Systematic assessment of nymphs of Diesingiinae (Pentastomida: Sebekidae) parasitizing Palloceros harpagos (Cyprinodontiformes: Poeciliidae) from Parque Nacional Iguazú, Argentina: filling gaps in an incomplete phylogenetic framework.

During a search for parasites in fishes from Iguazu River, Argentina, a nymph of pentastomid was found encysted on mesenteries of Phalloceros harpagos. The 28S rDNA and COI mt-DNA were used to compare with the sequences deposited in the GenBank. Pentastomid nymphs belong to the subfamily Diesingiinae (Sebekidae) for having chloride cell pores distributed in a single row per annulus; also, the hooks and rows of spines of our material differ to other genera. Present specimens are most likely Diesingia sp., having 63-74 annuli, a U shaped oral cadre with fibers closing anteriorly and a peg like extension of the oral cadre. The 28S rDNA analysis places our samples into a sister group of Alofia sp., but the COI mt-DNA situate them on the base of the clade. In conclusion, our pentastomid positively belongs to Diesingia sp., however, indisputable assignation requires a reliable description of the nymph, or the availability of sequences linking nymphs and adults, which even could provide evidence of a new hitherto undescribed genus. Aditionally, the systematic position of Sebekia oxycephala previously described by P. harpagos is discussed on the basis of our results, allowing us to suggest a re-assignation of such specimens to the genus Diesingia.

Perturbed hematopoiesis in individuals with germline DNMT3A overgrowth Tatton-Brown-Rahman syndrome.

Tatton-Brown-Rahman syndrome (TBRS) is an overgrowth disorder caused by germline heterozygous mutations in the DNA methyltransferase DNMT3A. DNMT3A is a critical regulator of hematopoietic stem cell (HSC) differentiation and somatic DNMT3A mutations are frequent in hematologic malignancies and clonal hematopoiesis. Yet, the impact of constitutive DNMT3A mutation on hematopoiesis in TBRS is undefined. In order to establish how constitutive mutation of DNMT3A impacts blood development in TBRS we gathered clinical data and analyzed blood parameters in 18 individuals with TBRS. We also determined the distribution of major peripheral blood cell lineages by flow cytometric analyses. Our analyses revealed non-anemic macrocytosis, a relative decrease in lymphocytes and increase in neutrophils in TBRS individuals compared to unaffected controls. We were able to recapitulate these hematologic phenotypes in multiple murine models of TBRS and identified rare hematological and non-hematological malignancies associated with constitutive Dnmt3a mutation. We further show that loss of DNMT3A in TBRS is associated with an altered DNA methylation landscape in hematopoietic cells affecting regions critical to stem cell function and tumorigenesis. Overall, our data identify key hematopoietic effects driven by DNMT3A mutation with clinical implications for individuals with TBRS and DNMT3A-associated clonal hematopoiesis or malignancies.

Taxonomic status of Rhabdochona ictaluri (Nematoda: Rhabdochonidae) based on molecular and morphological evidence.

The genus Rhabdochona includes more than 100 species infecting freshwater fishes in all zoogeographical regions of the world. In Mexico, 12 nominal species of Rhabdochona have been recorded. Of these, Rhabdochona ictaluri was originally described as a parasite of endemic catfishes of the family Ictaluridae; however, the species was later considered on morphological grounds as a junior synonym of Rhabdochona kidderi. In this study, newly sampled specimens of R. ictaluri were obtained from the type host and type locality and were used to perform a detailed morphological analysis and molecular phylogenetic inferences through one mitochondrial and two nuclear genes; data were used in an integrative taxonomy context to test the taxonomic status of R. ictaluri. This approach proved to be very useful to confirm the validity of this species, and robust species limits were established between these two putative species considering morphology, molecular data, host association, and biogeography.

PREVALENCE OF OPECOELID TREMATODES (TREMATODA: DIGENEA: OPECOELIDAE) IN THE WOOLLY SCULPIN CLINOCOTTUS ANALIS FROM THE PACIFIC COAST OF THE BAJA CALIFORNIA PENINSULA.

