In-silico study of antisense oligonucleotide antibiotics.

Background: The rapid emergence of antibiotic-resistant bacteria directly contributes to a wave of untreatable infections. The lack of new drug development is an important driver of this crisis. Most antibiotics today are small molecules that block vital processes in bacteria. To optimize such effects, the three-dimensional structure of targeted bacterial proteins is imperative, although such a task is time-consuming and tedious, impeding the development of antibiotics. The development of RNA-based therapeutics has catalyzed a new platform of antibiotics-antisense oligonucleotides (ASOs). These molecules hybridize with their target mRNAs with high specificity, knocking down or interfering with protein translation. This study aims to develop a bioinformatics pipeline to identify potent ASO targets in essential bacterial genes. Methods: Three bacterial species (P. gingivalis, H. influenzae, and S. aureus) were used to demonstrate the utility of the pipeline. Open reading frames of bacterial essential genes were downloaded from the Database of Essential Genes (DEG). After filtering for specificity and accessibility, ASO candidates were ranked based on their self-hybridization score, predicted melting temperature, and the position on the gene in an operon. Enrichment analysis was conducted on genes associated with putative potent ASOs. Results: A total of 45,628 ASOs were generated from 348 unique essential genes in P. gingivalis. A total of 1,117 of them were considered putative. A total of 27,273 ASOs were generated from 191 unique essential genes in H. influenzae. A total of 847 of them were considered putative. A total of 175,606 ASOs were generated from 346 essential genes in S. aureus. A total of 7,061 of them were considered putative. Critical biological processes associated with these genes include translation, regulation of cell shape, cell division, and peptidoglycan biosynthetic process. Putative ASO targets generated for each bacterial species are publicly available here: https://github.com/EricSHo/AOA. The results demonstrate that our bioinformatics pipeline is useful in identifying unique and accessible ASO targets in bacterial species that post major public health issues.

Are "outsiders" in? Exploring the impact of outsourced workers' perceived insider status and job value status on job performance.

Introduction: Outsourcing, one of the nonstandard employment forms, has been increasingly popular with a wide variety of industries and employers. However, much less is known about its consequences at the employee level, especially relative to standard-employed colleagues. Drawing on social categorization theory and the human resource architecture model, the study was to investigate how outsourced (vs. standard) employment form impacts employees' perceived insider status and then job performance, as well as the moderating role of job value status. Methods: To examine these effects, we collected two-wave and multi-source questionnaires from a sample of 147 outsourced employees, 279 standard employees, and their immediate supervisors. And interviews with 31 employees, their supervisors, and human resources personnel provided further support for our findings. Results: The results showed that relative to standard employees, outsourced employees were lower in perceived insider status and indirectly worse in job performance. Furthermore, both the comparative effects were stronger among core-status than peripheral-status employees. Discussion: Our study contributes to outsourcing and widely nonstandard employment literature, bringing the research focus from employers to outsourced employees' psychological and behavioral consequences. Also, we extended literature on the human resource architecture, through a deeper investigation on the issue of employment form-job value status (mis)matching as well as its impacts on employees.

A protein aggregation platform that distinguishes oligomers from amyloid fibrils.

Deposition of aggregated proteins is a pathological feature in many neurodegenerative disorders such as Alzheimer's and Parkinson's. In addition to insoluble amyloid fibrils, protein aggregation leads to the formation of soluble oligomers, which are more toxic and pathogenic than fibrils. However, it is challenging to screen for inhibitors targeting oligomers due to the overlapping processes of oligomerization and fibrillization. Here we report a protein aggregation platform that uses intact and split TEM-1 ß-lactamase proteins as reporters of protein aggregation. The intact ß-lactamase fused with an amyloid protein can report the overall protein aggregation, which leads to loss of lactamase activity. On the other hand, reconstitution of active ß-lactamase from the split lactamase construct requires the formation of amyloid oligomers, making the split lactamase system sensitive to oligomerization. Using Aß, a protein that forms amyloid plaques in Alzheimer's disease, we show that the growth curves of bacterial cells expressing either intact or split lactamase-Aß fusion proteins can report changes in the Aß aggregation. The cell lysate lactamase activity assays show that the oligomer fraction accounts for 20% of total activity for the split lactamase-Aß construct, but only 3% of total activity for the intact lactamase-Aß construct, confirming the sensitivity of the split lactamase to oligomerization. The combination of the intact and split lactamase constructs allows the distinction of aggregation modulators targeting oligomerization from those targeting overall aggregation. These low-cost bacterial cell-based and biochemical assays are suitable for high-throughput screening of aggregation inhibitors targeting oligomers of various amyloid proteins.

