Restoration of oligodendrocyte pools in a mouse model of chronic cerebral hypoperfusion

Chronic cerebral hypoperfusion, a sustained modest reduction in cerebral blood flow, is associated with damage to myelinated axons and cognitive decline with ageing. Oligodendrocytes (the myelin producing cells) and their precursor cells (OPCs) may be vulnerable to the effects of hypoperfusion and in some forms of injury OPCs have the potential to respond and repair damage by increased proliferation and differentiation. Using a mouse model of cerebral hypoperfusion we have characterised the acute and long term responses of oligodendrocytes and OPCs to hypoperfusion in the corpus callosum. Following 3 days of hypoperfusion, numbers of OPCs and mature oligodendrocytes were significantly decreased compared to controls. However following 1 month of hypoperfusion, the OPC pool was restored and increased numbers of oligodendrocytes were observed. Assessment of proliferation using PCNA showed no significant differences between groups at either time point but showed reduced numbers of proliferating oligodendroglia at 3 days consistent with the loss of OPCs. Cumulative BrdU labelling experiments revealed higher numbers of proliferating cells in hypoperfused animals compared to controls and showed a proportion of these newly generated cells had differentiated into oligodendrocytes in a subset of animals. Expression of GPR17, a receptor important for the regulation of OPC differentiation following injury, was decreased following short term hypoperfusion. Despite changes to oligodendrocyte numbers there were no changes to the myelin sheath as revealed by ultrastructural assessment and fluoromyelin however axon-glial integrity was disrupted after both 3 days and 1 month hypoperfusion. Taken together, our results demonstrate the initial vulnerability of oligodendroglial pools to modest reductions in blood flow and highlight the regenerative capacity of these cells

Human-facilitated metapopulation dynamics in an emerging pest species, Cimex lectularius

Peer reviewe

Report on Midden Exposed by Coastal Erosion in Lapakahi State Historical Park, North Kohala District, Hawai‘i Island

Climate change is impacting coastal sites at an alarming rate.We report on coastal midden exposed by storm damage in the archaeological interpretive area of Lapakahi State Historical Park, North Kohala District, Hawai‘i Island, specifically, Site 50-10-02-04043, a canoe shed (halau). Site 04043 was first recorded, but not excavated, in the 1970s. Radiocarbon dating reported here suggests deposits did not begin accumulating until ca. cal AD 1700–1900, surprisingly late given its coastal location and previous dating of leeward Kohala sites. To help understand this we considered how the coastline has changed over time. We estimate, based on high-resolution airborne LiDAR bathometry, that this location was around 100m inland at the time people first arrived in the Hawaiian Islands. The subsidence of Hawai‘i Island slowly brought the coastline closer and it would have been around 10m from this location when deposits began accumulating. The contents of the midden are consistent with previous studies of subsistence in leeward Kohala.We attempted to improve on the specificity of the faunal inventory through ancient DNA but failed to recover intact DNA in fragmentary faunal bone samples. We note that reporting negative results is important for the judicious use of this technique. In sum, our results highlight the critical importance of a targeted, systematic study of early settlement—something that has never been done in the Hawaiian Islands—rather than relying on the type of salvage excavations described here

The sources of sea‐level changes in the Mediterranean Sea since 1960

Past sea-level changes in the Mediterranean Sea are highly non-uniform and can deviate significantly from both the global average sea-level rise and changes in the nearby Atlantic. Understanding the causes of this spatial non-uniformity is crucial to the success of coastal adaptation strategies. This, however, remains a challenge owing to the lack of long sea-level records in the Mediterranean. Previous studies have addressed this challenge by reconstructing past sea levels through objective analysis of sea-level observations. Such reconstructions have enabled significant progress toward quantifying sea-level changes, however, they have difficulty capturing long-term changes and provide little insight into the causes of the changes. Here, we combine data from tide gauges and altimetry with sea-level fingerprints of contemporary land-mass changes using spatial Bayesian methods to estimate the sources of sea-level changes in the Mediterranean Sea since 1960. We find that, between 1960 and 1989, sea level in the Mediterranean fell at an average rate of −0.3 ± 0.5 mm yr−1, due to an increase in atmospheric pressure over the basin and opposing sterodynamic and land-mass contributions. After 1989, Mediterranean sea level started accelerating rapidly, driven by both sterodynamic changes and land-ice loss, reaching an average rate of 3.6 ± 0.3 mm yr−1 in the period 2000–2018. The rate of sea-level rise shows considerable spatial variation in the Mediterranean Sea, primarily reflecting changes in the large-scale circulation of the basin. Since 2000, sea level has been rising faster in the Adriatic, Aegean, and Levantine Seas than anywhere else in the Mediterranean Sea

