Botanical Gazette最新文献

FoxP3 is a transcription factor (TF) essential for development of regulatory T cells (Tregs), a branch of T cells that suppress excessive inflammation and autoimmunity ^1-5 . Molecular mechanisms of FoxP3, however, remain elusive. We here show that FoxP3 utilizes the Forkhead domain--a DNA binding domain (DBD) that is commonly thought to function as a monomer or dimer--to form a higher-order multimer upon binding to T _n G repeat microsatellites. A cryo-electron microscopy structure of FoxP3 in complex with T ₃ G repeats reveals a ladder-like architecture, where two double-stranded DNA molecules form the two "side rails" bridged by five pairs of FoxP3 molecules, with each pair forming a "rung". Each FoxP3 subunit occupies TGTTTGT within the repeats in the manner indistinguishable from that of FoxP3 bound to the Forkhead consensus motif (FKHM; TGTTTAC). Mutations in the "intra-rung" interface impair T _n G repeat recognition, DNA bridging and cellular functions of FoxP3, all without affecting FKHM binding. FoxP3 can tolerate variable "inter-rung" spacings, explaining its broad specificity for T _n G repeat-like sequences in vivo and in vitro . Both FoxP3 orthologs and paralogs show similar T _n G repeat recognition and DNA bridging. These findings thus reveal a new mode of DNA recognition that involves TF homo-multimerization and DNA bridging, and further implicates microsatellites in transcriptional regulation and diseases.

While the HIV/AIDS epidemic has informed the responses to the COVID-19 pandemic, there is a lack of understanding of the empirical links between stigmas associated with COVID-19 and HIV/AIDS. Surveying 247 adults in the United States online, this study aims to examine the relationships between COVID-19 and HIV/AIDS stigmas in order to understand how they are similar and different from each other, taking into consideration the context relevant to the COVID-19 pandemic. Four scales of stigmas conveying different attitudes (i.e., rejection, despise, accusation, and caution) were used to examine the relationships between the stigmas of these two infectious diseases. Findings based on the mean comparisons from paired t tests showed the mean difference in scores between respondents who supported the exclusion of COVID-19-infected individuals versus HIV-infected individuals was statistically significant. In addition, the mean difference in scores between respondents who were wary of their need to protect their rights around COVID-19-infected persons versus HIV-infected persons was statistically significant. Controlling for the respondents' sociodemographics and factors that were relevant to the COVID-19 pandemic, multiple regression analyses showed that all four types of COVID-19 stigmas were positively associated with their corresponding types of HIV/AIDS stigmas. The preliminary findings between COVID-19 and HIV/AIDS stigmas suggested that HIV/AIDS stigma mitigation strategies may present a fruitful approach to inform stigma mitigation of COVID-19.

Background: In December 2020, Canada began its coronavirus disease 2019 (COVID-19) vaccine rollout campaign. Canadians were vaccinated with differing time intervals between doses, vaccine products and vaccine schedules, based on age, timing of vaccination and jurisdiction. The objective of this study is to describe the epidemiology and association between the incidence of COVID-19 cases following vaccination, time since completion of primary series, time between doses and/or product combination and probability of developing severe outcomes.

Methods: The national COVID-19 case data and vaccination coverage data were extracted from the National COVID-19 Surveillance System, and the Canadian COVID-19 Vaccination Coverage Surveillance System. Population estimates from Statistics Canada were used as denominators for rates and for number of people "not fully vaccinated". Two binomial generalized linear models were constructed for analysis.

Results: Within the analysis period, fully vaccinated (i.e. completed primary series) cases (n=17,206) were more commonly female and older, and had fewer reported severe outcomes relative to not fully vaccinated cases (n=615,999). Episode date of fully vaccinated cases most frequently occurred two months after receiving their second dose, and time-between doses of 29-49 and 50-77 days were most common. The probability of becoming a detected COVID-19 case in not fully vaccinated individuals was higher than those fully vaccinated. Those receiving two doses of AstraZeneca and those with shortest time intervals between doses had higher probabilities of becoming COVID-19 cases.

Conclusion: Findings from Canada's national surveillance systems support that being fully vaccinated against COVID-19, having a longer time interval between doses and receiving a messenger ribonucleic acid (mRNA) COVID-19 vaccine schedule compared to other vaccines reduce the probability of becoming a case, using data from January to August 2021.

Objective: The authors investigated a new standardized technique for evaluating lumbar stability in lumbar lateral flexion-extension (LFE) radiographs. For patients with lumbar spondylolisthesis, a three-part fulcrum with a support platform that included a semiarc leaning tool with armrests, a lifting platform for height adjustment, and a base for stability were used. Standard functional radiographs were used for comparison to determine whether adequate flexion-extension was acquired through use of the fulcrum method.

