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Rivers that do not flow year-round are the predominant type of running waters on Earth. Despite a burgeoning literature on natural flow intermittence (NFI), knowledge about the hydrological causes and ecological effects of human-induced, anthropogenic flow intermittence (AFI) remains limited. NFI and AFI could generate contrasting hydrological and biological responses in rivers because of distinct underlying causes of drying and evolutionary adaptations of their biota. We first review the causes of AFI and show how different anthropogenic drivers alter the timing, frequency and duration of drying, compared with NFI. Second, we evaluate the possible differences in biodiversity responses, ecological functions, and ecosystem services between NFI and AFI. Last, we outline knowledge gaps and management needs related to AFI. Because of the distinct hydrologic characteristics and ecological impacts of AFI, ignoring the distinction between NFI and AFI could undermine management of intermittent rivers and ephemeral streams and exacerbate risks to the ecosystems and societies downstream.

Hydrologic data collected from river gauges inform critical decisions for allocating water resources, conserving ecosystems and predicting the occurrence of droughts and floods. The current global river gauge network is biased towards large, perennial rivers, and strategic adaptations are needed to capture the full scope of rivers on Earth. Knowing where and when rivers flow is paramount to managing freshwater ecosystems. Yet stream gauging stations are distributed sparsely across rivers globally and may not capture the diversity of fluvial network properties and anthropogenic influences. Here we evaluate the placement bias of a global stream gauge dataset on its representation of socioecological, hydrologic, climatic and physiographic diversity of rivers. We find that gauges are located disproportionally in large, perennial rivers draining more human-occupied watersheds. Gauges are sparsely distributed in protected areas and rivers characterized by non-perennial flow regimes, both of which are critical to freshwater conservation and water security concerns. Disparities between the geography of the global gauging network and the broad diversity of streams and rivers weakens our ability to understand critical hydrologic processes and make informed water-management and policy decisions. Our findings underscore the need to address current gauge placement biases by investing in and prioritizing the installation of new gauging stations, embracing alternative water-monitoring strategies, advancing innovation in hydrologic modelling, and increasing accessibility of local and regional gauging data to support human responses to water challenges, both today and in the future. US National Science Foundation [DEB-1754389, 2207232] Published version US National Science Foundation(National Science Foundation (NSF)) Public domain – authored by a U.S. government employee

Increasing salinization of freshwater threatens water supplies that support a range of human and ecological uses. The latest assessments of Delaware River Basin (DRB) surface-water-quality changes indicate widespread salinization has occurred in recent decades, which may lead to meaningful degradation in water quality. To better understand how and when salinity transport occurs and implications for DRB streams, this study: 1) explores the variability of specific conductance (SC) trends spatially and seasonally from 1998 to 2018, and 2) investigates how trends relate to streamflow, land disturbance, and impervious surface area to better understand regional salinization drivers. We find widespread increases in SC across the DRB, with several sites in the lower basin exceeding thresholds for aquatic life and experiencing increasing frequencies of exceedance over time. In general, the greatest basin wide increases in SC occurred during low flow conditions, indicating that a legacy component resulting from subsurface retention and transport processes has driven observed changes in riverine SC. For a subset of sites in the lower basin, where impervious area and cumulative land disturbance are higher, the greatest SC increases occurred during high flow conditions in winter months. Given the patterns of SC and watershed changes across the basin, as well as strong relationships between SC trends and sodium and chloride trends, deicing salt appears to be a likely driver of observed SC change. Even if deicing salt application plateaus or declines in coming years, the continued release and transport of the legacy subsurface component may still contribute to elevated DRB riverine SC.

River managers often need estimates of streamflow for ungauged streams. These estimates can be used in water rights acquisitions, in‐stream flow management, habitat assessment, water quality planning, and stream hazard identification. This publication describes new regression models for predicting mean annual and mean monthly streamflow in Colorado. Unlike previous regional regression studies, the new models incorporate snow persistence (SP), the fraction of time a watershed remains snow covered. Models were developed using streamflow data from 131 watersheds with drainage areas 0.75), but predictions were biased low by 14–28% in wetter decades. All equations and coefficients needed to run the models are presented in the publication appendix, and the associated data release includes the spatial data and model code, which can be applied using R or within an R‐based Shiny web app.

