The effect of cadmium on plasma melanocyte-stimulating hormone and morphological changes of melanophores in the cichlid fish Oreochromis niloticus,at different salinity levels

ABSTRACT

The effects of cadmium concentration (0, 2.5 and 5 mg L^?1) on melanocyte-stimulating hormone (MSH), melanophore index (MI), and melanophore number (MN), as well as a microscopic examination of scale melanocytes in tilapia (Oreochromis niloticus Linnaeus, 1757) was evaluated at different salinity levels (0, 5 and 15 ppt). The levels of MSH, MI, and MN were lower in Cd-exposed fish than in control fish (not exposed to Cd) at salinity level of 0 and 5 ppt. In ppt, however these levels of MSH, MI and MN in control and Cd-exposed fish were not significantly different. In the media without Cd, the levels of MSH, MI and MN were not significantly different at all salinities. The morphological changes of melanophores were higher in Cd-exposed fish than in control fish at salinity 0 and 5 ppt, respectively. These morphological changes were not significantly different in the control fish at all salinities as well as in fish exposed to 0–5 mg L^?1 Cd at salinity of 15 ppt. This study therefore demonstrates that the toxic effect of Cd on MSH levels and melanophore morphology decreased with increasing salinity. Further, due to the sensitivity of chromatophores to Cd, melanophore morphology is proposed as a biomarker of Cd exposure in aquatic ecosystems.     

Time effect of rutaecarpine on caffeine pharmacokinetics in rats

Rutaecarpine is reported as a potent inducer of CYP1A2 enzyme in rats. There are natural herbal supplements containing rutaecarpine that are designed to enhance the CYP1A2-dependent removal of caffeine from blood so that people can have coffee later in the day without causing sleep interference. This study aimed to determine the minimum amount of time needed from oral rutaecarpine administration until the observed effect of rutaecarpine on caffeine pharmacokinetics (PK) in 15 male Sprague-Dawley rats. PK parameters for caffeine and its metabolites in the control and rutaecarpine groups were calculated using WinNonlin®. Results showed that orally administered rutaecarpine at 100 mg/kg dose as early as 3 h before oral caffeine administration significantly decreased the oral systemic exposure and mean residence time of caffeine and its metabolites due to decreased caffeine bioavailability (by up to 75%) and increased clearance. The systemic exposure of caffeine and its metabolites were also decreased when caffeine was given intravenously, though this effect was less pronounced than when caffeine was given orally. Although plasma level of rutaecarpine was undetectable (less than 10 ng/mL), rutaecarpine still induced hepatic CYP1A2 activity. Results from 7-methoxyresorufin O-demethylation activity, which is specific to CYP1A2, showed that 3 h after one rutaecarpine oral dose, CYP1A2 activity in rat liver tissue was increased by 3- fold. This finding suggested that rutaecarpine effectively induced CYP1A2 activity in the liver.     

UHPLC-Q-Orbitrap HR-MS-Based Metabolomics for Profiling the Sida rhombifolia Metabolites with Different Plant Organs and Cultivation Ages

Plant organs and cultivation ages can result in different compositions and concentration levels of plant metabolites. The metabolite profile of plants can be determined using liquid chromatography. This study determined the metabolite profiles of leaves, stems, and roots of Sida rhombifolia at different cultivation ages at 3, 4, and 5 months post-planting (MPP) using liquid chromatography-mass spectrometry/mass spectrometry (LC/MS/MS). The results identified that 41 metabolites in S. rhombifolia extract for all plant organs and cultivation ages. We successfully identified approximately 36 (leaves), 22 (stems), and 18 (roots) compounds in all extract. Using principal component analysis (PCA) with peak area as the variable, we clustered all sample extracts based on plant organs and cultivation ages. As a result of PCA, S. rhombifolia extracts were grouped according to plant organs and cultivation ages. In conclusion, a clear difference in the composition and concentration levels of metabolites was observed in the leaves, stems, and roots of S. rhombifolia harvested at 3-, 4-, and 5-MPP.     

