bluuebunny/crossref_metadata_2025 huggingface dataset:
FRMD8 promotes inflammatory and growth factor signalling by stabilising the iRhom/ADAM17 sheddase complex
Authors: Künzel Ulrike , Grieve Adam Graham , Meng Yao , Sieber Boris , Cowley Sally A , Freeman Matthew
Published: June 2018

Many intercellular signals are synthesised as transmembrane precursors that are released by proteolytic cleavage (‘shedding’) from the cell surface. ADAM17, a membrane-tethered metalloprotease, is the primary shedding enzyme responsible for the release of the inflammatory cytokine TNFα and several EGF receptor ligands. ADAM17 exists in complex with the rhomboid-like iRhom proteins, which act as cofactors that regulate ADAM17 substrate shedding. Here we report that the poorly characterised FERM domain-containing protein FRMD8 is a new component of the iRhom2/ADAM17 sheddase complex. FRMD8 binds to the cytoplasmic N-terminus of iRhoms and is necessary to stabilise iRhoms and ADAM17 at the cell surface. In the absence of FRMD8, iRhom2 and ADAM17 are degraded via the endolysosomal pathway, resulting in the reduction of ADAM17-mediated shedding. We have confirmed the pathophysiological significance of FRMD8 in iPSC-derived human macrophages and mouse tissues, thus demonstrating its role in the regulated release of multiple cytokine and growth factor signals.
iTAP, a novel iRhom interactor, controls TNF secretion by policing the stability of iRhom/TACE
Authors: Oikonomidi Ioanna , Burbridge Emma , Cavadas Miguel , Sullivan Graeme , Collis Blanka , Naegele Heike , Clancy Danielle , Brezinova Jana , Hu Tianyi , Bileck Andrea , Gerner Christopher , Bolado Alfonso , von Kriegsheim Alex , Martin Seamus J , Steinberg Florian , Strisovsky Kvido , Adrain Colin
Published: June 2018

The apical inflammatory cytokine TNF regulates numerous important biological processes including inflammation and cell death, and drives inflammatory diseases. TNF secretion requires TACE (also called ADAM17), which cleaves TNF from its transmembrane tether. The trafficking of TACE to the cell surface, and stimulation of its proteolytic activity, depends on membrane proteins, called iRhoms. To delineate how the TNF/TACE/iRhom axis is regulated, we performed an immunoprecipitation/mass spectrometry screen to identify iRhom-binding proteins. This identified a novel protein, that we name iTAP (iRhom Tail-Associated Protein) that binds to iRhoms, enhancing the cell surface stability of iRhoms and TACE, preventing their degradation in lysosomes. Depleting iTAP in primary human macrophages profoundly impaired TNF production and tissues from iTAP KO mice exhibit a pronounced depletion in active TACE levels. Our work identifies iTAP as a physiological regulator of TNF signalling and a novel target for the control of inflammation.
Cellular aspect ratio and cell division mechanics underlie the patterning of cell progeny in diverse mammalian epithelia
Authors: McKinley Kara L , Stuurman Nico , Royer Loic A , Schartner Christoph , Castillo-Azofeifa David , Delling Markus , Klein Ophir D , Vale Ronald D
Published: June 2018

Cell division is essential to expand, shape, and replenish epithelia. In the adult small intestine, cells from a common progenitor intermix with other lineages, whereas cell progeny in many other epithelia form contiguous patches. The mechanisms that generate these distinct patterns of progeny are poorly understood. Using light sheet and confocal imaging of intestinal organoids, we show that lineages intersperse during cytokinesis, when elongated interphase cells insert between apically displaced daughters. Reducing the cellular aspect ratio to minimize the height difference between interphase and mitotic cells disrupts interspersion, producing contiguous patches. Cellular aspect ratio is similarly a key parameter for division-coupled interspersion in the early mouse embryo, suggesting that this physical mechanism for patterning progeny may pertain to many mammalian epithelia. Our results reveal that the process of cytokinesis in elongated mammalian epithelia allows lineages to intermix and that cellular aspect ratio is a critical modulator of the progeny pattern.
The effect of recent competition between the nativeAnolis oculatusand the invasiveA. cristatelluson display behavior
Authors: Dufour Claire M. S. , Herrel Anthony , Losos Jonathan B.
Published: June 2018

Invasive species are a global threat to biodiversity. Cases where the invasion has been tracked since its beginning are rare, however, such that the first interactions between invasive and native species remain poorly understood. Communication behavior is an integral part of species identity and is subject to selection. Consequently, resource use and direct interference competition between native and invasive species may drive its evolution. Here, we tested the role of interactions between the recently introduced invasive lizardAnolis cristatellusand the nativeAnolis oculatuson variation in behavior and communication in Calibishie (Dominica). From May to June 2016, we filmed 122 adult males of both species displaying in banana farms under two contexts (allopatry and sympatry). We then recorded (i) the proportion of time spent displaying and (ii) the relative frequency of dewlap vs. push-up displays. To control for habitat variation, we measured and compared the habitat characteristics (canopy openness and habitat openness) of 228 males in allopatry and sympatry. While the habitat characteristics and total display-time did not differ between the contexts for the two species, the proportion of display-time spent dewlapping byA. cristatellusdecreased in sympatry. The display ofA. oculatusdid not differ between the contexts, however. Shifts in microhabitat use, predation pressure, or interspecific interference are potential factors which might explain the behavioral changes in display observed inA. cristatellus. This study highlights the role of behavioral traits as a first response of an invasive species to recent competition with a closely related native species.
A novel thymidylate synthase from theVibrionales,Alteromonadales,Aeromonadales, andPasteurellales(VAAP) clade with altered nucleotide and folate binding sites
Authors: Lopez-Zavala Alonso A. , Guevara-Hernandez Eduardo , Vazquez-Lujan Luz H. , Sanchez-Paz Arturo , Garcia-Orozco Karina D. , Contreras-Vergara Carmen A. , Lopez-Leal Gamaliel , Arvizu-Flores Aldo A. , Ochoa-Leyva Adrian , Sotelo-Mundo Rogerio R.
Published: June 2018

