Aberrant lysosomal carbohydrate storage accompanies endocytic defects and neurodegeneration in Drosophila benchwarmer

Lysosomal storage is the most common cause of neurodegenerative brain disease in preadulthood. However, the underlying cellular mechanisms that lead to neuronal dysfunction are unknown. Here, we report that loss of Drosophila benchwarmer (bnch), a predicted lysosomal sugar carrier, leads to carbohydrate storage in yolk spheres during oogenesis and results in widespread accumulation of enlarged lysosomal and late endosomal inclusions. At the bnch larval neuromuscular junction, we observe similar inclusions and find defects in synaptic vesicle recycling at the level of endocytosis. In addition, loss of bnch slows endosome-to-lysosome trafficking in larval garland cells. In adult bnch flies, we observe age-dependent synaptic dysfunction and neuronal degeneration. Finally, we find that loss of bnch strongly enhances tau neurotoxicity in a dose-dependent manner. We hypothesize that, in bnch, defective lysosomal carbohydrate efflux leads to endocytic defects with functional consequences in synaptic strength, neuronal viability, and tau neurotoxicity

Comparative studies on the toxicological, antiinflammatory and analgesic properties of three sources of Xuedan in mice and their rapid identification by electronic tongue

Purpose: To compare the toxicological, anti-inflammatory and analgesic properties of three sources of Xuedan, viz, Hemsleya omeiensis (HO), Hemsleya giganth (HG) and Hemsleya dolichocarpa (HD) in mice, and to study their rapid identification based on electronic tongue (E-tongue).Methods: After 7 days of administration, the median lethal doses (LD50) of the three xuedan decoctions in mice were determined. In addition, the anti-inflammatory and analgesic effects of the three xuedans were evaluated in mice using xylene-induced ear edema and acetic acid-induced pain. Furthermore, Etongue technology was used to identify HO, HG and HD. Principal component analysis (PCA) and discriminant factor analysis (DFA) were used to analyze the data acquired by E-tongue.Results: The median lethal dose (LD50) values of H. omeiensis, H. gigantha and H. dolichocarpa were 32.3, 17.4 and 13.7g/kg, respectively. Compared with normal control group, the anti-inflammatory effects of Xuedan were obvious in xylene-induced ear edema (p < 0.05), and pain sensation was significantly inhibited in acetic acid-induced writhing test (p < 0.05). Furthermore, E-tongue technology effectively identified HO, HG and HD.Conclusion: H. omeiensis exhibits the highest LD50 value and best analgesic effect among the three sources of xuedan. E-tongue technology is effective and rapid in identifying HO, HG and HD.Keywords: Xuedan, Hemsleya omeiensis, Hemsleya gigantha, Hemsleya dolichocarpa, Antiinflammation, Analgesia, Electronic tongu

Effect of solvent fractions of crude extract of Liushenqu on gastrointestinal motility in guinea pigs, and the underlying mechanism(s)

Purpose: To study the effect of solvent fractions of the crude extract of liushenqu on gastrointestinal motility in guinea pigs, and the mechanism of action. Methods: The effects of solvent fractions of crude extract of liushenqu (LSQ) on receptors in guinea pig isolated small intestinal cells were determined by treatment with different receptor blockers, including diphenhydramine (0.067 mg/mL), atropine sulfate (0.064 mg/mL), propranolol hydrochloride (0.033mg/mL), phentolamine mesylate (0.04mg/mL) and ondansetron hydrochloride (0.048mg/mL), to investigate the possible pharmacological mechanism of action. Results: There was no significant change in the maximum amplitude of muscle tension before and after administration in the control group, petroleum ether fraction group, and dichlormethane fraction group, while muscle tension in the 95 % ethanol and n-butanol fractions significantly increased (p < 0.01). The mean changes in tension were significantly different from that of control group (p < 0.01), but ethyl acetate fraction showed significant intestinal muscle inhibition (p < 0.01). Addition of LSQ did not alleviate the inhibition caused by diphenhydramine, but it significantly reversed the inhibition caused by blockers of cholinergic muscarinic receptor, adrenergic alpha- and beta- receptors, and 5-HT receptor (p < 0.01). Conclusion: These results indicate that n-butanol fraction is the most effective bioactive fraction of LSQ, while ethyl acetate fraction has the opposite effect. In addition, its mechanism of action is related to increase in the amplitude of small intestine smooth muscle contraction and acceleration of small intestine peristalsis

