In Vivo Activation of the Intracrine Vitamin D Pathway in Innate Immune Cells and Mammary Tissue during a Bacterial Infection

Numerous in vitro studies have shown that toll-like receptor signaling induces 25-hydroxyvitamin D3 1α-hydroxylase (1α-OHase; CYP27B1) expression in macrophages from various species. 1α-OHase is the primary enzyme that converts 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Subsequently, synthesis of 1,25(OH)2D3 by 1α-OHase in macrophages has been shown to modulate innate immune responses of macrophages. Despite the numerous in vitro studies that have shown 1α-OHase expression is induced in macrophages, however, evidence that 1α-OHase expression is induced by pathogens in vivo is limited. The objective of this study was to evaluate 1α-OHase gene expression in macrophages and mammary tissue during an in vivo bacterial infection with Streptococcus uberis. In tissue and secreted cells from the infected mammary glands, 1α-OHase gene expression was significantly increased compared to expression in tissue and cells from the healthy mammary tissue. Separation of the cells by FACS9 revealed that 1α-OHase was predominantly expressed in the CD14+ cells isolated from the infected mammary tissue. The 24-hydroxylase gene, a gene that is highly upregulated by 1,25(OH)2D3, was significantly more expressed in tissue and cells from the infected mammary tissue than from the healthy uninfected mammary tissue thus indicating significant local 1,25(OH)2D3 production at the infection site. In conclusion, this study provides the first in vivo evidence that 1α-OHase expression is upregulated in macrophages in response to bacterial infection and that 1α-OHase at the site of infection provides 1,25(OH)2D3 for local regulation of vitamin D responsive genes

Intramanual and intermanual transfer of the curvature aftereffect

The existence and transfer of a haptic curvature aftereffect was investigated to obtain a greater insight into neural representation of shape. The haptic curvature aftereffect is the phenomenon whereby a flat surface is judged concave if the preceding touched stimulus was convex and vice versa. Single fingers were used to touch the subsequently presented stimuli. A substantial aftereffect was found when the adaptation surface and the test surface were touched by the same finger. Furthermore, a partial, but significant transfer of the aftereffect was demonstrated between fingers of the same hand and between fingers of both the hands. These results provide evidence that curvature information is not only represented at a level that is directly connected to the mechanoreceptors of individual fingers but is also represented at a stage in the somatosensory cortex shared by the fingers of both the hands

Deletion of parasite immune modulatory sequences combined with immune activating signals enhances vaccine mediated protection against filarial nematodes

<p>Background: Filarial nematodes are tissue-dwelling parasites that can be killed by Th2-driven immune effectors, but that have evolved to withstand immune attack and establish chronic infections by suppressing host immunity. As a consequence, the efficacy of a vaccine against filariasis may depend on its capacity to counter parasite-driven immunomodulation.</p> <p>Methodology and Principal Findings: We immunised mice with DNA plasmids expressing functionally-inactivated forms of two immunomodulatory molecules expressed by the filarial parasite Litomosoides sigmodontis: the abundant larval transcript-1 (LsALT) and cysteine protease inhibitor-2 (LsCPI). The mutant proteins enhanced antibody and cytokine responses to live parasite challenge, and led to more leukocyte recruitment to the site of infection than their native forms. The immune response was further enhanced when the antigens were targeted to dendritic cells using a single chain Fv-αDEC205 antibody and co-administered with plasmids that enhance T helper 2 immunity (IL-4) and antigen-presenting cell recruitment (Flt3L, MIP-1α). Mice immunised simultaneously against the mutated forms of LsALT and LsCPI eliminated adult parasites faster and consistently reduced peripheral microfilaraemia. A multifactorial analysis of the immune response revealed that protection was strongly correlated with the production of parasite-specific IgG1 and with the numbers of leukocytes present at the site of infection.</p> <p>Conclusions: We have developed a successful strategy for DNA vaccination against a nematode infection that specifically targets parasite-driven immunosuppression while simultaneously enhancing Th2 immune responses and parasite antigen presentation by dendritic cells.</p&gt

Affordances-in-practice:an ethnographic critique of social media logic and context collapse

Drawing on data gathered during ethnographic fieldwork in Mardin, a medium-sized town in southeast Turkey, this article shows that social media users actively appropriate online platforms and change privacy settings in order to keep different social spheres and social groups apart. Keeping different online social contexts distinct from each other is taken for granted as a way of using social media in Mardin. By contrast, social media scholars have extensively discussed the effects of social media in terms of context collapse. The article highlights how context collapse is the result of patterns of usage within Anglo-American contexts and not the consequence of a platform's architecture or social media logic. It then suggests a theoretical refinement of affordances, and proposes the concept of affordances-in-practice

An Efficient Rule-Based Distributed Reasoning Framework for Resource-bounded Systems

© 2018, The Author(s). Over the last few years, context-aware computing has received a growing amount of attention among the researchers in the IoT and ubiquitous computing community. In principle, context-aware computing transforms a physical environment into a smart space by sensing the surrounding environment and interpreting the situation of the user. This process involves three major steps: context acquisition, context modelling, and context-aware reasoning. Among other approaches, ontology-based context modelling and rule-based context reasoning are widely used techniques to enable semantic interoperability and interpreting user situations. However, implementing rich context-aware applications that perform reasoning on resource-bounded mobile devices is quite challenging. In this paper, we present a context-aware systems development framework for smart spaces, which includes a lightweight efficient rule engine and a wide range of user preferences to reduce the number of rules while inferring personalized contexts. This shows rules can be reduced in order to optimize the inference engine execution speed, and ultimately to reduce total execution time and execution cost

