Robertsonian rearrangements in Neotropical Meliponini karyotype evolution (Hymenoptera: Apidae: Meliponini).

Genome changes, evidenced through karyotype or nuclear genome size data, can result in reproductive isolation, diversification and speciation. The aim of this study was to understand how changes in the karyotype such as chromosome number and nuclear genome size accompanied the evolution of neotropical stingless bees, and to discuss these data in a phylogenetic context focusing on the karyotype evolution of this clade. We sampled 38 species representing the three Neotropical Meliponini groups; 35 for karyotype analyses and 16 for 1C value measurement. The chromosome number varied from 2n = 16 to 2n = 34, with distinct karyotypic formulae and the presence of a few polymorphisms, such as B chromosomes in one species and arm size differences between homologous chromosomes in two species. The mean 1C value varied from 0.31 pg to 0.92 pg. We associated empirical data on chromosome number and mean 1C value to highlight the importance of Robertsonian fusion rearrangements, leading to a decrease in chromosome number during the Neotropical Meliponini evolution. These data also allowed us to infer the independent heterochromatin amplification in several genera. Although less frequent, Melipona species with 2n = 22 represent evidence of Robertsonian fissions. We also pointed out the importance of chromosomal rearrangements that did not alter chromosome number, such as inversions and heterochromatin amplification.

Evolutionary insights into the genomic organization of major ribosomal DNA in ant chromosomes.

The major rDNA genes are composed of tandem repeats and are part of the nucleolus organizing regions (NORs). They are highly conserved and therefore useful in understanding the evolutionary patterns of chromosomal locations. The evolutionary dynamics of the karyotype may affect the organization of rDNA genes within chromosomes. In this study, we physically mapped 18S rDNA genes in 13 Neotropical ant species from four subfamilies using fluorescence in situ hybridization. Furthermore, a survey of published rDNA cytogenetic data for 50 additional species was performed, which allowed us to detect the evolutionary patterns of these genes in ant chromosomes. Species from the Neotropical, Palearctic, and Australian regions, comprising a total of 63 species from 19 genera within six subfamilies, were analysed. Most of the species (48 out of 63) had rDNA genes restricted to a single chromosome pair in their intrachromosomal regions. The position of rDNA genes within the chromosomes appears to hinder their dispersal throughout the genome, as translocations and ectopic recombination are uncommon in intrachromosomal regions because they can generate meiotic abnormalities. Therefore, rDNA genes restricted to a single chromosome pair seem to be a plesiomorphic feature in ants, while multiple rDNA sites, observed in distinct subfamilies, may have independent origins in different genera.

Characterisation of peripheral and central components of the rat monoiodoacetate model of Osteoarthritis.

OBJECTIVE: Pain is the main reason patients report Osteoarthritis (OA), yet current analgesics remain relatively ineffective. This study investigated both peripheral and central mechanisms that lead to the development of OA associated chronic pain. DESIGN: The monoiodoacetate (MIA) model of OA was investigated at early (2-6 days post injection) and late (>14 days post injection) time points. Pain-like behaviour and knee histology were assessed to understand the extent of pain due to cartilage degradation. Electrophysiological single-unit recordings were taken from spinal wide dynamic range (WDR) neurons to investigate Diffuse Noxious Inhibitory Controls (DNIC) as a marker of potential changes in descending controls. Immunohistochemistry was performed on dorsal root ganglion (DRG) neurons to assess any MIA induced neuronal damage. Furthermore, qPCR was used to measure levels of glia cells and cytokines in the dorsal horn. RESULTS: Both MIA groups develop pain-like behaviour but only late phase (LP) animals display extensive cartilage degradation. Early phase animals have a normally functioning DNIC system but there is a loss of DNIC in LP animals. We found no evidence for neuronal damage caused by MIA in either group, yet an increase in IL-1ß mRNA in the dorsal horn of LP animals. CONCLUSION: The loss of DNIC in LP MIA animals suggests an imbalance in inhibitory and facilitatory descending controls, and a rise in the mRNA expression of IL-1ß mRNA suggest the development of central sensitisation. Therefore, the pain associated with OA in LP animals may not be attributed to purely peripheral mechanisms.

Cri du Chat syndrome: Characteristics of 73 Brazilian patients.