Streamflow generation and deep groundwater recharge in high elevation and high latitude locations may be vulnerable to loss of snow, making it important to quantify how snowmelt is partitioned between soil storage, deep drainage, evapotranspiration, and runoff. Based on previous findings, we hypothesize that snowmelt produces greater streamflow and deep drainage than rainfall and that this effect is greatest in dry climates. To test this hypothesis we examine how snowmelt and rainfall partitioning vary with climate and soil properties using a physically based variably saturated subsurface flow model, HYDRUS-1D. To represent climate variability we use historical inputs from five SNOTEL sites in each of three mountain regions with humid to semiarid climates: Northern Cascades, Sierra Nevada, and Uinta. Each input scenario is run with three soil profiles of varying hydraulic conductivity, soil texture, and bulk density. We also create artificial input scenarios to test how the concentration of input in time, conversion of snow to rain input, and soil profile depth affect partitioning of input into deep drainage and runoff. Results indicate that event-scale runoff is higher for snowmelt than for rainfall due to higher antecedent moisture and input rates in both wet and dry climates. At the annual scale, surface runoff also increases with snowmelt fraction, whereas deep drainage is not correlated with snowmelt fraction. Deep drainage is less affected by changes from snowmelt to rainfall because it is controlled by deep soil moisture changes over longer time scales. However, extreme scenarios with input highly concentrated in time, such as during melt of a deep snowpack, yield greater deep drainage below the root zone than intermittent input. Soil texture modifies daily wetting and drying patterns but has limited effect on annual scale partitioning of rain and snowmelt, whereas increases in soil depth decrease runoff and increase deep drainage. Overall these results indicate that runoff may be substantially reduced with seasonal snowpack decline in all climates. These mechanisms help explain recent observations of streamflow sensitivity to changing snowpack and emphasize the need to develop strategies to mitigate impacts of reduced streamflow generation in places most at risk for shifts from snow to rain.

Recent research showed that, snow persistence, defined here as the fraction of time that snow is present on the ground, can play an important role in explaining spatial variability of average annual streamflow in moderately snowmelt-dominated regions. Here, we extend this work and explore the following questions: 1) whether globally available snow persistence data is useful for estimating a suite of streamflow signatures explaining the shape, flashiness and components of streamflow hydrograph, and 2) whether snow persistence could be useful for reconstructing streamflow patterns in ungauged watersheds, both spatially and temporally. We explore these questions across a spectrum of climatic dryness, snowiness, and geological settings. The motivations for the study are the need to understand how loss of snow may affect the components of streamflow in different climatic and geological settings, as well as the need for simple methods to predict components of streamflow in snow-dominated ungauged basins.

