Demographic characteristics, clinical information, and neuropsychological tests of three participating groups.

Demographic characteristics, clinical information, and neuropsychological tests of three participating groups.</p

Flow chart.

IntroductionSchizophrenia (SCZ) is characterized by widespread cognitive impairments, such as executive functions. Most of the available research indicate that executive impairment has a certain genetic predisposition. Shared neuropathological characteristics of patients with SCZ and their siblings may reveal intermediate behavioral phenotypes that can be used to further characterize the illness.MethodsOur study involved 32 SCZ patients, 32 unaffected siblings (US), and 33 persons as healthy controls (HCS). These three groups underwent a computerized version of the Wisconsin Card Sorting Test (WCST), and a battery of cognitive neuropsychological assessments. These tests also evaluate executive function and several cognitive domains.ResultsThe performed study on SCZ patients and their unaffected siblings showed an inferior WCST performance to the HCS subjects, further indicating that unaffected siblings have a functional impairment, and they also performed poorly on the neuropsychological assessment compared with the HCS.ConclusionThis result supports the claim that the development of functional impairment is not limited to SCZ patients and unaffected siblings may also have a certain level of abnormal brain function. Consequently. neurological abnormalities lead to the abnormal functioning in siblings and patients, suggesting that genetics plays a considerable role in such results.</div

Assessent of executive functions for SCZ, Unaffected siblings and HCS groups.

TC = the total number of correct responses; TE = the total number of error responses,PR = the number of persistent responses;PE = the number of persistent errors; TCFC = the number of trials to complete the first category;* Significant at P<0.017 ((α = 0.05/3)).</p

Correlation analysis between WCST and neuropsychological tests in patients and unaffected siblings.

Correlation analysis between WCST and neuropsychological tests in patients and unaffected siblings.</p

Correlation analysis between WCST and Clinical symptoms in patients with SCZ.

Correlation analysis between WCST and Clinical symptoms in patients with SCZ.</p

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IntroductionSchizophrenia (SCZ) is characterized by widespread cognitive impairments, such as executive functions. Most of the available research indicate that executive impairment has a certain genetic predisposition. Shared neuropathological characteristics of patients with SCZ and their siblings may reveal intermediate behavioral phenotypes that can be used to further characterize the illness.MethodsOur study involved 32 SCZ patients, 32 unaffected siblings (US), and 33 persons as healthy controls (HCS). These three groups underwent a computerized version of the Wisconsin Card Sorting Test (WCST), and a battery of cognitive neuropsychological assessments. These tests also evaluate executive function and several cognitive domains.ResultsThe performed study on SCZ patients and their unaffected siblings showed an inferior WCST performance to the HCS subjects, further indicating that unaffected siblings have a functional impairment, and they also performed poorly on the neuropsychological assessment compared with the HCS.ConclusionThis result supports the claim that the development of functional impairment is not limited to SCZ patients and unaffected siblings may also have a certain level of abnormal brain function. Consequently. neurological abnormalities lead to the abnormal functioning in siblings and patients, suggesting that genetics plays a considerable role in such results.</div

Quantification of microRNA by DNA–Peptide Probe and Liquid Chromatography–Tandem Mass Spectrometry-Based Quasi-Targeted Proteomics

The distorted and unique expression of microRNAs (miRNAs) in cancer makes them an attractive source of biomarkers. However, one of prerequisites for the application of miRNAs in clinical practice is to accurately profile their expression. Currently available assays normally require pre-enrichment, amplification, and labeling steps, and most of them are semiquantitative. In this study, we converted the signal of target miR-21 into reporter peptide by a DNA-peptide probe and the reporter peptide was ultimately quantified using LC-MS/MS-based targeted proteomics. Specifically, substrate peptide GDKAVLGVDPFR containing reporter peptide AVLGVDPFR and tryptic cleavage site (lysine at position 3) was first designed, followed by the conjugation with DNA sequence that was complementary to miR-21. The newly formed DNA-peptide probe was then hybridized with miR-21, which was biotinylated and attached to streptavidin agarose in advance. After trypsin digestion, the reporter peptide was released and monitored by a targeted proteomics assay. The obtained limit of quantification (LOQ) was 1 pM, and the detection dynamic range spanned ∼5 orders of magnitude. Using this assay, the developed quasi-targeted proteomics approach was applied to determine miR-21 level in breast cells and tissue samples. Finally, qRT-PCR was also performed for a comparison. This report grafted the strategy of targeted proteomics into miRNA quantification

Compositional Analysis of Asymmetric and Symmetric Dimethylated H3R2 Using Liquid Chromatography–Tandem Mass Spectrometry-Based Targeted Proteomics

