Visualization of facet-dependent pseudo-photocatalytic behavior of TiO2 nanorods for water splitting using In situ liquid cell TEM

We report an investigation of the pseudo-photocatalytic behavior of rutile TiO2 nanorods for water splitting observed with liquid cell transmission electron microscopy (TEM). The electron beam serves as a “light” source to initiate the catalytic reaction and a “water-in-salt” aqueous solution is employed as the electrolyte. The observation reveals that bubbles are generated preferentially residing near the {110} facet of a rutile TiO2 nanorod under a low electron dose rate (9.3–18.6 e-/Å2·s). These bubbles are ascribed to hydrogen gas generated from the pseudo-photocatalytic water splitting. As the electron beam current density increases to 93 e-/Å2 ·s, bubbles are also found at the {001} and {111} facets as well as in the bulk liquid solution, demonstrating the dominant effects of water electrolysis by electron beam under higher dose rates. The facet-dependent pseudo-photocatalytic behavior of rutile TiO2 nanorods is further validated using density functional theory (DFT)calculation. Our work establishes a facile liquid cell TEM setup for the study of pseudo-photocatalytic water splitting and it may also be applied to investigation of other photo-activated phenomena occurring at the solid-liquid interfaces

The endogenous hydrogen sulfide producing enzyme cystathionine-β synthase contributes to visceral hypersensitivity in a rat model of irritable bowel syndrome

<p>Abstract</p> <p>Background</p> <p>The pathogenesis of visceral hypersensitivity, a characteristic pathophysiological feature of irritable bowel syndrome (IBS), remains elusive. Recent studies suggest a role for hydrogen sulfide (H₂S) in pain signaling but this has not been well studied in visceral models of hyperalgesia. We therefore determined the role for the endogenous H₂S producing enzyme cystathionine-β-synthetase (CBS) in a validated rat model of IBS-like chronic visceral hyperalgesia (CVH). CVH was induced by colonic injection of 0.5% acetic acid (AA) in 10-day-old rats and experiments were performed at 8–10 weeks of age. Dorsal root ganglion (DRG) neurons innervating the colon were labeled by injection of DiI (1,1'-dioleyl-3,3,3',3-tetramethylindocarbocyanine methanesulfonate) into the colon wall.</p> <p>Results</p> <p>In rat DRG, CBS-immunoreactivity was observed in approximately 85% of predominantly small- and medium-sized neurons. Colon specific DRG neurons revealed by retrograde labeling DiI were all CBS-positive. CBS-positive colon neurons co-expressed TRPV1 or P2X3 receptors. Western blotting analysis showed that CBS expression was significantly increased in colon DRGs 8 weeks after neonatal AA-treatment. Furthermore, the CBS inhibitor hydroxylamine markedly attenuated the abdominal withdrawal reflex scores in response to colorectal distention in rats with CVH. By contrast, the H₂S donor NaHS significantly enhanced the frequency of action potentials of colon specific DRG neurons evoked by 2 times rheobase electrical stimulation.</p> <p>Conclusion</p> <p>Our results suggest that upregulation of CBS expression in colonic DRG neurons and H₂S signaling may play an important role in developing CVH, thus identifying a specific neurobiological target for the treatment of CVH in functional bowel syndromes.</p

Identity-by-descent filtering as a tool for the identification of disease alleles in exome sequence data from distant relatives

Large-scale, deep resequencing may be the next logical step in the genetic investigation of common complex diseases. Because each individual is likely to carry many thousands of variants, the identification of causal alleles requires an efficient strategy to reduce the number of candidate variants. Under many genetic models, causal alleles can be expected to reside within identity-by-descent (IBD) regions shared by affected relatives. In distant relatives, IBD regions constitute a small portion of the genome and can thus greatly reduce the search space for causal alleles. However, the effectiveness of this strategy is unknown. We test the simulated mini-exome data set in extended pedigrees provided by Genetic Analysis Workshop 17. At the fourth- and fifth-degree level of relatedness, case-case pairs shared between 1% and 9% of the genome identical by descent. As expected, no genes were shared identical by descent by all case subjects, but 43 genes were shared by many case subjects across at least 50 replicates. We filtered variants in these genes based on population frequency, function, informativeness, and evidence of association using the family-based association test. This analysis highlighted five genes previously implicated in triglyceride, lipid, and cholesterol metabolism. Comparison with the list of true risk alleles revealed that strict IBD filtering followed by association testing of the rarest alleles was the most sensitive strategy. IBD filtering may be a useful strategy for narrowing down the list of candidate variants in exome data, but the optimal degree of relatedness of affected pairs will depend on the genetic architecture of the disease under study

