Aquatic plants as potential sources of antimicrobial compounds active against bovine mastitis pathogens

Resistance of pathogens to common veterinary antibiotics hampers mastitis treatment and motivates the discovery of new antimicrobials. In this study, extracts from two aquatic plants, Salvinia auriculata and Hydrocleys nymphoides, were assayed against bovine mastitis pathogens. Selected parts of plants were extracted with different solvents. The extracts showed activity only against the Gram-positive strains tested and the largest inhibition zones were seen for hexane extracts. The minimum inhibitory concentration values ranged from 0.2 to 1.0 mg/ml. Growth of Streptococcus agalactiae in the presence of different extracts with concentrations below MIC reduced the number of CFU/ml by more than 90%. Sub-MIC concentrations of the hexane extracts prepared from roots of S. auriculata inhibited approximately 50% of biofilm formation. Greater reduction was achieved for ethanol extract prepared from leaves of H. nymphoides. We concluded that these aquatic plants are potential sources for the investigation of new antimicrobial compounds.Key words: Staphylococcus aureus, Streptococcus agalactiae, aquatic plants, Salvinia auriculata, Hydrocleys nymphoides, antimicrobial activity

Leptogenesis and CPT Violation

We construct a model in which neutrinos and anti-neutrinos acquire the same mass but slightly different energy dispersion relations.Despite CPT violation, spin-statistics is preserved. We find that leptogenesis can be easily explained within this model, without upsetting the solar, atmospheric and reactor neutrino data. Leptogenesis occurs without lepton number violation and the non-equilibrium condition. We consider only three active Dirac neutrinos, and no new particles or symmetries are introduced.Comment: 5 pages, v3: version to appear in PLB with improved discussion

Gene Expression Signature-Based Screening Identifies New Broadly Effective Influenza A Antivirals

Classical antiviral therapies target viral proteins and are consequently subject to resistance. To counteract this limitation, alternative strategies have been developed that target cellular factors. We hypothesized that such an approach could also be useful to identify broad-spectrum antivirals. The influenza A virus was used as a model for its viral diversity and because of the need to develop therapies against unpredictable viruses as recently underlined by the H1N1 pandemic. We proposed to identify a gene-expression signature associated with infection by different influenza A virus subtypes which would allow the identification of potential antiviral drugs with a broad anti-influenza spectrum of activity. We analyzed the cellular gene expression response to infection with five different human and avian influenza A virus strains and identified 300 genes as differentially expressed between infected and non-infected samples. The most 20 dysregulated genes were used to screen the connectivity map, a database of drug-associated gene expression profiles. Candidate antivirals were then identified by their inverse correlation to the query signature. We hypothesized that such molecules would induce an unfavorable cellular environment for influenza virus replication. Eight potential antivirals including ribavirin were identified and their effects were tested in vitro on five influenza A strains. Six of the molecules inhibited influenza viral growth. The new pandemic H1N1 virus, which was not used to define the gene expression signature of infection, was inhibited by five out of the eight identified molecules, demonstrating that this strategy could contribute to identifying new broad anti-influenza agents acting on cellular gene expression. The identified infection signature genes, the expression of which are modified upon infection, could encode cellular proteins involved in the viral life cycle. This is the first study showing that gene expression-based screening can be used to identify antivirals. Such an approach could accelerate drug discovery and be extended to other pathogens

Novel genetic mutations in genes AGBL5 and TULP1 for presumed unilateral retinitis pigmentosa managed with low vision rehabilitation: A case report and review

Background: Retinitis pigmentosa is a group of hereditary retinal diseases characterized by the degeneration of rod and cone photoreceptors. It commonly results in night blindness followed by tunnel vision and central vision reduction. The classic triad of clinical signs includes pigmented bone spicules, waxy disc pallor, and arterial attenuation. Unilateral retinitis pigmentosa is rare and can be supported with ancillary testing including genetic and laboratory studies to rule out differential diagnoses. Case Report: A 68-year-old Hispanic female was referred to the low vision rehabilitation clinic due to progressive vision loss in the left eye (OS) that began 15 years ago. The vision was normal in the right eye (OD). Additionally, she suffered from hearing loss in the right ear since age 3. Examination revealed abnormal visual acuity, visual field, fundus appearance, optical coherence tomography, and electrodiagnostic test results in the OS only. Laboratory studies ruled out various infectious, autoimmune, traumatic, and toxic drug etiologies. Genetic testing revealed novel mutations in genes associated with retinitis pigmentosa. Conclusion: The genetic testing results along with the clinical examination and electrodiagnostic evaluation supports the diagnosis of unilateral retinitis pigmentosa