Thymidylate synthase (TS, E.C. 2.1.1.45) is a crucial enzyme forde novodeoxythymidine monophosphate (dTMP) biosynthesis. The gene for this enzyme isthyA, which encodes the folate-dependent TS that converts deoxyuridine monophosphate group (dUMP) into (dTMP) using the cofactor 5,10-methylenetetrahydrofolate (mTHF) as a carbon donor. We identified thethyAgene in the genome of theVibrio parahaemolyticusstrain FIM-S1708+ that is innocuous to humans but pathogenic to crustaceans. Surprisingly, we found changes in the residues that bind the substrate dUMP and mTHF, previously postulated as invariant among all TSs known (Finer-Moore, Santi & Stroud, 2003). Interestingly, those amino acid changes were also found in a clade of microorganisms that containsVibrionales,Alteromonadales,Aeromonadales, andPasteurellales(VAAP) from theGammaproteobacteriaclass. In this work, we studied the biochemical properties of recombinant TS fromV. parahemolyticusFIM-S1708+ (VpTS) to address the natural changes in the TS amino acid sequence of the VAAP clade. Interestingly, theKmfor dUMP was 27.3 ± 4.3 µM, about one-fold larger compared to other TSs. TheKmfor mTHF was 96.3 ± 18 µM, about three- to five-fold larger compared to other species, suggesting also loss of affinity. Thus, the catalytic efficiency was between one or two orders of magnitude smaller for both substrates. We used trimethoprim, a common antibiotic that targets both TS and DHFR for inhibition studies. The IC50values obtained were high compared to other results in the literature. Nonetheless, this molecule could be a lead for the design antibiotics towards pathogens from the VAAP clade. Overall, the experimental results also suggest that in the VAAP clade the nucleotide salvage pathway is important and should be investigated, since thede novodTMP synthesis appears to be compromised by a less efficient thymidylate synthase.
Examining the “July effect” on patients undergoing pituitary surgery
Authors: Bashjawish Bassel , Patel Shreya , Kılıç Suat , Hsueh Wayne D. , Liu James K. , Baredes Soly , Eloy Jean Anderson
Published: June 2018

Background

Our aim in this study was to assess the impact of the turnover of residents in July on patients undergoing pituitary surgery.

Methods

This work was a retrospective cohort study of cases from the National Inpatient Sample (NIS). Patients who underwent pituitary surgery from 2005 to 2012 were selected in the NIS. Patients undergoing surgery in July and in non‐July months were compared to determine differences in demographics, comorbidities, and complications.

Results

Of the 12,939 patients, 1098 (8.5%) underwent pituitary surgery in July. Patients receiving surgery in July had similar demographics and Agency for Healthcare Research and Quality comorbidity values compared with patients receiving surgery in other months. There were no significant differences in mortality, cerebral edema, cerebrospinal fluid leakage, iatrogenic pituitary complications, iatrogenic cerebrovascular accidents, urinary tract infections, pulmonary edema, pulmonary complications, or acute cardiac complications. There were no differences in the rate of postoperative fistulas, hematomas, perforations, or infections. The use of meningeal suturing, pedicled or free‐flap reconstruction, and skin reconstruction was more frequent in July. Finally, hospitalization costs in July were similar to costs in other months.

Conclusion

The turnover of new residents in July showed no change in complication rates for patients undergoing pituitary surgery. Patient care in July is similar to care during other months, demonstrating that hospitals are adequately supervising surgical residents during this transition.
HOTAIRM1 competed endogenously with miR‐148a to regulate DLGAP1 in head and neck tumor cells
Authors: Zheng Mei , Liu Xingguang , Zhou Qin , Liu Gangli
Published: June 2018

This study is aimed to explore the regulatory effect of lncRNA HOTAIR/miR‐148a/DLGAP1 axis on head and neck tumor (HNT) cell growth, cell mobility, and invasiveness. HOTAIRM1, miR‐148a, and DLGAP1 level in HNT tissues and adjacent normal tissues were measured by qRT‐PCR. Cell Counting Kit‐8 (CCK‐8) and Transwell (migration and invasion) assay were used to survey the influence of HOTAIRM1, miR‐148a, and DLGAP1 on Fadu cells. Nude mouse xenograft was utilized to validate the influence of HOTAIRM1 in vivo. Dual‐luciferase reporter assay confirms the relationship between HOTAIRM1 and miR‐148a, miR‐148a, and DLGAP1. The expression level of HOTAIRM1 was downregulated in human HNT tissues and cells. Overexpression of HOTAIRM1 significantly moderated Fadu cells proliferation, apoptosis, migration, and invasion in vitro and impaired the tumorigenesis in vivo. The expression level of miR‐148a was upregulated in human HNT tissue compared to the adjacent tissues. We identified that miR‐148a was a target of HOTAIRM1 and its expression levels were reduced by HOTAIRM1. Transfection of miR‐148a mimics increased proliferation, migration, and invasion of Fadu cells. DLGAP1 was identified as a novel target of miR‐148a and its expression level was promoted by either HOTAIRM1 overexpression or miR‐148a knockdown. Overexpression of DLGAP1 also facilitated the cell viability and metastasis of Fadu cells. HOTAIRM1 was confirmed as a tumor suppressor via sponging miR‐148a and promote the expression of DLGAP1, which could be regarded as an important target for the prevention and treatment of HNT.
Low expression of WW domain‐containing oxidoreductase associates with hepatocellular carcinoma aggressiveness and recurrence after curative resection
Authors: Zhou Chenhao , Chen Wanyong , Sun Jialei , Atyah Manar , Yin Yirui , Zhang Wentao , Guo Lei , Ye Qinghai , Dong Qiongzhu , Shi Yi , Ren Ning
Published: June 2018

