Honey Bee Dopamine and Octopamine Receptors Linked to Intracellular Calcium Signaling Have a Close Phylogenetic and Pharmacological Relationship

BACKGROUND: Three dopamine receptor genes have been identified that are highly conserved among arthropod species. One of these genes, referred to in honey bees as Amdop2, shows a close phylogenetic relationship to the a-adrenergic-like octopamine receptor family. In this study we examined in parallel the functional and pharmacological properties of AmDOP2 and the honey bee octopamine receptor, AmOA1. For comparison, pharmacological properties of the honey bee dopamine receptors AmDOP1 and AmDOP3, and the tyramine receptor AmTYR1, were also examined. METHODOLOGY/PRINCIPAL FINDINGS: Using HEK293 cells heterologously expressing honey bee biogenic amine receptors, we found that activation of AmDOP2 receptors, like AmOA1 receptors, initiates a rapid increase in intracellular calcium levels. We found no evidence of calcium signaling via AmDOP1, AmDOP3 or AmTYR1 receptors. AmDOP2- and AmOA1-mediated increases in intracellular calcium were inhibited by 10 µM edelfosine indicating a requirement for phospholipase C-β activity in this signaling pathway. Edelfosine treatment had no effect on AmDOP2- or AmOA1-mediated increases in intracellular cAMP. The synthetic compounds mianserin and epinastine, like cis-(Z)-flupentixol and spiperone, were found to have significant antagonist activity on AmDOP2 receptors. All 4 compounds were effective antagonists also on AmOA1 receptors. Analysis of putative ligand binding sites offers a possible explanation for why epinastine acts as an antagonist at AmDOP2 receptors, but fails to block responses mediated via AmDOP1. CONCLUSIONS/SIGNIFICANCE: Our results indicate that AmDOP2, like AmOA1, is coupled not only to cAMP, but also to calcium-signalling and moreover, that the two signalling pathways are independent upstream of phospholipase C-β activity. The striking similarity between the pharmacological properties of these 2 receptors suggests an underlying conservation of structural properties related to receptor function. Taken together, these results strongly support phylogenetic analyses indicating that the AmDOP2 and AmOA1 receptor genes are immediate paralogs

Varroakvalstrets effekt på virus i angripna honungsbisamhällen

Vilken effekt har varroakvalster på de virus som infekterar bisamhällen? Forskare vid INRA (Frankrikes nationella institution för jordbruksforskning) i Avignon, Frankrike, University of Otago i Nya Zeeland och Sveriges lantbruksuniversitet (SLU), nyttjade en unik situation i Nya Zeeland där landet, liksom Sverige, har varroaangripna respektive icke angripna regioner. Varroa är relativt nyetablerad i Nya Zeeland. Den påvisades först på Nordön år 2000, och har stadigt spridits söderut under de 14 åren som gått sedan introduktionen. Forskarna har undersökt virusprofilen hos bisamhällena sedan etablering av kvalstret i de olika regionerna. Studien, som publicerades 2014, visar en drastisk ändring av det virala landskapet i bisamhällena som sammanfaller med etablering av varroa, vilket ökar risken för synergier mellan olika virus som är skadliga för bina

Mitsui-7, heat-treated, and nitrogen-doped multi-walled carbon nanotubes elicit genotoxicity in human lung epithelial cells.

Background: The unique physicochemical properties of multi-walled carbon nanotubes (MWCNT) have led to many industrial applications. Due to their low density and small size, MWCNT are easily aerosolized in the workplace making respiratory exposures likely in workers. The International Agency for Research on Cancer designated the pristine Mitsui-7 MWCNT (MWCNT-7) as a Group 2B carcinogen, but there was insufficient data to classify all other MWCNT. Previously, MWCNT exposed to high temperature (MWCNT-HT) or synthesized with nitrogen (MWCNT-ND) have been found to elicit attenuated toxicity; however, their genotoxic and carcinogenic potential are not known. Our aim was to measure the genotoxicity of MWCNT-7 compared to these two physicochemically-altered MWCNTs in human lung epithelial cells (BEAS-2B & SAEC). Results: Dose-dependent partitioning of individual nanotubes in the cell nuclei was observed for each MWCNT material and was greatest for MWCNT-7. Exposure to each MWCNT led to significantly increased mitotic aberrations with multi- and monopolar spindle morphologies and fragmented centrosomes. Quantitative analysis of the spindle pole demonstrated significantly increased centrosome fragmentation from 0.024-2.4 [mu]g/mL of each MWCNT. Significant aneuploidy was measured in a dose-response from each MWCNT-7, HT, and ND; the highest dose of 24 [mu]g/mL produced 67, 61, and 55%, respectively. Chromosome analysis demonstrated significantly increased centromere fragmentation and translocations from each MWCNT at each dose. Following 24 h of exposure to MWCNT-7, ND and/or HT in BEAS-2B a significant arrest in the G1/S phase in the cell cycle occurred, whereas the MWCNT-ND also induced a G2 arrest. Primary SAEC exposed for 24 h to each MWCNT elicited a significantly greater arrest in the G1 and G2 phases. However, SAEC arrested in the G1/S phase after 72 h of exposure. Lastly, a significant increase in clonal growth was observed one month after exposure to 0.024 [mu]g/mL MWCNT-HT & ND. Conclusions: Although MWCNT-HT & ND cause a lower incidence of genotoxicity, all three MWCNTs cause the same type of mitotic and chromosomal disruptions. Chromosomal fragmentation and translocations have not been observed with other nanomaterials. Because in vitro genotoxicity is correlated with in vivo genotoxic response, these studies in primary human lung cells may predict the genotoxic potency in exposed human populations

