Combined application of biochar and nitrogen (N) fertilizer has the potential to reduce N losses from soil. However, the effectiveness of biochar amendment on N management can vary with biochar types ...with different physical and chemical properties. This study aimed to assess the effect of two types of hardwood biochar with different ash contents and cation exchange capacity (CEC) on soil N mineralization and nitrous oxide (N2O) production when applied alone and in combination with N fertilizer. Soil samples collected from a temperate pasture system were amended with two types of biochar (B1 and B2), urea, and urea plus biochar, and incubated for 60 days along with soil control (without biochar or urea addition). Soil nitrate N, ammonium N, ammonia-oxidizing bacteria amoA gene transcripts, and N2O production were measured during the experiment. Compared to control, addition of B1 (higher CEC and lower ash content) alone decreased nitrate N concentration by 21% to 45% during the incubation period while the addition of B2 (lower CEC and higher ash content) alone increased the nitrate N concentration during the first 10 days. Biochar B1 also reduced the abundance of amoA transcripts by 71% after 60 days. Compared to B1 + urea, B2 + urea resulted in a significantly greater initial increase in soil ammonium and nitrate N concentrations. However, B2 + urea had a significantly lower 60-day cumulative N2O emission compared to B1 + urea. Overall, when applied with urea, the biochar with higher CEC reduced ammonification and nitrification rates, while biochar with higher ash content reduced N N2O production. Our study demonstrated that biochar has the potential to enhance N retention in soil and reduce N2O emission when it is applied with urea, but the specific effects of the added biochar depend on its physical and chemical properties.
Developing mammals are exposed to progesterone through several sources; however, the role of progesterone in early development is not well understood. Males express more progestin receptors (PRs) ...than females within several brain regions during early postnatal life, suggesting that PRs may be important for the organization of the sex differences in the brain and behavior. Indeed, previous studies showed cognitive impairments in male rats treated neonatally with a PR antagonist. In the present study, we examined the role of PRs in organizing juvenile behaviors. Social play behavior and social discrimination were examined in juvenile male and female rats that had been treated with CDB, a PR antagonist, during the first week of postnatal life. Interestingly, neonatal PR antagonism altered different juvenile behaviors in males and females. A transient disruption in PR signaling during development had no effect on social discrimination but increased play initiation and pins in females. These data suggest that PRs play an important role in the organization of sex differences in some social behaviors.
The Signal Transducer and Activator of Transcription (STAT)-5 proteins are required in immune regulation and homeostasis and play a crucial role in the development and function of several ...hematopoietic cells. STAT5b activation is involved in the expression of genes that participate in cell development, proliferation, and survival. STAT5a and STAT5b are paralogs and only human mutations in
have been identified leading to immune dysregulation and hematopoietic malignant transformation. The inactivating
mutations cause impaired post-natal growth, recurrent infections and immune dysregulation, whereas gain of function somatic mutations cause dysregulated allergic inflammation. These mutations are rare, and they are associated with a wide spectrum of clinical manifestations which provide a disease model elucidating the biological mechanism of STAT5 by studying the consequences of perturbations in STAT5 activity. Further, the use of Jak inhibitors as therapy for a variety of autoimmune and malignant disorders has increased substantially heading relevant lessons for the consequences of Jak/STAT immunomodulation from the human model. This review summarizes the biology of the STAT5 proteins, human disease associate with molecular defects in STAT5b, and the connection between aberrant activation of STAT5b and the development of certain cancers.
Background Gain-of-function (GOF) mutations in the human signal transducer and activator of transcription 1 (STAT1) manifest in immunodeficiency and autoimmunity with impaired TH 17 cell ...differentiation and exaggerated responsiveness to type I and II interferons. Allogeneic bone marrow transplantation has been attempted in severely affected patients, but outcomes have been poor. Objective We sought to define the effect of increased STAT1 activity on T helper cell polarization and to investigate the therapeutic potential of ruxolitinib in treating autoimmunity secondary to STAT1 GOF mutations. Methods We used in vitro polarization assays, as well as phenotypic and functional analysis of STAT1 -mutated patient cells. Results We report a child with a novel mutation in the linker domain of STAT1 who had life-threatening autoimmune cytopenias and chronic mucocutaneous candidiasis. Naive lymphocytes from the affected patient displayed increased TH 1 and follicular T helper cell and suppressed TH 17 cell responses. The mutation augmented cytokine-induced STAT1 phosphorylation without affecting dephosphorylation kinetics. Treatment with the Janus kinase 1/2 inhibitor ruxolitinib reduced hyperresponsiveness to type I and II interferons, normalized TH 1 and follicular T helper cell responses, improved TH 17 differentiation, cured mucocutaneous candidiasis, and maintained remission of immune-mediated cytopenias. Conclusions Autoimmunity and infection caused by STAT1 GOF mutations are the result of dysregulated T helper cell responses. Janus kinase inhibitor therapy could represent an effective targeted treatment for long-term disease control in severely affected patients for whom hematopoietic stem cell transplantation is not available.
