Effect of a group-based acceptance and commitment therapy (ACT) intervention on self-esteem and psychological flexibility in patients with schizophrenia in remission.

The present study explored whether acceptance and commitment therapy (ACT), a cognitive behavioral therapy approach, could improve the symptoms of schizophrenia spectrum disorders among patients with schizophrenia in remission. A pre- and post-treatment design with two evaluation time points was employed. Sixty outpatients with schizophrenia in remission were randomly divided into two groups: the ACT plus treatment as usual (ACT+TAU) and treatment as usual (TAU) groups. The ACT+TAU group participated in 10 group-based ACT interventions and TAU in the hospital, and the TAU group only received TAU interventions. General psycho-pathological symptoms, self-esteem, and psychological flexibility were assessed before intervention (baseline; pre-test) and after intervention (five weeks; post-test). Results indicated that, compared to the TAU group, the ACT+TAU group exhibited a more significant improvement in general psychopathological symptoms, self-esteem, cognitive fusion, and acceptance and action at post-test. ACT intervention could effectively decrease the general psycho-pathological symptoms and increase self-esteem level and psychological flexibility in people with schizophrenia in remission.

Comparative proteomic analysis of wild-type and a SlETR-3 (Nr) mutant reveals an ethylene-induced physiological regulatory network in fresh-cut tomatoes.

Ethylene plays a crucial role in regulating fruit ripening, quality, and defense response. However, the mechanism(s) responsible for wound-induced ethylene regulation of fruit physiology at a network level is unclear. We used mass spectrometry (MS) to identify differences in the physiological response between fresh-cut fruits of wild-type (WT) tomato and an ethylene receptor mutant (SlETR-3) (also referred to as Nr) during storage. We found that Nr mutants exhibited better appearance and quality, as well as higher ethylene levels during the first 3 d of storage at 4 °C. Thirty-seven (0 h), eighty-two (12 h) and twelve (24 h) differentially abundant proteins were identified between the fresh-cut slices of the two genotypes during storage at the designated timepoints. In particular, antioxidant enzymes, such as ascorbate peroxidase, glutathione S-transferase, and peroxiredoxin were highly expressed in WT fruit, which was associated with higher H2O2 production, and high levels of transcription of cell-wall degrading enzymes. Leucine aminopeptidase, a marker enzyme for response to wounding exhibited higher levels in the Nr mutant, which is consistent with its higher production of ethylene. Collectively, our results provide a deeper insight into the ethylene-induced physiological regulatory network that is activated in fresh-cut tomatoes.

Integrative Physiological and Transcriptome Analysis Reveals the Mechanism for the Repair of Sub-Lethally Injured Escherichia coli O157:H7 Induced by High Hydrostatic Pressure.

The application of high hydrostatic pressure (HHP) technology in the food industry has generated potential safety hazards due to sub-lethally injured (SI) pathogenic bacteria in food products. To address these problems, this study explored the repair mechanisms of HHP-induced SI Escherichia coli O157:H7. First, the repair state of SI E. coli O157:H7 (400 MPa for 5 min) was identified, which was cultured for 2 h (37 °C) in a tryptose soya broth culture medium. We found that the intracellular protein content, adenosine triphosphate (ATP) content, and enzyme activities (superoxide dismutase, catalase, and ATPase) increased, and the morphology was repaired. The transcriptome was analyzed to investigate the molecular mechanisms of SI repair. Using cluster analysis, we identified 437 genes enriched in profile 1 (first down-regulated and then tending to be stable) and 731 genes in profile 2 (up-regulated after an initial down-regulation). KEGG analysis revealed that genes involved in cell membrane biosynthesis, oxidative phosphorylation, ribosome, and aminoacyl-tRNA biosynthesis pathways were enriched in profile 2, whereas cell-wall biosynthesis was enriched in profile 1. These findings provide insights into the repair process of SI E. coli O157:H7 induced by HHP.

Highly diverged lineages of Saccharomyces paradoxus in temperate to subtropical climate zones in China.

