Expression of LDL receptor-related proteins (LRPs) in common solid malignancies correlates with patient survival

LDL receptor-related proteins (LRPs) are transmembrane receptors involved in endocytosis, cell-signaling, and trafficking of other cellular proteins. Considerable work has focused on LRPs in the fields of vascular biology and neurobiology. How these receptors affect cancer progression in humans remains largely unknown. Herein, we mined provisional data-bases in The Cancer Genome Atlas (TCGA) to compare expression of thirteen LRPs in ten common solid malignancies in patients. Our first goal was to determine the abundance of LRP mRNAs in each type of cancer. Our second goal was to determine whether expression of LRPs is associated with improved or worsened patient survival. In total, data from 4,629 patients were mined. In nine of ten cancers studied, the most abundantly expressed LRP was LRP1; however, a correlation between LRP1 mRNA expression and patient survival was observed only in bladder urothelial carcinoma. In this malignancy, high levels of LRP1 mRNA were associated with worsened patient survival. High levels of LDL receptor (LDLR) mRNA were associated with decreased patient survival in pancreatic adenocarcinoma. High levels of LRP10 mRNA were associated with decreased patient survival in hepatocellular carcinoma, lung adenocarcinoma, and pancreatic adenocarcinoma. LRP2 was the only LRP for which high levels of mRNA expression correlated with improved patient survival. This correlation was observed in renal clear cell carcinoma. Insights into LRP gene expression in human cancers and their effects on patient survival should guide future research

Paper Session III-D - The Effects of Hydrophilic and Hydrophobic Coatings and Container Shape on Fluids and Containers in a Microgravity Environment

This experiment demonstrates the fluid property of hydrophilic attraction and hydrophobic repulsion and their relation to surface tension. This study gives an approximation of the amount of control that can be exerted passively over a mass system of fluid. By using cylinders of various sizes and shapes that are coated with various substances, in various patterns, containers along with baffles, a demonstration of the force of attraction between fluid and coating can be observed. The properties studied in this experiment are of great use to the aerospace industry. The control of fluids in a microgravity environment is of major concern to any space project. In the case of a rocket or similar launch vehicle, the fuel of the spacecraft can make up to 70 percent of the weight. If this fluid were to start oscillating, the results would be catastrophic. If the fluid drifted away from the side of the fuel tank that the fuel need to be drawn from while in orbit, the spacecraft would have no way of using the fuel. Life support systems can also benefit from this technology. Water must be stored aboard just like fuel. In fact, the storage of water might be considered even more crucial because it is carried throughout the entire flight, where fuel is usually spent in the initial stages of the flight. Water and other life supporting fluids are a direct necessity for astronauts and cosmonauts and must be readily available. By studying the relationship between fluid, coatings of containers, and the shape of the container, NASA, the aerospace industry, and science in general will learn to control fluids passively, not actively, conserving energy weight, and increasing efficiency

Rural Appalachian Women Will Suffer Disproportionately if Attempts to Further Restrict Emergency Contraception are Successful

The removal of federal abortion protection has incited fear that restrictions on contraception may be next. Many states now imposing abortion restrictions and bans are in the South and Appalachian Regions of the U.S., where rates of unplanned pregnancy and poor health outcomes are already disproportionately high. Numerous studies have documented variable access to levonorgestrel EC (LNG EC) in community pharmacies, with particularly low rates of access at independent pharmacies that are more likely to be located in rural communities than chain pharmacies. Since the overturn of Roe v. Wade, some large chain pharmacies and online retailers are restricting the purchase of LNG EC, limiting its availability. Some legislators and activists are calling for a ban on EC based on a misunderstanding about its mechanism of action, equating it with abortion. At a time when access to the full range of contraceptive options is more critical than ever, already limited access to LNG EC is worsening. Extensive data on LNG EC availability in 509 pharmacies and 400 health clinics across West Virginia, contextualized with socioeconomic demographics, illustrate existing disparities in LNG EC access

Dietary long-chain, but not medium-chain, triglycerides impair exercise performance and uncouple cardiac mitochondria in rats.

Short-term consumption of a high-fat diet impairs exercise capacity in both rats and humans, and increases expression of the mitochondrial uncoupling protein, UCP3, in rodent cardiac and skeletal muscle via activation of the transcription factor, peroxisome proliferator-activated receptor α (PPARα). Unlike long-chain fatty acids however, medium-chain fatty acids do not activate PPARα and do not increase muscle UCP3 expression. We therefore investigated exercise performance and cardiac mitochondrial function in rats fed a chow diet (7.5% kcal from fat), a long-chain triglyceride (LCT) rich diet (46% kcal from LCTs) or a medium-chain triglyceride (MCT) rich diet (46% kcal from MCTs). Rats fed the LCT-rich diet for 15 days ran 55% less far than they did at baseline, whereas rats fed the chow or MCT-rich diets neither improved nor worsened in their exercise capacities. Moreover, consumption of an LCT-rich diet increased cardiac UCP3 expression by 35% and decreased oxidative phosphorylation efficiency, whereas consumption of the MCT-rich diet altered neither UCP3 expression nor oxidative phosphorylation efficiency. Our results suggest that the negative effects of short-term high-fat feeding on exercise performance are predominantly mediated by long-chain rather than medium-chain fatty acids, possibly via PPARα-dependent upregulation of UCP3.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Structure-based inhibitors of amyloid beta core suggest a common interface with tau.

