Hemeproteins play an important role in the signaling processes mediated by nitric oxide (NO). For example, the production of NO by nitric oxide synthase, the activation of guanylate cyclase by ...binding NO, and the scavenging of NO by hemoglobin, myoglobin, and cytochrome c oxidase all occur through unique mechanisms of interaction between NO and hemeproteins. Unlike carbon monoxide (CO) and oxygen (O2), which have been studied extensively, the reactions of NO with ferric and ferrous hemeproteins are not as well characterized. In this work, NO binding to myoglobin is studied using cryogenic optical spectroscopy and Fourier transform infrared spectroscopy (FTIR) in order to characterize the ligand-bound and photoproduct states involved in the interaction of NO with the heme iron and the distal pocket of the protein. For ferrous nitrosyl myoglobin (MbIINO), optical spectroscopy is used to show that the ligand-bound state can be converted to >95% stable photoproduct below 10 K. The Soret peak of the photoproduct is red-shifted by 4 nm relative to deoxy-myoglobin (Mb), similar to previous results for carbonmonoxy- (MbCO) and oxy-myoglobin (MbO2) (Miller et al., 1996). MbIINO completely rebinds by 35 K, indicating that the rebinding barrier for NO is lower than MbCO, consistent with room temperature picosecond kinetic measurements. For ferric nitrosyl myoglobin (MbIIINO), we find that the photoproduct yield at cryogenic temperatures is less than unity and dependent on the distal pocket residue. Native MbIIINO has a lower photoproduct yield than the mutant, MbIII(H64L)NO, where the distal histidine is replaced by leucine. The rebinding rates for the native and mutant species are similar to each other and to MbIINO. By using FTIR difference spectroscopy (photolyzed/unphotolyzed) of isotopically labeled ferrous nitrosyl myoglobin (MbIINO), the NO stretching frequencies in both the ligand-bound states and photoproduct states are determined. Two ligand-bound conformational states (1607 and 1613 cm-1) and two photoproduct conformational states (1852 and 1857 cm-1) are observed for MbIINO. This is the first direct observation of photolyzed NO in the distal pocket of myoglobin. The ligand-bound frequencies are consistent with a bent MbIINO moiety, where the unpaired π*(NO) electron remains localized on NO, causing ν(N−O) to be ∼300 cm-1 lower than MbIIINO. Similar to MbO2, we suggest that Nε of the distal histidine is protonated, forming a hydrogen bond to the NO ligand. For native MbIIINO, a single ligand-bound conformational state with respect to ν(N−O) is observed at 1927 cm-1. This frequency decreases to 1904 cm-1 for the mutant, MbIII(H64L)NO, contrary to the increase of the carbon monoxide (CO) stretching frequency in the isoelectronic MbII(H64L)CO mutant versus native MbCO. For linear MbIIINO, we suggest that backbonding from the unpaired π*(NO) electron to iron results in an increased positive charge on the NO ligand, Fe(δ-)−NO(δ+). This can be facilitated by tautomerism of the distal histidine, leaving Nε of the imidazole ring unprotonated and able to accept positive charge from the Fe(δ-)−NO(δ+) moiety, resulting in a higher bond order (and a 23 cm-1 shift to higher frequency) for native MbIIINO versus MbIII(H64L)NO, where this interaction is absent. These different interactions between the distal histidine and the ferrous versus ferric species illustrate potential ways the protein can stabilize the bound ligand and demonstrate the versatile nature by which NO can bind to hemeproteins.
The exchange of phosphorus (P) and carbon (C) between plants and arbuscular mycorrhizal fungi (AMF) is a major determinant of their mutualistic symbiosis. We explored the C dynamics in tomato ...(Solanum lycorpersicum) inoculated or not with Rhizophagus irregularis to study their growth response under different NaH2PO4 concentrations (Null P, 0 mM; Low P, 0.065 mM; High P, 1.3 mM). The percentage of AMF colonization was similar in plants under Null and Low P, but severely reduced under High P. However, the AMF mass biomarker 16:1ω5 revealed higher fungal accumulation in inoculated roots under Low P, while more AMF spores were produced in the Null P. Under High P, AMF biomass and spores were strongly reduced. Plant growth response to mycorrhiza was negative under Null P, showing reduction in height, biovolume index, and source leaf (SL) area. Under Low P, inoculated plants showed a positive response (e.g., increased SL area), while inoculated plants under High P were similar to non‐inoculated plants. AMF promoted the accumulation of soluble sugars in the SL under all fertilization levels, whereas the soluble sugar level decreased in roots under Low P in inoculated plants. Transcriptional upregulation of SlLIN6 and SlSUS1, genes related to carbohydrate metabolism, was observed in inoculated roots under Null P and Low P, respectively. We conclude that P‐limiting conditions that increase AMF colonization stimulate plant growth due to an increase in the source and sink strength. Our results suggest that C partitioning and allocation to different catabolic pathways in the host are influenced by AMF performance.
