Avoidable mortality attributable to anthropogenic fine particulate matter (Pm2.5) in Australia

Ambient fine particulate matter 2.5) air pollution increases premature mortalityglobally. Some PM2.5 is natural, but anthropogenic PM2.5 is comparatively avoidable. We determinedthe impact of long-term exposures to the anthropogenic PM component on mortality in Australia.PM2.5-attributable deaths were calculated for all Australian Statistical Area 2 (SA2; n = 2310) regions.All-cause death rates from Australian mortality and population databases were combined withannual anthropogenic PM2.5 exposures for the years 2006–2016. Relative risk estimates were derivedfrom the literature. Population-weighted average PM2.5 concentrations were estimated in eachSA2 using a satellite and land use regression model for Australia. PM2.5-attributable mortality wascalculated using a health-impact assessment methodology with life tables and all-cause death rates.The changes in life expectancy (LE) from birth, years of life lost (YLL), and economic cost of lostlife years were calculated using the 2019 value of a statistical life. Nationally, long-term populationweighted average total and anthropogenic PM2.5 concentrations were 6.5 µg/m3(min 1.2–max 14.2)and 3.2 µg/m3(min 0–max 9.5), respectively. Annually, anthropogenic PM2.5-pollution is associatedwith 2616 (95% confidence intervals 1712, 3455) deaths, corresponding to a 0.2-year (95% CI 0.14, 0.28)reduction in LE for children aged 0–4 years, 38,962 (95%CI 25,391, 51,669) YLL and an average annualeconomic burden of $6.2 billion (95$4.0 billion, $8.1 billion). We conclude that the anthropogenicPM2.5-related costs of mortality in Australia are higher than community standards should allow,and reductions in emissions are recommended to achieve avoidable mortality

Multiple Invasions into Freshwater by Pufferfishes (Teleostei: Tetraodontidae): A Mitogenomic Perspective

Pufferfishes of the Family Tetraodontidae are the most speciose group in the Order Tetraodontiformes and mainly inhabit coastal waters along continents. Although no members of other tetraodontiform families have fully discarded their marine lives, approximately 30 tetraodontid species spend their entire lives in freshwaters in disjunct tropical regions of South America, Central Africa, and Southeast Asia. To investigate the interrelationships of tetraodontid pufferfishes and thereby elucidate the evolutionary origins of their freshwater habitats, we performed phylogenetic analysis based on whole mitochondrial genome sequences from 50 tetraodontid species and closely related species (including 31 newly determined sequences). The resulting phylogenies reveal that the family is composed of four major lineages and that freshwater species from the different continents are independently nested in two of the four lineages. A monophyletic origin of the use of freshwater habitats was statistically rejected, and ancestral habitat reconstruction on the resulting tree demonstrates that tetraodontids independently entered freshwater habitats in different continents at least three times. Relaxed molecular-clock Bayesian divergence time estimation suggests that the timing of these invasions differs between continents, occurring at 0–10 million years ago (MA) in South America, 17–38 MA in Central Africa, and 48–78 MA in Southeast Asia. These timings are congruent with geological events that could facilitate adaptation to freshwater habitats in each continent

Structural Basis for Specificity of Propeptide-Enzyme Interaction in Barley C1A Cysteine Peptidases

C1A cysteine peptidases are synthesized as inactive proenzymes. Activation takes place by proteolysis cleaving off the inhibitory propeptide. The inhibitory capacity of propeptides from barley cathepsin L and B-like peptidases towards commercial and barley cathepsins has been characterized. Differences in selectivity have been found for propeptides from L-cathepsins against their cognate and non cognate enzymes. Besides, the propeptide from barley cathepsin B was not able to inhibit bovine cathepsin B. Modelling of their three-dimensional structures suggests that most propeptide inhibitory properties can be explained from the interaction between the propeptide and the mature cathepsin structures. Their potential use as biotechnological tools is discussed

Genus Paracoccidioides: Species Recognition and Biogeographic Aspects

Background: Paracoccidioidomycosis is a systemic mycosis caused by Paracoccidioides brasiliensis (species S1, PS2, PS3), and Paracoccidioides lutzii. This work aimed to differentiate species within the genus Paracoccidioides, without applying multilocus sequencing, as well as to obtain knowledge of the possible speciation processes. Methodology/Principal Findings: Single nucleotide polymorphism analysis on GP43, ARF and PRP8 intein genes successfully distinguished isolates into four different species. Morphological evaluation indicated that elongated conidia were observed exclusively in P. lutzii isolates, while all other species (S1, PS2 and PS3) were indistinguishable. To evaluate the biogeographic events that led to the current geographic distribution of Paracoccidioides species and their sister species, Nested Clade and Likelihood Analysis of Geographic Range Evolution (LAGRANGE) analyses were applied. The radiation of Paracoccidioides started in northwest South America, around 11–32 million years ago, as calculated on the basis of ARF substitution rate, in the BEAST program. Vicariance was responsible for the divergence among S1, PS2 and P. lutzii and a recent dispersal generated the PS3 species, restricted to Colombia. Taking into account the ancestral areas revealed by the LAGRANGE analysis and the major geographic distribution of L. loboi in the Amazon basin, a region strongly affected by the Andes uplift and marine incursions in the Cenozoic era, we also speculate about the effect of these geological events on the vicariance between Paracoccidioides and L. loboi. Conclusions/Significance: The use of at least 3 SNPs, but not morphological criteria, as markers allows us to distinguish among the four cryptic species of the genus Paracoccidioides. The work also presents a biogeographic study speculating on how these species might have diverged in South America, thus contributing to elucidating evolutionary aspects of the genus Paracoccidioides

