Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic mice

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disease, but it can also affect other organs including the central nervous system. Several animal models have been developed to address different key questions related to Coronavirus Disease 2019 (COVID-19). Wild-type mice are minimally susceptible to certain SARS-CoV-2 lineages (beta and gamma variants), whereas hACE2-transgenic mice succumb to SARS-CoV-2 and develop a fatal neurological disease. In this article, we aimed to chronologically characterize SARS-CoV-2 neuroinvasion and neuropathology. Necropsies were performed at different time points, and the brain and olfactory mucosa were processed for histopathological analysis. SARS-CoV-2 virological assays including immunohistochemistry were performed along with a panel of antibodies to assess neuroinflammation. At 6 to 7 days post inoculation (dpi), brain lesions were characterized by nonsuppurative meningoencephalitis and diffuse astrogliosis and microgliosis. Vasculitis and thrombosis were also present and associated with occasional microhemorrhages and spongiosis. Moreover, there was vacuolar degeneration of virus-infected neurons. At 2 dpi, SARS-CoV-2 immunolabeling was only found in the olfactory mucosa, but at 4 dpi intraneuronal virus immunolabeling had already reached most of the brain areas. Maximal distribution of the virus was observed throughout the brain at 6 to 7 dpi except for the cerebellum, which was mostly spared. Our results suggest an early entry of the virus through the olfactory mucosa and a rapid interneuronal spread of the virus leading to acute encephalitis and neuronal damage in this mouse model.

Manifestation of heterosis in F1 petunia hybrids

The article presents the results of a study of the manifestation of hypothetical and true heterosis in the hybrid petunia according to some decorative features in the conditions of the protected ground of Moscow. The presence of a heterosis effect and overdomination in the time of flowering of the first flower, the diameter of the flower and the number of flowers for the first two weeks of flowering was established. All hybrid combinations showed a small negative hypothetical and true heterosis effect on the early entry of petunia plants into the flowering phase. Keywords: PETUNIA, HETEROSIS, HYBRID, DOMINANCE, OVERDOMINATION

SPEED OF DIFFUSION, RETHINKING TIME AND FIRMS’ STRATEGY: ANALYSIS OF THE INTERACTIONS TO LEAP ACROSS THE CHASM

Although the literature has recognised short time to market and early entry as relevant factors, they are not enough alone to ensure success. In fact, an early entrant may successfully serve early adopters, but then fail in developing products suitable for those who adopt later (i.e., the early majority), dissipating the first-mover advantages previously gained. This paper argues that the likelihood of being successful in the early majority segment depends also on the rethinking time, defined as the time available to firms serving early adopters for planning and developing products that will be offered to the upcoming early majority segment. The rethinking time is here analytically defined through the Bass model and its relationship with product success is investigated. The paper shows that the market leader in the early majority segment is expected to be the incumbent when rapid diffusion occurs and, conversely, new entrants when rethinking time is longer.

Substance use and HIV stage at entry into care among people with HIV

Background Information regarding the impact of substance use on the timing of entry into HIV care is lacking. Better understanding of this relationship can help guide approaches and policies to improve HIV testing and linkage. Methods We examined the effect of specific substances on stage of HIV disease at entry into care in over 5000 persons with HIV (PWH) newly enrolling in care. Substance use was obtained from the AUDIT-C and ASSIST instruments. We examined the association between early entry into care and substance use (high-risk alcohol, methamphetamine, cocaine/crack, illicit opioids, marijuana) using logistic and relative risk regression models adjusting for demographic factors, mental health symptoms and diagnoses, and clinical site. Results We found that current methamphetamine use, past and current cocaine and marijuana use was associated with earlier entry into care compared with individuals who reported no use of these substances. Conclusion Early entry into care among those with substance use suggests that HIV testing may be differentially offered to people with known HIV risk factors, and that individuals with substances use disorders may be more likely to be tested and linked to care due to increased interactions with the healthcare system.

Evaluation of the source material for the creation of new apple cultivars

The article presents the results of the study of the gene pool collection of the Crimean Experimental Horticulture Station - branch of the FSFIS “NBG-NSC”. Genotypes with economically valuable and breeding traits in the conditions of the foothill Crimea were identified. New sources of valuable qualities are proposed for inclusion in the breeding process for the given traits: low growth and compactness of the crown - 7 cultivars and 2 breeding forms; late flowering - 5 cultivars and 1 breeding form; long flowering period - 6 cultivars, 1 breeding form; early summer and late winter maturation periods - 8 cultivars; high and stable pollen viability - 6 cultivars and forms; self-fertility - 6 cultivars, including 3 breeding forms; frost resistance of generative buds - 8 samples; complex resistance to scab and powdery mildew - 10 cultivars and 2 breeding forms; drought resistance and heat resistance - 5 cultivars and 5 breeding forms. 12 cultivars and 5 breeding forms were identified with a trait of early entry into fruiting, 11 cultivars of various geographical origin and 5 breeding forms were distinguished by high and stable yield; 17 cultivars and 7 forms have high commercial and consumer qualities; 15 cultivars, including 5 breeding forms, were identified with a valuable chemical composition of fruits. As a result of the study of the storage life of the fruits, 7 cultivars and 7 breeding forms with a long storage period in a conventional gas environment were identified. For the food industry, 3 cultivars and 3 breeding forms are recommended as a source of valuable raw materials in the production of dried fruit products and natural apple puree without preservatives. On the basis of the work done, 3 breeding forms of apple trees with a complex of economic and consumer qualities are identified, recommended for establishment perennial plantings of an intensive type and passing the State variety testing - 1-8-ю, 2-1-18-79, 3-5-с.