Prevalence values for 3 digenean species of the family Opecoelidae were calculated during a half-year period from 20 individuals per month of the fish species Clinocottus analis, collected from an intertidal environment of Baja California, Mexico. Trematode species recovered were Opecoelus adsphaericus, Opecoelus cameroni, and Opecoelus pacificus. Of these, only O. adsphaericus was present throughout the study, whereas O. pacificus and O. cameroni were recorded for 1 or 2 mo, respectively, exhibiting relatively low prevalence values. The decrease in prevalence of O. adsphaericus coincides with the appearance of O. pacificus and O. cameroni; these last 2 species were found only in the largest hosts, and their presence represents new records for Mexican marine fauna.

Dose-dependent effects of Dnmt3a in an inducible murine model of KrasG12D-driven leukemia.

DNMT3A mutations are frequently found in clonal hematopoiesis and a variety of hematologic malignancies, including acute myeloid leukemia. An assortment of mouse models have been engineered to explore the tumorigenic potential and malignant lineage bias due to loss of function of DNMT3A in consort with commonly comutated genes in myeloid malignancies, such as Flt3, Nras, Kras, and c-Kit. We employed several tamoxifen-inducible Cre-ERT2 murine model systems to study the effects of constitutively active KrasG12D-driven myeloid leukemia (Kras) development together with heterozygous (3aHet) or homozygous Dnmt3a deletion (3aKO). Due to the rapid generation of diverse nonhematologic tumors appearing after tamoxifen induction, we employed a transplantation model. With pretransplant tamoxifen induction, most Kras mice died quickly of T-cell malignancies regardless of Dnmt3a status. Using posttransplant induction, we observed a dose-dependent effect of DNMT3A depletion that skewed the leukemic phenotype toward a myeloid lineage. Specifically, 64% of 3aKO/Kras mice had exclusively myeloid disease compared with 36% of 3aHet/Kras and only 13% of Kras mice. Here, 3aKO combined with Kras led to increased disease burden, multiorgan infiltration, and faster disease progression. DOT1L inhibition exerted profound antileukemic effects in malignant 3aKO/Kras cells, but not malignant cells with Kras mutation alone, consistent with the known sensitivity of DNMT3A-mutant leukemia to DOT1L inhibition. RNAseq from malignant myeloid cells revealed that biallelic Dnmt3a deletion was associated with loss of cell-cycle regulation, MYC activation, and TNF⍺ signaling. Overall, we developed a robust model system for mechanistic and preclinical investigations of acute myeloid leukemia with DNMT3A and Ras-pathway lesions.

Hematologic DNMT3A reduction and high-fat diet synergize to promote weight gain and tissue inflammation.

During aging, blood cell production becomes dominated by a limited number of variant hematopoietic stem cell (HSC) clones. Differentiated progeny of variant HSCs are thought to mediate the detrimental effects of such clonal hematopoiesis on organismal health, but the mechanisms are poorly understood. While somatic mutations in DNA methyltransferase 3A (DNMT3A) frequently drive clonal dominance, the aging milieu also likely contributes. Here, we examined in mice the interaction between high-fat diet (HFD) and reduced DNMT3A in hematopoietic cells; strikingly, this combination led to weight gain. HFD amplified pro-inflammatory pathways and upregulated inflammation-associated genes in mutant cells along a pro-myeloid trajectory. Aberrant DNA methylation during myeloid differentiation and in response to HFD led to pro-inflammatory activation and maintenance of stemness genes. These findings suggest that reduced DNMT3A in hematopoietic cells contributes to weight gain, inflammation, and metabolic dysfunction, highlighting a role for DNMT3A loss in the development of metabolic disorders.

Erratum: Hematologic DNMT3A reduction and high-fat diet synergize to promote weight gain and tissue inflammation.

[This corrects the article DOI: 10.1016/j.isci.2024.109122.].

SWI/SNF Blockade Disrupts PU.1-Directed Enhancer Programs in Normal Hematopoietic Cells and Acute Myeloid Leukemia.

