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The historic building investigation was conducted following the CIfA Standards and guidance for archaeological building surveys (updated 2020), and was commensurate with a Historic England Level 3Photographic Archive: type survey (Historic England 2016). a comprehensive photographic archive of the historic elements of the ferry terminal was produced utilising a highresolution digital camera. All frames, excluding general contextual views, incorporated a graduated metric scale. Site Drawings: measured surv ey plans and elevations of the bridges were supplied by the Client, and there were checked on site for accuracy. The archaeological investigation of Compstall Printworks has provided a valuable opportunity to record an example of a 19th-century Bleach Croft and a 20th-century warpsizing building, to mitigate any loss of historic fabric as part of the redevelopment. It has also enabled a review of the available documentary material to be combined with the physical evidence embedded in the historic fabric to produce a detailed narrative of the building's development, enhancing, and amending the existing record that was created during the Greater Manchester Textile Mill Survey in the mid-1980s.

Aims: \ud Transient Receptor Potential Melastatin 7 (TRPM7) cation channel is a chanzyme (channel + kinase) that influences cellular Mg2+ homeostasis and vascular signalling. However, the pathophysiological significance of TRPM7 in the cardiovascular system is unclear. The aim of this study was to investigate the role of this chanzyme in the cardiovascular system focusing on inflammation and fibrosis.\ud \ud Methods and results: \ud TRPM7-deficient mice with deletion of the kinase domain (TRPM7+/Δkinase) were studied and molecular mechanisms investigated in TRPM7+/Δkinase bone marrow-derived macrophages (BMDM) and co-culture systems with cardiac fibroblasts. TRPM7-deficient mice had significant cardiac hypertrophy, fibrosis, and inflammation. Cardiac collagen and fibronectin content, expression of pro-inflammatory mediators (SMAD3, TGFβ) and cytokines [interleukin (IL)-6, IL-10, IL-12, tumour necrosis factor-α] and phosphorylation of the pro-inflammatory signalling molecule Stat1, were increased in TRPM7+/Δkinase mice. These processes were associated with infiltration of inflammatory cells (F4/80+CD206+ cardiac macrophages) and increased galectin-3 expression. Cardiac [Mg2+]i, but not [Ca2+]i, was reduced in TRPM7+/Δkinase mice. Calpain, a downstream TRPM7 target, was upregulated (increased expression and activation) in TRPM7+/Δkinase hearts. Vascular functional and inflammatory responses, assessed in vivo by intra-vital microscopy, demonstrated impaired neutrophil rolling, increased neutrophil: endothelial attachment and transmigration of leucocytes in TRPM7+/Δkinase mice. TRPM7+/Δkinase BMDMs had increased levels of galectin-3, IL-10, and IL-6. In co-culture systems, TRPM7+/Δkinase macrophages increased expression of fibronectin, proliferating cell nuclear antigen, and TGFβ in cardiac fibroblasts from wild-type mice, effects ameliorated by MgCl2 treatment.\ud \ud Conclusions: \ud We identify a novel anti-inflammatory and anti-fibrotic role for TRPM7 and suggest that its protective effects are mediated, in part, through Mg2+-sensitive processes.

Prior to the commencement of the archaeological watching brief, Salford Archaeology undertook a detailed archaeological survey of the weir. Following the archaeological survey, the client liaised with Salford Archaeology to provide notice of operations regarding the demolition of the weir and watching brief. placed within a westward-flowing curve within Eagley Brook, and associated with the nearby paper mill. Such features are typical of the Pennine region, where rivers are fast-flowing and plentiful for the majority of the year, but had the potential to have insufficient flow during short periods of the summer. Weirs were originally constructed in the region to provide a reliable water source for water wheels, which powered agricultural mills from the medieval period, but became more common in the early part of the Industrial revolution of the eighteenth century, when powered mills were placed adjacent to watercourses. With the development of steam power in the late 18th century, and its widespread adoption, the use of water power for the dominant textile industry within the region became less prevalent, although notable exceptions, such as the relatively nearby Higher Mill, Helmshore, continued to use water power throughout the 19th century. The weir itself was almost certainly contemporar

