Repetitive conundrums of centromere structure and function

In the last few years, a paradox has emerged regarding the relationship of centromere structure and its function. Most centromeric DNAs analyzed to date are composed of a remarkably complex array of repeat structures. In contrast, recent analyses of neocentromeric DNA reveal that repetitive DNA is not a prerequisite for centromere activity. The ubiquity of repetitive sequences among diverse species at sites of primary constriction argues that there is a strong evolutionary link between centromere structure and function. Dynamic mutational processes resulting in amplification, deletion and transposition of repetitive sequences appear to occur frequently in such regions, resulting in considerable interspecific diversity in structure and sequence. One possible solution to this conundrum may be that the rapid accumulation of repetitive sequences within centromeric and pericentromeric DNA is a consequence of functionally active centromeres. Emerging repetitive structures at centromeric sites may be an important byproduct of a functional centromere which ensures that site as an evolutionarily favored position in subsequent meiotic and mitotic lineages. The recent identification of large gene duplications in the vicinity of centromeres may be another example of the enhanced mutational lability of such regions of the genome.      

Effects of inhaled corticosteroids and inhaled cromolyn sodium on urinary growth hormone excretion in asthmatic children

Over the past few years there has been an increasing awareness that asthma is a chronic inflammatory airways disease. The current therapeutic strategies for treating asthma focus on suppressing the inflammatory process by using cromones or inhaled corticosteroids (ICS). The beneficial effects of ICS in asthma are now well known, but its detrimental effect on linear growth remains a controversial issue. The aim of this open label, nonrandomized, cross-sectional, one-time study was to determine the influence of these drugs on urinary growth hormone (U-GH) levels in prepubertal asthmatic children. U-GH levels were measured in 47 prepubertal asthmatic children who had been treated for at least 6 months with either ICS (beclomethasone or budesonide at a mean daily dose of 360 μg) or with 80 mg daily dose of cromolyn sodium (CrS). There were also nine healthy children who served as a control. These three groups of children were matched for age and gender ratio. The mean level of U-GH in the CrS-treated group was 2.94 ± 0.96 ng/night; this was significantly higher compared to the mean level of the ICS-treated group (1.99 ± 0.83 ng/night; P < 0.001) and to the mean level of the control group (1.98 ± 0.39 ng/night; P < 0.006). There was no significant difference between the mean level of U-GH in the group treated by ICS and the controls (P < 0.9). These results show that the mean levels of U-GH secretion of the children who were treated by CrS for 6 months was significantly increased, compared to the mean U-GH level of the ICS-treated group and the controls. The mean U-GH levels in the last two groups showed no statistically significant difference. Pediatr Pulmonol. 1998; 26:339–343. © 1998 Wiley-Liss, Inc.     

Socio—cultural factors influencing insecticide treated bed net utilization in a malaria endemic city in north—central Nigeria

ObjectiveTo ascertain the socio-cultural factors influencing the rate of utilization of insecticide treated bed nets (ITNs) in a malaria endemic city of Makurdi, north central Nigeria.MethodsThe study was cross-sectional in nature using systematic sampling method to identify households. Both quantitative and qualitative data was generated from adult women using structured and semi structured questionnaires, and focused group discussions (FGDs) to obtain information on rate and patterns of utilization of ITNs. Information such as age, educational level, marital status, awareness or otherwise of the existence of malaria, and factors influencing rate of ownership and utilization of ITNs were obtained. FGDs were used to obtain qualitative information on rate of utilization of ITNs not captured in the questionnaires. Data obtained was analysed using Epi Info 6 statistical software.ResultsAmong the respondents interviewed, 97.0% (2 013/2 075) were aware of existence of malaria and 87.0% of these (1 751/2 013) would associate it with mosquitoes. The rate of ownership of any bed net, ITNs and untreated bed nets (UTNs) was 25.1%, 17.0% and 8.3%, respectively. Utilization of ITNs among children was 30.0% (112/373) and UTNs 12.9% (48/373). Positive contributors to ITNs utilization were literacy, enhanced economy, experience of marriage, and being gainfully employed (P<0.05); while negative contributors were ignorance, poverty and some cultural beliefs and values.ConclusionsA more synchronized advocacy should be carried out on the potential benefits of ITNs utilization and sustained. Also ITNs should be made available to the people of the community at minimal or no cost.     