WW domain‐containing oxidoreductase (WWOX), which has a protein‐interaction domain and is regarded to be a tumor suppressor, has been known to play an important role in anti‐angiogenesis and cancer progression. This study aimed to investigate prognostic values of WWOX expression in hepatocellular carcinoma (HCC) patients after hepatectomy. Additionally, we intended to formulate a valuable prognostic nomogram for HCCs. 182 HCC patients who underwent hepatectomy from January 2009 to January 2010 were enrolled in our study. qRT‐PCR, Western blot, and immunohistochemistry on tissue microarrays were then used to determine the expression levels of WWOX. An evaluation of the role of WWOX expression levels in the prognosis and outcome of patients was established. A decrease in the expression of WWOX was found when compared to adjacent tumor‐free tissues, which led to worse overall survival (OS) and recurrence‐free survival (RFS) and, therefore, was considered as an independent negative factor in the prognosis of HCC. Two nomograms, comprising WWOX, alpha‐fetoprotein (AFP), tumor size, and γ‐glutamyltransferase (γ‐GT), were constructed to obtain superior discriminatory abilities than conventional staging systems in terms of C‐index and clinical net benefit on decision curve analysis (DCA) for OS and RFS. Our data suggest that WWOX expression is strongly related to HCC post‐resection aggressiveness and recurrence. Additional advanced and accurate predictive model through the incorporation of WWOX into nomogram could help predict OS or RFS for HCC patients.
Chronic myelogenous leukemia on target
Authors: Némethová Veronika , Rázga Filip
Published: June 2018

Chronic myelogenous leukemia (CML) is commonly treated with tyrosine kinase inhibitors (TKIs) that inhibit the pro‐leukemic activity of the BCR‐ABL1 oncoprotein. Despite the therapeutic progress mediated by TKI use, off‐target effects, treatment‐induced drug resistance, and the limited effect of these drugs on CML stem cells (SCs) are major drawbacks frequently resulting in insufficient or unsustainable treatment. Therefore, intense research efforts have focused on development of improved TKIs and alternative treatment strategies to eradicate CML SCs. Alongside efforts to design superior protein inhibitors, the need to overcome the poor therapeutic effect of TKIs on CML SCs has led to a renaissance of antisense strategies, as they are reported as effective in more primitive cell types. Despite the greater drug design flexibility offered by antisense sequence variability and remarkable chemical improvements, antisense drugs exhibit unacceptable levels of off‐target effects, precluding them from large‐scale clinical testing. Recent advances in antisense drug design have led to a pioneering mRNA recognition concept that may offer a helping hand in eliminating off‐target effects, and has potential to bridge the gap between research and clinical practice.
Pharmacokinetics, Safety, and Tolerability of Rolapitant Administered Intravenously Following Single Ascending and Multiple Ascending Doses in Healthy Subjects
Authors: Wang Xiaodong , Zhang Zhi‐Yi , Wang Jing , Powers Dan , Arora Sujata , Lu Sharon , Kansra Vikram
Published: June 2018

Rolapitant is a selective and long‐acting neurokinin‐1 receptor antagonist approved in an oral formulation in combination with dexamethasone and a 5‐hydroxytryptamine type 3 receptor antagonist for the prevention of delayed chemotherapy‐induced nausea and vomiting in adults. The pharmacokinetic and safety profiles of intravenous (IV) rolapitant were evaluated in two open‐label, phase 1 trials in healthy subjects. Single ascending dose (SAD) and multiple ascending dose studies were conducted in one trial (PR‐11‐5012‐C), and a supratherapeutic SAD study was conducted in a separate trial (PR‐11‐5022‐C). In the SAD and supratherapeutic studies, rolapitant maximum plasma concentration, area under the plasma drug concentration‐time curve (AUC) from time zero to time of last measured concentration, and AUC from time zero to infinity increased dose‐proportionally following single IV infusions of 18 to 270 mg. In the multiple ascending dose study, following 10 daily IV infusions of rolapitant 18, 36, or 54 mg, the mean day 10:day 1 maximum concentration ratio was 1.97, 1.52, and 2.07, respectively, and the mean day 10:day 1 ratio of AUC from 0 to 24 hours was 4.30, 4.59, and 5.38, respectively, indicating drug accumulation over time. Across all studies, rolapitant was gradually eliminated from plasma, with a half‐life of 135‐231 hours. Rolapitant was safe and well tolerated across all studies, with no serious or severe rolapitant‐related treatment‐emergent adverse events. The most common rolapitant‐related treatment‐emergent adverse events were headache, dry mouth, and dizziness, which were predominantly mild in severity. Overall, the pharmacokinetic and safety profiles of IV rolapitant were consistent with those of the oral formulation.
Are seeds able to germinate before fruit color ripening? Evidence from six Neotropical bird‐dispersed plant species
Authors: Cruz‐Tejada Diana María , Acosta‐Rojas Diana Carolina , Stevenson Pablo R.
Published: June 2018