Obesity is a common comorbidity for pulmonary arterial hypertension (PAH). Additionally, oestrogen and its metabolites are risk factors for the development of PAH. Visceral adipose tissue (VAT) is a major site of oestrogen production; however, the influence of obesity-induced changes in oestrogen synthesis and metabolism on the development of PAH is unclear. To address this we investigated the effects of inhibiting oestrogen synthesis and metabolism on the development of pulmonary hypertension in male and female obese mice.\ud \ud We depleted endogenous oestrogen in leptin-deficient (ob/ob) mice with the oestrogen inhibitor anastrozole (ANA) and determined the effects on the development of pulmonary hypertension, plasma oestradiol and urinary 16α-hydroxyestrone (16αOHE1). Oestrogen metabolism through cytochrome P450 1B1 (CYP1B1) was inhibited with 2,2′,4,6′-tetramethoxystilbene (TMS).\ud \ud ob/ob mice spontaneously develop pulmonary hypertension, pulmonary vascular remodelling and increased reactive oxygen species production in the lung; these effects were attenuated by ANA. Oestradiol levels were decreased in obese male mice; however, VAT CYP1B1 and 16αOHE1 levels were increased. TMS also attenuated pulmonary hypertension in male ob/ob mice. Intra-thoracic fat from ob/ob mice and VAT conditioned media produce 16αOHE1 and can contribute to oxidative stress, effects that are attenuated by both ANA and TMS.\ud \ud Obesity can induce pulmonary hypertension and changes in oestrogen metabolism, resulting in increased production of 16αOHE1 from VAT that contributes to oxidative stress. Oestrogen inhibitors are now in clinical trials for PAH. This study has translational consequences as it suggests that oestrogen inhibitors may be especially beneficial in treating obese individuals with PAH.

The excavation followed on from a desk-based assessment that was compiled in 2016 by TEP, and a subsequent geophysical survey undertaken by Magnitude Surveys Ltd and trial trenching carried out by OA North in 2017 (OA North 2017), which confirmed that buried remains of the Warrington to Wigan Roman road survived across the site. In the light of the significant results obtained from the initial evaluation, it was recommended that a programme of further archaeological investigation was carried out, comprising a 'strip and record' exercise of two targeted areas, followed by controlled detailed excavation where extensive archaeological remains were exposed. The road's foundation layer, however, has survived and is in the form of large blocks of red and yellow sandstone (red sandstone known as the Sherwood Group was quarried in Ashton in the 19th century). It shows the road to have been about 6m wide, and whilst this is slightly narrower that may be expected, it corresponds closely with the section of the road excavated in 1993 on the other side of Bryn Road.

All archaeological work followed the CIfA Standards and Guidance for archaeological watching brief. All excavation work undertaken by the site investigation contractors was supervised closely by a suitably experienced archaeologist. Where archaeological remains were identified during the works, the excavated area was rapidly cleaned, and the need for any further archaeological investigation was assessed. Where appropriate, any features and finds were excavated by hand, sampled and recorded, within the confines of the excavated area. Excavated soil was searched as practicable for artefacts. The areas subject to ground disturbance, and any features of archaeological interest, were located accurately on a site plan, and recorded by photography, scale drawings, and written descriptions. All information identified in the course of the site works was recorded stratigraphically. Results of the watching brief were, where appropriate, recorded on pro-forma context sheets, and were accompanied with sufficient pictorial record (plans, sections and highresolution digital photographs) to identify and illustrate individual features No archaeological finds or features were encountered during the archaeological works other than the foundations for the structural columns of the 1830 Warehouse. Several layers were identified within the vertical sections of all three trial pits, but these are likely to represent river deposits pertaining to the River Irwell, situated less than 90m to the west of the 1830 Warehouse; no evidence for pre-19th-century activity on the site was identified.

Open area excavation designed to uncover any in situ remains of the silk mill, potentially a wheel pit, water management and boiler house The archaeological excavation successfully exposed several significant aspects of the mill's former power systems. This included an underground tailrace that was identified in two of the excavation areas and an engine bed that may have been associated with the mill's early conversion to steam, which lay beyond the footprint of the boiler and engine houses shown on successive Ordnance Survey maps. Although evidence for the mill's original wheel pit was not definitively identified, evidence from the excavation, combined with historical research has produced an interesting body of evidence that can be compared to other silk mills in Cheshire and the North West region.

