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Background Respiratory viruses (RVs) are among the most common pathogens for both upper and lower respiratory tract infections (RTIs). However, the viral epidemiology of RV-associated RTIs in adults has long been under-recognized. Through a sensitive molecular assay, it would be possible to have a better understanding of the epidemiology of RV-associated RTIs. Material and methods Respiratory tract (RT) specimens from adults hospitalized due to RTIs were tested for RVs, using the multiplex PCR-based Luminex xTAG® Respiratory Viral Panel assay. A total of nineteen RVs, including influenza viruses and non-influenza respiratory viruses (NIRVs) were detected. Positive rates were compared using a chi-square test. Results A total of 2292 samples from adult patients hospitalized with RTIs were screened for RVs. The overall positive rate was 22%, with 17.8% samples positive for at least one NIRV. NIRVs had a higher positive rate in non-winter seasons. As many as 12.7% (46/363) of the samples collected through broncho-alveolar lavage and 20.5% (176/859) of the samples collected in ICUs were positive for RVs. Distribution of corona virus (CoV), human metapneumovirus (hMPV) and parainfluenza virus (PIV) demonstrated seasonal variation. Also, temperature was associated with the positive rates of specific viruses, including CoV, respiratory syncytial virus (RSV), hMPV and PIV. Conclusion Respiratory viruses, notably NIRVs, were frequently detected in adults hospitalized with RTIs. Several RVs were detected with distinctive seasonal variations. A substantial number of RVs were identified in lower RT specimens or from patients admitted to ICU, highlighting their important role in causing severe respiratory infection.

Background/aim The benefit of direct-acting antiviral therapy (DAA) in chronic hepatitis C (CHC) infected patients who received curative treatment for early-stage hepatocellular carcinoma (HCC) is well known, but is unclear for intermediate stage HCC. Patients and methods CHC patients with Barcelona Clinic Liver Cancer (BCLC) stage B HCC receiving chemoembolization were identified. Univariate, multivariate analyses, and Kaplan-Meier curve were used to identify factors associated with survival outcomes. Results Among 113 included patients, the median survival of DAA treated group (n=14) and non-treated group (n=99) were 40.1 months and 22.9 months, respectively. Multivariate analysis showed that Eastern Cooperative Oncology Group (ECOG) score, DAA, and serum albumin were key independent factors associated with overall survival. Moreover, the time-to-complete remission (TTCR) was improved in the DAA treated group. Conclusion ECOG, DAA, and serum albumin were prognostic factors for CHC/intermediate-stage HCC patients. DAA was also a beneficial factor for TTCR.

Strain XY-J91T, a Gram-stain-negative, reddish orange, non-spore-forming and short-rod-shaped marine bacterium, was isolated from rhizosphere soil of the mangrove plant Kandelia candel (L.) Druce in Mai Po Nature Reserve, Hong Kong. The strain showed growth at 15–50 °C (optimum 40 °C), at pH 5.5–9.5 (optimum 7.0–8.0) and with 0–8 % (w/v) NaCl (optimum 1–2 %). The only respiratory quinone was MK-7 and the major fatty acids were iso-C15 : 0 and iso-C17 : 0 3-OH. The major polar lipids were phosphatidylethanolamine, an unidentified aminolipid and an unidentified phospholipid. The G+C content of strain XY-J91T was 40.4 mol%. Strain XY-J91T exhibited highest 16S rRNA gene sequence similarities to the type strains of Algoriphagus marincola SW-2T (96.66 %), Algoriphagus taiwanensis CC-PR-82T (96.21%), Algoriphagus ornithinivorans JC2052T (96.16%), Algoriphagus confluentis HJM-2T (95.73%) and Algoriphagus zhangzhouensis 12C11T (95.52 %). Based on the phylogenetic, phenotypic and chemotaxonomic evidence presented, strain XY-J91T represents a novel species of the genus Algoriphagus , for which the name Algoriphagus kandeliae sp. nov. is proposed. The type strain is XY-J91T (=MCCC 1K03612T=KCTC 72216T).

Mifepristone (RU-486), a synthetic steroid with potent antiprogestogen and anti-glucocorticoid properties, has been widely used in clinical practice. Its effect on the endometrium, ovary, and fallopian tube has been well reported in many human and animal studies. However, its direct impact on post-implantation embryos remains underexplored. Additionally, some women choose to keep their pregnancy after mifepristone treatment fails. Thus, the potential risk remains controversial. Hence, this study investigated the direct effects of mifepristone on the development of mice blastocysts in vitro in terms of implantation and post-implantation. We detected the level of progesterone (P4) associated with ovulation in vivo. The presence of progesterone receptors (PRs) in blastocysts and post-implantation embryos was also evaluated. Cultured embryos were treated directly with mifepristone. We further examined embryonic implantation and post-implantation of blastocysts in vitro to evaluate the direct effects of mifepristone on embryos by the assessment of embryonic outgrowth and differential cell staining. In the oviduct lumen, the P4 level dramatically increased at 48 h and slightly decreased at 72 and 96 h following ovulation. PR was expressed in blastocysts not only in the preimplantation stage but also in the early post-implantation period. In the evaluation of developmental stages, mifepristone significantly reduced the successful ratio of developing into the late egg cylinder and the early somite stage. In addition, it further decreased the cell number of the embryos’ inner cell mass and trophectoderm. We herein provide evidence that mifepristone affects blastocyst viability directly and inhibits post-implantation embryo development in vitro. Furthermore, our data reveal a potential risk of fetus fatality and developmental problems when pregnancies are continued after mifepristone treatment fails.

An orchestrated wound healing program drives skin repair via collective epidermal cell proliferation and migration. However, the molecular determinants of the tissue microenvironment supporting wound healing remain poorly understood. Herein we discover that proteoglycan Agrin is enriched within the early wound-microenvironment and is indispensable for efficient healing. Agrin enhances the mechanoperception of keratinocytes by augmenting their stiffness, traction stress and fluidic velocity fields in retaliation to bulk substrate rigidity. Importantly, Agrin overhauls cytoskeletal architecture via enhancing actomyosin cables upon sensing geometric stress and force following an injury. Moreover, we identify Matrix Metalloproteinase-12 (MMP12) as a downstream effector of Agrin’s mechanoperception. We also reveal a promising potential of a recombinant Agrin fragment as a bio-additive material that assimilates optimal mechanobiological and pro-angiogenic parameters by engaging MMP12 in accelerated wound healing. Together, we propose that Agrin-MMP12 pathway integrates a broad range of mechanical stimuli to coordinate a competent skin wound healing niche., Replenishing key extracellular matrix (ECM) proteins facilitate wound healing through unclear mechanisms. Here the authors report that injury-triggered Agrin, an ECM proteoglycan, tunes a mechanocompetent niche by engaging MMP-12, thereby enforcing efficient skin wound healing.

ELKS1 controls mast cell degranulation by regulating the transcription of Stxbp2 and Syntaxin 4 via Kdm2b stabilization., ELKS1 is a protein with proposed roles in regulated exocytosis in neurons and nuclear factor κB (NF-κB) signaling in cancer cells. However, how these two potential roles come together under physiological settings remain unknown. Since both regulated exocytosis and NF-κB signaling are determinants of mast cell (MC) functions, we generated mice lacking ELKS1 in connective tissue MCs (Elks1f/f Mcpt5-Cre) and found that while ELKS1 is dispensable for NF-κB–mediated cytokine production, it is essential for MC degranulation both in vivo and in vitro. Impaired degranulation was caused by reduced transcription of Syntaxin 4 (STX4) and Syntaxin binding protein 2 (Stxpb2), resulting from a lack of ELKS1-mediated stabilization of lysine-specific demethylase 2B (Kdm2b), which is an essential regulator of STX4 and Stxbp2 transcription. These results suggest a transcriptional role for active-zone proteins like ELKS1 and suggest that they may regulate exocytosis through a novel mechanism involving transcription of key exocytosis proteins.

