Panchromatic Imaging of a Transitional Disk: The Disk of GM Aur in Optical and FUV Scattered Light

We have imaged GM Aur with HST, detected its disk in scattered light at 1400A and 1650A, and compared these with observations at 3300A, 5550A, 1.1 microns, and 1.6 microns. The scattered light increases at shorter wavelengths. The radial surface brightness profile at 3300A shows no evidence of the 24AU radius cavity that has been previously observed in sub-mm observations. Comparison with dust grain opacity models indicates the surface of the entire disk is populated with sub-micron grains. We have compiled an SED from 0.1 microns to 1 mm, and used it to constrain a model of the star+disk system that includes the sub-mm cavity using the Monte Carlo Radiative Transfer code by Barbara Whitney. The best-fit model image indicates that the cavity should be detectable in the F330W bandpass if the cavity has been cleared of both large and small dust grains, but we do not detect it. The lack of an observed cavity can be explained by the presence of sub-microns grains interior to the sub-mm cavity wall. We suggest one explanation for this which could be due to a planet of mass <9 Jupiter masses interior to 24 AU. A unique cylindrical structure is detected in the FUV data from the Advanced Camera for Surveys/Solar Blind Channel. It is aligned along the system semi-minor axis, but does not resemble an accretion-driven jet. The structure is limb-brightened and extends 190 +/- 35 AU above the disk midplane. The inner radius of the limb-brightening is 40 +/- 10 AU, just beyond the sub-millimeter cavity wall.Comment: 40 pages, 11 figures, 4 tables, accepted to Ap

Transcriptomics and proteomics reveal two waves of translational repression during the maturation of malaria parasite sporozoites.

Plasmodium sporozoites are transmitted from infected mosquitoes to mammals, and must navigate the host skin and vasculature to infect the liver. This journey requires distinct proteomes. Here, we report the dynamic transcriptomes and proteomes of both oocyst sporozoites and salivary gland sporozoites in both rodent-infectious Plasmodium yoelii parasites and human-infectious Plasmodium falciparum parasites. The data robustly define mRNAs and proteins that are upregulated in oocyst sporozoites (UOS) or upregulated in infectious sporozoites (UIS) within the salivary glands, including many that are essential for sporozoite functions in the vector and host. Moreover, we find that malaria parasites use two overlapping, extensive, and independent programs of translational repression across sporozoite maturation to temporally regulate protein expression. Together with gene-specific validation experiments, these data indicate that two waves of translational repression are implemented and relieved at different times during sporozoite maturation, migration and infection, thus promoting their successful development and vector-to-host transition

Edgetic perturbation models of human inherited disorders

Cellular functions are mediated through complex systems of macromolecules and metabolites linked through biochemical and physical interactions, represented in interactome models as ‘nodes' and ‘edges', respectively. Better understanding of genotype-to-phenotype relationships in human disease will require modeling of how disease-causing mutations affect systems or interactome properties. Here we investigate how perturbations of interactome networks may differ between complete loss of gene products (‘node removal') and interaction-specific or edge-specific (‘edgetic') alterations. Global computational analyses of ∼50 000 known causative mutations in human Mendelian disorders revealed clear separations of mutations probably corresponding to those of node removal versus edgetic perturbations. Experimental characterization of mutant alleles in various disorders identified diverse edgetic interaction profiles of mutant proteins, which correlated with distinct structural properties of disease proteins and disease mechanisms. Edgetic perturbations seem to confer distinct functional consequences from node removal because a large fraction of cases in which a single gene is linked to multiple disorders can be modeled by distinguishing edgetic network perturbations. Edgetic network perturbation models might improve both the understanding of dissemination of disease alleles in human populations and the development of molecular therapeutic strategies

Results of endoscopic transsphenoidal pituitary surgery in 40 patients with a growth hormone-secreting macroadenoma

