ANTI-HELICOBACTER PYLORI ACTIVITY AND IMMUNOSTIMULATORY EFFECT OF OLIGOSACCHARIDE ISOLATED FROM AVERRHOA CARAMBOLA L.

Objective: The main goals of the study were to isolate oligosaccharide as a secondary metabolite from indigenous fruit, Averrhoa carambola L. (star fruit), and analyze its anti-Helicobacter pylori and immunostimulatory potential. Methods: The oligosaccharide (S3W) isolated using adsorption chromatography was partially characterized using tandem mass spectrometry in atmospheric pressure chemical ionization/electron spray ionization (APCI/ESI) positive and negative mode and nuclear magnetic resonance. The use of microtiter well method determined anti-H. pylori activity in the form of percentage inhibition of microbial growth, while the determination of the immunostimulatory potential of S3W implemented a protection of DNA, buccal cells, and macrophages against damage by oxidant and N-nitroso-N- methylurea (MNU) and percentage splenocyte proliferative potential. Results: S3W was a (1→2) β-heptaglucosaccharide with (4→6) α-branching at every second residue. APCI/ESI-positive mode showed B and A fragmentation patterns, while the negative mode showed abundance of A and C fragments. Anomeric hydrogen displayed integration values at 4.8 and 4.2 ppm indicating the presence of α-glucopyranose and β-glucopyranose. The compound protected DNA from oxidant-induced fragmentation. It expressed anti-H. pyloric activity with an IC50 value of 10.71 μg/ml. At 20 μg/ml, S3W protected buccal cells and macrophages significantly from damage due to oxidants and MNU carcinogens, while >50% splenocyte proliferation was induced as compared to that of an untreated control group. Conclusion: Our studies constitute the first report on the significant immunostimulatory activity of the oligosaccharide isolated from star fruit. The study, thus, supports its application as a therapeutic potential in curbing gastric diseases caused by H. pylori

Heat Stress and Goat Welfare: Adaptation and Production Considerations

This review attempted to collate and synthesize information on goat welfare and production constraints during heat stress exposure. Among the farm animals, goats arguably are considered the best-suited animals to survive in tropical climates. Heat stress was found to negatively influence growth, milk and meat production and compromised the immune response, thereby significantly reducing goats’ welfare under extensive conditions and transportation. Although considered extremely adapted to tropical climates, their production can be compromised to cope with heat stress. Therefore, information on goat adaptation and production performance during heat exposure could help assess their welfare. Such information would be valuable as the farming communities are often struggling in their efforts to assess animal welfare, especially in tropical regions. Broadly three aspects must be considered to ensure appropriate welfare in goats, and these include (i) housing and environment; (ii) breeding and genetics and (iii) handling and transport. Apart from these, there are a few other negative welfare factors in goat rearing, which differ across the production system being followed. Such negative practices are predominant in extensive systems and include nutritional stress, limited supply of good quality water, climatic extremes, parasitic infestation and lameness, culminating in low production, reproduction and high mortality rates. Broadly two types of methodologies are available to assess welfare in goats in these systems: (i) animal-based measures include behavioral measurements, health and production records and disease symptoms; (ii) resources based and management-based measures include stocking density, manpower, housing conditions and health plans. Goat welfare could be assessed based on several indicators covering behavioral, physical, physiological and productive responses. The important indicators of goat welfare include agonistic behavior, vocalization, skin temperature, body condition score (BCS), hair coat conditions, rectal temperature, respiration rate, heart rate, sweating, reduced growth, reduced milk production and reduced reproductive efficiency. There are also different approaches available by which the welfare of goats could be assessed, such as naturalistic, functional and subjective approaches. Thus, assessing welfare in goats at every production stage is a prerequisite for ensuring appropriate production in this all-important species to guarantee optimum returns to the marginal and subsistence farmers

A computed tomography based study on rotational alignment accuracy of the femoral component in total knee arthroplasty using computer-assisted orthopaedic surgery

Rotation of the femoral component in total knee arthroplasty (TKA) is of high importance in respect of the balancing of the knee and the patellofemoral joint. Though it is shown that computer assisted surgery (CAOS) improves the anteroposterior (AP) alignment in TKA, it is still unknown whether navigation helps in finding the accurate rotation or even improving rotation. Therefore the aim of our study was to evaluate the postoperative femoral component rotation on computed tomography (CT) with the intraoperative data of the navigation system. In 20 navigated TKAs the difference between the intraoperative stored rotation data of the femoral component and the postoperative rotation on CT was measured using the condylar twist angle (CTA). This is the angle between the epicondylar axis and the posterior condylar axis. Statistical analysis consisted of the intraclass correlation coefficient (ICC) and Bland-Altman plot. The mean intraoperative rotation CTA based on CAOS was 3.5° (range 2.4–8.6°). The postoperative CT scan showed a mean CTA of 4.0° (1.7–7.2). The ICC between the two observers was 0.81, and within observers this was 0.84 and 0.82, respectively. However, the ICC of the CAOS CTA versus the postoperative CT CTA was only 0.38. Though CAOS is being used for optimising the position of a TKA, this study shows that the (virtual) individual rotational position of the femoral component using a CAOS system is significantly different from the position on a postoperative CT scan

