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Land use impacts from agriculture, industrialization, and human population should be considered in surface water quality management. In this study, we utilized an integrated statistical analysis approach mainly including a seasonal Mann-Kendall test, clustering analysis, self-organizing map, Boruta algorithm, and positive matrix factorization to the assessment of the interactions between land use types and water quality in a typical catchment in the Huai River Basin, China, over seven years (2012-2019). Spatially, water quality was clustered into three groups: upstream, midstream, and downstream/mainstream areas. The water quality of upstream sites was better than of mid-, down-, and mainstream. Temporally, water quality did not change significantly during the study period. However, the temporal variation in water quality of up-, down-, and mainstream areas was more stable than in the midstream. The interactions between land use types and water quality parameters at the sub-basin scale varied with seasons. Increasing forest/grassland areas could substantially improve the water quality during the wet season, while nutrients such as phosphorus from cropland and developed land was a driver for water quality deterioration in the dry season. Water area was not a significant factor influencing the variations of ammonia nitrogen (NH

mAbs have revolutionized the treatment of autoimmune disorders. Even though mAbs have shown impressive efficacy in blocking T cell or B cell activation and/or recruitment to sites of inflammation, this group of biologicals are not devoid of adverse effects. The most serious adverse effects include infusion reactions, including the activation of the complement pathway. In this study, we present a detailed structure–function study of an anti-CCL20 humanized IgG1 mAb that neutralizes CCL20 chemokine and prevents the recruitment of Th17 cells to sites of inflammation. We demonstrate that the anti-CCL20 Ab changes significantly following administration to humans and monkeys and exposure to human serum. Analysis of the drug product revealed that the anti-CCL20 Ab has unexpectedly high C1q binding. This high binding was linked to immune complex formation in vivo but not during in vitro serum incubation. The immune complex contained multiple complement components. Anti-CCL20 Ab-mediated, complement-dependent cytotoxicity occurred when the Ab bound to CCL20 tethered to the cell membrane of target cells. Taken together, these results provide a likely cause for the animal toxicity observed. In addition, anti-CCL20 revealed progressive acidification because of N100 (located in CDR) deamidation over time, which did not directly impact Ag binding. Our study demonstrates that the safety profiling of mAbs should include the evaluation of effector functions in addition to typical stressed conditions.

Chinese hamster ovary (CHO) cells are a mammalian cell line used in the production of therapeutic proteins. Host cell proteins (HCPs) are process-related impurities that are derived from the host cell expression system. During biopharmaceutical drug development, removal of HCPs is required. Enzyme-linked immunosorbent assay (ELISA) is a common technique to quantitate HCPs, but is a labor-intensive process that takes up to 7 h. Ella® is an automated instrument that utilizes microfluidics and glass nanoreactors to quantitate HCPs in 75 min using similar ELISA reagents. The antibodies and antigens are captured on three distinct glass nanoreactors, resulting in sensitive reproducible data. Our results indicate that Ella quantitates CHO HCPs with precision, accuracy, sensitivity and trends comparable with our traditional CHO HCP ELISA.

MODIS satellite imagery and in situ water measurements were used to quantify inorganic sediment concentration (ISC) and, subsequently, sediment plume motion and evolution during the 2016 diversion of the Mississippi River through the Bonnet Carre Spillway (BCS) within Lake Pontchartrain (LP) estuary in Louisiana, USA. Satellite images revealed that sediment plume areal distribution was closely linked to BCS discharge rate. The plume flowed eastward along the southern LP coastline at an average speed of ~ 0.3 m s−1 during the first week of the event and attained its maximum areal extent (~ 1117 km2; 68% of the total LP area) on 23 January. In an attempt to examine the plume kinematics and potential sediment resuspension impacts, wind information was also assessed. Following BCS closure, the prevailing wind direction, but not wind speed, corresponded to significant differences in LP ISC. LP was further subdivided into four separate quadrants to assess relationships between ISC within each quadrant to BCS discharge rate and winds. While the BCS was open, the plume’s eastward motion was associated with a high correlation (r2 = 0.93) between BCS discharge and ISC in the southeast quadrant. However, the weak relationship (r2 = 0.42) between BCS discharge and ISC in the northwest quadrant was attributed to influences from other tributaries. These results will benefit future research regarding impacts of freshwater diversions on coastal and estuarine processes that are sensitive to sediment influx by providing a satellite-based sediment map time series that can be used to help validate numerical circulation and sediment transport models.

