The Mycobacterium tuberculosis PE_PGRS Protein Family Acts as an Immunological Decoy to Subvert Host Immune Response

Mycobacterium tuberculosis (M.tb) is a successful pathogen that can reside within the alveolar macrophages of the host and can survive in a latent stage. The pathogen has evolved and developed multiple strategies to resist the host immune responses. M.tb escapes from host macrophage through evasion or subversion of immune effector functions. M.tb genome codes for PE/PPE/PE_PGRS proteins, which are intrinsically disordered, redundant and antigenic in nature. These proteins perform multiple functions that intensify the virulence competence of M.tb majorly by modulating immune responses, thereby affecting immune mediated clearance of the pathogen. The highly repetitive, redundant and antigenic nature of PE/PPE/PE_PGRS proteins provide a critical edge over other M.tb proteins in terms of imparting a higher level of virulence and also as a decoy molecule that masks the effect of effector molecules, thereby modulating immuno-surveillance. An understanding of how these proteins subvert the host immunological machinery may add to the current knowledge about M.tb virulence and pathogenesis. This can help in redirecting our strategies for tackling M.tb infections.

Challenges of an Emerging Disease: The Evolving Approach to Diagnosing Devil Facial Tumour Disease

Devil Facial Tumour Disease (DFTD) is an emerging infectious disease that provides an excellent example of how diagnostic techniques improve as disease-specific knowledge is generated. DFTD manifests as tumour masses on the faces of Tasmanian devils, first noticed in 1996. As DFTD became more prevalent among devils, karyotyping of the lesions and their devil hosts demonstrated that DFTD was a transmissible cancer. The subsequent routine diagnosis relied on microscopy and histology to characterise the facial lesions as cancer cells. Combined with immunohistochemistry, these techniques characterised the devil facial tumours as sarcomas of neuroectodermal origin. More sophisticated molecular methods identified the origin of DFTD as a Schwann cell, leading to the Schwann cell-specific protein periaxin to discriminate DFTD from other facial lesions. After the discovery of a second facial cancer (DFT2), cytogenetics and the absence of periaxin expression confirmed the independence of the new cancer from DFT1 (the original DFTD). Molecular studies of the two DFTDs led to the development of a PCR assay to differentially diagnose the cancers. Proteomics and transcriptomic studies identified different cell phenotypes among the two DFTD cell lines. Phenotypic differences were also reflected in proteomics studies of extracellular vesicles (EVs), which yielded an early diagnostic marker that could detect DFTD in its latent stage from serum samples. A mesenchymal marker was also identified that could serve as a serum-based differential diagnostic. The emergence of two transmissible cancers in one species has provided an ideal opportunity to better understand transmissible cancers, demonstrating how fundamental research can be translated into applicable and routine diagnostic techniques.

Silencing of an efflux pump coding gene decreases the efflux rate of pyrazinoic acid in Mycobacterium smegmatis

Background: Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB). The recommended treatment for TB is based on the use of first-line drugs, including pyrazinamide (PZA). PZA is also a drug used in the treatment of multidrug-resistant TB (MDR-TB) because of its main effect against the latent stage. The main cause of resistance to PZA is mutations in the pncA gene, which compromise the activity of the encoded enzyme pyrazinamidase (PZAse), which hydrolyzes PZA into POA, the active antituberculosis molecule. The mechanism of action of PZA requires that POA is expelled from the bacterium by an efflux mechanism. After that, if the extracellular medium is sufficiently acidic, POA is protonated and returns to the cytosol, releasing the proton and repeating the cycle, resulting lethal to the bacteria. The efflux pump responsible for extruding the POA to the extracellular environment is not yet known. Mycobacterium smegmatis is naturally resistant to PZA and has a 900-fold faster POA efflux rate than MTB, and has the advantage to be a faster growing mycobacterium. Methods: In the present study we have silenced the transcription of several genes encoding efflux pumps in M. smegmatis by CRISPRi (CRISPR interference). These genes (MSMEG_0250, MSMEG_3815, MSMEG_0241, MSMEG_5046 and MSMEG_0410) were homologous to efflux pump genes in MTB. POA efflux rate was measured, and a quantitative Wayne's test was performed after silencing each gene. Results: Silencing of MSMEG_0250, resulted in an approximately 5-fold decrease in the POA efflux rate in M. smegmatis (P<0.0001). None of the other silenced genes showed a notable decrease in the POA efflux rate.

