Monitoring for multiple malformations in the detection of epidemics of birth defects

Although most known human teratogens often produce a combination of birth defects in an affected infant, surveillance programs aimed at detecting epidemics of birth defects usually only monitor rates of individual defects. A drawback to this approach is that an increase in the rate of infants affected with a specific combination of defects may lead to little or no increase in the rates of component defects. Using the Poisson distribution, we show that, compared with monitoring for individual defects, monitoring for combinations of two and three defects may require fewer numbers of births to detect an epidemic. In general, an increase can be detected more rapidly by monitoring the rates of defect combinations than by monitoring the rates of individual defects if most affected infants have combinations of defects rather than isolated defects. For example, in the case of Congenital rubella syndrome (CRS), monitoring for the combination of cataracts with deafness and/or patent ductus arteriosus could have led to earlier detection of an epidemic than could monitoring for cataracts alone. In contrast, in the case of thalidomide embryopathy, monitoring for reduction defects of upper limbs in combination with reduction defects of lower limbs and/or microtia/anotia would not have led to earlier detection of an epidemic than would monitoring for reduction defects of upper limbs alone. This is due mainly to the low frequency of defect combinations among affected cases. When used with regular monitoring for individual defects, surveillance of defect combinations can enhance the ability of monitoring programs to detect epidemics of birth defects.     

Comparative cradle to grave environmental life cycle assessment of traditional and extensive vegetative roofs: an application for the Lebanese context

The International Journal of Life Cycle Assessment - Vegetative roofs (VRs) are fully planted roof spaces that offer aesthetic view, storm water management, sound insulation, energy savings, and...     

Chaperonin 60: a paradoxical,evolutionarily conserved protein family with multiple moonlighting functions

Chaperonin 60 is the prototypic molecular chaperone, an essential protein in eukaryotes and prokaryotes, whose sequence conservation provides an excellent basis for phylogenetic analysis. Escherichia coli chaperonin 60 (GroEL), the prototype of this family of proteins, has an established oligomeric‐structure‐based folding mechanism and a defined population of folding partners. However, there is a growing number of examples of chaperonin 60 proteins whose crystal structures and oligomeric composition are at variance with GroEL, suggesting that additional complexities in the protein‐folding function of this protein should be expected. In addition, many organisms have multiple chaperonin 60 proteins, some of which have lost their protein‐folding ability. It is emerging that this highly conserved protein has evolved a bewildering variety of additional biological functions – known as moonlighting functions – both within the cell and in the extracellular milieu. Indeed, in some organisms, it is these moonlighting functions that have been left after the loss of the protein‐folding activity. This highlights the major paradox in the biology of chaperonin 60. This article reviews the relationship between the folding and non‐folding (moonlighting) activities of the chaperonin 60 family and discusses current knowledge on their molecular evolution focusing on protein domains involved in the non‐folding chaperonin functions in an attempt to understand the emerging biology of this evolutionarily ancient protein family.     

Isoaspartate Accumulation in Mouse Brain Is Associated with Altered Patterns of Protein Phosphorylation and Acetylation,Some of Which Are Highly Sex-Dependent

Isoaspartate (isoAsp) formation is a major source of protein damage that is kept in check by the repair function of protein L-isoaspartyl methyltransferase (PIMT). Mice deficient in PIMT accumulate isoAsp-containing proteins, resulting in cognitive deficits, abnormal neuronal physiology and cytoarchitecture, and fatal epileptic seizures 30–60 days after birth. Synapsins I and II, dynamin-1, collapsin response mediator protein 2 (CRMP2), and α/β-tubulin are major targets of PIMT in brain. To investigate links between isoAsp accumulation and the neurological phenotype of the KO mice, we used Western blotting to compare patterns of in vivo phosphorylation or acetylation of the major PIMT targets listed above. Phosphorylations of synapsins I and II at Ser-9 were increased in female KO vs. WT mice, and acetylation of tubulin at Lys-40 was decreased in male KO vs. WT mice. Average levels of dynamin-1 phosphorylation at Ser-778 and Ser-795 were higher in male KO vs. WT mice, but the statistical significance (P>0.1) was low. No changes in phosphorylation were found in synapsins I and II at Ser-603, in CRMP2 at Ser-522 or Thr-514, in DARPP-32 at Thr-34, or in PDK1 at Ser-241. General levels of phosphorylation assessed with Pro-Q Diamond stain, or an anti-phosphotyrosine antibody, appeared similar in the WT and KO mice. We conclude that isoAsp accumulation is associated with altered functional status of several neuronal proteins that are highly susceptible to this type of damage. We also uncovered unexpected differences in how male and female mice respond to isoAsp accumulation in the brain.     