The paradigm of surface water flow regimes is central to the aquatic sciences, where the timing, duration, frequency, magnitude, and rate of change of flow drive physical, chemical, and biological functions in aquatic systems. However, non-perennial streams comprise the majority of the global river network and there is a need to understand not just whether or not a stream periodically dries, but how it dries. Here, we propose to flip the script on flow regimes by presenting a comprehensive 'drying regime' framework to characterize stream drying. We then identify similar drying characteristics in streams across watersheds with a broad range of climates, physiographic regions, and land uses. Using daily streamflow from 894 U.S. Geological Survey streamflow gages we isolated over 25,000 unique drying events over a period from 1979 - 2018. From these drying events we identified and calculated streamflow metrics that describe timing, duration, magnitude, frequency, and rate of change of stream drying. Using multivariate statistics, k-means clustering, and random forest analyses we grouped drying events into distinct drying regimes and determined the drivers of the clustered regimes. K-means clustering resulted in 4 distinct drying regimes characterized by (1) more frequent drying, (2) longer no-flow duration, (3) drying occurring following low antecedent flows, and (4) flashy high frequency drying, respectively. The majority of gages had more than one drying regime present at different times within each year, suggesting that dominant flow paths or drivers varied through time Clustered drying regimes show low event-scale spatial coherence, and while drying regimes (1) and (2) show similar frequency throughout the year, (3) and (4) are substantially more frequent during summer months. Based on random forest analysis, land cover characteristics appear to drive drying event assignment to drying regimes more than climate variables. Furthermore, increased importance of individual watershed properties shows that the structural makeup of the watershed is notably more important to how an intermittent system dries than climate or physiographic characteristics. Non-perennial systems have unique functions due to the occurrence of both flowing and dry states, yet most of the past efforts rely on frameworks built around perennial streamflow behavior. Our work presents a novel drying regime framework to allow future studies to more effectively connect river drying to the physical, chemical, and biological functioning in these systems. This framework may also aid in current sustainable river management, including engineered flow regimes that are designed to balance water allocations with ecosystem requirements.

Over half of global rivers and streams lack perennial flow, and understanding the distribution and drivers of their flow regimes is critical for understanding their hydrologic, biogeochemical, and ecological functions. We analyzed nonperennial flow regimes using 540 U.S. Geological Survey watersheds across the contiguous United States from 1979 to 2018. Multivariate analyses revealed regional differences in no-flow fraction, date of first no flow, and duration of the dry-down period, with further divergence between natural and human-altered watersheds. Aridity was a primary driver of no-flow metrics at the continental scale, while unique combinations of climatic, physiographic and anthropogenic drivers emerged at regional scales. Dry-down duration showed stronger associations with nonclimate drivers compared to no-flow fraction and timing. Although the sparse distribution of nonperennial gages limits our understanding of such streams, the watersheds examined here suggest the important role of aridity and land cover change in modulating future stream drying. Plain Language Summary A majority of global streams are nonperennial, flowing only part of the year, and are critical for sustaining flow downstream, providing habitat for many organisms, and regulating chemical and biological processes. Using long-term U.S. Geological Survey measurements for 540 watersheds across the contiguous United States, we mapped patterns and examined the causes of no-flow fraction, the fraction of each climate year with no flow, no-flow timing, the date of the climate year on which the first recorded no flow takes place, and length of the dry-down period, the average number of days from a local peak in daily flow to the first occurrence of no flow. We found differences in patterns of no-flow characteristics between regions, with higher no-flow fraction, earlier timing, and shorter dry-down duration in the western United States. No-flow fractions were greater and less variable in natural watersheds, while no-flow timing was earlier and dry-down duration was shorter in human-modified watersheds. Aridity had the greatest effect on intermittence across the United States, but unique combinations of climate, biophysical, and human impacts were important in different regions. The number of gages measuring streamflow in nonperennial streams is small compared to perennial streams, and increased monitoring is needed to better understand drying behavior. Key Points . Three metrics reveal regional and human-driven patterns of nonperennial flow: no-flow fraction, day of first no flow, and dry-down duration Streams with human modifications generally dry more quickly than unmodified streams, especially in California and the Southern Great Plains Climate strongly influences no-flow fraction and timing, but physiographic variables are more important for the duration of dry down National Science FoundationNational Science Foundation (NSF) [DEB-1754389]; Kansas Water Resources Institute Published version This manuscript is a product of the Dry Rivers Research Coordination Network, supported by funding from the National Science Foundation (DEB-1754389). Although this work was approved for publication by the EPA, it may not reflect official Agency policy. S.C.Z. was supported by the Kansas Water Resources Institute. We thank David Wolock and two anonymous reviewers for their suggestions and edits. Public domain – authored by a U.S. government employee

