Abstract.Heterochromatin is one of the most dynamic components in the genome of species. Previous studies on the heterochromatin content and distribution in Heteroptera (insects with holokinetic chromosomes) have shown that the species belonging to the family Coreidae are interesting model organisms since they show very diverse C bands patterns. In the present work, we analyzed the C-band pattern in individuals of Holhymenia rubiginosa from different populations collected in different years. This species has the diploid karyotype 2n = 27/28 = 24 + 2m + X0/XX (male/female). C-bands are terminally, subterminally or interstitially located on 10-17 chromosomes and a remarkable heterochromatin heteromorphism is observed in the meiotic bivalents: in the presence/absence of bands, in the size of bands and number of bands. A heteromorphism is also inferred in the number of ribosomal genes from the difference in the fluorescent in situ hybridization signals between NOR-homologues. Chiasmata are generally located opposite to conspicuous C-bands, but in some bivalents chiasmata are also observed in close proximity to C-bands. Considering the striking variation in heterochromatin content between individuals and populations it is suggested that heterochromatin should be selectively neutral in H. rubiginosa.

In organisms with chiasmatic meiosis two different relationships have been described between crossing over and synapsis: in one group of organisms synapsis depends on the initiation of meiotic recombination while in the other group it is independent of this initiation. These patterns have been observed mainly in organisms where all meiotic bivalents in the set have similar behaviors. In some heteropteran insects a pair of chromosomes named m chromosomes is known to behave differently from autosomes regarding synapsis and recombination. Here we used immunodetection of a synaptonemal complex component and acid-fixed squashes to investigate the conduct of the small m chromosome pair during the male meiosis in the coreid bug Holhymenia rubiginosa. We found that the m chromosomes form a synaptonemal complex during pachytene, but they are not attached by a chiasma in diakinesis. On the other hand, the autosomal bivalents synapse and recombine regularly. The co-existence of these variant chromosome behaviors during meiosis I add further evidence to the absence of unique patterns regarding the interdependence of synapsis and recombination.

Background: Retrospective observational studies suggest that transmission of Trypanosoma cruzi does not occur in treated women when pregnant later in life. The level of parasitemia is a known risk factor for congenital transmission. Benznidazole (BZN) is the drug of choice for preconceptional treatment to reduce parasitic load. The fear of treatment-related side effects limits the implementation of the Argentine guideline recommending BZN 60d/300 mg (or equivalent) treatment of T. cruzi seropositive women during the postpartum period to prevent transmission in a future pregnancy. A short and low dose BZN treatment might reduce major side effects and increase compliance, but its efficacy to reduce T. cruzi parasitic load compared to the standard 60d/300 mg course is not yet established. Clinical trials testing alternative BZN courses among women of reproductive age are urgently needed. Methods and design: We are proposing to perform a double-blinded, non-inferiority randomized controlled trial comparing a short low dose 30-day treatment with BZN 150 mg/day (30d/150 mg) vs. BZN 60d/300 mg. We will recruit not previously treated T. cruzi seropositive women with a live birth during the postpartum period in Argentina, randomize them at 6 months postpartum, and follow them up with the following specific aims: Specific aim 1: to measure the effect of BZN 30d/150 mg compared to 60d/300 mg preconceptional treatment on parasitic load measured by the frequency of positive Polymerase Chain Reaction (PCR) (primary outcome) and by real-time quantitative PCR (qPCR), immediately and 10 months after treatment. Specific aim 2: to measure the frequency of serious adverse events and/or any adverse event leading to treatment

Background Retrospective observational studies suggest that transmission of Trypanosoma cruzi does not occur in treated women when pregnant later in life. The level of parasitemia is a known risk factor for congenital transmission. Benznidazole (BZN) is the drug of choice for preconceptional treatment to reduce parasitic load. The fear of treatment-related side effects limits the implementation of the Argentine guideline recommending BZN 60d/300mg (or equivalent) treatment of T. cruzi seropositive women during the postpartum period to prevent transmission in a future pregnancy. A short and low dose BZN treatment might reduce major side effects and increase compliance, but its efficacy to reduce T. cruzi parasitic load compared to the standard 60d/300mg course is not yet established. Clinical trials testing alternative BZN courses among women of reproductive age are urgently needed.Methods and design We are proposing to perform a double-blinded, non-inferiority randomized controlled trial comparing a short low dose 30-day treatment with BZN 150mg/day (30d/150mg) vs. BZN 60d/300mg. We will recruit not previously treated T. cruzi seropositive women with a live birth during the postpartum period in Argentina, randomize them at six months postpartum, and follow them up with the following specific aims:Specific aim 1: to measure the effect of BZN 30d/150mg compared to 60d/300mg preconceptional treatment on parasitic load measured by the frequency of positive Polymerase Chain Reaction (PCR) (primary outcome) and by real-time quantitative PCR (qPCR), immediately and 10 months after treatment.Specific aim 2: to measure the frequency of serious adverse events and/or any adverse event leading to treatment interruption.Trial registration: ClinicalTrials.gov. Identifier: NCT03672487. Registered 14 September 2018, https://clinicaltrials.gov/ct2/show/NCT03672487?recrs=a&cond=Chagas+Disease&cntry=AR&draw=2&rank=3