The wild yeast Saccharomyces paradoxus has become a new model in ecology and evolutionary biology. Different lineages of S. paradoxus have been recognized across the world, but the distribution and genetic diversity of the species remain unknown in China, where the origin of its sibling species S. cerevisiae lies. In this study, we investigated the ecological and geographic distribution of S. paradoxus through an extensive field survey in China and performed population genomic analysis on a set of S. paradoxus strains, including 27 strains, representing different geographic and ecological origins within China, and 59 strains representing all the known lineages of the species recognized in the other regions of the world so far. We found two distinct lineages of S. paradoxus in China. The majority of the Chinese strains studied belong to the Far East lineage, and six strains belong to a novel highly diverged lineage. The distribution of these two lineages overlaps ecologically and geographically in temperate to subtropical climate zones in China. With the addition of the new China lineage, the Eurasian population of S. paradoxus exhibits higher genetic diversity than the American population. We observed more possible lineage-specific introgression events from the Eurasian lineages than from the American lineages. Our results expand the knowledge on ecology, genetic diversity, biogeography, and evolution of S. paradoxus.

Improved redox homeostasis owing to the up-regulation of one-carbon metabolism and related pathways is crucial for yeast heterosis at high temperature.

Heterosis or hybrid vigor is a common phenomenon in plants and animals; however, the molecular mechanisms underlying heterosis remain elusive, despite extensive studies on the phenomenon for more than a century. Here we constructed a large collection of F1 hybrids of Saccharomyces cerevisiae by spore-to-spore mating between homozygous wild strains of the species with different genetic distances and compared growth performance of the F1 hybrids with their parents. We found that heterosis was prevalent in the F1 hybrids at 40°C. A hump-shaped relationship between heterosis and parental genetic distance was observed. We then analyzed transcriptomes of selected heterotic and depressed F1 hybrids and their parents growing at 40°C and found that genes associated with one-carbon metabolism and related pathways were generally up-regulated in the heterotic F1 hybrids, leading to improved cellular redox homeostasis at high temperature. Consistently, genes related with DNA repair, stress responses, and ion homeostasis were generally down-regulated in the heterotic F1 hybrids. Furthermore, genes associated with protein quality control systems were also generally down-regulated in the heterotic F1 hybrids, suggesting a lower level of protein turnover and thus higher energy use efficiency in these strains. In contrast, the depressed F1 hybrids, which were limited in number and mostly shared a common aneuploid parental strain, showed a largely opposite gene expression pattern to the heterotic F1 hybrids. We provide new insights into molecular mechanisms underlying heterosis and thermotolerance of yeast and new clues for a better understanding of the molecular basis of heterosis in plants and animals.

Adaptive Gene Content and Allele Distribution Variations in the Wild and Domesticated Populations of Saccharomyces cerevisiae.

Recent studies on population genomics of Saccharomyces cerevisiae have substantially improved our understanding of the genetic diversity and domestication history of the yeast. However, the origin of the domesticated population of S. cerevisiae and the genomic changes responsible for ecological adaption of different populations and lineages remain to be fully revealed. Here we sequenced 64 African strains from various indigenous fermented foods and forests in different African countries and performed a population genomic analysis on them combined with a set of previously sequenced worldwide S. cerevisiae strains representing the maximum genetic diversity of the species documented so far. The result supports the previous observations that the wild and domesticated populations of S. cerevisiae are clearly separated and that the domesticated population diverges into two distinct groups associated with solid- and liquid-state fermentations from a single ancestor. African strains are mostly located in basal lineages of the two domesticated groups, implying a long domestication history of yeast in Africa. We identified genes that mainly or exclusively occur in specific groups or lineages and genes that exhibit evident group or lineage specific allele distribution patterns. Notably, we show that the homing endonuclease VDE is generally absent in the wild but commonly present in the domesticated lineages of S. cerevisiae. The genes with group specific allele distribution patterns are mostly enriched in functionally similar or related fundamental metabolism processes, including the evolutionary conserved TOR signaling pathway.

Brain Homotopic Connectivity in Mild Cognitive Impairment APOE-ε4 Carriers.

