Street working children in lima: The child's ‘Surcharge’ between survival strategies and socialisation

Child labour is usually analysed within the framework of exploitation. This essay is an attempt to analyse children's economic activities in the street using the concept ‘surcharge”, which may be defined as a child's negative experience of overload or over work. In the comparison between dissatisfactory and satisfactory working conditions, it has been argued that the first is linked not only to a lack of protection, but also to a lack of autonomy and recognition. Analyses include examinations of extreme conditions, different representations of the family, childhood and labour, as too women's roles. Such dimensions are considered essential for the comprehension of children's experience, since they are often surcharged due to the lack of economic resources, the unequal division of labour within the family and contradictory practices found in the research population. Examples of those difficulties draw on children and families' experiences of compulsory and ‘free’ education. The author concludes the need for better knowledge of socialisation processes and children's experience of work that should ideally integrate into the theoretical framework of exploitation.     

Air trapping on chest CT is associated with worse ventilation distribution in infants with cystic fibrosis diagnosed following newborn screening

Background

In school-aged children with cystic fibrosis (CF) structural lung damage assessed using chest CT is associated with abnormal ventilation distribution. The primary objective of this analysis was to determine the relationships between ventilation distribution outcomes and the presence and extent of structural damage as assessed by chest CT in infants and young children with CF.

Methods

Data of infants and young children with CF diagnosed following newborn screening consecutively reviewed between August 2005 and December 2009 were analysed. Ventilation distribution (lung clearance index and the first and second moment ratios [LCI, M₁/M₀ and M₂/M₀, respectively]), chest CT and airway pathology from bronchoalveolar lavage were determined at diagnosis and then annually. The chest CT scans were evaluated for the presence or absence of bronchiectasis and air trapping.

Results

Matched lung function, chest CT and pathology outcomes were available in 49 infants (31 male) with bronchiectasis and air trapping present in 13 (27%) and 24 (49%) infants, respectively. The presence of bronchiectasis or air trapping was associated with increased M₂/M₀ but not LCI or M₁/M₀. There was a weak, but statistically significant association between the extent of air trapping and all ventilation distribution outcomes.

Conclusion

These findings suggest that in early CF lung disease there are weak associations between ventilation distribution and lung damage from chest CT. These finding are in contrast to those reported in older children. These findings suggest that assessments of LCI could not be used to replace a chest CT scan for the assessment of structural lung disease in the first two years of life. Further research in which both MBW and chest CT outcomes are obtained is required to assess the role of ventilation distribution in tracking the progression of lung damage in infants with CF.     

Microbial modification of host long-distance dispersal capacity

Background  

Dispersal plays a key role in shaping biological and ecological processes such as the distribution of spatially-structured populations or the pace and scale of invasion. Here we have studied the relationship between long-distance dispersal behaviour of a pest-controlling money spider,Erigone atra, and the distribution of maternally acquired endosymbionts within the wider meta-population. This spider persists in heterogeneous environments because of its ability to recolonise areas through active long-distance airborne dispersal using silk as a sail, in a process termed 'ballooning'.     

Gradient of distribution in Europe of the major CF mutation and of its associated haplotype

Summary In this collaborative European study, a total of 4871 cystic fibrosis (CF) chromosomes and 3539 normal chromosomes have been characterized for the haplotypes defined by the 2 extragenic polymorphic sequences revealed by XV2c and KM19. The association between one of these haplotypes (B haplotype) and the most frequent CF mutation, ΔF508, suggests for the latter a single origin and a subsequent diffusion according to a South East-North West gradient. The linkage disequilibrium data between CF and the B haplotype in different European populations are compatible with a relatively more recent appearance of the mutation in Northern Europe whereas in Southern Europe a longer history of the same mutation would have allowed time for recombination with other haplotypes. This model is also compatible with a selective advantage of carriers but does not account for (1) the excess of B haplotypes observed among both normal and non-ΔF508 CF chromosomes; (2) the correlation between the B haplotype and the severity of the phenotypic effect caused by CF mutations, as measured by pancreatic insufficiency and meconium ileus.     

