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Melanism is widespread in different taxa and has been hypothesized to provide adaptive benefits in certain environments. Melanism is typically caused by mutations in one of two regulatory genes: the Melanocortin 1 Receptor ( MC1R ) or the Agouti Signaling Protein ( ASIP ). Melanism has repeatedly evolved among tree squirrels and their relatives (tribe Sciurini) in at least 12 different species based on our review of the literature. The causal mutations for melanism have been characterized in two species so far. This study examines Abert's Squirrel ( Sciurus aberti ), which has a melanistic morph whose genetic basis has not yet been established. We sequenced the MC1R and ASIP genes for five wild-type and seven melanistic S. aberti individuals to search for melanism-associated mutations. A novel single base pair mutation in the ASIP gene, unique to S. aberti , was found to be associated with melanism in the species, indicating that melanism in S. aberti evolved independently from other tree squirrels and thus represents an example of convergent evolution. The independent evolution of melanism in this species suggests that there is an adaptive advantage to the melanistic phenotype. The geographic range and habitat of S. aberti suggest possible benefits associated with thermoregulation, post-forest-fire camouflage, or other untested hypotheses.

Dogs play an important role in transmission of Leishmania infantum , but epidemiologic and clinical studies of canine tegumentary leishmaniasis (CTL) are scarce. In an endemic area of human American tegumentary leishmaniasis (ATL) caused by Leishmania braziliensis, we determine the prevalence and incidence of both CTL and subclinical (SC) L. braziliensis infection in dogs and evaluated if the presence of dogs with CTL or SC L. braziliensis infection is associated with the occurrence of human ATL. SC infection in healthy animals and CTL in animals with ulcers were determined by PCR on biopsied healthy skin or on ulcers or by detecting antibodies against soluble leishmania antigen. We compared the occurrence of human ATL in homes with dogs with CTL or SC infection with control homes without dogs or with dogs without CTL or SC infection. The prevalence of SC infection was 35% and of CTL 31%. The incidence of SC infection in dogs was 4.6% and of CTL 9.3%. The frequency of ATL in humans was 50% in homes with infected dogs and 13% in homes without L. braziliensis infection in dogs. CTL and SC infection is highly prevalent, and dogs may participate in the transmission chain of L. braziliensis .

Purpose: The use of FDG-PET for cancer staging has led to the increasing incidence of adrenal lesions, which are usually a clinical challenge. We aimed to characterize the adrenal lesions found in FDG-PET of patients followed in a cancer center., Methods: Retrospective analysis was conducted of all FDG-PET studies performed in our center in the last 10 years. Exams reporting adrenal lesions in the CT component and/or anomalous adrenal FDG uptake were selected. Cases were characterized by the clinical, laboratory, imaging, and pathological findings., Results: We identified 27,427 FDG-PET studies. Of those, 7.6% reported adrenal findings. We included 1364 exams corresponding to 1021 patients. Only 15.6% of the patients were referred to the Endocrinology Department and 38% of the lesions were not studied. In 38.9% of the studied patients, malignant lesions were present, including metastases in 37.5%, carcinoma in 1.2%, and other malignant tumors in 0.4%. The median SUVmax of malignant lesions was significantly higher than the SUVmax of the benign findings (p < 0.05). We also observed a higher median SUVmax in adrenal metastases than in adenomas (p < 0.05). There was a tendency for higher SUVmax of adrenal carcinomas when compared with other malignant lesions (p = 0.066). The median SUVmax was not different between pheochromocytomas and other tumors (p > 0.05)., Conclusion: Occult adrenal lesions discovered during FDG-PET/CT are common in the cancer context and are frequently benign. SUVmax may be a useful tool in the workup of adrenal lesions but with several important caveats., (© 2022. The Author(s), under exclusive licence to Hellenic Endocrine Society.)