A detailed analysis of the HD 73526 2:1 resonant planetary system

We present six years of new radial velocity data from the Anglo-Australian and Magellan Telescopes on the HD 73526 2:1 resonant planetary system. We investigate both Keplerian and dynamical ( interacting) fits to these data, yielding four possible configurations for the system. The new data now show that both resonance angles are librating, with amplitudes of 40 degrees and 60 degrees, respectively. We then perform long-term dynamical stability tests to differentiate these solutions, which only differ significantly in the masses of the planets. We show that while there is no clearly preferred system inclination, the dynamical fit with i = 90 degrees provides the best combination of goodness-of-fit and long-term dynamical stability.Peer reviewe

Validation and optimization of AFP-based biomarker panels for early HCC detection in Latin America and Europe

Background: HCC is a major cause of cancer death worldwide. Serum biomarkers such as alpha-fetoprotein (AFP), protein induced by vitamin K absence-II, and the Gender, Age, AFP-L3, AFP, Des-gamma-carboxy prothrombin (GALAD) score have been recommended for HCC surveillance. However, inconsistent recommendations in international guidelines limit their clinical utility.Methods: In this multicenter study, over 2000 patient samples were collected in 6 Latin American and 2 European countries. The performance of the GALAD score was validated in cirrhotic cases, and optimized versions were tested for early-stage HCC and prediagnostic HCC detection.Results: The GALAD score could distinguish between HCC and cirrhosis in Latin American patients with an AUC of 0.76, sensitivity of 70%, and specificity of 83% at the conventional cutoff value of −0.63. In a European cohort, GALAD had an AUC of 0.69, sensitivity of 66%, and specificity of 72%. Optimizing the score in the 2 large multicenter cohorts revealed that AFP-L3 contributed minimally to early-stage HCC detection. Thus, we developed a modified GALAD score without AFP-L3, the ASAP (age, sex, AFP, and protein induced by vitamin K absence-II), which showed promise for early-stage HCC detection upon validation. The ASAP score also identified patients with cirrhosis at high risk for advanced-stage HCC up to 15 months before diagnosis (p < 0.0001) and differentiated HCC from hemangiomas, with a specificity of 100% at 71% sensitivity.Conclusion: Our comprehensive analysis of large sample cohorts validates the GALAD score’s utility in Latin American, Spanish, and Dutch patients for early-stage HCC detection. The optimized GALAD without AFP-L3, the ASAP score, is a good alternative and shows greater promise for HCC prediction

Growth differentiation factor-15 is associated with muscle mass in chronic obstructive pulmonary disease and promotes muscle wasting in vivo.

BACKGROUND: Loss of muscle mass is a co-morbidity common to a range of chronic diseases including chronic obstructive pulmonary disease (COPD). Several systemic features of COPD including increased inflammatory signalling, oxidative stress, and hypoxia are known to increase the expression of growth differentiation factor-15 (GDF-15), a protein associated with muscle wasting in other diseases. We therefore hypothesized that GDF-15 may contribute to muscle wasting in COPD. METHODS: We determined the expression of GDF-15 in the serum and muscle of patients with COPD and analysed the association of GDF-15 expression with muscle mass and exercise performance. To determine whether GDF-15 had a direct effect on muscle, we also determined the effect of increased GDF-15 expression on the tibialis anterior of mice by electroporation. RESULTS: Growth differentiation factor-15 was increased in the circulation and muscle of COPD patients compared with controls. Circulating GDF-15 was inversely correlated with rectus femoris cross-sectional area (P < 0.001) and exercise capacity (P < 0.001) in two separate cohorts of patients but was not associated with body mass index. GDF-15 levels were associated with 8-oxo-dG in the circulation of patients consistent with a role for oxidative stress in the production of this protein. Local over-expression of GDF-15 in mice caused wasting of the tibialis anterior muscle that expressed it but not in the contralateral muscle suggesting a direct effect of GDF-15 on muscle mass (P < 0.001). CONCLUSIONS: Together, the data suggest that GDF-15 contributes to the loss of muscle mass in COPD

Rheumatoid arthritis and pregnancy: evolution of disease activity and pathophysiological considerations for drug use

It has long been known that pregnancy and childbirth have a profound effect on the disease activity of rheumatic diseases. For clinicians, the management of patients with RA wishing to become pregnant involves the challenge of keeping disease activity under control and adequately adapting drug therapy during pregnancy and post-partum. This article aims to summarize the current evidence on the evolution of RA disease activity during and after pregnancy and the use of anti-rheumatic drugs around this period. Of recent interest is the potential use of anti-TNF compounds in the preconception period and during pregnancy. Accumulating experience with anti-TNF therapy in other immune-mediated inflammatory diseases, such as Crohn’s disease, provides useful insights for the use of TNF blockade in pregnant women with RA, or RA patients wishing to become pregnant