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The Mississippi Embayment aquifer is one of the largest alluvial groundwater aquifers in the United States. It is being excessively used, located along the lower Mississippi River covering approximately 202,019 km2 (78,000 square miles). Annual average groundwater depletion in the aquifer has been estimated at 5.18 billion cubic meters (Gm3) (4.2 million acre-feet) in 1981–2000. However, since 2000, annual groundwater depletion has increased abruptly to 8 Gm3 (2001–2008). In recent years, multi-state efforts have been initiated to improve the Mississippi Embayment aquifer sustainability. One management strategy of interest for preserving groundwater resources is managed aquifer recharge (MAR). In this study, we evaluate the impact of different MAR scenarios on land and water use decisions and the overall groundwater system using an economic model able to assess profitability of crop and land use decisions coupled to the Mississippi Embayment Regional Aquifer Study (MERAS) hydrogeologic model. We run the coupled model for 60 years by considering the hydrologic conditions from the MERAS model for the years 2002–2007 and repeating them 10 times. We find MAR is not economically attractive when the water cost is greater than $0.05/m3. Groundwater storage is unlikely to improve when relying solely on MAR as groundwater management strategy but rather should be implemented jointly with other groundwater conservation policies.

ObjectivesChronic endobronchial infections with Pseudomonas aeruginosa contribute to bronchiectasis and progressive loss of lung function in patients with cystic fibrosis. This study aimed to evaluate the therapeutic potential of a novel macrocyclic peptide, rhesus θ-defensin-1 (RTD-1), by characterizing its in vitro antipseudomonal activity and in vivo efficacy in a murine model of chronic Pseudomonas lung infection.MethodsAntibacterial testing of RTD-1 was performed on 41 clinical isolates of P. aeruginosa obtained from cystic fibrosis patients. MIC, MBC, time-kill and post-antibiotic effects were evaluated following CLSI-recommended methodology, but using anion-depleted Mueller-Hinton broth. RTD-1 was nebulized daily for 7 days to cystic fibrosis transmembrane conductance regulator (CFTR) F508del-homozygous mice infected using the agar bead model of chronic P. aeruginosa lung infection. In vivo activity was evaluated by change in lung bacterial burden, airway leucocytes and body weight.ResultsRTD-1 exhibited potent in vitro bactericidal activity against mucoid and non-mucoid strains of P. aeruginosa (MIC90 = 8 mg/L). Cross-resistance was not observed when tested against MDR and colistin-resistant isolates. Time-kill studies indicated very rapid, concentration-dependent bactericidal activity of RTD-1 with ≥3 log10 cfu/mL reductions at concentrations ≥4× MIC. No post-antibiotic effect was observed. In vivo, nebulized treatment with RTD-1 significantly decreased lung P. aeruginosa burden (mean difference of -1.30 log10 cfu; P = 0.0061), airway leucocytes (mean difference of -0.37 log10; P = 0.0012) and weight loss (mean difference of -12.62% at day 7; P

θ-Defensins are cyclic antimicrobial peptides expressed in leukocytes of Old world monkeys. To get insight into their antibacterial mode of action, we studied the activity of RTDs (rhesus macaque θ-defensins) against staphylococci. We found that in contrast to other defensins, RTDs do not interfere with peptidoglycan biosynthesis, but rather induce bacterial lysis in staphylococci by interaction with the bacterial membrane and/or release of cell wall lytic enzymes. Potassium efflux experiments and membrane potential measurements revealed that the membrane impairment by RTDs strongly depends on the energization of the membrane. In addition, RTD treatment caused the release of Atl-derived cell wall lytic enzymes probably by interaction with membrane-bound lipoteichoic acid. Thus, the premature and uncontrolled activity of these enzymes contributes strongly to the overall killing by θ-defensins. Interestingly, a similar mode of action has been described for Pep5, an antimicrobial peptide of bacterial origin.

The working lands programs in the United States are specifically tailored to support farmers in initiating or enhancing conservation practices. The expectation is that farmers receiving financial assistance will continue implementing these practices even after their initial contracts end, thereby increasing the programs' cost‐effectiveness and promoting natural resources conservation. However, little is known about the likelihood of persistence and disadoption of conservation practices once the initial cost‐share contracts expire. Using the first‐order Markov chain framework on state‐level conservation practices acreage data from the Mississippi Delta region (2005–2022), this study provides quantitative estimates of changing (dis)adoption patterns of four conservation practices: cover crops (CCs), conservation tillage (CT), nutrient and irrigation management (NIM), and conservation crop rotation (CCR). The findings reveal a higher probability of persistence of NIM practices. In contrast, acres devoted to CCs and CT tend to transition into other alternative practices, indicating a greater likelihood of disadoption. Importantly, the likelihood of acres that initially adopt conservation practices with funding shifting to a condition of no conservation activity is minimal. The transition probability estimates facilitate the prediction of future adoption rates of conservation practices and aid funding agencies in prioritizing their conservation efforts. Core Ideas: Conservation practices face risk of disadoption after the end of funding period.Cover crops and conservation tillage are disadopted more, while nutrient and irrigation management practices persist.Farmers chose alternative conservation practices instead of moving to the state of no conservation. [ABSTRACT FROM AUTHOR]