We present a novel Ti64/20Ag highly porous composite fabricated by powder metallurgy for biomedical applications and provide an insight into its microstructure and mechanical proprieties. In this ...work, the Ti64/20Ag highly porous composites were successfully fabricated by the space holder technique and consolidated by liquid phase sintering, at lower temperatures than the ones used for Ti64 materials. The sintering densification was evaluated by dilatometry tests and the microstructural characterization and porosity features were determined by scanning electron microscopy and computed microtomography. Permeability was estimated by numerical simulations on the 3D real microstructure. Mechanical properties were evaluated by simple compression tests. Densification was achieved by interparticle pore filling with liquid Ag that does not drain to the large pores, with additional densification due to the macroscopical deformation of large pores. Pore characteristics are closely linked to the pore formers and the permeability was highly increased by increasing the pore volume fraction, mainly because the connectivity was improved. As expected, with the increase in porosity, the mechanical properties decreased. These results permitted us to gain a greater understanding of the microstructure and to confirm that we developed a promising Ti64/20Ag composite, showing E of 7.4 GPa, σy of 123 MPa and permeability of 3.93 × 10−11 m2. Enhanced adaptability and antibacterial proprieties due to Ag were obtained for bone implant applications.
Arbuscular mycorrhizal fungi (AMF) are obligate biotrophs that supply mineral nutrients to the host plant in exchange for carbon derived from photosynthesis. Sucrose is the end-product of ...photosynthesis and the main compound used by plants to translocate photosynthates to non-photosynthetic tissues. AMF alter carbon distribution in plants by modifying the expression and activity of key enzymes of sucrose biosynthesis, transport, and/or catabolism. Since sucrose is essential for the maintenance of all metabolic and physiological processes, the modifications addressed by AMF can significantly affect plant development and stress responses. AMF also modulate plant lipid biosynthesis to acquire storage reserves, generate biomass, and fulfill its life cycle. In this review we address the most relevant aspects of the influence of AMF on sucrose and lipid metabolism in plants, including its effects on sucrose biosynthesis both in photosynthetic and heterotrophic tissues, and the influence of sucrose on lipid biosynthesis in the context of the symbiosis. We present a hypothetical model of carbon partitioning between plants and AMF in which the coordinated action of sucrose biosynthesis, transport, and catabolism plays a role in the generation of hexose gradients to supply carbon to AMF, and to control the amount of carbon assigned to the fungus.
Humanity is on a deeply unsustainable trajectory. We are exceeding planetary boundaries and unlikely to meet many international sustainable development goals and global environmental targets. Until ...recently, there was no broadly accepted framework of interventions that could ignite the transformations needed to achieve these desired targets and goals.
As a component of the IPBES Global Assessment, we conducted an iterative expert deliberation process with an extensive review of scenarios and pathways to sustainability, including the broader literature on indirect drivers, social change and sustainability transformation. We asked, what are the most important elements of pathways to sustainability?
Applying a social–ecological systems lens, we identified eight priority points for intervention (leverage points) and five overarching strategic actions and priority interventions (levers), which appear to be key to societal transformation. The eight leverage points are: (1) Visions of a good life, (2) Total consumption and waste, (3) Latent values of responsibility, (4) Inequalities, (5) Justice and inclusion in conservation, (6) Externalities from trade and other telecouplings, (7) Responsible technology, innovation and investment, and (8) Education and knowledge generation and sharing. The five intertwined levers can be applied across the eight leverage points and more broadly. These include: (A) Incentives and capacity building, (B) Coordination across sectors and jurisdictions, (C) Pre‐emptive action, (D) Adaptive decision‐making and (E) Environmental law and implementation. The levers and leverage points are all non‐substitutable, and each enables others, likely leading to synergistic benefits.