Alzheimer's disease (AD) pathology is characterized by plaques of amyloid beta (Aβ) and neurofibrillary tangles of tau. Aβ aggregation is thought to occur at early stages of the disease, and ultimately gives way to the formation of tau tangles which track with cognitive decline in humans. Here, we report the crystal structure of an Aβ core segment determined by MicroED and in it, note characteristics of both fibrillar and oligomeric structure. Using this structure, we designed peptide-based inhibitors that reduce Aβ aggregation and toxicity of already-aggregated species. Unexpectedly, we also found that these inhibitors reduce the efficiency of Aβ-mediated tau aggregation, and moreover reduce aggregation and self-seeding of tau fibrils. The ability of these inhibitors to interfere with both Aβ and tau seeds suggests these fibrils share a common epitope, and supports the hypothesis that cross-seeding is one mechanism by which amyloid is linked to tau aggregation and could promote cognitive decline

A Clinical Investigation of Motivation to Change Standards and Cognitions about Failure in Perfectionism

Background: Clinical perfectionism is a transdiagnostic process that has been found to maintain eating disorders, anxiety disorders and depression. Cognitive behavioural models explaining the maintenance of clinical perfectionism emphasize the contribution of dichotomous thinking and resetting standards higher following both success and failure in meeting their goals. There has been a paucity of research examining the predictions of the models and motivation to change perfectionism. Motivation to change is important as individuals with clinical perfectionism often report many perceived benefits of their perfectionism; they are, therefore, likely to be ambivalent regarding changing perfectionism. Aims: The aim was to compare qualitative responses regarding questions about motivation to change standards and cognitions regarding failure to meet a personal standard in two contrasting groups with high and low negative perfectionism. Negative perfectionism refers to concern over not meeting personal standards. Method: A clinical group with a range of axis 1 diagnoses who were elevated on negative perfectionism were compared to a group of athletes who were low on negative perfectionism. Results: Results indicated that the clinical group perceived many negative consequences of their perfectionism. They also, however, reported numerous benefits and the majority stated that they would prefer not to change their perfectionism. The clinical group also reported dichotomous thinking and preferring to either keep standards the same or reset standards higher following failure, whilst the athlete group reported they would keep standards the same or set them lower. Conclusions: The findings support predictions of the cognitive behavioural model of clinical perfectionism

Inhaled mannitol for cystic fibrosis.