THE EFFECT OF ASTRAGALUS EXTRACTIVE ON ALVEOLAR BONE REBUILDING PROGRESS OF TOOTH EXTRACTED SOCKET OF OVARIECTOMIED RATS

Background: Postmenopausal osteoporosis (PMO) is an estrogen deficiency condition that causes severe loss of bone mass in the vertebrae and long bones. We explored the effect and the possible underlying mechanism of the extracts of Astragalus (AE) on the tooth alveolar bone rebuilding progress of postmenopausal osteoporosis of PMO animal models. Material and methods: The PMO models were acquired by ovariectomy. After 8 weeks the first left maxillary molars of the rats were extracted and AE was administered orally for 8 weeks. Then the histological morphology and the transcription and expression of TGF-β1 and TNF-α in the tooth extracted socket were detected by HE dying, QRT-PCR and ELISA. Results: The results showed that the new bone volume and TGF-β1 was significantly lower in PMO group than the control group and AE group at the observing period. At the same time TNF-α in PMO group was significantly higher than the other two groups. Moreover AE group had no significant differences with the control group in all data at the observing period. Conclusion: AE has positive effect on alveolar bone rebuilding progress of tooth extracted socket of PMO rats. AE also has the potential to enhance the expression of TGF-β1and decrease the expression of TNF-α of the rebuilding tooth extracted socket

Weighted Species Sensitivity Distribution Method to Derive Site-specific Quality Criteria for

Abstract Tai Lake (Ch: Taihu), which is the largest lake in Jiangsu province, China, has been affected by human activities. As part of a concerted effort to improve water quality to protect the integrity of the Tai Lake ecosystem, a water quality criterion (WQC) was developed for copper (Cu) II. The acute WQC was based on 440 values for acute toxicity of Cu to 24 species from 6 phyla, 16 families, and 20 genera. In addition, 255 values for chronic toxicity of Cu to 10 species from 5 phyla, 8 families, and 9 genera were used to derive chronic WQC. Instead of using a traditional approach based species sensitivity distributions (SSD), a weighted species sensitivity distribution (WSSD) approach was used to calculate the cumulative probability based on endemic species to Tai Lake. Acute and chronic WQC developed by use of the WSSD were 5.3 and 3.7 μg Cu/L, respectively. While the WQC values were comparable to those of other countries, there were slight differences due to variability in species composition of different regions. The site-specific criteria indicated that the current standard set for surface water by the Chinese government might not be protective of aquatic organisms in Tai Lake

Eps15 and Dap160 control synaptic vesicle membrane retrieval and synapse development

Epidermal growth factor receptor pathway substrate clone 15 (Eps15) is a protein implicated in endocytosis, endosomal protein sorting, and cytoskeletal organization. Its role is, however, still unclear, because of reasons including limitations of dominant-negative experiments and apparent redundancy with other endocytic proteins. We generated Drosophila eps15-null mutants and show that Eps15 is required for proper synaptic bouton development and normal levels of synaptic vesicle (SV) endocytosis. Consistent with a role in SV endocytosis, Eps15 moves from the center of synaptic boutons to the periphery in response to synaptic activity. The endocytic protein, Dap160/intersectin, is a major binding partner of Eps15, and eps15 mutants phenotypically resemble dap160 mutants. Analyses of eps15 dap160 double mutants suggest that Eps15 functions in concert with Dap160 during SV endocytosis. Based on these data, we hypothesize that Eps15 and Dap160 promote the efficiency of endocytosis from the plasma membrane by maintaining high concentrations of multiple endocytic proteins, including dynamin, at synapses

Clinical Syndromes and Genetic Screening Strategies of Pheochromocytoma and Paraganglioma