Transformative change towards sustainable pathways requires more than a simple scaling‐up of sustainability initiatives—it entails addressing these levers and leverage points to change the fabric of legal, political, economic and other social systems. These levers and leverage points build upon those approved within the Global Assessment's Summary for Policymakers, with the aim of enabling leaders in government, business, civil society and academia to spark transformative changes towards a more just and sustainable world.
A free Plain Language Summary can be found within the Supporting Information of this article.
A free Plain Language Summary can be found within the Supporting Information of this article.
Dysregulation of splicing variants (SVs) expression has recently emerged as a novel cancer hallmark. Although the generation of aberrant SVs (e.g. AR-v7/sst5TMD4/etc.) is associated to ...prostate-cancer (PCa) aggressiveness and/or castration-resistant PCa (CRPC) development, whether the molecular reason behind such phenomena might be linked to a dysregulation of the cellular machinery responsible for the splicing process spliceosome-components (SCs) and splicing-factors (SFs) has not been yet explored.
Expression levels of 43 key SCs and SFs were measured in two cohorts of PCa-samples: 1) Clinically-localized formalin-fixed paraffin-embedded PCa-samples (n = 84), and 2) highly-aggressive freshly-obtained PCa-samples (n = 42).
A profound dysregulation in the expression of multiple components of the splicing machinery (i.e. 7 SCs/19 SFs) were found in PCa compared to their non-tumor adjacent-regions. Notably, overexpression of SNRNP200, SRSF3 and SRRM1 (mRNA and/or protein) were associated with relevant clinical (e.g. Gleason score, T-Stage, metastasis, biochemical recurrence, etc.) and molecular (e.g. AR-v7 expression) parameters of aggressiveness in PCa-samples. Functional (cell-proliferation/migration) and mechanistic gene-expression (qPCR) and protein-levels (western-blot) assays were performed in normal prostate cells (PNT2) and PCa-cells (LNCaP/22Rv1/PC-3/DU145 cell-lines) in response to SNRNP200, SRSF3 and/or SRRM1 silencing (using specific siRNAs) revealed an overall decrease in proliferation/migration-rate in PCa-cells through the modulation of key oncogenic SVs expression levels (e.g. AR-v7/PKM2/XBP1s) and alteration of oncogenic signaling pathways (e.g. p-AKT/p-JNK).
These results demonstrate that the spliceosome is drastically altered in PCa wherein SNRNP200, SRSF3 and SRRM1 could represent attractive novel diagnostic/prognostic and therapeutic targets for PCa and CRPC.
Several studies have demonstrated that lysophosphatidic acid (LPA) acts through its LPA receptors in multiple biological and behavioral processes, including adult hippocampal neurogenesis, ...hippocampal-dependent memory, and emotional regulation. However, analyses of the effects have typically involved acute treatments, and there is no information available regarding the effect of the chronic pharmacological modulation of the LPA/LPA receptors-signaling pathway. Thus, we analyzed the effect of the chronic (21 days) and continuous intracerebroventricular (ICV) infusion of C18:1 LPA and the LPA1-3 receptor antagonist Ki16425 in behavior and adult hippocampal neurogenesis. Twenty-one days after continuous ICV infusions, mouse behaviors in the open field test, Y-maze test and forced swimming test were assessed. In addition, the hippocampus was examined for c-Fos expression and α-CaMKII and phospho-α-CaMKII levels.
The current study demonstrates that chronic C18:1 LPA produced antidepressant effects, improved spatial working memory, and enhanced adult hippocampal neurogenesis. In contrast, chronic LPA1-3 receptor antagonism disrupted exploratory activity and spatial working memory, induced anxiety and depression-like behaviors and produced an impairment of hippocampal neurogenesis. While these effects were accompanied by an increase in neuronal activation in the DG of C18:1 LPA-treated mice, Ki16425-treated mice showed reduced neuronal activation in CA3 and CA1 hippocampal subfields. Treatment with the antagonist also induced an imbalance in the expression of basal/activated α-CaMKII protein forms.
These outcomes indicate that the chronic central modulation of the LPA receptors-signaling pathway in the brain regulates cognition and emotion, likely comprising hippocampal-dependent mechanisms. The use of pharmacological modulation of this pathway in the brain may potentially be targeted for the treatment of several neuropsychiatric conditions.
