Underway spectrophotometry along the Atlantic Meridional Transect reveals high performance in satellite chlorophyll retrievals

This is the final version. Available on open access from Elsevier via the DOI in this recordTo evaluate the performance of ocean-colour retrievals of total chlorophyll-a concentration requires direct comparison with concomitant and co-located in situ data. For global comparisons, these in situ match-ups should be ideally representative of the distribution of total chlorophyll-a concentration in the global ocean. The oligotrophic gyres constitute the majority of oceanic water, yet are under-sampled due to their inaccessibility and under-represented in global in situ databases. The Atlantic Meridional Transect (AMT) is one of only a few programmes that consistently sample oligotrophic waters. In this paper, we used a spectrophotometer on two AMT cruises (AMT19 and AMT22) to continuously measure absorption by particles in the water of the ship's flow-through system. From these optical data continuous total chlorophyll-a concentrations were estimated with high precision and accuracy along each cruise and used to evaluate the performance of ocean-colour algorithms. We conducted the evaluation using level 3 binned ocean-colour products, and used the high spatial and temporal resolution of the underway system to maximise the number of match-ups on each cruise. Statistical comparisons show a significant improvement in the performance of satellite chlorophyll algorithms over previous studies, with root mean square errors on average less than half (~0.16 in log10 space) that reported previously using global datasets (~0.34 in log10 space). This improved performance is likely due to the use of continuous absorption-based chlorophyll estimates, that are highly accurate, sample spatial scales more comparable with satellite pixels, and minimise human errors. Previous comparisons might have reported higher errors due to regional biases in datasets and methodological inconsistencies between investigators. Furthermore, our comparison showed an underestimate in satellite chlorophyll at low concentrations in 2012 (AMT22), likely due to a small bias in satellite remote-sensing reflectance data. Our results highlight the benefits of using underway spectrophotometric systems for evaluating satellite ocean-colour data and underline the importance of maintaining in situ observatories that sample the oligotrophic gyres.NEODAASCMEMSNatural Environment Research Council (NERC

Facial onset sensory and motor neuronopathy: new cases, cognitive changes and pathophysiology

Purpose of review To improve our clinical understanding of facial onset sensory and motor neuronopathy (FOSMN). Recent findings We identified 29 new cases and 71 literature cases, resulting in a cohort of 100 patients with FOSMN. During follow-up, cognitive and behavioral changes became apparent in 8 patients, suggesting that changes within the spectrum of frontotemporal dementia (FTD) are a part of the natural history of FOSMN. Another new finding was chorea, seen in 6 cases. Despite reports of autoantibodies, there is no consistent evidence to suggest an autoimmune pathogenesis. Four of 6 autopsies had TAR DNA-binding protein (TDP) 43 pathology. Seven cases had genetic mutations associated with neurodegenerative diseases. Summary FOSMN is a rare disease with a highly characteristic onset and pattern of disease progression involving initial sensory disturbances, followed by bulbar weakness with a cranial to caudal spread of pathology. Although not conclusive, the balance of evidence suggests that FOSMN is most likely to be a TDP-43 proteinopathy within the amyotrophic lateral sclerosis–FTD spectrum

CMB Telescopes and Optical Systems

The cosmic microwave background radiation (CMB) is now firmly established as a fundamental and essential probe of the geometry, constituents, and birth of the Universe. The CMB is a potent observable because it can be measured with precision and accuracy. Just as importantly, theoretical models of the Universe can predict the characteristics of the CMB to high accuracy, and those predictions can be directly compared to observations. There are multiple aspects associated with making a precise measurement. In this review, we focus on optical components for the instrumentation used to measure the CMB polarization and temperature anisotropy. We begin with an overview of general considerations for CMB observations and discuss common concepts used in the community. We next consider a variety of alternatives available for a designer of a CMB telescope. Our discussion is guided by the ground and balloon-based instruments that have been implemented over the years. In the same vein, we compare the arc-minute resolution Atacama Cosmology Telescope (ACT) and the South Pole Telescope (SPT). CMB interferometers are presented briefly. We conclude with a comparison of the four CMB satellites, Relikt, COBE, WMAP, and Planck, to demonstrate a remarkable evolution in design, sensitivity, resolution, and complexity over the past thirty years.Comment: To appear in: Planets, Stars and Stellar Systems (PSSS), Volume 1: Telescopes and Instrumentatio