In acute myeloid leukemia (AML), SWI/SNF chromatin remodeling complexes sustain leukemic identity by driving high levels of MYC. Previous studies have implicated the hematopoietic transcription factor PU.1 (SPI1) as an important target of SWI/SNF inhibition, but PU.1 is widely regarded to have pioneer-like activity. As a result, many questions have remained regarding the interplay between PU.1 and SWI/SNF in AML as well as normal hematopoiesis. Here we found that PU.1 binds to most of its targets in a SWI/SNF-independent manner and recruits SWI/SNF to promote accessibility for other AML core regulatory factors, including RUNX1, LMO2, and MEIS1. SWI/SNF inhibition in AML cells reduced DNA accessibility and binding of these factors at PU.1 sites and redistributed PU.1 to promoters. Analysis of nontumor hematopoietic cells revealed that similar effects also impair PU.1-dependent B-cell and monocyte populations. Nevertheless, SWI/SNF inhibition induced profound therapeutic response in an immunocompetent AML mouse model as well as in primary human AML samples. In vivo, SWI/SNF inhibition promoted leukemic differentiation and reduced the leukemic stem cell burden in bone marrow but also induced leukopenia. These results reveal a variable therapeutic window for SWI/SNF blockade in AML and highlight important off-tumor effects of such therapies in immunocompetent settings. SIGNIFICANCE: Disruption of PU.1-directed enhancer programs upon SWI/SNF inhibition causes differentiation of AML cells and induces leukopenia of PU.1-dependent B cells and monocytes, revealing the on- and off-tumor effects of SWI/SNF blockade.

Comparative exploration of the morphological plasticity of Trichodina centrostrigeata (Peritrichia: Mobilida), ectoparasite from the gills of two tilapia species (Oreochromis niloticus and O. mossambicus) in a global context.

Trichodina centrostrigeata Basson, Van As et Paperna, 1983 from Oreochromis mossambicus (Peters) and O. niloticus (Linnaeus) from different host populations from Argentina, Mexico and South Africa was reviewed. Although T. centrostrigeata has a distinct denticle structure that makes morphological taxonomic inferences uncomplicated, variation of the denticles within and among individuals and populations were still observed. While traditional taxonomy of mobilines is heavily reliant on morphometrics, and recently even more so on molecular analysis, this paper proposes the use of geometric morphometry, specifically elliptical Fourier analysis, to address morphological conflicts that arise when comparing different populations. By applying this technique, combined with traditional taxonomy, it was found that T. centrostrigeata in this study can be grouped into two separate morphotypes, the first (type a) from aquaculture farms in Argentina and Mexico and the second (type b) from a natural habitat in Glen Alpine Dam, South Africa. This study supports the validity of geometric morphometry as an additional technique to distinguish not only between species but also evolutionary plasticity of the same species from different localities and habitats.

[Nutrition iodine status in pregnant women in the sanitary district Sierra de Huelva-Andévalo, South of Spain]. / Deficiencia nutricional de yodo en gestantes pertenecientes al distrito sanitario Sierra de Huelva-Andévalo, sur de España.

BACKGROUND: Iodine is an essential trace element implicated in synthesis of thyroid hormones. Iodine requirements vary throughout life. This iodine requirement is increased during pregnancy and breastfeeding. In a previous study carried out by our group in 2008, we detected an iodine-deficient area in the province of Huelva, specially in district Sierra de Huelva-Andévalo by means of neonatal TSH determinations. OBJECTIVE: To reinforce the iodine supplementation campaign and its impact on their newborns in order to assess nutrition iodine status in pregnant women using questionnaire and ioduria determination. MATERIAL AND METHODS: This study has been jointly carried out by Congenital Hypothyroidism Unit of the Clinical Biochemistry Department of the Virgen Macarena University Hospital (Seville) and the Gynecology and Clinical Analysis Unit of the Río Tinto Hospital (Huelva) during two years. We studied 313 pregnant women. All of them filled out a personal questionnaire to know the iodine nutritional status in their area. Ioduria was determinated by high-resolution liquid chromatography. Data from pregnant women and results of the studied variables were analyzed with SPSS v13.0. CONCLUSIONS: Pregnant women from the sanitary district Sierra de Huelva-Andévalo present a median for ioduria which corresponds to an insufficient iodine intake according to the WHO classification. The questionnaires suggest that this iodine deficiency is consequence of an insufficient iodine intake and a low adherence to the treatment.

