In vitro methylation of the U7 snRNP subunits Lsm11 and SmE by the PRMT5/MEP50/pICln methylosome.

U7 snRNP is a multisubunit endonuclease required for 3' end processing of metazoan replication-dependent histone pre-mRNAs. In contrast to the spliceosomal snRNPs, U7 snRNP lacks the Sm subunits D1 and D2 and instead contains two related proteins, Lsm10 and Lsm11. The remaining five subunits of the U7 heptameric Sm ring, SmE, F, G, B, and D3, are shared with the spliceosomal snRNPs. The pathway that assembles the unique ring of U7 snRNP is unknown. Here, we show that a heterodimer of Lsm10 and Lsm11 tightly interacts with the methylosome, a complex of the arginine methyltransferase PRMT5, MEP50, and pICln known to methylate arginines in the carboxy-terminal regions of the Sm proteins B, D1, and D3 during the spliceosomal Sm ring assembly. Both biochemical and cryo-EM structural studies demonstrate that the interaction is mediated by PRMT5, which binds and methylates two arginine residues in the amino-terminal region of Lsm11. Surprisingly, PRMT5 also methylates an amino-terminal arginine in SmE, a subunit that does not undergo this type of modification during the biogenesis of the spliceosomal snRNPs. An intriguing possibility is that the unique methylation pattern of Lsm11 and SmE plays a vital role in the assembly of the U7 snRNP.

The Arabidopsis splicing factor PORCUPINE/SmE1 orchestrates temperature-dependent root development via auxin homeostasis maintenance.

Appropriate abiotic stress response is pivotal for plant survival and makes use of multiple signaling molecules and phytohormones to achieve specific and fast molecular adjustments. A multitude of studies has highlighted the role of alternative splicing in response to abiotic stress, including temperature, emphasizing the role of transcriptional regulation for stress response. Here we investigated the role of the core-splicing factor PORCUPINE (PCP) on temperature-dependent root development. We used marker lines and transcriptomic analyses to study the expression profiles of meristematic regulators and mitotic markers, and chemical treatments, as well as root hormone profiling to assess the effect of auxin signaling. The loss of PCP significantly alters RAM architecture in a temperature-dependent manner. Our results indicate that PCP modulates the expression of central meristematic regulators and is required to maintain appropriate levels of auxin in the RAM. We conclude that alternative pre-mRNA splicing is sensitive to moderate temperature fluctuations and contributes to root meristem maintenance, possibly through the regulation of phytohormone homeostasis and meristematic activity.

Evaluating the effectiveness of artifact correction and rejection in event-related potential research.

Eyeblinks and other large artifacts can create two major problems in event-related potential (ERP) research, namely confounds and increased noise. Here, we developed a method for assessing the effectiveness of artifact correction and rejection methods in minimizing these two problems. We then used this method to assess a common artifact minimization approach, in which independent component analysis (ICA) is used to correct ocular artifacts, and artifact rejection is used to reject trials with extreme values resulting from other sources (e.g., movement artifacts). This approach was applied to data from five common ERP components (P3b, N400, N170, mismatch negativity, and error-related negativity). Four common scoring methods (mean amplitude, peak amplitude, peak latency, and 50% area latency) were examined for each component. We found that eyeblinks differed systematically across experimental conditions for several of the components. We also found that artifact correction was reasonably effective at minimizing these confounds, although it did not usually eliminate them completely. In addition, we found that the rejection of trials with extreme voltage values was effective at reducing noise, with the benefits of eliminating these trials outweighing the reduced number of trials available for averaging. For researchers who are analyzing similar ERP components and participant populations, this combination of artifact correction and rejection approaches should minimize artifact-related confounds and lead to improved data quality. Researchers who are analyzing other components or participant populations can use the method developed in this study to determine which artifact minimization approaches are effective in their data.

Novel and Proven Models of Public, Private, and Public-Private Partnerships in Healthcare: An Update.