The Relationship between Aggregation and Toxicity of Polyglutamine-Containing Ataxin-3 in the Intracellular Environment of Escherichia coli

Several neurodegenerative diseases are triggered by proteins containing a polyglutamine (polyQ) stretch expanded beyond a critical threshold. Among these, ataxin-3 (AT3) is the causative agent of spinocerebellar ataxia type-3. We expressed three authentic AT3 variants in Escherichia coli: one normal (AT3-Q24), one expanded (AT3-Q55) and one truncated immediately upstream of the polyQ (AT3-291Δ). Then, based on growth rate reduction, we quantified protein toxicity. We show that AT3-Q55 and -291Δ strongly reduced the growth rate in the early stages (2–4 h), unlike AT3-Q24. This correlated well with the appearance of soluble cytosolic oligomers, but not with the amount of insoluble protein in inclusion bodies (IBs). The impact of AT3-291Δ on cell growth suggests an intrinsic toxicity of the AT3 fragment. Besides the typical Fourier Transform Infrared Spectroscopy (FTIR) signal for intermolecular β-sheets, the expanded form displayed an additional infrared signature, which was assigned to glutamine side-chain hydrogen bonding and associated with SDS-insoluble fibrils. The elongation of the latter was monitored by Atomic Force Microscopy (AFM). This mirrors the well-known in vitro two-step aggregation pattern of expanded AT3. We also demonstrated that final aggregates of strains expressing expanded or truncated AT3 play a protective role against toxicity. Furthermore, our findings suggest that the mechanisms of toxicity are evolutionarily conserved.     

Clinical and molecular findings in children with complex I deficiency

Isolated complex I deficiency, the most frequent OXPHOS disorder in infants and children, is genetically heterogeneous. Mutations have been found in seven mitochondrial DNA (mtDNA) and eight nuclear DNA encoded subunits, respectively, but in most of the cases the genetic basis of the biochemical defect is unknown. We analyzed the entire mtDNA and 11 nuclear encoded complex I subunits in 23 isolated complex I-deficient children, classified into five clinical groups: Leigh syndrome, progressive leukoencephalopathy, neonatal cardiomyopathy, severe infantile lactic acidosis, and a miscellaneous group of unspecified encephalomyopathies. A genetic definition was reached in eight patients (35%). Mutations in mtDNA were found in six out of eight children with Leigh syndrome, indicating a prevalent association between this phenotype and abnormalities in ND genes. In two patients with leukoencephalopathy, homozygous mutations were detected in two different nuclear-encoded complex I genes, including a novel transition in NDUFS1 subunit. In addition to these, a child affected by mitochondrial encephalomyopathy had heterozygous mutations in NDUFA8 and NDUFS2 genes, while another child with neonatal cardiomyopathy had a complex rearrangement in a single NDUFS7 allele. The latter cases suggest the possibility of unconventional patterns of inheritance in complex I defects.     

Inhibition of L- and P-selectin by a rationally synthesized novel core 2-like branched structure containing GalNAc-Lewisx and Neu5Acalpha2- 3Galbeta1-3GalNAc sequences

