Spatial distribution of early red lesions is a risk factor for development of vision-threatening diabetic retinopathy

Aims/hypothesis Diabetic retinopathy is characterised by morphological lesions related to disturbances in retinal blood flow. It has previously been shown that the early development of retinal lesions temporal to the fovea may predict the development of treatment-requiring diabetic maculopathy. The aim of this study was to map accurately the area where lesions could predict progression to vision-threatening retinopathy. Methods The predictive value of the location of the earliest red lesions representing haemorrhages and/or microaneurysms was studied by comparing their occurrence in a group of individuals later developing vision-threatening diabetic retinopathy with that in a group matched with respect to diabetes type, age, sex and age of onset of diabetes mellitus who did not develop vision-threatening diabetic retinopathy during a similar observation period. Results The probability of progression to vision-threatening diabetic retinopathy was higher in a circular area temporal to the fovea, and the occurrence of the first lesions in this area was predictive of the development of vision-threatening diabetic retinopathy. The calculated peak value showed that the risk of progression was 39.5% higher than the average. There was no significant difference in the early distribution of lesions in participants later developing diabetic maculopathy or proliferative diabetic retinopathy. Conclusions/interpretation The location of early red lesions in diabetic retinopathy is predictive of whether or not individuals will later develop vision-threatening diabetic retinopathy. This evidence should be incorporated into risk models used to recommend control intervals in screening programmes for diabetic retinopathy

The effects of weather and climate change on dengue

There is much uncertainty about the future impact of climate change on vector-borne diseases. Such uncertainty reflects the difficulties in modelling the complex interactions between disease, climatic and socioeconomic determinants. We used a comprehensive panel dataset from Mexico covering 23 years of province-specific dengue reports across nine climatic regions to estimate the impact of weather on dengue, accounting for the effects of non-climatic factors

The Ecm11-Gmc2 complex promotes synaptonemal complex formation through assembly of transverse filaments in budding yeast

During meiosis, homologous chromosomes pair at close proximity to form the synaptonemal complex (SC). This association is mediated by transverse filament proteins that hold the axes of homologous chromosomes together along their entire length. Transverse filament proteins are highly aggregative and can form an aberrant aggregate called the polycomplex that is unassociated with chromosomes. Here, we show that the Ecm11-Gmc2 complex is a novel SC component, functioning to facilitate assembly of the yeast transverse filament protein, Zip1. Ecm11 and Gmc2 initially localize to the synapsis initiation sites, then throughout the synapsed regions of paired homologous chromosomes. The absence of either Ecm11 or Gmc2 substantially compromises the chromosomal assembly of Zip1 as well as polycomplex formation, indicating that the complex is required for extensive Zip1 polymerization. We also show that Ecm11 is SUMOylated in a Gmc2-dependent manner. Remarkably, in the unSUMOylatable ecm11 mutant, assembly of chromosomal Zip1 remained compromised while polycomplex formation became frequent. We propose that the Ecm11-Gmc2 complex facilitates the assembly of Zip1 and that SUMOylation of Ecm11 is critical for ensuring chromosomal assembly of Zip1, thus suppressing polycomplex formation

Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic divisions

During meiosis, Structural Maintenance of Chromosome (SMC) complexes underpin two fundamental features of meiosis: homologous recombination and chromosome segregation. While meiotic functions of the cohesin and condensin complexes have been delineated, the role of the third SMC complex, Smc5/6, remains enigmatic. Here we identify specific, essential meiotic functions for the Smc5/6 complex in homologous recombination and the regulation of cohesin. We show that Smc5/6 is enriched at centromeres and cohesin-association sites where it regulates sister-chromatid cohesion and the timely removal of cohesin from chromosomal arms, respectively. Smc5/6 also localizes to recombination hotspots, where it promotes normal formation and resolution of a subset of joint-molecule intermediates. In this regard, Smc5/6 functions independently of the major crossover pathway defined by the MutLγ complex. Furthermore, we show that Smc5/6 is required for stable chromosomal localization of the XPF-family endonuclease, Mus81-Mms4Eme1. Our data suggest that the Smc5/6 complex is required for specific recombination and chromosomal processes throughout meiosis and that in its absence, attempts at cell division with unresolved joint molecules and residual cohesin lead to severe recombination-induced meiotic catastroph

Mass Mortality of Adult Male Subantarctic Fur Seals: Are Alien Mice the Culprits?

Background: Mass mortalities of marine mammals due to infectious agents are increasingly reported. However, in contrast to previous die-offs, which were indiscriminate with respect to sex and age, here we report a land-based mass mortality of Subantarctic fur seals with apparent exclusivity to adult males. An infectious agent with a male-predilection is the most plausible explanation for this die-off. Although pathogens with gender-biased transmission and pathologies are unusual, rodents are known sources of male-biased infectious agents and the invasive Mus musculus house mouse, occurs in seal rookeries. Methodology / Principal Findings: Molecular screening for male-biased pathogens in this potential rodent reservoir host revealed the absence of Cardiovirus and Leptospirosis genomes in heart and kidney samples, respectively, but identified a novel Streptococcus species with 30 % prevalence in mouse kidneys. Conclusions / Significance: Inter-species transmission through environmental contamination with this novel bacterium, whose congenerics display male-bias and have links to infirmity in seals and terrestrial mammals (including humans)

Growth Factors Regulate Expression of Osteoblast‐Associated Genes

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141995/1/jper1345.pd

Proteomic analysis of the Plasmodium male gamete reveals the key role for glycolysis in flagellar motility.

BACKGROUND: Gametogenesis and fertilization play crucial roles in malaria transmission. While male gametes are thought to be amongst the simplest eukaryotic cells and are proven targets of transmission blocking immunity, little is known about their molecular organization. For example, the pathway of energy metabolism that power motility, a feature that facilitates gamete encounter and fertilization, is unknown. METHODS: Plasmodium berghei microgametes were purified and analysed by whole-cell proteomic analysis for the first time. Data are available via ProteomeXchange with identifier PXD001163. RESULTS: 615 proteins were recovered, they included all male gamete proteins described thus far. Amongst them were the 11 enzymes of the glycolytic pathway. The hexose transporter was localized to the gamete plasma membrane and it was shown that microgamete motility can be suppressed effectively by inhibitors of this transporter and of the glycolytic pathway. CONCLUSIONS: This study describes the first whole-cell proteomic analysis of the malaria male gamete. It identifies glycolysis as the likely exclusive source of energy for flagellar beat, and provides new insights in original features of Plasmodium flagellar organization

Inverse Relationship Between Organ-Specific Autoantibodies and Systemic Immune Mediators in Type 1 Diabetes and Type 2 Diabetes: Action LADA 11

5th Framework Programme of EU and DeveloGen