Many plants attract seed dispersers and indicate the presence of ripe, fleshy fruits with coloration changes. If seed maturation is simultaneous with visual signs for frugivorous, a portion of seeds can be removed before being ready for dispersal. In this study, we tested the delay visual signal hypothesis (DVSH), which implies high reproductive success when seed maturation precedes the visual signal of the fruit ripening, limiting the dispersal of unviable seeds. We evaluated this hypothesis with six tropical species that have fruits with discrete coloration for the immature, intermediate, and mature stages, testing the prediction that the development of mature and intermediate seeds is similar. First, we verified that the coloration of three categories was differentiable with color analysis. Next, we carried out germination and viability tests (i.e., electrical conductivity [EC] and tetrazolium) as an approach to evaluate the germination potential along development. We found that the EC of three species decreased constantly during fruit ripening, suggesting that the seed maturation is a gradual process, with a substantial germination of intermediate seeds. In the other species, the conductivity of seeds of fruits with intermediate coloration was lower than that of mature fruit, because mature seeds are more affected by predators and pathogens. The tetrazolium tests indicated that the viability of seeds of three species increased with maturity and smaller differences between intermediate and mature stages were observed, supporting the DVSH. Only two species achieved high percentages of germination, and for Myrcia splendens, the pattern was very consistent with the hypothesis. We concluded that the germination and viability rates of the seeds of each plant species depend on many factors (e.g., dormancy and time of exposure to predators); however, for all the species studied, there is some evidence that seeds can germinate before they reach maturity by color.
Strategies for Transmission‐Line Siting
Authors: Hietter Laurie , Heim Susanne , Fisher Iain
Published: June 2018

Siting and permitting gas, water, or electric transmission lines can be one of the biggest costs and source of delays in project development. Why devote significant resources to siting? Early stakeholder engagement is the best opportunity to scope the issues that need to be addressed in the environmental process to do the following.
Inflatable sewer plug rescues pump tailpiece from well
Authors: Kenyon Robert
Published: June 2018

When a pump tailpiece vibrated off and fell to the bottom of a 200 foot (60 m) well and became lodged in 2 feet (0.6 m) of sand, employees of the Water Treatment Plant in Boynton Beach, Florida used a reinforced inflatable sewer plug with metal plates on the top and bottom to retrieve the tailpiece.
Bryozoa—An Uncommon Biological Problem
Authors: Beer Charles R.
Published: June 2018

The bryozoa are a group of freshwater and marine invertebrate animals that live in colonies. The formation of bryozoa at water treatment plants is troublesome to operators. This article describes the growth and structure of bryozoa, operating problems they cause, and a solution to the problem. The best solution is to prevent the formation of the bryozoan colonies through the addition of chlorine. Experience at the Marston Water Treatment Plant in Denver, Colorado with bryozoa is discussed.
Massachusetts Businesses Boost Conservation
Authors: McGrath Laura
Published: June 2018

Water is becoming a significant expense for business and industry. Many businesses, however, are taking steps to reduce and manage rising water, sewer, and other water‐related costs. Included in the article are examples of savings made by various businesses including a hotel, a manufacturer of industrial ceramics and a copy shop. Suggestions for reducing water use are given.
When Is Meter Replacement Cost‐Effective?
Authors: McDonald Joe
Published: June 2018

This month's question asks whether or not replacing meters for a small water system would be worth the expense. The point at which it becomes cost‐effective to replace or repair a meter is a question of the replacement or repair costs, water rates, and the amount of water the customer uses. AWWA has guidelines for accuracy of new, rebuilt, and repaired meters. General considerations for a meter replacement program are listed.
Process Control Testing Using a $6 Filter
Authors: Hancock Keith W. , Klonicki Tricia
Published: June 2018

To optimize water treatment processes, water treatment plant operators need access to a variety of techniques for monitoring and measuring how well the treatment plant is operating. This article describes using a $6 polypropylene filter cartridge to observe filter color, wash‐water characteristics, and centrifugate characteristics as an effective technique. Samples of raw and finished water are collected following the protocol used for microscopic particulate analysis (MPA) for filter plant optimization. Sample collection points along with frequency, length, and timing of sampling are determined by the individual utility, depending on the goals and resources of that utility and operations‐process control staff availability.
What's Required for Certification?
Authors: Stubbart John
Published: June 2018

This month's question asked for recommendations on training and resource materials for new operators to become certified, and for more experienced operators to advance. The article lists the minimum basic requirements for operators, acceptable subject matter for continuing education requirements and contact hours of actual training on one subject, and several types of training. Related handbooks, study guides and field guides are listed.
Avoiding Pink Stain Pain
Authors: Soucle William J. , Schuler Bill
Published: June 2018

This article discusses an investigative approach developed by Central Lake County Joint Action Water Agency (CLCJAWA) in Lake Bluff, Illinois, to identify the organisms that cause pink staining on bathroom fixtures, toilet bowls, sinks, shower curtains, laundry tubs, etc. The article describes laboratory analyses on pink stains and the cleaning process required to rid households of the stain. Suggestions for minimizing pink staining are given, along with further resources.
Treating Water Nature's Way
Authors:   AWWA Organic Contaminants Control Committee
Published: June 2018

