bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptation to Chronic Nutritional Stress Leads to Reduced Dependence on Microbiota in
Drosophila melanogaster
Authors: Erkosar Berra , Kolly Sylvain , van der Meer Jan R. , Kawecki Tadeusz J. 
Published: October 2017

ABSTRACT

Numerous studies have shown that animal nutrition is tightly linked to gut microbiota, especially under nutritional stress. In
Drosophila melanogaster
, microbiota are known to promote juvenile growth, development, and survival on poor diets, mainly through enhanced digestion leading to changes in hormonal signaling. Here, we show that this reliance on microbiota is greatly reduced in replicated
Drosophila
populations that became genetically adapted to a poor larval diet in the course of over 170 generations of experimental evolution. Protein and polysaccharide digestion in these poor-diet-adapted populations became much less dependent on colonization with microbiota. This was accompanied by changes in expression levels of dFOXO transcription factor, a key regulator of cell growth and survival, and many of its targets. These evolutionary changes in the expression of dFOXO targets to a large degree mimic the response of the same genes to microbiota, suggesting that the evolutionary adaptation to poor diet acted on mechanisms that normally mediate the response to microbiota. Our study suggests that some metazoans have retained the evolutionary potential to adapt their physiology such that association with microbiota may become optional rather than essential.

IMPORTANCE
Animals depend on gut microbiota for various metabolic tasks, particularly under conditions of nutritional stress, a relationship usually regarded as an inherent aspect of animal physiology. Here, we use experimental evolution in fly populations to show that the degree of host dependence on microbiota can substantially and rapidly change as the host population evolves in response to poor diet. Our results suggest that, although microbiota may initially greatly facilitate coping with suboptimal diets, chronic nutritional stress experienced over multiple generations leads to evolutionary adaptation in physiology and gut digestive properties that reduces dependence on the microbiota for growth and survival. Thus, despite its ancient evolutionary history, the reliance of animal hosts on their microbial partners can be surprisingly flexible and may be relaxed by short-term evolution.
Momentary level of slow default mode network activity is associated with distinct propagation and connectivity patterns in the anesthetized mouse cortex
Authors: Kang Minseok , Lee Young-Beom , Gohel Bakul , Yoo Kwangsun , Lee Peter , Chung Jinyong , Jeong Yong 
Published: October 2017

Complex spatiotemporal changes of slow spontaneous activity occur in the form of propagating waves in the cortex, leading to the transient formation of a specific activation topography, followed by a transition in the topography. The topographies resemble the stimulation-induced activation patterns and the underlying structural projections, suggesting that they contain motifs of task-related activation. However, little is known about how propagation-mediated transitions between topographies are structured in terms of functional connectivity. Therefore, we investigated whether specific topographies or regions are associated with transitions involving long-range connections and hub modulation. We hypothesized that the activity level of the default mode network (DMN) at a given topography would affect the pattern of upcoming transitions, since high activity levels of the DMN are a distinct feature of the brain at rest. Using mesoscale voltage-sensitive dye imaging in the cortex of lightly anesthetized mice, we revealed that momentary levels of DMN activity are associated with distinct patterns of activity propagation and functional connectivity. High levels of DMN activity led to activity propagation across secondary and association cortices, increasing the centrality of a main hub region, whereas low-level activity led to global, diffuse, yet efficient changes in functional connectivity. Furthermore, low levels of activity resulted in increased long-range connectivity between frontal and posterior regions of the cortex. Our results indicate that DMN activity is associated with functional connectivity and wave propagation patterns, raising the possibility that the DMN may be involved in the modulation of long-range information processing associated with upcoming transitions. NEW & NOTEWORTHY Using voltage-sensitive dye imaging with high spatiotemporal resolution, we have revealed that increased DMN activity is associated with activity propagation to secondary/association cortices, whereas decreased activity is associated with stronger long-range frontal-posterior connections in the mouse cortex. Hub metric and global functional connectivity parameters were accompanied by activity level changes. These results indicate that the DMN may aid in modulating the structure of transitions.
Object maintenance beyond their visible parts in working memory
Authors: Chen Siyi , Töllner Thomas , Müller Hermann J. , Conci Markus 
Published: October 2017