Streamflow observations can be used to understand, predict, and contextualize hydrologic, ecological, and biogeochemical processes and conditions in streams. Stream gages are point measurements along rivers where streamflow is measured, and are often used to infer upstream watershed-scale processes. When stream gages read zero, this may indicate that the stream has dried at this location; however, zero-flow readings can also be caused by a wide range of other factors. Our ability to identify whether or not a zero-flow gage reading indicates a dry fluvial system has far reaching environmental implications. Incorrect identification and interpretation by the data user can lead to inaccurate hydrologic, ecological, and/or biogeochemical predictions from models and analyses. Here, we describe several causes of zero-flow gage readings: frozen surface water, flow reversals, instrument error, and natural or human-driven upstream source losses or bypass flow. For these examples, we discuss the implications of zero-flow interpretations. We also highlight additional methods for determining flow presence, including direct observations, statistical methods, and hydrologic models, which can be applied to interpret causes of zero-flow gage readings and implications for reach- and watershed-scale dynamics. Such efforts are necessary to improve our ability to understand and predict surface flow activation, cessation, and connectivity across river networks. Developing this integrated understanding of the wide range of possible meanings of zero-flows will only attain greater importance in a more variable and changing hydrologic climate. This article is categorized under: Science of Water > Methods Science of Water > Hydrological Processes Water and Life > Conservation, Management, and Awareness National Science FoundationNational Science Foundation (NSF) [DEB-1754389]; NSFNational Science Foundation (NSF) [DEB-1830178, EAR-1653998, EAR-1652293]; NSF Konza Long Term Ecological Research grant [1440484]; Department of Energy Office of Science Multisector Dynamics ProgramUnited States Department of Energy (DOE); Australian Research CouncilAustralian Research Council [DE150100302]; Department of EnergyUnited States Department of Energy (DOE) [DE-SC0019377] This manuscript is a product of the Dry Rivers Research Coordination Network, which was supported by funding from the National Science Foundation (DEB-1754389). DelVecchia was supported in part by funding from NSF DEB-1830178. Dodds was supported in part by NSF Konza Long Term Ecological Research grant number 1440484. Godsey was supported in part by NSF award EAR-1653998. Kaiser was supported in part by the Department of Energy Office of Science Multisector Dynamics Program. Shanafield was supported in part by funding from the Australian Research Council under grant DE150100302. Ward was supported in part by Department of Energy award DE-SC0019377 and NSF award EAR-1652293. The opinions expressed are those of the researchers, and not necessarily the funding agencies. Although this work was reviewed by the USGS and USEPA, and approved for publication, it might not necessarily reflect official USEPA policy. Any use of trade, firm, or product names is for descriptive purposes only and does not imply endorsement by the U.S. Government. The authors thank Heather Golden, Brent Johnson, Rosemary Fanelli, Albert Ruhi, as well as two anonymous reviewers for helpful comments on earlier versions of the manuscript. USGS data used to support this study are available from the U.S. Geological Survey National Water Information System database (U.S. Geological Survey, 2019). For the exact dataset used in this study, see: Hammond (2020). Public domain – authored by a U.S. government employee

Nonperennial rivers are a major—and growing—part of the global river network. New research and science-based policies are needed to ensure the sustainability of these long-overlooked waterways.

Forest management guidelines are designed to protect water quality from unintended effects of land use changes such as timber harvest, mining, or forest road construction. Although streams that periodically cease to flow (nonperennial) drain the majority of forested areas, these streams are not consistently included in forest management guidelines. This paper reviews management guidelines for nonperennial (intermittent and ephemeral) streams draining temperate forests in the continental U.S., evaluates potential impacts of land use activities on ecosystem services provided by these streams, and identifies information needed to incorporate nonperennial streams into water quality protection practices. For federally administered lands, national management guidance is deliberately nonprescriptive, deferring to regional and forest-level recommendations for both perennial and nonperennial streams. Most state guidelines recommend riparian management zone (RMZ) protection for perennial streams (48/50 states) and intermittent streams (45/50 states), but only Alaska and West Virginia require RMZs around ephemeral streams. Based on the National Hydrography Dataset, an average of 58% of forested land area in the U.S. drains to nonperennial headwater streams, making these stream types the most common connectors between forested lands and the aquatic system. Land uses that modify flow regimes in these streams can affect sediment and organic matter transport and distribution, stream temperature dynamics, and biogeochemical processing. Nonperennial streams also provide material subsidies to downstream waters and serve as temporary habitats for some aquatic species. However, limited research has examined how forest land uses affect ecosystem services and biota in these streams. Therefore we highlight a set of key questions about nonperennial streams in forests, not the least of which is simply understanding where headwater stream channels are located and associated patterns of flow duration. Although many questions remain, we also note where recent advances in data collection, modeling and process-level research provide opportunties to resolve uncertainties around nonperennial streams in forested landscapes of the continental U.S.

