Identification of Genes Directly Involved in Shell Formation and Their Functions in Pearl Oyster, Pinctada fucata

Mollusk shell formation is a fascinating aspect of biomineralization research. Shell matrix proteins play crucial roles in the control of calcium carbonate crystallization during shell formation in the pearl oyster, Pinctada fucata. Characterization of biomineralization-related genes during larval development could enhance our understanding of shell formation. Genes involved in shell biomineralization were isolated by constructing three suppression subtractive hybridization (SSH) libraries that represented genes expressed at key points during larval shell formation. A total of 2,923 ESTs from these libraries were sequenced and gave 990 unigenes. Unigenes coding for secreted proteins and proteins with tandem-arranged repeat units were screened in the three SSH libraries. A set of sequences coding for genes involved in shell formation was obtained. RT-PCR and in situ hybridization assays were carried out on five genes to investigate their spatial expression in several tissues, especially the mantle tissue. They all showed a different expression pattern from known biomineralization-related genes. Inhibition of the five genes by RNA interference resulted in different defects of the nacreous layer, indicating that they all were involved in aragonite crystallization. Intriguingly, one gene (UD_Cluster94.seq.Singlet1) was restricted to the ‘aragonitic line’. The current data has yielded for the first time, to our knowledge, a suite of biomineralization-related genes active during the developmental stages of P.fucata, five of which were responsible for nacreous layer formation. This provides a useful starting point for isolating new genes involved in shell formation. The effects of genes on the formation of the ‘aragonitic line’, and other areas of the nacreous layer, suggests a different control mechanism for aragonite crystallization initiation from that of mature aragonite growth

Slit2–Robo4 signalling promotes vascular stability by blocking Arf6 activity

Slit–Roundabout (Robo) signalling has a well-understood role in axon guidance1–5. Unlike in the nervous system, however, Slitdependent activation of an endothelial-specific Robo, Robo4, does not initiate a guidance program. Instead, Robo4 maintains the barrier function of the mature vascular network by inhibiting neovascular tuft formation and endothelial hyperpermeability induced by pro-angiogenic factors 6. In this study, we used cell biological and biochemical techniques to elucidate the molecular mechanism underlying the maintenance of vascular stability by Robo4. Here, we demonstrate that Robo4 mediates Slit2-dependent suppression of cellular protrusive activity through direct interaction with the intracellular adaptor protein paxillin and its paralogue, Hic-5. Formation of a Robo4–paxillin complex at the cell surface blocks activation of the small GTPase Arf6 and, consequently, Rac by recruitment of Arf-GAPs (ADP-ribosylation factor- directed GTPase-activating proteins) such as GIT1. Consistent with these in vitro studies, inhibition of Arf6 activity in vivo phenocopies Robo4 activation by reducing pathologic angiogenesis in choroidal and retinal vascular disease and VEGF-165 (vascular endothelial growth factor-165)-induced retinal hyperpermeability. These data reveal that a Slit2–Robo4–paxillin–GIT1 network inhibits the cellular protrusive activity underlying neovascularization and vascular leak, and identify a new therapeutic target for ameliorating diseases involving the vascular system

Repairing Integrity-Based Trust Violations in Ascription Disputes for Potential E-Commerce Customers

Trust violations of online sellers are widely reported in customer reviews and are often ascribed to the sellers’ lack of integrity. These reported violations reduce potential customers’ trust in the accused sellers, given the critical role of seller integrity in e-commerce. However, accused sellers and buyers often dispute the ascriptions of trust violations (e.g., sellers may argue that a violation is due to their lack of competence instead of their integrity). The trust repair literature has inadequately focused on effective strategies to repair reported integrity-based trust violations in ascription disputes. Drawing upon attribution theory and individuals’ cognitive sensemaking process regarding trust violations, we propose an account-based approach through re-ascription and stability attributions, enabling accused sellers to repair potential customers’ trust in them in the event of such disputes. We theorize the effectiveness of this approach by considering the contingent role of the accused seller’s reputation. The results of our laboratory experiments confirm the effectiveness of our approach in repairing potential customers’ trust for sellers with a high reputation but not for sellers with a low reputation. We further investigate the effectiveness of disclosing substantive amends (i.e., financial compensation) made by the accused seller to the victim as an alternative approach to repairing potential customers’ trust in sellers with a low reputation. The results reveal the significant effects of disclosing substantive amends on repairing potential customers’ trust in the seller, regardless of the seller’s reputation

Can Positive Online Social Cues Always Reduce User Avoidance of Sponsored Search Results?

Online social cues that utilize user-generated data, such as user reviews and product ratings, have become one of the key factors influencing online user behavior and decisions. Online users who shared their reviews and ratings about a product (or a seller) become an abstract reference group to a focal user interested in the same product. This study focuses on sponsored search results (SSRs), a type of unsolicited information that matches users’ search queries and receives high evaluations from prior consumers. We investigate the effects of positive social cues on alleviating users’ avoidance responses toward an encountered SSR when searching for a product in a C2C e-commerce context. We synthesize the avoidance literature and identify three forms of SSR avoidance, namely, cognitive, behavioral, and affective avoidance. We apply users’ implicit concerns on SSRs to explain users’ avoidance of an encountered SSR. In addition, we extend social influence theory to online settings where abstract reference groups are posited to trigger social influence. We examine how and under what conditions the three forms of SSR avoidance can be reduced by various positive online social cues (i.e., product- and seller-related). We conduct three laboratory experiments. Results attest to users’ implicit concerns on SSRs and their avoidance of SSRs and reveal different effects of various social cues on reducing the three forms of SSR avoidance. This study uncovers the theoretical mechanisms of social influence on reducing SSR avoidance in online settings. It also offers practical implications for online search service providers to help online users’ decision making in their search process

Timing of Alzheimers Disease by Intellectual Disability Level in Down Syndrome.

BACKGROUND: Trisomy 21 causes Down syndrome (DS) and is a recognized cause of early-onset Alzheimers disease (AD). OBJECTIVE: The current study sought to determine if premorbid intellectual disability level (ID) was associated with variability in age-trajectories of AD biomarkers and cognitive impairments. General linear mixed models compared the age-trajectory of the AD biomarkers PET Aβ and tau and cognitive decline across premorbid ID levels (mild, moderate, and severe/profound), in models controlling trisomy type, APOE status, biological sex, and site. METHODS: Analyses involved adults with DS from the Alzheimers Biomarkers Consortium-Down Syndrome. Participants completed measures of memory, mental status, and visuospatial ability. Premorbid ID level was based on IQ or mental age scores prior to dementia concerns. PET was acquired using [11C] PiB for Aβ, and [18F] AV-1451 for tau. RESULTS: Cognitive data was available for 361 participants with a mean age of 45.22 (SD = 9.92) and PET biomarker data was available for 154 participants. There was not a significant effect of premorbid ID level by age on cognitive outcomes. There was not a significant effect of premorbid ID by age on PET Aβ or on tau PET. There was not a significant difference in age at time of study visit of those with mild cognitive impairment-DS or dementia by premorbid ID level. CONCLUSION: Findings provide robust evidence of a similar time course in AD trajectory across premorbid ID levels, laying the groundwork for the inclusion of individuals with DS with a variety of IQ levels in clinical AD trials