Completion of a partially occluded object requires that a representation of the whole is constructed based on the information provided by the physically specified parts of the stimulus. Such processes of amodal completion rely on the generation and maintenance of a mental image that renders the completed object in visual working memory (VWM). The present study examined this relationship between VWM storage and processes of object completion. We recorded event-related potentials to track VWM maintenance by means of the contralateral delay activity (CDA) during a change detection task in which composite objects (notched shapes abutting an occluding shape) to be memorized were primed to induce either a globally completed object or a noncompleted, mosaic representation. The results revealed an effect of completion in VWM despite physically identical visual input: change detection was more accurate for completed compared with mosaic representations when observers were required to memorize two objects, and these differences were reduced with four memorized items. At the electrophysiological level, globally completed (vs. mosaic) objects gave rise to a corresponding increase in CDA amplitudes. These results indicate that although incorporating the occluded portions of the presented shapes requires mnemonic resources, the complete object representations thus formed in VWM improve change detection performance by providing a more simple, regular shape. Overall, these findings demonstrate that mechanisms of object completion modulate VWM, with the memory load being determined by the structured representations of the memorized stimuli. NEW & NOTEWORTHY This study shows that completion of partially occluded objects requires visual working memory (VWM) resources. In the experiment reported, we induced observers to memorize a given visual input either as completed or as noncompleted objects. The results revealed both a behavioral performance advantage for completed vs. noncompleted objects despite physically identical input, and an associated modulation of an electrophysiological component that reflects VWM object retention, thus indicating that constructing an integrated object consumes mnemonic resources.
A Subpopulation of Stromal Cells Controls Cancer Cell Homing to the Bone Marrow
Authors: Rossnagl Stephanie , Ghura Hiba , Groth Christopher , Altrock Eva , Jakob Franz , Schott Sarah , Wimberger Pauline , Link Theresa , Kuhlmann Jan Dominik , Stenzl Arnulf , Hennenlotter Jörg , Todenhöfer Tilmann , Rojewski Markus , Bieback Karen , Nakchbandi Inaam A. 
Published: October 2017

Abstract
Breast and prostate cancer cells home to the bone marrow, where they presumably hijack the hematopoietic stem cell niche. We characterize here the elusive premetastatic niche by examining the role of mesenchymal stromal cells (MSC) in cancer cell homing. Decreasing the number of MSC pharmacologically enhanced cancer cell homing to the bone marrow in mice. In contrast, increasing the number of these MSCs by various interventions including G-CSF administration diminished cancer cell homing. The MSC subpopulation that correlated best with cancer cells expressed stem, endothelial, and pericytic cell markers, suggesting these cells represent an undifferentiated component of the niche with vascular commitment. In humans, a MSC subpopulation carrying markers for endothelial and pericytic cells was lower in the presence of cytokeratin+ cells in bone marrow. Taken together, our data show that a subpopulation of MSC with both endothelial and pericytic cell surface markers suppresses the homing of cancer cells to the bone marrow. Similar to the presence of cytokeratin+ cells in the bone marrow, this MSC subpopulation could prove useful in determining the risk of metastatic disease, and its manipulation might offer a new possibility for diminishing bone metastasis formation.
Significance: These findings establish an inverse relationship between a subpopulation of mesenchymal stromal cells and cancer cells in the bone marrow. Cancer Res; 78(1); 129–42. ©2017 AACR.
CBX8 Exhibits Oncogenic Activity via AKT/β-Catenin Activation in Hepatocellular Carcinoma
Authors: Zhang Chris Zhiyi , Chen Shi-Lu , Wang Chun-Hua , He Yang-Fan , Yang Xia , Xie Dan , Yun Jing-Ping 
Published: October 2017

