Nitrate reduction capacity is limited by belowground plant recovery in a 32‐year‐old created salt marsh

Human activities have decreased global salt marsh surface area with a subsequent loss in the ecosystem functions they provide. The creation of marshes in terrestrial systems has been used to mitigate this loss in marsh cover. Although these constructed marshes may rapidly recover ecosystem structure, biogeochemical processes may be slow to recover. We compared denitrification and dissimilatory nitrate reduction to ammonium (DNRA) rates between a 32‐year‐old excavation‐created salt marsh (CON‐2) and a nearby natural reference salt marsh (NAT) to assess the recovery of ecosystem function. These process rates were measured at 5 cm increments to a depth of 25 cm to assess how plant rooting depth and organic matter accumulation impact N‐cycling. We found that, for both marshes, denitrification and DNRA declined with depth with the highest rates occurring in the top 10 cm. In both systems, N‐retention by DNRA accounted for upwards of 75% of nitrate reduction, but denitrification and DNRA rates were nearly 2× and 3× higher in NAT than CON‐2, respectively. Organic matter was 6× lower in CON‐2, likely due to limited plant belowground biomass production. However, there was no response to glucose additions, suggesting that the microbial functional community, not substrate limitation, limited nitrate reduction recovery. Response ratios showed that denitrification in CON‐2 recovered in surficial sediments where belowground biomass was highest, even though biomass recovery was minimal. This indicates that although recovery of ecosystem function was constrained, it occurred on a faster trajectory than that of ecosystem structure.     

Methylation of protein phosphatase 2A—Influence of regulators and environmental stress factors

Protein phosphatase 2A catalytic subunit (PP2A‐C) has a terminal leucine subjected to methylation, a regulatory mechanism conserved from yeast to mammals and plants. Two enzymes, LCMT1 and PME1, methylate and demethylate PP2A‐C, respectively. The physiological importance of these posttranslational modifications is still enigmatic. We investigated these processes in Arabidopsis thaliana by mutant phenotyping, by global expression analysis, and by monitoring methylation status of PP2A‐C under different environmental conditions. The lcmt1 mutant, possessing essentially only unmethylated PP2A‐C, had less dense rosettes, and earlier flowering than wild type (WT). The pme1 mutant, with 30% reduction in unmethylated PP2A‐C, was phenotypically comparable with WT. Approximately 200 overlapping genes were twofold upregulated, and 200 overlapping genes were twofold downregulated in both lcmt1 and pme1 relative to WT. Differences between the 2 mutants were also striking; 97 genes were twofold upregulated in pme1 compared with lcmt1, indicating that PME1 acts as a negative regulator for these genes. Analysis of enriched GO terms revealed categories of both abiotic and biotic stress genes. Furthermore, methylation status of PP2A‐C was influenced by environmental stress, especially by hypoxia and salt stress, which led to increased levels of unmethylated PP2A‐C, and highlights the importance of PP2A‐C methylation/demethylation in environmental responses.     

A Quartet of Leucine Residues in the Guanylate Kinase Domain of CaVβ Determines the Plasma Membrane Density of the CaV2.3 Channel

Ca_Vβ subunits are formed by a Src homology 3 domain and a guanylate kinase-like (GK) domain connected through a variable HOOK domain. Complete deletion of the Src homology 3 domain (75 residues) as well as deletion of the HOOK domain (47 residues) did not alter plasma membrane density of Ca_V2.3 nor its typical activation gating. In contrast, six-residue deletions in the GK domain disrupted cell surface trafficking and functional expression of Ca_V2.3. Mutations of residues known to carry nanomolar affinity binding in the GK domain of Ca_Vβ (P175A, P179A, M195A, M196A, K198A, S295A, R302G, R307A, E339G, N340G, and A345G) did not significantly alter cell surface targeting or gating modulation of Ca_V2.3. Nonetheless, mutations of a quartet of leucine residues (either single or multiple mutants) in the α3, α6, β10, and α9 regions of the GK domain were found to significantly impair cell surface density of Ca_V2.3 channels. Furthermore, the normalized protein density of Ca_V2.3 was nearly abolished with the quadruple Ca_Vβ3 Leu mutant L200G/L303G/L337G/L342G. Altogether, our observations suggest that the four leucine residues in Ca_Vβ3 form a hydrophobic pocket surrounding key residues in the α-interacting domain of Ca_V2.3. This interaction appears to play an essential role in conferring Ca_Vβ-induced modulation of the protein density of Ca_Vα1 subunits in Ca_V2 channels.     

Risk assessment of workers exposed to crystalline silica aerosols

This study was conducted to determine the concentration of airborne respirable crystalline silica (ARCS) particles and to evaluate its risk level among workers employed in eight different workplaces in Iran. They included sandblasting operations, ceramic production, sand and gravel work, brick production, asphalt manufacturing, foundry operation, glass making, and stone cutting. Personal exposure to ARCS was measured in randomly selected samples from each workplace. The maximum and minimum average of ARCS concentration in the eight workplaces were observed in foundry operation (0.338 ± 0.110 mg/m³) and glass manufacturing (0.125 ± 0.093 mg/m³), respectively. The average concentration of ARCS in all assessed working conditions were higher than the permitted limit of occupational contact recommended by Technical Committee of the Iranian Ministry of Health, treatment and medical education (0.025 mg/m³). Overall, the results showed a serious lack of control in Iranian industries with respect to workers' exposures to ARCS.     