The Role of Programmed Cell Death Ligand-1 (PD-L1/CD274) in the Development of Graft versus Host Disease

Programmed cell death ligand-1 (PD-L1/CD274) is an immunomodulatory molecule involved in cancer and complications of bone marrow transplantation, such as graft rejection and graft-versus-host disease. The present study was designed to assess the dynamic expression of this molecule after hematopoietic stem cell transplantation in relation to acute graft-versus-host disease. Female BALB/c mice were conditioned with busulfan and cyclophosphamide and transplanted with either syngeneic or allogeneic (male C57BL/6 mice) bone marrow and splenic cells. The expression of PD-L1 was evaluated at different time points employing qPCR, western blot and immunohistochemistry. Allogeneic- but not syngeneic-transplanted animals exhibited a marked up-regulation of PD-L1 expression in the muscle and kidney, but not the liver, at days 5 and 7 post transplantation. In mice transplanted with allogeneic bone marrow cells, the enhanced expression of PD-L1 was associated with high serum levels of IFNγ and TNFα at corresponding intervals. Our findings demonstrate that PD-L1 is differently induced and expressed after allogeneic transplantation than it is after syngeneic transplantation, and that it is in favor of target rather than non-target organs at the early stages of acute graft-versus-host disease. This is the first study to correlate the dynamics of PD-L1 at the gene-, protein- and activity levels with the early development of acute graft-versus-host disease. Our results suggest that the higher expression of PD-L1 in the muscle and kidney (non-target tissues) plays a protective role in skeletal muscle during acute graft-versus-host disease.     

Grazing in remnant wetland habitats in an arid region: direct and indirect effects on two specialist bird species

Capsule: Grazing by livestock can have complex effects on drivers of population change in the Clamorous Reed Warbler Acrocephalus stentoreus and Dead Sea Sparrow Passer moabiticus.

Aims: To investigate the effect on two specialist bird species on wetland degradation in the Jordan Valley.

Methods: The direct and indirect effects of grazing on the probability of occurrences of two specialist bird species, Clamorous Reed Warbler A. stentoreus and Dead Sea Sparrow P. moabiticus, were analysed during the breeding season at the patch scale, using path analysis.

Results: Tamarix shrub density was a strong predictor for the presence of both species. Grazing had a negative total effect on both; a significant indirect effect on Dead Sea Sparrow via its impact on the mean height of shrubs, and a significant, negative indirect effect on Clamorous Reed Warbler by reducing reed cover. Intensive grazing and browsing by livestock including goats, sheep and camels, apparently had a negative effect on the overall density of native Tamarix shrubs, while promoting encroachment by invasive Prosopis juliflora.

Conclusion: This may be part of a long-term cascade leading to an ecological transition and loss of important wetland habitats in the arid Jordan Valley.     

Habitat associations and communities of breeding birds in the highlands of south-west Jordan

Abstract

Habitat associations and communities of breeding birds were studied for the first time in a semi-arid region in the southern highlands of Jordan. Birds were censused and habitat variables estimated in different habitat types, ranging from steppe to open, Mediterranean-type woodland. The variation of abundance of several species was explained adequately with multiple regressions of up to five habitat variables. A distinct bird community was identified by using principal component analysis on the highland plateau (e.g. Short-toed Lark, Isabelline Wheatear), in steppe habitats modified by dry farming methods. The plateau was identified as a transition zone of Palaeoxeric/Turkestanian and Mediterranean faunal types. The remainding cluster included species of diverse origins (Palaearctic, Mediterranean, Saharo-Sindian, Afrotropical and others). It was subdivided into three bird assemblages with preferences for following habitat types: Mediterranean-type open woodlands (e.g. Syrian Serin), dwarf shrub formations of higher altitudes (e.g. Spectacled Warbler), dwarf shrub formations, including clearings and the edge of woodlands at lower altitudes (e.g. Scrub Warbler).