Individuals with mild cognitive impairment (MCI) are regarded as being at high risk of developing Alzheimer's disease (AD). The apolipoprotein E (APOE) ε4 allele is a well-established genetic risk factor for developing AD. In the present study, by using voxel-mirrored homotopic connectivity (VMHC), we aimed to explore the potential functional disruptions in MCI APOE-ε4 carriers. Resting-state functional magnetic resonance imaging was performed in 35 MCI APOE-ε4 carriers (27 APOE-ε3ε4, 8 APOE-ε4ε4) and 42 MCI APOE-ε4 noncarriers (APOE-ε3ε3). VMHC was employed to investigate the alterations in functional connectivity in MCI APOE-ε4 carriers. We further investigated the seed-based functional connectivity between the VMHC values of altered regions and other brain regions in the two groups. The results showed that MCI APOE-ε4 carriers presented increased VMHC in the inferior frontal gyrus/insula and middle frontal gyrus/superior frontal gyrus in comparison with noncarriers. We found that MCI APOE-ε4 carriers showed increased functional connectivity between the seed regions (bilateral inferior frontal gyri/insula and bilateral middle frontal gyri/superior frontal gyri) and broad brain areas, including the frontal, temporal, parietal, and cerebellar regions. Our findings provide neuroimaging evidence for the modulation of the APOE genotype on the neurodegenerative disease phenotype and may be potentially important for monitoring disease progression in double-high-risk populations of AD.

Reverse Evolution of a Classic Gene Network in Yeast Offers a Competitive Advantage.

Glucose repression is a central regulatory system in yeast that ensures the utilization of carbon sources in a highly economical manner. The galactose (GAL) metabolism network is stringently regulated by glucose repression in yeast and has been a classic system for studying gene regulation. We show here that a Saccharomyces cerevisiae (S. cerevisiae) lineage in spontaneously fermented milk has swapped all its structural GAL genes (GAL2 and the GAL7-10-1 cluster) with early diverged versions through introgression. The rewired GAL network has abolished glucose repression and conversed from a strictly inducible to a constitutive system through polygenic changes in the regulatory components of the network, including a thymine (T) to cytosine (C) and a guanine (G) to adenine (A) transition in the upstream repressing sequence (URS) sites of GAL1 and GAL4, respectively, which impair Mig1p-mediated repression, loss of function of the repressor Gal80p through a T146I substitution in the protein, and subsequent futility of GAL3. Furthermore, the milk lineage of S. cerevisiae has achieved galactose-utilization rate elevation and galactose-over-glucose preference switch through the duplication of the introgressed GAL2 and the loss of function of the main glucose transporter genes HXT6 and HXT7. In addition, we demonstrate that GAL2 requires GAL7 or GAL10 for its expression, and Gal2p likely requires Gal1p for its transportation function in the milk lineage of S. cerevisiae. We show a clear case of reverse evolution of a classic gene network for ecological adaptation and provide new insights into the regulatory model of the canonical GAL network.

The origin and adaptive evolution of domesticated populations of yeast from Far East Asia.

The yeast Saccharomyces cerevisiae has been an essential component of human civilization because of its long global history of use in food and beverage fermentation. However, the diversity and evolutionary history of the domesticated populations of the yeast remain elusive. We show here that China/Far East Asia is likely the center of origin of the domesticated populations of the species. The domesticated populations form two major groups associated with solid- and liquid-state fermentation and appear to have originated from heterozygous ancestors, which were likely formed by outcrossing between diverse wild isolates primitively for adaptation to maltose-rich niches. We found consistent gene expansion and contraction in the whole domesticated population, as well as lineage-specific genome variations leading to adaptation to different environments. We show a nearly panoramic view of the diversity and life history of S. cerevisiae and provide new insights into the origin and evolution of the species.

Herceptin functionalized microfluidic polydimethylsiloxane devices for the capture of human epidermal growth factor receptor 2 positive circulating breast cancer cells.