Pheochromocytomas (PCCs) are rare neuroendocrine tumors that originate from chromaffin cells of the adrenal medulla, and paragangliomas (PGLs) are extra-adrenal pheochromocytomas. These can be mainly found in clinical syndromes including multiple endocrine neoplasia (MEN), von Hippel–Lindau (VHL) syndrome, neurofibromatosis-1 (NF-1) and familial paraganglioma (FPGL). PCCs and PGLs are thought to have the highest degree of heritability among human tumors, and it has been estimated that 60% of the patients have genetic abnormalities. This review provides an overview of the clinical syndrome and the genetic screening strategies of PCCs and PGLs. Comprehensive screening principles and strategies, along with specific screening based on clinical symptoms, biochemical tests and immunohistochemistry, are discussed

Characterization of Fungal nirK-Containing Communities and N2O Emission From Fungal Denitrification in Arable Soils

Fungal denitrifiers play important roles in soil nitrogen cycling, but we have very limited knowledge about their distribution and functions in ecosystems. In this study, three types of arable soils were collected across different climate zones in China, including quaternary red clay soils, alluvial soils, and black soils. The composition and abundance of fungal nirK-containing denitrifiers was determined by MiSeq high-throughput sequencing and qPCR, respectively. Furthermore, a substrate-induced inhibition approach was used to explore N2O emissions from fungal denitrification. The results showed that the arable soils contained a wide range of nirK-containing fungal denitrifiers, with four orders and eight genera. Additionally, approximately 57.30% of operational taxonomic unit (OTUs) belonged to unclassified nirK-containing fungi. Hypocreales was the most predominant order, with approximately 40.51% of the total number of OTUs, followed by Sordariales, Eurotiales, and Mucorales. It was further indicated that 53% of fungal nirK OTUs were shared by the three types of soils (common), and this group of fungi comprised about 98% of the total relative abundance of the nirK-containing population, indicating that the distribution of fungal nirK-containing denitrifiers was quite homogenous among the soil types. These common OTUs were determined by multiple soil characteristics, while the composition of unique OTUs was manipulated by the specific properties of each soil type. Furthermore, fungal N2O emissions were significantly and positively correlated with fungal nirK abundance in the soils, whereas it was not clearly related to fungal nirK compositions. In conclusion, although the arable soils hosted diverse nirK-containing fungal denitrifiers, fungal nirK compositions were highly homogenous among the soil types, which could be a consequence of enduring agricultural practices. The abundance of fungal nirK-containing denitrifiers, rather than their composition, may play more significant roles in relation to N2O emission from fungal denitrification

A Journey into the City. Migrant Workers' Relation with the Urban Space and Struggle for Existence in Xu Zechen's Early Jingpiao Fiction

In contemporary China, rural-urban migrants constitute a new urban subject with entirely new identity-related issues. This study aims at demonstrating how literature can be a valid field in investigating such evolving subjectivities, through an analysis of Xu Zechen’s early novellas depicting migrants’ vicissitudes in Beijing. Combining a close reading of the texts and a review of the main social problems characterising rural-urban migration in China, this paper focuses on the representation of the identity crisis within the migrant self in Xu’s stories, taking into account the network of meanings employed by the writer to signify the objective and subjective tension between the city and the countryside

Comment on “Topically Applied Connective Tissue Growth Factor/CCN2 Improves Diabetic Preclinical Cutaneous Wound Healing: Potential Role for CTGF in Human Diabetic Foot Ulcer Healing”

A recent paper in this journal, presented a novel method by topical application of growth factors in stimulating diabetic cutaneous wound healing that caught our attention. We believe that the experimental method in the article is efficient and creative, but it also has some controversies and shortcomings to be discussed. We noted that the authors used “Tegaderm” as a semiocclusive dressing film and stated that it exerted a “splinting effect” on the wound margins and controlled contraction. Indeed, the “Tegaderm” itself can serve as a dressing film to isolate the wound bed with outside environments while the “splinting effect” is mainly achieved by adding silicone splints around the wound. Considering the unique properties of silicone splints and “Tegaderm,” our experimental group propose an alternative method named “combined-suturing” technique that is not only suturing the silicone splints but also securing the “Tegaderm” around the wound. The specific reasons and operative procedures are explained in detail in this letter