This article discusses combining natural and traditional treatment systems to provide multiple barriers, improve source water quality, minimize treatment costs by lowering chemical doses, and improve finished water quality. Examples of natural treatment systems include natural and man‐made wetlands, tree farms used for landfill leachate, and water moved through soil or aquifers. The article discusses riverbank filtration and aquifer storage and recovery as natural treatment options, along with biological processes, physical processes, and chemical processes. It also discusses how the quantity and quality of water from these systems depends on the hydrology of surface and groundwater sources, such as riverbed infiltration rate and contact time in the soil, and the soil's geology.
Fast Response, Early Boost: Eliminate Ammonia‐Oxidizing Bacteria
Authors: Bleth Joel
Published: June 2018

This article reports on experiments conducted during 2006 and 2007 in more than 50 tanks at two California locations that indicate nitrite formation and loss of residual disinfectant can be minimized or eliminated with a fast response and early chlorine boost. The solution offers many benefits and eliminates some complexity in complying with the Stage 2 Disinfection Byproduct Rule. The article presents a fast response‐early boost plan that consists of implementing an aggressive water quality monitoring plan for warm weather conditions, as well as establishing trigger points in tanks that signal situations requiring a boost in chlorine levels. The article provides a table illustrating breakpoint chlorination, along with a list of resources.
Not So Fast!: Close Hydrants Slowly
Authors: Walski Thomas M.
Published: June 2018

This article discusses how the magnitude of a transient pressure surge is directly related to the speed with which a hydrant is opened or closed. Field data observations are presented, along with modeling transients including pressure plots, transient profiles, mapping transients, and transients on opening.
Use the Right Source at the Right Time
Authors: Laidlaw P. Scott , Heath Gene
Published: June 2018

The Southwest Florida Water Management District was prompted to focus on creative water management practices when years of drought conditions caused a severe water shortage in southwest Florida. The Southern Water Use Caution Area was created to manage the state's water resources in eight counties of the SWFWMD, reduce the region's dependency on groundwater, and halt saltwater intrusion along the coast. Created in 1982 by interlocal agreement, the Peace River Manasota Regional Water Supply Authority consists of four member governments: Charlotte, DeSoto, Manatee, and Sarasota counties. Working with its members and SWFWMD, the authority turned to conjunctive use–harmoniously combining surface water and groundwater supplies–to maximize use of existing infrastructure and sources to meet projected short‐term supply deficits.
Neurexin Superfamily Cell Membrane Receptor Contactin-Associated Protein Like-4 (Cntnap4) Is Involved in Neural EGFL-Like 1 (Nell-1)-Responsive Osteogenesis
Authors: Li Chenshuang , Zheng Zhong , Ha Pin , Chen Xiaoyan , Jiang Wenlu , Sun Shan , Chen Feng , Asatrian Greg , Berthiaume Emily A , Kim Jong Kil , Chen Eric C , Pang Shen , Zhang Xinli , Ting Kang , Soo Chia
Published: June 2018

Contactin-associated protein-like 4 (Cntnap4) is a member of the neurexin superfamily of transmembrane molecules that have critical functions in neuronal cell communication. Cntnap4 knockout mice display decreased presynaptic gamma-aminobutyric acid (GABA) and increased dopamine release that is associated with severe, highly penetrant, repetitive, and perseverative movements commonly found in human autism spectrum disorder patients. However, no known function of Cntnap4 has been revealed besides the nervous system. Meanwhile, secretory protein neural EGFL-like 1 (Nell-1) is known to exert potent osteogenic effects in multiple small and large animal models without the off-target effects commonly found with bone morphogenetic protein 2. In this study, while searching for a Nell-1-specific cell surface receptor during osteogenesis, we identified and validated a ligand/receptor-like interaction between Nell-1 and Cntnap4 by demonstrating: 1) Nell-1 and Cntnap4 colocalization on the surface of osteogenic-committed cells; 2) high-affinity interaction between Nell-1 and Cntnap4; 3) abrogation of Nell-1-responsive Wnt and MAPK signaling transduction, as well as osteogenic effects, via Cntnap4 knockdown; and 4) replication of calvarial cleidocranial dysplasias-like defects observed in Nell-1-deficient mice in Wnt1-Cre-mediated Cntnap4-knockout transgenic mice. In aggregate, these findings indicate that Cntnap4 plays a critical role in Nell-1-responsive osteogenesis. Further, this is the first functional annotation for Cntnap4 in the musculoskeletal system. Intriguingly, Nell-1 and Cntnap4 also colocalize on the surface of human hippocampal interneurons, implicating Nell-1 as a potential novel ligand for Cntnap4 in the nervous system. This unexpected characterization of the ligand/receptor-like interaction between Nell-1 and Cntnap4 indicates a novel biological functional axis for Nell-1 and Cntnap4 in osteogenesis and, potentially, in neural development and function. © 2018 American Society for Bone and Mineral Research.
A New Money Attitudes Questionnaire
Authors: Lay Alixe , Furnham Adrian
Published: June 2018

Abstract. This study reports on the development and validation of a new questionnaire to measure money attitudes and beliefs. In all, 268 participants from diverse backgrounds, who were recruited online, completed a 30-item questionnaire. Exploratory and confirmatory factor analyses verified a five-factor model. The factors were labeled: Achievement and Success, Power and Status, Mindful and Responsible, Saving Concerns, and Financial Literacy Worries. Results showed that demography (sex, age, and education), ideology (politics and religious practices), and self-rated happiness, success, and adjustment were related to all five factors, particularly the first two. Worries about Financial Literacy is an important and neglected factor in money attitudes research, which has implications for consumer well-being and protection. Limitations and implications are noted.
Focus Switching in Working Memory
Authors: Linares Rocío , Pelegrina Santiago
Published: June 2018