Ecosystem service value (ESV) is influenced by land use and land cover (LULC), and is closely related to natural conditions and human activities. However, the interactions between human and natural systems and ESV remain unclear, especially concerning widely discussed meteorological and socioeconomic factors. In this study, three periods of LULC patterns (2000, 2010, and 2020) in the Haihe River Basin, northern China, were collected to determine the relationship between changes in LULC and ESV over time. Natural and socioeconomic data associated with ESV were obtained and the structural equation model was used to decouple interactions between these factors. Results showed that the total value of regional ecosystem services has decreased as cultivated land shrunk and artificial surfaces increased over the past two decades. The ESV was significantly decreased in the middle of the basin. The direct effects of meteorological factors and socioeconomic factors on ESV were positive (0.094) and negative (-0.203), respectively. The indirect effect of socioeconomic factors on ESV through meteorological and LULC factors was 0.149. Structural equation modeling demonstrated that under the dominance of LULC, interactions between natural and socioeconomic factors affected ESV in a complex manner. These results implied that identifying the direct and indirect effects of economic development and human activities on ESV could guide and implement effective land management policies.

International audience; Following the emerging bluetongue virus transmission in European temperate regions, we question the vector competence of the abundant Culicoides austropalpalis Lee and Reye in South-East temperate Australia. Field collected Culicoides midges were membrane fed with a bluetongue virus serotype 1 (BTV-1). The average feeding rate was 50%. After 13 days, survival rate was 25% and virus RNA presence was checked by quantitative PCR targeting viral genome segment 10. Virus RNA was found in 7.4% of individually tested females with relative viral RNA load values lower than freshly fed females, indicating that viral replication was low or null. A second qPCR targeting viral genome segment 1 confirmed the presence of virus RNA in only four out of 29 previously positive specimens. After 10 days culture on Culicoides cells, none of these four confimed positive samples did show subsequent cytopathogenic effect on Vero cells or BTV antigen detection by ELISA. As control for this virus activity detection, 12 days after microinjection of BTV-1, Culex annulirostris mosquitoes showed, after culture on Kc cells, cytopathogenic effect on Vero cells, with ELISA-confirmed infection. Despite its abundance in farm environment of the temperate Australian regions, the results of this study make C. austropalpalis of unlikely epidemiological importance in the transmission of BTV in Australia.

Hands-On Archaeology immerses students in the world of real-life archaeologists. Through engaging authentic learning experiences, students will discover artifacts from the past and participate in archaeological digs while building STEM skills, as well as making connections to geography, history, art, and English language arts. This book is packed with activities that can easily be conducted in the classroom using everyday materials and includes everything teachers need to help students conduct real-life archaeological digs. From participating in digs in the classroom to conducting digs in the community, students will not just learn about archaeology—they will be archaeologists!Grades 4-5

Lack of simple and robust methods to determine complement activation in human serum induced by antigen-antibody complexes is a major hurdle for monitoring therapeutic antibody drug quality and stability. Dezamizumab is a humanized IgG1 monoclonal antibody that binds to serum amyloid P component (SAP) for potential treatment of systemic amyloidosis. The mechanism of action of Dezamizumab includes the binding of SAP, complement activation through classical pathway, and phagocytosis; however, the steps in this process cannot be easily monitored. We developed two novel methods to determine Dezamizumab-SAP complex-induced complement activation. Complement component 3 (C3) depletion was detected by homogeneous time-resolved fluorescence (HTRF), and C3a desArg fragment, formed after the cleavage of C3 to yield C3a followed by removal of its C-terminal arginine residue, was determined using Meso Scale Discovery (MSD) technology. We found that the presence of both Dezamizumab and SAP was required for complement activation via both methods. The optimal molar ratio of Dezamizumab:SAP was 6:1 in order to obtain maximal complement activation. The relative potency from both methods showed a good correlation to Dezamizumab-SAP-dependent complement component 1q (C1q) binding activity in Dezamizumab thermal-stressed samples. Both SAP and C1q binding, as determined by surface plasmon resonance and the two complement activation potency methods described here, reflect the mechanism of action of Dezamizumab. We conclude that these methods can be used to monitor Dezamizumab quality for drug release and stability testing, and the novel potency methods reported here can be potentially used to evaluate complement activity induced by other antigen-antibody complexes.