Non-perennial streams are widespread, critical to ecosystems and society, and the subject of ongoing policy debate. Prior large-scale research on stream intermittency has been based on long-term averages, generally using annually aggregated data to characterize a highly variable process. As a result, it is not well understood if, how, or why the hydrology of non-perennial streams is changing. Here, we investigate trends and drivers of three intermittency signatures that describe the duration, timing, and dry-down period of stream intermittency across the continental United States (CONUS). Half of gages exhibited a significant trend through time in at least one of the three intermittency signatures, and changes in no-flow duration were most pervasive (41% of gages). Changes in intermittency were substantial for many streams, and 7% of gages exhibited changes in annual no-flow duration exceeding 100 days during the study period. Distinct regional patterns of change were evident, with widespread drying in southern CONUS and wetting in northern CONUS. These patterns are correlated with changes in aridity, though drivers of spatiotemporal variability were diverse across the three intermittency signatures. While the no-flow timing and duration were strongly related to climate, dry-down period was most strongly related to watershed land use and physiography. Our results indicate that non-perennial conditions are increasing in prevalence over much of CONUS and binary classifications of 'perennial' and 'non-perennial' are not an accurate reflection of this change. Water management and policy should reflect the changing nature and diverse drivers of changing intermittency both today and in the future. US National Science FoundationNational Science Foundation (NSF) [DEB-1754389] Published version This manuscript is a product of the Dry Rivers Research Coordination Network, which was supported by funding from the US National Science Foundation (DEB-1754389). Any use of trade, firm, or product names is for descriptive purposes only and does not imply endorsement by the US Government. This manuscript was improved by constructive feedback from Kristin Jaeger and three anonymous reviews.

In the humid, temperate Delaware River Basin (DRB) where water availability is generally reliable, summer low flows can cause competition between various human and ecological water uses. As temperatures continue to rise, population increases and development expands, it is critical to understand historical low flow variability to anticipate and plan for future flows. Using a sample of 325 U.S. Geological Survey gages, we evaluated spatial patterns in several low flow metrics, the biophysical and climatic drivers of these metrics, and trends in low flows for two periods: 1950–2018 and 1980–2018. We calculated the annual 7-day low flow and date, low flow deficit as the departure below a long-term daily flow threshold and the number of discrete low flow periods below this threshold. We also aggregated several climate metrics to watershed scale and used existing watershed properties quantifying land cover, topography, soils, geology, and human activity. Random forest models were used to assess the hierarchy of variable importance in explaining mean-annual low flow variability for each low flow metric using all gages. We find muted regional patterns in mean-annual low flow and low flow variability, likely due to the myriad of anthropogenic, landscape, and flow modifications that obscure flow regimes from their natural characteristics. In contrast, individual years show markedly different spatial patterns in low flow magnitude and severity. Coincident with increases in precipitation, 7-day low flows have generally increased and low flow deficits decreased for both 1950–2018 and 1980–2018 periods. However, 7-day low flows have decreased in the Coastal Plain physiographic province where water use and impervious area have increased in recent decades, highlighting the effects of land and water management on low flows. With continued change expected in the DRB, additional research needs are highlighted to enable estimation of future low flows and to plan for periods of prolonged low flow.