Recent advances in drug discovery for diabetic kidney disease

Introduction: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD), and 40% of patients with diabetes develop DKD. Although some pathophysiological mechanisms and drug targets of DKD have been described, the effectiveness or clinical usefulness of such treatment has not been well validated. Therefore, searching for new targets and potential therapeutic candidates has become an emerging research area. Areas covered: The pathophysiological mechanisms, new drug targets and potential therapeutic compounds for DKD are addressed in this review. Expert opinion: Although preclinical and clinical evidence has shown some positive results for controlling DKD progression, treatment regimens have not been well developed to reduce the mortality in patients with DKD globally. Therefore, the discovery of new therapeutic targets and effective target-based drugs to achieve better and safe treatment are urgently required. Preclinical screening and clinical trials for such drugs are needed

Serologic response to culture filtrate antigens of Mycobacterium ulcerans during Buruli ulcer disease.

Buruli ulcer (BU) is an emerging necrotic skin disease caused by Mycobacterium ulcerans. To assess the potential for a serodiagnostic test, we measured the humoral immune response of BU patients to M. ulcerans antigens and compared this response with delayed-type hypersensitivity responses to both Burulin and PPD. The delayed-type hypersensitivity response generally supported the diagnosis of BU, with overall reactivity to Burulin in 28 (71.8%) of 39 patients tested, compared with 3 (14%) of 21 healthy controls. However, this positive skin test response was observed primarily in patients with healed or active disease, and rarely in patients with early disease (p=0.009). When tested for a serologic response to M. ulcerans culture filtrate, 43 (70.5%) of 61 BU patients had antibodies to these antigens, compared with 10 (37.0%) of 27 controls and 4 (30. 8%) of 13 tuberculosis patients. There was no correlation between disease stage and the onset of this serum antibody response. Our findings suggest that serologic testing may be useful in the diagnosis and surveillance of BU

Low-Cost, Open-Source, and Low-Power: But What to Do With the Data?

There are now many ongoing efforts to develop low-cost, open-source, low-power sensors and datalogging solutions for environmental monitoring applications. Many of these have advanced to the point that high quality scientific measurements can be made using relatively inexpensive and increasingly off-the-shelf components. With the development of these innovative systems, however, comes the ability to generate large volumes of high-frequency monitoring data and the challenge of how to log, transmit, store, and share the resulting data. This paper describes a new web application that was designed to enable citizen scientists to stream sensor data from a network of Arduino-based dataloggers to a web-based Data Sharing Portal. This system enables registration of new sensor nodes through a Data Sharing Portal website. Once registered, any Internet connected data-logging device (e.g., connected via cellular or Wi-Fi) can then post data to the portal through a web service application programming interface (API). Data are stored in a back-end data store that implements Version 2 of the Observations Data Model (ODM2). Live data can then be viewed using multiple visualization tools, downloaded from the Data Sharing Portal in a simple text format, or accessed via WaterOneFlow web services for machine-to-machine data exchange. This system was built to support an emerging network of open-source, wireless water quality monitoring stations developed and deployed by the EnviroDIY community for do-it-yourself environmental science and monitoring, initially within the Delaware River Watershed. However, the architecture and components of the ODM2 Data Sharing Portal are generic, open-source, and could be deployed for use with any Internet connected device capable of making measurements and formulating an HTTP POST request

Hippocampal capillary pericytes in post-stroke and vascular dementias and Alzheimer’s disease and experimental chronic cerebral hypoperfusion

\ua9 The Author(s) 2024. Neurovascular unit mural cells called ‘pericytes’ maintain the blood-brain barrier and local cerebral blood flow. Pathological changes in the hippocampus predispose to cognitive impairment and dementia. The role of hippocampal pericytes in dementia is largely unknown. We investigated hippocampal pericytes in 90 post-mortem brains from post-stroke dementia (PSD), vascular dementia (VaD), Alzheimer’s disease (AD), and AD-VaD (Mixed) subjects, and post-stroke non-demented survivors as well as similar age controls. We used collagen IV immunohistochemistry to determine pericyte densities and a mouse model of VaD to validate the effects of chronic cerebral hypoperfusion. Despite increased trends in hippocampal microvascular densities across all dementias, mean pericyte densities were reduced by ~25–40% in PSD, VaD and AD subjects compared to those in controls, which calculated to 14.1 \ub1 0.7 per mm capillary length, specifically in the cornu ammonis (CA) 1 region (P = 0.01). In mice with chronic bilateral carotid artery occlusion, hippocampal pericyte loss was ~60% relative to controls (P < 0.001). Pericyte densities were correlated with CA1 volumes (r = 0.54, P = 0.006) but not in any other sub-region. However, mice subjected to the full-time environmental enrichment (EE) paradigm showed remarkable attenuation of hippocampal CA1 pericyte loss in tandem with CA1 atrophy. Our results suggest loss of hippocampal microvascular pericytes across common dementias is explained by a vascular aetiology, whilst the EE paradigm offers significant protection