bluuebunny/crossref_metadata_2025 huggingface dataset:
Docosahexaenoic Acid has stem cell-specific effects in the SVZ and restores olfactory neurogenesis and function in the aging brain
Authors: Le Belle JE , Sperry J , Ludwig K , Harris NG , Caldwell MA , Kornblum HI
Published: February 2020

Fatty acids are well known as important constituents for the synthesis of membrane lipids and as sources of cellular energy in the CNS. However, fatty acids can also act as vital second messenger molecules in the nervous system and regulate the activity of many proteins affecting cell growth and survival. Here, we show that an essential dietary fatty acid, Decosahexaenoic acid, (DHA), can enhance stem cell function in vitro and in vivo. We found that this effect is not due to an increase in the overall proliferation rate of all neural progenitors, but is due to an increase in the number of multipotent stem cells that leads to greater levels of subventricular zone (SVZ) neurogenesis with restoration of olfactory function in aged mice. These effects were likely mediated through increased EGF-receptor sensitivity, a conversion of EGRFR+ progenitors back into an EGRFR+/GFAP+ stem cell state, and the activation of the PI3K/AKT signaling pathway, which is a critical pathway in many NSC cell functions including cell growth and survival. Together these data demonstrate that neural stem cells in the aged and quiescent neurogenic niche of the mouse SVZ retain their ability to self-renew and contribute to neurogenesis when apparently rejuvenated by DHA and PI3K/AKT pathway activation. DHA stimulation of this signaling enhances the number of multipotent stem cells and neurogenesis in young and aged rodent and human stem cells and hence may have implications for the manipulation of neural stem cells for brain repair.

Significance Statement

We have identified potentially important effects of DHA on the stem cell population which may be unique to the SVZ stem cell niche. Our studies demonstrate that DHA can promote the production of neural stem cells, possibly via a non-proliferative mechanism stimulated by EGF receptor activation, and prolongs their viability. Aging animals undergo an apparent loss in SVZ stem cells and an associated decline in olfactory bulb function. We find that dietary DHA supplementation at least partially restores stem cell numbers, olfactory bulb neurogenesis and olfactory discrimination and memory in aged mice, demonstrating a capacity for rejuvenation is retained despite age-related changes to the niche, which has significant implications for ameliorating cognitive decline in aging and for endogenous brain repair.
Benchmarking DNA Methylation Assays for Marine Invertebrates
Authors: Dixon Groves , Matz Mikhail
Published: February 2020

Interrogation of chromatin modifications, such as DNA methylation, has potential to improve forecasting and conservation of marine ecosystems. The standard method for assaying DNA methylation (Whole Genome Bisulfite Sequencing), however, is too costly to apply at the scales required for ecological research. Here we evaluate different methods for measuring DNA methylation for ecological epigenetics. We compare Whole Genome Bisulfite Sequencing (WGBS) with Methylated CpG Binding Domain Sequencing (MBD-seq), and a modified version of MethylRAD we term methylation-dependent Restriction site-Associated DNA sequencing (mdRAD). We evaluate these three assays in measuring variation in methylation across the genome, between genotypes, and between polyp types in the reef-building coral Acropora millepora. We find that all three assays measure absolute methylation levels similarly, with tight correlations for methylation of gene bodies (gbM), as well as exons and 1Kb windows. Correlations for differential gbM between genotypes were weaker, but still concurrent across assays. We detected little to no reproducible differences in gbM between polyp types. We conclude that MBD-seq and mdRAD are reliable cost-effective alternatives to WGBS. Moreover, the considerably lower sequencing effort required for mdRAD to produce comparable methylation estimates makes it particularly useful for ecological epigenetics.
Puf4 Mediates Post-transcriptional Regulation of Caspofungin Resistance inCryptococcus neoformans
Authors: Kalem Murat C. , Subbiah Harini , Leipheimer Jay , Glazier Virginia E. , Panepinto John C.
Published: February 2020