A Flavonoid, Luteolin, Cripples HIV-1 by Abrogation of Tat Function

Despite the effectiveness of combination antiretroviral treatment (cART) against HIV-1, evidence indicates that residual infection persists in different cell types. Intensification of cART does not decrease the residual viral load or immune activation. cART restricts the synthesis of infectious virus but does not curtail HIV-1 transcription and translation from either the integrated or unintegrated viral genomes in infected cells. All treated patients with full viral suppression actually have low-level viremia. More than 60% of treated individuals also develop minor HIV-1 –associated neurocognitive deficits (HAND) due to residual virus and immune activation. Thus, new therapeutic agents are needed to curtail HIV-1 transcription and residual virus. In this study, luteolin, a dietary supplement, profoundly reduced HIV-1 infection in reporter cells and primary lymphocytes. HIV-1inhibition by luteolin was independent of viral entry, as shown by the fact that wild-type and VSV–pseudotyped HIV-1 infections were similarly inhibited. Luteolin was unable to inhibit viral reverse transcription. Luteolin had antiviral activity in a latent HIV-1 reactivation model and effectively ablated both clade-B- and -C -Tat-driven LTR transactivation in reporter assays but had no effect on Tat expression and its sub-cellular localization. We conclude that luteolin confers anti–HIV-1 activity at the Tat functional level. Given its biosafety profile and ability to cross the blood-brain barrier, luteolin may serve as a base flavonoid to develop potent anti–HIV-1 derivatives to complement cART

The Interplay Between GUT and Flavour Symmetries in a Pati-Salam x S4 Model

Both Grand Unified symmetries and discrete flavour symmetries are appealing ways to describe apparent structures in the gauge and flavour sectors of the Standard Model. Both symmetries put constraints on the high energy behaviour of the theory. This can give rise to unexpected interplay when building models that possess both symmetries. We investigate on the possibility to combine a Pati-Salam model with the discrete flavour symmetry $S_4$ that gives rise to quark-lepton complementarity. Under appropriate assumptions at the GUT scale, the model reproduces fermion masses and mixings both in the quark and in the lepton sectors. We show that in particular the Higgs sector and the running Yukawa couplings are strongly affected by the combined constraints of the Grand Unified and family symmetries. This in turn reduces the phenomenologically viable parameter space, with high energy mass scales confined to a small region and some parameters in the neutrino sector slightly unnatural. In the allowed regions, we can reproduce the quark masses and the CKM matrix. In the lepton sector, we reproduce the charged lepton masses, including bottom-tau unification and the Georgi-Jarlskog relation as well as the two known angles of the PMNS matrix. The neutrino mass spectrum can present a normal or an inverse hierarchy, and only allowing the neutrino parameters to spread into a range of values between $\lambda^{-2}$ and $\lambda^2$, with $\lambda\simeq0.2$. Finally, our model suggests that the reactor mixing angle is close to its current experimental bound.Comment: 62 pages, 4 figures; references added, version accepted for publication in JHE

Induction of aromatic ring: cleavage dioxygenases in Stenotrophomonas maltophilia strain KB2 in cometabolic systems

Stenotrophomonas maltophilia KB2 is known to produce different enzymes of dioxygenase family. The aim of our studies was to determine activity of these enzymes after induction by benzoic acids in cometabolic systems with nitrophenols. We have shown that under cometabolic conditions KB2 strain degraded 0.25–0.4 mM of nitrophenols after 14 days of incubation. Simultaneously degradation of 3 mM of growth substrate during 1–3 days was observed depending on substrate as well as cometabolite used. From cometabolic systems with nitrophenols as cometabolites and 3,4-dihydroxybenzoate as a growth substrate, dioxygenases with the highest activity of protocatechuate 3,4-dioxygenase were isolated. Activity of catechol 1,2- dioxygenase and protocatechuate 4,5-dioxygenase was not observed. Catechol 2,3-dioxygenase was active only in cultures with 4-nitrophenol. Ability of KB2 strain to induce and synthesize various dioxygenases depending on substrate present in medium makes this strain useful in bioremediation of sites contaminated with different aromatic compounds

Bryostatin Modulates Latent HIV-1 Infection via PKC and AMPK Signaling but Inhibits Acute Infection in a Receptor Independent Manner

HIV's ability to establish long-lived latent infection is mainly due to transcriptional silencing in resting memory T lymphocytes and other non dividing cells including monocytes. Despite an undetectable viral load in patients treated with potent antiretrovirals, current therapy is unable to purge the virus from these latent reservoirs. In order to broaden the inhibitory range and effectiveness of current antiretrovirals, the potential of bryostatin was investigated as an HIV inhibitor and latent activator. Bryostatin revealed antiviral activity against R5- and X4-tropic viruses in receptor independent and partly via transient decrease in CD4/CXCR4 expression. Further, bryostatin at low nanomolar concentrations robustly reactivated latent viral infection in monocytic and lymphocytic cells via activation of Protein Kinase C (PKC) -α and -δ, because PKC inhibitors rottlerin and GF109203X abrogated the bryostatin effect. Bryostatin specifically modulated novel PKC (nPKC) involving stress induced AMP Kinase (AMPK) inasmuch as an inhibitor of AMPK, compound C partially ablated the viral reactivation effect. Above all, bryostatin was non-toxic in vitro and was unable to provoke T-cell activation. The dual role of bryostatin on HIV life cycle may be a beneficial adjunct to the treatment of HIV especially by purging latent virus from different cellular reservoirs such as brain and lymphoid organs