Heteropteran insects exhibit a remarkable diversity of meiotic processes, including coexistence of different chromosomes types with different behavior during the first meiotic division, non-chiasmatic segregation, and inverted meiosis. Because of this diversity they represent suitable models to study fundamental questions about the mechanisms of chromosome behavior during cell division. All heteropteran species possess holokinetic chromosomes and in most of them the autosomal chromosomes synapse, recombine, and undergoe pre-reductional meiosis. In contrast, the sex chromosomes are achiasmatic, behave as univalents at metaphase I and present an inverted or post-reductional meiosis. An exception to this typical behavior is found in Pachylis argentinus, where both the autosomes and the X-chromosome divide reductionally at anaphase I and then divide equationally at anaphase II. In the present report, we analyzed the distribution of histones H3K9me2 and H3K9me3 in P. argentinus and in five species that have simple and multiple sex chromosome systems with typical chromosome segregation, Belostoma elegans, B. oxyurum, Holhymenia rubiginosa, Phthia picta, and Oncopeltus unifasciatellus. We found that H3K9me3 is a marker for sex-chromosomes from early prophase I to the end of the first division in all the species. H3K9me2 also marks the sex chromosomes since early prophase but shows different dynamics at metaphase I depending on the sex-chromosome segregation: it is lost in species with equationally dividing sex chromosomes but remains on one end of the X chromosome of P. argentinus, where chromatids migrate together at anaphase I. It is proposed that the loss of H3K9me2 from the sex chromosomes observed at metaphase I may be part of a set of epigenetic signals that lead to the reductional or equational division of autosomes and sex chromosomes observed in most Heteroptera. The present observations suggest that the histone modifications analyzed here evolved in Heteroptera as markers for asynaptic and achiasmatic sex chromosomes during meiosis to allow the distinction from the chiasmatic autosomal chromosomes.

BackgroundRetrospective observational studies suggest that transmission of the Trypanosoma cruzi does not occur in treated women when pregnant later in life. The level of parasitemia is a known risk factor for congenital transmission. Benznidazole (BZN) is the drug of choice for preconceptional treatment to reduce parasitic load. The BENEFIT trial, conducted in Argentina, compared a BZN 60-day/300 mg per day (60d/300mg) course (for subjects weighing 60kg) vs. placebo among patients with Chagas’ cardiomyopathy. The rate of conversion to negative conventional PCR (PCR) in the blood was 66.2% in the BZN group vs. 33.5% in the placebo group. Of concern, the rate of treatment interruption caused by adverse events was 23.9% in the BZN group.The fear of treatment-related side effects limits the implementation of the Argentine guideline recommending BZN 60d/300mg (or equivalent) treatment of T. cruzi seropositive women during the postpartum period to prevent transmission in a future pregnancy. A short and low dose BZN treatment might reduce major side effects and increase compliance, but its efficacy to reduce T. cruzi parasitic load compared to the standard 60d/300mg course is not yet established. Observational, animal, and pharmacokinetics (PK) studies suggest that the 60d/300mg course may be overdosing patients unnecessarily and increasing adverse events. Young and healthy subjects might have lower rates of treatment failures and adverse events. Clinical trials testing alternative BZN courses among women of reproductive age are urgently needed.Methods and designWe are proposing to perform a double-blinded, non-inferiority randomized controlled trial comparing a short low dose 30-day treatment with BZN 150mg/day (30d/150mg) vs. BZN 60d/300mg. We will recruit not previously treated T. cruzi seropositive women with a live birth during the postpartum period in Argentina, randomize them at six months postpartum, and follow them up with the following specific aims:Specific Aim 1: to measure the effect of BZN 30d/150mg compared to 60d/300mg preconceptional treatment on parasitic load measured by the frequency of positive Polymerase Chain Reaction (PCR) (primary outcome) and by real-time quantitative PCR (qPCR), immediately (Specific Aim 1a) and 10 months (Specific Aim 1b) after treatment.Hypothesis 1a: the frequency of positive PCR and the parasitic load measured by qPCR immediately after BZN 30d/150mg will be non-inferior (Non-Inferiority (NI) margin for PCR: 10% absolute difference) to BZN 60d/300mg.Hypothesis 1b: the frequency of positive PCR and the parasitic load measured by qPCR 10 months after BZN 30d/150mg will be non-inferior (NI margin for PCR: 9% absolute difference) to BZN 60d/300mg.Specific Aim 2: to measure the frequency of serious adverse events and/or any adverse event leading to treatment interruption of BZN 30d/150mg compared to 60d/300mg.Hypothesis 2: the frequency of serious adverse events and/or any adverse event leading to treatment interruption will be 50% lower with BZN 30d/150mg than with BZN 60d/300mg.Trial registration: ClinicalTrials.gov. Identifier: NCT03672487. Registed 14 September 2018, https://clinicaltrials.gov/ct2/show/NCT03672487?recrs=a&cond=Chagas+Disease&cntry=AR&draw=2&rank=3