Polymorphisms of Glutathione S-transferases Omega-1 among ethnic populations in China

<p>Abstract</p> <p>Background</p> <p>Glutathione S-transferases (GSTs) is a genetic factor for many diseases and exhibits great diversities among various populations. We assessed association of the genotypes of Glutathione S-transferases Omega-1 (GSTO1) A140D with ethnicity in China.</p> <p>Results</p> <p>Peripheral blood samples were obtained from 1314 individuals from 14 ethnic groups. Polymorphisms of GSTO1 A140D were measured using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Logistic regression was employed to adjustment for regional factor. The frequency of GSTO1 140A allele was 15.49% in the total 14 ethnic populations. Compared to Han ethnic group, two ethnic populations were more likely to have AA or CA genotype [odds ratio (OR): 1.77, 95% confidence interval (95% CI): 1.05–2.98 for Uygur and OR: 1.78, 95% CI: 1.18–2.69 for Hui]. However, there were no statistically significant differences across 14 ethnic groups when region factor was adjusted. In Han ethnicity, region was significantly associated with AA or CA genotype. Han individuals who resided in North-west of China were more likely to have these genotypes than those in South of China (OR: 1.63, 95% CI: 1.21–2.20).</p> <p>Conclusion</p> <p>The prevalence of the GSTO1 140A varied significantly among different regional populations in China, which showed that geography played a more important role in the population differentiation for this allele than the ethnicity/race.</p

The motivational drive to natural rewards is modulated by prenatal glucocorticoid exposure

Exposure to elevated levels of glucocorticoids (GCs) during neurodevelopment has been identified as a triggering factor for the development of reward-associated disorders in adulthood. Disturbances in the neural networks responsible for the complex processes that assign value to rewards and associated stimuli are critical for disorders such as depression, obsessive–compulsive disorders, obesity and addiction. Essential in the understanding on how cues influence behavior is the Pavlovian–instrumental transfer (PIT), a phenomenon that refers to the capacity of a Pavlovian stimulus that predicts a reward to elicit instrumental responses for that same reward. Here, we demonstrate that in utero exposure to GCs (iuGC) impairs both general and selective versions of the PIT paradigm, suggestive of deficits in motivational drive. The iuGC animals presented impaired neuronal activation pattern upon PIT performance in cortical and limbic regions, as well as morphometric changes and reduced levels of dopamine in prefrontal and orbitofrontal cortices, key regions involved in the integration of Pavlovian and instrumental stimuli. Normalization of dopamine levels rescued this behavior, a process that relied on D2/D3, but not D1, dopamine receptor activation. In summary, iuGC exposure programs the mesocorticolimbic dopaminergic circuitry, leading to a reduction in the attribution of the incentive salience to cues, in a dopamine-D2/D3-dependent manner. Ultimately, these results are important to understand how GCs bias incentive processes, a fact that is particularly relevant for disorders where differential attribution of incentive salience is critical.We thank Pedro Morgado for discussions and help in the technical aspects of PIT procedure. This project was supported by a grant of Institute for the Study of Affective Neuroscience (ISAN) and by Janssen Neuroscience Prize. CS-C, SB, MMC and AJR are recipients of Fundacao para a Ciencia e Tecnologia (FCT) fellowships (CS-C: SFRH/BD/51992/2012; SB: SFRH/BD/89936/2012; MMC: SRFH/BD/51061/2010; AJR: SFRH/BPD/33611/2009)

Assisted evolution enables HIV-1 to overcome a high trim5α-imposed genetic barrier to rhesus macaque tropism

Diversification of antiretroviral factors during host evolution has erected formidable barriers to cross-species retrovirus transmission. This phenomenon likely protects humans from infection by many modern retroviruses, but it has also impaired the development of primate models of HIV-1 infection. Indeed, rhesus macaques are resistant to HIV-1, in part due to restriction imposed by the TRIM5α protein (rhTRIM5α). Initially, we attempted to derive rhTRIM5α-resistant HIV-1 strains using two strategies. First, HIV-1 was passaged in engineered human cells expressing rhTRIM5α. Second, a library of randomly mutagenized capsid protein (CA) sequences was screened for mutations that reduced rhTRIM5α sensitivity. Both approaches identified several individual mutations in CA that reduced rhTRIM5α sensitivity. However, neither approach yielded mutants that were fully resistant, perhaps because the locations of the mutations suggested that TRIM5α recognizes multiple determinants on the capsid surface. Moreover, even though additive effects of various CA mutations on HIV-1 resistance to rhTRIM5α were observed, combinations that gave full resistance were highly detrimental to fitness. Therefore, we employed an 'assisted evolution' approach in which individual CA mutations that reduced rhTRIM5α sensitivity without fitness penalties were randomly assorted in a library of viral clones containing synthetic CA sequences. Subsequent passage of the viral library in rhTRIM5α-expressing cells resulted in the selection of individual viral species that were fully fit and resistant to rhTRIM5α. These viruses encoded combinations of five mutations in CA that conferred complete or near complete resistance to the disruptive effects of rhTRIM5α on incoming viral cores, by abolishing recognition of the viral capsid. Importantly, HIV-1 variants encoding these CA substitutions and SIVmac239 Vif replicated efficiently in primary rhesus macaque lymphocytes. These findings demonstrate that rhTRIM5α is difficult to but not impossible to evade, and doing so should facilitate the development of primate models of HIV-1 infection