A “Learning Revolution”? Investigating Pedagogic Practices around Interactive Whiteboards in British Primary Classrooms

Interactive whiteboards have been rapidly introduced into all primary schools under UK Government initiatives. These large, touch-sensitive screens, which control a computer connected to a digital projector, seem to be the first type of educational technology particularly suited for whole-class teaching and learning. Strong claims are made for their value by manufacturers and policy makers, but there has been little research on how, if at all, they influence established pedagogic practices, communicative processes and educational goals. This study has been designed to examine this issue, using observations in primary (elementary) school classrooms. It is funded by the UK Economic and Social Research Council and builds on the authors’ previous research on ICT in educational dialogues and collaborative activities

The sexual attitudes and lifestyles of London's Eastern Europeans (SALLEE Project): design and methods.

BACKGROUND: Since May 2004, ten Central and Eastern European (CEE) countries have joined the European Union, leading to a large influx of CEE migrants to the United Kingdom (UK). The SALLEE project (sexual attitudes and lifestyles of London's Eastern Europeans) set out to establish an understanding of the sexual lifestyles and reproductive health risks of CEE migrants. CEE nationals make up a small minority of the population resident in the UK with no sampling frame from which to select a probability sample. There is also difficulty estimating the socio-demographic and geographical distribution of the population. In addition, measuring self-reported sexual behaviour which is generally found to be problematic, may be compounded among people from a range of different cultural and linguistic backgrounds. This paper will describe the methods adopted by the SALLEE project to address these challenges. METHODS: The research was undertaken using quantitative and qualitative methods: a cross-sectional survey of CEE migrants based on three convenience samples (recruited from community venues, sexual health clinics and from the Internet) and semi-structured in-depth interviews with a purposively selected sample of CEE migrants. A detailed social mapping exercise of the CEE community was conducted prior to commencement of the survey to identify places where CEE migrants could be recruited. A total of 3,005 respondents took part in the cross-sectional survey, including 2,276 respondents in the community sample, 357 in the clinic sample and 372 in the Internet sample. 40 in-depth qualitative interviews were undertaken with a range of individuals, as determined by the interview quota matrix. DISCUSSION: The SALLEE project has benefited from using quantitative research to provide generalisable data on a range of variables and qualitative research to add in-depth understanding and interpretation. The social mapping exercise successfully located a large number of CEE migrants for the community sample and is recommended for other migrant populations, especially when little or no official data are available for this purpose. The project has collected timely data that will help us to understand the sexual lifestyles, reproductive health risks and health service needs of CEE communities in the UK

Difficulty accessing condoms because of the COVID-19 pandemic reported by gay, bisexual and other men who have sex with men in the UK: findings from a large, cross-sectional, online survey

BACKGROUND: COVID-19 restrictions severely reduced face-to-face sexual health services, an important access point for condoms. We examine whether gay, bisexual and other men who have sex with men (GBMSM) in the UK had difficulty accessing condoms during the first year of the pandemic, and if so, which groups were most affected. METHODS: Questions about difficulty accessing condoms were asked as part of a short, online cross-sectional survey of GBMSM undertaken November/December 2021, recruited via social media and Grindr. Eligible participants were UK-resident GBMSM (cis/trans/gender-diverse person assigned male at birth [AMAB]), aged ≥16 years who were sexually active (reported sex with men in the last year). Multivariable logistic regression was used to examine if and how reporting this outcome varied by key sociodemographic, health and behavioural factors independent of the potential confounding effect of numbers of new male sex partners. RESULTS: Of all participants (N = 1039), 7.4% (n = 77) reported difficulty accessing condoms due to the pandemic. This was higher among younger GBMSM (aged 16-29 years vs. ≥45; 12.8% vs. 4.9%; aOR: 2.78); trans/gender-diverse AMAB participants (vs. cis gender males; 24.4% vs. 6.6%; aOR = 4.86); bisexually-identifying participants (vs. gay-identifying; 11.1% vs. 6.5%; aOR = 1.78); and those without degree level education (vs. having a degree; 9.8% vs. 5.6%; aOR = 2.01). CONCLUSIONS: A minority of sexually active GBMSM reported difficulty accessing condoms because of the pandemic, however, this was more common amongst those who already experience a disproportionate burden of poor sexual health. Interventions are needed to address these inequalities in accessing this important primary STI/HIV prevention measure