Protein arginine methylation is one of the common post-translational modifications in cellular processes. To date, two isomeric forms of dimethylated arginine have been identified: asymmetric <i>N</i>^G,<i>N</i>^G-dimethylarginine (aDMA), and symmetric <i>N</i>^G,<i>N</i>′^G-dimethylarginine (sDMA). Evidence indicated that these isomers can coexist and have different or even opposite functions, with aDMA and sDMA forms of arginine 2 on histone H3 (i.e., H3R2me2a and H3R2me2s) being an example. Thus, specific detection and quantification of each isomeric form is important. Current methods are capable of predicting and detecting thousands of methylarginine sites in proteins, whereas differentiation and stoichiometric measurement of dimethylated protein isomers are still challenging. Liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS)-based targeted proteomics has emerged as a promising technique for site-specific quantification of protein methylation using enzymatic peptides as surrogates of target proteins. However, it should be pointed out that a routine targeted proteomics strategy cannot easily distinguish sDMA- and aDMA-containing surrogate peptides due to their common nature. The estimated amount should be considered as the sum of both arginine dimethylated isomers. In this study, compositional analysis based on a linear algebra algorithm as an add-on to targeted proteomics was employed to quantify H3R2me2a and H3R2me2s (i.e., surrogate peptides of AR­(me2a)­TK­(me1/2)­QT and AR­(me2s)­TK­(me1/2)­QT). To achieve this simultaneous quantification, a targeted proteomics assay was developed and validated for each isomer first. With the slope and intercept of their calibration curves for each multiple reaction monitoring (MRM) transition, linear algebraic equations were derived. Using a series of mock mixtures consisting of isomers in varying concentrations, the reliability of the method was confirmed. Finally, the H3R2 dimethylation status was analyzed in normal MCF-10A cells, parental drug-sensitive MCF-7/WT cancer cells, and drug-resistant MCF-7/ADR cancer cells. Dimethylated H3R2 was also monitored in MCF-7/WT cells with the treatment of doxorubicin (DOX) for confirmation

Duplex-Specific Nuclease-Mediated Amplification Strategy for Mass Spectrometry Quantification of MiRNA-200c in Breast Cancer Stem Cells

MicroRNAs (miRNAs) play a significant role in numerous biological processes and are implicated in a range of cancers, including breast cancer. MiRNAs have the potential to be biomarkers in clinical practice because of their distorted and unique expression, especially with regard to their presence in cancer stem cells (CSCs) that have applications in cancer diagnosis and treatment. Thus, the absolute determination of miRNA expression levels is a prerequisite for exploring their applications. Nevertheless, currently available methods may not be adequate for the detection of miRNAs in CSCs due to the inherently low population of these cells. Therefore, we combined a duplex-specific nuclease (DSN)-mediated amplification strategy with liquid chromatography–tandem mass spectrometry (LC–MS/MS) for use in this study. We designed the substrate peptide GDKAVLGVDPFR, which contains the reporter peptide AVLGVDPFR and a tryptic cleavage site (lysine at position 3) in combination with a biotinylated DNA sequence that was complementary to a target miRNA (i.e., miR-200c). Then, this newly synthesized DNA-peptide probe was hybridized with the target miRNA. Upon the introduction of the DSN, the enzyme degraded the probe into two parts where the target miRNA was integrated and thereby triggered further cleavage. The accumulated peptide fragments were ultimately digested with trypsin to release the reporter peptide for LC–MS/MS quantification. Under these circumstances, the miRNA signal was converted and amplified into a mass response of the reporter peptide. After optimization of the parameters, including temperature, hybridization/DSN time, and the amounts of DSN and streptavidin agarose beads, we demonstrated a linear detection range between 1 fM and 200 fM for miR-200c. The detection limit obtained was 3 orders of magnitude lower than those previously reported. Finally, quantification of miR-200c in breast cancer stem cells (BCSCs) and in stem cells isolated from breast tumors was performed. We also compared these data with quantitative reverse transcription PCR (qRT-PCR) results

Data_Sheet_1_How Does the Horizontal Position of Pictures and Text Affect Product Evaluation? Based on Left and Right Position Effect.ZIP

Due to the untouchability of online shopping environment, image and text description, as two main ways of product information display, are important indicators for consumers to evaluate products. However, few studies have discussed the synergistic effects of image and text information on consumers. In the present study, in conjunction with the left-right position effect, we examine the expectation that horizontal placement of visual stimuli in different directions has a strong influence on consumers’ product evaluation preferences. This implicit assumption is based on consumers’ unconscious psychological need for closure when processing information. The authors conducted three studies to investigate the relative effects of image information and text statements at different locations in online shopping pages on consumer product evaluations. The results show that: (1) when the evaluation object is a search product, compared with the display mode of left text-right image, the display mode of left image-right text plays a more significant role in consumer product evaluation. The results of experiential products were just the opposite. The way of presenting the text declaration on the left and image on the right has a stronger impact on consumers’ evaluation preference for experiential products (Study 1 and Study 3). (2) The difference in consumers’ evaluation mode of different presentation sequences based on product attributes is driven by their visual information processing fluency (Study 2). These preferences are robust, and it is worth noting that only the order of graphic presentation has no significant influence on consumer product evaluation preference.</p