In the present study, anti-inflammatory activity of the methanol extracts of soymilk and soymilk fermented with Streptococcus salivarius subsp. thermophilus CCRC 14805 alone or in conjunction with Bificobacterium infantis CCRC 14603 was evaluated. It was found that extracts of soymilk and the prepared fermented soymilk dose-dependently suppress nitric oxide (NO) production of lipopolysaccharide (LPS)-induced macrophages, with soymilk showing the highest inhibition ability followed by S. thermophilus-fermented soymilk. Extracts of soymilk and fermented soymilk did not affect the activity of inducible nitric oxide synthase (iNOS). The extracts of the fermented soymilk inhibited the protein expression of iNOS in LPS-induced macrophages, but soymilk did not. Moreover, these extracts did not show obvious inhibition on cyclooxygenase-2 (COX-2) protein expression, while all showed the inhibitory effect on LPS-induced pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β and prostaglandin E2 (PGE2) produced by RAW 264.7 macrophages.

In this study, Bacillus cereus was subjected to acid adaptation at pH 6.3 for 40 min. It was found that acid-adapted B. cereus exhibited a higher survival percentage than non-adapted cells after exposure to an acidic condition of pH 4.6. The viable population of both acid-adapted and non-adapted B. cereus increased during the first 12-18 hr of lactic fermentation of skim milk by Streptococcus thermophilus or Lactobacillus bulgaricus, and then declined as the fermentation extended. However, the acid-adapted cells exhibited a lower population reduction rate than the non-adapted B. cereus. A higher viable population of acid-adapted B. cereus than the non-adapted cells was also noted in Str. thermophilus-fermented skim milk and the two commercial lactic fermented products kept at 5℃. Additionally, the acid adaptation could reduce the susceptibility of B. cereus to acidity, refrigerated temperature and other detrimental principles present in lactic fermented milk products.

In the present study, the ethanol extract of propolis (EEP) collected in Taiwan was prepared and assayed for the effects concentration, incubation temperature, pH and cell age on the antimicrobial activity against Streptococcus mutans, a dental cavitycausing oral pathogen. Additionally, cell leakage of Str. mutans in presence of EEP was also examined. It was found EEP exerted bacteriostatic and bactericidal effects against Str. mutans, respectively, at concentrations of 1.875 and 3.75 µg/mL or more. At 37°C, Str. mutans was more sensitive to EEP than at 25°C while most resistant at 4°C. Cells of test organism were most susceptible to EEP at acid pH followed by neutral and alkaline pH. It was also noted that cells of Str. mutans in the stationary phase were more resistant, while cells in the mid-exponential phase were more susceptible to EEP. After exposure to EEP, a marked increase in the 260 nm absorbance for the supernatant of culture, was observed, indicating the release of UV-absorbing materials. Scanning electron micrographs also showed an increase in material with irregular shape on the surface of EEP-treated Str. mutans cells.

TAR DNA‐binding protein 43 (TDP‐43) has been implicated in frontotemporal lobar degeneration with ubiquitin‐positive inclusions (FTLD‐TDP) and amyotrophic lateral sclerosis. Histone deacetylase 1 (HDAC1) is involved in DNA repair and neuroprotection in numerous neurodegenerative diseases. However, the pathological mechanisms of FTLD‐TDP underlying TDP‐43 proteinopathies are unclear, and the role of HDAC1 is also poorly understood. Here, we found that aberrant cell cycle activity and DNA damage are important pathogenic factors in FTLD‐TDP transgenic (Tg) mice, and we further identified these pathological features in the frontal cortices of patients with FTLD‐TDP. TDP‐43 proteinopathies contributed to pathogenesis by inducing cytosolic mislocalization of HDAC1 and reducing its activity. Pharmacological recovery of HDAC1 activity in FTLD‐TDP Tg mice ameliorated their cognitive and motor impairments, normalized their aberrant cell cycle activity, and attenuated their DNA damage and neuronal loss. Thus, HDAC1 deregulation is involved in the pathogenesis of TDP‐43 proteinopathies, and HDAC1 is a potential target for therapeutic interventions in FTLD‐TDP., TDP‐43 proteinopathies cause pathogenesis through inducing cytosolic mislocalization of HDAC1. Pharmacological recovery of HDAC1 activity in FTLD‐TDP transgenic (Tg) mice improves cognitive and motor functions, also attenuates aberrant cell cycle activity, DNA damage and neuronal death.

Small heat shock proteins (shsps) are conserved across invertebrate species. They are implicated in the modulation of various biological processes, such as immune responses, abiotic stress tolerance metamorphosis, and embryonic development. Herein, we identified a heat shock protein 20 from the red swamp crayfish, Procambarus clarkii (named as Pc-Hsp20), and performed in vivo studies to elucidate its physiological functions in the innate immunity. The open reading frame of Pc-Hsp20 was 609 base pair, encoding a protein of 202 amino acid residues with a hsp20/alpha crystallin family domain. Pc-Hsp20 was ubiquitously expressed in various tissues; however, it was highest in the hepatopancreas. The challenge with immune elicitors remarkably enhanced the transcript level of Pc-Hsp20 in the hepatopancreas when compared with the control. Administration of double-stranded RNA could significantly reduce expression of the Pc-Hsp20 mRNAs, and most of the immune-related genes expression enhanced with a variable concentration in the hepatopancreas. Altogether, these results suggest that Pc-Hsp20 may participate in innate immunity against microbial pathogens.

Starting from the May to August 2020 (average humidity 76.6% and temperature 25.2°C in Taipei), Boston ivy (Parthenocissus tricuspidata) plants on the campus of National Taiwan University (25°01'05.4"N 121°32'36.6"E) exhibited leaf rusts caused by Phakopsora ampelopsidis (Tzean et al., 2019) and leaf spots caused by an unknown pathogen. The leaf spots appeared reddish to brown color and mostly irregular to round shape on the simple and trifoliate leaflets (Supplemental Figure 1A-C). The leaf spots were surface-disinfected with 1% NaOCl for 30 seconds, and the margin of healthy and infected tissues was cut and placed onto water agar, which were incubated at room temperature. Hyphae grown out from leaf spots were sub-cultured on potato dextrose agar (PDA), and the majority of isolates exhibited white colony with black pycnidial conidiomata embedded in PDA. The pycnidial conidiomata of two-week-old has an average diameter of 463±193 μm (n=30) and the sizes of α-conidia were 5.71±0.49 μm in length and 2.42±0.32 μm in width (n=50) similar to the previous records (Crous et al. 2015). The α-conidium was one-celled, hyaline, and ovoid with two droplets (Supplemental Figure 1D-G). This putative pathogen was re-inoculated to confirm its pathogenicity on the leaves of Boston ivy plants. A PDA block with actively growing fungal edge was placed on the tiny needle-wounded leaves of detached branches (Supplemental Figure H-I) and the whole plants in pots (Supplemental Figure 1J-M) in a moist chamber at 28°C in dark. Reddish to brown leaf spots were observed by 2 days post-inoculation (dpi) and the leaf spots expanded by 5 dpi. To complete the Koch's postulates, the pathogen was re-isolated from inoculated leaves and the re-isolated pathogen exhibited identical morphology to the original isolate. The internal transcribed spacer (ITS), translational elongation factor subunit 1-α gene (EF1α), β-tubulin (BT), and calmodulin (CAL) was amplified using the primers ITS1/ITS4 (Martin and Rygiewicz. 2005), EF1-728F/EF1-986R, Bt2a/Bt2b, and CAL-228F/CAL-737R, respectively (Manawasinghe et al. 2019). Using BLAST in the NCBI database, the ITS (MT974186), EF1α (MT982963), and β-tubulin (MT982962) sequences showed 98.57% (NR_147574.1, 553 out of 561 bp), 98.04% (KR936133.1, 350 out of 357 bp), and 99.23% (KR936132.1, 518 out of 522 bp) identity to the Diaporthe tulliensis ex-type BRIP 62248a, respectively (Dissanayake et al. 2017). Phylogenetic analysis using concatenated sequences of ITS, EF1α, and β-tubulin grouped the D. tulliensis isolated from Boston ivy leaf spots with the D. tulliensis ex-type (Supplemental Figure 1N). In summary, the morphological and molecular characterizations supported the causal pathogen of Boston ivy leaf spot as D. tulliensis. While Diaporthe ampelopsidis was reported to infect Parthenocissus quinquefolia and P. tricuspidata (Anonymous, 1960; Wehmeyer, 1933), there is no record for D. tulliensis infecting Boston ivy according to the USDA National Fungus Collections (Farr and Rossman. 2020). Because pathogens of Boston ivy such as P. ampelopsidis may also infect close-related crops like grape (Vitis vinifera L.) and D. tulliensis has been known to infect kiwifruits (Actinidia chinensis) and cocoa (Theobroma cacao) (Bai et al. 2016; Yang et al. 2018), the emergence of D. tulliensis should be aware to avoid potential damage to economic crops.