Classification Learning of Latent Bruise Damage to Apples Using Shortwave Infrared Hyperspectral Imaging

Bruise damage is a very commonly occurring defect in apple fruit which facilitates disease occurrence and spread, leads to fruit deterioration and can greatly contribute to postharvest loss. The detection of bruises at their earliest stage of development can be advantageous for screening purposes. An experiment to induce soft bruises in Golden Delicious apples was conducted by applying impact energy at different levels, which allowed to investigate the detectability of bruises at their latent stage. The existence of bruises that were rather invisible to the naked eye and to a digital camera was proven by reconstruction of hyperspectral images of bruised apples, based on effective wavelengths and data dimensionality reduced hyperspectrograms. Machine learning classifiers, namely ensemble subspace discriminant (ESD), k-nearest neighbors (KNN), support vector machine (SVM) and linear discriminant analysis (LDA) were used to build models for detecting bruises at their latent stage, to study the influence of time after bruise occurrence on detection performance and to model quantitative aspects of bruises (severity), spanning from latent to visible bruises. Over all classifiers, detection models had a higher performance than quantitative ones. Given its highest speed in prediction and high classification performance, SVM was rated most recommendable for detection tasks. However, ESD models had the highest classification accuracy in quantitative (>85%) models and were found to be relatively better suited for such a multiple category classification problem than the rest.

Dynamics and optimal control in transmission of tungiasis diseases

This paper aims to model the transmission of tungiasis disease and assess the optimal control schemes to stop its occurrence. Based on the development stage of fleas and propagation process of diseases, we propose a human-flea model without control, in which the susceptible-infected in latent stage-infectious populations and the egg-larva-pupa-adult stage of fleas are all in involved. In the light of the Lyapunov function method, we prove global stability of equilibria. The model is extended by reformulating it as an optimal control problem, with the use of four time-dependent controls, to assess the impact of individual protection, treatment and two flea control strategies (killing adult fleas and reduction of eggs and larvae). By using Pontryagin’s maximum principle, we characterize the optimal control. Using the data of human and flea in Brazil and Nigeri, numerical simulations are performed. The numerical results show that enhancing the protection and treatment of people and increasing the killing efficacy of flea adults would contribute to prevent and control the spread of the disease appreciably.

Exploring the Stochastic Host-Pathogen Tuberculosis Model with Adaptive Immune Response

In this literature, we probe a stochastic host-pathogen tuberculosis model with the adaptive immune response of four states of epidemiological classification: Mycobacterium tuberculosis, uninfected macrophages, infected macrophages, and immune response CD4+ T cells. This model is pertinent to the latent stage of tuberculosis infection and active tuberculosis-infected individuals. The stochastic host-pathogen tuberculosis model in pathology is constituted based on the environmental influence on the Mycobacterium tuberculosis and macrophage population, elucidated by stochastic perturbations, and it is proportional to each state. We evince the existence and a unique global positive solution of a stochastic tuberculosis model. We attain sufficient conditions for the extinction of the tubercle bacillus. Moreover, we acquire the existence of the stationary distribution of the positive solutions by the Lyapunov function method. Eventually, numerical simulations validate analytical findings and the dynamics of the stochastic TB model.

