Nitrogen nutrition effects on development, growth and nitrogen accumulation of vegetables

In order to be able to match nitrogen supply and nitrogen requirement of vegetable crops, insight is necessary in the responses to nitrogen of important processes of growth and development. This study focused on effects of amount of nitrogen applied and fractionation of nitrogen supply on leaf attributes, accumulation and partitioning of dry matter and nitrogen in potato (Solanum tuberosum L.), Brussels sprouts ( Brassica oleracea L. var gemmifera DC), leek ( Allium porrum L.) and spinach ( Spinacia oleracea L.). Effects of amount of nitrogen applied were always much more important than effects of fractionation of nitrogen supply. Rate of leaf appearance varied among crops from 0. 15-0.60 leaves d -1; it increased with more nitrogen in Brussels sprouts and spinach. Rates of leaf senescence were enhanced by nitrogen in Brussels sprouts. Life span of leaves was about 70 d for all crops. Rates of leaf expansion and maximum sizes of leaves increased with leaf number until a certain leaf number after which they gradually decreased. Both characteristics increased with more nitrogen. Duration of leaf expansion varied among crops from 18-40 d and decreased in Brussels sprouts with more nitrogen. Maximum size of a leaf was mainly determined by rate of leaf expansion. Except in potato, more nitrogen increased specific leaf area. Differences among nitrogen treatments in total green leaf area reflected the effects of nitrogen on rates of leaf expansion.Total dry matter production was strongly related to leaf area duration. Although more nitrogen applied resulted in more nitrogen taken up and more total dry matter produced, considerable variation was observed in the relation between total nitrogen uptake and total dry matter production. Harvest indices for dry matter varied among crops and treatments from about 0.10-0.87; more nitrogen increased it for Brussels sprouts, but decreased it for leek. Harvest indices for nitrogen varied from about 0.22-0.86; more nitrogen increased it for Brussels sprouts. In general, organic nitrogen concentration increased with increasing node number for leaf blades, petioles and leaf sheaths but not for sprouts. The gradient with node number resulted from a decreasing nitrogen concentration during the leafs life. High nitrate concentrations in the marketable produce were only observed in spinach. Nitrate nitrogen concentrations of leaf blades, petioles and leaf sheaths decreased with increasing leaf number at any time of observation, but were not related to leaf age. However, in stems of Brussels sprouts and stems and tubers of potato, total nitrogen and nitrate nitrogen concentration were closely related.The present findings elucidate the reactions of the crops to nitrogen fertilisation. This is helpful for the fine-tuning of nitrogen fertilisation and to develop modules on plant development in crop simulation models

Physical, mental, and social health of adult patients with sickle cell disease after allogeneic hematopoietic stem cell transplantation: a mixed-methods study

Patients with sickle cell disease (SCD) experience a considerable physical and psychosocial disease burden. In recent years, the application of allogeneic hematopoietic stem cell transplantation (HSCT) to treat adults with SCD has increased. A thorough understanding of patients' physical, mental, and social health before and after cure is needed to meet the needs of this growing group of patients. We aimed to explore the perspectives of adult SCD patients on the changes in their experienced health and personal life goals after being cured. A mixed-methods approach was used, comprising a semistructured interview and a set of 9 Patient Reported Outcomes Measurement Information System (PROMIS) measures. Adult SCD patients who underwent HSCT at least 1 year earlier were eligible to participate in the study. Interviews were thematically analyzed using MAXQDA software. PROMIS T scores were compared with reference scores of the general population using SPSS Statistics. Ten patients participated in the study; their median age was 29.5 years (range, 19 to 49 years), and their median time since HSCT was 2.7 years (range, 1.0 to 3.5 years). Themes from the interviews were (1) pain/living pain free, (2) physical wellbeing, (3) mental well-being, (4) perspective/outlook, (5) education/work, (6) family/friends, and (7) activities/participation. Following the PROMIS framework, we described these themes in a narrative synthesis according to health domain and categorized in 4 chronological time phases: before HSCT, first year post-transplantation, current situation, and future expectations. Physical health improved greatly, but transplantation-related toxicity, ongoing pain from avascular osteonecrosis, and fatigue negatively impacted quality of life in some patients. Furthermore, emotional struggles during the post-transplantation period were common, and patients expressed a need for psychological help. Patients reported improvements in social health and the ability to pursue personal life goals. The mean T scores of all PROMIS measures fell within the normal symptom limits compared with reference data of the general population, although, large variations were observed among the participants, matching our qualitative findings. In general, adult SCD patients experienced improved physical, mental, and social health after cure by HSCT and were able to pursue personal life goals. Yet they found themselves confronted with a new and unfamiliar reality that brought different challenges. Pain due to irreversible avascular osteonecrosis continued to have a negative impact. Clinicians should aim to help patients have realistic expectations before transplantation and offer timely psychological care. (c) 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.Transplantation and immunomodulatio

Assessment of bone ingrowth potential of biomimetic hydroxyapatite and brushite coated porous E-beam structures