The human neuronal receptor NgR1 bridges reovirus capsid proteins to initiate infection

Human Nogo-66 receptor 1 (NgR1) is a receptor for mammalian orthoreoviruses (reoviruses), but the mechanism of virus-receptor engagement is unknown. NgR1 binds a variety of structurally dissimilar ligands in the adult central nervous system (CNS) to inhibit axon outgrowth. Disruption of ligand binding to NgR1 and subsequent signaling can improve neuron regrowth, making NgR1 an important therapeutic target for diverse conditions such as spinal crush injuries and Alzheimer disease. To elucidate how NgR1 mediates cell binding and entry of reovirus, we defined the affinity of interaction between virus and receptor, determined the structure of the virus-receptor complex, and identified residues in the receptor required for virus binding and infection. These studies revealed that NgR1 sequences in a central concave region of the molecule establish a bridge between two copies of the viral capsid protein, σ3. This unusual binding interface produces high-avidity interactions between virus and receptor and likely primes early entry steps. NgR1 sequences engaged by reovirus also are required for NgR1 binding to ligands expressed by neurons and oligodendrocytes. These studies redefine models of reovirus cell-attachment and highlight the evolution of viruses to engage multiple receptors using distinct capsid components.

Brazilian craft breweries and internationalization in the born global perspective

PurposeThis paper aims to analyze how the internationalization process of Brazilian microbreweries takes place, especially in factors of propensity to internationalization, competition and survival in the national and international market.Design/methodology/approachThe authors adopted qualitative approach research, using a multiple case study strategy, analyzing seven Brazilian craft breweries. The authors developed this study through documentary research, semi-structured interviews and nonparticipant observation.FindingsThe research findings made it possible to characterize the internationalization process motivated by the background and international experience of entrepreneurs that adopted different strategies for expansion in the international market. The authors noticed that the networks developed in production partnerships, festivals and international missions represent an increase in the ease of internationalization and helps to reduce the risk perception.Research limitations/implicationsThe contributions refer to the conjecture that the born global's evolution related to the high competitiveness of the market is influenced by the international background of the founders and by the influence of the international network, overcoming institutional and market challenges in emerging countries, assuming risks associated with rapid and early entry into the international arena.Practical implicationsThe paper is potentially useful for managerial practice and policymakers by providing insights into the characteristics of entrepreneurs and companies considering their propensity to internationalize, presenting how entrepreneurs and managers can seek resources and develop their skills and capacities to manage such companies and processes of internationalization.Originality/valueThe research is presented as a complementary study to the limited number of studies examining born globals from emerging markets, also challenging the arguments of the dominant theory regarding gradual and nonlinear internationalization.

“Looking for a Golden Needle in the Haystack”: Perspectives on Talent Identification and Development in Paralympic Sport

Despite rapid increases in research on talent identification and development in able-bodied sports, there remains limited knowledge regarding how talent is identified and developed in Paralympic contexts. The purpose of this study was to capture the perspectives of experts (coaches, high-performance managers, and pathway specialists) working in elite Paralympic sport to better understand how they conceptualize, measure, and develop talent. Eight coaches and three performance directors from six Paralympic sports, along with two pathway specialists from Paralympics Australia participated in semi-structured interviews. The results suggest impairment type and, therefore, classification are key indicators of identification and anticipated success, highlighting the importance of educating talent selectors in these areas. In addition, familial (e.g., overprotectiveness, sporting background) and biopsychosocial factors (e.g., resilience, work-ethic, sport-specific skills, other life commitments) were noted as being influential when selecting athletes. There were concerns regarding the disproportionately low number of female athletes in the system, suggesting a need for new initiatives to support early-entry points for female athletes (e.g., education on the benefits of sport participation, supportive environments). High-performance staff also lacked resources to better understand the nuances associated with different impairments and their implications (physiological response to training, associated psychological stresses from injury, identity change). Recruitment strategies included “talent search” days, collaborations with school programs and rehabilitation centers, and helping local clubs support “drop-in” athletes. However, limited funding impacted the sustainability of programs, resulting in a regular turnover of staff, loss of intellectual property, and a weakened pathway system. Results from this study generated several practical implications and future directions for research.

Generation of fluorescent HCV pseudoparticles to study early viral entry events-involvement of Rab1a in HCV entry

Understanding the early events in viral biology holds the key to the development of preventives. In this study fluorescent Hepatitis C Virus pseudoparticles have been generated where the envelope glycoprotein has a GFP tag. Using these pseudoparticles entry assays were conducted where the entry of the pseudoparticles was tracked via confocal microscopy. Using this system, fusion of host and viral membranes is predicted to occur within 15 minutes of entry in HCV. Using cells with a knockdown for Rab1a, HCV trafficking was observed to be altered, indicating a role of Rab1a in HCV trafficking. In conclusion, this study reports the generation and use of fluorescent pseudoparticles which may be used to understand the early events of viral entry. This system may be adapted for the study of other enveloped viruses as well.HighlightsFluorescent HCV pseudoparticles have been created to study early entry events.HCV entry tracking via confocal microscopy reveals fusion within 15 minutes.Rab1a is important for HCV trafficking within the cell.