Preparation and Fractionation of Heterogeneous Aß42 Oligomers with Different Aggregation Properties.

Deposition of amyloid-ß (Aß) aggregates in the form of amyloid plaques is a central feature of Alzheimer's disease. The end products of Aß aggregation are amyloid fibrils. Soluble Aß aggregates called oligomers are also formed either on or off the pathway of fibril formation. The amyloid fibrils from different clinical subtypes of Alzheimer's disease have been found to adopt different structures, a phenomenon called fibril polymorphism. Meanwhile, different types of Aß oligomers have also been found. Recently, it has been shown that different types of Aß42 oligomers may form fibrils of different structures, linking oligomer heterogeneity to fibril polymorphism. In this chapter, we describe methods to prepare heterogeneous Aß42 oligomers and to quantify the concentration of these oligomers at a low micromolar range using a fluorescamine method. Fractionation of these oligomers by size using ultrafiltration filters allows for the formation of Aß42 fibrils with different structural properties.

Patterns of allergenic food introduction in Los Angeles inner-city children.

Background: Early introduction of allergenic foods is recommended to reduce the risk of developing food allergies, but it is unclear whether recommendations are being followed. Objective: We examine patterns of allergenic food introduction in inner-city children enrolled in an academic pediatric practice in the greater Los Angeles area. Methods: This was a prospective study with patients ages 12 to 24 months recruited from the pediatrics continuity clinic at an inner-city tertiary medical center in the greater Los Angeles area. Caregivers were asked via anonymous surveys about their child's history of atopic diseases and at what age they first introduced egg, soy, wheat, peanut, tree nuts, fish, shrimp, and shellfish into their child's diet. Results: Two hundred caregivers responded to the survey. The average age of introduction of egg was 9.2 months, soy 10 months, wheat 9.3 months, peanut 10.5 months, tree nuts 10.9 months, fish 10.9 months, shrimp 11.3 months, and shellfish 11.5 months. Between ages 4-11 months, 65.3% of children were introduced egg, 19.1% soy, 55.8% wheat, 28.6% peanut, 17.1% tree nuts, 28.1% fish, 13.6% shrimp, and 7.0% shellfish. By age 24 months, 92% of children were introduced egg, 37.7% soy, 85.4% wheat, 67.3% peanut, 47.7% tree nuts, 67.8% fish, 48.2% shrimp, and 30.2% shellfish. Of the 14 children with eczema or egg allergy, 26.1% were introduced peanut by age 4-6 months and 50% by age 4-11 months. Conclusion: Despite recommendations, inner-city caregivers may not be introducing allergenic foods in a timely manner to their children.

Online Social Networking and Mental Health among Older Adults: A Scoping Review.

As the number of older adults is expected to increase exponentially within the next few decades, loneliness, social isolation, and depression among seniors are growing public health concerns. Although formal treatment options, such as therapy and medication, can be helpful for depression, they can also be expensive and sometimes ineffective. It is therefore important to consider other potential treatment options and social interventions. Alternative methods for addressing mental health issues are especially important for older adults, as they may encounter barriers associated with aging such as limited mobility and decreased social networks. In these circumstances, online social networking may offer a potential "social cure" to alleviate loneliness, social isolation, and depression. The purpose of this scoping review was to gather and summarize the current literature on associations between online social networking and mental health outcomes (e.g., depression, life satisfaction, loneliness) among older adults. An initial search of 3,699 articles resulted in 52 articles that met criteria for inclusion. Five common themes were identified: (1) enhanced communication with family and friends, (2) greater independence and self-efficacy, (3) creation of online communities, (4) positive associations with well-being and life satisfaction, and (5) decreased depressive symptoms. Implications for older adults' mental health, social connectedness, programs and policies are discussed.

Corporate Sustainability Paradox Management: A Systematic Review and Future Agenda.

