How to Set Focal Categories for Brief Implicit Association Test? “Good” Is Good, “Bad” Is Not So Good

Three studies were conducted to examine the validity of the four versions of BIATs that are supposed to measure the same construct but differ in shared focal category. Study 1 investigated the criterion validity of four BIATs measuring attitudes toward flower versus insect. Study 2 examined the experimental sensitivity of four BIATs by considering attitudes toward induced ingroup versus outgroup. Study 3 examined the predictive power of the four BIATs by investigating attitudes toward the commercial beverages Coke versus Sprite. The findings suggested that for the two attributes good and bad, good rather than bad proved to be good as a shared focal category; for two targets, so long as they clearly differed in goodness or valence, the good rather than bad target emerged as good for a shared focal category. Beyond this case, either target worked well. These findings may facilitate the understanding of the BIAT and its future applications

Stereotactic Body Radiation Therapy for Patients with Heavily Pretreated Liver Metastases and Liver Tumors

We present our initial experience with CyberKnife stereotactic body radiation therapy (SBRT) in a heavily pretreated group of patients with liver metastases and primary liver tumors. From October 2007 to June 2009, 48 patients were treated at the Philadelphia CyberKnife Center for liver metastases or primary liver tumors. We report on 30 patients with 41 discrete lesions (1–4 tumors per patient) who received an ablative radiation dose (BED ≥ 79.2 Gy10 = 66 Gy EQD2). The treatment goal was to achieve a high SBRT dose to the liver tumor while sparing at least 700 cc of liver from radiation doses above 15 Gy. Twenty-three patients were treated with SBRT for metastatic cancer to the liver; the remainder (n = 7) were primary liver tumors. Eighty-seven percent of patients had prior systemic chemotherapy with a median 24 months from diagnosis to SBRT; 37% had prior liver directed therapy. Local control was assessed for 28 patients (39 tumors) with 4 months or more follow-up. At a median follow-up of 22 months (range, 10–40 months), 14/39 (36%) tumors had documented local failure. A decrease in local failure was found with higher doses of SBRT (p = 0.0237); 55% of tumors receiving a BED ≤ 100 Gy10 (10/18) had local failure compared with 19% receiving a BED > 100 Gy10 (4/21). The 2-year actuarial rate of local control for tumors treated with BED > 100 Gy10 was 75% compared to 38% for those patients treated with BED ≤ 100 Gy10 (p = 0.04). At last follow-up, 22/30 patients (73%) had distant progression of disease. Overall, seven patients remain alive with a median survival of 20 months from treatment and 57 months from diagnosis. To date, no patient experienced persistent or severe adverse effects. Despite the heavy pretreatment of these patients, SBRT was well tolerated with excellent local control rates when adequate doses (BED > 100 Gy10) were used. Median survival was limited secondary to development of further metastatic disease in the majority of patients

Dopaminergic neuronal differentiation from the forebrain-derived human neural stem cells induced in cultures by using a combination of BMP-7 and pramipexole with growth factors

Transplantation of dopaminergic (DA) neurons is considered to be the most promising therapeutic strategy for replacing degenerated dopamine cells in the midbrain of Parkinson’s disease (PD), thereby restoring normal neural circuit function and slow clinical progression of the disease. Human neural stem cells (hNSCs) derived from fetal forebrain are thought to be the important cell sources for producing DA neurons because of their multipotency for differentiation and long-term expansion property in cultures. However, low DA differentiation of the forebrain-derived hNSCs limited their therapeutic potential in PD. In the current study, we explored a combined application of Pramipexole (PRX), bone morphogenetic proteins 7 (BMP-7), and growth factors, including acidic fibroblast factor (aFGF), forskolin, and phorbol-12-myristae-13-acetate (TPA), to induce differentiation of forebrain-derived hNSCs towards DA neurons in cultures. We found that DA neuron-associated genes, including Nurr1, Neurogenin2 (Ngn2), and tyrosine hydroxylase (TH) were significantly increased after 24h of differentiation by RT-PCR analysis (p<0.01). Fluorescent examination showed that about 25% of cells became TH-positive neurons at 24h, about 5% of cells became VMAT2 (vascular monoamine transporter 2)-positive neurons, and less than 5% of cells became DAT (dopamine transporter)-positive neurons at 72h following differentiation in cultures. Importantly, these TH-， VMAT2- and DAT-expressing neurons were able to release dopamine into cultures under both of the basal and evoked conditions. Dopamine levels released by DA neurons produced using our protocol were significantly higher compared to the control groups (P<0.01), as examined by ELISA. Our results demonstrated that the combination of PRX, BMP-7, and growth factors was able to greatly promote differentiation of the forebrain-derived hNSCs into DA-releasing neurons

iTRAQ protein profile analysis of Neuroblastoma (NA) cells infected with the Rabies Viruses rHep-Flury and Hep-dG