The selectins interact in important normal and pathological situations with certain sialylated, fucosylated glycoconjugate ligands containing sialyl Lewisx(Neu5Acalpha2-3Galbeta1-4(Fucalpha1-3)GlcN Ac). Much effort has gone into the synthesis of sialylated and sulfated Lewisxanalogs as competitive ligands for the selectins. Since the natural selectin ligands GlyCAM-1 and PSGL-1 carry sialyl Lewisxas part of a branched Core 2 O-linked structure, we recently synthesized Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-6(SE-3Galbeta1++ +-3)GalNAc1alphaOMe and found it to be a moderately superior ligand for L and P-selectin (Koenig et al. , Glycobiology 7, 79-93, 1997). Other studies have shown that sulfate esters can replace sialic acid in some selectin ligands (Yeun et al. , Biochemistry, 31, 9126-9131, 1992; Imai et al. , Nature, 361, 555, 1993). Based upon these observations, we hypothesized that Neu5Acalpha2-3Galbeta1-3GalNAc might have the capability of interacting with L- and P-selectin. To examine this hypothesis, we synthesized Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-6(Neu5Acalpha2++ +-3Galbeta1-3)- GalNAc alpha1-OB, which was found to be 2- to 3-fold better than sialyl Lexfor P and L selectin, respectively. We also report the synthesis of an unusual structure GalNAcbeta1-4(Fucalpha1- 3)GlcNAcbeta1-OMe (GalNAc- Lewisx-O-methyl glycoside), which also proved to be a better inhibitor of L- and P-selectin than sialyl Lewisx-OMe. Combining this with our knowledge of Core 2 branched structures, we have synthesized a molecule that is 5- to 6-fold better at inhibiting L- and P-selectin than sialyl Lewisx-OMe, By contrast to unbranched structures, substitution of a sulfate ester group for a sialic acid residue in such a molecule resulted in a considerable loss of inhibition ability. Thus, the combination of a sialic acid residue on the primary (beta1-3) arm, and a modified Lexunit on the branched (beta1-6) arm on an O-linked Core 2 structure generated a monovalent synthetic oliogosaccharide inhibitor superior to SLexfor both L- and P-selectin.      

In vivo aggregation of bovine beta-lactoglobulin is affected by Cys at position 121

Bovine beta-lactoglobulin (BLG) has been widely used as a model system to study protein folding and aggregation and for biotechnology applications. Native BLG contains two disulfide bonds and one free cysteine at position 121. This free thiol group has been shown to be responsible for the irreversibility of BLG denaturation in vitro, but nothing is known about its relevance during protein folding inside the cell. Here, we report the expression of soluble wild type recombinant BGL in Escherichia coli cells at about 109 mg rBLG/g wet weight cells and a comparison between the aggregation of wt BLG and its variant C121S upon intracellular expression. We show that in E. coli C121SBLG is more prone to aggregation than the wild type protein and that their different behavior depends on the oxidation of disulfide bonds. Our results underline the key contribution of the unpaired cysteine residue during the oxidative folding pathway and indicate BLG as a useful tool for the study of protein aggregation in vivo.     

Stimulation of 5-hydroxytryptamine (5-HT(2C) ) receptors in the ventrotegmental area inhibits stress-induced but not basal dopamine release in the rat prefrontal cortex

The present study investigated whether 5-HT(2C) receptors in the ventrotegmental area and prefrontal cortex regulate basal and stimulus-evoked dopamine release in the prefrontal cortex. Using the in vivo microdialysis technique in conscious rats, we studied the effect of a selective 5-HT(2C) receptor agonist, Ro60-0175, on basal and immobilization stress-induced dopamine release in the prefrontal cortex. Ro60-0175 intraperitoneally (2.5 mg/kg) and into the ventrotegmental area (10 microg/0.5 microL) completely antagonized the effect of stress on extracellular dopamine without altering basal levels. Infusion of 10 microm Ro60-0175 through the cortical probe had no significant effect on basal and stress-induced dopamine release. SB242084 (10 mg/kg), a selective antagonist of 5-HT(2C) receptors, significantly increased basal extracellular dopamine and completely prevented the effect of intraperitoneal and intraventrotegmental Ro60-0175 on the stress-induced rise of extracellular dopamine, but had no effect itself in stressed rats. The results show that Ro60-0175 suppresses cortical dopamine release induced by immobilization stress through the stimulation of 5-HT(2C) receptors in the ventrotegmental area. While confirming that endogenous 5-HT acting on 5-HT(2C) receptors tonically inhibit basal dopamine release in the prefrontal cortex, the present findings suggest that the stimulation of 5-HT(2C) receptors with an exogenous agonist preferentially inhibit stimulated release.