Serious mental illnesses (SMIs), including schizophrenia, bipolar disorder, and major depressive disorder (MDD), are often treated with antipsychotic medications. Unfortunately, medication non-adherence is widespread and is associated with serious adverse outcomes. However, little real-world data are available describing adherence, compliance, or other medication-taking-related discussions between providers and patients. This study described these communications in ambulatory care.Commercially insured patients having acute (emergency or inpatient) behavioral health (BH) events were included by specific criteria: age 18-65 years; diagnoses of schizophrenia, bipolar disorder, or MDD; continuous health insurance coverage 6 months before to 12 months after the first claim (index) date during 01/01/2014‒12/31/2015; and prescribed antipsychotic medication. Medical charts were abstracted for ambulatory visits with a BH diagnosis through 12 months after the acute event, describing any treatment compliance discussions that occurred. BH-related healthcare utilization and costs were measuredNinety patients were included: 62% female, mean age 41 years. Only 58% had antipsychotic compliance discussions during the first abstracted ambulatory visit. A total of 680 BH-related visits were abstracted for the 90 patients. Providers frequently discussed any psychotropic medication use (97% of all visits abstracted); however, discussion of compliance with BH talk therapies was less common (49% of visits among patients with a first visit antipsychotic discussion and 23% without,Increasing the frequency of antipsychotic treatment-related adherence/compliance discussions may represent an opportunity to improve the quality of care for these vulnerable patients and reduce the overall economic burden associated with the treatment of SMI diagnosis.

Biological activity is a critical quality attribute for biopharmaceuticals, which is accurately measured using an appropriate relative potency bioassay. Developing a bioassay is a complex, rigorous undertaking that needs to address several challenges including modelling all of the mechanisms of action associated with the biotherapeutic. Bioassay development is also an exciting and fast evolving field, not only from a scientific, medical and technological point of view, but also in terms of statistical approaches and regulatory expectations. This has led to an industry-wide discussion on the most appropriate ways to develop, validate and control the bioassays throughout the drug lifecycle.

Coastal Louisiana is dominated by the Mississippi River Deltaic Plain, which is composed of a series of overlapping and truncated sub-delta lobes that formed an extensive coastal wetland – open water shallow bay and low relief upland mosaic across the entire coastal zone (∼25,000 km2). These coastal wetlands have been eroding at an alarming rate during the past century, coincident with major modifications to the deltaic landscape. One of these former modifications included extensive leveeing of the Mississippi River, essentially isolating the river from the coastal basins. One restoration technique involves re-connecting the previously isolated coastal basins to the river via diversions, which would once again allow the influx of freshwater, sediments and nutrients into the coastal basins. We review issues on potential impacts of nutrient loading from the river as a consequence of river diversions, focused on nitrogen (N) and phosphorus (P) dynamics including denitrification related to carbon dynamics. We also examined how water residence times in these shallow systems, compared to deeper, often seasonally stratified, coastal systems, are more likely to lead to greater N removal potential in the context of a large scale river diversion helping to reduce N transport to the coastal ocean.

River systems worldwide have become substantially influenced by human activities, including land use changes, river diversion operations, and flood control measures. Some of the unambiguous and best studied examples of effects of enhanced eutrophication on biotic resources can be found in Louisiana estuaries at the terminus of the Mississippi-Atchafalaya River system. The Mississippi River delta has experienced large losses of coastal wetlands due to a combination of human impacts and sea-level rise. State and Federal agencies are moving ahead with plans for building large-scale river sediment diversions, which will capture maximum sediment during spring flood pulses and direct a sediment subsidy into the eroding coastal basins. These large-scale river sediment diversions will also substantially increase freshwater and nutrient inputs and are likely to affect algal bloom formation, including harmful cyanobacterial blooms. There are concerns that discharge of river water containing high concentrations of N, P and Si may trigger algal blooms in the coastal receiving basins. River sediment diversions, as any other flood pulsing, will likely be disruptive to the coastal ecology and so balancing the benefits of slowing coastal land loss against potential negative effects on water quality remains a formidable management challenge. We review here the physical, chemical and biological factors affecting primary production in shallow coastal systems and provide known data on ecosystem response to freshwater diversions, large and small. We also discuss potential management approaches to mitigate the negative impacts of the diversions on the health and stability of the coastal food webs.