COVID-19 infection and vaccination uptake in men and gender-diverse people who have sex with men in the UK: analyses of a large, online community cross-sectional survey (RiiSH-COVID) undertaken November–December 2021

BACKGROUND: Men and gender-diverse people who have sex with men are disproportionately affected by health conditions associated with increased risk of severe illness due to COVID-19 infection. METHODS: An online cross-sectional survey of men and gender-diverse people who have sex with men in the UK recruited via social networking and dating applications from 22 November-12 December 2021. Eligible participants included self-identifying men, transgender women, or gender-diverse individuals assigned male at birth (AMAB), aged ≥ 16, who were UK residents, and self-reported having had sex with an individual AMAB in the last year. We calculated self-reported COVID-19 test-positivity, proportion reporting long COVID, and COVID-19 vaccination uptake anytime from pandemic start to survey completion (November/December 2021). Logistic regression was used to assess sociodemographic, clinical, and behavioural characteristics associated with SARS-CoV-2 (COVID-19) test positivity and complete vaccination (≥ 2 vaccine doses). RESULTS: Among 1,039 participants (88.1% white, median age 41 years [interquartile range: 31-51]), 18.6% (95% CI: 16.3%-21.1%) reported COVID-19 test positivity, 8.3% (95% CI: 6.7%-10.1%) long COVID, and 94.5% (95% CI: 93.3%-96.1%) complete COVID-19 vaccination through late 2021. In multivariable models, COVID-19 test positivity was associated with UK country of residence (aOR: 2.22 [95% CI: 1.26-3.92], England vs outside England) and employment (aOR: 1.55 [95% CI: 1.01-2.38], current employment vs not employed). Complete COVID-19 vaccination was associated with age (aOR: 1.04 [95% CI: 1.01-1.06], per increasing year), gender (aOR: 0.26 [95% CI: 0.09-0.72], gender minority vs cisgender), education (aOR: 2.11 [95% CI: 1.12-3.98], degree-level or higher vs below degree-level), employment (aOR: 2.07 [95% CI: 1.08-3.94], current employment vs not employed), relationship status (aOR: 0.50 [95% CI: 0.25-1.00], single vs in a relationship), COVID-19 infection history (aOR: 0.47 [95% CI: 0.25-0.88], test positivity or self-perceived infection vs no history), known HPV vaccination (aOR: 3.32 [95% CI: 1.43-7.75]), and low self-worth (aOR: 0.29 [95% CI: 0.15-0.54]). CONCLUSIONS: In this community sample, COVID-19 vaccine uptake was high overall, though lower among younger age-groups, gender minorities, and those with poorer well-being. Efforts are needed to limit COVID-19 related exacerbation of health inequalities in groups who already experience a greater burden of poor health relative to other men who have sex with men

'Stay at home …': exploring the impact of the COVID-19 public health response on sexual behaviour and health service use among men who have sex with men: findings from a large online survey in the UK.

OBJECTIVES: The first UK national lockdown began on 23 March 2020, in response to the COVID-19 pandemic, and led to reduced STI/HIV service provision in the UK. We investigated sexual behaviour, use and need for sexual healthcare during the pandemic. METHODS: Participants (N=2018), including men (cis/transgender), transwomen and gender-diverse people reporting sex with another man (cis/transgender) or non-binary person assigned male at birth, completed an online cross-sectional survey (23 June 2020-14 July 2020), in response to adverts on social media and dating apps.Sexual behaviour, service use and unmet need for STI testing (any new male and/or multiple condomless anal sex (CAS) partners without STI testing) in the 3 months since lockdown began were examined and compared using multivariable analyses with an equivalent 3-month period in a 2017 survey (N=1918), conducted by the same research team. RESULTS: Since lockdown began, 36.7% of participants reported one or more new partners, 17.3% reported CAS with multiple partners, 29.7% HIV testing (among 1815 of unknown/negative status), 24.9% STI testing and 15.4% using pre-exposure prophylaxis (PrEP).Since lockdown began, 25.3% of participants had unmet need for STI testing. This was more likely among Asian versus white participants (adjusted OR (aOR)=1.76, (1.14 to 2.72), p=0.01); for participants living in Scotland (aOR=2.02, (1.40 to 2.91), p<0.001) or Northern Ireland (aOR=1.93, (1.02-3.63), p=0.04) versus England; and for those living with HIV (aOR=1.83, (1.32 to 2.53), p<0.001).Compared to 2017, the equivalent 2020 subsample were less likely to report new male partners (46.8% vs 71.1%, p<0.001), multiple CAS partners (20.3% vs 30.8%, p<0.001) and have unmet need for STI testing (32.8% vs 42.5%, p<0.001) in the past 3 months. CONCLUSIONS: We found potential for ongoing STI/HIV transmission among men who have sex with men during the initial UK lockdown, despite reduced sexual activity, and inequalities in service access. These findings will support public health planning to mitigate health risks during and after the COVID-19 response