Global similarity with local differences in linkage disequilibrium between the Dutch and HapMap–CEU populations

The HapMap project has facilitated the selection of tagging single nucleotide polymorphisms (tagSNPs) for genome-wide association studies (GWAS) under the assumption that linkage disequilibrium (LD) in the HapMap populations is similar to the populations under investigation. Earlier reports support this assumption, although in most of these studies only a few loci were evaluated. We compared pair-wise LD and LD block structure across autosomes between the Dutch population and the CEU-HapMap reference panel. The impact of sampling distribution on the estimation of LD blocks was studied by bootstrapping. A high Pearson correlation (genome-wide; 0.93) between pair-wise

Fibrocytes and the tissue niche in lung repair

Human fibrocytes are bone marrow-derived mesenchymal progenitor cells that express a variety of markers related to leukocytes, hematopoietic stem cells and a diverse set of fibroblast phenotypes. Fibrocytes can be recruited from the circulation to the tissue where they further can differentiate and proliferate into various mesenchymal cell types depending on the tissue niche. This local tissue niche is important because it modulates the fibrocytes and coordinates their role in tissue behaviour and repair. However, plasticity of a niche may be co-opted in chronic airway diseases such as asthma, idiopathic pulmonary fibrosis and obliterative bronchiolitis. This review will therefore focus on a possible role of fibrocytes in pathological tissue repair processes in those diseases

Bcl-2 and β1-integrin predict survival in a tissue microarray of small cell lung cancer.

INTRODUCTION: Survival in small cell lung cancer (SCLC) is limited by the development of chemoresistance. Factors associated with chemoresistance in vitro have been difficult to validate in vivo. Both Bcl-2 and β(1)-integrin have been identified as in vitro chemoresistance factors in SCLC but their importance in patients remains uncertain. Tissue microarrays (TMAs) are useful to validate biomarkers but no large TMA exists for SCLC. We designed an SCLC TMA to study potential biomarkers of prognosis and then used it to clarify the role of both Bcl-2 and β(1)-integrin in SCLC. METHODS: A TMA was constructed consisting of 184 cases of SCLC and stained for expression of Bcl-2 and β(1)-integrin. The slides were scored and the role of the proteins in survival was determined using Cox regression analysis. A meta-analysis of the role of Bcl-2 expression in SCLC prognosis was performed based on published results. RESULTS: Both proteins were expressed at high levels in the SCLC cases. For Bcl-2 (n=140), the hazard ratio for death if the staining was weak in intensity was 0.55 (0.33-0.94, P=0.03) and for β(1)-integrin (n=151) was 0.60 (0.39-0.92, P=0.02). The meta-analysis showed an overall hazard ratio for low expression of Bcl-2 of 0.91(0.74-1.09). CONCLUSIONS: Both Bcl-2 and β(1)-integrin are independent prognostic factors in SCLC in this cohort although further validation is required to confirm their importance. A TMA of SCLC cases is feasible but challenging and an important tool for biomarker validation

Dual isotope analyses indicate efficient processing of atmospheric nitrate by forested watersheds in the northeastern U.S.

Author Posting. © Springer, 2008. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Biogeochemistry 90 (2008): 15-27, doi:10.1007/s10533-008-9227-2.Nitrogen from atmospheric deposition serves as the dominant source of new nitrogen to forested ecosystems in the northeastern U.S.. By combining isotopic data obtained using the denitrifier method, with chemistry and hydrology measurements we determined the relative importance of sources and control mechanisms on nitrate (NO3-) export from five forested watersheds in the Connecticut River watershed. Microbially produced NO3- was the dominant source (82-100%) of NO3- to the sampled streams as indicated by the δ15N and δ18O of NO3-. Seasonal variations in the δ18O-NO3- in streamwater are controlled by shifting hydrology and temperature affects on biotic processing, resulting in a relative increase in unprocessed NO3- export during winter months. Mass balance estimates find that the unprocessed atmospherically derived NO3- stream flux represents less than 3% of the atmospherically delivered wet NO3- flux to the region. This suggests that despite chronically elevated nitrogen deposition these forests are not nitrogen saturated and are retaining, removing, and reprocessing the vast majority of NO3- delivered to them throughout the year. These results confirm previous work within Northeastern U.S. forests and extend observations to watersheds not dominated by a snow-melt driven hydrology. In contrast to previous work, unprocessed atmospherically derived NO3- export is associated with the period of high recharge and low biotic activity as opposed to spring snowmelt and other large runoff events.This work was funded by an EPA STAR Fellowship (FP-91637501-1) and a grant from QLF/The Sound Conservancy to RTB

