The role and regulation of CD1d in normal and pathological B cells

This work provides novel insights into the intersection between two critical areas of immunology, the CD1d-invariant NKT (iNKT) axis and B cells. CD1d is a non-polymorphic, MHC class I-like molecule, which presents phospho- and glycosphingo-lipid antigens to a subset of CD1d-restricted T cells called iNKT cells. CD1d is expressed on a variety of antigen presenting cells and the CD1d-iNKT cell axis regulates nearly all aspects of the innate and adaptive immune response. Expression of CD1d on B cells allows these cells to form cognate interactions with iNKT cells. Emerging evidence suggests, however, that expression of CD1d on B cells is variable, both on “normal” B cells during humoral immune responses, and also on “pathological” B cells in certain B cell disorders. In this work, I investigate in detail the expression of CD1d on B cells across a range of conditions. Using both human and murine germinal centre (GC) B cells as a model for normal B cells, I show for the first time that CD1d expression changes dynamically, both at the surface protein and transcriptional level. CD1d falls to a nadir as a naïve B cell enters the GC, and subsequently rises again in post GC B cells. I then provide evidence that the loss of CD1d expression is paralleled in pathological B cells, specifically in Epstein-Barr Virus infection of B cells and the plasma cell disorder Multiple Myeloma. In these conditions, CD1d is again downregulated at both the surface and transcriptional level. Having established that CD1d expression is lost in certain scenarios, I attempt to elucidate the biological significance of this downregulation. I approach this aim by attempting to constitutively express CD1d in murine GC B cells, and subsequently assessing the GC reaction. Constitutive expression of CD1d is achieved by two distinct methods, either by using adoptive transfer of Cd1d1 transduced haematopoietic stem cells or by using a CD1d transgenic mouse model. I show that both of these approaches represent a feasible way to constitutively express CD1d in murine GC B cells, but cannot establish a definitive biological role for CD1d downregulation in murine GC B cells. Finally, I investigate the transcriptional mechanisms governing the downregulation of CD1d, in either normal or pathological B cells. By analysing GC and MM B cells, I provide the first evidence that both retinoic acid signalling and bivalent chromatin domains act as a dual regulatory mechanism of CD1d. These findings demonstrate a new concept in the field of MM biology, specifically that MM B cells (like lymphomas) are able to “hijack” physiological pathways for disease propagation. Although previous work has highlighted the ability of all-trans retinoic acid (ATRA) alone to increase CD1d expression, this uncovering of a dual mechanism provides the rationale to use both ATRA and the polycomb-repressive complex inhibitor GSK343 to restore CD1d expression. I show that this is a more effective strategy than ATRA alone in increasing CD1d expression. Although this will need to be validated in further in vivo models, this ability to further increase CD1d expression may be of great therapeutic importance in the emerging field of tumour immunotherapy.Open Acces

Characterization of Isolated Bioactive Phytoconstituents from Flacourtia Indica as Potential Phytopharmaceuticals-An in Silico Perspective

The dependence of mankind for therapeutic applications on plants dates back to the start of the human race. Natural remedies from ethnobotanicals are found to be safe and cost effective. Due to the poor pharmacokinetic profiles and toxicity problems many synthetic drugs often fails to enter the market thus, the pharmacologically active compounds from plants continued to provide an important source of novel drug leads. The early inclusion of pharmacokinetics consideration in the drug discovery process using in silico methods is becoming popular due to improved generation of software’s. The problems with conventional method required time-consuming multi-step processes against a battery of in vivo biological screening and high cost thus, In silico prediction of the pharmacokinetic parameters, biological properties and toxicity due to advent of chemo-informatics tools, has reduced the cost dramatically and early application in drug design are realized. The present investigation deals with computational evaluation of six isolated phytocompounds from Flacourtia indica for their pharmacological potential and biological activities. These compounds were evaluated for drug likeness properties, bioactivity score, ADME/T profiles, and health affects by using various bioinformatics tools. The result indicated that all the six compounds analyzed were non mutagens, non-carcinogens and having good drug-likeness properties were seen. The ADMET parameters and probability of health effects were analyzed by admet SAR and ACD/I-Lab online tools respectively and results shows the ADMET and probability of health effects values are also in satisfying ranges. Pharmacological activities of these compounds were predicted individually using PASS server many different pharmacological activities and mechanisms of action shown by these compounds were reported. The results of our analysis clearly depict that all six phytocompounds were having good pharmacokinetic profiles with numerous biological activities. These compounds can be further studied in vitro and in vivo for the discovery of novel preventive and therapeutic drug

