The adenomatous polyposis coli protein unambiguously localizes to microtubule plus ends and is involved in establishing parallel arrays of microtubule bundles in highly polarized epithelial cells

Loss of full-length adenomatous polyposis coli (APC) protein correlates with the development of colon cancers in familial and sporadic cases. In addition to its role in regulating β-catenin levels in the Wnt signaling pathway, the APC protein is implicated in regulating cytoskeletal organization. APC stabilizes microtubules in vivo and in vitro, and this may play a role in cell migration (Näthke, I.S., C.L. Adams, P. Polakis, J.H. Sellin, and W.J. Nelson. 1996. J. Cell Biol. 134:165–179; Mimori-Kiyosue, Y., N. Shiina, and S. Tsukita. 2000. J. Cell Biol. 148:505–517; Zumbrunn, J., K. Inoshita, A.A. Hyman, and I.S. Näthke. 2001. Curr. Biol. 11:44–49) and in the attachment of microtubules to kinetochores during mitosis (Fodde, R., J. Kuipers, C. Rosenberg, R. Smits, M. Kielman, C. Gaspar, J.H. van Es, C. Breukel, J. Wiegant, R.H. Giles, and H. Clevers. 2001. Nat. Cell Biol. 3:433–438; Kaplan, K.B., A. Burds, J.R. Swedlow, S.S. Bekir, P.K. Sorger, and I.S. Näthke. 2001. Nat. Cell Biol. 3:429–432). The localization of endogenous APC protein is complex: actin- and microtubule-dependent pools of APC have been identified in cultured cells (Näthke et al., 1996; Mimori-Kiyosue et al., 2000; Reinacher-Schick, A., and B.M. Gumbiner. 2001. J. Cell Biol. 152:491–502; Rosin-Arbesfeld, R., G. Ihrke, and M. Bienz. 2001. EMBO J. 20:5929–5939). However, the localization of APC in tissues has not been identified at high resolution. Here, we show that in fully polarized epithelial cells from the inner ear, endogenous APC protein associates with the plus ends of microtubules located at the basal plasma membrane. Consistent with a role for APC in supporting the cytoskeletal organization of epithelial cells in vivo, the number of microtubules is significantly reduced in apico-basal arrays of microtubule bundles isolated from mice heterozygous for APC

Life Cycle Assessment across the Food Supply Chain

The environmental impact is one of the major pillars of concerns when addressing the sustainability of food production and sustainable food consumption strategies. To assess to what extent food production affects the environment, one needs to choose a proper environmental assessment tool. Different types of assessment tools have been developed to establish environmental indicators, which can be used to determine the environmental impact of livestock production systems or agricultural products. The environmen¬tal assessment tools can be divided into the area based or product based (Halberg et al., 2005). Area-based indicators are, for example, nitrate leached per hectare from a pig farm, and product-based indicators are, for example, global warming potential per kg pork (Dalgaard, 2007). The area-based indicators are useful for evaluating farm emissions of nutrients such as nitrate that has an effect on the local environment. On the other hand, when considering the greenhouse gas emissions from the agricultural production, the product-based indicators are useful for evaluating the impact of food productions on the global environment (e. g., climate change) and have the advantage that in addition to emis-sions from the farms, emissions related to the production of input s (e.g., soybean and artificial fertilizer) and outputs (e.g., slurry exported to other farms) are also included. In that way it is easier to avoid pollution swapping, which means that the solving of one pollution problem creates a new (Dalgaard, 2007)

Functional status in ICU survivors and out of hospital outcomes: a cohort study

OBJECTIVES: Functional status at hospital discharge may be a risk factor for adverse events among survivors of critical illness. We sought to examine the association between functional status at hospital discharge in survivors of critical care and risk of 90-day all-cause mortality after hospital discharge. DESIGN: Single-center retrospective cohort study. SETTING: Academic Medical Center. PATIENTS: Ten thousand three hundred forty-three adults who received critical care from 1997 to 2011 and survived hospitalization. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The exposure of interest was functional status determined at hospital discharge by a licensed physical therapist and rated based on qualitative categories adapted from the Functional Independence Measure. The main outcome was 90-day post hospital discharge all-cause mortality. A categorical risk-prediction score was derived and validated based on a logistic regression model of the function grades for each assessment. In an adjusted logistic regression model, the lowest quartile of functional status at hospital discharge was associated with an increased odds of 90-day postdischarge mortality compared with patients with independent functional status (odds ratio, 7.63 [95% CI, 3.83-15.22; p < 0.001]). In patients who had at least 7 days of physical therapy treatment prior to hospital discharge (n = 2,293), the adjusted odds of 90-day postdischarge mortality in patients with marked improvement in functional status at discharge was 64% less than patients with no change in functional status (odds ratio, 0.36 [95% CI, 0.24-0.53]; p < 0.001). CONCLUSIONS: Lower functional status at hospital discharge in survivors of critical illness is associated with increased postdischarge mortality. Furthermore, patients whose functional status improves before discharge have decreased odds of postdischarge mortality.L30 TR001257 - NCATS NIH HH

Acute referral of patients from general practitioners: should the hospital doctor or a nurse receive the call?

