Paracentric inversion involving a NOR-bearing chromosome of rainbow trout (Oncorhyncus mykiss): Electron microscopy studies of the synaptonemal complex

Cytogenetic studies conduced on a sample of 19 specimens of rainbow trout (Oncorhyncus mykiss) showed that 6 presented two chromosomes with a single subterminal AgNOR on the short arms and 13 presented one chromosome with a single subterminal Ag-NOR and a second chromosome with two small subterminal Ag-NORs. Synaptonemal complex studies showed the presence of a pairing failure involving the two lateral elements (LEs) of the NOR-bearing chromosomes only in those specimens with two different NOR-bearing chromosomes, suggesting that the chromosomes with two Ag-NORs originated from a paracentric inversion involving a terminal segment of the original NOR-bearing chromosome. A comparative analysis between three normal and three heterozygous fishes suggest that in the latter group the LEs of the NOR-bearing chromosomes initiate the synaptic process in a more delayed manner, the synapsis develops more quickly, and the nucleolus stays associated with chromosomes for a longer time

Relationships among growth and different NOR phenotypes in a specific stock of rainbow trout (Oncorhynchus mykiss)

Growth is one of the most important aspects in the genetic improvement of cultured fish species. Consequently, genetic parameters related to this feature and their response to selection have been the focus of most research in this area. Such research indicates that, in general, there is enough additive genetic variance related to growth, justifying the use of selection. Based on the usefulness of cytogenetic and molecular markers in the fish culture, the aim of the present work was to analyze the possible relationships among cytogenetic characteristics, specifically the NOR phenotypes, and the increase in length and weight in specimens of the rainbow trout (Oncorhynchus mykiss), resultant from directed mating between homozygous females and heterozygous males according to their NOR phenotypic patterns. The equations of the relationship between length and weight of the analyzed specimens followed the model Wt = a Lt b, showing b values higher than 3, determinant of a positive allometric growth. The results showed that the different NOR phenotypes were not related with the growth values for length and weight in any statistical test

Relationships among growth and different NOR phenotypes in a specific stock of rainbow trout (Oncorhynchus mykiss)

Growth is one of the most important aspects in the genetic improvement of cultured fish species. Consequently, genetic parameters related to this feature and their response to selection have been the focus of most research in this area. Such research indicates that, in general, there is enough additive genetic variance related to growth, justifying the use of selection. Based on the usefulness of cytogenetic and molecular markers in the fish culture, the aim of the present work was to analyze the possible relationships among cytogenetic characteristics, specifically the NOR phenotypes, and the increase in length and weight in specimens of the rainbow trout (Oncorhynchus mykiss), resultant from directed mating between homozygous females and heterozygous males according to their NOR phenotypic patterns. The equations of the relationship between length and weight of the analyzed specimens followed the model Wt = a Lt b, showing b values higher than 3, determinant of a positive allometric growth. The results showed that the different NOR phenotypes were not related with the growth values for length and weight in any statistical test

NORs inheritance analysis in crossings including individuals from two stocks of rainbow trout (Oncorhynchus mykiss)

Silver nitrate staining of rainbow trouts (Oncorhynchus mykiss) chromosomes, for the identification of the nucleolar organizing regions (NORs), revealed that in individuals from Nucleo Experimental de Salmonicultura de Campos do Jordao (Brazil) NORs were located in the long arms of a submetacentric pair while in specimens from Mount Shasta (USA) NORs were located in the short arms of a submetacentric pair. Cytogenetic analysis of the offspring, obtained through artificial crosses including individuals from both stocks, allowed the identification of NORs in two submetacentric chromosomes, one in the short arms and the other in the long arms, confirming the effectiveness of the hybridization process. Complementary results obtained using the FISH technique with 18S and 5S rDNA probes showed that NOR-bearing chromosomes exhibited a cluster of 5S genes located in tandem with the 18S gene cluster in both stocks. The results allow us to suggest that the difference in NOR-bearing chromosomes found between the two stocks is likely to be due to a pericentric inversion involving the chromosome segment where 18S and 5S rDNA genes are located. The presence of ribosomal genes in the long arms of a submetacentric chromosome is apparently a particular characteristic of the rainbow trout stock of Campos do Jordao and might be used as a chromosome marker in studies of controlled crosses in this species

A calcium- and calpain-dependent pathway determines the response to lenalidomide in myelodysplastic syndromes

Despite the high response rates of individuals with myelodysplastic syndrome (MDS) with deletion of chromosome 5q (del(5q)) to treatment with lenalidomide (LEN) and the recent identification of cereblon (CRBN) as the molecular target of LEN, the cellular mechanism by which LEN eliminates MDS clones remains elusive. Here we performed an RNA interference screen to delineate gene regulatory networks that mediate LEN responsiveness in an MDS cell line, MDSL. We identified GPR68, which encodes a G-protein-coupled receptor that has been implicated in calcium metabolism, as the top candidate gene for modulating sensitivity to LEN. LEN induced GPR68 expression via IKAROS family zinc finger 1 (IKZF1), resulting in increased cytosolic calcium levels and activation of a calcium-dependent calpain, CAPN1, which were requisite steps for induction of apoptosis in MDS cells and in acute myeloid leukemia (AML) cells. In contrast, deletion of GPR68 or inhibition of calcium and calpain activation suppressed LEN-induced cytotoxicity. Moreover, expression of calpastatin (CAST), an endogenous CAPN1 inhibitor that is encoded by a gene (CAST) deleted in del(5q) MDS, correlated with LEN responsiveness in patients with del(5q) MDS. Depletion of CAST restored responsiveness of LEN-resistant non-del(5q) MDS cells and AML cells, providing an explanation for the superior responses of patients with del(5q) MDS to LEN treatment. Our study describes a cellular mechanism by which LEN, acting through CRBN and IKZF1, has cytotoxic effects in MDS and AML that depend on a calcium- and calpain-dependent pathway

Repetitive transcranial magnetic stimulation is as effective as fluoxetine in the treatment of depression in patients with Parkinson's disease

Methods: 42 patients were enrolled into two groups: group 1, active rTMS (15 Hz rTMS for 10 days) and placebo drug treatment; group 2, sham rTMS and fluoxetine 20 mg/day. A specially designed sham coil was used for sham stimulation. The unified Parkinson's disease rating scale (UPDRS), activities of daily living (ADL), Hamilton rating scale for depression (HRSD), Beck depression inventory (BDI), and mini-mental state examination (MMSE) were assessed by a rater blinded to treatment arm. Results: HRSD and BDI were improved to the same extent in both groups after two weeks of treatment (38% and 32% for group 1, 41% and 33% for group 2, respectively). At week 8 there was a tendency for worse motor UPDRS scores in group 2 (NS). ADL showed improvement at week 8 only in group 1. MMSE improved in both groups after treatment, but faster in group 1 than in group 2. There were fewer adverse effects in group 1 than in group 2. Conclusions: rTMS has the same antidepressant efficacy as fluoxetine and may have the additional advantage of some motor improvement and earlier cognitive improvement, with fewer adverse effects