Modeling IKZF1 lesions in B-ALL reveals distinct chemosensitivity patterns and potential therapeutic vulnerabilities.

IKAROS family zinc finger 1 (IKZF1) alterations represent a diverse group of genetic lesions that are associated with an increased risk of relapse in B-cell acute lymphoblastic leukemia. Due to the heterogeneity of concomitant lesions, it remains unclear how IKZF1 abnormalities directly affect cell function and therapy resistance, and whether their consideration as a prognostic indicator is valuable in improving outcome. CRISPR/Cas9 strategies were used to engineer multiple panels of isogeneic lymphoid leukemia cell lines with a spectrum of IKZF1 lesions to measure changes in chemosensitivity, gene expression, cell cycle, and in vivo engraftment that can be linked to loss of IKAROS protein. IKZF1 knockout and heterozygous null cells displayed relative resistance to a number of common therapies for B-cell acute lymphoblastic leukemia, including dexamethasone, asparaginase, and daunorubicin. Transcription profiling revealed a stem/myeloid cell-like phenotype and JAK/STAT upregulation after IKAROS loss. A CRISPR homology-directed repair strategy was also used to knock-in the dominant-negative IK6 isoform into the endogenous locus, and a similar drug resistance profile, with the exception of retained dexamethasone sensitivity, was observed. Interestingly, IKZF1 knockout and IK6 knock-in cells both have significantly increased sensitivity to cytarabine, likely owing to marked downregulation of SAMHD1 after IKZF1 knockout. Both types of IKZF1 lesions decreased the survival time of xenograft mice, with higher numbers of circulating blasts and increased organ infiltration. Given these findings, exact specification of IKZF1 status in patients may be a beneficial addition to risk stratification and could inform therapy.

A checklist of trichodinid species (Ciliophora: Trichodinidae) on tilapia fishes (Cichlidae), with new records from Mexico and the first data from Argentina.

Tilapia is the common name for a wide spectrum of cichlid fishes usually selected for aquaculture activities. However, some aspects of the natural history of these fishes, such as the diversity of certain ectoparasitic protistan groups remain understudied. In order to understand the diversity of ciliates of the family Trichodinidae parasitizing tilapia around the world, a database with all available accounts was assembled. This information, along with records derived from our own recent research, allowed us to generate a checklist containing all the records for tilapia-Trichodinidae associations. The checklist is presented as a host-parasite list containing 44 nominal taxa from 29 countries on four continents, and it also presents the first data from Argentina, where tilapia culture is still an incipient, but growing activity. The observed high species richness of trichodinids is probably derived from a set of specific taxa for tilapia, along with an important component of species acquired from the new environments where tilapia have been introduced. Data presented here could be used along with existing information of metazoan parasites to build a general view about diseases that affect tilapia.

New morphological and molecular data for Xystretrum solidum (Gorgoderidae, Gorgoderinae) from Sphoeroides testudineus (Tetraodontiformes, Tetraodontidae) in Mexican waters.

Adults of trematodes in the genus Xystretrum Linton, 1910 (Gorgoderidae, Gorgoderinae) are parasites found exclusively in the urinary bladders of tetraodontiform fishes. However, limited and unclear morphological data were used to describe the type species, X. solidum Linton, 1910. Here, we present the first detailed morphological information for a member of Xystretrum. Morphological characters were described using light and scanning electron microscopy (SEM) of Xystretrum specimens from Sphoeroides testudineus (Linnaeus) (Tetraodontiformes, Tetraodontidae), collected at six localities off the northern Yucatan Peninsula coast of the Gulf of Mexico. We also compared sequence fragments of the 28S (region D1-D3) ribosomal DNA and mitochondrial Cytochrome c oxidase subunit 1 (COI) gene with those available for other gorgoderine taxa. We assigned these Xystretrum specimens to X. solidum, despite the incompleteness of published descriptions. The data provide a foundation for future work to validate the identities of X. solidum, X. papillosum Linton, 1910 and X. pulchrum (Travassos, 1920) with new collections from the type localities and hosts. Comparisons of 28S and COI regions described here also provide an opportunity to evaluate the monophyletic status of Xystretrum.