The aim of the excavation was strip and map the extent of 18th and 19th century buildings on the site, to assess the potential of any relict soils and to fully excavate and record any pre-industrial features associated with those soils. This was a process which would fit with several of the initiatives for archaeological research of the industrial and modern periods stated in the current Archaeological Research Framework for North West England (Newman and McNeil 2007; McNeil and Newman 2007). The results of the archaeological evaluation prompted further investigations by request from GMAAS, comprising two open-area excavations, one within the former Globe & Simpson building (Area 1) and a second within the triangular plot of land to the north between Back Quay Street and New Quay Street (Area 2; Figure 12). The excavation was undertaken as a 'strip and plan' to the level of any ground floor wall footings, and the top of any cellar walls. Once the area was stripped to the appropriate level, the remains were rapidly cleaned, photographed and planned. Following the strip and plan investigation, a number of cellared structures were chosen to be fully excavated. The final phase of archaeological investigation included the identification of relict soils and associated post-medieval features, which were excavated, recorded and sampled.

Manchester Metropolitan University, has obtained planning consent (Ref: 121487/FO/2018) to redevelop land at Higher Chatham Street, Manchester (centred on NGR 384229 396867). The consented scheme allows for the erection of a five storey building and associated landscaping works. The delivery of these proposals will necessitate considerable earth-moving works, which will impact on buried archaeological remains. The evidence from the excavation, combined with the historical research has produced an interesting body of evidence for the planned development of a Manchester suburb. The city of Manchester was in the process of massive rapid expansion due to industrialisation and the textile industry during the late 18th century. The sparsely populated rural area that became Chorlton-on-Medlock appears to have been purchased and laid out as a suburb of Manchester, designed to attract an affluent middle class population with ornamental parks and squares. During the early 19th century the huge population increase and severe lack of housing led to smaller terraced houses being built within the area, from at least 1818-19. These included both double depth housing and back-to-backs. By 1824 the area was entirely infilled with housing. Although the addition of the terraced housing was perhaps a downgrade � Salford Archaeology School of Digital Arts, Higher Chatham Street: Archaeological Excavation 4 from the initial intention of the development it was clearly of a superior quality to that in many other areas of Manchester. The double depth houses had rear yards and privies from the outset, 14 to 20 years before the first of the housing improvement Acts required them to do so, and had better access to clean water than was standard for worker's housing at that time. This was clearly a deliberate move to attract more affluent skilled workers and professionals, many of whom are listed in the census as journeymen. Throughout the 19th century the area was mainly populated with locals from Manchester and Salford, the few immigrants being from other areas of England and occasionally Wales or Scotland. Until the 1871 census there were no Irish immigrants, itinerant workers or textile workers, and very few houses contained lodgers

Allied London, has obtained planning consent (Ref: 121511/FO/2018/) to redevelop land at Water Street, Manchester (centred on NGR 383097 398059). The consented scheme allows for the erection of two mixed use buildings comprising 11 storeys and 10 storeys with rooftop amenity spaces basement parking for 391 cars and cycle storage, together with new public realm, landscaping, provision of external seating areas, access and other associated works. The delivery of these proposals will necessitate considerable earth-moving works, which will impact on buried archaeological remains. The site is situated on the south-western edge of Manchester city centre, in an area known as the St John's Quarter, bounded by Water Street to the west, the Grade II Listed Bonded Warehouse and Railway Viaducts to the south, Atherton Street and Old Granada Studios to the east and Quay Street to the north. The area has been identified as a regeneration priority by Manchester City Council and is situated within the Castlefield Conservation Area and adjacent to St John Street Conservation Area. (Plate 1; Figure 1). The evidence from the excavation, combined with the historical research has produced an interesting body of evidence for the planned development of a Manchester suburb. The city of Manchester was in the process of massive rapid expansion due to industrialisation and the textile industry during the late 18th century. The earlier 18th century houses were of a higher quality, in both construction and provision of sanitation, than those built in the early 19th century. The improvement of the toilet provision, and the continued use of cellars as dwellings beyond the banning of such practices, indicates that some regulations were being adhered to and some not, possibly f or economic reasons. The census r eturns showed that, similar to many sites in the local area, the population, although not particularly wealthy, were not the lowest sections of society as seen in the slum areas. The severe overcrowding and extreme poverty areas such as Ancoats and seen in Angel Meadow were not present in this area and the population were mainly local, or from other parts of England.