In this study, Mg–Al layered double hydride (LDH) was prepared and the impact of LDH addition on the biomass and surfactin yield for cultures of Bacillus subtilis CWS1 was examined. Various solid additives, including montmorillonite (MMT), activated carbon (AC) and LDH, were tested. Among these, LDH triggered the highest surfactin yield at 3789 mg/L. The optimal conditions for surfactin production were 2 g/L LDH supplied on the beginning of a 5-day cultivation, resulting in a 3.8-fold increase in yield. To reveal the mechanism of surfactin enhancement, observation was conducted via the optical microscope. The resulted images showed that when LDH was added, the cells became segmented, short and narrow compared to cells without any addition. It is apparent that LDH exhibits a slightly toxic effect, limiting cell growth. The surviving cells were forced to secrete more surfactin to protect themselves from the harsh environment. Since the cells could no longer grow, their only function was to secrete surfactin into the broth, leading to an extraordinarily high surfactin yield with a low biomass production. This suggests that an alternative means for efficient surfactin production is through the addition of LDH.

Disease resistance is one of the most successful strategies in crop protection. For example, the implementation of PI 88788 type resistance, which contains high copy numbers of Resistance to Heterodera glycines 1 (rhg1) loci, into the commercial soybean varieties of the United States has significantly reduced the yield losses caused by soybean cyst nematode (SCN, H. glycines). Vegetable soybean, or edamame, has become a major exporting agricultural product in Taiwan with an annual revenue over $80 million USD since 2017. Several local varieties have been developed to fulfill the market needs such as the traits of flavor and sweetness. However, it remains unclear if the historical breeding programs ever incorporated rhg1 resistance into the varieties of Taiwan. This study applied the TaqMan qPCR method to measure the fluorescent signals specific to the rhg1 locus on the chromosome 18 of soybean, and the ratio of VIC and FAM signals were analyzed to predict the rhg1 copy number in the 21 soybean varieties of Taiwan. The results indicated the copy number and the single nucleotide polymorphisms of the 21 soybean varieties were identical to the susceptible soybean variety ‘Williams 82’. As importation of soybean will be continuously needed to fulfill the market and because SCN is absent in the soybean fields of Taiwan, lacking rhg1 resistance in the local soybean varieties may put the edamame industry at risk and early implementation of SCN resistance in the breeding program, alongside the application of quarantine regulations, will be the key to maintain the SCN-free status and to sustain the edamame industry in Taiwan.

Recent studies reported granulocyte colony-stimulating factor (G-CSF) treatment can improve the cognitive function of Alzheimer's disease (AD) mice, and the mobilized hematopoietic stem cells (HSCs) or bone marrow mesenchymal stem cells (BM-MSCs) are proposed to be involved in this recovery effect. However, the exact role of mobilized HSC/BM-MSC in G-CSF-based therapeutic effects is still unknown. Here, we report that C-X-C chemokine receptor type 4 (CXCR4)/stromal cell-derived factor 1 (SDF-1) chemotaxis was a key mediator in G-CSF-based therapeutic effects, which was involved in the recruitment of repair-competent cells. Furthermore, we found both mobilized HSCs and BM-MSCs were able to infiltrate into the brain, but only BM-MSCs replenished the neural lineage cells and contributed to neurogenesis in the brains of AD mice. Together, our data show that mobilized BM-MSCs are involved in the replenishment of neural lineages following G-CSF treatment via CXCR4/SDF-1 chemotaxis and further support the potential use of BM-MSCs for further autogenically therapeutic applications.

Polybrominated diphenyl ethers (PBDEs), commonly used as a flame retardants for industrial and commercial products, have a strong tendency to accumulate in the interface of water/soil/sediments and are difficult to biodegrade. An effective biological treatment for PBDE removal is needed. In this study, we investigated the use of 3 organic compost materials (BM-2, BM-6, and BP-2) to remove 20 mg kg−1 decabromodiphenyl ether (BDE-209) from contaminated sediment in anaerobic microcosms for 120 days and detected the bacterial community in samples. Organic substance of compost had sorption and biodegradation ability. BM-6 showed the highest sorption of BDE-209, at 38.95%, and BM-3 the highest biological activity, at 34.90%. Methylophilus spp., Pseudomonas spp., Clostridium spp., and Dehalococcoides sp. were identified in anaerobic microcosms with PBDE biodegradation. The pathway of anaerobic DBDE biodegradation from higher to lower brominated PBDE was identified by the appearance of PBDE biometabolites and functional genes related to reductive debromination. We have identified an effective approach for bioremediating PBDE-contaminated sediment by using organic compost; this approach is highly recommended for practical engineering for off-site remediation.

Production of staphylococcal enterotoxin A (SEA) and enterotoxin D (SED) by Staphylococcus warneri was first examined in three different media including brain heart infusion (BHI) broth, NZ-amine (NZA) medium, and 3 + 3 medium containing 3% NZ-amine A plus 3% Hy-Case Amino. Results of these investigations revealed that S. warneri produced the highest amount of SEA in BHI broth. SED yields were higher when BHI broth or NZA medium was used as the culture medium. On the other hand, SEA and SED production was found to be lowest in 3 + 3 medium. Further study showed that the optimum pH, for both SEA production and SED production was 7.0. Addition of 10% (wt/vol) sodium chloride to BHI broth reduced enterotoxin production by S. warneri . SEA production was reduced and SED production was completely inhibited in the presence of 15% (wt/vol) NaCl. Supplementation of the media with 0.4 or 1.5 mM magnesium sulfate markedly reduced SED production by S. warneri . Reduced production of both SEA and SED was also observed when BHI broth was supplemented with 0.1 M glucose or glycerol.

The growth and survival of Yersinia enterocolitica 0:3 and 0:8 were determined using Brain Heart Infusion Broth at pH 5.5 or 6.5, with 0, 250, 500, 1000, 1500, 2500, or 5000 ppm potassium sorbate, and incubated at 25 or 3°C. Results showed that Y. enterocolitica was susceptible to the antimicrobial activity of potassium sorbate. At 25°C and pH 5.5, a population increase of 6.8 and 6.9 log CFU/ml was noted for Y. enterocolitica serotypes 0:3 and 0:8, respectively, in broth without potassium sorbate. The presence of 1000-1500 ppm potassium sorbate in broth retarded the growth of the inoculated Y. enterocolitica cells or partially or completely inactivated them. At 25°C and pH 6.5, potassium sorbate at a concentration as high as 5000 ppm did not inactivate this pathogen. All the concentrations of potassium sorbate tested only retarded the growth of Y. enterocolitica . A 3°C and pH 5.5, Y. enterocolitica grew slightly in the control broth. The presence of 250-500 ppm or more potassium sorbate in broth completely inhibited the growth of Y. enterocolitica or reduced the number of viable cells. At 3°C and pH 6.5, a slight increase in the population of Y. enterocolitica was observed in the broth with or without potassium sorbate, but the increase slacked off as the amount of potassium sorbate was increased.