Building on recent breakthroughs in the field of microfluidic-based capture of rare cancer cells circulating in the blood, the present article reports on the use of Herceptin functionalized PDMS devices designed to efficiently capture from blood cancer cells, overexpressing the tyrosine kinase human epidermal growth factor receptor (HER2). The identification of patients overexpressing HER2 is critical as it typically associates with an aggressive disease course in breast cancer and poor prognosis. Importantly, HER2 positive patients have been found to significantly benefit from Herceptin (Trastuzumab), a humanized monoclonal antibody (MAb) against HER2. Disposable PDMS devices prepared using standard soft lithography were functionalized by the plasma polymerization of an epoxy-containing monomer. The epoxy-rich thin film (AGEpp) thus created could be conjugated with Herceptin either directly or through a polyethylene glycol interlayer. The properties and reactivity toward the monoclonal antibody conjugation of these coatings were determined using x-ray photoelectron spectroscopy; direct conjugation provided a good compromise in reactivity and resistance to biologically nonspecific fouling and was selected. Using the breast cancer cell line SK-BR-3 as a model for cells overexpressing HER2, the immunocapture efficacy of the Herceptin functionalized PDMS was demonstrated in model studies. Validation studies confirmed the ability of the device to efficiently capture (∼80% capture yield) HER2 positive cells from full blood.

In vitro susceptibility testing of Aspergillus spp. against voriconazole, itraconazole, posaconazole, amphotericin B and caspofungin.

BACKGROUND: During recent years, the incidence of serious infections caused by opportunistic fungi has increased dramatically due to alterations of the immune status of patients with hematological diseases, malignant tumors, transplantations and so forth. Unfortunately, the wide use of triazole antifungal agents to treat these infections has lead to the emergence of Aspergillus spp. resistant to triazoles. The present study was to assess the in vitro activities of five antifungal agents (voriconazole, itraconazole, posaconazole, amphotericin B and caspofungin) against different kinds of Aspergillus spp. that are commonly encountered in the clinical setting. METHODS: The agar-based Etest MIC method was employed. One hundred and seven strains of Aspergillus spp. (5 species) were collected and prepared according to Etest Technique Manuel. Etest MICs were determined with RPMI agar containing 2% glucose and were read after incubation for 48 hours at 35°C. MIC(50), MIC(90) and MIC range were acquired by Whonet 5.4 software. RESULTS: The MIC(90) of caspofungin against A. fumigatus, A. flavus and A. nidulans was 0.094 µg/ml whereas the MIC(90) against A. niger was 0.19 µg/ml. For these four species, the MIC(90) of caspofungin was the lowest among the five antifungal agents. For A. terrus, the MIC(90) of posaconazole was the lowest. For A. fumigatus and A. flavus, the MIC(90) in order of increasing was caspofungin, posaconazole, voriconazole, itraconazole, and amphotericin B. The MIC of amphotericin B against A. terrus was higher than 32 µg/ml in all 7 strains tested. CONCLUSIONS: The in vitro antifungal susceptibility test shows the new drug caspofungin, which is a kind of echinocandins, has good activity against the five species of Aspergillus spp. and all the triazoles tested have better in vitro activity than traditional amphotericin B.

Short hairpin RNA-mediated inhibition of measles virus replication in vitro.

Rab9 has been identified as a key component for the replication of measles virus (MV). In this study, gene-specific shRNAs were developed to suppress the replication of MV in culture cells by silencing the expression of Rab9 GTPase gene. Rab9 GTPase gene-specific shRNAs were designed and cloned into the expression vector of pSUPER.neo+EGFP. Vero-E6 cells were transfected with the recombinant plasmid via liposome and then infected with MV. The expression of Rab9 GTPase mRNA and protein were assayed by RT-PCR and Western blotting, respectively. ShRNA-mediated inhibition of MV replication was further evaluated by detecting the titer of MV. The results showed that the expression of Rab9 GTPase was dramatically and stably downregulated by the generated shRNAs targeting Rab9 GTPase gene, which contribute to the inhibition of MV replication, indicating these shRNAs could be potentially developed into therapeutic agents for the treatment of MV infection in the future.

{4,4'-Dimeth-oxy-2,2'-[ethyl-enedioxy-bis(nitrilo-methyl-idyne)]diphenolato}copper(II).

The title complex, [Cu(C(18)H(18)N(2)O(6))], was synthesized by the reaction of copper(II) acetate mono-hydrate with the ligand 4,4'-dimeth-oxy-2,2'-[ethyl-enedioxy-bis(nitrilo-methyl-idyne)]diphenol (H(2)L). The Cu atom is coordinated by two O atoms and two N atoms of the L(2-) unit. A bridged dimer is formed through inter-molecular Cu⋯O inter-actions [Cu⋯O = 1.9408 (15) Å], creating a distorted square-pyramidal geometry about the Cu atoms.