Differences in Immunoglobulin Light Chain Species Found in Urinary Exosomes in Light Chain Amyloidosis (AL)

Renal involvement is a frequent consequence of plasma cell dyscrasias. The most common entities are light chain amyloidosis, monoclonal immunoglobulin deposition disease and myeloma cast nephropathy. Despite a common origin, each condition has its own unique histologic and pathophysiologic characteristic which requires a renal biopsy to distinguish. Recent studies have shown urinary exosomes containing kidney-derived membrane and cytosolic proteins that can be used to probe the proteomics of the entire urinary system from the glomerulus to the bladder. In this study, we analyzed urine exosomes to determine the differences between exosomes from patients with light chain amyloidosis, multiple myeloma, monoclonal gammopathy of undetermined significance, and non-paraproteinemia related kidney disease controls. In patients with light chain amyloidosis, multiple myeloma and monoclonal gammopathy of undetermined significance, immunoreactive proteins corresponding to monomeric light chains were found in exosomes by western blot. In all of the amyloidosis samples with active disease, high molecular weight immunoreactive species corresponding to a decamer were found which were not found in exosomes from the other diseases or in amyloidosis exosomes from patients in remission. Few or no light chains monomeric bands were found in non-paraproteinemia related kidney disease controls. Our results showed that urinary exosomes may have tremendous potential in furthering our understanding of the pathophysiology and diagnosis of plasma cell dyscrasia related kidney diseases

Global Analysis of Arabidopsis/Downy Mildew Interactions Reveals Prevalence of Incomplete Resistance and Rapid Evolution of Pathogen Recognition

Interactions between Arabidopsis thaliana and its native obligate oomycete pathogen Hyaloperonospora arabidopsidis (Hpa) represent a model system to study evolution of natural variation in a host/pathogen interaction. Both Arabidopsis and Hpa genomes are sequenced and collections of different sub-species are available. We analyzed ∼400 interactions between different Arabidopsis accessions and five strains of Hpa. We examined the pathogen's overall ability to reproduce on a given host, and performed detailed cytological staining to assay for pathogen growth and hypersensitive cell death response in the host. We demonstrate that intermediate levels of resistance are prevalent among Arabidopsis populations and correlate strongly with host developmental stage. In addition to looking at plant responses to challenge by whole pathogen inoculations, we investigated the Arabidopsis resistance attributed to recognition of the individual Hpa effectors, ATR1 and ATR13. Our results suggest that recognition of these effectors is evolutionarily dynamic and does not form a single clade in overall Arabidopsis phylogeny for either effector. Furthermore, we show that the ultimate outcome of the interactions can be modified by the pathogen, despite a defined gene-for-gene resistance in the host. These data indicate that the outcome of disease and disease resistance depends on genome-for-genome interactions between the host and its pathogen, rather than single gene pairs as thought previously

Suppression of Plant Resistance Gene-Based Immunity by a Fungal Effector

The innate immune system of plants consists of two layers. The first layer, called basal resistance, governs recognition of conserved microbial molecules and fends off most attempted invasions. The second layer is based on Resistance (R) genes that mediate recognition of effectors, proteins secreted by pathogens to suppress or evade basal resistance. Here, we show that a plant-pathogenic fungus secretes an effector that can both trigger and suppress R gene-based immunity. This effector, Avr1, is secreted by the xylem-invading fungus Fusarium oxysporum f.sp. lycopersici (Fol) and triggers disease resistance when the host plant, tomato, carries a matching R gene (I or I-1). At the same time, Avr1 suppresses the protective effect of two other R genes, I-2 and I-3. Based on these observations, we tentatively reconstruct the evolutionary arms race that has taken place between tomato R genes and effectors of Fol. This molecular analysis has revealed a hitherto unpredicted strategy for durable disease control based on resistance gene combinations

Pentalogy of Cantrell: two patients and a review to determine prognostic factors for optimal approach

Two patients with incomplete pentalogy of Cantrell are described. The first was a girl with a large omphalocele with evisceration of the heart, liver and intestines with an intact sternum. Echocardiography showed profound intracardiac defects. The girl died 33 h after birth. The second patient was a female fetus with ectopia cordis (EC) without intracardiac anomalies; a large omphalocele with evisceration of the heart, stomach, spleen and liver; a hypoplastic sternum and rib cage; and a scoliosis. The pregnancy was terminated. A review of patients described in the literature is presented with the intention of finding prognostic factors for an optimal approach to patients with the pentalogy of Cantrell. In conclusion the prognosis seems to be poorer in patients with the complete form of pentalogy of Cantrell, EC, and patients with associated anomalies. Intracardial defects do not seem to be a prognostic factor

Loss of susceptibility as a novel breeding strategy for durable and broad-spectrum resistance

Recent studies on plant immunity have suggested that a pathogen should suppress induced plant defense in order to infect a plant species, which otherwise would have been a nonhost to the pathogen. For this purpose, pathogens exploit effector molecules to interfere with different layers of plant defense responses. In this review, we summarize the latest findings on plant factors that are activated by pathogen effectors to suppress plant immunity. By looking from a different point of view into host and nonhost resistance, we propose a novel breeding strategy: disabling plant disease susceptibility genes (S-genes) to achieve durable and broad-spectrum resistance