Ischemic stroke is the leading cause of disability and death worldwide. An effective therapeutic approach is urgently needed. Stroke-induced angiogenesis and neurogenesis are essential mechanisms in the long-term repair. Extracellular matrix proteins are also involved in tissue self-repair. Recently, a PHSRN (Pro-His-Ser-Arg-Asn) peptide from the fibronectin synergistic motif that can promote wound healing in epithelia and induce endothelial proliferation and cancer cell migration was identified. The therapeutic potential of this peptide in stroke is unknown. Here, we examined the potential of PHSRN in stroke therapy using an ischemic rat model of middle cerebral artery occlusion (MCAO). PHSRN reduced the infarct volume in MCAO rats, improved neurological function, and alleviated motor function impairment. PHSRN targeted the damaged brain region and distributed to endothelial cells after intraperitoneal injection. PHSRN significantly promoted angiogenesis and vascular endothelial growth factor secretion through activation of integrin α5β1 and its downstream intracellular signals, e.g., focal adhesion kinase, Ras, cRaf, and extracellular-signal-regulated kinase. PHSRN treatment also stimulated neurogenesis in MCAO rats, and maintained neuronal survival and neuronal morphologic complexity via induction of VEGF secretion. Together, these results provide insights into the role of integrin α5β1 following ischemia and support the feasibility of using PHSRN peptide in stroke therapy.

The 2011 oil spill in the Bohai Sea was the largest spill event in China. Nine sediment cores were taken near the spill site and environmental factors including Polycyclic Aromatic Hydrocarbon (PAHs), oils, sulfides, organic carbon were measured 6 months later. Benthic foraminifera were separated into >150 mu m (large) and 63-150 mu m (small) size fractions for 2-cm depth interval of each sediment core. Statistical analyses suggested that the species composition of living foraminifera was impacted by oils, PAHs and sulfides. Large foraminifera were more sensitive to the oils than the small. Abnormal specimens were positively correlated with oils or PAHs. Small forms, however, tended to have high reproduction and mortality. Pollution-resistant and opportunistic taxa were identified to calculate a Foraminiferal Index of Environmental Impacts (FIEI). The FIEI increased from low to high oil-polluted station and from deep layer to surface sediment reflects the impact of oil pollution in this area. (C) 2015 The Authors. Published by Elsevier Ltd.

Plant somatic embryogenesis (SE) is similar to zygotic embryogenesis and considered as a potential model for studying the regulation of gene expression during plant embryogenesis. Ran protein was shown to be crucial in longan SE. Ran is a highly conserved Small GTPase that plays crucial roles in multiple biological processes, such as cell proliferation. The function of Ran has been extensively studied in past years, but regulation of Ran expression remains elusive. In this study, 11 Ran 3′-untranslated regions (3′UTR) differing in their sequences and length were demonstrated and long 3′UTR contain more putative miRNA target sites. Quantitative reverse transcription PCR (qPCR) was employed to study expression of Ran 3′UTRs during longan SE. We showed that Ran 3′UTRs developmentally expressed during longan SE without lengthening as SE progress. Our results demonstrated that Ran 3′UTRs were highly expressed at the developmental stages of somatic embryogenesis that the cells divided rapidly and supported the role of Ran in cell proliferation. Developmental regulation of Ran 3′UTRs lengthen during longan SE suggested that the polymorphism of be Ran 3′UTRs could be functional.

Diabetes mellitus is associated with dementia, but whether diabetes is associated with Alzheimer's disease remains controversial. Alzheimer's disease is characterized by amyloid beta aggregation. We hypothesized that genes, involved in amyloid beta degradation, may be altered due to diabetes and thus participate in progression of Alzheimer's disease. Expression profiling of amyloid beta-degrading enzymes in streptozotocin-induced diabetic mice and their correlation with expression of amyloid precursor protein in hippocampus of Alzheimer's disease patients were accessed. We found that matrix metalloproteinase 14 decreased in brain but not in other tissues of streptozotocin-induced diabetic mice, and was negatively correlated with expression of amyloid precursor protein in hippocampus of Alzheimer's disease patients. These findings suggested matrix metalloproteinase 14 may link insulin-deficient diabetes to Alzheimer's disease.

This study used three-dimensional (3D) micro-computed tomography (μCT) imaging to examine petal form variation in a hybrid cross of Sinningia speciosa between a cultivar with actinomorphic flowers and a variety with zygomorphic flowers. The major objectives were to determine the genotype–phenotype associations between the petal form variation and CYCLOIDEA2-like alleles in S. speciosa (SsCYC) and to morphologically investigate the differences in petal types between actinomorphic and zygomorphic flowers. In this study, μCT was used to accurately acquire 3D floral images. Landmark-based geometric morphometrics (GM) was applied to evaluate the major form variations of the petals. Nine morphological traits of the petals were defined according to the form variations quantified through the GM analysis. The results indicated that the outward curvature of dorsal petals, the midrib asymmetry of lateral petals, and the dilation of ventral region of the tube were closely associated with the SsCYC genotype. Multiple analyses of form similarity between the petals suggested that the dorsal and ventral petals of actinomorphic plants resembled the ventral petals of zygomorphic plants. This observation indicated that the transition from zygomorphic to actinomorphic flowers in S. speciosa might be caused by the ventralization of the dorsal petals. We demonstrated that the 3D-GM approach can be used to determine genotype–phenotype associations and to provide morphological evidence for the transition of petal types between actinomorphic and zygomorphic flowers in S. speciosa.

Matrix metalloproteinase-9 (MMP-9) appears to play an important role in acute skin inflammation. Subantimicrobial dose of tetracycline has been demonstrated to inhibit the activity of MMP-9 protein. However, long-term use tetracycline will induce side effect. The catalytic site of MMP-9 is located at zinc-binding amino acids, His401, His405 and His411. We attempted to search novel medicine formula as MMP-9 inhibitors from traditional Chinese medicine (TCM) database by using in silico studies. We utilized high-throughput virtual screening to find which natural compounds could bind to the zinc-binding site. The quantitative structure-activity relationship (QSAR) models, which constructed by scaffold of MMP-9 inhibitors and its activities, were employed to predict the bio-activity of the natural compounds for MMP-9. The results showed that Celacinnine, Lobelanidine and Celallocinnine were qualified to interact with zinc-binding site and displayed well predictive activity. We found that celallocinnine was the best TCM compound for zinc binging sites of MMP-9 because the stable interactions were observed under dynamic condition. In addition, Celacinnine and Lobelanidine could interact with MMP-9 related protein that identified by drug-target interaction network analysis. Thus, we suggested the herbs Hypericum patulum, Sedum acre, and Tripterygium wilfordii that containing Celallocinnine, Celacinnine and Lobelanidine might be a novel medicine formula to avoid the side effect of tetracycline and increase the efficacy of treatment.

The etiology of Tourette syndrome (TS) is multifactorial. TS vulnerability may be associated with genetic and environmental factors. From the genetic point of view, TS is heterogeneous. Previous studies showed that some single-nucleotide polymorphisms (SNPs) of the glutathione-S-transferase P1 (GSTP1) gene can affect cellular proliferation and apoptotic activity and TS is a neurodevelopmental disorder. We guessed that there was a relationship between TS and genetic variants of the GSTP1 gene. Therefore, in this study, we aimed to test the hypothesis that GSTP1 SNPs were associated with TS. We performed a case-control study. One hundred twenty-one TS children and 105 normal children were included in the study. Polymerase chain reaction was used to identify the GSTP1 gene polymorphism at position rs6591256 (A/G, promoter polymorphism) in TS patients and normal children. The polymorphism at position rs6591256 in the GSTP1 gene revealed significant differences in the allele (p=0.0135) and genotype (p=0.0159) distributions between the TS patients and the control group. The A allele was present at a higher frequency than the G allele in the TS patients compared with the control group (odds ratio [OR]=1.91, 95% confidence interval [CI]: 1.14-3.21). The AA genotype was associated with susceptibility to TS with an OR of 2.38 for the AA versus AG genotype (95% CI: 1.29-4.41). These findings suggest that variants in the GSTP1 gene may play a role in susceptibility to TS.