BACKGROUND: Cri du Chat syndrome (CdCS) is a genetic syndrome caused by deletions in the short arm of chromosome 5. Although the main clinical features of CdCS are well known, the neurocognitive and behavioural characteristics of the phenotype are rarely described in detail in the literature. In this study, we analysed the main phenotypic features of CdCS from a parental perspective. METHOD: A questionnaire was sent to 700 Brazilian families that were registered in the Brazilian Association of CdCS. The questions involved specific domains of CdCS, such as pregnancy and birth conditions, recurrence of the disease in the family, current major health problems, and aspects of cognitive development. RESULTS: In total, 73 questionnaires were completed: 44 females and 29 males, ranging from 9.5 months old to 40 years old (mean = 13.8 years; median = 12 years). Most of the parents noticed the typical cat-like cry at birth (94.4%). The age at diagnosis of CdCS ranged from the time of birth to 180 months (mean = 14 months; median = 6 months), while one case was diagnosed during pregnancy. In all of the cases, the diagnosis of CdCS was made by G-banding karyotype analysis. In 66.2% of the cases, the parents underwent cytogenetic investigation. A total of 52.1% of the parents answered that they did not remember what the recurrence risk of CdCS was in their family. The main health problems that were reported were as follows: swallowing problems (80.3%), feeding problems (80.3%), congenital heart disease (31.5%), spine abnormalities (28.8%), and neurological symptoms (20.5%), including seizures (11%). The behavioural problems that were reported were as follows: aggressive behaviour, stereotypies, anxiety, phobias, and genital manipulation/masturbation. Neurodevelopmental delay was reported in all of the cases. Independent walking was achieved in 72.2% of the patients. Approximately 50% of the patients never presented expressive language, and most of the patients are dependent on others for their daily activities. CONCLUSIONS: The questionnaire was a pioneer initiative in the CdCS support group, and the answers used in this study can improve the health care assistance to these patients because they focus attention on the demands from a parental perspective. In addition, nearly half of the families stated that they did not remember information regarding recurrence risk, which reinforces the importance of genetic counselling follow-up and the need for the expansion of genetic services in Brazil.

Efficacy of auditory training using the auditory brainstem response to complex sounds: auditory processing disorder and specific language impairment.

OBJECTIVES: This study verified the efficacy of a formal auditory training (AT) program in children with hearing and language disorders using the auditory brainstem response to complex sounds (c-ABR) with and without background noise. PATIENTS AND METHODS: Thirty children (7-13 years) were distributed into four groups: typical development (TD: n = 7), auditory processing disorder (APD: n = 9) and specific language disorder (SLIa: n = 6, and SLIb: n = 8). All children underwent behavioral assessment of auditory processing and c-ABR with and without background noise. The APD and SLIa groups underwent 8 weeks of formal AT, but all children were reevaluated 12 weeks after the initial assessment. RESULTS: The TD group presented better behavioral performance than the other groups. For c-ABR in silence, no significant differences were observed among groups or assessments, except regarding VA complex measures, which were altered in the APD group. For c-ABR with background noise, however, the APD, SLIa and SLIb groups presented delayed latencies. Groups that underwent formal AT improved behavioral performance and decreased latencies to c-ABR in background noise at final assessment. CONCLUSIONS: These data suggest that efficacy of formal AT can be demonstrated by c-ABR with background noise.

Microbubble stability is a major determinant of the efficiency of ultrasound and microbubble mediated in vivo gene transfer.

In the search for an efficient nonviral gene therapy approach for the treatment of genetic disorders of cardiac and skeletal muscle such as Duchenne muscular dystrophy, ultrasound in combination with contrast enhancing microbubbles has emerged as a promising tool for safe and site-specific enhancement of gene delivery. Indeed, microbubble-enhanced gene transfer (MBGT) has been investigated for a wide variety of target sites using both reporter and therapeutic genes. Although a range of different microbubbles have been used for MBGT studies, comparison of their efficiencies is difficult because microbubble concentration and the ultrasound settings used for the application vary considerably. Only two studies to date have attempted a direct comparison of commercially available microbubbles, and both concluded that not all microbubbles show the same efficiencies with MBGT. Thus far, the reason for this is unclear. Here, the efficiency of three commercially available microbubbles--Optison, SonoVue and Sonazoid--was analyzed to understand the microbubble properties that are important for their function as an effective enhancer for gene transfer in vivo. In this study, plasmid DNA or antisense oligonucleotides were delivered by systemic injection with MBGT, focused on the heart. Gene delivery to the heart with equalized concentrations of the three microbubbles showed that Optison and Sonazoid are more efficient in MBGT compared with SonoVue, which showed the weakest gene transfer to the myocardium. Investigations into the properties of these microbubbles showed that size and shell composition did not directly influence MBGT, whereas the microbubbles with increased stability in an ultrasound field showed better MBGT results than those degrading faster. Moreover, the microbubble concentration used for MBGT was also found to be an important factor influencing the efficiency of MBGT. In conclusion, the stability of a microbubble was shown to be a major influential factor for its performance in MBGT, as is the concentration of the microbubbles used. These findings emphasize the importance of detailed investigations into the properties of microbubbles to allow the production of a microbubble specifically designed for optimum performance with MBGT.

Common variations in the pretest environment influence genotypic comparisons in models of anxiety.