The bone ingrowth potential of biomimetic hydroxyapatite and brushite coatings applied on porous E-beam structure was examined in goats and compared to a similar uncoated porous structure and a conventional titanium plasma spray coating. Specimens were implanted in the iliac crest of goats for a period of 3 (4 goats) or 15 weeks (8 goats). Mechanical implant fixation generated by bone ingrowth was analyzed by a push out test. Histomorphometry was performed to assess the bone ingrowth depth and bone implant contact. The uncoated and hydroxyapatite-coated cubic structure had significantly higher mechanical strength at the interface compared to the Ti plasma spray coating at 15 weeks of implantation. Bone ingrowth depth was significantly larger for the hydroxyapatite- and brushite-coated structures compared to the uncoated structure. In conclusion, the porous E-beam surface structure showed higher bone ingrowth potential compared to a conventional implant surface after 15 weeks of implantation. Addition of a calcium phosphate coating to the E-beam structure enhanced bone ingrowth significantly. Furthermore, the calcium phosphate coating appears to work as an accelerator for bone ingrowth

The role of tunneling in enzyme catalysis of C–H activation

AbstractRecent data from studies of enzyme catalyzed hydrogen transfer reactions implicate a new theoretical context in which to understand C–H activation. This is much closer to the Marcus theory of electron transfer, in that environmental factors influence the probability of effective wave function overlap from donor to acceptor atoms. The larger size of hydrogen and the availability of three isotopes (H, D and T) introduce a dimension to the kinetic analysis that is not available for electron transfer. This concerns the role of gating between donor and acceptor atoms, in particular whether the system in question is able to tune distance between reactants to achieve maximal tunneling efficiency. Analysis of enzyme systems is providing increasing evidence of a role for active site residues in optimizing the inter-nuclear distance for nuclear tunneling. The ease with which this optimization can be perturbed, through site-specific mutagenesis or an alteration in reaction conditions, is also readily apparent from an analysis of the changes in the temperature dependence of hydrogen isotope effects

One-year safety and efficacy of mitapivat in sickle cell disease:follow-up results of a phase 2, open-label study

Targeting the primary pathogenic event of sickle cell disease (SCD), the polymerization of sickle hemoglobin (HbS), may prevent downstream clinical events. Mitapivat, an oral pyruvate kinase (PK) activator, has therapeutic potential by increasing adenosine triphosphate (ATP) and decreasing 2,3-diphosphoglycerate (2,3-DPG), a glycolytic red blood cell (RBC) intermediate. In the previously reported 8-week dose-finding period of this phase 2, investigator-initiated, open-label study, mitapivat was well tolerated and showed efficacy in SCD. Here, the 1-year fixed-dose extension period is reported in which 9 of 10 included patients (90%) aged ≥16 years with SCD (HbSS, HbS/β0, or HbS/β+) continued with mitapivat. Mostly mild treatment-emergent adverse events (AEs) (most commonly, transaminase increase and headache) were still reported. Apart from the reported nontreatment-related serious AE (SAE) of a urinary tract infection in the dose-finding period, 1 nontreatment-related SAE occurred in the fixed-dose extension period in a patient who died of massive pulmonary embolism due to COVID-19. Importantly, sustained improvement in Hb level (mean increase, 1.1 ± 0.7 g/dL; P = .0014) was seen, which was accompanied by decreases in markers of hemolysis. In addition, the annualized rate of vaso-occlusive events reduced significantly from a historic baseline of 1.33 ± 1.32 to 0.64 ± 0.87 (P = .0489) when combining the dose-finding period and fixed-dose extension period. Cellularly, the ATP:2,3-DPG ratio and Hb-oxygen affinity significantly increased and RBC sickling (point of sickling) nonsignificantly reduced. Overall, this study demonstrated 1-year safety and efficacy of treatment with mitapivat in SCD, supporting further evaluation in ongoing phase 2/3 study (RISE UP, NCT05031780). This trial was registered at https://www.clinicaltrialsregister.eu/as NL8517 and EudraCT 2019-003438-18.</p

Metabolic blood profile and response to treatment with the pyruvate kinase activator mitapivat in patients with sickle cell disease

Mitapivat is an investigational, oral, small-molecule allosteric activator of pyruvate kinase (PK). PK is a regulatory glycolytic enzyme that is key in providing the red blood cell (RBC) with sufficient amounts of adenosine triphosphate (ATP). In sickle cell disease (SCD), decreased 2,3-DPG levels increase the oxygen affinity of hemoglobin, thereby preventing deoxygenation and polymerization of sickle hemoglobin. The PK activator mitapivat has been shown to decrease levels of 2,3-DPG and increase levels of ATP in RBCs in patients with SCD. In this phase 2, investigator-initiated, open-label study (https://www.clinicaltrialsregister.eu/ NL8517; EudraCT 2019-003438-18), untargeted metabolomics was used to explore the overall metabolic effects of 8-week treatment with mitapivat in the dose-finding period. In total, 1773 unique metabolites were identified in dried blood spots of whole blood from ten patients with SCD and 42 healthy controls (HCs). The metabolic phenotype of patients with SCD revealed alterations in 139/1773 (7.8%) metabolites at baseline when compared to HCs (false discovery rate-adjusted p &lt; 0.05), including increases of (derivatives of) polyamines, purines, and acyl carnitines. Eight-week treatment with mitapivat in nine patients with SCD altered 85/1773 (4.8%) of the total metabolites and 18/139 (12.9%) of the previously identified altered metabolites in SCD (unadjusted p &lt; 0.05). Effects were observed on a broad spectrum of metabolites and were not limited to glycolytic intermediates. Our results show the relevance of metabolic profiling in SCD, not only to unravel potential pathophysiological pathways and biomarkers in multisystem diseases but also to determine the effect of treatment.</p