Contains fulltext : 96290.pdf (Publisher’s version ) (Open Access)OBJECTIVE: Transsphenoidal pituitary surgery (TS) is the primary treatment of choice for patients with acromegaly. Macroadenomas (>1 cm) are more difficult to resect than microadenomas (remission rate +/- 50% compared to +/- 90%). Besides the conventional microscopic TS, the more recently introduced endoscopic technique is nowadays frequently used. However, no large series reporting on its results have yet been published. We evaluated the outcome of endoscopic TS in 40 patients with a growth hormone (GH)-secreting macroadenoma treated in our hospital between 1998 and 2007. METHODS: Medical records were retrospectively reviewed. Remission was defined as disappearance of clinical symptoms of acromegaly, normal serum insulin-like growth factor-1 levels (</=2 SD) and serum GH levels suppressed to <2 mU/l after an oral glucose tolerance test within the first 4 months after TS. RESULTS: In four patients TS aimed at debulking of the tumour. In the remaining 36 patients, remission was achieved in 20 patients. In the first 5 years remission was achieved in 6 out of 18 patients (33%) compared to 14 out of 22 patients (63%) in the following 5 years (p = 0.06). Thirteen patients had a mild perioperative complication. Before TS 15 patients received hormonal substitution therapy compared to 12 patients (33%) after TS. CONCLUSION: Endoscopic TS is a good primary therapeutic option for patients with a GH-secreting macroadenoma, resulting in a remission rate of up to 63% in experienced hands. This technique can potentially improve the outcome of TS in these patients

Cognition in chronic kidney disease: a systematic review and meta-analysis

Background Cognitive impairment is common in people with chronic kidney disease (CKD) and associated with increased morbidity and mortality. Subtle changes can impact engagement with healthcare, comprehension, decision-making, and medication adherence. We aimed to systematically summarise evidence of cognitive changes in CKD. Methods We searched MEDLINE (March 2016) for cross-sectional, cohort or randomised studies that measured cognitive function in people with CKD (PROSPERO, registration number CRD42014015226). The CKD population included people with eGFR < 60 mL/min/1.73 m2, not receiving renal replacement therapy, in any research setting. We conducted a meta-analysis using random effects, expressed as standardised mean differences (SMD) with 95% confidence intervals (CI). Outcomes were performance in eight cognitive domains. Bias was assessed with the Newcastle-Ottawa Scale (NOS). Results We identified 44 studies reporting sufficient data for synthesis (51,575 participants). Mean NOS score for cohort studies was 5.8/9 and for cross-sectional 5.4/10. Studies were deficient in NOS outcome and selection due to poor methods reporting and in comparison group validity of demographics and chronic disease status. CKD patients (eGFR < 60 mL/min/1.73 m2) performed worse than control groups (eGFR ≥ 60 mL/min/1.73 m2) on Orientation & Attention (SMD –0.79, 95% CI, –1.44 to –0.13), Language (SMD –0.63, 95% CI, –0.85 to –0.41), Concept Formation & Reasoning (SMD –0.63, 95% CI, –1.07 to –0.18), Executive Function (SMD –0.53, 95% CI, –0.85 to –0.21), Memory (SMD –0.48, 95% CI, –0.79 to –0.18), and Global Cognition (SMD –0.48, 95% CI, –0.72 to –0.24). Construction & Motor Praxis and Perception were unaffected (SMD –0.29, 95% CI, –0.90 to 0.32; SMD –1.12, 95% CI, –4.35 to 2.12). Language scores dropped with eGFR (<45 mL/min/1.73 m2 SMD –0.86, 95% CI, –1.25 to –46; 30 mL/min/1.73 m2 SMD –1.56, 95% CI, –2.27 to –0.84). Differences in Orientation & Attention were greatest at eGFR < 45 mL/min/1.73 m2 (SMD –4.62, 95% CI, –4.68 to –4.55). Concept Formation & Reasoning differences were greatest at eGFR < 45 mL/min/1.73 m2 (SMD –4.27, 95% CI, –4.23 to –4.27). Differences in Executive Functions were greatest at eGFR < 30 mL/min/1.73 m2 (SMD –0.54, 95% CI, –1.00 to –0.08). Conclusions Cognitive changes occur early in CKD, and skills decline at different rates. Orientation & Attention and Language are particularly affected. The cognitive impact of CKD is likely to diminish patients’ capacity to engage with healthcare decisions. An individual’s cognitive trajectory may deviate from average