Echinocandins have been on the market for 20 years, yet they are the newest class of antifungal drugs. The human fungal pathogenCryptococcus neoformansis intrinsically resistant to the echinocandin antifungal drug caspofungin, which targets theβ-1,3-glucan synthase encoded by theFKS1. Analysis of aC. neoformans puf4Δ mutant, lacking the pumilio/FBF RNA binding protein family member Puf4, revealed exacerbated caspofungin resistance. In contrast, overexpression ofPUF4resulted in caspofungin sensitivity. TheFKS1mRNA contains three Puf4-binding elements (PBEs) in its 5’ untranslated region. Puf4 binds with specificity to this region of theFKS1. TheFKS1mRNA was destabilized in thepuf4Δ mutant, and the abundance of theFKS1mRNA was reduced compared to wild type, suggesting that Puf4 is a positive regulatorFKS1mRNA stability. In addition toFKS1, the abundance of additional cell wall biosynthesis genes, including chitin synthases (CHS3,CHS4,CHS6) and deacetylases (CDA1,CDA2,CDA3) as well as aβ-1,6-glucan synthase gene (SKN1) was regulated by Puf4 during a caspofungin time course. The use of fluorescent dyes to quantify cell wall components revealed that thepuf4Δ mutant had increased chitin content, suggesting a cell wall composition that is less reliant onβ-1,3-glucan. Overall, our findings suggest a mechanism by which caspofungin resistance, and more broadly, cell wall biogenesis, is regulated post-transcriptionally by Puf4.

Importance

Cryptococcus neoformansis an environmental fungus that causes pulmonary and central nervous system infections. It is also responsible for 15% of AIDS-related deaths. A major contributor to the high morbidity and mortality statistics is the lack of safe and effective antifungal therapies, especially in resource-poor settings. Yet, antifungal drug development has stalled in the pharmaceutical industry. Therefore, it is of importance to understand the mechanism by whichC. neoformansis resistant to caspofungin in order to design adjunctive therapies to potentiate its activity toward this important pathogen.
Cortical processing of chemosensory and hedonic features of taste in active licking mice
Authors: Bouaichi Cecilia , Vincis Roberto
Published: February 2020

In the last two decades, a considerable amount of work has been devoted to investigating the neural processing and dynamics of the primary taste cortex of rats. Surprisingly, much less information is available on cortical taste electrophysiology in awake mice, an animal model that is taking a more prominent role in taste research. Here we present electrophysiological evidence demonstrating how the gustatory cortex (GC) encodes information pertaining the basic taste qualities (sweet, salty, sour, and bitter) when stimuli are actively sampled through licking, the stereotyped behavior by which mice control the access of fluids in the mouth. Mice were trained to receive each stimulus on a fixed ratio schedule in which they had to lick a dry spout six times to receive a tastant on the seventh lick. Electrophysiological recordings confirmed that GC neurons encode both chemosensory and hedonic aspects of actively sampled tastants. In addition, our data revealed two other main findings; GC neurons encoded information about taste identity in as little as 120 ms. Consistent with the ability of GC neurons to rapidly encode taste information, nearly half of the recorded neurons exhibited spiking activity that was entrained to licking at rates up to 8 Hz. Overall, our results highlight how the GC of mice processes tastants when they are actively sensed through licking, reaffirming and expanding our knowledge on cortical taste processing.

NEW & NOTEWORTHY

Relatively little information is available on the neural dynamics of taste processing in the mouse gustatory cortex (GC). In this study we investigate how the GC encodes information of the qualities and hedonics of a broad panel of gustatory stimuli when tastants are actively sampled through licking. Our results show that the GC neurons broadly encode taste qualities but also process taste hedonics and licking information in a temporally dynamic manner.
Tough Hydrogel-Based Biocontainment of Engineered Organisms for Continuous, Self-Powered Sensing and Computation
Authors: Tang Tzu-Chieh , Tham Eleonore , Liu Xinyue , Yehl Kevin , Rovner Alexis J. , Yuk Hyunwoo , Isaacs Farren J. , Zhao Xuanhe , Lu Timothy K.
Published: February 2020