BackgroundSeveral agents are used to clear secretions from the airways of people with cystic fibrosis. Mannitol increases mucociliary clearance, but its exact mechanism of action is unknown. The dry powder formulation of mannitol may be more convenient and easier to use compared with established agents which require delivery via a nebuliser. Phase III trials of inhaled dry powder mannitol for the treatment of cystic fibrosis have been completed and it is now available in Australia and some countries in Europe. This is an update of a previous review.ObjectivesTo assess whether inhaled dry powder mannitol is well tolerated, whether it improves the quality of life and respiratory function in people with cystic fibrosis and which adverse events are associated with the treatment.Search methodsWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic databases, handsearching relevant journals and abstracts from conferences. Date of last search: 12 December 2019.Selection criteriaAll randomised controlled studies comparing mannitol with placebo, active inhaled comparators (for example, hypertonic saline or dornase alfa) or with no treatment.Data collection and analysisAuthors independently assessed studies for inclusion, carried out data extraction and assessed the risk of bias in included studies. The quality of the evidence was assessed using GRADE.Main resultsSix studies (reported in 36 unique publications) were included with a total of 784 participants. Duration of treatment in the included studies ranged from 12 days to six months, with open-label treatment for an additional six months in two of the studies. Five studies compared mannitol with control (a very low dose of mannitol or non-respirable mannitol) and the final study compared mannitol to dornase alfa alone and to mannitol plus dornase alfa. Two large studies had a similar parallel design and provided data for 600 participants, which could be pooled where data for a particular outcome and time point were available. The remaining studies had much smaller sample sizes (ranging from 22 to 95) and data could not be pooled due to differences in design, interventions and population. Pooled evidence from the two large parallel studies was judged to be of low to moderate quality and from the smaller studies was judged to be of low to very low quality. In all studies, there was an initial test to see if participants tolerated mannitol, with only those who could tolerate the drug being randomised; therefore, the study results are not applicable to the cystic fibrosis population as a whole. While the published papers did not provide all the data required for our analysis, additional unpublished data were provided by the drug's manufacturer and the author of one of the studies. Pooling the large parallel studies comparing mannitol to control, up to and including six months, lung function (forced expiratory volume at one second) measured in both mL and % predicted was significantly improved in the mannitol group compared to the control group (moderate-quality evidence). Beneficial results were observed in these studies in adults and in both concomitant dornase alfa users and non-users in these studies. In the smaller studies, statistically significant improvements in lung function were also observed in the mannitol groups compared to the non-respirable mannitol groups; however, we judged this evidence to be of low to very low quality. For the comparisons of mannitol and control, we found no consistent differences in health-related quality of life in any of the domains except for burden of treatment, which was less for mannitol up to four months in the two pooled studies of a similar design; this difference was not maintained at six months. It should be noted that the tool used to measure health-related quality of life was not designed to assess mucolytics and pooling of the age-appropriate tools (as done in some of the included studies) may not be valid so results were judged to be low to very low quality and should be interpreted with caution. Cough, haemoptysis, bronchospasm, pharyngolaryngeal pain and post-tussive vomiting were the most commonly reported side effects in both treatment groups. Where rates of adverse events could be compared, statistically no significant differences were found between mannitol and control groups; although some of these events may have clinical relevance for people with CF. For the comparisons of mannitol to dornase alfa alone and to mannitol plus dornase alfa, very low-quality evidence from a 12-week cross-over study of 28 participants showed no statistically significant differences in the recorded domains of health-related quality of life or measures of lung function. Cough was the most common side effect in the mannitol alone arm but there was no occurrence of cough in the dornase alfa alone arm and the most commonly reported reason of withdrawal from the mannitol plus dornase alfa arm was pulmonary exacerbations. In terms of secondary outcomes of the review (pulmonary exacerbations, hospitalisations, symptoms, sputum microbiology), evidence provided by the included studies was more limited. For all comparisons, no consistent statistically significant and clinically meaningful differences were observed between mannitol and control treatments (including dornase alfa).Authors' conclusionsThere is moderate-quality evidence to show that treatment with mannitol over a six-month period is associated with an improvement in some measures of lung function in people with cystic fibrosis compared to control. There is low to very low-quality evidence suggesting no difference in quality of life for participants taking mannitol compared to control. This review provides very low-quality evidence suggesting no difference in lung function or quality of life comparing mannitol to dornase alfa alone and to mannitol plus dornase alfa. The clinical implications from this review suggest that mannitol could be considered as a treatment in cystic fibrosis; but further research is required in order to establish who may benefit most and whether this benefit is sustained in the longer term. Furthermore, studies comparing its efficacy against other (established) mucolytic therapies need to be undertaken before it can be considered for mainstream practice

The Iowa Homemaker vol.4, no.7

Table of Contents Accomplish Your Work by Scheduling Your Time by Gertrude Lynn, page 3 A Vision Come True by Eveleth Pederson, page 4 Norwegian Cookery by Ethel Rayness, page 4 Flowers as Decoration by Sarah Palon, page 5 Glimpses Into Child Problems by Helen Herr, page 6 “That School Girl Complexion” by Mrs. Linda S. Brown, page 7 Attractive, Tho Inexpensive Hangings by Grace Heidbreder, page 7 “Women’s Place In The Home?” by Eleanor Murray, page 8 Silverware by Edna Carlson, page 9 Successful Cake Baking by Pauline Peacock, page 10 Who’s There and Where by Helen Putnam, page 11 Editorial Page, page 12 Eternal Question, page 13 Homemaker as Citizen, page 1

The SINS/zC-SINF survey of z~2 galaxy kinematics: Outflow properties

Based on SINFONI Ha, [NII] and [SII] AO data of 30 z \sim 2 star-forming galaxies (SFGs) from the SINS and zcSINF surveys, we find a strong correlation of the Ha broad flux fraction with the star formation surface density of the galaxy, with an apparent threshold for strong outflows occurring at 1 Msun yr^-1 kpc^-2. Above this threshold, we find that SFGs with logm_\ast>10 have similar or perhaps greater wind mass loading factors (eta = Mdotout/SFR) and faster outflow velocities than lower mass SFGs. This trend suggests that the majority of outflowing gas at z \sim 2 may derive from high-mass SFGs, and that the z \sim 2 mass-metallicity relation is driven more by dilution of enriched gas in the galaxy gas reservoir than by the efficiency of outflows. The mass loading factor is also correlated with the SFR and inclination, such that more star-forming and face-on galaxies launch more powerful outflows. For galaxies that have evidence for strong outflows, we find that the broad emission is spatially extended to at least the half-light radius (\sim a few kpc). We propose that the observed threshold for strong outflows and the observed mass loading of these winds can be explained by a simple model wherein break-out of winds is governed by pressure balance in the disk. Using the ratio of the [SII] doublet in a broad and narrow component, we find that outflowing gas has a density of \sim10-100 cm^-3, significantly less than that of the star forming gas (600 cm^-3).Comment: 7 pages, 3 figures, accepted by Ap