Recent streamflow declines in the Upper Colorado River Basin raise concerns about the sensitivity of water supply for 40 million people to rising temperatures. Yet, other studies in western US river basins present a paradox: streamflow has not consistently declined with warming and snow loss. A potential explanation for this lack of consistency is warming-induced production of winter runoff when potential evaporative losses are low. This mechanism is more likely in basins at lower elevations or latitudes with relatively warm winter temperatures and intermittent snowpacks. We test whether this accounts for streamflow patterns in nine gaged basins of the Salt River and its tributaries, which is a sub-basin in the Lower Colorado River Basin (LCRB). We develop a basin-scale model that separates snow and rainfall inputs and simulates snow accumulation and melt using temperature, precipitation, and relative humidity. Despite significant warming from 1968&ndash, 2011 and snow loss in many of the basins, annual and seasonal streamflow did not decline. Between 25% and 50% of annual streamflow is generated in winter (NDJF) when runoff ratios are generally higher and potential evapotranspiration losses are one-third of potential losses in spring (MAMJ). Sub-annual streamflow responses to winter inputs were larger and more efficient than spring and summer responses and their frequencies and magnitudes increased in 1968&ndash, 2011 compared to 1929&ndash, 1967. In total, 75% of the largest winter events were associated with atmospheric rivers, which can produce large cool-season streamflow peaks. We conclude that temperature-induced snow loss in this LCRB sub-basin was moderated by enhanced winter hydrological inputs and streamflow production.

Citizen scientists keep a watchful eye on the world's streams, catching intermittent streams in action and filling data gaps to construct a more complete hydrologic picture.

Reports regarding the associations between major depressive disorder (MDD) and diabetes remain heterogeneous. Our aim was to investigate whether glucose homeostasis and insulin sensitivity were impaired in the MDD patients and its mechanisms. A total of 30 patients with MDD and 30 matched controls were recruited. The oral glucose tolerance test and dual-energy X-ray absorptiometry scan were performed in each participant. Insulin signaling in postmortem brain tissues from other depressive patients and controls (obtained from Alabama brain bank) was examined. Insulin sensitivity was reduced substantially in the MDD patients, however, the fasting and 2-h glucose concentrations remained within the normal range through compensatory insulin secretion. Despite increased insulin secretion, 1-h glucose concentrations in the MDD patients were significantly elevated compared with the controls. MDD patients had greater visceral fat mass but lower adiponectin levels compared with the controls. Furthermore, phosphorylated-AKT levels in insulin signaling were decreased in postmortem brain tissues in patients with MDD. These results suggest that MDD patients are at a greater risk for diabetes due to decreased insulin sensitivity, reduced disposition index, and impaired glucose tolerance as manifested by elevated 1-h glucose concentrations following an oral glucose challenge. Mechanistic studies reveal that decreased insulin sensitivity is associated with increased visceral fat mass, lower adiponectin levels and impaired insulin action in postmortem brain tissues in the MDD patients. Our findings emphasize the importance of screening depressive patients to identify susceptible individuals for developing future diabetes with the hope of improving their health outcomes.

Several lines of evidence point to alterations of alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor trafficking in schizophrenia. Multiple proteins, including synapse-associated protein 97 (SAP97), glutamate receptor-interacting protein 1 (GRIP1), and N-ethylmaleimide sensitive factor (NSF), facilitate the forward trafficking of AMPA receptors toward the synapse. Once localized to the synapse, AMPA receptors are trafficked in a complex endosomal system. We hypothesized that alterations in the expression of these proteins and alterations in the subcellular localization of AMPA receptors in endosomes may contribute to the pathophysiology of schizophrenia. Accordingly, we measured protein expression of SAP97, GRIP1, and NSF in the dorsolateral prefrontal cortex and found an increase in the expression of SAP97 and GRIP1 in schizophrenia. To determine the subcellular localization of AMPA receptor subunits, we developed a technique to isolate early endosomes from post-mortem tissue. We found increased GluR1 receptor subunit protein in early endosomes in subjects with schizophrenia. Together, these data suggest that there is an alteration of forward trafficking of AMPA receptors as well as changes in the subcellular localization of an AMPA receptor subunit in schizophrenia.