Rolul ultrasonografiei la pacienții cu boli renale

Discipline of Rheumatology and Nephrology, Nicolae Testemitanu SUMPhBackground. The use of ultrasound in nephrology has been on the increase in recent years. Doctors are increasingly performing ultrasonography, which has applications including investigations of the kidneys and lower urinary tract, as well as guiding percutaneous operations. Objective of the study. Systemic review of why ultrasonography is so crucial in today's society for nephrology and urinary illness diagnosis. Material and Methods. Systematic review of the published article was done with criteria as: 1) English language; 2) the 2008 -2020 period of publications; 3) 10 or more citations of articles. using WHO data, PubMed and National library of medicine medical databases. Results. As the number of people with chronic renal disease rises, there is a strong need for procedures that are less timeconsuming, less costly, and non-invasive. The technique is simple to learn and improves nephrology related diseases, hence ultrasonography mediated diagnosis is becoming more popular. The usefulness of ultrasound in the hands of the nephrologist is not limited exclusively to the ultrasound study of the kidney. By ultrasound, the nephrologist can also optimize the management of arterio-venous fistula for hemodialysis, measure cardiovascular risk, as well as the patient's volemia using basic cardiac ultrasound. Conclusion. Ultrasonography plays a significant role in assisting nephrologists in becoming more self-independent, efficient and cost- effective while improving patient treatment, hence nowadays nephrologists are striving to do this procedure to increase efficacy in treatment.Introducere. Utilizarea ultrasunetelor în nefrologie a crescut în ultimii ani. Medicii efectuează tot mai mult ultrasunografia, care are aplicații extinse, inclusiv investigația rinichilor și a tractului urinar inferior, precum și ghidarea operațiilor percutanate. Scopul lucrării. Revizuirea sistemică a motivului pentru care ultrasonografia este atât de crucială în societatea actuală pentru diagnosticarea maladiilor de rinichi și a aparatului urinar. Material și Metode. Revizuirea sistemică a articolelor publicate s-a făcut conform criteriilor: 1) limba engleză; 2) perioada 2008-2020; 3) 10 sau mai multe citări de articole, folosind datele OMS, PubMed și a Bibliotecii naționale de baze de date medicale. Rezultate. Pe măsură ce crește numărul persoanelor cu boli renale cronice, există o necesitate stringentă de proceduri care consumă mai puțin timp, sunt mai puțin costisitoare și neinvazive. Utilitatea ultrasunetelor în activitatea nefrologului nu se limitează exclusiv la studiul cu ultrasunete al rinichiului. Prin ultrasunete, nefrologul poate optimiza, de asemenea, managementul fistulei arterio-venoase pentru hemodializă, poate măsura riscul cardiovascular, precum și volemia pacientului utilizând ultrasunete cardiace de bază. Concluzii. US joacă un rol semnificativ în asistarea nefrologilor în a deveni mai independenți, mai eficienți și mai rentabili, îmbunătățind în același timp tratamentul pacientului, prin urmare, în prezent, nefrologii se străduiesc să facă această procedură, care crește eficacitatea în tratament

