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Biology subjects

Mori, G.

Publications and source records attributed to Mori, G..

5 recordsLinked to original sources

Human ASPDH is a 2-aminomuconate reductase that produces L-2-aminohex-3-enedioic acid in tryptophan catabolism

Most tryptophan catabolism in animals occurs through the kynurenine pathway, which generates the essential NAD cofactor and multiple bioactive metabolites. Knowledge of this pathway in eukaryotes ends at the unstable intermediate 2-aminomuconate (2-AM). Here, by leveraging evolutionary information from more than 5,000 eukaryotes, we identify two distinct genes acting downstream of 2-AM in fungi and metazoa. The fungal gene is homologous to bacterial 2-AM deaminase, whereas the metazoan gene is homologous to aspartate dehydrogenase (ASPDH), which in prokaryotes catalyses the first reaction of NAD biosynthesis. Biochemical and structural analyses show that human ASPDH has evolved an unprecedented function as an NAD(P)H-dependent 2-AM reductase (AMR) in tryptophan catabolism. The reaction forms L-2-aminohex-3-enedioic acid, an unsaturated -amino acid absent from current biological databases. Isotope-labeling NMR experiments and structural modelling support a mechanism in which hydride transfer is coupled to double-bond rearrangement of the conjugated system. These findings reveal a previously unknown metazoan branch of the kynurenine pathway, expand the repertoire of endogenous amino acids, and illustrate how comparative genomics can uncover hidden reactions in human metabolism.

biochemistry↗

Toward passive acoustic occupancy surveys of rare red uakari monkeys (Cacajao ucayalii): using automatic signal recognition and cluster analysis to organize signals?

We tested a workflow using a cluster analysis to develop a classifier to detect red uakari monkey calls using clustering and Hidden Markov Models, and Kaleidoscope viewer to review and discount false positives. We used recordings collected in a series of behavioral studies on a habituated group of red uakari monkeys on the Yavari-Miri River in the Peruvian Amazon as training data to develop the classifier and tested it on a passive acoustic survey at the same site where uakari distributions were known to us. We estimated detection probabilities for red uakaris and used an occupancy model to estimate habitat use to compare with use determined by behavioral research. We assessed a workflow for processing passive acoustic primate surveys that would eliminate false positives and demand minimal time and coding expertise from those implementing the analyses and reviewing audio recordings. These are key considerations in the design of landscape-scale PAM surveys for rare species.

ecology↗

Cysteine enrichment mediates co-option of uricase in reptilian skin and transition to uricotelism

Uric acid is the main means of nitrogen excretion in uricotelic vertebrates (birds and reptiles) and the end product of purine catabolism in humans and a few other mammals. While uricase is inactivated in mammals unable to degrade urate, the presence of orthologous genes without inactivating mutations in avian and reptilian genomes is unexplained. Here we show that the Gallus gallus gene we name cysteine-rich urate oxidase (CRUOX) encodes a functional protein representing a unique case of cysteine enrichment in the evolution of vertebrate orthologous genes. CRUOX retains the ability to catalyze urate oxidation to hydrogen peroxide and 5-hydroxyisourate (HIU), albeit with a 100-fold reduced efficiency. However, differently from all uricases hitherto characterized, it can also facilitate urate regeneration from HIU, a catalytic property which we propose depends on its enrichment in cysteine residues. X-ray structural analysis highlights differences in the active site compared to known orthologs and suggests a mechanism for cysteine-mediated self-aggregation under H2O2-oxidative conditions. Cysteine enrichment was concurrent with transition to uricotelism and a shift in gene expression from the liver to the skin where CRUOX is co-expressed with {beta}-keratins. Therefore, the loss of urate degradation in amniotes has followed opposite evolutionary trajectories: while uricase has been eliminated by pseudogenization in some mammals, it has been repurposed as a redox-sensitive enzyme in the reptilian skin.

evolutionary biology↗

A CUG-initiated CATSPERθ functions in the CatSper channel assembly and serves as a checkpoint for flagellar trafficking

Calcium signaling is critical for successful fertilization. In spermatozoa, calcium influx into the sperm flagella mediated by the sperm specific CatSper calcium channel is necessary for hyperactivated motility and male fertility. CatSper is a macromolecular complex and is repeatedly arranged in zigzag rows within four linear nanodomains along the sperm flagella. Here, we report that the Tmem249-encoded transmembrane domain containing protein, CATSPER{theta}, is essential for the CatSper channel assembly during sperm tail formation. CATSPER{theta} facilitates the channel assembly by serving as a scaffold for a pore forming subunit CATSPER4. CATSPER{theta} is specifically localized at the interface of a CatSper dimer and can self-interact, suggesting its potential role in CatSper dimer formation. Male mice lacking CATSPER{theta} are infertile because the sperm lack the entire CatSper channel from sperm flagella, rendering sperm unable to hyperactivate, regardless of their normal expression in the testis. In contrast, genetic abrogation of any of the other CatSper transmembrane subunits results in loss of CATSPER{theta} protein in the spermatid cells during spermatogenesis. CATSPER{theta} might acts as a checkpoint for the properly assembled CatSper channel complex to traffic to sperm flagella. This study provides insights into the CatSper channel assembly and elucidates the physiological role of CATSPER{theta} in sperm motility and male fertility.

cell biology↗

Ciliated protozoa from industrial WWTP activated sludge: a biodiversity survey including trophic interactions and redescription of Bakuella subtropica (Spirotrichea, Hypotrichia) according to Next Generation Taxonomy

Optimization of wastewater treatment with biological processes is a fundamental challenge of modern society. During past years new technologies have been developed for the purpose and prokaryotic organisms involved in the process extensively investigated. Nevertheless, relatively few studies so far analysed the protozoan community in these systems using modern integrative approaches, despite its obvious role in shaping ecological dynamics and, possibly, process efficiency. In the present study, we characterized the ciliate community in biological reactors of an Italian industrial (tannery) wastewater treatment plant (WWTP) applying modified Ludzack-Ettinger (MLE) process. This plant is characterized by moderate salinity, high solids retention time and high concentration of organic compounds, including a significant recalcitrant fraction. We performed the morphological and 18S rDNA characterizations of almost all the 21 ciliates retrieved along a one-year sampling period, and provided preliminary data on species occurrence, community dynamics, and trophic interactions. Only 16 species were observed on the sample collection day and most of them had an occurrence higher than 50%. The most frequently occurring and highly abundant organisms were Aspidisca cf. cicada, Euplotes spp., Paramecium calkinsi, and Phialina sp. Cyclidium cf. marinum was only found on a single date and its presence was possibly related to a summer break-induced perturbation. All the species showed the capability to survive the short oxic/anoxic cycling typical of the studied WWTP process. Intriguingly, some of them (i.e., Bakuella subtropica and Trochiliopsis australis) turned out to be species isolated from brackish natural environment rich in organic load as well. As for B. subtropica, we provided an emended redescription according to the most recent taxonomy standards that include also mitogenomic sequencing.

zoology↗