Submillimetre Transient Science in the Next Decade

White paper from the EAO Submillimetre Futures Meeting, 20-23 May 2019, Nanjing, ChinaThis white paper gives a brief summary of the time domain science that has been performed with the JCMT in recent years and highlights the opportunities for continuing work in this field over the next decade. The main focus of this document is the JCMT Transient Survey, a large program initiated in 2015 to measure the frequency and amplitude of variability events associated with protostars in nearby star-forming regions. After summarising the major accomplishments so far, an outline is given for extensions to the current survey, featuring a discussion on what will be possible with the new 850 micron camera that is expected to be installed in late 2022. We also discuss possible applications of submillimetre monitoring to active galactic nuclei, X-ray binaries, asymptotic giant branch stars, and flare stars.Science and Technology Facilities Counci

A putative relay circuit providing low-threshold mechanoreceptive input to lamina I projection neurons via vertical cells in lamina II of the rat dorsal horn

Background: Lamina I projection neurons respond to painful stimuli, and some are also activated by touch or hair movement. Neuropathic pain resulting from peripheral nerve damage is often associated with tactile allodynia (touch-evoked pain), and this may result from increased responsiveness of lamina I projection neurons to non-noxious mechanical stimuli. It is thought that polysynaptic pathways involving excitatory interneurons can transmit tactile inputs to lamina I projection neurons, but that these are normally suppressed by inhibitory interneurons. Vertical cells in lamina II provide a potential route through which tactile stimuli can activate lamina I projection neurons, since their dendrites extend into the region where tactile afferents terminate, while their axons can innervate the projection cells. The aim of this study was to determine whether vertical cell dendrites were contacted by the central terminals of low-threshold mechanoreceptive primary afferents. Results: We initially demonstrated contacts between dendritic spines of vertical cells that had been recorded in spinal cord slices and axonal boutons containing the vesicular glutamate transporter 1 (VGLUT1), which is expressed by myelinated low-threshold mechanoreceptive afferents. To confirm that the VGLUT1 boutons included primary afferents, we then examined vertical cells recorded in rats that had received injections of cholera toxin B subunit (CTb) into the sciatic nerve. We found that over half of the VGLUT1 boutons contacting the vertical cells were CTb-immunoreactive, indicating that they were of primary afferent origin. Conclusions: These results show that vertical cell dendritic spines are frequently contacted by the central terminals of myelinated low-threshold mechanoreceptive afferents. Since dendritic spines are associated with excitatory synapses, it is likely that most of these contacts were synaptic. Vertical cells in lamina II are therefore a potential route through which tactile afferents can activate lamina I projection neurons, and this pathway could play a role in tactile allodynia

An unusual presentation of anetoderma: a case report

BACKGROUND: Anetoderma is a benign condition with focal loss of dermal elastic tissue resulting in localized areas of flaccid or herniated saclike skin. Currently, anetoderma is classified as either primary (idiopathic), or secondary anetoderma (which is associated with a variety of skin conditions, penicillamine use, or neonatal prematurity). Lesions appear on the upper arms, trunk, and thighs. CASE PRESENTATION: We report a 14-year-old boy, which was noticed to have had multiple, white, non-pruritic areas on the acral sites of upper and lower extremities for two years. In physical examination, the patient had normal mental development. Skin lesions consisted of scattered, white to skin-colored papules, less than 1 cm in diameter, and with central protrusion, with distribution on dorsal part of the index finger, forearms, distal portion of thighs and calves. Lesions were detected neither on the trunk nor the proximal areas of extremities. There are no sensory changes associated with the lesions. Otherwise, his general health was good. He did not have any medication consumption history. Family history was negative. Laboratory examinations were within normal limits. Skin biopsy from one of his lesions was done, that confirmed the diagnosis of anetoderma. CONCLUSIONS: In summary, we report a case of anetoderma on unusual sites of the skin. We could not find similar reports of anetoderma developing on distal extremities without involvement of the upper trunk and proximal arms, in the medical literature

Розрахунок та проектування окремого фундаменту будівлі на природній ґрунтовій основі. Методичні рекомендації до виконання практичних завдань та курсового проекту з дисципліни «Механіка ґрунтів, основи і фундаменти» сту- дентами напрямів підготовки 6.060101 Будівництво та 6.050301 Гірництво