•Chronic C18:1 LPA in mouse hippocampus promoted active coping and improved learning.•Chronic C18:1 LPA increased hippocampal neurogenesis and neuronal activation.•LPA1-3 receptor antagonism induced anxiety and depression-like behaviors.•Antagonism resulted in defective neurogenesis and basal/activated α-CaMKII imbalance.
The tomato potato psyllid
Bactericera cockerelli
(Sulcer) (Hemiptera: Triozidae) is a serious pest of several solanaceous crops in different parts of the world. We examined the biological control ...potential of the zoophytophagous bug
Engytatus varians
(Distant) (Hemiptera: Miridae), in combination with the ectoparasitoid
Tamarixia triozae
(Burks) (Hymenoptera: Eulophidae) on
B. cockerelli
-infested pepper (
Capsicum annuum
L.) plants in cages under greenhouse conditions. A single release rate (one adult per plant) of either
E. varians
or
T. triozae
was used and the timing of predator releases varied (before or after pest establishment). The number of nymphs and adults of
B. cockerelli
or the number of mirids (nymphs plus adults) and parasitoids (pupae plus adults) was determined three or four weeks after release. Both
E. varians
and
T. triozae
successfully established on pepper plants and significantly reduced the pest population density (by 91 to 96% and by 84 to 100% of nymphs and adults, respectively) when they were released separately or in combination, even when the predator was released before the establishment of
B. cockerelli
. At the end of the experiment, the density of
E. varians
was between one and two individuals per leaf, whereas that of the parasitoid was between one and six individuals per leaf in the treatments in which each natural enemy was released. These results could contribute to the integrated pest management of
B. cockerelli
. However, further studies are needed to validate the impact of both natural enemies on the control of this pest at a larger scale.
Seventy-eight Rhizoctonia isolates were obtained from brassicas in five Brazilian states between 2015 and 2017. The isolates were identified by phylogenetic analysis of the rDNA internal transcribed ...spacer region (ITS) and tested for pathogenicity and aggressiveness. Sixty-eight isolates were identified as R. solani and 10 isolates as binucleate Rhizoctonia. The most prevalent anastomosis group (AG) was AG-4 HG-I (83.3% of isolates), followed by AG-A (7.7%), AG-1 IB (2.6%), AG-G (2.6%), AG-R (2.6%) and AG-2-2 IIIB (1.3%). AG-4 HG-I isolates were widely distributed and recovered from all Brazilian states sampled, including 12 brassicas-growing fields. All isolates were pathogenic to broccoli, cauliflower and kale, causing necrotic lesions on subterraneous stems. There was no significant difference in aggressiveness among the different AGs in broccoli, but AG-1 IB isolates were more aggressive to cauliflower and AG-4 HG-I isolates were more aggressive to kale. This study is the first report of AG-4 HG-I, AG-2-2 IIIB, AG-A, AG-G and AG-R infecting brassica plants in Brazil. To our knowledge, this is the first detailed research of the AG composition of Rhizoctonia populations causing brassica diseases in Brazil.
Objective: The present study aimed to determine whether the combined effects of environmental estrogens measured as the total effective xenoestrogen burden (TEXB-alpha) are a risk factor for breast ...cancer over and above the risk potentially linked to specific pesticides. Methods: We measured the levels of 16 organochlorine pesticides as well as TEXB in adipose tissue of 198 women at the time of breast cancer diagnosis. These were compared with findings in 260 age and hospital matched control women without breast cancer. Results: The median levels of p,p′-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene), aldrin, endosulfan ether and lindane (the pesticides detected in > 40% of the study population) were higher in cases than controls, although the differences did not reach statistical significance. After adjusting for potential confounders, the odds ratio (OR) for breast cancer in women with detectable levels of aldrin was 1.55 (95% confidence interval (CI) 1.00-2.40). Among the postmenopausal women, the OR for aldrin and lindane was 1.84 (95% CI 1.06-3.18) and 1.76 (95% CI 1.04-2.98), respectively. Among cases with body mass index (BMI) below the median (28.6 kg/m2), the OR was 3.42 (95% CI 1.22-9.58) for women in the highest quartile of TEXB-alpha versus those in the lowest. The subgroup of leaner postmenopausal women showed an increased risk (OR: 5.67; 95% CI 1.59-20.21) for those in the highest tertile versus those in the lowest. Conclusions: We found an increased risk for breast cancer in the leaner women, especially in the leaner postmenopausal subgroup, related to the TEXB-alpha. The pesticides aldrin and lindane are also individually associated with risk.
PDF