Abstract
Deregulation of polycomb proteins influences the development and progression of hepatocellular carcinoma. Here we show that chromobox 8 (CBX8) expression is increased in hepatocellular carcinoma and correlates with poor outcome in two independent cohorts containing a total of 879 cases. Ectopic expression of CBX8 facilitated tumor growth and metastasis, whereas CBX8 silencing suppressed these effects. CBX8 efficiently activated AKT/β-catenin signaling via upregulation of the transcription factor EGR1 and miR-365-3p in a noncanonical manner: CBX8 directly bound the EGR1 promoter to enhance its activity. In the nucleus, CBX8 also interacted with EGR1 to prevent its degradation. Furthermore, CBX8 increased the transcription of miR-365a-3p, which promoted the nuclear localization of β-catenin by targeting the 3′-UTR ZNRF1. Inhibiting either EGR1 or miR-365a-3p partially rescued CBX8-mediated malignant phenotypes. In clinical samples, CBX8 expression closely correlated with EGR1, miR-365a-3p, and nuclear β-catenin. Collectively, our results show that CBX8 functions as an oncogene to upregulate EGR1 and miR-365-3p to stimulate the AKT/β-catenin pathway. This newly identified signaling axis may suggest new therapeutic strategies against hepatocellular carcinoma.
Significance: Elucidation of a key new element of the β-catenin signaling pathway in liver cancer may suggest new therapeutic targets. Cancer Res; 78(1); 51–63. ©2017 AACR.
Chemical Profiling of Primary Mesothelioma Cultures Defines Subtypes with Different Expression Profiles and Clinical Responses
Authors: Schunselaar Laurel M. , Quispel-Janssen Josine M.M.F. , Kim Yongsoo , Alifrangis Constantine , Zwart Wilbert , Baas Paul , Neefjes Jacques 
Published: October 2017

AbstractPurpose: Finding new treatment options for patients with malignant pleural mesothelioma is challenging due to the rarity and heterogeneity of this cancer type. The absence of druggable targets further complicates the development of new therapies. Current treatment options are therefore limited, and prognosis remains poor.Experimental Design: We performed drug screening on primary mesothelioma cultures to guide treatment decisions of corresponding patients that were progressive after first- or second-line treatment.Results: We observed a high concordance between in vitro results and clinical outcomes. We defined three subgroups responding differently to the anticancer drugs tested. In addition, gene expression profiling yielded distinct signatures that segregated the differently responding subgroups. These genes signatures involved various pathways, most prominently the fibroblast growth factor pathway.Conclusions: Our primary mesothelioma culture system has proved to be suitable to test novel drugs. Chemical profiling of primary mesothelioma cultures allows personalizing treatment for a group of patients with a rare tumor type where clinical trials are notoriously difficult. This personalized treatment strategy is expected to improve the poor prospects of patients with mesothelioma. Clin Cancer Res; 24(7); 1761–70. ©2017 AACR.See related commentary by John and Chia, p. 1513
A Phase I Open-Label Study to Identify a Dosing Regimen of the Pan-AKT Inhibitor AZD5363 for Evaluation in Solid Tumors and in PIK3CA-Mutated Breast and Gynecologic Cancers
Authors: Banerji Udai , Dean Emma J. , Pérez-Fidalgo J. Alejandro , Batist Gerald , Bedard Philippe L. , You Benoit , Westin Shannon N. , Kabos Peter , Garrett Michelle D. , Tall Mathew , Ambrose Helen , Barrett J. Carl , Carr T. Hedley , Cheung S.Y. Amy , Corcoran Claire , Cullberg Marie , Davies Barry R. , de Bruin Elza C. , Elvin Paul , Foxley Andrew , Lawrence Peter , Lindemann Justin P.O. , Maudsley Rhiannon , Pass Martin , Rowlands Vicky , Rugman Paul , Schiavon Gaia , Yates James , Schellens Jan H.M. 
Published: October 2017