Methods: A total of 67 consecutive patients diagnosed with L4-5 degenerative lumbar spondylolisthesis were enrolled in the study. The authors analyzed LFE radiographs taken with the patient supported by a fulcrum (LFEF) and without a fulcrum. Sagittal translation (ST), segmental angulation (SA), posterior opening (PO), change in lumbar lordosis (CLL), and lumbar instability (LI) were measured for comparison using functional radiographs.

Results: The average value of SA was 5.76° ± 3.72° in LFE and 9.96° ± 4.00° in LFEF radiographs, with a significant difference between them (p < 0.05). ST and PO were also significantly greater in LFEF than in LFE. The detection rate of instability was 10.4% in LFE and 31.3% in LFEF, and the difference was significant. The CLL was 27.31° ± 11.96° in LFE and 37.07° ± 12.963.16° in LFEF, with a significant difference between these values (p < 0.05).

Conclusions: Compared with traditional LFE radiographs, the LFEF radiographs significantly improved the detection rate of LI. In addition, this method may reduce patient discomfort during the process of obtaining radiographs.

Gender-based violence and violence against children are significant problems in South Africa. Community mobilisation and gender-transformative programming are promising approaches to address and reduce violence. A quantitative evaluation of One Man Can, a gender-transformative community mobilisation programme in South Africa, found mixed results in increasing gender-equitable behaviours and reducing violence. To better understand these findings, we analyse longitudinal qualitative data from community mobilisers, community members and community action teams, exploring individual and community-level factors that facilitate and hinder change. Interviews and focus groups were transcribed and analysed. Participants self-reported changes in their gender-equitable attitudes and use of violence as a result of participation in the programme, although some participants also reported opposition to shifting to a more gender-equitable culture. Facilitators to change included the internalisation of gender-transformative messaging and supportive social networks, which was buoyed by a shared vocabulary in their community generated by One Man Can. Because the programme targeted a critical mass of community members with gender-transformative programming, mobilisers and community action teams were held accountable by community members to model non-violent behaviour. Results reinforce the importance of addressing facilitators and barriers to change at both individual and community levels.

Radiotherapy as one of the four pillars of cancer therapy plays a critical role in the multimodal treatment of thoracic cancers. Due to significant improvements in overall cancer survival, radiotherapy-induced heart disease (RIHD) has become an increasingly recognized adverse reaction which contributes to major radiation-associated toxicities including non-malignant death. This is especially relevant for patients suffering from diseases with excellent prognosis such as breast cancer or Hodgkin's lymphoma, since RIHD may occur decades after radiotherapy. Preclinical studies have enriched our knowledge of many potential mechanisms by which thoracic radiotherapy induces heart injury. Epidemiological findings in humans reveal that irradiation might increase the risk of cardiac disease at even lower doses than previously assumed. Recent preclinical studies have identified non-invasive methods for evaluation of RIHD. Furthermore, potential options preventing or at least attenuating RIHD have been developed. Ongoing research may enrich our limited knowledge about biological mechanisms of RIHD, identify non-invasive early detection biomarkers and investigate potential treatment options that might attenuate or prevent these unwanted side effects. Here, we present a comprehensive review about the published literature regarding clinical manifestation and pathological alterations in RIHD. Biological mechanisms and treatment options are outlined, and challenges in RIHD treatment are summarized.

Adolescence is characterized by high levels of playful social interaction, cognitive development, and increased risk-taking behavior. Juvenile exposure to social isolation or social stress can reduce myelin content in the frontal cortex, alter neuronal excitability, and disrupt hypothalamic pituitary adrenal (HPA) axis function. As compared to group housed animals, social isolation increases anxiety-like phenotypes and reduces social and cognitive performance in adulthood. We designed a neighbor housing environment to alleviate issues related to social isolation that still allowed individual homecages. Neighbor housing consists of four standard mouse cages fused together with semi-permeable ports that allow visual, olfactory, and limited social contact between mice. Adolescent C57BL/6J males and females were group housed (4/cage), single housed (1/cage), or neighbor housed (4/complex). As adults, mice were tested for social, anxiety-like, and cognitive behaviors. Living in this neighbor environment reduced anxiety-like behavior in the social interaction task and in the light-dark task. It also rescued cognitive deficits from single housing in the novel object recognition task. These data suggest that neighbor housing may partially ameliorate the social anxiety and cognitive deficits induced by social isolation. These neighbor cage environments may serve as a conduit by which researchers can house mice in individual cages while still enabling limited social interactions to better model typical adolescent development.