease

Deubiquitylating enzymes (DUBs) can hydrolyze a peptide, amide, ester or thiolester bond at the C-terminus of UBIQ (ubiquitin), including the post-translationally formed branched peptide bonds in mono- or multi-ubiquitylated conjugates. DUBs thus have the potential to regulate any UBIQ-mediated cellular process, the two best characterized being proteolysis and protein trafficking. Mammals contain some 80–90 DUBs in five different subfamilies, only a handful of which have been characterized with respect to the proteins that they interact with and deubiquitylate. Several other DUBs have been implicated in various disease processes in which they are changed by mutation, have altered expression levels, and/or form part of regulatory complexes. Specific examples of DUB involvement in various diseases are presented. While no specific drugs targeting DUBs have yet been described, sufficient functional and structural information has accumulated in some cases to allow their rapid development

Clinico-hematological profile of paediatric patient admitted with acute leukemia in tertiary care centre of central India

Background: Leukemia is the most prevalent childhood cancer. Acute lymphoblastic leukemia (ALL) constitutes 75% of allcases. Objective: To find out the most common clinical and hematological findings of pediatric patients with acute leukemia at atertiary care center of central India. Materials and Methods: This retrospective study was done on 30 pediatric patients diagnosedwith acute leukemia in the Department of Pediatrics and Oncology at Chirayu Medical College and Hospital, Bhopal. This studyincluded children aged from 6 months to 15 years, who were admitted from June 2014 to June 2015. Data were retrospectivelycollected by reviewing medical records of these patients. Clinical history, physical examination, hematological, and radiologicaldata were analyzed. Results: ALL was the most common hematological malignancy observed at our hospital. In addition, it wasfound to be more prevalent in males and fever was the most common presenting symptoms followed by fatigue and anorexia.Hepatosplenomegaly and pallor were the most common findings on clinical examination. Among patients with ALL, subtype L1was the most common type. Among patients with acute myeloid leukemia, M2 and M3 subtypes were most commonly documented

Molecular detection and characterization of phytoplasma associated with China aster (Callistephus chinensis) phyllody in India

China aster (Callistephus chinensis L.) is one of the most popular annual flowering plant grown through-out the world. Phyllody disease of China aster is a phytoplasma associated disease that induces severe economic losses. Phytoplasmal disease in China aster was assessed for phytoplasma by direct polymerase chain reaction primed by using phytoplasma universal primer pairs PI/P7. A 1.8 Kb DNA fragments encoding the portion of phyto-plasma 16SrDNA amplified by PCR was cloned and sequenced. Sequencing of the PCR product and BLAST analy-sis indicated that China aster phyllody phytoplasma strain shared maximum sequence identity (99%) with strains of Peanut Witches’ broom (16SrII) phytoplasma group. Phylogenetic relationship of 16SrDNA sequence of China aster phyllody phytoplasma strain in the present study confirmed association of Peanut Witches’ broom (16SrII) group of phytoplasmas with China aster phyllody disease in India

Cellular players that shape evolving pathology and neurodegeneration following traumatic brain injury

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide, and has emerged as a critical risk factor for multiple neurodegenerative diseases, particularly Alzheimer’s disease (AD). How the inflammatory cascade resulting from mechanical stress, axonal shearing and the loss of neurons and glia following initial impact in TBI, contributes to the development of AD-like disease is unclear. Neuroinflammation, characterized by blood-brain barrier (BBB) dysfunction and activation of brain-resident microglia and astrocytes, resulting in secretion of inflammatory mediators and subsequent recruitment of peripheral immune cells has been the focus of extensive research in attempts to identify drug-targets towards improving functional outcomes post TBI. While knowledge of intricate cellular interactions that shape lesion pathophysiology is incomplete, a major limitation in the field is the lack of understanding of how distinct cell types differentially alter TBI pathology. The aim of this review is to highlight functional differences between populations of bone marrow derived, infiltrating monocytes/macrophages and brain-resident microglia based on differential expression of the chemokine receptors CCR2 and CX3CR1. This review will focus on how unique subsets of mononuclear phagocytes shape TBI pathophysiology, neurotoxicity and BBB function, in a disease-stage dependent manner. Additionally, this review summarizes the role of multiple microglia and macrophage receptors, namely CCR2, CX3CR1 and Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) in pathological neuroinflammation and neurodegeneration vs. recovery following TBI. TREM2 has been implicated in mediating AD-related pathology, and variants in TREM2 are particularly important due to their correlation with exacerbated neurodegeneration. Finally, this review highlights behavioral outcomes associated with microglial vs. macrophage variances, the need for novel treatment strategies that target unique subpopulations of peripheral macrophages, and the importance of development of therapeutics to modulate inflammatory functions of brain-resident microglia at specific stages of TBI

Nine challenges in incorporating the dynamics of behaviour in infectious diseases models.

