Homozygous variant in TKFC abolishing triokinase activities is associated with isolated immunodeficiency.

BACKGROUND: Triokinase and FMN cyclase (TKFC) is a bifunctional enzyme involved in fructose metabolism. Triokinase catalyses the phosphorylation of fructose-derived glyceraldehyde (GA) and exogenous dihydroxyacetone (DHA), while FMN cyclase generates cyclic FMN. TKFC regulates the antiviral immune response by interacting with IFIH1 (MDA5). Previously reported pathogenic variants in TKFC are associated with either a multisystemic disease or isolated hypotrichosis with loose anagen hairs. METHODS: Whole-exome sequencing identified a homozygous novel variant in TKFC (c.1624G>A; p.Gly542Arg) in an individual with a complex primary immunodeficiency disorder. The variant was characterised using enzymatic assays and yeast studies of mutant recombinant proteins. RESULTS: The individual presented with chronic active Epstein-Barr virus disease and multiple bacterial and viral infections. Clinical investigations revealed hypogammaglobulinaemia, near absent natural killer cells and decreased memory B cells. Enzymatic assays showed that this variant displayed defective DHA and GA kinase activity while maintaining FMN cyclase activity. An allogenic bone marrow transplantation corrected the patient's immunodeficiency. CONCLUSION: Our report suggests that TKFC may have a role in the immunological system. The pathological features associated with this variant are possibly linked with DHA/GA kinase inactivation through a yet an unknown mechanism. This report thus adds a possible new pathway of immunometabolism to explore further.

Expanding ASM models towards integrated processes for short-cut nitrogen removal and bioplastic recovery.

In next-generation water resource recovery facilities (WRRFs), it is becoming increasingly important to save energy costs and promote resource recovery of valuable products. One way of reducing the substantial aeration energy costs at WRRFs is to employ shortcut N removal, while polyhydroxyalkanoate (PHA) production and recovery as bioplastic is a promising means of recovering a valuable product from biosolids. Both objectives can be achieved simultaneously through the Short-Cut Enhanced Phosphorus and PHA Recovery (SCEPPHAR) process. However, current mathematical models have not previously been employed to describe the behavior of such a process, which limits engineering design and optimisation of process operation. This work focusses on extending the ASM3 model towards the description of short-cut nitrogen removal and simultaneous PHA recovery in a sidestream treatment process. The calibrated and validated model described very well the nitritation process coupled with the aerobic feast/anoxic famine process for the selection of PHA producing organisms at a pilot-scale facility operated in Carbonera, Italy, where the normalised root mean squared error (NRMSE) was consistently <20%. Furthermore, the model applied to the PHA selection stage could effectively describe the PHA accumulation stage without recalibration. A simulation study was performed using the modified ASM3 model to assess the relative benefits of the SCEPPHAR process strategy as compared to the fully aerobic selection process for mixed culture PHA production. While the level of PHA production was found to be 34% lower with SCEPPHAR, a 43% savings in volatile fatty acids (VFAs) demand, a 15% decrease in Total suspended solids (TSS) production and a 28% decrease in oxygen demand were also achievable, which could lead to savings in operational costs. This study facilitates the design and optimisation of WRRFs that integrate short-cut N removal with PHA production, saving aeration energy costs while achieving resource recovery.

The TKFC Ala185Thr variant, reported as 'null' for fructose metabolism, is fully active as triokinase.

TKFC-encoded triokinase catalyses glyceraldehyde phosphorylation in fructose metabolism and favours lipogenesis in mice. In Tkfc knockouts or knockdowns, fructose oxidation predominates over lipogenesis. The highly prevalent human variant Ala185Thr-Triokinase/FMN cyclase (TKFC) has been reported to be 'null' for fructose metabolism, since Ala185-TKFC rescues the mouse TKFC-deficient phenotype, whereas Ala185Thr-TKFC does not. Such report implies that most humans would display a noncanonical fructose metabolism, but it ignores the well-characterized triokinase activity of Ala185Thr-TKFC. Here, earlier evidence is summarized, along with new evidence that both human variants are equally active in yeast. Therefore, future research on triokinase in the context of human fructose metabolism should consider that Ala185Thr-TKFC is not biochemically 'null'.

Performance of a two-stage anaerobic digestion system treating fruit pulp waste: The impact of substrate shift and operational conditions.

Food and beverage industry wastes present high amounts of organic matter, which may cause water quality degradation if not treated. Two-stage anaerobic digestion is a promising and efficient solution for the treatment of this type of wastes whilst producing bioenergy. The composition of fruit pulp waste varies throughout the different harvesting seasons, which may impact the process performance. In this study, a two-stage anaerobic digestion system was operated to assess the effect of substrate shift from peach to apple pulp wastes (obtained from a fruit juice company) on the microbial community activity and performance. During acidogenesis, the sugar conversion was higher than 95% for all operational conditions tested, obtaining a degree of acidification up to 89%. Principal Component Analysis was used to evaluate the relationship between the initial fermentation state of the residues in each operational condition and the obtained effluent. Methanogenic activity resulted in high organic carbon consumption (89%) and high methane productivities, achieving a maximum of 4.33 [Formula: see text] for peach waste influent. Overall, the results showed that the microbial community activity was not affected by the substrate shift, converting the sugars into biogas rich in methane (>70% CH4). Microbial analysis showed that the communities present in the acidogenic and methanogenic reactors were highly enriched in bacteria and archaea, respectively. The observed stability of the process, also demonstrated in pilot scale, confirmed the robustness of the process and thus, was suitable for implementation in companies producing seasonally different fruit wastes in a continuous operation.

Isoelectric point, electric charge, and nomenclature of the acid-base residues of proteins.

The main object of this work is to present the pedagogical usefulness of the theoretical methods, developed in this laboratory, for the determination of the isoelectric point (pI) and the net electric charge of proteins together with some comments on the naming of the acid-base residues of proteins.

Brachiocephalic vein thrombosis associated with Crohn's disease.

An association between macrovascular thrombosis and idiopathic inflammatory bowel disease has been described, although very few well-documented cases have been published. We report on a 39-year-old woman who presented with right hemifacial and upper limb edema that was shown to be due to an extensive right brachiocephalic vein thrombosis, diagnosed by magnetic resonance angiography. Laboratory findings suggested malabsorption, and a diagnosis of Crohn's disease was established. Moreover, elevation of the plasminogen activator inhibitor system was identified. This represents the first description of a spontaneous thrombosis in a patient with Crohn's disease involving the intrathoracic venous system and raises the possibility of impaired fibrinolysis being involved in the etiopathogenesis of this complication.