Upregulation of the cell-cycle regulator RGC-32 in Epstein-Barr virus-immortalized cells

Epstein-Barr virus (EBV) is implicated in the pathogenesis of multiple human tumours of lymphoid and epithelial origin. The virus infects and immortalizes B cells establishing a persistent latent infection characterized by varying patterns of EBV latent gene expression (latency 0, I, II and III). The CDK1 activator, Response Gene to Complement-32 (RGC-32, C13ORF15), is overexpressed in colon, breast and ovarian cancer tissues and we have detected selective high-level RGC-32 protein expression in EBV-immortalized latency III cells. Significantly, we show that overexpression of RGC-32 in B cells is sufficient to disrupt G2 cell-cycle arrest consistent with activation of CDK1, implicating RGC-32 in the EBV transformation process. Surprisingly, RGC-32 mRNA is expressed at high levels in latency I Burkitt's lymphoma (BL) cells and in some EBV-negative BL cell-lines, although RGC-32 protein expression is not detectable. We show that RGC-32 mRNA expression is elevated in latency I cells due to transcriptional activation by high levels of the differentially expressed RUNX1c transcription factor. We found that proteosomal degradation or blocked cytoplasmic export of the RGC-32 message were not responsible for the lack of RGC-32 protein expression in latency I cells. Significantly, analysis of the ribosomal association of the RGC-32 mRNA in latency I and latency III cells revealed that RGC-32 transcripts were associated with multiple ribosomes in both cell-types implicating post-initiation translational repression mechanisms in the block to RGC-32 protein production in latency I cells. In summary, our results are the first to demonstrate RGC-32 protein upregulation in cells transformed by a human tumour virus and to identify post-initiation translational mechanisms as an expression control point for this key cell-cycle regulator

How Can Home Care Patients and Their Caregivers Better Manage Fall Risks by Leveraging Information Technology?

Objectives: From the perspectives of home care patients and caregivers, this study aimed to (a) identify the challenges for better fall-risk management during home care episodes and (b) explore the opportunities for them to leverage health information technology (IT) solutions to improve fall-risk management during home care episodes. Methods: Twelve in-depth semistructured interviews with the patients and caregivers were conducted within a descriptive single case study design in 1 home health agency (HHA) in the mid-Atlantic region of the United States. Results: Patients and caregivers faced challenges to manage fall risks such as unmanaged expectations, deteriorating cognitive abilities, and poor care coordination between the HHA and physician practices. Opportunities to leverage health IT solutions included patient portals, telehealth, and medication reminder apps on smartphones. Conclusion: Effectively leveraging health IT could further empower patients and caregivers to reduce fall risks by acquiring the necessary information and following clinical advice and recommendations. The HHAs could improve the quality of care by adopting IT solutions that show more promise of improving the experiences of patients and caregivers in fall-risk management

Leadership Competencies for Digital Transformation : Evidence from Multiple Cases

Digital transformation (DT) is disrupting industrial organizations, which require significant changes in their properties to remain competitive. This calls for strong leadership to drive this transformation. However, what leadership competencies are required to lead DT impactfully is unclear. Therefore, we seek to identify the key leadership competencies by employing a qualitative, grounded theory approach. By conducting interviews of ten DT experts from two hardcore industrial organizations, we highlight five key leadership competencies that industrial organizations need to develop in their leaders: digital vision, digital knowledge, failing fast, empowerment, and managing diverse teams. The results of this study will help industrial organizations to strategically prepare their leadership for the requirements of DT.©2020 Springer. This is a post-peer-review, pre-copyedit version of an article published in Advances in Human Factors, Business Management and Leadership: Proceedings of the AHFE 2020 Virtual Conferences on Human Factors, Business Management and Society, and Human Factors in Management and Leadership, July 16-20, 2020, USA. The final authenticated version is available online at: http://dx.doi.org/0.1007/978-3-030-50791-6_11.fi=vertaisarvioitu|en=peerReviewed