Routine potency testing of Leptospira vaccines is mostly conducted using a vaccination–challenge test that involves large numbers of hamsters and unrelieved pain and distress. NICEATM, ICCVAM, and their international partners organized a workshop to review the state of the science of alternative methods that might replace, reduce, and refine the use of animals for veterinary Leptospira vaccine potency testing and to identify ways to advance improved alternative methods. Vaccine manufacturers were encouraged to initiate or continue product-specific validation using in vitro enzyme-linked immunosorbent assays as replacements for potency testing of four common Leptospira serogroups. Participants discussed the potential for eliminating the back-titration procedure in the hamster challenge assay, which could reduce animal use by 50% for each individual potency test. Further animal reduction may also be possible by using cryopreserved Leptospira stock to replace continual passaging through hamsters. Serology assays were identified as a way to further reduce and refine animal use but should be considered only after attempting in vitro assays. Workshop participants encouraged consideration of analgesics and use of earlier humane endpoints when the hamster vaccination–challenge potency assay is used. International harmonization of alternative potency methods was recommended to avoid duplicative potency testing to meet regionally different requirements. 相似文献
Complexes of 4-(((2-aminopyridin-3-yl)methylene)amino)benzoic acid ligand with cobalt(II) (1), nickel(II) (2), copper(II) (3), zinc(II) (4) and palladium(II) (5) are synthesized and characterized by using different spectroscopic methods like, UV–Visible, infrared, 1H, 13C NMR, molar conductance, ESR and elemental analysis. Quantum chemical computations were made using DFT (density functional theory), B3LYP functional and 6-31+?+G(d,p)/SDD basis set in order to determine optimized structure parameters, frontier molecular orbital parameters and NLO properties. Based on DFT and experimental evidence, the complexes ensured that the octahedral geometry have been proposed for complexes 1, 2 and 4, square planar for complexes 3 and 5. All the complexes showed only residual molar conductance values and hence they were considered as non-electrolytes in DMF. In addition, the anti-proliferative activity of the compounds was evaluated against different human cancer cell lines (IMR-32, MCF-7, COLO205, A549, HeLa and HEK 293) and cisplatin is used as a reference drug. Compounds 1 and 4 showed remarkable cytotoxicity in five cancer cell lines tested except MCF-7. Also, the compounds were examined for their in vitro antimicrobial and scavenging activities. The molecular docking results are well corroborated with the experimental anticancer activity results.
Osteoarthritis (OA) is a complex, multifactorial joint disease affecting both the cartilage and the subchondral bone. Animal
models of OA aid in the understanding of the pathogenesis of OA and testing suitable drugs for OA treatment. In this study
we characterized the temporal changes in the tibial subchondral bone architecture in a rat model of low-dose monosodium iodoacetate
(MIA)-induced OA using in vivo micro-computed tomography (CT). 相似文献
ADAMTS13 is a secreted zinc metalloprotease expressed by various cell types. Here, we investigate its cellular pathway in endogenously expressing liver cell lines and after transient transfection with ADAMTS13. Besides compartmentalizations of the cellular secretory system, we detected an appreciable level of endogenous ADAMTS13 within the nucleus. A positively charged amino acid cluster (R-Q-R-Q-R-Q-R-R) present in the ADAMTS13 propeptide may act as a nuclear localization signal (NLS). Fusing this NLS-containing region to eGFP greatly potentiated its nuclear localization. Bioinformatics analysis suggests that the ADAMTS13 CUB-2 domain has a double-stranded beta helix (DSBH) structural architecture characteristic of various protein-protein interaction modules like nucleoplasmins, class I collagenase, tumor necrosis factor ligand superfamily, supernatant protein factor (SPF) and the B1 domain of neuropilin-2. Based on this contextual evidence and that largely conserved polar residues could be mapped on to a template CUB domain homolog, we hypothesize that a region in the ADAMTS13 CUB-2 domain with conserved polar residues might be involved in protein-protein interaction within the nucleus. 相似文献
We have identified a novel component of the circadian clock that regulates its sensitivity to light at the evening light to dark transition. USP2 (Ubiquitin Specific Protease 2), which de-ubiquitinylates and stabilizes target proteins, is rhythmically expressed in multiple tissues including the SCN. We have developed a knockout model of USP2 and found that exposure to low irradiance light at ZT12 increases phase delays of USP2(-/-) mice compared to wildtype. We additionally show that USP2b is in a complex with several clock components and regulates the stability and turnover of BMAL1, which in turn alters the expression of several CLOCK/BMAL1 controlled genes. Rhythmic expression of USP2 in the SCN and other tissues offers a new level of control of the clock machinery through de-ubiqutinylation and suggests a role for USP2 during circadian adaptation to environmental day length changes. 相似文献