BackgroundMutations in signal transducer and activator of transcription (STAT) 1 cause a broad spectrum of disease, ranging from severe viral and bacterial infections (amorphic alleles) to mild disseminated mycobacterial disease (hypomorphic alleles) to chronic mucocutaneous candidiasis (CMC; hypermorphic alleles). The hypermorphic mutations are also associated with arterial aneurysms, autoimmunity, and squamous cell cancers.ObjectiveWe sought to investigate the role of STAT1 gain-of-function mutations in phenotypes other than CMC.MethodsWe initially screened patients with CMC and autoimmunity for STAT1 mutations. We functionally characterized mutations in vitro and studied immune profiles and regulatory T (Treg) cells. After our initial case identifications, we explored 2 large cohorts of patients with wild-type forkhead box protein 3 and an immune dysregulation-polyendocrinopathy-enteropathy-X-linked (IPEX)-like phenotype for STAT1 mutations.ResultsWe identified 5 children with polyendocrinopathy, enteropathy, and dermatitis reminiscent of IPEX syndrome; all but 1 had a variety of mucosal and disseminated fungal infections. All patients lacked forkhead box protein 3 mutations but had uniallelic STAT1 mutations (c.629 G>T, p.R210I; c.1073 T>G, p.L358W, c.796G>A; p.V266I; c.1154C>T, T385M [2 patients]). STAT1 phosphorylation in response to IFN-γ, IL-6, and IL-21 was increased and prolonged. CD4(+) IL-17-producing T-cell numbers were diminished. All patients had normal Treg cell percentages in the CD4(+) T-cell compartment, and their function was intact in the 2 patients tested. Patients with cells available for study had normal levels of IL-2-induced STAT5 phosphorylation.ConclusionsGain-of-function mutations in STAT1 can cause an IPEX-like phenotype with normal frequency and function of Treg cells.

The Mississippi Embayment aquifer is one of the largest alluvial groundwater aquifers in the United States. It is being excessively used, located along the lower Mississippi River covering approximately 202,019 km2 (78,000 square miles). Annual average groundwater depletion in the aquifer has been estimated at 5.18 billion cubic meters (Gm3) (4.2 million acre‐feet) in 1981–2000. However, since 2000, annual groundwater depletion has increased abruptly to 8 Gm3 (2001–2008). In recent years, multi‐state efforts have been initiated to improve the Mississippi Embayment aquifer sustainability. One management strategy of interest for preserving groundwater resources is managed aquifer recharge (MAR). In this study, we evaluate the impact of different MAR scenarios on land and water use decisions and the overall groundwater system using an economic model able to assess profitability of crop and land use decisions coupled to the Mississippi Embayment Regional Aquifer Study (MERAS) hydrogeologic model. We run the coupled model for 60 years by considering the hydrologic conditions from the MERAS model for the years 2002–2007 and repeating them 10 times. We find MAR is not economically attractive when the water cost is greater than $0.05/m3. Groundwater storage is unlikely to improve when relying solely on MAR as groundwater management strategy but rather should be implemented jointly with other groundwater conservation policies. [ABSTRACT FROM AUTHOR]

Owing to their very large piezoelectric coefficients and spontaneous polarizations, (Sc,Y) x Al1−xN alloys have emerged as a new class of III-nitride semiconductor materials with great potential for high-frequency electronic and acoustic devices. The thermal conductivity of constituent materials is a key parameter for design, optimization, and thermal management of such devices. In this study, transient thermoreflectance technique is applied to measure the thermal conductivity of ScxAl1−xN and YxAl1−xN (0 ≤ x ≤ 0.22) layers grown by magnetron sputter epitaxy in the temperature range of 100–400 K. The room-temperature thermal conductivity of both alloys is found to decrease significantly with increasing Sc(Y) composition compared to that of AlN. We also found that the thermal conductivity of YxAl1−xN is lower than that of ScxAl1−xN for all studied compositions. In both alloys, the thermal conductivity increases with the temperature up to 250 K and then saturates. The experimental data are analyzed using a model based on the solution of the phonon Boltzmann transport equation within the relaxation time approximation. The contributions of different phonon-scattering mechanisms to the lattice thermal conductivity of (Sc,Y) x Al1−xN alloys are identified and discussed. [ABSTRACT FROM AUTHOR]

TGF-[beta] family members are highly pleiotropic cytokines with diverse regulatory functions. TGF-[beta] is normally found in the latent form associated with latency-associated peptide (LAP). This latent complex can associate with latent TGF[beta]-binding protein (LTBP) to produce a large latent form. Latent TGF-[beta] is also found on the surface of activated FOXP[3.sup.+] regulatory T cells (Tregs), but it is unclear how it is anchored to the cell membrane. We show that GARP or LRRC32, a leucine-rich repeat molecule of unknown function, is critical for tethering TGF-[beta] to the cell surface. We demonstrate that platelets and activated Tregs co-express latent TGF-[beta] and GARP on their membranes. The knockdown of GARP mRNA with siRNA prevented surface latent TGF-[beta] expression on activated Tregs and recombinant latent TGF-[beta]1 is able to bind directly with GARP. Confocal microscopy and immunoprecipitation strongly support their interactions. The role of TGF-[beta] on Tregs appears to have dual functions, both for Treg-mediated suppression and infectious tolerance mechanism. transforming growth factor beta | Tregs | latency-associated peptide