Abstract. Focus switching in working memory involves accessing an object in the focus of attention in order to retrieve its content. Objects in working memory can be viewed as consisting of two types of information: contents (e.g., numerical information) and contexts (e.g., cues to retrieve the contents). This study examined the extent to which content retrieval and context access may be separated. Three experiments were carried out in which object switching and content retrieval were manipulated. In addition, the alternation between the retrieval operations was also manipulated. The main result was that content retrieval required time over and above that needed to access the object. This finding supports the idea that contexts and their contents may be accessed independently when an object is brought into the focus.
Adipocytes induce distinct gene expression profiles in mammary tumor cells and enhance inflammatory signaling in invasive breast cancer cells
Authors: Nickel Annina , Blücher Christina , Kadri Omaeir Al , Schwagarus Nancy , Müller Silvana , Schaab Michael , Thiery Joachim , Burkhardt Ralph , Stadler Sonja C.
Published: June 2018

Obesity is a known risk factor for breast cancer. Since obesity rates are constantly rising worldwide, understanding the molecular details of the interaction between adipose tissue and breast tumors becomes an urgent task. To investigate potential molecular changes in breast cancer cells induced by co-existing adipocytes, we used a co-culture system of different breast cancer cell lines (MCF-7 and T47D: ER+/PR+/HER2− and MDA-MB-231: ER−/PR−/HER2−) and murine 3T3-L1 adipocytes. Here, we report that co-culture with adipocytes revealed distinct changes in global gene expression pattern in the different breast cancer cell lines. Our microarray data revealed that in both ER+ cell lines, top upregulated genes showed significant enrichment for hormone receptor target genes. In triple-negative MDA-MB-231 cells, co-culture with adipocytes led to the induction of pro-inflammatory genes, mainly involving genes of the Nf-κB signaling pathway. Moreover, co-cultured MDA-MB-231 cells showed increased secretion of the pro-inflammatory interleukins IL-6 and IL-8. Using a specific NF-κB inhibitor, these effects were significantly decreased. Finally, migratory capacities were significantly increased in triple-negative breast cancer cells upon co-culture with adipocytes, indicating an enhanced aggressive cell phenotype. Together, our studies illustrate that factors secreted by adipocytes have a significant impact on the molecular biology of breast cancer cells.
Acetylcholine-modulated plasticity in reward-driven navigation: a computational study
Authors: Zannone Sara , Brzosko Zuzanna , Paulsen Ole , Clopath Claudia
Published: June 2018

Neuromodulation plays a fundamental role in the acquisition of new behaviours. In previous experimental work, we showed that acetylcholine biases hippocampal synaptic plasticity towards depression, and the subsequent application of dopamine can retroactively convert depression into potentiation. We also demonstrated that incorporating this sequentially neuromodulated Spike-Timing-Dependent Plasticity (STDP) rule in a network model of navigation yields effective learning of changing reward locations. Here, we employ computational modelling to further characterize the effects of cholinergic depression on behaviour. We find that acetylcholine, by allowing learning from negative outcomes, enhances exploration over the action space. We show that this results in a variety of effects, depending on the structure of the model, the environment and the task. Interestingly, sequentially neuromodulated STDP also yields flexible learning, surpassing the performance of other reward-modulated plasticity rules.
Symmetry broken spin reorientation transition in epitaxial MgO/Fe/MgO layers with competing anisotropies
Authors: Martínez Isidoro , Tiusan Coriolan , Hehn Michel , Chshiev Mairbek , Aliev Farkhad G.
Published: June 2018

The observation of perpendicular magnetic anisotropy (PMA) at MgO/Fe interfaces boosted the development of spintronic devices based on ultrathin ferromagnetic layers. Yet, magnetization reversal in the standard magnetic tunnel junctions (MTJs) with competing PMA and in-plane anisotropies remains unclear. Here we report on the field induced nonvolatile broken symmetry magnetization reorientation transition from the in-plane to the perpendicular (out of plane) state at temperatures below 50 K. The samples were 10 nm thick Fe in MgO/Fe(100)/MgO as stacking components of V/MgO/Fe/MgO/Fe/Co double barrier MTJs with an area of 20 × 20 μm2. Micromagnetic simulations with PMA and different second order anisotropies at the opposite Fe/MgO interfaces qualitatively reproduce the observed broken symmetry spin reorientation transition. Our findings open the possibilities to develop multistate epitaxial spintronics based on competing magnetic anisotropies.
Assessing agreement among alternative climate change projections to inform conservation recommendations in the contiguous United States
Authors: Belote R. Travis , Carroll Carlos , Martinuzzi Sebastián , Michalak Julia , Williams John W. , Williamson Matthew A. , Aplet Gregory H.
Published: June 2018