Alzheimer’s disease (AD) is caused by the hyperphosphorylation of Tau protein aggregation. FKBP52 (FK506 binding protein 52) has been found to inhibit Tau protein aggregation. This study found six different kinds of anthocyanins that have high binding potential. After analyzing the docking positions, hydrophobic interactions, and hydrogen bond interactions, several amino acids were identified that play important roles in protein and ligand interaction. The proteins’ variation is described using eigenvectors and the distance between the amino acids during a molecular dynamics simulation (MD). This study investigates the three loops based around Glu85, Tyr113, and Lys121—all of which are important in inducing FKBP52 activation. By performing a molecular dynamic simulation process between unbound proteins and the protein complex with FK506, it was found that ligand targets that docked onto the FK1 domain will decrease the distance between Glu85/Tyr113 and Glu85/Lys121. The FKBP52 structure variation may induce FKBP52 activation and inhibit Tau protein aggregation. The results indicate that anthocyanins might change the conformation of FKBP52 during binding. In addition, the purple anthocyanins, such as cyanidin-3-glucoside and malvidin-3-glucoside, might be better than FK506 in regulating FKBP52 and treating Alzheimer’s disease.

Nowadays, obesity becomes a serious global problem, which can induce a series of diseases such as type 2 diabetes mellitus, cancer, cardiovascular disease, metabolic syndrome, and stoke. For the mechanisms of diseases, the hedgehog signaling pathway plays an important role in body patterning during embryogenesis. For this reason, smoothened homologue (Smo) protein had been indicated as the drug target. In addition, the small-molecule Smo inhibitor had also been used in oncology clinical trials. To improve drug development of TCM compounds, we aim to investigate the potent lead compounds as Smo inhibitor from the TCM compounds in TCM Database@Taiwan. The top three TCM compounds, precatorine, labiatic acid, and 2,2′-[benzene-1,4-diylbis(methanediyloxybenzene-4,1-diyl)]bis(oxoacetic acid), have displayed higher potent binding affinities than the positive control, LY2940680, in the docking simulation. After MD simulations, which can optimize the result of docking simulation and validate the stability of H-bonds between each ligand and Smo protein under dynamic conditions, top three TCM compounds maintain most of interactions with Smo protein, which keep the ligand binding stable in the binding domain. Hence, we propose precatorine, labiatic acid, and 2,2′-[benzene-1,4-diylbis(methanediyloxybenzene-4,1-diyl)]bis(oxoacetic acid) as potential lead compounds for further study in drug development process with the Smo protein.

Cognitive repair by insulin-like growth factor-I (IGF-I) through activation of insulin-like growth factor-I receptor (IGF-IR) is well established, but not used for clinical therapy due to its link to cancer. We hypothesize that IGF-IR activation rather than IGF-I per se may be essential for cognitive repair and attempted to identify ligands from traditional Chinese medicine (TCM) with drug-like potential towards IGF-IR. TCM ligands, 3-(2-carboxyphenyl)-4(3H)-quinazolinone from Isatisin digotica, (+)-N-methyllaurotetanine from Lindera aggregate, and (+)-1(R)-Coclaurine from Nelumbonucifera Gaertn, exhibited high binding affinities and good blood brain barrier (BBB) penetration crucial for accessing IGF-IR. Stable complex formation of the candidates was observed during molecular dynamics (MD) simulation. Interactions with Leu975 and Gly1055 or Asp1056 were important for ligand binding. Amino acid distance analysis revealed residues 974/975, 984-986, 996-1006, 1040-1056, and 1122-1135 as "hotspots" for ligand binding in IGF-IR. Versatile entry pathways for the TCM candidates suggest high accessibility to the binding site. Blockage of the binding site opening by the TCM candidates limits binding site access by other compounds. Multiple linear regression (R² = 0.9715), support vector machine (R² = 0.9084), Bayesian network (R² =0.8233) comparative molecular field analysis (CoMFA, R² = 0.9941), and comparative molecular similarity indices analysis (CoMSIA, R² = 0.9877) models consistently suggest that the TCM candidates might exert bioactivity on IGF-IR. Contour of representative MD conformations to CoMFA and CoMSIA maps exhibits similar results. Properties including BBB passage, evidence of ability to form stable complexes with IGF-IR by MD simulation, and predicted bioactivity suggest that the TCM candidates have drug-like properties and might have potential as cognitive-enhancing drugs.

Although neoadjuvant chemotherapy has improved the survival rate of osteosarcoma patients, drug resistance remains a predominant obstacle to improving efficacy and necessitates the development of novel chemotherapeutical agents. The aim of this study was to investigate whether tetrandrine (TET) induces apoptosis in the U-2OS and MG-63 osteosarcoma cell lines and to further determine the under- lying mechanism. This study investigated the effects of TET on osteosarcoma in vitro. To examine the antitumor effects of TET on osteosarcoma, the two osteosarcoma cell lines were treated with TET and subjected to apoptosis assays. The results revealed that TET induced the apoptosis of osteosarcoma cells in a time- and dose-dependent manner. Furthermore, the apoptosis of osteosarcoma cells was accompanied by increased cytochrome c (Cyto-C), apoptotic protease-activating factor (Apaf)-1, Bid and Bax activation and reduced Bcl-2 and Bcl-xl activation, demonstrating that the apoptosis may have occurred through the mitochondrial pathway. In conclusion, the results suggest that TET is a promising agent for osteosarcoma therapy.

Background Genetic, environmental, immunological, and hormonal factors contribute to the etiology of Tourette syndrome (TS). From the genetic standpoint, TS is a heterogeneous disorder. In our previous study, we found that a single nucleotide polymorphism (SNP) of x-ray repair cross-complementing group 1 (XRCC1), a DNA repair gene, was associated with TS. Previous studies also showed that tyrosyl-DNA phosphodiesterase 1 (TDP1) interacts with XRCC1 to repair damaged DNA. However, the relationship between TS and SNPs of TDP1 gene is unknown. Therefore, the aim of this study was to test the hypothesis that if the TDP1 SNP, rs28365054 (c.400G>A, Ala134Thr), was associated with TS or not. Methods A case-control study was designed to test the hypothesis. A total of 122 TS children and 106 normal children participated in the study. We used polymerase chain reaction to identify the SNP, rs28365054, of the TDP1 gene in the TS patients and the normal children. Results A polymorphism at position rs28365054 in the TDP1 gene had a significant difference (P < 0.05) in the genotype distributions between the TS patients and the control group. The AG genotype was a risk factor for TS with an odds ratio of 2.26 for the AG versus AA genotype (95% CI 1.08–4.72). Conclusion The findings of this study suggested that variants in the TDP1 gene might play a role in TS susceptibility.

In the present study, Vibrio parahaemolyticus 690 in phosphate buffered-saline containing 3% NaCl was subjected to sublethal stresses: heat shock at 42 °C for 15 min, acid adaptation at pH 5.0 for 30 min, or cold shock at 20 °C for 4 h. The effect of sublethal stress on the susceptibility of V. parahaemolyticus to a chlorine-containing disinfectant (Clidox-S) and a quaternary ammonium compound (Quatricide) at 25 and 40 °C was investigated. It was found that the sublethal stresses examined enhanced the resistance of V. parahaemolyticus 690 to both disinfectants. Depending on the kinds of sublethal stress, V. parahaemolyticus 690 showed various degrees of enhanced resistance to disinfectants. Furthermore, the phenomenon of enhanced resistance to the disinfectants was more marked at 40 than at 25 °C.