Increasing evidence suggests that corporate sustainability is paradoxical in nature, as corporates and managers have to achieve economic, social, and environmental goals, simultaneously. While a paradox perspective has been broadly incorporated into sustainability research for more than a decade, it has resulted in limited improvement in our understanding of corporate sustainability paradox management. In this study, the authors conduct a systematic review of the literature of corporate sustainability paradox management by adopting the Smith-Lewis three-stage model of dynamic equilibrium. The results reveal the following: (1) Both environmental and cognitive factors manifest tensions arising from the sustainability paradox. (2) While both proactive and defensive strategies are adopted to manage the tensions embedded in the corporate sustainability, the proactive strategy is more extensively studied in the current literature. (3) Management strategies of corporate sustainability paradox are characterized as multi-level, multi-stage, and dealing with multiple paradoxes. (4) Proactive strategies enable organizations to enjoy short-term and long-term sustainability benefits. The authors call for further research explicitly addressing the following areas: (1) the paradoxical nature of corporate sustainability management; (2) corporate sustainability paradox management of for-profit organizations; (3) the micro-foundations of corporate sustainability paradox management; (4) defensive strategies and new proactive strategies; and (5) a unified standard of sustainability outcomes. The practical implications of this review are then elaborated. In practice, the results imply that organizations would best manage the corporate sustainability paradox by understanding the paradox and its equilibrium stages. This review and proposed research agenda are expected to deepen interdisciplinary knowledge and set the stage for interested scholars to undertake in their future inquiries.

Recognition and rejection each induce forgetting.

Recognition-induced forgetting, whereby the recognition of targeted memories induces the forgetting of related memories, results from the recognition of old objects and rejection of new objects. Here we asked whether both these tasks are necessary to induce forgetting. Our unique design allowed us to isolate the recognition of old objects from the rejection of new objects by presenting subjects with only new objects, only old objects, and a mixture of both in separate conditions of an old-new recognition task. In all three conditions, we successfully induced forgetting. The magnitude of forgetting was statistically indistinguishable across all three conditions, showing that recognition of old objects and rejection of new objects are each building blocks of forgetting. These findings pinpoint both recognition and rejection as mechanisms underlying recognition-induced forgetting and demonstrate the ubiquity of this forgetting effect.

Sustainable p-type copper selenide solar material with ultra-large absorption coefficient.

Earth-abundant solar absorber materials with large optical absorption coefficients in the visible enable the fabrication of low-cost high-efficiency single and multi-junction thin-film solar cells. Here, we report a new p-type semiconductor, Cu4TiSe4 (CTSe), featuring indirect (1.15 eV) and direct (1.34 eV) band gaps in the optimal range for solar absorber materials. CTSe crystallizes in a new noncentrosymmetric cubic structure (space group F4[combining macron]3c) in which CuSe4 tetrahedra share edges and corners to form octahedral anionic clusters, [Cu4Se4]4-, which in turn share corners to build the three-dimensional framework, with Ti4+ ions located at tetrahedral interstices within the channels. The unique crystal structure and the Ti 3d orbital character of the conduction band of CTSe give rise to near-optimal band gap values and ultra-large absorption coefficients (larger than 105 cm-1) throughout the visible range, which are promising for scalable low-cost high-efficiency CTSe-based thin-film solar cells.

CdS Aerogels as Efficient Photocatalysts for Degradation of Organic Dyes under Visible Light Irradiation.

Synthesis of efficient photocatalysts based on CdS nanomaterials for oxidative decomposition of organic effluents typically focuses on (a) enhancement of surface area of the catalysts and (b) promotion of the separation of photogenerated electron-hole pairs. CdS aerogel, which are synthesized by simple sol-gel assembly of discrete nanocrystals (NCs) into a porous network followed by supercritical drying, could provide higher surface area for photocatalytic reactions along with facile charge separation due to direct contact between NCs via covalent bonding. We evaluated the efficiency of CdS aerogel materials for degradation of organic dyes using methylene blue (MB) and methyl orange (MO) as test cases. CdS aerogel materials exhibited remarkable photocatalytic activity for dye degradation compared to typical, ligand-capped CdS NCs. The catalytic efficiency of CdS aerogels was further improved by decreasing the chain-length and extent of surface organics, leading to higher, and more hydrophilic, accessible surface area. The use of porous, chalcogenide-based solid state architectures for photocatalysis enables easy separation of catalyst while ensuring a high-interfacial surface area for analyte reactivity and visible light activation.