A study of anemia in women with asymptomatic malaria parasitaemia at their first antenatal care visit at the General Hospital,Ikot Ekpene,Akwa Ibom State,Nigeria

ObjectiveTo assess the prevalence of anemia and asymptomatia malaria parasitemia and the effect of prior antimalarials therapy on the parasite density in pregnant women at their first antenatal visit at the secondary level health care facility in Nigeria.MethodsThis cross sectional observational study was carried out in the antenatal clinic of General Hospital, Ikot Ekpene, Akwa Ibom State, Nigeria for 3 months period (1^st June to 31^st August, 2009). Five hundred and fourteen women attending their first antenatal registration visits in the hospital were recruited in the study. Socio-demographic information was obtained using pre-tested questionnaires. The malaria parasite was obtained by examining thick and thin blood films prepared on 2 glass slides while the hematocrit was obtained through 2 capillary tubes read by a Hawksleys microhematocrit reader.ResultsA total of 514 pregnant women participated in the study with a mean maternal age of 21.4 years and a mean gestational age at booking of 18.3 weeks. The primigravid women booked at significantly lower gestational age than multigravidae (16.2 weeks vs 21.6 weeks). Most of the women (59.3%) were anemic, out of which 60.4% were primigravida. More than half of the women had moderate to high parasite density and only 6.8% had no malaria parasitemia. All patients with severe anemia were parasitemic. Out of the 479 (93.2%) women with parasitemia, a third had taken antimalarial drugs. A majority (60.3%) of those without prior antimalarial drugs had moderate to high density parasitemia.ConclusionsThis study shows high prevalence of anemia in women with asymptomatic malarial parasitemia, particularly the primigravida. The severity of anemia is directly related to the density of malaria parasitemia. Those with effective antimalarial therapy appear to have low density parasitemia and therefore mild anemia. Routine screening for anemia and malaria parasites at booking, prompt parasite clearance and correction of anemia would reduce the associated maternal and perinatal complications.     

Objective and subjective evaluation of adaptive speech enhancement methods for functional MRI

Purpose:

To recover speech corrupted by functional magnetic resonance imaging (fMRI) acoustic noise using two‐channel adaptive speech enhancement techniques.

Materials and Methods:

Speech corrupted by noise generated from a 3 T MRI scanner was recorded using diffuse‐field microphones and a data acquisition board. Multiband and subband adaptive speech enhancement methods are used to recover the speech signal from the recordings. Normalized least mean squares (NLMS) algorithm was used for updating the filter coefficients in each band.

Results:

The methods are successful in enhancing the speech quality. They are successful in improving the convergence rate of the adaptive filter. Multiband and subband methods have a similar performance in terms of noise reduction and in the subjective tests. The subband method introduces less speech distortion compared to the multiband method. The subband method requires a lower number of computations per sample.

Conclusion:

Adaptive speech enhancement techniques are effective in reducing fMRI background noise in the recordings. Based on the analysis, we conclude that subband‐based methods are more suited for enhancing speech corrupted by fMRI noise. J. Magn. Reson. Imaging 2010;31:46–55. © 2009 Wiley‐Liss, Inc.     

Severe combined immunodeficiency (SCID): From the detection of a new mutation to preimplantation genetic diagnosis

Purpose

To describe the identification of a new mutation responsible for causing human severe combined immunodeficiency syndrome (SCID). In a large consanguineous Israeli Arab family, this served as a diagnostic tool and enabled us to carry out preimplantation genetic diagnosis (PGD). We also demonstrated that PGD for homozygosity alleles is feasible.

Methods

We carried out genome-wide screening followed by fine mapping and linkage analysis in order to identify the candidate genes. We then sequenced DCLRE1C in order to find the familial mutation. The family was anxious to avoid the birth of an affected child, and therefore, because of their religious beliefs, PGD was the only option open to them. The embryos were biopsied at day 3, and a single blastomere from each embryo was analyzed by multiplex polymerase chain reaction for the SCID mutation and 5 additional polymorphic markers flanking DCLRE1C.

Results

Linkage analysis revealed linkage to chromosome 10p13, which harbors the DNA Cross-Link Repair Protein 1 C (DCLRE1C) ARTEMIS gene. Sequencing identified an 8 bp insertion in exon 14 (1306ins8) of DCLRE1C in all the affected patients; this causes an alteration in amino acid 330 of the protein from cysteine to a stop codon (p.C330X). One cycle of PGD was performed and two embryos were transferred, one homozygous wild-type and one a heterozygous carrier, and healthy twins were born.

Conclusions

Identifying the familial mutation enabled us to design a reliable and accurate PGD protocol, even in this case of a consanguineous family.