Tourette syndrome (TS) is an etiologically heterogeneous disorder, the pathogenesis of which is incompletely understood. Poly(ADP-ribose) polymerase 1 (PARP1) is involved in regulation of developmental processes and cellular differentiation, in transcription regulation, in DNA repair, and in cell death. However, the relationship between TS and single nucleotide polymorphisms (SNPs) of PARP1 is unknown. Therefore, the aim of this experiment was to test the hypothesis that whether the PARP1 SNP, rs1805404 (c.243C>T, Asp81Asp), had an association with TS. A case-control experiment was designed to test this hypothesis. 123 TS children and 122 normal children were enrolled in this study. Polymerase chain reaction restriction fragment length polymorphism was used for the detection of the PARP1 SNP, rs1805404, in TS patients and normal children. The data showed that there is a significant difference in genotype distributions between these two groups. The CT genotype was a risk factor for TS with an odds ratio of 2.34 for the CT versus TT genotype (95% CI 1.16-4.74). The data also showed this SNP had an association with TS under recessive model (P = 0.0426), and TT genotype had a protective effect against TS with an odds ratio of 0.50 (95% CI 0.26-0.98). The findings of this study suggested that variants in the PARP1 gene might play a role in susceptibility to TS.

Cronobacter spp., formerly Enterobacter sakazakii, are human pathogens. They are the etiological agent of life-threating bacterial infections in infants. In this study, the survival behavior of C. sakazakii Bioresources Collection and Research Center (BCRC) 13988 in the presence of various ethanol concentrations was first examined. Besides, the test organism was subjected to treatment with 5% ethanol for 60 min (ethanol shock). The effect of ethanol shock on the resistance of C. sakazakii to lethal stresses, including high ethanol concentration (15%), low temperature (4°C and -20°C), high temperature (51°C) and high acidity (pH 3.3), was investigated. Results revealed that 4-5% ethanol is the maximum concentration that will allow C. sakazakii BCRC 13988 to grow in trypticase soy broth (TSB). Etthanol at 6% and 7% or more, respectively, exerted bacteriostatic and bactericidal effects, respectively, on the test organism. Although ethanol shock did not affect the resistance of C. sakazakii to a refrigerated temperature (4°C), the ethanol-shocked C. sakazakii survived better under other lethal stress conditions. After 50 min of exposure to 15% ethanol, the ethanol-shocked C. sakazakii showed a survival percentage of 16.11%, which was a 6400-fold increase over the control cells (

Streptococcus thermophilus is a thermophilic lactic acid bacterium which is used as the starter organism for the fermentation of yoghurt and some cheese. In the present study, S. thermophilus BCRC 14085 was subjected to cold shock treatment by exposure at 10 °C for 2 h. The effect of cold shock on the susceptibility of S. thermophilus in subsequent lethal stress environments such as simulated gastric juice (pH 2.0-3.0), bile solution (2.0%) and various organic acids (0.75 M, pH 3.5) including propionic, lactic, acetic, citric and tartaric acid was investigated. In addition, the survival of cold-shocked and non-shocked S. thermophilus exposed to disinfectants, Clidox-S and Quatricide, were compared. Results revealed that cold shock enhanced the tolerance of S. thermophilus in the presence of simulated gastric juice (pH 2.5 and 2.8), while in bile solution, the population increase of cold-shocked cells is higher than that of non-shocked cells after 12 h of incubation. Furthermore, the susceptibility of S. thermophilus, regardless of cold shock, to organic acid varied with the kinds of organic acid examined. The cold-shocked S. thermophilus showed a significantly less survival (P < 0.05) than that of the non-shocked cells when exposed to lactic or acetic acid. Furthermore, cold shock reduced the survival of S. thermophilus when exposed to Quatricide but not Clidox-S.

Background X-ray repair cross-complementing group 1 (XRCC1) plays a central role in mammalian DNA repair process. The polymorphism rs25487 (Arg>Gln at codon 399) of this gene is common in Han Chinese population. Objectives The objective of this study was to analyze the association between this functional SNP of XRCC1 and Tourette syndrome (TS) in Han Taiwan Chinese population. Methods Genotyping was performed by using PCR–RFLP method on 73 TS patients and 158 normal controls. Results Our data indicated that genotype frequency of A/G polymorphism at codon 399 of the patients differed from the controls (P = 0.026, OR: 2.22, 95% CI: 1.22–4.03). The allele frequency analysis also showed significant differences with higher A allele frequency in patients (P = 0.015, OR: 1.70, 95% CI: 1.11–2.62). Conclusion Our study indicates that the functional SNP at codon 399 of XRCC1 is associated with TS development. J. Clin. Lab. Anal. 26:321-324, 2012. © 2012 Wiley Periodicals, Inc.

Stem cell-based therapy is a potential treatment for neurodegenerative diseases, but its application to Alzheimer’s disease (AD) remains limited. Brain-derived neurotrophic factor (BDNF) is critical in the pathogenesis and treatment of AD. Here, we present a novel therapeutic approach for AD treatment using BDNF-overexpressing neural stem cells (BDNF-NSCs). In vitro, BDNF overexpression was neuroprotective to beta-amyloid-treated NSCs. In vivo, engrafted BDNF-NSCs-derived neurons not only displayed the Ca2+-response fluctuations, exhibited electrophysiological properties of mature neurons and integrated into local brain circuits, but recovered the cognitive deficits. Furthermore, BDNF overexpression improved the engrafted cells’ viability, neuronal fate, neurite complexity, maturation of electrical property and the synaptic density. In contrast, knockdown of the BDNF in BDNF-NSCs diminished stem cell-based therapeutic efficacy. Together, our findings indicate BDNF overexpression improves the therapeutic potential of engrafted NSCs for AD via neurogenic effects and neuronal replacement and further support the feasibility of NSC-based ex vivo gene therapy for AD.

To clone and examine expression profiles of DlRan genes during somatic embryogenesis in Dimocarpus longan Lour. Thirty cDNA sequences and two genomic sequences encoding DlRan proteins were isolated from longan embryogenic cultures. Structural analysis of DlRan genes revealed that the longan Ran gene family is more expanded than that of Arabidopsis. Expression analysis of DlRan genes during somatic embryogenesis uncovered a high abundance of DlRan genes in early embryogenic cultures and heart- and torpedo-shaped embryos. The expression of DlRan genes in embryogenic calli was affected by exogenous 2,4-dichlorophenoxyacetic acid treatment. DlRan is involved in 2,4-D induced somatic embryogenesis and development of somatic embryos in longan. Electronic supplementary material The online version of this article (doi:10.1186/s40064-016-1887-0) contains supplementary material, which is available to authorized users.

Soybean products (soyfoods), reported as potential functional foods, are implicated in several health-enhancing properties, such as easing the symptoms of postmenopausal women, reducing the risk of osteoporosis, preventing cardiovascular disease, and antimutagenic effects. Isoflavone, for example, is one of the most important compounds abundantly found in soybean, mainly accounting for the health-enhancing properties as mentioned earlier. However, most biological activities of isoflavones are mainly attributed to their aglycone forms. It has also been demonstrated that isoflavone aglycones are absorbed faster and in greater amount than their glycosides in human intestines. Fortunately, deglycosylation of isoflavones can be achieved during fermentation process by several strains such as lactic acid bacteria, basidiomycetes, filamentous fungus, and Bacillus subtilis with their β-glucosidase activity. This article presents an overview of soybean's chemistry, application, state-of-the-art advances in soybean fermentation processing and products as well as their applications in food and pharmaceutical industries. Different compounds, such as isoflavone, dietary fibers, and proteins which exhibit significant bioactivities, are summarized. The roles of different microorganisms in bioconversion and enhancement of bioactivities of fermented soybean are also discussed.