Abstract Daily variations in the colour temperature of the sun have been established as the Zeitgeber for arctic animals (Krüll, 1976, 1985). In the tropical regions too, there is a variation in the colour temperature from dawn to dusk. Experiments were performed to analyse whether cyclical 12 : 12h variations (Table 1) in the colour temperature assist the field mouse Mus booduga in programming the activity‐rest cycle or if the intensity of light plays a major role. Results suggest that the variations in the colour temperature used in the present experiment are not sufficient to entrain the system. Different colour temperatures given in light pulses did not evoke varying phase shifts indicating that the circadian system was not responding to the colour temperatures. The phase shifts tended to be of the same magnitude. It is speculated that it is the intensity of light that is more important for determining the day and night cycles of Mus booduga than the differences in colour temperature. 相似文献
BackgroundGuinea worm–Dracunculus medinensis–was historically one of the major parasites of humans and has been known since antiquity. Now, Guinea worm is on the brink of eradication, as efforts to interrupt transmission have reduced the annual burden of disease from millions of infections per year in the 1980s to only 54 human cases reported globally in 2019. Despite the enormous success of eradication efforts to date, one complication has arisen. Over the last few years, hundreds of dogs have been found infected with this previously apparently anthroponotic parasite, almost all in Chad. Moreover, the relative numbers of infections in humans and dogs suggests that dogs are currently the principal reservoir on infection and key to maintaining transmission in that country.Principal findingsIn an effort to shed light on this peculiar epidemiology of Guinea worm in Chad, we have sequenced and compared the genomes of worms from dog, human and other animal infections. Confirming previous work with other molecular markers, we show that all of these worms are D. medinensis, and that the same population of worms are causing both infections, can confirm the suspected transmission between host species and detect signs of a population bottleneck due to the eradication efforts. The diversity of worms in Chad appears to exclude the possibility that there were no, or very few, worms present in the country during a 10-year absence of reported cases.ConclusionsThis work reinforces the importance of adequate surveillance of both human and dog populations in the Guinea worm eradication campaign and suggests that control programs aiming to interrupt disease transmission should stay aware of the possible emergence of unusual epidemiology as pathogens approach elimination. 相似文献
Autism is a multi-factorial pathology observed in children with altered levels of essential and elevated levels of toxic elements.
There are also studies reporting a decrease in nutritional trace elements in the hair and nail of autistic children with healthy
controls; moreover, bioelements have been shown to play an important role in the central nervous system. Therefore, the purpose
of the present study was to assess the levels of trace elements like copper (Cu), zinc (Zn), magnesium (Mg), and selenium
(Se) and toxic elements like mercury (Hg), and lead (Pb) in the hair and nail samples of autistic children and to evaluate
whether the level of these elements could be correlated with the severity of autism. The subjects of the study were 45 autistic
children with different grades of severity (low (LFA), medium (MFA), and high (HFA) functioning autism) according to Childhood
Autism Rating Scale, n = 15 children in each group and 50 healthy children (age and sex matched). The boys and girls ratio involved in this study
was 4:1, and they were 4-12 years of age. The study observed a valid indication of Cu body burden in the autistic children.
The children with different grades of autism showed high significance (p < 0.001) in the level of copper in their hair and nail samples when compared to healthy controls. The level of Cu in the
autistic children could be correlated with their degree of severity (more the Cu burden severe is autism). The study showed
a significant elevation (p < 0.001) in the levels of toxic metals Pb and Hg in both hair and nail samples of autistic children when compared to healthy
control group. The elevation was much pronounced in LFA group subjects when compared among autistic groups MFA and HFA. The
levels of trace elements Mg and Se were significantly decreased (p < 0.001) in autistic children when compared to control. The trace element Zn showed significant variation in both hair and
nails of LFA group children when compared to control group and other study groups. The significant elevation in the concentration
of Cu, Pb, and Hg and significant decrease in the concentration of Mg and Se observed in the hair and nail samples of autistic
subjects could be well correlated with their degrees of severity. 相似文献