The first phase was to strip the designated excavation areas and record any structural remains, followed by detailed excavation of select buildings. On completion of this phase an area along the northern half of Area 1 was stripped to ascertain the extent of relict soils. The third and final phase of excavation was the recording of those soils and any features cut into them. Following completion of the fieldwork this postexcavation assessment report was written The excavations recorded the remains of a number of 18th and 19th century buildings including workers houses, and larger domestic buildings that were later converted into boarding houses, shops and workshops. A significant relict soil containing pottery spanning the medieval and post-medieval periods was excavated across the Quay Street side of the site and a number of post-medieval orchard/kitchen garden features were recorded. The excavations at Globe and Simpson spanned a period of large scale drastic change in the landscape and demography of Manchester, and the whole of Britain. The rapid move throughout the late 18th and early 19th centuries from rural and semi-rural pastoralism to urban industrialism was a change which affected much of the world, the repercussions of which are still felt into the 21st century. Although only a small keyhole area the excavation site demonstrated a trend which can be extrapolated across the city

The archaeological work consisted of two open area excavations trenches targeting terraced houses along the former Peel Street and Wilton Place. The archaeological remains present within Area 1 exclusively related to the terraced houses of Peel Street, constructed between 1831 and 1836 (Figure 22 and Plate 4). These structures remained extant until the 1970s when the site began to be cleared. Generally, the buried remains related to those dwellings survived to a considerable degree, though there was occasional disturbance and truncation related to later activity. Unfortunately, at the time of the demolition of the dwellings on the south side of Peel Street, c.1970, the ground-level of the entire site had been reduced with some building material potentially reclaimed. At the north of Area 1 where the roadway and pavement of Peel Street would once have been located, no remains of archaeological interest were found. The archaeological remains present within Area 2 exclusively related to the terraced houses of Wilton Place, originally known as Ackers Place, constructed between 1831 and 1836. These structures remained extant until the 1970s when the site began to be cleared. Generally, the buried remains related to those dwellings survived to a considerable degree, though there was occasional disturbance and truncation related to later activity. Unfortunately, at the time of the demolition of the dwellings on Wilton Place, the pavement was widened, which prevented the excavation of the front part of the houses. The presence of modern service pipes prohibited the excavation of the north part of the excavation area. As a result, the majority of the excavation was focused on House 2/4 Wilton Place.

Chemerin and its G protein-coupled receptor [chemerin receptor 23 (ChemR23)] have been associated with endothelial dysfunction, inflammation, and insulin resistance. However, the role of chemerin on insulin signaling in the vasculature is still unknown. We aimed to determine whether chemerin reduces vascular insulin signaling and whether there is interplay between chemerin/ChemR23, insulin resistance, and vascular complications associated with type 2 diabetes (T2D). Molecular and vascular mechanisms were probed in mesenteric arteries and cultured vascular smooth muscle cells (VSMCs) from C57BL/6J, nondiabetic lean db/m, and diabetic obese db/db mice as well as in human microvascular endothelial cells (HMECs). Chemerin decreased insulin-induced vasodilatation in C57BL/6J mice, an effect prevented by CCX832 (ChemR23 antagonist) treatment. In VSMCs, chemerin, via oxidative stress- and ChemR23-dependent mechanisms, decreased insulin-induced Akt phosphorylation, glucose transporter 4 translocation to the membrane, and glucose uptake. In HMECs, chemerin decreased insulin-activated nitric oxide signaling. AMP-activated protein kinase phosphorylation was reduced by chemerin in both HMECs and VSMCs. CCX832 treatment of db/db mice decreased body weight, insulin, and glucose levels as well as vascular oxidative stress. CCX832 also partially restored vascular insulin responses in db/db and high-fat diet-fed mice. Our novel in vivo findings highlight chemerin/ChemR23 as a promising therapeutic target to limit insulin resistance and vascular complications associated with obesity-related diabetes.

Children with intellectual disabilities have special needs when it comes to the learning environment. That is why in places with kids of these intellectual disabilities, such as autism, need specially designed rooms to provide sensory stimulation to the users. Sensory rooms not only function as a specially designed playroom, but also as a place that kids can learn while doing playtime activities. By creating a functional playroom, the kids will be able to feel comfortable in their environment, interviewing parents of children with these intellectual disabilities and researching multisensory development the information can be implemented to create a space that is comfortable for the users. The playroom will be a space of learning and development.