α_1L-adrenoceptors mediate contraction of human erectile tissue

α1-adrenoceptor antagonists can impact upon sexual function and have potential in the treatment of erectile dysfunction. Human erectile tissue contains predominantly α1A-adrenoceptors, and here we examined whether contractions of this tissue are mediated by the functional phenotype, the α1L-adrenoceptor. Functional experiments using subtype selective agonists and antagonists, along with radioligand ([3H]tamsulosin) binding assays, were used to determine the α1-adrenoceptor population. A61603, a α1A-adrenoceptor agonist, was a full agonist with a potency 21-fold greater than that of noradrenaline. The α1A- and α1D-adrenoceptor antagonist tamsulosin antagonized noradrenaline responses with high affinity (pKD = 9.7 ± 0.3), whilst BMY7378 (100 nM) (α1D-adrenoceptor antagonist) failed to antagonize responses. In contrast, relatively low affinity estimates were obtained for both prazosin (pKD = 8.2 ± 0.1) and RS17053 (pKD = 6.9 ± 0.2), antagonists which discriminate between the α1A- and α1L-adrenoceptors. [3H]Tamsulosin bound with high affinity to the receptors of human erectile tissue (pKD = 10.3 ± 0.1) with a receptor density of 28.1 ± 1.4 fmol mg−1 protein. Prazosin displacement of [3H]tamsulosin binding revealed a single homogenous population of binding sites with a relatively low affinity for prazosin (pKi = 8.9). Taken together these data confirm that the receptor mediating contraction in human erectile tissue has the pharmacological properties of the α1L-adrenoceptor. Keywords: Erectile tissue, α1-adrenoceptor subtypes, α1L-adrenoceptor, Tamsulosin, Prazosi

Impact of Tail Loss on the Behaviour and Locomotor Performance of Two Sympatric Lampropholis Skink Species

Caudal autotomy is an anti-predator behaviour that is used by many lizard species. Although there is an immediate survival benefit, the subsequent absence of the tail may inhibit locomotor performance, alter activity and habitat use, and increase the individuals' susceptibility to future predation attempts. We used laboratory experiments to examine the impact of tail autotomy on locomotor performance, activity and basking site selection in two lizard species, the delicate skink (Lampropholis delicata) and garden skink (L. guichenoti), that occur sympatrically throughout southeastern Australia and are exposed to an identical suite of potential predators. Post-autotomy tail movement did not differ between the two Lampropholis species, although a positive relationship between the shed tail length and distance moved, but not the duration of movement, was observed. Tail autotomy resulted in a substantial decrease in sprint speed in both species (28–39%), although this impact was limited to the optimal performance temperature (30°C). Although L. delicata was more active than L. guichenoti, tail autotomy resulted in decreased activity in both species. Sheltered basking sites were preferred over open sites by both Lampropholis species, although this preference was stronger in L. delicata. Caudal autotomy did not alter the basking site preferences of either species. Thus, both Lampropholis species had similar behavioural responses to autotomy. Our study also indicates that the impact of tail loss on locomotor performance may be temperature-dependent and highlights that future studies should be conducted over a broad thermal range

Back to live: Returning to in-person engagement with arts and culture in the Liverpool City Region

On July 19th 2021, the UK government lifted the COVID-19 restrictions that had been in place since March 2020, including wearing masks, social distancing, and all other legal requirements. The return to in-person events has been slow and gradual, showing that audiences are still cautious when (and if) they resume engaging in arts and culture. Patterns of audience behavior have also changed, shifting toward local attendance, greater digital and hybrid engagement, and openness to event format changes. As the arts and cultural industry recovers from the pandemic, it is important to adopt an audience-oriented approach and look at the changing patterns of engaging in arts and culture. This study aims to better understand the impact of the pandemic on the patterns of cultural and arts engagement. Eight qualitative interviews were conducted to explore the changes in arts and cultural engagement since the restrictions were lifted, focusing particularly on the audience’s experiences of returning to in-person arts and cultural events in the Liverpool City Region (LCR). Using framework analysis, three themes were identified from the data: The new normal: reframing pre-pandemic and pandemic experiences of arts and culture, Re-adjusting to in-person provision, and Moving forward: online and blended provision. The findings show that the pandemic altered the ways that people engage in arts and culture. The “new normal,” a blend of pandemic and pre-pandemic experiences, illustrates how the pandemic has highlighted and reconfigured the importance of arts and culture, in terms of personal and cultural identity. Resuming in-person engagement after a long break, participants noted that they were able to feel more like themselves again. Arts and culture were perceived to be beneficial in rebuilding personal resilience and confidence. Engaging in arts and culture, following the isolating experience of the pandemic, has also helped participants feel reconnected to others through their shared experiences. Finally, the findings suggest that online provision remains vital for many, ensuring wider inclusivity, particularly for vulnerable audiences. At the same time, it is important to acknowledge the barriers to online inclusion and the possibility of this resulting in a growing digital divide