The rabies virus (RABV) glycoprotein (G) is the principal contributor to the pathogenicity and protective immunity of RABV. In a previous work, we reported that recombinant rabies virus Hep-dG, which was generated by reverse genetics to carry two copies of the G-gene, showed lower virulence than the parental virus rHep-Flury in suckling mice with a better immune protection effect. To better understand the mechanisms underlying rabies virus attenuation and the role of glycoprotein G, isobaric tags for relative and absolute quantitation (iTRAQ) was performed to identify and quantify distinct proteins. 10 and 111 differentially expressed proteins were obtained in rHep-Flury and Hep-dG infection groups, respectively. Selected data were validated by western blot and qRT-PCR. Bioinformatics analysis of the distinct protein suggested that glycoprotein over-expression in the attenuated RABV strain can induce activation of the interferon signaling. Furthermore, it may promote the antiviral response, MHC-I mediated antigen-specific T cell immune response, apoptosis and autophagy in an IFN-dependent manner. These findings might not only improve the understanding of the dynamics of RABV and host interaction, but also help understand the mechanisms underlying innate and adaptive immunity during RABV infection

Expression of Agrobacterium homolog genes encoding T-complex recruiting protein under virulence induction conditions

Proteins encoded by three Agrobacterial genes atu5117, atu4860 and atu4856 are highly homologous to each other in amino acid sequence. All three proteins are able to bind VirD2 and named as VBP1, VBP2 and VBP3 (VirD2-binding protein) respectively. VBP is involved in the T-DNA transfer by recruiting the T-complex to T4SS and defined as T-complex recruiting protein. To know whether these three homologous genes are expressed differently under virulence induction conditions, we tested the effects of virulence induction conditions, including varied pH, temperature and acetosyringone concentration, on the expressions of three VBP-encoding genes. Our data showed that atu5117 and atu4856 maintained constant expression under the tested induction conditions, whereas the expression of atu4860 was affected by the culture conditions. The culture conditions favorable to the expression of atu4860 differ from the reported induction conditions for other virulence proteins. Especially, pH value was a crucial factor for the expression of atu4860. Moreover, the deletion of atu5117 affected the expression of atu4860. These results suggest that the mechanisms regulating the expression of these three homologous genes are different from the virulence induction mechanism and that VBP homologs are presumably involved in other biological processes in addition to T-complex recruitment

Listeria monocytogenes varies among strains to maintain intracellular pH homeostasis under stresses by different acids as analyzed by a high-throughput microplate-based fluorometry

Listeria monocytogenes, a food-borne pathogen, has the capacity to maintain intracellular pH (pHi) homeostasis in acidic environments, but the underlying mechanisms remain elusive. Here, we report a simple microplate-based fluorescent method to determine pHi of listerial cells that were prelabeled with the fluorescent dye carboxyfluorescein diacetate N-succinimidyl ester and subjected to acid stress. We found that L. monocytogenes responds differently among strains toward organic and inorganic acids to maintain pHi homeostasis. The capacity of L. monocytogenes to maintain pHi at extracellular pH 4.5 (pHex) was compromised in the presence of acetic acid and lactic acid, but not by hydrochloric acid and citric acid. Organic acids exhibited more inhibitory effects than hydrochloric acid at certain pH conditions. Furthermore, the virulent stains L. monocytogenes EGDe, 850658 and 10403S was more resistant to acidic stress than the avirulent M7 which showed a defect in maintaining pHi homeostasis. Deletion of sigB, a stress-responsive alternative sigma factor from 10403S, markedly altered intracellular pHi homeostasis, and showed a significant growth and survival defect under acidic conditions. Thus, this work provides new insights into bacterial survival mechanism to acidic stresses

A new tool to measure malevolent creativity: The malevolent creativity behavior scale