Addressing uncertainties in climate vulnerability remains a challenge for conservation planning. We evaluate how confidence in conservation recommendations may change with agreement among alternative climate projections and metrics of climate exposure. We assessed agreement among three multivariate estimates of climate exposure (forward velocity, backward velocity, and climate dissimilarity) using 18 alternative climate projections for the contiguous United States. For each metric, we classified maps into quartiles for each alternative climate projections, and calculated the frequency of quartiles assigned for each gridded location (high quartile frequency = more agreement among climate projections). We evaluated recommendations using a recent climate adaptation heuristic framework that recommends emphasizing various conservation strategies to land based on current conservation value and expected climate exposure. We found that areas where conservation strategies would be confidently assigned based on high agreement among climate projections varied substantially across regions. In general, there was more agreement in forward and backward velocity estimates among alternative projections than agreement in estimates of local dissimilarity. Consensus of climate predictions resulted in the same conservation recommendation assignments in a few areas, but patterns varied by climate exposure metric. This work demonstrates an approach for explicitly evaluating alternative predictions in geographic patterns of climate change.
Utilizing individual fish biomass and relative abundance models to map environmental niche associations of adult and juvenile targeted fishes
Authors: Galaiduk Ronen , Radford Ben T. , Harvey Euan S.
Published: June 2018

Many fishes undergo ontogenetic habitat shifts to meet their energy and resource needs as they grow. Habitat resource partitioning and patterns of habitat connectivity between conspecific fishes at different life-history stages is a significant knowledge gap. Species distribution models were used to examine patterns in the relative abundance, individual biomass estimates and environmental niche associations of different life stages of three iconic West Australian fishes. Continuous predictive maps describing the spatial distribution of abundance and individual biomass of the study species were created as well predictive hotspot maps that identify possible areas for aggregation of individuals of similar life stages of multiple species (i.e. spawning grounds, fisheries refugia or nursery areas). The models and maps indicate that processes driving the abundance patterns could be different from the body size associated demographic processes throughout an individual’s life cycle. Incorporating life-history in the spatially explicit management plans can ensure that critical habitat of the vulnerable stages (e.g. juvenile fish, spawning stock) is included within proposed protected areas and can enhance connectivity between various functional areas (e.g. nursery areas and adult populations) which, in turn, can improve the abundance of targeted species as well as other fish species relying on healthy ecosystem functioning.
Guanosine tetraphosphate relieves the negative regulation of Salmonella pathogenicity island-2 gene transcription exerted by the AT-rich ssrA discriminator region
Authors: Tapscott Timothy , Kim Ju-Sim , Crawford Matthew A. , Fitzsimmons Liam , Liu Lin , Jones-Carson Jessica , Vázquez-Torres Andrés
Published: June 2018

The repressive activity of ancestral histone-like proteins helps integrate transcription of foreign genes with discrepant AT content into existing regulatory networks. Our investigations indicate that the AT-rich discriminator region located between the −10 promoter element and the transcription start site of the regulatory genessrAplays a distinct role in the balanced expression of theSalmonellapathogenicity island-2 (SPI2) type III secretion system. The RNA polymerase-binding protein DksA activates thessrABregulon post-transcriptionally, whereas the alarmone guanosine tetraphosphate (ppGpp) relieves the negative regulation imposed by the AT-richssrAdiscriminator region. An increase in the GC-content of thessrAdiscriminator region enhancesssrABtranscription and SsrB translation, thus activating the expression of downstream SPI2 genes. ASalmonellastrain expressing a GC-richssrAdiscriminator region is attenuated in mice and grows poorly intracellularly. The combined actions of ppGpp and DksA on SPI2 expression enableSalmonellato grow intracellularly, and cause disease in a murine model of infection. Collectively, these findings indicate that (p)ppGpp relieves the negative regulation associated with the AT-rich discriminator region in the promoter of the horizontally-acquiredssrAgene, whereas DksA activatesssrBgene expression post-transcriptionally. The combined effects of (p)ppGpp and DksA on thessrABlocus facilitate a balanced SPI2 virulence gene transcription that is essential forSalmonellapathogenesis.
A milk formula containing maltodextrin, vs. lactose, as main carbohydrate source, improves cognitive performance of piglets in a spatial task
Authors: Clouard Caroline , Le Bourgot Cindy , Respondek Frédérique , Bolhuis J. Elizabeth , Gerrits Walter J. J.
Published: June 2018

In recent years, lactose-free and low-lactose infant formulas have been increasingly used. The impact of using different carbohydrates than lactose on later cognition of formula-fed infants remains, however, unknown. We examined the effects of providing formulas containing either digestible maltodextrin or lactose as main carbohydrate source (28% of total nutrient composition) on cognitive performance of piglets. Piglets received the formulas from 1 to 9 weeks of age and, starting at 12 weeks, were individually tested in a spatial holeboard task (n = 8 pens/formula), in which they had to learn and memorize a configuration of baited buckets. After 28 acquisition trials, piglets were subjected to 16 reversal trials in which the location of the baited buckets was changed. Piglets fed the maltodextrin-based formula had higher reference memory (RM) scores than piglets fed the lactose-based formula towards the end of acquisition. During the switch of configuration, piglets offered the maltodextrin-based formula tended to have higher RM scores and make fewer RM errors than piglets offered the lactose-based formula. Working (short-term) memory was not affected by the formulas. Compared to lactose, the use of maltodextrin in milk formulas improved long-term spatial memory of piglets, even weeks after the end of the intervention.
Methodology for Y Chromosome Capture: A complete genome sequence of Y chromosome using flow cytometry, laser microdissection and magnetic streptavidin-beads
Authors: Alvarez-Cubero M. J. , Santiago O. , Martínez-Labarga C. , Martínez-García B. , Marrero- Díaz R. , Rubio-Roldan A. , Pérez-Gutiérrez A. M. , Carmona-Saez P. , Lorente J. A. , Martinez-Gonzalez L. J.
Published: June 2018