Initiatives to share assets in the life science sector through dedicated partnerships had and still have a multitude of different aspects in the past few decades. The range goes from industry partners, small and big companies, in bilateral agreements with academic institutions up to large privately and publicly funded consortia. In general, the term public-private partnership (PPP) is used when at least one public (non-profit, academic, and/or government) part and one or more private for-profit partners are involved. A Public-Private Partnership is often driven by a public body, i.e. a ministry or a public agency. Their synergism has been described 10 years ago (Dearing, Science 315(19):344-347, 2007; Casty and Wieman, Ther Innov Regul Sci 47(3):375-383, 2013; Stevens et al., Biotechnol Law Rep 34(4):153-165, 2015). So why view this synergism again today? It will be shown that the situation in life science has changed: novel partners acting digital, data expertise being involved on many levels and novel partnering models arising. Success and challenges will be described in this chapter.

[Psychotherapeutic consultation at work: associations between company size and psychosomatic health]. / Psychotherapeutische Sprechstunde am Arbeitsplatz: Zusammenhänge zwischen Unternehmensgröße und psychosomatischer Gesundheit.

BACKGROUND: The utilization of psychotherapeutic consultation at work (PT-A) has so far been investigated in large enterprises (LEs). These differ structurally from small(est) and medium-sized enterprises (SMEs). Differences in the user profiles of a PT­A with regard to psychosomatic health, work-related self-efficacy, and work ability depending on company size have hardly been investigated. This study also examined differences in the employees' perception of the psychosocial safety climate (PSC) in the company, which represents management's efforts to promote mental health. METHODS: As part of the Early Intervention in the Workplace intervention study called "friaa", employees from LEs and SMEs interested in a PT­A were surveyed throughout Germany from September 2021 to January 2023. Using t­ and χ2-tests, differences between employees in LEs (n = 439) and SMEs (n = 109) were examined with regard to the ICD-10 F diagnostic code ("International Statistical Classification of Diseases and Related Health Problems"; mental and behavioral disorders), depression (PHQ-9), anxiety (GAD-2), level of functioning (GAF), somatic symptom burden (SSS-8), health (VR-12), ability to work (WAI), self-efficacy (SOSES), and psychosocial safety climate (PSC-4). The association between these variables and especially the PSC­4 were investigated using correlation analysis. RESULTS: Both groups showed similar levels of stress. From the employees' perspective, psychosocial issues were addressed significantly more frequently in LEs than in SMEs with a medium effect size. The study provided initial indications that in LEs there were positive correlations of the PSC­4 with SOSES and WAI and negative ones with PHQ­9 and SSS­8. DISCUSSION: The comparable psychological strain on employees in LEs and SMEs points to the need for behavioral and structural preventive measures regardless of the company size. Mainly in SMEs, organizational communication of psychosocial health should be given greater priority.

Impact of Minor Carbapenemases on Susceptibility to Novel ß-Lactam/ß-Lactamase Inhibitor Combinations and Cefiderocol in Enterobacterales.

The in vitro activity of imipenem-relebactam, meropenem-vaborbactam, ceftazidime-avibactam, and cefiderocol was evaluated against both clinical and isogenic enterobacterial isolates producing carbapenemases of the SME, NmcA, FRI, and IMI types. Ceftazidime-avibactam and meropenem-vaborbactam showed the highest activity against all tested isolates; imipenem-relebactam showed only moderate activity. All isolates remained susceptible to cefiderocol. Furthermore, avibactam and vaborbactam have greater inhibitory activity than relebactam against the tested carbapenemases. Overall, ceftazidime-avibactam, meropenem-vaborbactam, and cefiderocol were the most effective therapeutic options for treating infections caused by the tested minor carbapenemase producers.

Supporting employees with mental illness and reducing mental illness-related stigma in the workplace: an expert survey.