Unpacking the drivers of corporate social performance: a multilevel, multistakeholder, and multimethod analysis

The question of what drives corporate social performance (CSP) has become a vital concern for many managers and researchers of large corporations. This study addresses this question by adopting a multilevel, multistakeholder, and multimethod approach to theorize and estimate the relative influence of macro (national business system and country), meso (industry), and micro (firm-level) factors on CSP. Applying three different methods of variance decomposition analysis to an international sample of 2,060 large public companies over a time span of 5 years, our results show that firm-level factors explain the largest proportion of variance in aggregate CSP as well as CSP oriented toward communities, the natural environment, and employees. These results support our hypotheses according to which CSP is not primarily driven by macrolevel or meso level factors, except for shareholder-oriented CSP, which is relatively more influenced by country-level factors. As a whole, our findings also point to the value of subdividing CSP into its stakeholder-specific components as this disaggregation allows for a more careful examination of distinct drivers of distinct aspects of CSP

Proteomic Analysis of a Noninvasive Human Model of Acute Inflammation and Its Resolution: The Twenty-one Day Gingivitis Model

The 21-day experimental gingivitis model, an established noninvasive model of inflammation in response to increasing bacterial accumulation in humans, is designed to enable the study of both the induction and resolution of inflammation. Here, we have analyzed gingival crevicular fluid, an oral fluid comprising a serum transudate and tissue exudates, by LC−MS/MS using Fourier transform ion cyclotron resonance mass spectrometry and iTRAQ isobaric mass tags, to establish meta-proteomic profiles of inflammation-induced changes in proteins in healthy young volunteers. Across the course of experimentally induced gingivitis, we identified 16 bacterial and 186 human proteins. Although abundances of the bacterial proteins identified did not vary temporally, Fusobacterium outer membrane proteins were detected. Fusobacterium species have previously been associated with periodontal health or disease. The human proteins identified spanned a wide range of compartments (both extracellular and intracellular) and functions, including serum proteins, proteins displaying antibacterial properties, and proteins with functions associated with cellular transcription, DNA binding, the cytoskeleton, cell adhesion, and cilia. PolySNAP3 clustering software was used in a multilayered analytical approach. Clusters of proteins that associated with changes to the clinical parameters included neuronal and synapse associated proteins

Polycystin-2 is required for chondrocyte mechanotransduction and traffics to the primary cilium in response to mechanical stimulation

Primary cilia and associated intraflagellar transport are essential for skeletal development, joint homeostasis, and the response to mechanical stimuli, although the mechanisms remain unclear. Polycystin-2 (PC2) is a member of the transient receptor potential polycystic (TRPP) family of cation channels, and together with Polycystin-1 (PC1), it has been implicated in cilia-mediated mechanotransduction in epithelial cells. The current study investigates the effect of mechanical stimulation on the localization of ciliary polycystins in chondrocytes and tests the hypothesis that they are required in chondrocyte mechanosignaling. Isolated chondrocytes were subjected to mechanical stimulation in the form of uniaxial cyclic tensile strain (CTS) in order to examine the effects on PC2 ciliary localization and matrix gene expression. In the absence of strain, PC2 localizes to the chondrocyte ciliary membrane and neither PC1 nor PC2 are required for ciliogenesis. Cartilage matrix gene expression (Acan, Col2a) is increased in response to 10% CTS. This response is inhibited by siRNA-mediated loss of PC1 or PC2 expression. PC2 ciliary localization requires PC1 and is increased in response to CTS. Increased PC2 cilia trafficking is dependent on the activation of transient receptor potential cation channel subfamily V member 4 (TRPV4) activation. Together, these findings demonstrate for the first time that polycystins are required for chondrocyte mechanotransduction and highlight the mechanosensitive cilia trafficking of PC2 as an important component of cilia-mediated mechanotransduction

Micro-processes of translation in the transfer of practices from MNE headquarters to foreign subsidiaries: the role of subsidiary translators

Recent research has increasingly emphasized the micro-foundations of knowledge transformation in multi-national enterprises (MNEs). Although the literature has provided ample evidence of the enablers of and barriers to the translation of practices, less is known about the activities and efforts of translators that lead to specific types of translation in the context of the transfer of practices initiated at a MNE’s headquarters (HQ) to foreign subsidiaries. We apply a Scandinavian institutionalist approach to examine the translation of corporate social responsibility reporting, an HQ-initiated practice that is transferred to five foreign subsidiaries of a UK-based MNE. Our paper builds from a preliminary framework based on extant research to develop an extended framework of the micro-processes of translation. By theorizing the sequence of the micro-processes undertaken by translators, identifying the conditions under which they occur, and connecting them to the three types of translation, we provide a deep understanding of the micro-foundations of translation when transferring practices from HQ to subsidiaries. Our paper shows that translation is an evolving phenomenon and illuminates the importance of attending to the social, spatial, and temporal situatedness of translators. It also brings insights into the individual experience of institutional distance and its effects on translation