Подано методичні рекомендації до виконання практичних завдань та кур- сового проекту з дисципліни «Механіка ґрунтів, основи і фундаменти» для сту- дентів напрямів підготовки 6.060101 Будівництво та 6.050301 Гірництво. Розглянуто порядок проектування фундаменту будівлі мілкого закладан- ня на природній ґрунтовій основі. Методичні рекомендації передбачають виконання курсового проекту «Розрахунок та проектування окремого фундаменту будівлі на природній ґрун- товій основі» як із викладачем, так і під час самостійної роботи. Можна використовувати також у підготовці курсового та дипломного про- ектування

The Small GTPase RhoA Localizes to the Nucleus and Is Activated by Net1 and DNA Damage Signals

Rho GTPases control many cellular processes, including cell survival, gene expression and migration. Rho proteins reside mainly in the cytosol and are targeted to the plasma membrane (PM) upon specific activation by guanine nucleotide exchange factors (GEFs). Accordingly, most GEFs are also cytosolic or associated with the PM. However, Net1, a RhoA-specific GEF predominantly localizes to the cell nucleus at steady-state. Nuclear localization for Net1 has been seen as a mechanism for sequestering the GEF away from RhoA, effectively rendering the protein inactive. However, considering the prominence of nuclear Net1 and the fact that a biological stimulus that promotes Net1 translocation out the nucleus to the cytosol has yet to be discovered, we hypothesized that Net1 might have a previously unidentified function in the nucleus of cells.Using an affinity precipitation method to pulldown the active form of Rho GEFs from different cellular fractions, we show here that nuclear Net1 does in fact exist in an active form, contrary to previous expectations. We further demonstrate that a fraction of RhoA resides in the nucleus, and can also be found in a GTP-bound active form and that Net1 plays a role in the activation of nuclear RhoA. In addition, we show that ionizing radiation (IR) specifically promotes the activation of the nuclear pool of RhoA in a Net1-dependent manner, while the cytoplasmic activity remains unchanged. Surprisingly, irradiating isolated nuclei alone also increases nuclear RhoA activity via Net1, suggesting that all the signals required for IR-induced nuclear RhoA signaling are contained within the nucleus.These results demonstrate the existence of a functional Net1/RhoA signaling pathway within the nucleus of the cell and implicate them in the DNA damage response

Novel combination of feed enzymes to improve the degradation of Chlorella vulgaris recalcitrant cell wall

Research Areas: Science & TechnologyABSTRACT - In this study, a rational combination of 200 pre-selected Carbohydrate-Active enzymes (CAZymes) and sulfatases were tested, individually or combined, according to their ability to degrade Chlorella vulgaris cell wall to access its valuable nutritional compounds. The disruption of microalgae cell walls by a four enzyme mixture (Mix) in comparison with the control, enabled to release up to 1.21g/L of reducing sugars (p<0.001), led to an eight-fold increase in oligosaccharides release (p<0.001), and reduced the fuorescence intensity by 47% after staining with Calcofuor White (p<0.001). The Mix treatment was successful in releasing proteins (p<0.001), some MUFA (p<0.05), and the benefcial 18:3n-3 fatty acid (p0.05), total carotenoids were increased in the supernatant (p<0.05) from the Mix treatment, relative to the control. Taken together, these results indicate that this four-enzyme Mix displays an efective capacity to degrade C. vulgaris cell wall. Thus, these enzymes may constitute a good approach to improve the bioavailability of C. vulgaris nutrients for monogastric diets, in particular, and to facilitate the cost-efective use of microalgae by the feed industry, in general.info:eu-repo/semantics/publishedVersio

Hypoxic gene expression in chronic hepatitis B virus infected patients is not observed in state-of-the-art in vitro and mouse infection models

Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. The prolyl hydroxylase domain (PHD)-hypoxia inducible factor (HIF) pathway is a key mammalian oxygen sensing pathway and is frequently perturbed by pathological states including infection and inflammation. We discovered a significant upregulation of hypoxia regulated gene transcripts in patients with chronic hepatitis B (CHB) in the absence of liver cirrhosis. We used state-of-the-art in vitro and in vivo HBV infection models to evaluate a role for HBV infection and the viral regulatory protein HBx to drive HIF-signalling. HBx had no significant impact on HIF expression or associated transcriptional activity under normoxic or hypoxic conditions. Furthermore, we found no evidence of hypoxia gene expression in HBV de novo infection, HBV infected human liver chimeric mice or transgenic mice with integrated HBV genome. Collectively, our data show clear evidence of hypoxia gene induction in CHB that is not recapitulated in existing models for acute HBV infection, suggesting a role for inflammatory mediators in promoting hypoxia gene expression