An expert survey was designed to support the development of a workplace-based multi-country intervention tackling depression, anxiety, and mental illness-related stigma in small- and medium-sized enterprises (SMEs). Academic experts and representatives of SME organisations, specific sector organisations, labour or advocacy groups, and occupational health organisations, were contacted across eight European countries and Australia. The survey comprised closed and open text questions to assess expert opinion about interventions for employees with mental health difficulties, interventions supporting their managers, and anti-stigma interventions. The survey was available in six languages. The online platform Qualtrics was used for data collection. Quantitative data was analysed through descriptive statistics and qualitative data was analysed through thematic analysis. Sixty-five of 146 experts responded, representing a 42% response rate. Results showed only 26.2% of experts agreed that employees could speak openly about mental health issues, and 81.5% of experts indicated a large or medium unmet need for support for employees with mental health issues. Psychoeducational materials, face-to-face workshops and interventions based on cognitive behavioural therapy were ranked most likely to be taken up by employees. Experts rated as most useful for managers' guidelines on how to act if an employee has mental health issues (67.7%). The greatest number of experts indicated workshops of people with lived experience of mental illness (80.0%) and awareness campaigns (78.5%) were most required to tackle stigma. Responses were consistent between experts from different countries and areas of expertise. Experts in this multinational survey assessed that interventions supporting mental health in the workplace and tackling stigma are greatly needed. A multicomponent intervention with a wide range of materials and tools is supported.

Impact of CGIAR maize germplasm in Sub-Saharan Africa.

This study reports on the adoption and impacts of CGIAR-related maize varieties in 18 major maize-producing countries in sub-Saharan Africa (SSA) during 1995-2015. Of the 1345 maize varieties released during this timeframe, approximately 60% had a known CGIAR parentage. About 34% (9.5 million ha) of the total maize area in 2015 was cultivated with 'new' CGIAR-related maize varieties released between 1995 and 2015. In the same year, an additional 13% of the maize area was cultivated with 'old' CGIAR-related maize varieties released before 1995. The aggregate annual economic benefit of using new CGIAR-related maize germplasm for yield increase in SSA was estimated at US$1.1-1.6 billion in 2015, which we attributed equally to co-investments by CGIAR funders, public-sector national research and extension programs, and private sector partners. Given that the annual global investment in CGIAR maize breeding at its maximum was US$30 million, the benefit-cost ratios for the CGIAR investment and CGIAR-attributable portion of economic benefits varied from 12:1-17:1, under the assumption of a 5-year lag in the research investment to yield returns. The study also discusses the methodological challenges involved in large-scale impact assessments. Post-2015 CGIAR tropical maize breeding efforts have had a strong emphasis on stress tolerance.

First nosocomial outbreak of SME-4-producing Serratia marcescens in South America.

Carbapenemase-producing-Serratia marcescens isolates, although infrequent, are considered important nosocomial pathogens due to their intrinsic resistance to polymyxins, which limits therapeutic options. We describe a nosocomial outbreak of SME-4-producing S. marcescens in Buenos Aires city which, in our knowledge, represents the first one in South America.

Sports entrepreneurship during COVID-19: Technology as an ally to maintain the competitiveness of small businesses.

The sports sector, specifically the field of personal trainer entrepreneurship, has been severely affected by the COVID-19 crisis. However, there are still few empirical studies that analyze how the actions taken before and during this crisis can affect sports entrepreneurs' performance. This research aims to analyze which combinations of sports entrepreneurs' personal characteristics and actions performed have been most and least effective in minimizing the negative impact of COVID-19 on their businesses. A validated online questionnaire was administered to personal trainer entrepreneurs from May to June 2020 before they reopened their facilities. Fuzzy-set qualitative comparative analysis (fsQCA) was performed to assess the impacts. The results show that both post-COVID measures (adaptation of the business model) and previous strategic orientation seemed essential. Specifically, high levels of sports entrepreneurs' resilience and innovation/R&D when competing against their closest competitors before the COVID-19 pandemic and the increased use of technologies (sports services digitization) during the pandemic have been essential to maintaining the performance of the sports business. Thus, improvements in the digital competencies of personal trainers' sports entrepreneurs, the development of strategic plans and activities related to innovation/R&D and process improvements are important measures to maintain the competitiveness of small sports businesses during crises.