Abnormalities of the glutamate system are widely recognized to be involved in the pathophysiology of schizophrenia, though the exact mechanism is still unclear. Accumulating evidence from postmortem studies has implicated alterations in several components of glutamatergic synapses, including abnormalities of glutamate receptors and transporters. These data support the hypothesis that expression, trafficking, and downstream signaling pathways of N-methyl-D-aspartate (NMDA) receptors are altered in this illness. Changes in glutamate transporter expression suggest there may be chronic glutamate spillover from the synaptic cleft, leading to increased activation of extrasynaptic glutamate receptors. We propose that changes in NMDA-subtype glutamate receptor function and glutamate transporter expression are components of a common pathophysiological pathway leading to the schizophrenia phenotype.

Controlling microbial spoilage of beer is best achieved by elimination of sources of contamination. However it must be realised that the brewing process is not aseptic and the occasional chance contaminant will often be encountered. The effects of such events can be minimised by reducing the susceptibility of beer to spoilage and by the use of techniques capable of rapidly determining low numbers of contaminant organisms before any harm is done. A number of rapid methods have been available to the brewing industry for some years but all are hampered by a lack of sensitivity. Consequently, a number of techniques for concentrating micro-organisms prior to testing have been investigated. The most effective was membrane filtration modified by the use of top-pressure and relatively high temperatures. On the spoilability front, studies of the role of beer components such as dissolved carbon dioxide and phenolic compounds have been carried out. These materials reduce the susceptibility of beers to spoilage.

The treatment of schizophrenia has been focused on modulation of dopamine receptors for over 50 years. Recent developments have implicated other neurotransmitter systems in the pathophysiology of this illness. The discovery and characterization of glutamate receptors and their roles in the brain has lead to novel approaches for the treatment of schizophrenia. In this article, we review drugs that modulate ionotropic gluamate receptors and discuss their efficacy for the treatment of this often debilitating severe mental illness.

Several lines of evidence indicate altered trafficking of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptors in schizophrenia. Previous reports have shown potential changes in the trafficking of AMPA receptors based on subunit expression of endosomes, subcellular organelles located near post-synaptic sites. We hypothesized that alterations in AMPA receptor trafficking through the endoplasmic reticulum (ER) may also be altered in schizophrenia. Accordingly, we developed a technique to isolate and measure content of the ER from postmortem brain tissue. We used Western blot and electron microscopy to show that we isolated an ER enriched fraction. We found no changes in the expression of the AMPA receptor subunits, GluR1-4, in the ER from the dorsolateral prefrontal cortex in schizophrenia. These data suggest that AMPA receptor trafficking through the ER is largely intact in schizophrenia.

THEILER, Green, and Viljoen (1915) were the first to suggest that what was then known as vitamin B might be synthesized by the flora in the digestive tract of cattle. Scheunert and Schieblich (1923) were able to show that B. vulgatus, an organism found in the digestive tract of ruminants, synthesizes vitamin B. Bechdel, Honeywell, Dutcher, and Knutsen (1928) demonstrated that the synthesis of vitamin B took place in the rumen. More recently McElroy and Goss have made quantitative studies of the riboflavin and vitamin K (1940a), pyridoxine (1940b), thiamin (1941a), and pantothenic acid (1941b) synthesized in the rumen of sheep and cows fed diets of low vitamin content. Hunt, Kick, Burroughs, Bethke, Schalk, and Gerlaugh (1941) found that thiamin and riboflavin were synthesized in the rumens of steers fed corn, alfalfa hay, and a protein supplement. Wegner, Booth, Elvehjem, and Hart (1941) investigated the synthesis of thiamin, riboflavin, pyridoxine, . . .

