Berberine mitigates methotrexate-induced oxidative stress and inflammation in the cerebrum of rats

Berberine is a natural isoquinoline alkaloid with multiple beneficial therapeutic effects. This study was designed to evaluate the protective effect of berberine against methotrexate (MTX)-induced oxidative stress and inflammation in the brain of rats. Rats received a single intraperitoneal injection of MTX (20 mg/kg) and orally administered 25 mg/kg and 50 mg/kg body weight berberine for 7 days. MTX-induced rats showed significantly increased lipid peroxidation and nitric oxide levels in the cerebrum. Treatment of the MTXinduced rats with berberine produced a significant decrease in cerebral levels of lipid peroxidation and nitric oxide. In addition, berberine induced a significant increase in reduced glutathione, superoxide dismutase, glutathione peroxidase and glutathione-S-transferase in the cerebrum of MTX-induced rats. Rats received MTX showed a significant up-regulation of nuclear factor-kappaB (NF-κB), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α) and interleukin-1beta (IL-1β) expression in the cerebrum, an effect that was significantly reversed following treatment with berberine. In conclusion, berberine protects against MTXinduced neurotoxicity through attenuating oxidative stress and inflammation, and boosting the antioxidant defenses

Association between vitamin D receptor gene polymorphisms and chronic periodontitis among Libyans

Background: Chronic periodontitis (CP) is a common oral disease characterized by inflammation in the supporting tissue of the teeth ‘the periodontium’, periodontal attachment loss, and alveolar bone loss. The disease has a microbial etiology; however, recent findings suggest that the genetic factors, such as vitamin D receptor (VDR) gene polymorphisms, have also been included.Aim: Investigation of the relationship between VDR gene polymorphisms and CP among Libyans.Materials and methods: In this study, we examined 196 unrelated Libyans between the ages of 25 and 65 years, including 99 patients and 97 controls. An oral examination based on Ramfjord Index was performed at different dental clinics in Tripoli and information were collected using a self-reported questionnaire. DNA was extracted from buccal swabs; the VDR ApaI, BsmI, and FokI polymorphisms were genotyped using polymerase chain reaction and were sequenced using Sanger Method.Results: A significant difference in the newly detected ApaI SNP C/T rs#731236 was found (p0.022), whereas no significant differences were found in ApaI SNP G/T rs#7975232, BsmI SNPA/G rs#1544410, and FokI SNP A/G rs#2228570 between patients and controls (p0.939, 0.466, 0.239), respectively.Conclusion: VDR ApaI SNP C/T rs#731236 may be related to the risk of CP in the Libyan population.Keywords: chronic periodontitis; vitamin D receptor; gene; polymorphisms; variations; SN

New acute treatments for headache

Although we have several acute care medications for the treatment of migraine, we are always looking for new medications to treat our patients. Patients often say that their headaches are not under optimal control and would be happy to try another medication. Patients look for faster onset of relief, more complete relief, no recurrent headache and no adverse events. This article will cover some new and some anticipated acute care products, CGRP antagonists, sumatriptan by iontophoretic patch, sumatriptan by needle-free injections, DHE by oral inhalation and diclofenac potassium in a sachet. Botulinum toxin therapy, although a preventive measure, will be mentioned at the end

Electro-optically tunable microring resonators in lithium niobate

Optical microresonators have recently attracted a growing attention in the photonics community. Their applications range from quantum electro-dynamics to sensors and filtering devices for optical telecommunication systems, where they are likely to become an essential building block. The integration of nonlinear and electro-optical properties in the resonators represents a very stimulating challenge, as it would incorporate new and more advanced functionality. Lithium niobate is an excellent candidate material, being an established choice for electro-optic and nonlinear optical applications. Here we report on the first realization of optical microring resonators in submicrometric thin films of lithium niobate. The high index contrast films are produced by an improved crystal ion slicing and bonding technique using benzocyclobutene. The rings have radius R=100 um and their transmission spectrum has been tuned using the electro-optic effect. These results open new perspectives for the use of lithium niobate in chip-scale integrated optical devices and nonlinear optical microcavities.Comment: 15 pages, 8 figure

RNAi Screening in Drosophila Cells Identifies New Modifiers of Mutant Huntingtin Aggregation

The fruitfly Drosophila melanogaster is well established as a model system in the study of human neurodegenerative diseases. Utilizing RNAi, we have carried out a high-throughput screen for modifiers of aggregate formation in Drosophila larval CNS-derived cells expressing mutant human Huntingtin exon 1 fused to EGFP with an expanded polyglutamine repeat (62Q). 7200 genes, encompassing around 50% of the Drosophila genome, were screened, resulting in the identification of 404 candidates that either suppress or enhance aggregation. These candidates were subjected to secondary screening in normal length (18Q)-expressing cells and pruned to remove dsRNAs with greater than 10 off-target effects (OTEs). De novo RNAi probes were designed and synthesized for the remaining 68 candidates. Following a tertiary round of screening, 21 high confidence candidates were analyzed in vivo for their ability to modify mutant Huntingtin-induced eye degeneration and brain aggregation. We have established useful models for the study of human HD using the fly, and through our RNAi screen, we have identified new modifiers of mutant human Huntingtin aggregation and aggregate formation in the brain. Newly identified modifiers including genes related to nuclear transport, nucleotide processes, and signaling, may be involved in polyglutamine aggregate formation and Huntington disease cascades

