GABA(A) receptor phospho-dependent modulation is regulated by phospholipase C-related inactive protein type 1, a novel protein phosphatase 1 anchoring protein

GABA(A) receptors are critical in controlling neuronal activity. Here, we examined the role for phospholipase C-related inactive protein type 1 (PRIP-1), which binds and inactivates protein phosphatase 1alpha (PP1alpha) in facilitating GABA(A) receptor phospho-dependent regulation using PRIP-1(-/-) mice. In wild-type animals, robust phosphorylation and functional modulation of GABA(A) receptors containing beta3 subunits by cAMP-dependent protein kinase was evident, which was diminished in PRIP-1(-/-) mice. PRIP-1(-/-) mice exhibited enhanced PP1alpha activity compared with controls. Furthermore, PRIP-1 was able to interact directly with GABA(A) receptor beta subunits, and moreover, these proteins were found to be PP1alpha substrates. Finally, phosphorylation of PRIP-1 on threonine 94 facilitated the dissociation of PP1alpha-PRIP-1 complexes, providing a local mechanism for the activation of PP1alpha. Together, these results suggest an essential role for PRIP-1 in controlling GABA(A) receptor activity via regulating subunit phosphorylation and thereby the efficacy of neuronal inhibition mediated by these receptors

Analysis of volatile compounds of Malaysian Tualang (Koompassia excelsa) honey using gas chromatography mass spectrometry

The constituents of honey’s volatile compounds depend on the nectar source and differ depending on the place of origin. To date, the volatile constituents of Tualang honey have never been investigated. The objective of this study was to analyze the volatile compounds in local Malaysian Tualang honey. A continuous extraction of Tualang honey using five organic solvents was carried out starting from non-polar to polar solvents and the extracted samples were analysed using gas chromatography-massspectrometry (GC-MS). Overall, 35 volatile compounds were detected. Hydrocarbons constitute 58.5% of the composition of Tualang honey. Other classes of chemical compounds detected included acids, aldehydes, alcohols, ketones, terpenes, furans and a miscellaneous group. Methanol yielded the highest number of extracted compounds such as acids and 5-(Hydroxymethyl) furfural (HMF). This is the first study to describe the volatile compounds in Tualang honey. The use of a simple one tube, stepwise, non-thermal liquid-liquid extraction of honey is a advantageous as it prevents sample loss. Further research to test the clinical benefits of these volatile compounds is recommended

Food allergy

Food allergy is defined as an adverse immunologic response to a dietary protein. Food-related reactions are associated with a broad array of signs and symptoms that may involve many bodily systems including the skin, gastrointestinal and respiratory tracts, and cardiovascular system. Food allergy is a leading cause of anaphylaxis and, therefore, referral to an allergist for appropriate and timely diagnosis and treatment is imperative. Diagnosis involves a careful history and diagnostic tests, such as skin prick testing, serum-specific immunoglobulin E (IgE) testing and, if indicated, oral food challenges. Once the diagnosis of food allergy is confirmed, strict elimination of the offending food allergen from the diet is generally necessary. For patients with significant systemic symptoms, the treatment of choice is epinephrine administered by intramuscular injection into the lateral thigh. Although most children “outgrow” allergies to milk, egg, soy and wheat, allergies to peanut, tree nuts, fish and shellfish are often lifelong. This article provides an overview of the epidemiology, pathophysiology, diagnosis, management and prognosis of patients with food allergy

Embryofetal effects of the methanolic root extract of Cissampelos mucronata A. Rich in rats

This study was designed to examine the effect of the methanolic extract of the root of Cissampelos mucronata on embryo-foetal development in rats. A total of 60 nulliparous female rats weighing 143-215gm approximately 13 weeks of age in the proestrous stage were cohabited (1:1) with 60 male rats to obtain 40 pregnant rats which were assigned to four dosage groups (10 rats per group, I-IV) by random stratification to nearly equalized body weight difference between groups on gestataion day zero GD 0. Group I served as the control group while rats in Groups II, III and IV were administered with 100mgkg-1, 200mgkg-1and 300mgkg-1 doses of the extract respectively from implantation (GD6) to the day prior to the expected day of parturition (GD20). On GD20, the female rats were euthanized and uterine implantation data including live and dead foetuses were counted, weighed, gender determined and observed for external malformations. The results indicate that administration of the extract from gestation day 6 to 20 had no significant effect on the number of implantation sites while resorptions sites were significantly (p<0.05-0.001) high in a dose dependent manner. There was a decrease in the foetal weight, placental weight and crown rump length of the rats indicating that administration of the extract from gestation day 6 to 20 caused resorptions in pregnancy and decrease in foetal weight, placental weight and crown rump length rats in a dose dependent manner.Key words: Embryotoxic, crown rump, resorption, viable, foetu