A New Carvotacetone Derivative from the Aerial Part of Sphaeranthus africanus

Sphaeranthus africanus L. is native in Vietnam. Little is known about α-glucosidase inhibition of Sphaeranthus africanus and its isolated compounds. A bioactive-guided isolation was applied to the Vietnamese Sphaeranthus africanus to find α-glucosidase inhibitory components. Eight compounds were detected and structurally elucidated. They are 3-angeloyloxy-5-[2′′,3′′-epoxy-2′′-methylbutanoyloxy]-7-hydroxycarvotacetone, 3-angeloyloxy-5-[3′′-chloro-2′′-hydroxy-2′′-methylbutanoyloxy]-7-hydroxycarvotacetone, 3-angeloyloxy-5-[2′′R,3′′R-dihydroxy-2′′-methyl-butanoyloxy]-7-hydroxycarvotacetone, 3-angeloyloxy-5-[2′′S,3′′R-dihydroxy-2′′-methylbutanoyloxy]-7-hydroxycarvotacetone, 3-angeloyloxy-5-[2′′S,3′′S-dihydroxy-2′′-methylbutanoyloxy]-7-hydroxycarvotacetone, 5-angeloyloxy-7-hydroxy-3-tigloyloxycarvotacetone, 3-O-methylquercetin, and chrysosplenol D. Their chemical structures were elucidated by extensive 1D and 2D NMR analysis and high-resolution mass spectroscopy as well as comparisons in literature. 3-Angeloyloxy-5-[2′′S,3′′S-dihydroxy-2′′-methylbutanoyloxy]-7-hydroxycarvotacetone is a new compound. Isolated compounds were evaluated for the α-glucosidase inhibition. Isolated compounds showed moderate activity with IC₅₀ values ranging from 128.9–274.3 μM while others are weak. A molecular docking study was conducted, indicating that isolated compounds are potent α-glucosidase inhibitory compounds.     

Machine learning monitoring for laser osteotomy

This work proposes a new online monitoring method for an assistance during laser osteotomy. The method allows differentiating the type of ablated tissue and the applied dose of laser energy. The setup analyzes the laser-induced acoustic emission, detected by an airborne microphone sensor. The analysis of the acoustic signals is carried out using a machine learning algorithm that is pre-trained in a supervised manner. The efficiency of the method is experimentally evaluated with several types of tissues, which are: skin, fat, muscle, and bone. Several cutting-edge machine learning frameworks are tested for the comparison with the resulting classification accuracy in the range of 84–99%. It is shown that the datasets for the training of the machine learning algorithms are easy to collect in real-life conditions. In the future, this method could assist the doctors during laser osteotomy, minimizing the damage of the nearby healthy tissues and provide cleaner pathologic tissue removal.     

Nephronophthisis-Associated CEP164 Regulates Cell Cycle Progression,Apoptosis and Epithelial-to-Mesenchymal Transition

We recently reported that centrosomal protein 164 (CEP164) regulates both cilia and the DNA damage response in the autosomal recessive polycystic kidney disease nephronophthisis. Here we examine the functional role of CEP164 in nephronophthisis-related ciliopathies and concomitant fibrosis. Live cell imaging of RPE-FUCCI (fluorescent, ubiquitination-based cell cycle indicator) cells after siRNA knockdown of CEP164 revealed an overall quicker cell cycle than control cells, although early S-phase was significantly longer. Follow-up FACS experiments with renal IMCD3 cells confirm that Cep164 siRNA knockdown promotes cells to accumulate in S-phase. We demonstrate that this effect can be rescued by human wild-type CEP164, but not disease-associated mutants. siRNA of CEP164 revealed a proliferation defect over time, as measured by CyQuant assays. The discrepancy between accelerated cell cycle and inhibited overall proliferation could be explained by induction of apoptosis and epithelial-to-mesenchymal transition. Reduction of CEP164 levels induces apoptosis in immunofluorescence, FACS and RT-QPCR experiments. Furthermore, knockdown of Cep164 or overexpression of dominant negative mutant allele CEP164 Q525X induces epithelial-to-mesenchymal transition, and concomitant upregulation of genes associated with fibrosis. Zebrafish injected with cep164 morpholinos likewise manifest developmental abnormalities, impaired DNA damage signaling, apoptosis and a pro-fibrotic response in vivo. This study reveals a novel role for CEP164 in the pathogenesis of nephronophthisis, in which mutations cause ciliary defects coupled with DNA damage induced replicative stress, cell death, and epithelial-to-mesenchymal transition, and suggests that these events drive the characteristic fibrosis observed in nephronophthisis kidneys.     