Abstract
Purpose: This phase I, open-label study (Study 1, D3610C00001; NCT01226316) was the first-in-human evaluation of oral AZD5363, a selective pan-AKT inhibitor, in patients with advanced solid malignancies. The objectives were to investigate the safety, tolerability, and pharmacokinetics of AZD5363, define a recommended dosing schedule, and evaluate preliminary clinical activity.
Experimental Design: Patients were aged ≥18 years with World Health Organization (WHO) performance status of 0 to 1. Dose escalation was conducted within separate continuous and intermittent [4 days/week (4/7) or 2 days/week (2/7)] schedules with safety, pharmacokinetic, and pharmacodynamic analyses. Expansion cohorts of approximately 20 patients each explored AZD5363 activity in PIK3CA-mutant breast and gynecologic cancers.
Results: MTDs were 320, 480, and 640 mg for continuous (n = 47), 4/7 (n = 21), and 2/7 (n = 22) schedules, respectively. Dose-limiting toxicities were rash and diarrhea for continuous, hyperglycemia for 2/7, and none for 4/7. Common adverse events were diarrhea (78%) and nausea (49%) and, for Common Terminology Criteria for Adverse Events grade ≥3 events, hyperglycemia (20%). The recommended phase II dose (480 mg bid, 4/7 intermittent) was assessed in PIK3CA-mutant breast and gynecologic expansion cohorts: 46% and 56% of patients, respectively, showed a reduction in tumor size, with RECIST responses of 4% and 8%. These responses were less than the prespecified 20% response rate; therefore, the criteria to stop further recruitment to the PIK3CA-mutant cohort were met.
Conclusions: At the recommended phase II dose, AZD5363 was well tolerated and achieved plasma levels and robust target modulation in tumors. Proof-of-concept responses were observed in patients with PIK3CA-mutant cancers treated with AZD5363. Clin Cancer Res; 24(9); 2050–9. ©2017 AACR.
See related commentary by Costa and Bosch, p. 2029
Reluctant Feminists? Islamist MP s and the Representation of Women in Kuwait after 2005
Authors: Maktabi Rania 
Published: October 2017

Drawing on theories of representation in general, and “the politics of presence” perspective in particular, this article explores whether and how female parliamentarians in Kuwait influenced male MP s to support female civil and economic rights after women’s enfranchisement in 2005. A review of parliamentary documents between 2006 and 2016 reveals that a sharp rise in the number of law proposals occurred in the parliamentary Family and Woman Affairs Committee (FWAC) after the four first-ever female legislators were elected in 2009. Roughly half of all issues regarding women’s interests – 45 per cent – over the past decade were raised during the two years when women were present in the Kuwaiti parliament. In explaining this fact, the paper argues that male Islamist MP s acted as reluctant feminists and diligent opportunists by responding to new opportunities and expectations created by the presence of female MP s. Islamist MP s reformulated demands pertaining to poverty alleviation and social assistance by focusing on women as mothers, widows, and caregivers. They emphasized gender relations in ways where Kuwaiti women, particularly those married to non-Kuwaitis and stateless bidun, were seen as capacitated citizens. Kuwaiti women, some Islamist MP s argued, should be able to act as legal guardians (kafīl) of their husbands and children, be brokers of material welfare services such as free education and health services, and get access to public housing. After the exit of female MP s from parliament in 2011, Islamist MP s stopped arguing along these lines, and their demands on behalf of women through the FWAC dropped sharply.1
Manifestations of Religion or Belief in the Case Law of the European Court of Human Rights
Authors: Martínez-Torrón Javier 
Published: October 2017

Abstract
This article analyses the case law of the European Courts of Human Rights on manifestation of religion or belief under Article 9 echr, excluding particular types of manifestation that are covered in other articles in this special issue. It provides an overview of the main holdings of the Court in this area, together with some critical comments about aspects of the Court’s case law that, in the author’s view, should be improved.
Kokkinakis at the Grassroots Level
Authors: Fokas Effie 
Published: October 2017

Abstract
This contribution considers the impact of Kokkinakis at the grassroots level: to what extent do grassroots level actors know about the case of Kokkinakis and see in it an opportunity to further their own religion-related rights claims? To what extent has the case inspired social actors such as rights activists, cause lawyers or faith group members to mobilise for their own religion-related rights, whether in court, in the halls of government, or in the streets? Has Kokkinakis left a mark on the individual citizen with concerns to do with religious freedoms? These questions are addressed through empirical research conducted on the indirect effects of ECtHR religion-related case law, including Kokkinakis, at the grassroots level in Greece.
Katabatically Driven Cold Air Intrusions into a Basin Atmosphere
Authors: Whiteman C. David , Lehner Manuela , Hoch Sebastian W. , Adler Bianca , Kalthoff Norbert , Haiden Thomas 
Published: October 2017