Cisplatin induces tolerogenic dendritic cells in response to TLR agonists via the abundant production of IL-10, thereby promoting Th2-and Tr1-biased T-cell immunity

Although many advantageous roles of cisplatin (cis-diamminedichloroplatinum (II), CDDP) have been reported in cancer therapy, the immunomodulatory roles of cisplatin in the phenotypic and functional alterations of dendritic cells (DCs) are poorly understood. Here, we investigated the effect of cisplatin on the functionality of DCs and the changes in signaling pathways activated upon toll-like receptor (TLR) stimulation. Cisplatin-treated DCs down-regulated the expression of cell surface molecules (CD80, CD86, MHC class I and II) and up-regulated endocytic capacity in a dose-dependent manner. Upon stimulation with various TLR agonists, cisplatin-treated DCs showed markedly increased IL-10 production through activation of the p38 MAPK and NF-kappa B signaling pathways without altering the levels of TNF-alpha and IL-12p70, indicating the cisplatin-mediated induction of tolerogenic DCs. This effect was dependent on the production of IL-10 from DCs, as neither DCs isolated from IL-10(-/-) mice nor IL-10-neutralized DCs generated tolerogenic DCs. Interestingly, DCs that were co-treated with cisplatin and lipopolysaccharide (LPS) exhibited a decreased immunostimulatory capacity for inducing the proliferation of Th1- and Th17-type T cells; instead, these DCs contributed to Th2-type T cell immunity. Furthermore, in vitro and in vivo investigations revealed a unique T cell population, IL-10-producing CD3(+)CD4(+)LAG-3(+)CD49b(+)CD25(-)Foxp3(-) Tr1 cells, that was significantly increased without altering the Foxp3(+) regulatory T cell population. Taken together, our results suggest that cisplatin induces immune-suppressive tolerogenic DCs in TLR agonist-induced inflammatory conditions via abundant IL-10 production, thereby skewing Th cell differentiation towards Th2 and Tr1 cells. This relationship may provide cancer cells with an opportunity to evade the immune system.1123Ysciescopu

The spirit of sport: the case for criminalisation of doping in the UK

This article examines public perceptions of doping in sport, critically evaluates the effectiveness of current anti-doping sanctions and proposes the criminalisation of doping in sport in the UK as part of a growing global movement towards such criminalisation at national level. Criminalising doping is advanced on two main grounds: as a stigmatic deterrent and as a form of retributive punishment enforced through the criminal justice system. The ‘spirit of sport’ defined by the World Anti-Doping Agency (WADA) as being based on the values of ethics, health and fair-play is identified as being undermined by the ineffectiveness of existing anti-doping policy in the current climate of doping revelations, and is assessed as relevant to public perceptions and the future of sport as a whole. The harm-reductionist approach permitting the use of certain performance enhancing drugs (PEDs) is considered as an alternative to anti-doping, taking into account athlete psychology, the problems encountered in containing doping in sport through anti-doping measures and the effect of these difficulties on the ‘spirit of sport’. This approach is dismissed in favour of criminalising doping in sport based on the offence of fraud. It will be argued that the criminalisation of doping could act as a greater deterrent than existing sanctions imposed by International Federations, and, when used in conjunction with those sanctions, will raise the overall ‘price’ of doping. The revelations of corruption within the existing system of self-governance within sport have contributed to a disbelieving public and it will be argued that the criminalisation of doping in sport could assist in satisfying the public that justice is being done and in turn achieve greater belief in the truth of athletic performances

Dynamics of fully coupled rotators with unimodal and bimodal frequency distribution

We analyze the synchronization transition of a globally coupled network of N phase oscillators with inertia (rotators) whose natural frequencies are unimodally or bimodally distributed. In the unimodal case, the system exhibits a discontinuous hysteretic transition from an incoherent to a partially synchronized (PS) state. For sufficiently large inertia, the system reveals the coexistence of a PS state and of a standing wave (SW) solution. In the bimodal case, the hysteretic synchronization transition involves several states. Namely, the system becomes coherent passing through traveling waves (TWs), SWs and finally arriving to a PS regime. The transition to the PS state from the SW occurs always at the same coupling, independently of the system size, while its value increases linearly with the inertia. On the other hand the critical coupling required to observe TWs and SWs increases with N suggesting that in the thermodynamic limit the transition from incoherence to PS will occur without any intermediate states. Finally a linear stability analysis reveals that the system is hysteretic not only at the level of macroscopic indicators, but also microscopically as verified by measuring the maximal Lyapunov exponent.Comment: 22 pages, 11 figures, contribution for the book: Control of Self-Organizing Nonlinear Systems, Springer Series in Energetics, eds E. Schoell, S.H.L. Klapp, P. Hoeve