Vibrio parahaemolyticus strain 690 was isolated from gastroenteritis patients. Its thermal and ethanol stress responses have been reported in our previous studies. In this study, we further investigated the effects of various acid adaptation conditions including pH (5.0-6.0) and time (30-90 min) on the acid tolerance in different growth phases of V. parahaemolyticus 690. Additionally, the adaptive acid tolerance among different V. parahaemolyticus strains was compared. Results indicated that the acid tolerance of V. parahaemolyticus 690 was significantly increased after acid adaptation at pH 5.5 and 6.0 for 30-90 min. Among the various acid adaptation conditions examined, V. parahaemolyticus 690 acid-adapted at pH 5.5 for 90 min exhibited the highest acid tolerance. The acid adaptation also influenced the acid tolerance of V. parahaemolyticus 690 in different growth phases with late-exponential phase demonstrating the greatest acid tolerance response (ATR) than other phases. Additionally, the results also showed that the induction of adaptive ATR varied with different strains of V. parahaemolyticus. An increase in acid tolerance of V. parahaemolyticus was observed after prior acid adaptation in five strains (556, 690, BCRC 13023, BCRC 13025, and BCRC 12864), but not in strains 405 and BCRC 12863.

SummaryOptimal insulin secretion required to maintain glucose homeostasis is the summation of total pancreatic islet β cell mass and intrinsic secretory capacity of individual β cells, which are regulated by distinct mechanisms that could be amplified by glucagon-like-peptide-1 (GLP-1). Because of these actions of GLP-1 on islet β cells, GLP-1 has been deployed to treat diabetes. We employed SNARE protein VAMP8-null mice to demonstrate that VAMP8 mediates insulin granule recruitment to the plasma membrane, which partly accounts for GLP-1 potentiation of glucose-stimulated insulin secretion. VAMP8-null mice also exhibited increased islet β cell mass from increased β cell mitosis, with β cell proliferative activity greatly amplified by GLP-1. Thus, despite the β cell exocytotic defect, VAMP8-null mice have an increased total insulin secretory capacity, which improved glucose homeostasis. We conclude that these VAMP8-mediated events partly underlie the therapeutic actions of GLP-1 on insulin secretion and β cell growth.

Impairment of learning and memory is a significant pathological feature of many neurodegenerative diseases including FTLD-TDP. Appropriate regulation and fine tuning of spinogenesis of the dendrites, which is an integral part of the learning/memory program of the mammalian brain, are essential for the normal function of the hippocampal neurons. TDP-43 is a nucleic acid-binding protein implicated in multi-cellular functions and in the pathogenesis of a range of neurodegenerative diseases including FTLD-TDP and ALS. We have combined the use of single-cell dye injection, shRNA knockdown, plasmid rescue, immunofluorescence staining, Western blot analysis and patch clamp electrophysiological measurement of primary mouse hippocampal neurons in culture to study the functional role of TDP-43 in mammalian spinogenesis. We found that depletion of TDP-43 leads to an increase in the number of protrusions/spines as well as the percentage of matured spines among the protrusions. Significantly, the knockdown of TDP-43 also increases the level of Rac1 and its activated form GTP-Rac1, a known positive regulator of spinogenesis. Clustering of the AMPA receptors on the dendritic surface and neuronal firing are also induced by depletion of TDP-43. Furthermore, use of an inhibitor of Rac1 activation negatively regulated spinogenesis of control hippocampal neurons as well as TDP-43-depleted hippocampal neurons. Mechanistically, RT-PCR assay and cycloheximide chase experiments have indicated that increases in Rac1 protein upon TDP-43 depletion is regulated at the translational level. These data together establish that TDP-43 is an upstream regulator of spinogenesis in part through its action on the Rac1 → GTP-Rac1 → AMPAR pathway. This study provides the first evidence connecting TDP-43 with the GTP-Rac1 → AMPAR regulatory pathway of spinogenesis. It establishes that mis-metabolism of TDP-43, as occurs in neurodegenerative diseases with TDP-43 proteinopathies, e.g., FTLD-TDP, would alter its homeostatic cellular concentration, thus leading to impairment of hippocampal plasticity.

The foodborne pathogens Listeria monocytogenes and Salmonella Typhimurium were subjected to heat shock at 48°C for 10 and 30 min, respectively, and then cold shocked at 15°C for 3 h. The effect of these shocks on the viability of test organisms exposed to chlorine dioxide and quaternary ammonium compounds was then determined. After exposure to the disinfectants, the viable population of each test organism, regardless of heat shock or cold shock treatment, decreased as the exposure period was extended. Both heat shock and cold shock treatments reduced the susceptibility of L. monocytogenes to both disinfectants at 25°C. However, for Salmonella Typhimurium, exposure to the chlorine dioxide disinfectant or quaternary ammonium compounds at 25°C significantly reduced (P < 0.05) survival of heat-shocked cells but significantly increased (P < 0.05) survival of cold-shocked cells compared with control cells. Survival of both L. monocytogenes and Salmonella Typhimurium generally was reduced after exposure to disinfectants at 40°C compared with 25°C.

The quantification of floral shape variations is difficult because flower structures are both diverse and complex. Traditionally, floral shape variations are quantified using the qualitative and linear measurements of two-dimensional (2D) images. The 2D images cannot adequately describe flower structures, and thus lead to unsatisfactory discrimination of the flower shape. This study aimed to acquire three-dimensional (3D) images by using microcomputed tomography (μCT) and to examine the floral shape variations by using geometric morphometrics (GM). To demonstrate the advantages of the 3D-µCT-GM approach, we applied the approach to a second-generation population of florist’s gloxinia (Sinningia speciosa) crossed from parents of zygomorphic and actinomorphic flowers. The flowers in the population considerably vary in size and shape, thereby served as good materials to test the applicability of the proposed phenotyping approach. Procedures were developed to acquire 3D volumetric flower images using a μCT scanner, to segment the flower regions from the background, and to select homologous characteristic points (i.e., landmarks) from the flower images for the subsequent GM analysis. The procedures identified 95 landmarks for each flower and thus improved the capability of describing and illustrating the flower shapes, compared with typically lower number of landmarks in 2D analyses. The GM analysis demonstrated that flower opening and dorsoventral symmetry were the principal shape variations of the flowers. The degrees of flower opening and corolla asymmetry were then subsequently quantified directly from the 3D flower images. The 3D-µCT-GM approach revealed shape variations that could not be identified using typical 2D approaches and accurately quantified the flower traits that presented a challenge in 2D images. The approach opens new avenues to investigate floral shape variations.

Cell fractions including heat-treated cells, crude cell walls, intracellular extracts and exopolysaccharides (EPSs) obtained from Lactobacillus casei 01 were first studied for their effects on the proliferation of human intestinal epithelial cells, intestine 407 and the human colon cancer cell, HT-29. Their effects on the cytotoxicity of 4-nitroquinoline 1-oxide (4-NQO) against intestine 407 were further investigated. The results revealed that EPS exhibited the highest antiproliferation activity on HT-29 cells while the viability of intestine 407 cells was not affected by EPS at a concentration of 5-50μg/mL. It was also noted that all the cell fractions and EPS from L. casei 01 reduced the cytotoxicity of 4-NQO against intestine 407 with EPS showing the highest anticytotoxic activity. Additionally, it was found that EPS might exert blocking and bioanticytotoxic effects by both adjusting the function of intestine 407 and repairing the 4-NQO-damaged cells, thus reducing cytotoxicity of 4-NQO.