AbstractThe interactions between a katabatic flow on a plain and a circular basin cut into the plain and surrounded by an elevated rim were examined during a 5-h steady-state period during the Second Meteor Crater Experiment (METCRAX II) to explain observed disturbances to the nocturnal basin atmosphere. The approaching katabatic flow split horizontally around Arizona’s Meteor Crater below a dividing streamline while, above the dividing streamline, an ~50-m-deep stable layer on the plain was carried over the 30–50-m rim of the basin. A flow bifurcation occurred over or just upwind of the rim, with the lowest portion of the stable layer having negative buoyancy relative to the air within the crater pouring continuously over the crater’s upwind rim and accelerating down the inner sidewall. The cold air intrusion was deepest and coldest over the direct upwind crater rim. Cold air penetration depths varied around the inner sidewall depending on the temperature deficit of the inflow relative to the ambient environment inside the crater. A shallow but extremely stable cold pool on the crater floor could not generally be penetrated by the inflow and a hydraulic jump–like feature formed on the lower sidewall as the flow approached the cold pool. The upper nonnegatively buoyant portion of the stable layer was carried horizontally over the crater, forming a neutrally stratified, low–wind speed cavity or wake in the lee of the upwind rim that extended downward into the crater over the upwind sidewall.
Toward Improving Ice Water Content and Snow-Rate Retrievals from Radars. Part II: Results from Three Wavelength Radar–Collocated In Situ Measurements and CloudSat–GPM–TRMM Radar Data
Authors: Heymsfield Andrew , Bansemer Aaron , Wood Norman B. , Liu Guosheng , Tanelli Simone , Sy Ousmane O. , Poellot Michael , Liu Chuntao 
Published: October 2017

AbstractTwo methods for deriving relationships between the equivalent radar reflectivity factor Ze and the snowfall rate S at three radar wavelengths are described. The first method uses collocations of in situ aircraft (microphysical observations) and overflying aircraft (radar observations) from two field programs to develop Ze–S relationships. In the second method, measurements of Ze at the top of the melting layer (ML), from radars on the Tropical Rainfall Measuring Mission (TRMM), Global Precipitation Measurement (GPM), and CloudSat satellites, are related to the retrieved rainfall rate R at the base of the ML, assuming that the mass flux through the ML is constant. Retrievals of R are likely to be more reliable than S because far fewer assumptions are involved in the retrieval and because supporting ground-based validation data are available. The Ze–S relationships developed here for the collocations and the mass-flux technique are compared with those derived from level 2 retrievals from the standard satellite products and with a number of relationships developed and reported by others. It is shown that there are substantial differences among them. The relationships developed here promise improvements in snowfall-rate retrievals from satellite-based radar measurements.
A Real-Time Evaporation Correction Scheme for Radar-Derived Mosaicked Precipitation Estimations
Authors: Martinaitis Steven M. , Grams Heather M. , Langston Carrie , Zhang Jian , Howard Kenneth 
Published: October 2017

Abstract
Precipitation values estimated by radar are assumed to be the amount of precipitation that occurred at the surface, yet this notion is inaccurate. Numerous atmospheric and microphysical processes can alter the precipitation rate between the radar beam elevation and the surface. One such process is evaporation. This study determines the applicability of integrating an evaporation correction scheme for real-time radar-derived mosaicked precipitation rates to reduce quantitative precipitation estimate (QPE) overestimation and to reduce the coverage of false surface precipitation. An evaporation technique previously developed for large-scale numerical modeling is applied to Multi-Radar Multi-Sensor (MRMS) precipitation rates through the use of 2D and 3D numerical weather prediction (NWP) atmospheric parameters as well as basic radar properties. Hourly accumulated QPE with evaporation adjustment compared against gauge observations saw an average reduction of the overestimation bias by 57%–76% for rain events and 42%–49% for primarily snow events. The removal of false surface precipitation also reduced the number of hourly gauge observations that were considered as “false zero” observations by 52.1% for rain and 38.2% for snow. Optimum computational efficiency was achieved through the use of simplified equations and hourly 10-km horizontal resolution NWP data. The run time for the evaporation correction algorithm is 6–7 s.