Phosphorus (P) cycling in the coastal ocean along deltaic coastlines is predominantly controlled by river discharge and biogeochemical properties of the sediments. In the Louisiana shelf, sediment biogeochemistry is strongly influenced by seasonally-fluctuating bottom water O2, which, can potentially transition the shelf sediments from being a sink to source of P. Sediment P fluxes determined using persistent anaerobic and aerobic intact core incubations were 11.46 ± 3.2 mg m−2 d−1 and 0.67 ± 0.16 mg m−2 d−1 respectively, indicating a 17 times greater P efflux from O2-deprived sediments. During the transition from aerobic to anaerobic conditions, the high sedimentary O2 consumption rate of 889 ± 33.6 mg m−2 d−1 resulted in a progressive decrease in the dissolved O2 in the overlying water, leading to a sediment P flux of 7.2 ± 5.5 mg m−2 d−1, which was mostly driven by P release towards the end of the incubation when the overlying water became near anoxic. This P flux led to a 34.6% loss in sedimentary Fe-bound P during the two-day incubation period which underscores the importance of coupled Fe P biogeochemistry and O2 penetration depth in a coastal hypoxia setting. The high DIN: DIP ratio of river water (∼50:1; P limited) coupled with high potential release of P from the shelf sediments can further increase primary production, further exacerbating hypoxic conditions though increased organic matter (OM) deposition and subsequent decomposition.

Sediment diversions along the lower Mississippi River have been proposed to help slow the rate of wetland loss in Louisiana by transferring sediment from the river to coastal marshes, facilitating wetland accretion. While diversions will provide relief to sediment starved coastal wetlands, they will also deliver significant amounts of nutrients (primarily N as NO3–) to receiving basins with potential for negative water quality impacts. There is a paucity of data on nitrate removal rates in the “near-field” area of diversions, identified as areas in immediate proximity to diversion outfalls. In these environments, well-mixed turbulent water column conditions can impart significant shear stress on the sediment surface, suspending fine grained sediments. It is critical to determine nitrate reduction in this near-field environment to predict the potential impact of N on the receiving basins of sediment diversions. Sediment cores were collected from three sites within a mudflat in an active deltaic setting in coastal Louisiana, representative of sediment in the receiving basins, and subjected to shear stress using a flow-through erosional microcosm system for 24 h. Nitrate reduction rates were 18.7 ± 20.2, 186 ± 55.1 and 303 ± 65.6 mg N m−2 d−1 determined under zero, medium and high shear stress conditions of 0, 0.2, and 0.45 Pa, respectively. Nitrate reduction rates were ∼10–16 times faster as shear stress increased. These results indicate that even under well-oxygenated, turbulent flow water column conditions, nitrate can be significantly reduced through the reworking and resuspension of sediment. This research can help inform diversion models and assist natural resource managers in predicting potential nutrient loads and associated impacts of river diversions on shallow estuarine receiving basins as well as being applicable to other flowing systems.

Coastal wetland submergence can occur when rates of relative sea-level rise exceed that of soil elevation gain or landward transgression. In highly organic soils, the collapse of the wetland platform into open water can cause disarticulation of the soil structure, exposing previously protected anaerobic microzones to oxygenated seawater, which may accelerate mineralization rates. Nine soil cores (1 m deep) were collected from three sites within Barataria Bay, LA (USA), a region known for high rates of wetland submergence. Both the biogeochemical properties of the soils with depth were determined, as well as the impacts of the introduction of oxygenated seawater on carbon mineralization rates. Both field enzyme activity (β‑glucosidase, N‑acetyl‑beta‑ d ‑glucosaminidase, alkaline phosphatase, β‑xylosidase, and β‑cellobiosidase) and microbial biomass carbon (MBC) did not significantly change with depth until 50 cm, where activity increased dramatically, then gradually decreased. Total carbon (C), total nitrogen, and percent organic matter were highest between 50 and 100 cm. Following initial biogeochemical characterization, soil microcosms were created for 11 depth segments under anaerobic conditions (mimicking an intact wetland) and aerobic conditions (mimicking a submerging wetland mixing with oxygenated water); carbon dioxide (CO2) production was measured within the bottles over 14 days. Carbon dioxide production averaged 66% greater in the aerobic treatment than the anaerobic treatment. Both treatments exhibited a general trend of increasing CO2 production with depth (particularly from 40 to 100 cm), with the difference in CO2 production between aerobic and anaerobic treatments being 4× greater at 90–100 cm than at the soil surface (0–5 cm). The increase in C mineralization rates observed at depth was positively correlated with indicators of greater microbial activity (i.e., higher enzyme activity and MBC) and greater nutrient availability. Study results indicate coastal wetland submergence into open water could significantly enhance CO2 emissions, even in deep (40+ cm) soils, contrary to the typically observed pattern of soil microbial activity and soil quality decreasing with depth. These findings underline the need to analyze deeper soil samples (1+ m) in order to fully understand the implications of sea level rise on C loss from submerging coastal wetland soils.