HISTORY OF DEVELOPING THE CONCEPT OF «LARGE SOCIAL GROUPS». PART 3: THE BEGGININGS of MODERN STAGE IN THE DEVELOPMENT OF SOCIAL PSYCHOLOGY (THE 1990s - 2000s of XX CENTURY)

Статья является продолжением историографического и психолого-исторического анализа научных представлений о больших социальных группах в соответствии с этапами развития социальной психологии и статуса таких групп в различные исторические периоды жизни страны. Начало этого анализа представлено в публикациях (Ковалева, 2020а, 2020б), в которых была реализована первая задача исследования по определению исторических рамок развития понятия «большие социальные группы», а также дана характеристика общественно-политическим условиям и уровню гуманитарного знания для следующих из выделенных периодов: становления социально-психологического направления исследований в России (вторая половина ХIХ - начало ХХ вв.); развития социальной психологии в 1920-е и до середины 1930-х гг.; латентного этапа в становлении социальной психологии (середина 1930-х - 1950-е гг.); возрождения отечественной социальной психологии (1960-е - середина 1970-х гг.) и оформления современной отечественной социальной психологии в систему научного знания (середина 1970-х - 1980-е гг.). В настоящей работе приводится анализ событий и исследований больших социальных групп в начале современного этапа в развитии социальной психологии - в 1990-е - 2000 гг. ХХ в., которые связаны с масштабными событиями - распадом СССР и радикальной реформой экономики. Показана последовавшая за ними социальная динамика, приведены описания новых больших социальных групп. В связи с трагичностью пережитых страной событий упор в работе делается на анализ информационных влияний на общество в изучаемый период, а также коллективных чувств, переживаемых представителями больших социальных групп, и динамики системы ценностей постсоветского социума. Отмечается значительное расширение объекта социально-психологических исследований в направлении изучения больших социальных групп. The paper is a continuation of historiographic and psychological-historical analysis of scientific ideas about large social groups in accordance with the stages of development of social psychology and the status of such groups in various historical periods of the country's life. The beginning of this analysis is presented in publications (Kovaleva, 2020a, 2020b), in which the first task of the study was realized to determine the historical framework for the development of the concept of «large social groups», and also a description was given of socio-political conditions and the level of humanitarian knowledge for the following of the selected periods: the formation of the socio-psychological direction of research in Russia (second half of the XIX - beginning of the XX centuries); the development of social psychology in the 1920s and until the mid-1930s.; latent stage in the formation of social psychology (mid-1930s - 1950s); the revival of domestic social psychology (1960s - mid-1970s) and the design of modern domestic social psychology into the system of scientific knowledge (mid-1970s - 1980s). This work provides an analysis of events and studies of large social groups at the beginning of the modern stage in the development of social psychology - in the 1990-s of XX century, which are associated with large-scale events - the collapse of the USSR and the shock reform of the economy. The following social dynamics were shown, descriptions of new large social groups were given. About the tragic character of the events experienced by the country, the emphasis in the work was on the analysis of information influences on society during the study period, as well as collective feelings experienced by representatives of large social groups and the dynamics of the system of values of the post-soviet society. There was a significant expansion of the object of socio-psychological research in the direction of studying large social groups.

CONCEPT OF DUSHI VISHA (CUMULATIVE TOXICITY) IN MODERN ERA: A CRITICAL REVIEW

In present era, thousands of harmful toxins are accumulated in environment are taken by human beings in different forms. These harmful toxins cause cumulative toxicity in human being which results in symptoms that can be seen slowly after their long- term use. These harmful toxins may be of Sthavara Visha/plant origin (e.g. Fruits and vegetables contaminated with pesticides, ripening agents, infections, heavy metal toxicity in plants, Maida, Pollen grains, dust, Latex from plants) Jangama Visha/ animal origin (e.g. Animal dander, adulteration in milk and milk products, Sea food containing heavy metals such as Hg, PCBs) Kritrim Visha (e.g. Toxic ingredients in cosmetics, Food preservatives, Food Flavouring agents, Synthetic Colour Additives, Environmental Pollution, Agricultural poisons, Medications like aspirin etc.). This Cumulative toxicity is similar to Dushi Visha as described in Ayurveda. A poison, which is having fewer properties, which means less than ten classical properties that a poison should contain, or either the poison which is having lesser potency of all the ten properties, attains a latent stage in the body is called as Dushi Visha (latent poison). The aim and objectives of this study is to study the concept of Dushi Visha in modern era and its toxic effects on human body.