Difficulty accessing condoms because of the COVID-19 pandemic reported by gay, bisexual and other men who have sex with men in the UK: findings from a large, cross-sectional, online survey

BACKGROUND: COVID-19 restrictions severely reduced face-to-face sexual health services, an important access point for condoms. We examine whether gay, bisexual and other men who have sex with men (GBMSM) in the UK had difficulty accessing condoms during the first year of the pandemic, and if so, which groups were most affected. METHODS: Questions about difficulty accessing condoms were asked as part of a short, online cross-sectional survey of GBMSM undertaken November/December 2021, recruited via social media and Grindr. Eligible participants were UK-resident GBMSM (cis/trans/gender-diverse person assigned male at birth [AMAB]), aged ≥16 years who were sexually active (reported sex with men in the last year). Multivariable logistic regression was used to examine if and how reporting this outcome varied by key sociodemographic, health and behavioural factors independent of the potential confounding effect of numbers of new male sex partners. RESULTS: Of all participants (N = 1039), 7.4% (n = 77) reported difficulty accessing condoms due to the pandemic. This was higher among younger GBMSM (aged 16-29 years vs. ≥45; 12.8% vs. 4.9%; aOR: 2.78); trans/gender-diverse AMAB participants (vs. cis gender males; 24.4% vs. 6.6%; aOR = 4.86); bisexually-identifying participants (vs. gay-identifying; 11.1% vs. 6.5%; aOR = 1.78); and those without degree level education (vs. having a degree; 9.8% vs. 5.6%; aOR = 2.01). CONCLUSIONS: A minority of sexually active GBMSM reported difficulty accessing condoms because of the pandemic, however, this was more common amongst those who already experience a disproportionate burden of poor sexual health. Interventions are needed to address these inequalities in accessing this important primary STI/HIV prevention measure

Sexual behaviour, STI and HIV testing and testing need among gay, bisexual and other men who have sex with men recruited for online surveys pre/post-COVID-19 restrictions in the UK.

OBJECTIVES: We examined sexual behaviour, sexually transmitted infection (STI) and HIV testing and testing need, and identified associated factors, among gay, bisexual and other men who have sex with men (GBMSM) in the UK after COVID-19 restrictions ended, and compared these with 'pre-pandemic' estimates. METHODS: We analysed survey data from GBMSM (N=1039) recruited via social media and Grindr in November-December 2021. We then compared Grindr-recruited 2021 participants (N=437) with those from an equivalent survey fielded in March-May 2017 (N=1902). Questions on sexual behaviour and service use had lookback periods of 3-4 months in both surveys. Unmet testing need was defined as reporting any new male and/or multiple condomless anal sex (CAS) partners without recent STI/HIV testing. Participants were UK residents, GBMSM, aged ≥16 years who reported sex with men in the last year. Multivariable logistic regression identified associated sociodemographic and health-related factors with unmet STI/HIV testing need in 2021, and then for 2017/2021 comparative analyses, adjusting for demographic differences. RESULTS: In 2021, unmet STI and HIV testing need were greater among older GBMSM (aged ≥45 years vs 16-29 years; adjusted OR (aOR): 1.45 and aOR: 1.77, respectively), and lower for pre-exposure prophylaxis (PrEP) users (vs non-PrEP users; aOR: 0.32 and aOR: 0.23, respectively). Less unmet STI testing need was observed among HIV-positive participants (vs HIV-negative/unknown; aOR: 0.63), and trans and non-binary participants (vs cisgender male; aOR: 0.34). Between 2017 (reference) and 2021, reported sexual risk behaviours increased: ≥1 recent new male sex partner (72.1%-81.1%, aOR: 1.71) and ≥2 recent CAS partners (30.2%-48.5%, aOR: 2.22). Reporting recent STI testing was greater in 2021 (37.5%-42.6%, aOR: 1.34) but not recent HIV testing, and there was no significant change over time in unmet STI (39.2% vs 43.7%) and HIV (32.9% vs 39.0%) testing need. DISCUSSION: Comparable community surveys suggest that UK resident GBMSM may have engaged in more sexual risk behaviours in late 2021 than pre-pandemic. While there was no evidence of reduced STI/HIV service access during this time, there remained considerable unmet STI/HIV testing need