This study is a comparison of the efficiency of three technologies used for Y chromosome capture and the next-generation sequencing (NGS) technologies applied for determining its whole sequence. Our main findings disclose that streptavidin–biotin magnetic particle-based capture methodology offers better and a deeper sequence coverage for Y chromosome capture, compared to chromosome sorting and microdissection procedures. Moreover, this methodology is less time consuming and the most selective for capturing only Y chromosomal material, in contrast with other methodologies that result in considerable background material from other, non-targeted chromosomes. NGS results compared between two platforms, NextSeq 500 and SOLID 5500xl, produce the same coverage results. This is the first study to explore a methodological comparison of Y chromosome capture and genetic analysis. Our results indicate an improved strategy for Y chromosome research with applications in several scientific fields where this chromosome plays an important role, such as forensics, medical sciences, molecular anthropology and cancer sciences.
Towards the indium nitride laser: obtaining infrared stimulated emission from planar monocrystalline InN structures
Authors: Andreev B. A. , Kudryavtsev K. E. , Yablonskiy A. N. , Lobanov D. N. , Bushuykin P. A. , Krasilnikova L. V. , Skorokhodov E. V. , Yunin P. A. , Novikov A. V. , Davydov V. Yu , Krasilnik Z. F.
Published: June 2018

The observation of a stimulated emission at interband transitions in monocrystalline n-InN layers under optical pumping is reported. The spectral position of the stimulated emission changes over a range of 1.64 to 1.9 μm with variations of free electron concentration in InN layers from 2·1019 cm−3 to 3·1017 cm−3. The main necessary conditions for achieving the stimulated emission from epitaxial InN layers are defined. In the best quality samples, a threshold excitation power density is obtained to be as low as 400 W/cm2 at T = 8 K and the stimulated emission is observed up to 215 K. In this way, the feasibility of InN-based lasers as well as the potentials of crystalline indium nitride as a promising photonic material are demonstrated.
Mechanical behaviour and microstructural evolution of Ni-based single crystal alloys under shock loading
Authors: Li Ben , Dong Chao , Yu Jingui , Zhang Qiaoxin , Zhou Hongyan , Liu Rong
Published: June 2018

Through molecular dynamics simulations, we find that the (001) phase interface has the strongest resistance to shock loading.
Non-targeted metabolite profiling and specific targeted discrimination strategy for quality evaluation of Cortex Phellodendri from different varieties
Authors: Zhu Guoxue , Feng Fang
Published: June 2018

Non-targeted metabolite profiling and specific targeted discrimination strategy coupled with pattern recognition to differentiate the two varieties in rats.
Antibody-pHPMA functionalised fluorescent silica nanoparticles for colorectal carcinoma targeting
Authors: Lizoňová Denisa , Majerská Monika , Král Vlastimil , Pechar Michal , Pola Robert , Kovář Marek , Štěpánek František
Published: June 2018

Nanoparticles functionalised with pHPMA and monoclonal antibody IgG M75 show specific adhesion to tumour cells expressing carbonic anhydrase IX bothin vitroandin vivo.
Large interlayer spacing vanadium oxide nanotubes as cathodes for high performance sodium ion batteries
Authors: Zhang Kun , Gao Guohua , Sun Wei , Liang Xing , Liu Yindan , Wu Guangming
Published: June 2018

Sodium ion batteries (SIBs), as a potential alternative to Li-ion batteries (LIBs), have attracted great attention from researchers.
Copper-catalyzed tandem reaction of 2-alkynylanilines with benzoquinones: efficient access to 3-indolylquinones
Authors: Jillella Raveendra , Oh Chang Ho
Published: June 2018

Copper-catalyzed domino cyclization of 2-alkynylanilines followed by C–C bond formation with quinones is an efficient method of accessing 3-indolyl quinones.
Biochar supported sulfide-modified nanoscale zero-valent iron for the reduction of nitrobenzene
Authors: Zhang Dejin , Li Yang , Tong Siqi , Jiang Xinbai , Wang Lianjun , Sun Xiuyun , Li Jiansheng , Liu Xiaodong , Shen Jinyou
Published: June 2018

Biochar (BC)-supported S-nZVI was prepared to enhance the reactivity of S-nZVI for nitrobenzene (NB) reduction.
Application of ceramic dust as a modifier reducing the extent of rheological deformations in airfield pavement concrete
Authors: Linek Małgorzata
Published: June 2018

The article presents material solution based on the application of ceramic dust as concrete mix component intended for airfield pavements. Material composition is intended for the application on the selected areas of pavement exposed to the influence of imposed thermal loads intensifying the stress strain state of concrete slabs. Due to the nature of loading of these parts it is necessary to reduce the extent of registered rheological deformations. Concrete containing dust additive is distinguished by more favourable porosity properties, more consistent cement matrix without visible discontinuities and with the formed different hydration products. Diversification of internal micro structure of cement concrete using the suggested dust has significant influence on the improvement of mechanical, physical and performance parameters. Also, assessment of the applied dust influence on the extent of the registered rheological deformations was presented. The analyses included concretes curing in standard conditions and concretes subject to thermal cycles representing the destructive influence of imposed loading. The obtained laboratory test results prove clearly the validity of the suggested solution. Reducing the extent of deformations is derivative of favourable changes observed in internal structure of concrete composite. Better formed contact areas provide the increased concrete parameters and consequently influence extending concrete durability.