Stuck in short-term, daily operations, or not?: Unraveling SME's long-term orientation.

Long-term orientation (LTO) is an essential strategic option for firms to shape their future success, in particular for SMEs which are often submerged by daily operations. Surprisingly, little is known about the underlying personal and contextual drivers of LTO in an SME context. To unravel why some SME entrepreneurs adopt an LTO, while others seem to be stuck in short term and daily operations, we consider the (interacting) impact of both personal and contextual drivers. We carefully select well known drivers for their impact on various other aspects of SME's LTO: Need for achievement, as a personal driver, and the entrepreneur's perception of the institutional entrepreneurial support (PIES), as a contextual driver. The latter consists of a regulative, normative and cognitive institutional dimension. Based on a study on 176 SMEs in an emerging country, Indonesia, we confirm that both personal as well as contextual drivers individually and interactively impact an SME's LTO. Specifically, when highly achievement motivated entrepreneurs perceive that institutional regulations support entrepreneurial activities, they tend to adopt a higher level of LTO. We discuss implications for SMEs and policy makers, and provide suggestions for future research.

Event-related potentials data quality in young children: Standardized measurement error of ERN and Pe.

Most methods used to quantify event-related potential (ERP) data were developed for use with typical adult populations. Questions regarding how these methods apply to child ERP data remain. Here, we focused on two widely used ERP scoring methods, namely, time-window mean amplitude and peak amplitude measures, for two ERP error monitoring components, the error-related negativity (ERN) and the error positivity (Pe), collected from Kindergarteners during a child-friendly cognitive control task (N = 170). We first established the presence of error-related ERPs and examined the relations between ERP scores and children's behavioral task performance. We then assessed the data quality (precision) of mean and peak ERP amplitude scores at the level of individual participants using the standardized measurement error of ERPs. We also compared the effects of choosing baseline correction periods that were relatively distal versus proximal to responses on data quality. Across each of these analyses, we found that time-window mean amplitude scoring was comparable to, and in some cases outperformed, peak amplitude scoring. In addition, the proximal baseline provided higher data quality than the distal baseline. We conclude with specific recommendations regarding the scoring and baseline correction for ERP data collected from young children.

Impact of COVID-19 on psychological distress among SME owners in Ghana: Partial least square-structural equation modeling (PLS-SEM) approach.

A critical part of the national economy is small and medium enterprises (SMEs). SME owners are vital contributors to the overall economy. Due to their limited capital and assets, they are more vulnerable. In comparison to their contribution, the value of assessing SME owner's depression, anxiety, and mental stress has been very minimal during the COVID-19 outbreak. Firms were forced to close due to lockdown, and they faced substantial business losses. Thus, this study aims to investigate SME owners' psychological distress due to business losses during this pandemic. The study used psychological parameters: Depression, Anxiety, Stress Scale-21 (DASS-21) to examine SME owners' psychological distress. A total number of 217 owners were surveyed through a judgmental sampling technique using a structured questionnaire. Data were analyzed employing partial least square-based structural equation modeling (PLS-SEM). The findings showed that DASS-21 parameters and fear of business loss affected psychological distress. Besides, fear of business loss increases psychological distress, whereas government support lessens the distress. Theoretically, this study extended the scope of DASS-21 scale and contributed to the literature of psychology. In terms of policy implications, this study provides useful information for government, policymakers, and SME owners about the effects mentioned above.

Using gravity model to make store closing decisions: A data driven approach.