Application of ultrasound in patients with kidney diseases

Discipline of Rheumatology and NephrologyIntroduction The use of ultrasound in nephrology has been on the increase in recent years all over the world . Doctors are increasingly performing ultrasonography, which has applications across the spectrum of nephrology, including investigations of the kidneys and lower urinary tract, as well as guiding percutaneous operations. Purpose To evaluate the application of the ultrasound in patient with kidney disease and draw a conclusion. Material and methods Study design - systematic review. The use of ultrasound in a patient with kidney illness is investigated using WHO data and scientific papers from the PubMed,MedLine databases. Results As the number of people with chronic renal disease rises, there is a strong need for procedures that are less time-consuming, less costly, and noninvasive. The technique is simple to learn and improves nephrology related diseases, hence ultrasonography-mediated diagnosis is becoming more popular. Conclusions Ultrasonography plays a significant part in today's environment, assisting nephrologists in becoming more self-independent, efficient, and cost-effective while improving patient treatment. Nowadays, more nephrologists are striving to do these procedures. As a consequence, appropriate training in diverse approaches, as well as create recognized certification and teaching programmes, should begin

Global shocks and their impact on Nigeria: Lessons from global Financial crisis.

Developed a-five variable VAR model of the Nigeria economy for period 1970 – 2010, the study tested the general wisdom, ―Global financial crisis does not impact on Nigeria economy‖. Data were mainly sourced from both the National Bureau of Statistics (NBS) and the publication of the Central Bank of Nigeria (CBN). Augmented Dickey Fuller (ADF) and Philips-Perron (PP) tests were used in testing the null hypothesis that there is a unit root in the time series of interest. The variables considered were (1) log of GDP (2) log of FDI (3) log of REM (4) EXR and (5) CPI. Impulse-response functions were employed to examine the recovery from shocks makes full use of the within-country variation. We introduced the constant term and two lagged values of each variable in each equation and found that the impact of financial crisis on Nigeria was possible through financial links, trade links, remittances and other capital flows.This implies that the common believe about the Nigeria economy that global shocks through financial crisis does not have any impact is not quite accurate, for initially the global shocks made unstable the Nigerian economy through the macroeconomic variables understudied although after the initial instability resulting from the global shocks, the Nigeria economy then dependent less on fluctuations in the global economic crisis. We on that premise opined that the crisis presented an opportunity for Nigeria to unbalance the Nigeria economy by concentrate on leading sectors like power, education, agriculture so that the development of these sector can bring about a locomotive growth and results in balanced sector in the long run

A Cross-Sectional Comparative Study Of select Cognitive Functions in Adolescent Medical Students Engaged in Physical Activities and Video Gaming

Background: This study was conducted to compare the performance of cognitive function tests among adolescent students involved in physical activities, video-gaming, and board-gaming groups. Methods: A cohort of 300 participants (150 males and 150 females) were included in the study. The participants were divided into 3 groups (50 boys and 50 girls each) who were engaged regularly in physical activity, video gaming activity and board gaming activity respectively. The participants of all the groups were tested on selected neurocognitive tests from Wechsler Memory Scale – III (WMS – III) and NIMHANS Neuropsychological Battery. After acquiring baseline data, they were instructed to continue their respective gaming activities for a minimum of 2 hours each day. After 30 days of respective gaming activity, the battery of cognitive tests was administered again, and the pre and post results compared. Results: There was a statistically significant difference in the subset scores of Tests for Visual Presentation (Faces I and II) in the boys and girls of the Physical Activity group and gaming group independently. The AVLT scores showed statistically significant difference between girls and boys who were engaged in 30 days of board or video gaming activity. Conclusions: Our study shows that in the short term, there are differences in the cognitive performances of participants of the 3 groups of activities. Along-term follow-up study will help to differentiate the effect of these 3 activities upon cognitive function. Cognitive functions of young adults of both gender is influenced by physical and gaming activity

Quality education: Delhi government initiatives

Education is the foundation stone of a successful life: it empowers learners with knowledge and skills for overall development. Quality education must emphasise better acquisition of knowledge, skills, attitudes and values that help an individual deal with human, societal, national and universal goals. Cognitive and non-cognitive skills developed in schools contribute to economic as well as social development. It helps learners become socially more acceptable individuals and plays a pivotal role in creating peaceful, blissful and justifiable societies. Imparting quality education in schools is important for the development of skilful human beings as a resource for the country. Presently, children in different parts of the country are receiving unequal education with respect to quality parameters, though their success is completely associated with the level of quality education they are receiving. It is a fact that a person with quality education is able to innovate efficiently leading to enhanced economic developmen