Dogs living in areas of Leishmania (Viannia) braziliensis transmission may present canine tegumentary leishmaniasis (CTL) characterized by cutaneous or muzzle ulcers as well as asymptomatic L. braziliensis infection. It is not clear if dogs participate in the transmission chain of L. braziliensis to humans. However, dogs may remain with chronic ulcers for a long time, and as there are no public policies about CTL, these animals die or are sacrificed. Here we compare the efficacy of intralesional meglumine antimoniate with intralesional 0.9% NaCl solution in CTL treatment. This randomized control study included 32 dogs with cutaneous or muzzle lesions who had L. braziliensis DNA detected by PCR in tissue biopsied. Group one received 5ml of intralesional Glucantime, and group two received 5ml 0.9% NaCl solution, both applied in the four cardinal points on days 0, 15, and 30. Cure was defined as complete healing of the ulcers in the absence of raised borders on day 90. There was no difference in animals' demographic and clinical features in the two groups (p >.05). While at the endpoint, the cure rate was 87.5% in the group test, and in those who received 0.9 NaCl the cure rate was only 12.5%. As important as the high cure rate, the healing time was faster in dogs treated with antimony than in those treated with saline (p < .001). Intralesional meglumine antimoniate is effective in the treatment of dogs with L. braziliensis infection and accelerates the healing time of CTL., Competing Interests: We declare that there is no relationship or support which might be perceived as constituting a conflict of interest., (Copyright: © 2023 Lago et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The genome of the unicellular molluscan parasite Perkinsus marinus contains at least five genes coding for putative creatine kinases (CK), a phosphoryl transfer enzyme which plays a key role in cellular energy transactions. Expression and kinetic analyses of three of the P. marinus CKs revealed them to be true CKs with catalytic properties in the range of typical metazoan CKs. A sequence comparison of the P. marinus CKs with a range of CK dimers and other dimeric phosphoryl transfer enzymes in this family (phosphagen kinases) showed that the P. marinus CKs lacked some of the critical residues involved in dimer stabilization, a trait all previously characterized CKs share. Size exclusion chromatography of all three expressed P. marinus CK constructs indicated they are monomeric, consistent with the observed lack of some critical dimer stabilizing residues. Phylogenetic analyses of the P. marinus CKs and putative dinoflagellate CKs with a broad range of monomeric and dimeric phosphagen kinases revealed that the Perkinsus CKs form a distinct, well-supported clade with dinoflagellate CKs which also lack the dimer stabilizing residues. Analysis of the genomic data for P. marinus showed the presence of putative genes for the two enzymes associated with creatine biosynthesis. CK in higher organisms plays a critical role in energy buffering in cell types displaying high and variable rates of ATP turnover. The presence of multiple CKs and the creatine biosynthetic pathway in P. marinus indicates that this unicellular parasite has the full complement of molecular machinery for CK-mediated energy buffering., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Activity-dependent myelination can fine-tune neural network dynamics. Conversely, aberrant neuronal activity, as occurs in disorders of recurrent seizures (epilepsy), could promote maladaptive myelination, contributing to pathogenesis. In this study, we tested the hypothesis that activity-dependent myelination resulting from absence seizures, which manifest as frequent behavioral arrests with generalized electroencephalography (EEG) spike-wave discharges, promote thalamocortical network hypersynchrony and contribute to epilepsy progression. We found increased oligodendrogenesis and myelination specifically within the seizure network in two models of generalized epilepsy with absence seizures (Wag/Rij rats and Scn8a +/mut mice), evident only after epilepsy onset. Aberrant myelination was prevented by pharmacological seizure inhibition in Wag/Rij rats. Blocking activity-dependent myelination decreased seizure burden over time and reduced ictal synchrony as assessed by EEG coherence. These findings indicate that activity-dependent myelination driven by absence seizures contributes to epilepsy progression; maladaptive myelination may be pathogenic in some forms of epilepsy and other neurological diseases., (© 2022. The Author(s).)

Foodborne pathogens significantly impact public health globally. Excessive antimicrobial use plays a significant role in the development of the public health crisis of antibiotic resistance. Here, we determined the prevalence and antimicrobial resistance profiles of E. coli O157, Salmonella , L. monocytogenes , and Campylobacter isolated between 2016 and 2020 from small scale agricultural settings that were amended with dairy cattle or poultry manure in Northeastern Ohio. The total prevalence of the foodborne pathogens was 19.3%: Campylobacter 8%, Listeria monocytogenes 7.9%, Escherichia coli O157 1.8%, and Salmonella 1.5%. The prevalence was significantly higher in dairy cattle (87.7%) compared to poultry (12.2%) manure amended farms. Furthermore, the prevalence was higher in manure samples (84%) compared to soil samples (15.9%; p < 0.05). Multiple drug resistance was observed in 73%, 77%, 100%, and 57.3% of E. coli O157, Salmonella, &nbsp; L. monocytogenes , and Campylobacter isolates recovered, respectively. The most frequently observed resistance genes were mphA, aadA , and aphA1 in E. coli O157; blaTEM, tet(B) , and strA in Salmonella ; penA, ampC , lde , ermB, tet(O) , and aadB in L. monocytogenes and blaOXA-61, tet(O) , and aadE in Campylobacter . Our results highlight the critical need to address the dissemination of foodborne pathogens and antibiotic resistance in agricultural settings.