A checklist of ciliate parasites (Ciliophora) of fishes from Mexico.

A database with all available published accounts of the ciliate parasite species of Mexican fishes was assembled. This information, along with records derived from own recent research, allow generating a checklist containing all the records, which is a necessary first step to address future questions in the areas of ecology, evolutionary biology and biogeography of these host-parasite associations. The checklist is presented as a parasite-host list, and a host-parasite list. The checklist contains 30 nominal species, from 9 genera and 8 families of ciliate parasites. Most of the primary records were done for exotic fish species, artificially introduced to Mexico for aquaculture purposes; however, recent works have been conducted in diverse species of native fishes. Excepting one, all the ciliate species listed here have been previously recorded for diverse fish species from different localities around the world. Based on the amount of information contained in this checklist, much more effort is necessary to accurately know the diversity of species of this type of parasites in fish fauna of Mexico.

Neophilometroides n. gen. (Nematoda: Philometridae) for Philometroides caudatus Moravec, Scholz and Vivas-Rodríguez, 1995, with erection of Neophilometroidinae n. subfam.

A detailed examination (including scanning electron microscopy) of newly collected nematode specimens (subgravid females) referable to Philometroides caudatus Moravec, Scholz and Vivas-Rodríguez, 1995, from the swimbladder of the pimelodid catfish, Rhamdia guatemalensis, in the Papaloapan River in Tlacotalpan, State of Veracruz, Mexico, as well as the paratype specimens of this species, revealed the presence of a small buccal capsule armed with peribuccal teeth in the female. Because of this unique morphological feature within the Philometridae, and considering other taxonomically important characters such as the structure of the male tail and the shape of the anterior end of the esophagus in the gravid female, Neophilometroidinae n. subfam, and Neophilometroides n. gen. are proposed to accommodate this species. Philometra paraguayensis Petter, 1995, is transferred to Neophilometroides as N. paraguayensis (Petter, 1995) n. comb. Newly collected specimens are briefly described and illustrated.

Rhabdochona guerreroensis n. sp. (Nematoda: Rhabdochonidae) from the intestine of the gobiid Sicydium multipunctatum from fresh waters in Mexico.

Rhabdochona guerreroensis n. sp. is described on the basis of specimens recovered from the intestine of Sicydium multipunctatum (Regan) (Gobiidae, Perciformes) from 2 localities in Mexico. This species is characterized by 12 teeth in the prostom (occasionally 11), asymmetrical numbers of postanal papillae, a broad distal tip of the larger (left) spicule with a small bifurcation covered by narrow cuticular membrane, a smaller (right) spicule with a dorsal barb on its distal tip, and filamented eggs.

Helminth parasites of Chapalichthys encaustus (Pisces: Goodeidae), an endemic freshwater fish from Lake Chapala, Jalisco, Mexico.

A total of 6 helminth species were recorded during helminthological examination of 50 Chapalichthys encaustus from Lake Chapala, Jalisco, Mexico. Helminth species identified included: Salsuginus sp. (an undescribed monogenea); Posthodiplostomum minimum (metacercariae); Cyclustera ralli (metacestode); Polymorphus brevis (cystacanth); Contracaecum sp. (nematode larvae); and Rhabdochona lichtenfelsi (adult nematode). Of these, 2 (Salsuginus sp. and R. lichtenfelsi) are specialist species. The observed species richness, individual parasite abundance, and diversity were low. Data suggest that host specificity is an important factor contributing to observed community composition and richness. Host feeding habits and helminth species availability seem to determine the characteristics of these helminth assemblages.