Many studies propose methods for finding the best location for new stores and facilities, but few studies address the store closing problem. As a result of the recent COVID-19 pandemic, many companies have been facing financial issues. In this situation, one of the most common solutions to prevent loss is to downsize by closing one or more chain stores. Such decisions are usually made based on single-store performance; therefore, the under-performing stores are subject to closures. This study first proposes a multiplicative variation of the well-known Huff gravity model and introduces a new attractiveness factor to the model. Then a forward-backward approach is used to train the model and predict customer response and revenue loss after the hypothetical closure of a particular store from a chain. In this research the department stores in New York City are studied using large-scale spatial, mobility, and spending datasets. The case study results suggest that the stores recommended being closed under the proposed model may not always match the single store performance, and emphasizes the fact that the performance of a chain is a result of interaction among the stores rather than a simple sum of their performance considered as isolated and independent units. The proposed approach provides managers and decision-makers with new insights into store closing decisions and will likely reduce revenue loss due to store closures.

Sustainability in the beer and pub industry during the COVID-19 period: An emerging new normal.

The COVID-19 pandemic created significant challenges for the British pub industry, due to the uncertain conditions caused by the virus, changes in consumption patterns and government measures. Studies recommend that organisations adopt innovative and flexible business models to generate added value for customers and other stakeholders as a survival and growth strategy. However, such measures require business ecosystems which encourage co-creative engagement. This qualitative study extends the concept of value co-creation beyond its current boundary as a customer-driven experiential paradigm, reconceptualising it as a driver for societal benefits. Over the period March - December 2020, we carried out in-depth interviews with pub and brewery owners, managers, and customers, combined with netnographic and offline observations of pubs' engagement with customers. We uncovered three stages of strategies and innovation during this period, which we term 'survive', 'secure', and 'sustain'. We demonstrate how multiple stakeholders benefit from the innovations of pubs and breweries negotiating each stage, advancing current scholarship on sustainable value co-creation.

Blockchain-based online education content ranking.

Nowadays, internet technology plays a vital role in all the fields of our daily lives ranging from the world economy, professional careers, higher education, and almost all the spheres that are deeply impacted. In the current situation, due to COVID19, the dependence on the Internet for almost everything, including learning, getting daily needs, etc., is heavily dependent on the Internet. Online learning is made possible by the Internet, and today most students, educators, researchers are leveraging online learning platforms to enhance their knowledge at their own pace. Generally, the quality of the E-learning courses is evaluated with the help of the courses' review and rating mechanisms. In the present context, review systems are centralized, storing highly valuable information at one location and are liable to manipulation, hacking, and tampering. In this paper, the Blockchain-based Online Education Content Ranking system is proposed for an online review and ranking system that offers a decentralized trustworthy system, ensuring the integrity of the rating and the independence and integrity of content reviews by Subject Matter Experts (SME).

Mobile apps for SME business sustainability during COVID-19 and onwards.

Small and Medium-Sized Enterprises (SMEs) are struggling to cope with the business uncertainty caused by the COVID-19 pandemic. This study examines how SMEs in developing economies have used mobile apps to improve their business efficiency during the pandemic. We aim to recognize effective measures and actions taken by SMEs that have turned to mobile-app-based business to improve their sustainability during the crisis. The study bridges a literature gap by extending the Theory of Consumption Values and the Theory of Planned Behavior to SMEs that incorporate mobile-app-based business. Data was collected from 343 SMEs from three Industrial Development Corporations (IDCs) in India. Using the covariance-based structural equation modeling method, we investigated the efficiency of a conceptual model of mobile-app-based business for SMEs. The results revealed that consumer choice behavior, perceived behavior control, subjective behavior control and attitude towards the mobile app all influence SMEs' decision-making and business strategy. As such, SMEs need a powerful mobile-app-based business network to succeed in the entrepreneurial business process. Using instrumental variable analysis, we discovered that increased mobile app usage significantly improves SMEs' long-term efficiency. The analysis provides several theoretical and managerial ramifications.