Perkembangan Psikoseksual Santri Pada Usia Dini

Anak-anak usia dini terutama pada usia 4 hingga 6 tahun umumnya sudah mulai dikenalkan pada pendidikan formal dan non formal, salah satunya ialah pendidikan di pesantren. Pesantren dipilih oleh orang tua agar anak dapat belajar pengetahuan agama dan pengetahuan umum, serta pembentukan kemandirian dan kedisiplinan yang diharapkan orang tua. Pada santri usia dini, fase perkembangan psikoseksual yang dilalui diantaranya adalah fase falik dan laten. Dua fase krusial yang sangat berpengaruh terhadap kepribadian anak pada masa mendatang. Pada fase falik kepuasan terletak di daerah kemaluan yang normalnya akan mmebentuk identitas dan orientasi seksual anak. Sementara pada fase laten kepuasan terletak pada aspek kognitif dan interaksi sosial yang terealisasi melalui keterbukaan diri untuk berinteraksi dan bersosialiasi dengan lingkungan secara baik. Kehadiran orang tua sangat dibutuhkan oleh santri untuk bisa melewati fase falik dan laten dengan baik dan menyelesaikan konflik pada dua fase tersebut. Maka dari itu, meski pesantren memiliki tradisi yang kuat dalam pendidikan agama, namun orang tua tetap memiliki tanggung jawab utama dalam pendidikan dan pembimbingan anak-anak mereka.[Children especially at age 4 untill 6 years old have been introduced to formal and non-formal education where pesantren (islamic boarding school) is one of the most popular educatonal institutions in Indonesia. Commonly, pesantren is chosen by parents for their childs’ education to learn both religious and modern knowledge. Furthermore, pesantren education will form students’ independence. During their early-age development phase, santri (students who learn in pesantren) is remain similar to other children who experience psychosexual development; the two crucial stages are phallic and latent stage. Those periods would significantly affect santri’s personality. The phallic stage is closely corresponded to genitalia as the specific erotogenic zone. Normally this stage is related to sexual identity and sexual orientation. Meanwhile, latent period is a time of childs’ exploration into intellectual pursuits and social interactions, it is realized through self-disclosure towards interaction and adaptive socialization with their circumstances. On the other hand, parents are the important figure for children since they need to adapt to their psychosexual development phase including how to resolve several conflicts which may be dealed with them. Therefore, even though pesantren has a strong tradition in religious education, parents steady have main responsibility of their childs’ education and guidance].

Duration of anti-treponemal immunoglobulin M seroreversion after successful syphilis treatment in HIV-positive and -negative patients

Treponemal immunoglobulin M (IgM) antibody detection is currently among serologic tests used for syphilis diagnosis. However, the exact role of these antibodies is unclear. In this retrospective study of 326 (198 HIV positive and 128 negative) patients with early syphilis and positive IgM serology, data were analysed to investigate the time of IgM seroreversion after treatment and correlation with covariate factors. Median time of IgM seroreversion in the study population was 9 months (range 3–84, interquartile range 5–12). No statistically significant difference was observed between HIV-positive and -negative patients. At 12 months, 80.1% of the patients had a negative IgM test. At 6 months, 100% of HIV-positive patients had a fourfold decrease or greater in Venereal Disease Research Laboratory titres, but only 35.4% had a negative treponemal IgM. Secondary and early latent stage patients had a slower seroreversion of IgM (Hazard Ratio (HR) = 0.73, p = 0.064 and HR = 0.60, p = 0.023, respectively) than those with primary syphilis. A very strong association was observed of time to seroreversion of treponemal IgM with baseline VDRL titre ( p < 0.001). Treponemal IgM antibody detection often cannot distinguish between active and successfully treated syphilis. Treponemal IgM may only be useful in the cases recommended in the guidelines, and in cases of untreated syphilis, it could support but not confirm the diagnosis.