Calcium-activated proteolysis of neurofilament proteins in goldfish Mauthner axons

We have examined the proteolytic breakdown of neurofilament proteins (NFPs) in isolated Mauthner axoplasm (M-axoplasm). Documentation of proteolytic breakdown of NFPs in M-axoplasm is important because NFPs are not degraded in distal segments of severed Mauthner axons (M-axons) maintained in vivo for up to 62 days at 20°C. By incubating M-axoplasm with 2 mM calcium in vitro, we have demonstrated that M-axoplasm contains an endogenous calcium-activated neutral protease that degrades NFPs. This calcium-activated proteolysis of M-axoplasm NFPs produced novel bands on silver-stained gels. These novel bands were presumed to be NFP breakdown products because they reacted with antibodies to the α-intermediate filament antigen (anti-IFA) on immunoblots from these gels. Incubations of M-axoplasm with 2 mM calcium plus exogenous calpain produced novel bands similar to those observed for M-axoplasm incubated with 2 mM calcium. Incubations of M-axoplasm with 2m M calcium plus calpain inhibitors did not produce these novel bands. These in vitro data indicate that M-axoplasm contains calpain that degrades NFPs and produces novel bands similar to those observed from distal segments of severed M-axons maintained in vivo longer than 62 days postseverance. Factors that affect the activity of calpain or affect the ability of calpain to degrade NFPs could account for the delayed degradation of NFPs in distal segments of severed M-axons maintained in vivo. © 1995 John Wiley & Sons, Inc.     

Reproductive features of the Russian vole in laboratory breeding.

Reproductive features of newly bred Russian voles (Microtus rossiaemeridionalis) as a laboratory animal were studied. This species is a copulatory ovulator, and most couples copulated 6 to 16 h after pairing. The gestation period varied from 18 to 22 days (mean +/- SD: 20.6 +/- 0.9, n = 72), and the average litter size was 4.6 +/- 1.9 (n = 125). Compared with the litter size at the first parturition (3.6 +/- 1.6, n = 72), the litter size in the subsequent parturitions increased to 5.9 +/- 1.4 (n = 53). The animals exhibited postpartum estrus, and repeated pregnancy accompanied with suckling pups and parturition continuously in the laboratory condition unlike other vole species. In view of their complex stomach and good proliferation, the Russian voles were evaluated as a good laboratory animal, especially as a model animal for ruminant studies.     

Molecular Phylogenetics and Chronometrics of Tarsiidae Based on 12S mtDNA Haplotypes: Evidence for Miocene Origins of Crown Tarsiers and Numerous Species within the Sulawesian Clade

We report new mitochondrial DNA sequence data from tarsiers sampled from several populations, including the extreme northeast and southwest of the range of the Tarsius tarsier species complex, the most extensive sampling ever reported for this taxon. Our results provide the opportunity to produce the first ever molecular chronometric analysis of Tarsiidae. These results date the age of crown tarsiers, minimally, to the middle Miocene, and each of the 3 tarsier species groups, Tarsius bancanus, T. syrichta, and the T. tarsier complex, to the early or middle Miocene. Thus, each of these 3 species has evolved in isolation for a period of time that is consistent with that which would be expected for multiple speciation events. Our analysis of the Tarsius tarsier complex reveals 5 subclades, each of which is interpreted to represent a haplogroup at, or above, the species level, a result that is consistent with current hypotheses about numerous cryptic species within this species complex. The implications for conservation within the Sulawesi biogeographic region are that Sulawesi is subdivided into numerous subregions of endemism and that, by extrapolating the example of cryptic tarsier species to other taxa, biodiversity may be underestimated by an order of magnitude. The practical realties of conservation in Sulawesi are such that it is most reasonable to assume that anthropogenic extinctions are occurring, and that some species will go extinct before they have even been identified.