A Fine-Mapping Study of 7 Top Scoring Genes from a GWAS for Major Depressive Disorder

Major depressive disorder (MDD) is a psychiatric disorder that is characterized -amongst others- by persistent depressed mood, loss of interest and pleasure and psychomotor retardation. Environmental circumstances have proven to influence the aetiology of the disease, but MDD also has an estimated 40% heritability, probably with a polygenic background. In 2009, a genome wide association study (GWAS) was performed on the Dutch GAIN-MDD cohort. A non-synonymous coding single nucleotide polymorphism (SNP) rs2522833 in the PCLO gene became only nominally significant after post-hoc analysis with an Australian cohort which used similar ascertainment. The absence of genome-wide significance may be caused by low SNP coverage of genes. To increase SNP coverage to 100% for common variants (m.a.f.>0.1, r2>0.8), we selected seven genes from the GAIN-MDD GWAS: PCLO, GZMK, ANPEP, AFAP1L1, ST3GAL6, FGF14 and PTK2B. We genotyped 349 SNPs and obtained the lowest P-value for rs2715147 in PCLO at P = 6.8E−7. We imputed, filling in missing genotypes, after which rs2715147 and rs2715148 showed the lowest P-value at P = 1.2E−6. When we created a haplotype of these SNPs together with the non-synonymous coding SNP rs2522833, the P-value decreased to P = 9.9E−7 but was not genome wide significant. Although our study did not identify a more strongly associated variant, the results for PCLO suggest that the causal variant is in high LD with rs2715147, rs2715148 and rs2522833

Fibrotic Myofibroblasts Manifest Genome-Wide Derangements of Translational Control

Background: As a group, fibroproliferative disorders of the lung, liver, kidney, heart, vasculature and integument are common, progressive and refractory to therapy. They can emerge following toxic insults, but are frequently idiopathic. Their enigmatic propensity to resist therapy and progress to organ failure has focused attention on the myofibroblast–the primary effector of the fibroproliferative response. We have recently shown that aberrant beta 1 integrin signaling in fibrotic fibroblasts results in defective PTEN function, unrestrained Akt signaling and subsequent activation of the translation initiation machinery. How this pathological integrin signaling alters the gene expression pathway has not been elucidated. Results: Using a systems approach to study this question in a prototype fibrotic disease, Idiopathic Pulmonary Fibrosis (IPF); here we show organized changes in the gene expression pathway of primary lung myofibroblasts that persist for up to 9 sub-cultivations in vitro. When comparing IPF and control myofibroblasts in a 3-dimensional type I collagen matrix, more genes differed at the level of ribosome recruitment than at the level of transcript abundance, indicating pathological translational control as a major characteristic of IPF myofibroblasts. To determine the effect of matrix state on translational control, myofibroblasts were permitted to contract the matrix. Ribosome recruitment in control myofibroblasts was relatively stable. In contrast, IPF cells manifested large alterations in the ribosome recruitment pattern. Pathological studies suggest an epithelial origin for IPF myofibroblasts through the epithelial to mesenchymal transition (EMT). In accord wit

Insulin-resistance and metabolic syndrome are related to executive function in women in a large family-based study

While type 2 diabetes is well-known to be associated with poorer cognitive performance, few studies have reported on the association of metabolic syndrome (MetS) and contributing factors, such as insulin-resistance (HOMA-IR), low adiponectin-, and high C-reactive protein (CRP)- levels. We studied whether these factors are related to cognitive function and which of the MetS components are independently associated. The study was embedded in an ongoing family-based cohort study in a Dutch population. All participants underwent physical examinations, biomedical measurements, and neuropsychological testing. Linear regression models were used to determine the association between MetS, HOMA-IR, adiponectin levels, CRP, and cognitive test scores. Cross-sectional analyses were performed in 1,898 subjects (mean age 48 years, 43% men). People with MetS had significantly higher HOMA-IR scores, lower adiponectin levels, and higher CRP levels. MetS and high HOMA-IR were associated with poorer executive function in women (P = 0.03 and P = 0.009). MetS and HOMA-IR are associated with poorer executive function in women