Pro-apoptotic and immunotherapeutic effects of carbon nanotubes functionalized with recombinant human surfactant protein d on leukemic cells

Data Availability Statement: Not applicable.Copyright: © 2021 by the authors. Nanoparticles are efficient drug delivery vehicles for targeting specific organs as well as systemic therapy for a range of diseases, including cancer. However, their interaction with the immune system offers an intriguing challenge. Due to the unique physico-chemical properties, carbon nanotubes (CNTs) are considered as nanocarriers of considerable interest in cancer diagnosis and therapy. CNTs, as a promising nanomaterial, are capable of both detecting as well as delivering drugs or small therapeutic molecules to tumour cells. In this study, we coupled a recombinant fragment of human surfactant protein D (rfhSP-D) with carboxymethyl-cellulose (CMC) CNTs (CMC-CNT, 10–20 nm diameter) for augmenting their apoptotic and immunotherapeutic properties using two leukemic cell lines. The cell viability of AML14.3D10 or K562 cancer cell lines was reduced when cultured with CMC-mwCNT-coupled-rfhSP-D (CNT + rfhSP-D) at 24 h. Increased levels of caspase 3, 7 and cleaved caspase 9 in CNT + rfhSP-D treated AML14.3D10 and K562 cells suggested an involvement of an intrinsic pathway of apoptosis. CNT + rfhSP-D treated leukemic cells also showed higher mRNA expression of p53 and cell cycle inhibitors (p21 and p27). This suggested a likely reduction in cdc2-cyclin B1, causing G2/M cell cycle arrest and p53-dependent apoptosis in AML14.3D10 cells, while p53-independent mechanisms appeared to be in operation in K562 cells. We suggest that CNT + rfhSP-D has therapeutic potential in targeting leukemic cells, irrespective of their p53 status, and thus, it is worth setting up pre-clinical trials in animal modelsFunding: This project was funded by the National Plan for Science, Technology and Innovation (MAARIFAH), King Abdulaziz City for Science and Technology, Kingdom of Saudi Arabia, Award Number (15-NAN-3664-02)

Glycyrrhizic Acid Can Attenuate Metabolic Deviations Caused by a High-Sucrose Diet without Causing Water Retention in Male Sprague-Dawley Rats

Glycyrrhizic acid (GA) ameliorates many components of the metabolic syndrome, but its potential therapeutic use is marred by edema caused by inhibition of renal 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2). We assessed whether 100 mg/kg per day GA administered orally could promote metabolic benefits without causing edema in rats fed on a high-sucrose diet. Groups of eight male rats were fed on one of three diets for 28 days: normal diet, a high-sucrose diet, or a high-sucrose diet supplemented with GA. Rats were then culled and renal 11β-HSD2 activity, as well as serum sodium, potassium, angiotensin II and leptin levels were determined. Histological analyses were performed to assess changes in adipocyte size in visceral and subcutaneous depots, as well as hepatic and renal tissue morphology. This dosing paradigm of GA attenuated the increases in serum leptin levels and visceral, but not subcutaneous adipocyte size caused by the high-sucrose diet. Although GA decreased renal 11β-HSD2 activity, it did not affect serum electrolyte or angiotensin II levels, indicating no onset of edema. Furthermore, there were no apparent morphological changes in the liver or kidney, indicating no toxicity. In conclusion, it is possible to reap metabolic benefits of GA without edema using the current dosage and treatment time

The Web of Human Sexual Contacts

Many ``real-world'' networks are clearly defined while most ``social'' networks are to some extent subjective. Indeed, the accuracy of empirically-determined social networks is a question of some concern because individuals may have distinct perceptions of what constitutes a social link. One unambiguous type of connection is sexual contact. Here we analyze data on the sexual behavior of a random sample of individuals, and find that the cumulative distributions of the number of sexual partners during the twelve months prior to the survey decays as a power law with similar exponents $\alpha \approx 2.4$ for females and males. The scale-free nature of the web of human sexual contacts suggests that strategic interventions aimed at preventing the spread of sexually-transmitted diseases may be the most efficient approach.Comment: 7 pages with 2 eps figures. Latex file. For more details or for downloading the PDF file of the published article see http://polymer.bu.edu/~amaral/WebofContacts.html . For more results on teh structure of complex networks see http://polymer.bu.edu/~amaral/Networks.htm