Evidence that infectious diseases cause wildlife population extirpation or extinction remains anecdotal and it is unclear whether the impacts of a pathogen at the individual level can scale up to ...population level so drastically. Here, we quantify the response of a Common eider colony to emerging epidemics of avian cholera, one of the most important infectious diseases affecting wild waterfowl. We show that avian cholera has the potential to drive colony extinction, even over a very short period. Extinction depends on disease severity (the impact of the disease on adult female survival) and disease frequency (the number of annual epidemics per decade). In case of epidemics of high severity (i.e., causing >30% mortality of breeding females), more than one outbreak per decade will be unsustainable for the colony and will likely lead to extinction within the next century; more than four outbreaks per decade will drive extinction to within 20 years. Such severity and frequency of avian cholera are already observed, and avian cholera might thus represent a significant threat to viability of breeding populations. However, this will depend on the mechanisms underlying avian cholera transmission, maintenance, and spread, which are currently only poorly known.
Conformational isomers (conformers) of molecules play a decisive role in biology and organic chemistry. However, experimental methods for investigating chemical reaction dynamics are typically not ...conformer-sensitive. We report on a gas-phase megaelectronvolt ultrafast electron diffraction investigation of α-phellandrene undergoing an electrocyclic ring-opening reaction. We directly imaged the evolution of a specific set of α-phellandrene conformers into the product isomer predicted by the Woodward-Hoffmann rules in real space and time. Our experimental results are in quantitative agreement with nonadiabatic quantum molecular dynamics simulations, which provide considerable detail of how conformation influences the time scale and quantum efficiency of photoinduced ring-opening reactions.
Mutations in the Nramp1 gene (Slc11a1) cause susceptibility to infection by intracellular pathogens. The Nramp1 protein is expressed at the phagosomal membrane of macrophages and neutrophils and is a ...paralog of the Nramp2 (Slc11a2) iron transporter. The Nramp1 transport mechanism at the phagosomal membrane has remained controversial. An Nramp1 protein modified by insertion of a hemagglutinin epitope into the predicted TM7/8 loop was expressed at the plasma membrane of Chinese hamster ovary cells as demonstrated by immunofluorescence and surface biotinylation. Experiments in Nramp1HA transfectants using the metal-sensitive fluorophors calcein and Fura2 showed that Nramp1HA can mediate Fe2+, Mn2+, and Co2+ uptake. Similar results were obtained in transport studies using radioisotopic 55Fe2+ and 54Mn2+. Nramp1HA transport was dependent on time, temperature, and acidic pH, occurring down the proton gradient. These experiments suggest that Nramp1HA may be a more efficient transporter of Mn2+ compared to Fe2+ and a more efficient Mn2+ transporter than Nramp2HA. The membrane topology and transport properties of Nramp1HA and Nramp2HA were indistinguishable, suggesting that Nramp1 divalent-metal transport at the phagosomal membrane is mechanistically similar to that of Nramp2 at the membrane of acidified endosomes. These results clarify the mechanism by which Nramp1 contributes to phagocyte defenses against infections.
The Fc receptor on NK cells, FcγRIIIA (CD16), has been extensively studied for its role in mediating antibody-dependent cellular cytotoxicity (ADCC). A homozygous missense mutation in CD16 (encoding ...a L66H substitution) is associated with severe herpesvirus infections in rare patients. Here, we identified a new patient with this CD16 mutation and compared the patient's NK cells to those of the originally reported patient. Patients with the L66H mutation had intact ADCC, but deficient spontaneous NK cell cytotoxicity and decreased surface expression of CD2, a coactivation receptor. Mechanistic studies in a human NK cell line, NK-92, demonstrated that CD16 expression correlated with CD2 surface levels and enabled killing of a melanoma cell line typically resistant to CD16-deficient NK-92 cells. An association between CD16 and CD2 was identified biochemically and at the immunological synapse, which elicited CD16 signaling after CD2 engagement. Stable expression of CD16 L66H in NK-92 cells recapitulated the patient phenotype, abrogating association of CD16 with CD2 as well as CD16 signaling after CD2 ligation. Thus, CD16 serves a role in NK cell-mediated spontaneous cytotoxicity through a specific association with CD2 and represents a potential mechanism underlying a human congenital immunodeficiency.
PDF