SEVERAL investigators have made extensive studies of gizzard erosion in growing chickens. Dam (1929, 1930, 1934a, 1934b, 1935) and Almquist and Stokstad (1935a, 1935b) observed the condition in chickens fed vitamin K-deficient diets. Almquist and Stokstad (1936a, 1936b) concluded that it is not due to a deficiency of vitamin K but of an unidentified fat-soluble factor. Later Almquist (1938) reported beneficial results were obtained from feeding bile, bile acids, or bile salts to growing chickens. Bird and co-workers (1938) reported that chondroitin is effective in preventing gizzard erosion but Crandall and co-workers (1939) could not confirm this. Lansing, Miller, and Titus (1939) and Miller and Titus (1942) found that a very high percentage of chicks are hatched with deposits of extravasated blood in or under their gizzard linings. Inasmuch as they concluded that these deposits of extravasated blood develop into erosions in the growing chickens, it was desirable to study . . .

IT HAS frequently been noted that the thymus of rapidly growing chickens is large, whereas that of slowly growing chickens is relatively very small. Ackert (1924) found that the thymus glands of chickens parasitized with Ascaridia perspicillum were smaller than those of non-parasitized chickens. However, Riddle and Krizenecky (1931) reported that the removal of both the thymus and the bursa Fabricius from 17 common pigeons did not affect development or function of the reproductive organs. They suggested that other organs, particularly lymph nodes, might have thymic functions. Plagge (1941) has concluded that the thymus glands of male and female albino rats are definitely sensitive to varying concentrations of sex hormones as indicated by gross changes in the thymus at puberty and by both gross and histological changes following castration or injections of sex hormones. Thymectomy does not affect the reproduction system of either sex. As the physiological relationship between the . . .

INTRODUCTION JULL (1923) called attention to an increase in variability in live weight in Barred Plymouth Rock chicks during the first four or five weeks of life. He found that after a period of high variability which lasted until the tenth week for males and the twelfth week for females, there was a general tendency toward decrease in variability in live weight for both sexes. Latimer (1924) found that the variability in live weight of White Leghorn chicks was greatest at five weeks of age. Jull and Quinn (1924) found that the weight of the chick was closely related to the weight of the egg. Schneider and Dunn (1924) showed that the inheritance of body weight in the domestic fowl is extremely complicated, for they found that body weight was three to six times as variable as bone measurements. Jull and Quinn (1931), using a cross between Barred Plymouth Rocks . . .

THE CHIEF NATURAL SOURCES of androgenic substances have been male and female human urine and testes (1, 2). After comparing the male-hormone content of urine from several sources, Koch (1) reported relatively high concentrations in male human urine (40–100 I.U. per 24 hours) and female human urine (30–100 I.U. per 24 hours) as compared with 8, less than 1, and 4 I.U. per liter in urines from the stallion, bull, and ram, respectively. Although, according to Dohrn and Faure (3), considerable quantities of estrogens are excreted in the feces of gravid women, there appears to be no information concerning the excretion of androgens in the feces. In the course of experiments on chick nutrition (4) at the Beltsville Research Center to determine whether or not feces of cattle could be used as a source of certain members of the vitamin B-G complex, one of us (J. C. H.) observed precocious comb and wattle growth in chicks when their diet was supplemented with either dried feces from cows or a 60 per cent alcohol ex...

ACCORDING to Benjamin and Pierce (1937) the skin color in market chickens may range from white through cream to golden yellow and even to a dark brownish yellow. They stated that the white, cream, or golden yellow colors are satisfactory, although the lighter colors are preferred by discriminating consumers. They also stated that the market preference is for smooth yellow shanks. It is common knowledge among producers that there is a marked preference for yellow shanks and skin in broilers on the New York live poultry market. Lee (1911) reported that packers did not care about skin color except when they were supplying a special market that wanted deep yellow skin. These packers believed that deep yellow color could be obtained by adding molasses or, sometimes, artificial butter color to the fattening diet. Later, Lee (1914) found that the bleach produced by fattening with buttermilk varies with the quantity of . . .