The present study developed the malevolent creativity behavior scale (MCBS), which contains 13 items and was designed to measure individuals’ malevolent creativity through the behavior of daily lives. A total of 958 participants from different regions of China completed the MCBS in an online fashion. Cronbach’α coefficient, using the 908 MCBSs with entirely complete data, indicated that the MCBS had satisfactory reliability. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) revealed that the MCBS had 3 dimensions: hurting people, lying, and playing tricks. MCBS scores were positively correlated with individuals’ aggression, openness, extraversion, and scores on the Runco Ideational Behavior Scale (RIBS). MCBS scores also predicted individuals’ malevolent creativity performances when solving realistic, open-ended problems. The MCBS has a simple response medium and scoring procedure. This, along with the adequate psychometric properties uncovered here, indicates that it is a useful tool for research on malevolent creativity. Given that the MCBS contains a relatively small number of categories and items, further research could expand the categories of items and develop and test more items. Moreover, it would be useful to test MCBS’s reliability and validity with other criteria. Perhaps future research could obtain actual MC data from criminal or other unambiguously malevolent samples

Intrinsic plasmids influence MicF-mediated translational repression of ompF in Yersinia pestis

Yersinia pestis, which is the causative agent of plague, has acquired exceptional pathogenicity potential during its evolution from Y. pseudotuberculosis. Two laterally acquired plasmids, namely, pMT1 and pPCP1, are specific to Y. pestis and are critical for pathogenesis and flea transmission. Small regulatory RNAs (sRNAs) commonly function as regulators of gene expression in bacteria. MicF, is a paradigmatic sRNA that acts as a post-transcriptional repressor through imperfect base pairing with the 5’-UTR of its target mRNA, ompF, in Escherichia coli. The high sequence conservation and minor variation in the RNA duplex of MicF-ompF has been reported in Yersinia. In this study, we utilized super-folder GFP reporter gene fusion to validate the post-transcriptional MicF-mediated regulation of target mRNA ompF in Y. pestis. Unexpectedly, upon MicF overexpression, the slightly upregulated expression of OmpF were found in the wild-type strain, which contradicted the previously established model. Interestingly, the translational repression of ompF target fusions was restored in the intrinsic plasmids-cured Y. pestis strain, suggesting intrinsic plasmids influence the MicF-mediated translational repression of ompF in Y. pestis. Further examination showed that plasmid pPCP1 is likely the main contributor to the reversal of MicF-mediated translational repression of ompF. It represents that the possible roles o

Altered morphologies and functions of the olfactory bulb and hippocampus induced by miR-30c

Adult neurogenesis is considered to contribute to a certain degree of plasticity for the brain. However, the effects of adult-born neurons on the brain are still largely unknown. Here, we specifically altered the expression of miR-30c in the subventricular zone (SVZ) and dentate gyrus (DG) by stereotaxic injection with their respective up-and down-regulated lentiviruses. Results showed an increased level of miR-30c enhanced adult neurogenesis by prompting cell-cycles of stem cells, whereas down-regulated miR-30c led to the opposite results. When these effects of miR-30c lasted for three months, we detected significant morphological changes in the olfactory bulb (OB) and lineage alteration in the hippocampus. Tests of olfactory sensitivity and associative and spatial memory showed that a certain amount of adult-born neurons are essential for the normal functions of the OB and hippocampus, but there also exist redundant newborn neurons that do not further improve the functioning of these areas. Our study revealed the interactions between miRNA, adult neurogenesis, brain morphology and function, and this provides a novel insight into understanding the role of newborn neurons in the adult brain

Heat shock proteins IbpA and IbpB are required for NlpI-participated cell division in Escherichia coli

Lipoprotein NlpI of Escherichia coli is involved in the cell division, virulence and bacterial interaction with eukaryotic host cells. To elucidate the functional mechanism of NlpI, we examined how NlpI affects cell division and found that induction of NlpI inhibits nucleoid division and halts cell growth. Consistent with these results, the cell division protein FtsZ failed to localize at the septum but diffused in the cytosol. Elevation of NlpI expression enhanced the transcription and the outer membrane localization of the heat shock protein IbpA and IbpB. Deletion of either ibpA or ibpB abolished the effects of NlpI induction, which could be restored by complementation. The C-terminus of NlpI is critical for the enhancement in IbpA and IbpB production, and the N-terminus of NlpI is required for the outer membrane localization of NlpI, IbpA, and IbpB. Furthermore, NlpI physically interacts with IbpB. These results indicate that over-expression of NlpI can interrupt the nucleoids division and the assembly of FtsZ at the septum, mediated by IbpA/IbpB, suggesting a role of the NlpI/IbpA/IbpB complex in the cell division