Predilection of Segmental Glomerulosclerosis Lesions for the Glomerulotubular Junction Area in Type 1 Diabetic Patients: A Novel Mapping Method

The location of segmental glomerular lesions in relation to the vascular or tubular pole may have diagnostic or prognostic significance. We have developed a model-based method to estimate the distance from a glomerular lesion to a given landmark (vascular or tubular pole) or the glomerular center and applied this to biopsies from 5 microalbuminuric, 5 normoalbuminuric and 7 proteinuric type 1 diabetic patients and 5 normal controls. The distance from each glomerular adhesion to the glomerulotubular junction was measured and divided by the glomerular radius, allowing comparability among different glomeruli, assuming a spherical shape for Bowman''s capsule, an assumption which was validated. The frequency of adhesions in 6 glomerular zones with equal height (zone I adjacent to the glomerulotubular junction and zones II–VI progressively farther away) was determined: 59% of adhesions were in zone I, 15% in zone II, 16% in zone III, 7% in zone IV and 3% in zone VI (adjacent to the hilus). In glomeruli with only one adhesion, 82% of these were in zone I. This new method accurately localizes segmental lesions within glomeruli and revealed a marked predilection in type 1 diabetic patients for segmental sclerosis to develop at the glomerulotubular junction.     

Diurnal variation of the delta 13C of pine needle respired CO2 evolved in darkness

The delta 13C of pine needle CO2 evolved in darkness (delta 13Cr) for slash pine trees (Pinus elliottii) was determined by placing recently collected pine needles in darkness and collecting respired CO2 over a short time period (<15 min). Delta 13Cr measurements were made over several 24 h periods to test the hypothesis that significant variation in delta 13Cr would be observed during a diurnal cycle. The delta 13Cr measurements from the 24 h time series trials showed a consistent midday 13C-enrichment (5-10 per thousand) relative to bulk biomass. The delta 13Cr values became more 13C-depleted at night and following shading, and approached bulk-biomass delta 13C values by dawn. The effect of night-time respired 13C-enriched CO2 on the delta 13C value of the remaining assimilate is shown to be minimal (13C depleted by 0.22 per thousand) under field conditions for P. elliottii needles.     

PD-1/PD-L1-dependent immune response in colorectal cancer

Colorectal cancer (CRC) is still considered as the third most frequent cancer in the world. Microsatellite instability (MSI), inflammation, and microRNAs have been demonstrated as the main contributing factors in CRC. Subtype 1 CRC is defined by NK cells infiltration, induction of Th1 lymphocyte and cytotoxic T cell responses as well as upregulation of immune checkpoint proteins including programmed cell death-1 (PD-1). Based on the diverse features of CRC, such as the stage and localization of the tumor, several treatment approaches are available. However, the efficiency of these treatments may be decreased due to the development of diverse resistance mechanisms. It has been proven that monoclonal antibodies (mAbs) can increase the effectiveness of CRC treatments. Nowadays, several mAbs including nivolumab and pembrolizumab have been approved for the treatment of CRC. Immune checkpoint receptors including PD-1 can be inhibited by these antibodies. Combination therapy gives an opportunity for advanced treatment for CRC patients. In this review, an update has been provided on the molecular mechanisms involved in MSI colorectal cancer immune microenvironment by focusing on PD-ligand 1 (PD-L1) and treatment of patients with advanced immunotherapy, which were examined in the different clinical trial phases. Considering induced expression of PD-L1 by conventional chemotherapeutics, we have summarized the role of PD-L1 in CRC, the chemotherapy effects on the PD-1/PD-L1 axis and novel combined approaches to enhance immunotherapy of CRC by focusing on PD-L1.     

MicroRNAs and breast cancer stem cells: Potential role in breast cancer therapy

MicroRNAs (miRNAs) can control cancer and cancer stem cells (CSCs), and this topic has drawn immense attention recently. Stem cells are a tiny population of a bulk of tumor cells that have enormous potential in expansion and metastasis of the tumor. miRNA have a crucial role in the management of the function of stem cells. This role is to either promote or suppress the tumor. In this review, we investigated the function and different characteristics of CSCs and function of the miRNAs that are related to them. We also demonstrated the role and efficacy of these miRNAs in breast cancer and breast cancer stem cells (BCSC). Eventually, we revealed the metastasis, tumor formation, and their role in the apoptosis process. Also, the therapeutic potential of miRNA as an effective method for the treatment of BCSC was described. Extensive research is required to investigate the employment or suppression of these miRNAs for therapeutics approached in different cancers in the future.