REST mediates resolution of HIF-dependent gene expression in prolonged hypoxia

The hypoxia-inducible factor (HIF) is a key regulator of the cellular response to hypoxia which promotes oxygen delivery and metabolic adaptation to oxygen deprivation. However, the degree and duration of HIF-1α expression in hypoxia must be carefully balanced within cells in order to avoid unwanted side effects associated with excessive activity. The expression of HIF-1α mRNA is suppressed in prolonged hypoxia, suggesting that the control of HIF1A gene transcription is tightly regulated by negative feedback mechanisms. Little is known about the resolution of the HIF-1α protein response and the suppression of HIF-1α mRNA in prolonged hypoxia. Here, we demonstrate that the Repressor Element 1-Silencing Transcription factor (REST) binds to the HIF-1α promoter in a hypoxia-dependent manner. Knockdown of REST using RNAi increases the expression of HIF-1α mRNA, protein and transcriptional activity. Furthermore REST knockdown increases glucose consumption and lactate production in a HIF-1α- (but not HIF-2α-) dependent manner. Finally, REST promotes the resolution of HIF-1α protein expression in prolonged hypoxia. In conclusion, we hypothesize that REST represses transcription of HIF-1α in prolonged hypoxia, thus contributing to the resolution of the HIF-1α response

REST is a hypoxia-responsive transcriptional repressor

Cellular exposure to hypoxia results in altered gene expression in a range of physiologic and pathophysiologic states. Discrete cohorts of genes can be either up- or down-regulated in response to hypoxia. While the Hypoxia-Inducible Factor (HIF) is the primary driver of hypoxia-induced adaptive gene expression, less is known about the signalling mechanisms regulating hypoxia-dependent gene repression. Using RNA-seq, we demonstrate that equivalent numbers of genes are induced and repressed in human embryonic kidney (HEK293) cells. We demonstrate that nuclear localization of the Repressor Element 1-Silencing Transcription factor (REST) is induced in hypoxia and that REST is responsible for regulating approximately 20% of the hypoxia-repressed genes. Using chromatin immunoprecipitation assays we demonstrate that REST-dependent gene repression is at least in part mediated by direct binding to the promoters of target genes. Based on these data, we propose that REST is a key mediator of gene repression in hypoxia

Bacterial community development in experimental gingivitis.

Current knowledge of the microbial composition of dental plaque in early gingivitis is based largely on microscopy and cultural methods, which do not provide a comprehensive description of oral microbial communities. This study used 454-pyrosequencing of the V1-V3 region of 16S rRNA genes (approximately 500 bp), and bacterial culture, to characterize the composition of plaque during the transition from periodontal health to gingivitis. A total of 20 healthy volunteers abstained from oral hygiene for two weeks, allowing plaque to accumulate and gingivitis to develop. Plaque samples were analyzed at baseline, and after one and two weeks. In addition, plaque samples from 20 chronic periodontitis patients were analyzed for cross-sectional comparison to the experimental gingivitis cohort. All of the healthy volunteers developed gingivitis after two weeks. Pyrosequencing yielded a final total of 344,267 sequences after filtering, with a mean length of 354 bases, that were clustered into an average of 299 species-level Operational Taxonomic Units (OTUs) per sample. Principal coordinates analysis (PCoA) plots revealed significant shifts in the bacterial community structure of plaque as gingivitis was induced, and community diversity increased significantly after two weeks. Changes in the relative abundance of OTUs during the transition from health to gingivitis were correlated to bleeding on probing (BoP) scores and resulted in the identification of new health- and gingivitis-associated taxa. Comparison of the healthy volunteers to the periodontitis patients also confirmed the association of a number of putative periodontal pathogens with chronic periodontitis. Taxa associated with gingivitis included Fusobacterium nucleatum subsp. polymorphum, Lachnospiraceae [G-2] sp. HOT100, Lautropia sp. HOTA94, and Prevotella oulorum, whilst Rothia dentocariosa was associated with periodontal health. Further study of these taxa is warranted and may lead to new therapeutic approaches to prevent periodontal disease.BBSRC Industrial Case Studentship ref no. BB/G01714X/1 in collaboration with GlaxoSmithKline