Activity of Imipenem-Relebactam and Meropenem-Vaborbactam against Carbapenem-Resistant, SME-Producing Serratia marcescens.

The Serratia marcescens enzyme (SME) is a chromosomally encoded carbapenemase with no known optimal treatment. Various ß-lactam/ß-lactamase inhibitors and comparators were evaluated against 8 SME producers via broth microdilution. Four isolates were subsequently tested via time-kill analyses. All isolates were resistant to imipenem, imipenem-relebactam, and meropenem but susceptible to ceftazidime, ceftazidime-avibactam, and meropenem-vaborbactam. Ceftazidime, imipenem-relebactam, and meropenem-vaborbactam were bactericidal against 3, 0, and 4 isolates, respectively. Meropenem-vaborbactam may be a potential option for severe SME-producing infections.

The Effect of POSS Type on the Shape Memory Properties of Epoxy-Based Nanocomposites.

Thermally activated shape memory polymers (SMPs) can memorize a temporary shape at low temperature and return to their permanent shape at higher temperature. These materials can be used for light and compact space deployment mechanisms. The control of transition temperature and thermomechanical properties of epoxy-based SMPs can be done using functionalized polyhedral oligomeric silsesquioxane (POSS) additives, which are also known to improve the durability to atomic oxygen in the space environment. In this study, the influence of varying amounts of two types of POSS added to epoxy-based SMPs on the shape memory effect (SME) were studied. The first type contained amine groups, whereas the second type contained epoxide groups. The curing conditions were defined using differential scanning calorimetry and glass transition temperature (Tg) measurements. Thermomechanical and SME properties were characterized using dynamic mechanical analysis. It was found that SMPs containing amine-based POSS show higher Tg, better shape fixity and faster recovery speed, while SMPs containing epoxide-based POSS have higher crosslinking density and show superior thermomechanical properties above Tg. This work demonstrates how the Tg and SME of SMPs can be controlled by the type and amount of POSS in an epoxy-based SMP nanocomposite for future space applications.

Formulation, production, in vitro release and in vivo pharmacokinetics of cinnamaldehyde sub-micron emulsions.

Objective: The purpose of this study was to study the effects of formulation of cinnamaldehyde submicron emulsion (CA-SME) and optimize the preparation process parameters of CA-SME, characterize CA-SME and study on in vitro release kinetics and in vivo pharmacokinetics.Methods: Single factor methodology was used to screen the formulation of CA-SME. Response surface methodology combined with Box-Behnken design (BBD) was used to optimize the process variables of CA-SME. The dynamic dialysis method was used to investigate the in vitro release of CA from CA-SME. The blood concentrations of CA in rats were measured after oral administration of CA-SME, with CA solution as reference.Results: The optimal formulation of CA-SME was as follows: 2.5% CA + 1.5% Tween-80 and Span-80 (1:1)+1.5% medium chain triglyceride (MCT)+1.5% Poloxamer-188 + 1.5% lecithin + 91.5% ultrapure water. With the entrapment efficiency (EE/%) of CA-SME as index, BBD experiments indicated that the optimum emulsification temperature, homogenization pressure and cycles were 56 °C, 52 MPa, and two cycles, respectively. The mean particle size and EE of optimum CA-SME were 257.23 ± 3.74 nm and 80.31 ± 0.68%, respectively. The in vitro release study exhibited that the release kinetics of CA-SME was first-order model. Pharmacokinetic parameters of CA-SME in rats were Tmax 60 min, Cmax 1063.41 mg/L, AUC0-∞ 113102.61 mg/L*min, respectively. Tmax, Cmax, and AUC0-∞ of CA-SME were 3, 3.5, and 2.3 times higher than that of CA solution, respectively. The pharmacokinetic parameters of CA-SME in rats were significantly higher than those of CA solution. Submicron emulsion shows great potential as delivery strategy for this volatile herbal oil in oral administration.