Traditionally, the spread of infectious diseases in human populations has been modelled with static parameters. These parameters, however, can change when individuals change their behaviour. If these changes are themselves influenced by the disease dynamics, there is scope for mechanistic models of behaviour to improve our understanding of this interaction. Here, we present challenges in modelling changes in behaviour relating to disease dynamics, specifically: how to incorporate behavioural changes in models of infectious disease dynamics, how to inform measurement of relevant behaviour to parameterise such models, and how to determine the impact of behavioural changes on observed disease dynamics

Traumatic brain injury in hTau model mice: Enhanced acute macrophage response and altered long-term recovery

TBI induces widespread neuroinflammation and accumulation of microtubule associated protein tau (MAPT) - two key pathological features of tauopathies. This study sought to characterize the microglial/macrophage response to TBI in genomic-based MAPT transgenic mice in a Mapt knockout background (called hTau). Two-month-old hTau and age-matched control male and female mice received a single lateral fluid percussion TBI or sham injury. Separate groups of mice were aged to an acute (3 days post-injury [DPI]) or chronic (135 DPI) post-injury time point. As judged by tissue immunostaining for macrophage markers, microglial/macrophage response to TBI was enhanced at 3 DPI in hTau mice compared to control TBI and sham mice. However, MAPT phosphorylation increased in hTau mice regardless of injury group. Flow cytometric analysis revealed distinct populations of microglia and macrophages within all groups at 135 DPI. Unexpectedly, microglial reactivity was significantly reduced in hTau TBI mice compared to all other groups. Instead, hTau TBI mice showed a persistent macrophage response. In addition, TBI enhanced MAPT pathology in the temporal cortex and hippocampus of hTau TBI mice compared to controls 135 DPI. A battery of behavioral test revealed that TBI in hTau mice resulted in compromised use of spatial search strategies to complete a water maze task despite lack of motor or visual deficits. Collectively, these data indicate that the presence of wild-type human tau alters the microglial/macrophage response to a single TBI, induces delayed, region-specific MAPT pathology, and alters cognitive recovery; however, the causal relationship between these events remains unclear. These results highlight the potential significance of communication between MAPT and microglia/macrophages following TBI and emphasize the role of neuroinflammation in post-injury recovery

Attenuation of camptothecin production and negative relation between hyphal biomass and camptothecin content in endophytic fungal strains isolated from Nothapodytes nimmoniana Grahm (Icacinaceae)

Endophytic fungi, a group of fungi living inside the host plant tissues without causing visible symptoms of disease, are known to occur ubiquitously in plants. Existing in a mutualistic association with their host plants, they have been shown to enhance the plant’s ability to tolerate abiotic and biotic stresses3. In culture, many endophytic species have been shown to produce a number of important secondary metabolites including anticancer,antidiabetic, antifungal and immunosuppressant compounds. Many of these compounds closely mimic those produced by the respective host plants, suggesting that the fungi could in fact potentially serve as an alternative source of plant secondary metabolites. Notwithstanding these findings, to date, there has been no major breakthrough in commercially exploiting the endophytic fungi as a source of important secondary metabolites. Among the reasons attributed is the severe attenuation of production of the secondary metabolite by the fungi in culture. Li et al. showed that successive cultures of an endophytic fungi Pericornia sp. isolated from Torreya grandifolia, resulted in the attenuation of taxol production, though the fungal growth itself was unaffected. Although the reasons for such attenuation are not extensively studied, it is conjectured that it could be due to lack of host stimulus in the culture media

Comparative Analysis of Big Data Computing in Industry 4.0 and Industry 5.0: An Experimental Study

A comparison of the use of big data computing in Industry 4.0 and Industry 5.0 was carried out utilizing data collected from the actual world for the purpose of this research. The findings suggest that there has been a 2% drop in the number of faulty items produced in Industry 5.0, coupled with a 1% decrease in the amount of energy used in highly automated companies. According to the findings of the quality control, fault Type B accounts for around 65 percent of the overall defects in Industry 4.0. The results highlight the benefits of Industry 5.0, which capitalizes on human-machine cooperation, data-driven processes, and customized products and services. These insights help to contribute to manufacturing processes that are more efficient, more sustainable, and more quality-driven. Big data computing, Industry 4.0 and 5.0, quality control, and energy efficiency are some of the keywords to look for