The "flip-flop" phenomenon may be present in differentiated progressive thyroid cancer. A high suspicion index must be maintained when this phenomenon coexists with a high tumor burden, due to the risk of the appearance of distinct tumors., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2021 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Visceral leishmaniasis is associated with a variety of hematological abnormalities. In this study, we correlated the hematological changes in the peripheral blood of dogs naturally infected with Leishmania infantum (L. infantum) with the distribution of cell lineages and cytokine gene expression patterns in the bone marrow. Samples from 63 naturally semidomiciled dogs living in an endemic area of visceral leishmaniasis were analyzed. L. infantum infection was detected in 50 dogs (79.3%). Among those, 18 (32%) had positive splenic cultures and showed more clinical signs. They also had lower red blood cell counts and leukocytosis with an increased number of neutrophils and monocytes in peripheral blood compared to dogs negative to this test. L. infantum DNA was detected in the bone marrow of 8/14 dogs with positive splenic culture. Dogs with L. infantum infection in the bone marrow presented with histiocytosis ( p = 0.0046), fewer erythroid cell clusters ( p = 0.0127) and increased gene expression levels of IFN-γ ( p = 0.0015) and TNF ( p = 0.0091). The data shown herein suggest that inflammatory and cytokine gene expression changes in bone marrow may contribute to the peripheral blood hematological changes observed in visceral leishmaniasis.

The ongoing biotechnological revolution is rooted in our knowledge of enzymes. However, metagenomics is showing how little we know about Earth's enzyme repertoire. Deep sequencing has revolutionized our view of the tree of life. The genomes of newly-discovered organisms are replete with novel sequences, emphasizing the trove of enzyme structures and functions waiting to be explored by biochemists. Here, we sought to draw attention to the vastness of the "enzymatic dark matter" within the tree of life by placing enzymological knowledge in the context of phylogeny. We used kinetic parameters from the BRaunschweig ENzyme DAtabase (BRENDA) as our proxy for enzymological knowledge. Mapping 12,677 BRENDA entries onto the phylogenetic tree revealed that 55% of these data were from eukaryotes, even though they are the least diverse part of the tree. At the next taxonomic level, only four of 18 archaeal phyla and 24 of 111 bacterial phyla are represented in the BRENDA dataset. One phylum, the Proteobacteria, accounts for over half of all bacterial entries. Similarly, the supergroup Amorphea, which includes animals and fungi, contains over half the data on eukaryotes. Many major taxonomic groups are notable for their complete absence from BRENDA, including the ultra-diverse bacterial Candidate Phyla Radiation. At the species level, five mammals (including human) contribute 15% of BRENDA entries. The taxonomic bias in enzymology is strong, but in the era of gene synthesis we now have the tools to address it. Doing so promises to enrich our biochemical understanding of life and uncover powerful new biocatalysts., (© 2021 The Protein Society.)

A gene encoding creatine kinase was identified in two cryptosporidia species, Cryptosporidium muris and C. andersonii. They were syntenic and shared 91% identity 94% identity at the amino acid level and nucleotide levels respectively. The C. muris creatine kinase was characterized biochemically and shown to phosphorylate both creatine and glycocyamine with a 20-fold greater preference for creatine. The observed catalytic turnover with creatine was k cat  = 30 s -1 with a catalytic efficiency of 15.4 mM -1  s -1 . These values were within the range observed for other creatine kinases. A search of all the apicomplexa genomes available on EuPathDB did not reveal any other phosphagen kinase genes raising the possibility of horizontal gene transfer. However, no definitive conclusion could be drawn regarding this hypothesis given the massive amount of gene loss in the apicomplexa species which are primarily parasitic species. The implications of a creatine kinase in the parasites' infection cycle are discussed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)