Haptic adaptation to slant: No transfer between exploration modes

Human touch is an inherently active sense: to estimate an object’s shape humans often move their hand across its surface. This way the object is sampled both in a serial (sampling different parts of the object across time) and parallel fashion (sampling using different parts of the hand simultaneously). Both the serial (moving a single finger) and parallel (static contact with the entire hand) exploration modes provide reliable and similar global shape information, suggesting the possibility that this information is shared early in the sensory cortex. In contrast, we here show the opposite. Using an adaptation-and-transfer paradigm, a change in haptic perception was induced by slant-adaptation using either the serial or parallel exploration mode. A unified shape-based coding would predict that this would equally affect perception using other exploration modes. However, we found that adaptation-induced perceptual changes did not transfer between exploration modes. Instead, serial and parallel exploration components adapted simultaneously, but to different kinaesthetic aspects of exploration behaviour rather than object-shape per se. These results indicate that a potential combination of information from different exploration modes can only occur at down-stream cortical processing stages, at which adaptation is no longer effective

Plasma concentrations of 25-hydroxyvitamin D among Jordanians: Effect of biological and habitual factors on vitamin D status

<p>Abstract</p> <p>Background</p> <p>Vitamin D is cutaneously synthesized following sun exposure (vitamin D₃) as well as it is derived from dietary intake (vitamin D₃and D₂). Vitamin D₂and D₃are metabolized in the liver to 25-hydroxyvitamin D (25(OH)D). This metabolite is considered the functional indicator of vitamin D stores in humans. Since Jordan latitude is 31°N, cutaneous synthesis of vitamin D₃should be sufficient all year round. However, many indications reveal that it is not the case. Thus, this study was conducted to determine the 25(OH)D status among Jordanians.</p> <p>Methods</p> <p>Three hundred healthy volunteers were enrolled in a cross sectional study; 201 females and 99 males. 25(OH)D and calcium concentrations were measured by enzyme linked immunosorbent assay and spectroscopy techniques, respectively. All participants filled a study questionnaire that covered age, sex, height, weight, diet, and dress style for females. Females were divided according to their dress style: Western style, Hijab (all body parts are covered except the face and hands), and Niqab (all body parts are covered including face and hands).</p> <p>Results</p> <p>The average plasma 25(OH)D levels in males and females were 44.5 ± 10.0 nmol/l and 31.1 ± 12.0 nmol/l, respectively. However, when female 25(OH)D levels were categorized according to dress styles, the averages became 40.3, 31.3 and 28.5 nmol/l for the Western style, Hijab and Niqab groups, respectively. These 25(OH)D levels were significantly less than those of males (p < 0.05, 0.001, 0.001, respectively). In addition, the plasma 25(OH)D levels of the Western style group was significantly higher than those of Hijab and Niqab groups (p < 0.001). Furthermore, dairy consumption in males was a positive significant factor in vitamin D status. Even though calcium concentrations were within the reference range, the Hijab and Niqab-dressed females have significantly less plasma calcium levels than males (p < 0.01).</p> <p>Conclusions</p> <p>Very low plasma 25(OH)D levels in females wearing Hijab or Niqab are highly attributed to low sunlight or UVB exposure. In addition, most of males (76%) and Western style dressed females (90%) have 25(OH)D concentrations below the international recommended values (50 nmol/l), suggesting that although sun exposure should be enough, other factors do play a role in these low concentrations. These findings emphasize the importance of vitamin D supplementation especially among conservatively dressed females, and determining if single nucleotide polymorphisms of the genes involved in vitamin D metabolism do exist among Jordanians.</p

General practitioners apply the usual care for shoulder complaints better than expected – analysis of videotaped consultations

BACKGROUND: The education and activation program (EAP) is a newly developed intervention to prevent the development of chronic shoulder complaints (SCs). Trained general practitioners (GPs) administer the EAP. The EAP addresses inadequate cognitions and maladaptive behavior related to the SCs. The effect of the EAP is evaluated in a randomized clinical trial. The aim of the present study is to use videotaped consultations to study (1) the performance of trained GPs administering the EAP and (2) the presence of key features of the EAP already embedded in usual care (UC). METHODS: Five trained GPs were videotaped while treating a standardized patient with EAP. Additionally, five GPs administering UC were videotaped. Two blinded observers evaluated the videotapes in relation to key features of the EAP which were scored on the EAP checklist. RESULTS: The mean total score on the EAP checklist was 4.7 (SD = 2.9) for the UC group and 7.1 (SD = 2.1) for the EAP group. Neither group reached a score higher than 8, which was considered to reflect an acceptable number of key EAP features. CONCLUSION: Our comparison of the presence of key features of EAP shows that the UC and EAP groups differed less than was expected. GPs in the UC group performed above expectation, with a mean total score of 4.7. Moreover, the low number of key features present in the EAP group may very well have led to a reduced effectiveness of the EAP. The results of this study can be used to optimize the training of GPs using the EAP