The behavioral characterization of rodent strains in different studies and laboratories can provide unreplicable results even when genotypes are kept constant and environmental control is maximized. In the present study, the influence of common laboratory environmental variables and their interaction with genotype on the results of behavioral tests of anxiety/emotionality were investigated. To this end, the inbred rat strains Lewis (LEW) and spontaneously hypertensive rats (SHR), which are known to differ for numerous emotionality-related behaviors, were tested in the open field (OF), elevated plus maze (EPM) and black/white box (BWB), while three environmental factors were systematically controlled and analyzed: (1) the experimenter handling the animal (familiar or unfamiliar); (2) the position of the home cage (top or bottom shelf of the rack) and (3) the behavioral state of the animal immediately before the test (arousal or rest). Experimenter familiarity did not alter the behavior of rats in the OF. Cage position, on the other hand, influenced the behavior in the OF and BWB, with rats housed in top cages appearing less anxious than those housed in the bottom. In the BWB (but not in the OF), these effects were genotype dependent. Finally, the behavioral state of the animals prior to testing altered the results of the EPM in a strain-dependent manner, with some anxiety-related genotypic differences being found only among rats that were aroused in their home cages. This study showed that common variations in the laboratory environment interact with genotype in behavioral tests of anxiety/emotionality. Recognizing and understanding such variations can help in the design of more effective experiments.

Pair housing affects anxiety-like behaviors induced by a social but not by a physiological stressor in male Swiss mice.

The role of pair housing in the modulation of anxiety-like behaviour in socially and physiologically stressed mice was investigated. The protocol of psychosocial stress consisted of submitting male adult mice to daily social confrontation with a male conspecific for a period of thirteen days. In an attempt to study a possible effect of pair housing as a social support, each male mouse was housed with a female throughout the period of experimentation, except during the agonistic interactions. As a physiological stressor, 10(9) sheep red blood cells (SRBC)/ml were injected intraperitoneally on the 1st and 7th days of the experiments. The respective control groups were as follows: non-socially stressed, non-pair housed and saline-injected mice. The humoral immune response was analysed by haemagglutination assay. The level of anxiety-like behaviours was measured in the elevated plus-maze test on the 13th day of the experiment. As a result, no significant changes in humoral immunity to SRBC were observed in mice subjected to social confrontation in a neutral arena as compared to non-socially stressed mice. As a consequence, no effect of pair housing on humoral immunity to SRBC could be evaluated. Concerning the effects of pair housing on the anxiety-like behaviours, it was possible to demonstrate that the pair housing proved to be effective in modulating anxiety-like behaviour, although in the stressed groups the percentage of time in the open arms and the time in risk assessment did not change in a symmetrical opposite form, as expected. The physiological stressor induced an anxiety-like behaviour that was not reversed by the pair housed condition. This suggests that different types of stressors activate different neural and peripheral pathways, which may or may not be modulated by pair housing, a finding that deserves our attention as a way to better understand the mechanisms that influence adaptations to stress.

Relação entre as habilidades fonológicas e pragmáticas nos distúrbios específicos de linguagem / Relation between phonologic and pragmatic habilities in specific language impairment

BACKGROUND: Specific language impairment. AIM: To establish relations between the performance of subjects in phonologic and pragmatic tests. METHOD: Tabulation and analyses of the data of phonologic and pragmatic tests of 20 children with ages raging from 3:0 to 5:11 years, with the diagnoses of Specific Language Impairment (SLI). RESULTS: The statistic analyses showed good correlations between developmental processes (DP) and non-developmental processes (NDP), DP and the use of verbal mean, vocal mean and number of communication acts per minute. CONCLUSION: The performance in the phonological and pragmatic tests does not seem to have a direct correlation in subjects with specific language impairment.

Tema: distúrbios específicos de linguagem. Objetivo: estabelecer relações a partir do desempenho dos sujeitos nas provas de pragmática e fonologia. Método: tabulação eanálise dos dados das provas de fonologia e pragmática de 20 crianças, com idade entre 3:00 e 5:11 anos, com diagnóstico de Distúrbio Especifico de Linguagem (DEL). Resultados:a análise estatística mostrou correlações boas e regulares entre processos de desenvolvimento (PD) e processos de não desenvolvimento (PnD), PD e meio verbal, meiovocal e atos por minuto. Conclusão: o desempenho nas provas de fonologia e pragmática parece não apresentar correlação estritamente direta nos sujeitos com DEL.

Use of recombinant granulocyte-macrophage colony stimulating factor in the Brazil radiation accident.

8 patients with bone marrow failure after a caesium-137 radiation accident were treated with recombinant human granulocyte-macrophage colony stimulating factor (rHuGM-CSF). The 7 who were evaluable had prompt increases in granulocytes and bone marrow cellularity. 2 patients died of radiation toxicity and haemorrhage and 2 of bacterial sepsis acquired before the start of rHuGM-CSF treatment. 4 patients survive, including 2 who were treated early and never became infected. This therapeutic approach to radiation-induced granulocytopenia may therefore be useful after radiation and nuclear accidents.