<p>Abstract</p> <p>Background</p> <p>Surprisingly little is known about the most efficient organization of admissions to an emergency hospital. It is important to know, who should be in front when the GP requests an acute admission. The aim of the study was to analyse how experienced ED nurses perform when assessing requests for admissions, compared with hospital physicians.</p> <p>Methods</p> <p>Before- and after ED nurse assessment study, in which two cohorts of patients were followed from the time of request for admission until one month later. The first cohort of patients was included by the physicians on duty in October 2008. The admitting physicians were employed in the one of the specialized departments and only received request for admission within their speciality. The second cohort of patients was included by the ED in May 2009. They received all request from the GPs for admission, independent of the speciality in question.</p> <p>Results</p> <p>A total of 944 requests for admission were recorded. There was a non-significant trend towards the nurses admitting a smaller fraction of patients than the physicians (68 versus 74%). While the nurses almost never rejected an admission, the physicians did this in 7% of the requests. The nurses redirected 8% of the patients to another hospital, significantly more than the physicians with only 1%. (p < 0.0001). The nurses referred significantly more patients to the correct hospital than the doctors (78% vs. 70% p: 0.03). There were no differences in the frequency of unnecessary admissions between the groups. The self-reported use of time for assessment was twice as long for the physicians as for the nurses. (p < 0.0001).</p> <p>Conclusions</p> <p>We found no differences in the frequency of admitted patients or unnecessary admissions, but the nurses redirected significantly more patients to the right hospital according to the catchment area, and used only half the time for the assessment. We find, that nurses, trained for the assignment, are able to handle referrals for emergency admissions, but also advise the subject to be explored in further studies including other assessment models and GP satisfaction.</p

Toward an Energy Efficient Language and Compiler for (Partially) Reversible Algorithms

We introduce a new programming language for expressing reversibility, Energy-Efficient Language (Eel), geared toward algorithm design and implementation. Eel is the first language to take advantage of a partially reversible computation model, where programs can be composed of both reversible and irreversible operations. In this model, irreversible operations cost energy for every bit of information created or destroyed. To handle programs of varying degrees of reversibility, Eel supports a log stack to automatically trade energy costs for space costs, and introduces many powerful control logic operators including protected conditional, general conditional, protected loops, and general loops. In this paper, we present the design and compiler for the three language levels of Eel along with an interpreter to simulate and annotate incurred energy costs of a program.Comment: 17 pages, 0 additional figures, pre-print to be published in The 8th Conference on Reversible Computing (RC2016

Photonic crystal resonator integrated in a microfluidic system

We report on a novel optofluidic system consisting of a silica-based 1D photonic crystal, integrated planar waveguides and electrically insulated fluidic channels. An array of pillars in a microfluidic channel designed for electrochromatography is used as a resonator for on-column label-free refractive index detection. The resonator was fabricated in a silicon oxynitride platform, to support electroosmotic flow, and operated at 1.55 microns. Different aqueous solutions of ethanol with refractive indices ranging from n = 1.3330 to 1.3616 were pumped into the column/resonator and the transmission spectra were recorded. Linear shifts of the resonant wavelengths yielded a maximum sensitivity of 480 nm/RIU and a minimum difference of 0.007 RIU was measured

Exon duplications in the ATP7A gene: Frequency and Transcriptional Behaviour

<p>Abstract</p> <p>Background</p> <p>Menkes disease (MD) is an X-linked, fatal neurodegenerative disorder of copper metabolism, caused by mutations in the <it>ATP7A </it>gene. Thirty-three Menkes patients in whom no mutation had been detected with standard diagnostic tools were screened for exon duplications in the <it>ATP7A </it>gene.</p> <p>Methods</p> <p>The <it>ATP7A </it>gene was screened for exon duplications using multiplex ligation-dependent probe amplification (MLPA). The expression level of <it>ATP7A </it>was investigated by real-time PCR and detailed analysis of the <it>ATP7A </it>mRNA was performed by RT-PCR followed by sequencing. In order to investigate whether the identified duplicated fragments originated from a single or from two different X-chromosomes, polymorphic markers located in the duplicated fragments were analyzed.</p> <p>Results</p> <p>Partial <it>ATP7A </it>gene duplication was identified in 20 unrelated patients including one patient with Occipital Horn Syndrome (OHS). Duplications in the <it>ATP7A </it>gene are estimated from our material to be the disease causing mutation in 4% of the Menkes disease patients. The duplicated regions consist of between 2 and 15 exons. In at least one of the cases, the duplication was due to an intra-chromosomal event. Characterization of the <it>ATP7A </it>mRNA transcripts in 11 patients revealed that the duplications were organized in tandem, in a head to tail direction. The reading frame was disrupted in all 11 cases. Small amounts of wild-type transcript were found in all patients as a result of exon-skipping events occurring in the duplicated regions. In the OHS patient with a duplication of exon 3 and 4, the duplicated out-of-frame transcript coexists with an almost equally represented wild-type transcript, presumably leading to the milder phenotype.</p> <p>Conclusions</p> <p>In general, patients with duplication of only 2 exons exhibit a milder phenotype as compared to patients with duplication of more than 2 exons. This study provides insight into exon duplications in the <it>ATP7A </it>gene.</p