OBJECTIVE Previous studies have demonstrated that the VAMP8 protein plays a complex role in the control of granule secretion, transport vesicle trafficking, phagocytosis, and endocytosis. The present study was aimed to investigate the role of VAMP8 in mediating GLUT4 trafficking and therefore insulin action in mice. RESEARCH DESIGN AND METHODS Physiological parameters were measured using Oxymax indirect calorimetry system in 12-week-old VAMP8 null mice. Dynamic analysis of glucose homeostasis was assessed using euglycemic–hyperinsulinemic clamp coupled with tracer radioactively labeled 2-deoxyglucose. Insulin stimulated GLUT4 protein expressions on muscle cell surface were examined by immunofluorescence microscopy. RESULTS VAMP8 null mice display reduced adiposity with increased energy expenditure despite normal food intake and reduced spontaneous locomotor activity. In parallel, the VAMP8 null mice also had fasting hypoglycemia (84 ± 11 vs. 115 ± 4) and enhanced glucose tolerance with increased insulin sensitivity due to increases in both basal and insulin-stimulated glucose uptake in skeletal muscle (0.19 ± 0.04 vs. 0.09 ± 0.01 mmol/kg/min during basal, 0.6 ± 0.04 vs. 0.31 ± 0.06 mmol/kg/min during clamp in red-gastrocnemius muscle, P < 0.05). Consistent with a role for VAMP8 in the endocytosis of the insulin-responsive GLUT4, sarcolemma GLUT4 protein levels were increased in both the basal and insulin-stimulated states without any significant change in the total amount of GLUT4 protein or related facilitative glucose transporters present in skeletal muscle, GLUT1, GLUT3, and GLUT11. CONCLUSIONS These data demonstrate that, in the absence of VAMP8, the relative subcellular distribution of GLUT4 is altered, resulting in increased sarcolemma levels that can account for increased glucose clearance and insulin sensitivity.

Listeria innocua retains many conserved homologous domains with Listeria monocytogenes, which is a food-borne and water-borne diarrhea-causing bacterium. Studies of antimicrobial resistance in L. innocua showed that this microbe is more prone to acquire resistance than other bacteria in the genus Listeria. However, little is known about the seasonal population distribution and antimicrobial resistance patterns of L. innocua in natural water environments. The aims of the study were: (1) to investigate the occurrence of L. innocua isolates in a subtropical watershed and reconstruct the population structure and (2) to analyze the antibacterial resistance patterns of the identified L. innocua isolates according to ERIC type. A total of 288 water samples was collected from the Puzi River basin (23&deg, 28&rsquo, N, 120&deg, 13&rsquo, E) between March 2014 and March 2015, and 36 L. innocua isolates were recovered from 15 positive water samples. With regard to seasonal variation, L. innocua was only detected in the spring and summer. Eighteen enterobacterial repetitive intergenic consensus (ERIC)-PCR types were identified, and two genogroups with four subgroups were reconstructed in a minimum spanning tree. Isolates from different sampling areas that were located near each other were genetically different. All L. innocua isolates (including 41.7% of the multidrug-resistant (MDR) isolates) were resistant to oxacillin and showed high minimum inhibitory concentrations of tetracycline. These findings demonstrate the seasonal variations and differing geographical distributions of L. innocua in this subtropical water environment, as well as the existence of strong population structures and MDR and antimicrobial resistance patterns. Phylogenetic analysis based on ERIC-type showed that the Cluster A isolates were resistant to more antibiotics, and two types, ERIC8 and ERIC15 were multidrug resistant. The more commonly detected types, such as ERIC1 and ERIC12, were also more likely to be resistant to two or more antibiotics. Close monitoring of drug resistance in environmental L. innocua is warranted due to its potential for transferring antimicrobial resistance determinants to pathogenic Listeria.

Wilson disease is a copper metabolism disorder caused by mutations in ATP7B, a copper-transporting adenosine triphosphatase. A molecular diagnosis was performed on 135 patients with Wilson disease in Taiwan. We identified 36 different mutations, eight of which were novel: five missense mutations (Ser986Phe, Ile1348Asn, Gly1355Asp, Met1392Lys, and Ala1445Pro), one deletion (2810delT) in the coding region, and two nucleotide substitutions (−133A→C and −215A→T) in the promoter region. These mutations were not observed in 100 control subjects and reduced the activity of the mutated protein by at least 50% when compared with wild-type ATP7B. In addition to exon 8, our data indicate another mutation hotspot in exon 12 where 9.62% of all mutations occurred. An alternative splice variant of ATP7B lacking exon 12 was observed in one patient who had a homozygous 2810delT mutation and very mild clinical symptoms. Clinical examination and functional characterization of alternative splice variants of ATP7B lacking exon 12 showed that they retained 80% of their biological activity. The 2810delT mutation increased the expression of these variants, which may have explained the mild symptoms in the patient with the 2810delT mutation. We also discovered that treating liver cancer cells with a Na+/H+ exchanger inhibitor, 5-(N-ethyl-N-isopropyl)-amiloride, significantly enhanced the expression of the alternative splice variant of ATP7B lacking exon 12. Conclusion: This study suggests a novel therapeutic strategy for patients with mutations in exon 12. (Hepatology 2010;52:1662-1670)

Tourette syndrome has a multifactorial etiology in which genetic, environmental, and immunologic factors interact to establish vulnerability. Various interleukin 1 genes are associated with several immunoinflammatory diseases. It is not known whether polymorphisms in those genes are involved in the pathogenesis of Tourette syndrome. In this association study, single nucleotide polymorphisms were used to investigate the distribution of genotypes of the interleukin 1 receptor antagonist gene (IL1RN; alias IL1RA) and of the interleukin 1beta gene (IL1B) in patients with Tourette syndrome. A total of 159 children with Tourette syndrome and 175 healthy control subjects were included in the study. There was no significant difference between patients and control subjects in the distribution of genotype and allele frequencies for IL1B exon 5 and promoter region; however, the number of individuals homozygotic for IL1RN( *)1 was significantly greater (P0.0001), and the IL1RN( *)1 allele frequency was significantly higher (P0.0001), among patients than among control subjects. The odds ratio for developing Tourette syndrome in individuals with the IL1RN( *)1 allele, compared with IL1RN( *)2, was 7.65. Thus, the IL1RN gene may be a useful marker for prediction of the susceptibility to Tourette syndrome.

Aflatoxin B1 (AFB1), among other aflatoxins of the aflatoxin family, is the most carcinogenic and hazardous mycotoxin to animals and human beings with very high potency leading to aflatoxicosis. Selenium is an essential trace mineral possessing powerful antioxidant functions. Selenium is widely reported as an effective antioxidant against aflatoxicosis. By preventing oxidative liver damage, suppressing pro-apoptotic proteins and improving immune status in AFB1 affected animals; selenium confers specific protection against AFB1 toxicity. Meticulous supplementation of animal feed by elemental selenium in the organic and inorganic forms has proven to be effective to ameliorate AFB1 toxicity. Curcumin is another dietary agent of importance in tackling aflatoxicosis. Curcumin is one of the major active ingredients in the tubers of a spice Curcuma longa L., a widely reported antioxidant, anticarcinogenic agent with reported protective potential against aflatoxin-mediated liver damage. Curcumin restricts the aflatoxigenic potential of Aspergillus flavus. Curcumin inhibits cytochrome P450 isoenzymes, particularly CYP2A6 isoform; thereby reducing the formation of AFB1-8, 9-epoxide and other toxic metabolites causing aflatoxicosis. In this review, we have briefly reviewed important aflatoxicosis symptoms among animals. With the main focus on curcumin and selenium, we have reviewed their underlying protective mechanisms in different animals along with their extraction and production methods for feed applications.

Vesicle-associated-membrane protein 8 (VAMP8) is highly expressed in the kidney, but the exact physiological and molecular functions executed by this v-SNARE protein in nephrons remain elusive. Here, we show that the depletion of VAMP8 in mice resulted in hydronephrosis. Furthermore, the level of the vasopressin-responsive water channel aquaporin 2 (AQP2) was increased by three- to fivefold in VAMP8-null mice. Forskolin and [desamino-Cys(1), D-Arg(8)]-vasopressin (DDAVP)-induced AQP2 exocytosis was impaired in VAMP8-null collecting duct cells. VAMP8 was revealed to colocalize with AQP2 on intracellular vesicles and to interact with the plasma membrane t-SNARE proteins syntaxin4 and syntaxin3, suggesting that VAMP8 mediates the regulated fusion of AQP2-positive vesicles with the plasma membrane.