New roles for Fc receptors in neurodegeneration-the impact on immunotherapy for Alzheimer's disease

There are an estimated 18 million Alzheimer's disease (AD) sufferers worldwide and with no disease modifying treatment currently available, development of new therapies represents an enormous unmet clinical need. AD is characterized by episodic memory loss followed by severe cognitive decline and is associated with many neuropathological changes. AD is characterized by deposits of amyloid beta (A?), neurofibrillary tangles, and neuroinflammation. Active immunization or passive immunization against A? leads to the clearance of deposits in transgenic mice expressing human A?. This clearance is associated with reversal of associated cognitive deficits, but these results have not translated to humans, with both active and passive immunotherapy failing to improve memory loss. One explanation for these observations is that certain anti-A? antibodies mediate damage to the cerebral vasculature limiting the top dose and potentially reducing efficacy. Fc gamma receptors (Fc?R) are a family of immunoglobulin-like receptors which bind to the Fc portion of IgG, and mediate the response of effector cells to immune complexes. Data from both mouse and human studies suggest that cross-linking Fc?R by therapeutic antibodies and the subsequent pro-inflammatory response mediates the vascular side effects seen following immunotherapy. Increasing evidence is emerging that Fc?R expression on CNS resident cells, including microglia and neurons, is increased during aging and functionally involved in the pathogenesis of age-related neurodegenerative diseases. Therefore, we propose that increased expression and ligation of Fc?R in the CNS, either by endogenous IgG or therapeutic antibodies, has the potential to induce vascular damage and exacerbate neurodegeneration. To produce safe and effective immunotherapies for AD and other neurodegenerative diseases it will be vital to understand the role of Fc?R in the healthy and diseased brain. Here we review the literature on Fc?R expression, function and proposed roles in multiple age-related neurological diseases. Lessons can be learnt from therapeutic antibodies used for the treatment of cancer where antibodies have been engineered for optimal efficacy

Splendide Mendax: False Label Claims about High and Rising Alcohol Content of Wine

Many economists and others are interested in the phenomenon of rising alcohol content of wine and its potential causes. Has the alcohol content of wine risen—and if so, by how much, where, and when? What roles have been played by climate change and other environmental factors compared with evolving consumer preferences and expert ratings? In this paper we explore these questions using international evidence, combining time-series data on the alcohol content of wine from a large number of countries that experienced different patterns of climate change and influences of policy and demand shifts. We also examine the relationship between the actual alcohol content of wine and the alcohol content stated on the label. The systematic patterns here suggest that rising alcohol content of wine may be a nuisance by-product of producer responses to perceived market preferences for wines having riper, more-intense flavors, possibly in conjunction with evolving climate.wine grapes, alcohol percentage, climate change, labeling errors, Agricultural and Food Policy, Crop Production/Industries, Demand and Price Analysis, Food Consumption/Nutrition/Food Safety, Marketing,

Theology, News and Notes - Vol. 43, No. 02

Theology News & Notes was a theological journal published by Fuller Theological Seminary from 1954 through 2014.https://digitalcommons.fuller.edu/tnn/1125/thumbnail.jp

Theology, News and Notes - Vol. 18, No. 04

Theology News & Notes was a theological journal published by Fuller Theological Seminary from 1954 through 2014.https://digitalcommons.fuller.edu/tnn/1040/thumbnail.jp

An Analysis of the Long-Term Salinity Patterns in the Louisiana Coastal Zone

Saltwater intrusion is believed to be one of the greatest threats to Louisiana\u27s fishery and wildlife resources. The Louisiana Department of Wildlife and Fisheries has maintained salinity recording stations throughout the state\u27s coastal marshes since the 1960\u27s. We applied several different analytical approaches to the salinity data from 17 stations to determine whether this data base could be used to detect and quantity long-term salinity trends in coastal Louisiana. We did not detect a large-scale, consistent trend over time in coastal salinities across the state. Problems that hindered the detection of long-term trends included short periods of record and the placement of the recording stations in salt and brackish marsh areas, where we would not expect to find great changes in salinity. For the data to be useful in monitoring salinity trends in coastal marshes, especially with respect to saltwater intrusion, stations should be added in fresh and intermediate marshes. In addition, the relationships our study revealed between short- and long-term data indicate that records covering less than a decade are insufficient to denote long-term salinity changes, barring some major modification of the hydrologic regime

Re-active Passive (RAP) Devices for Control of Noise Transmission through a Panel

Re-Active Passive (RAP) devices have been developed to control low frequency (200 Hz), reactive distributed vibration absorber) to cover the medium frequency range (75 to 250 Hz), and active control for controlling low frequencies (<200 Hz). The device was applied to control noise transmission through a panel mounted in a transmission loss test facility. Experimental results are presented for the bare panel, and combinations of passive treatment, reactive treatment, and active control. Results indicate that three RAP devices were able to increase the overall broadband (15-1000 Hz) transmission loss by 9.4 dB. These three devices added a total of 285 grams to the panel mass of 6.0 kg, or approximately 5%, not including control electronics

Theology, News and Notes - Vol. 11, No. 01

Theology News & Notes was a theological journal published by Fuller Theological Seminary from 1954 through 2014.https://digitalcommons.fuller.edu/tnn/1186/thumbnail.jp

Versatile Potentiostat with Optional Computer Control

A versatile potentiostat which can supply a maximum of 125 ma is described. The potentiostat uses readily available electronic components and an interface is detailed which allows the potentiostat optional computer control

Using citizen science to identify Australia’s least known birds and inform conservation action

Citizen science is a popular approach to biodiversity surveying, whereby data that are collected by volunteer naturalists may help analysts to understand the distribution and abundance of wild organisms. In Australia, birdwatchers have contributed to two major citizen science programs, eBird (run by the Cornell Lab of Ornithology) and Birdata (run by Birdlife Australia), which collectively hold more than 42 million records of wild birds from across the country. However, these records are not evenly distributed across space, time, or taxonomy, with particularly significant variation in the number of records of each species in these datasets. In this paper, we explore this variation and seek to determine which Australian bird species are least known as determined by rates of citizen science survey detections. We achieve this by comparing the rates of survey effort and species detection across each Australian bird species? range, assigning all 581 species to one of the four groups depending on their rates of survey effort and species observation. We classify 56 species into a group considered the most poorly recorded despite extensive survey effort, with Coxen?s Fig Parrot Cyclopsitta coxeni, Letter-winged Kite Elanus scriptus, Night Parrot Pezoporus occidentalis, Buff-breasted Buttonquail Turnix olivii and Red-chested Buttonquail Turnix pyrrhothorax having the very lowest numbers of records. Our analyses provide a framework to identify species that are poorly represented in citizen science datasets. We explore the reasons behind why they may be poorly represented and suggest ways in which targeted approaches may be able to help fill in the gaps.Publisher PDFPeer reviewe