Helminth parasites of the tropical gar, Atractosteus tropicus Gill, from Tabasco, Mexico.

A total of 8 helminth species were recorded in an examination of 43 tropical gar, Atractosteus tropicus Gill, collected at the Pantanos de Centla Biosphere Reserve, Tabasco, Mexico. The parasite species included 1 adult trematode, 3 metacercariae, 1 cestode, 1 adult nematode, and 2 nematode larvae. Six of these 8 species were rare, with low prevalence (< 17%) and abundance (< 1.0 helminths per examined fish). The larvae of Contracaecum sp. were the most abundant in the sample, constituting 60% of the total helminths (64% prevalence, 3.8 +/- 5.2 abundance), followed by the cestode Proteocephalus singularis, constituting 18% of the worms (30.5% prevalence, 1.1 +/- 3.0 abundance). Species richness, individual parasite abundance, and diversity were low in the infracommunities. The recording of 3 specialist species in the tropical gar confirms that the helminth fauna of gar has an appreciable degree of specificity. This study indicates the importance of ecological determinants of richness in helminth communities of the tropical gar.

Two new nematodes, Paraseuratoides ophisterni gen. et sp. n. (Quimperiidae) and Philometra ophisterni sp. n. (Philometridae), from the swamp-eel Ophisternon aenigmaticum in Mexico.

Two new nematodes, Paraseuratoides ophisterni gen. et sp. n. (Seuratoidea: Quimperiidae) and Philometra ophisterni sp. n. (Dracunculoidea: Philometridae) are described based on specimens recovered from the intestine and mesentery, respectively, of the swamp-eel Ophisternon aenigmaticum Rosen et Greenwood (Synbranchiformes: Synbranchidae) from a canal of the Papaloapan River in Tlacotalpan, State of Veracruz, Mexico. The genus Paraseuratoides is mot similar to Paraseuratum Johnston et Mawson, 1940, differing from it mainly in the absence of a bulbous inflation on the anterior end of the oesophagus and in the structure of the mouth (presence of 6 spines in addition to 6 oesophageal teeth). Neoquimperia Wang, Zhao, Wang et Zhang, 1979 and Wuinema Yu et Wang, 1992 are synonymised with Ezonema Boyce, 1971 and Paragendria Baylis, 1939, respectively, and Haplonema hamulatum Moulton, 1931 is considered a junior synonym of Ichthyobronema conoura Gnedina et Savina, 1930. Philometra ophisterni (only females) is mainly characterised by minute cephalic papillae, a greatly developed anterior oesophageal bulb separated from the cylindrical part of the oesophagus, anterior extension of the oesophageal gland anterior to the nerve ring, and by the character of large caudal projections. This is the first Philometra species recorded from inland fishes in Mexico.

A simple index for detection of gestational diabetes mellitus.

The conventional screening test for gestational diabetes mellitus is measurement of plasma glucose 1 hour after 50 g glucose by mouth. The sensitivity and specificity of this test are lower than desirable; we therefore developed an index including other plasma constituents. In a preliminary study, 138 pregnant women had the standard oral glucose load screening test, and plasma fructosamine and total proteins were measured, in addition to glucose, in the 1-hour samples. An index value (I) was calculated as [fructosamine (micro mol/L) divided by total proteins (g/L)]x[glucose (mmol/L) divided by 100]. Cut-off values for I were then assessed in a second prospective study, of 642 pregnant women. Definitive diagnosis of gestational diabetes was by oral glucose tolerance test (OGTT). The index was also assessed in terms of fetal macrosomia (birthweight>or=4000 g). With a cut-off value of I=27.2, sensitivity was 98%, specificity 89%, diagnostic efficiency 90%, positive likelihood ratio 8.76. Application of the index would have avoided 42% of the OGTTs demanded by the standard screening test, reducing false positives from about 24% to 10%. Predictive efficacy for macrosomia was 10.3% versus 7.9%. Our index offers an efficient screening test for gestational diabetes, and with more stringent cut-off points may be applicable as a single-step diagnostic procedure.