Scalable Architecture for a Room Temperature Solid-State Quantum Information Processor

The realization of a scalable quantum information processor has emerged over the past decade as one of the central challenges at the interface of fundamental science and engineering. Much progress has been made towards this goal. Indeed, quantum operations have been demonstrated on several trapped ion qubits, and other solid-state systems are approaching similar levels of control. Extending these techniques to achieve fault-tolerant operations in larger systems with more qubits remains an extremely challenging goal, in part, due to the substantial technical complexity of current implementations. Here, we propose and analyze an architecture for a scalable, solid-state quantum information processor capable of operating at or near room temperature. The architecture is applicable to realistic conditions, which include disorder and relevant decoherence mechanisms, and includes a hierarchy of control at successive length scales. Our approach is based upon recent experimental advances involving Nitrogen-Vacancy color centers in diamond and will provide fundamental insights into the physics of non-equilibrium many-body quantum systems. Additionally, the proposed architecture may greatly alleviate the stringent constraints, currently limiting the realization of scalable quantum processors.Comment: 15 pages, 6 figure

Optimization of the Balanced Steady State Free Precession (bSSFP) Pulse Sequence for Magnetic Resonance Imaging of the Mouse Prostate at 3T

INTRODUCTION: MRI can be used to non-invasively monitor tumour growth and response to treatment in mouse models of prostate cancer, particularly for longitudinal studies of orthotopically-implanted models. We have optimized the balanced steady-state free precession (bSSFP) pulse sequence for mouse prostate imaging. METHODS: Phase cycling, excitations, flip angle and receiver bandwidth parameters were optimized for signal to noise ratio and contrast to noise ratio of the prostate. The optimized bSSFP sequence was compared to T1- and T2-weighted spin echo sequences. RESULTS: SNR and CNR increased with flip angle. As bandwidth increased, SNR, CNR and artifacts such as chemical shift decreased. The final optimized sequence was 4 PC, 2 NEX, FA 50°, BW ±62.5 kHz and took 14-26 minutes with 200 µm isotropic resolution. The SNR efficiency of the bSSFP images was higher than for T1WSE and T2WSE. CNR was highest for T1WSE, followed closely by bSSFP, with the T2WSE having the lowest CNR. With the bSSFP images the whole body and organs of interest including renal, iliac, inguinal and popliteal lymph nodes were visible. CONCLUSION: We were able to obtain fast, high-resolution, high CNR images of the healthy mouse prostate with an optimized bSSFP sequence

Genome-Wide Analysis of the Emerging Infection with Mycobacterium avium Subspecies paratuberculosis in the Arabian Camels (Camelus dromedarius)

Mycobacterium avium subspecies paratuberculosis (M. ap) is the causative agent of paratuberculosis or Johne's disease (JD) in herbivores with potential involvement in cases of Crohn's disease in humans. JD is spread worldwide and is economically important for both beef and dairy industries. Generally, pathogenic ovine strains (M. ap-S) are mainly found in sheep while bovine strains (M. ap-C) infect other ruminants (e.g. cattle, goat, deer), as well as sheep. In an effort to characterize this emerging infection in dromedary/Arabian camels, we successfully cultured M. ap from several samples collected from infected camels suffering from chronic, intermittent diarrhea suggestive of JD. Gene-based typing of isolates indicated that all isolates belong to sheep lineage of strains of M. ap (M. ap-S), suggesting a putative transmission from infected sheep herds. Screening sheep and goat herds associated with camels identified the circulation of this type in sheep but not goats. The current genome-wide analysis recognizes these camel isolates as a sub-lineage of the sheep strain with a significant number of single nucleotide polymorphisms (SNPs) between sheep and camel isolates (∼1000 SNPs). Such polymorphism could represent geographical differences among isolates or host adaptation of M. ap during camel infection. To our knowledge, this is the first attempt to examine the genomic basis of this emerging infection in camels with implications on the evolution of this important pathogen. The sequenced genomes of M. ap isolates from camels will further assist our efforts to understand JD pathogenesis and the dynamic of disease transmission across animal species

The host ubiquitin-dependent segregase VCP/p97 is required for the onset of human cytomegalovirus replication

The human cytomegalovirus major immediate early proteins IE1 and IE2 are critical drivers of virus replication and are considered pivotal in determining the balance between productive and latent infection. IE1 and IE2 are derived from the same primary transcript by alternative splicing and regulation of their expression likely involves a complex interplay between cellular and viral factors. Here we show that knockdown of the host ubiquitin-dependent segregase VCP/p97, results in loss of IE2 expression, subsequent suppression of early and late gene expression and, ultimately, failure in virus replication. RNAseq analysis showed increased levels of IE1 splicing, with a corresponding decrease in IE2 splicing following VCP knockdown. Global analysis of viral transcription showed the expression of a subset of viral genes is not reduced despite the loss of IE2 expression, including UL112/113. Furthermore, Immunofluorescence studies demonstrated that VCP strongly colocalised with the viral replication compartments in the nucleus. Finally, we show that NMS-873, a small molecule inhibitor of VCP, is a potent HCMV antiviral with potential as a novel host targeting therapeutic for HCMV infection