Genetically modified microorganisms (GMMs) can enable a wide range of important applications, including environmental sensing, precision therapeutics, and responsive materials. However, containment of GMMs to prevent environmental escape and satisfy regulatory requirements is a bottleneck for real-world use1–7. While biochemical strategies have been developed to restrict unwanted growth and replication of GMMs in the environment8–12, there is a need for deployable physical containment technologies to achieve redundant, multi-layered, and robust containment2. In addition, form factors that enable easy retrieval would be useful for environmental sensing. To address this challenge, we developed a hydrogel-based encapsulation system for GMMs that incorporates a biocompatible multilayer tough shell and an alginate-based core. This DEployable Physical COntainment Strategy (DEPCOS) allows no detectable GMM escape, bacteria to be protected against environmental insults including antibiotics and low pH, controllable lifespan, and easy retrieval of genetically recoded bacteria. To highlight the versatility of a DEPCOS, we demonstrate that robustly encapsulated cells can execute useful functions, including performing cell-cell communication with other encapsulated bacteria and sensing heavy metals in water samples from the Charles River. We envision that our multilayered physical and chemical containment strategy will facilitate the realization of a wide range of real-world applications for ‘living’ biosensors.
Phytochemical screening and antimicrobial activities studies ofAcacia niloticafruit cover
Authors: Abdalla Abdelhamed A. , Mustafa Mujahed I. , Makhawi Abdelrafie M.
Published: February 2020

This study was carried out in Khartoum state, during November, 2019.Acacia niloticawas chosen for this study because of its using traditionally in treatment of many diseases. The Phytochemical constitutions ofA. niloticawere investigated with aim to identify the antimicrobial effects of this plant. The dried fruit cover ofAcacia niloticawas extracted successively with petroleum-ether, chloroform, methanol and distilled water. The phytochemical screening carried out on different extracts ofAcacia niloticafruit cover showed high amount of Glycosides, Flavonoids and Terpenoids (in all extracts) and moderate amount of Tannin in methanol and distilled water extracts, Alkaloids (acid and base) in methanol extract and Saponin in methanol and petroleum-ether extracts. The antimicrobial activity of extracts were evaluated against four standard bacteria species (gram positive bacteria;Staphylococcus aureus, Bacillus subtilis) and (gram negative bacteria;Pseudomonas aeruginosa, Escherichia coli). The plates were inoculated for sensitivity testing, minimum inhibitory concentration (MIC) was measured. The results of antimicrobial investigation show that the distilled water and methanolic extracts inhibited the growth of all microorganisms (Specified by the zone of inhibition). The results provide promising baseline information for potential use of these crude extracts in drug development programs in the pharmaceutical industries.
Cryo-EM structures and functional properties of CALHM channels of the human placenta
Authors: Drożdżyk Katarzyna , Sawicka Marta , Bahamonde Santos Maria-Isabel , Zaugg Jonas , Deneka Dawid , Albrecht Christiane , Dutzler Raimund
Published: February 2020

The transport of substances across the placenta is essential for the development of the fetus. Here, we were interested in the role of channels of the calcium homeostasis modulator (CALHM) family in the human placenta. By transcript analysis, we found the paralogs CALHM2, 4, and 6 to be highly expressed in this organ and upregulated during trophoblast differentiation. Based on electrophysiology, we found that activation of these paralogs differs from the voltage- and calcium-gated channel CALHM1. Cryo-EM structures of CALHM4 display decameric and undecameric assemblies with large cylindrical pore, while in CALHM6 a conformational change has converted the pore shape into a conus that narrows at the intracellular side, thus describing distinct functional states of the channel. The pore geometry alters the distribution of lipids, which occupy the cylindrical pore of CALHM4 in a bilayer-like arrangement whereas they have redistributed in the conical pore of CALHM6 with potential functional consequences.
ApoE e2 and aging-related outcomes in 379,000 UK Biobank participants
Authors: Kuo Chia-Ling , Pilling Luke C. , Atkins Janice L. , Kuchel George A. , Melzer David
Published: February 2020

The Apolipoprotein E (APOE) e4 allele is associated with reduced longevity and increased Coronary Artery Disease (CAD) and Alzheimer’s disease, with e4e4 having markedly larger effect sizes than e3e4. The e2 longevity promoting variant is less studied. We conducted a phenome-wide association study of ApoE e2e3 and e2e2 with aging phenotypes, to assess their potential as targets for anti-aging interventions. Data were from 379,000 UK Biobank participants, aged 40 to 70 years. e2e3 (n=46,535) had mostly lower lipid-related biomarker levels including reduced total and LDL-cholesterol, and lower risks of CAD (Odds Ratio=0.87, 95% CI: 0.83 to 0.90, p=4.92×10−14) and hypertension(OR=0.94, 95% CI: 0.92 to 0.97, p=7.28×10−7) versus e3e3. However, lipid changes in e2e2 (n=2,398) were more extreme, including a marked increase in triglyceride levels (0.41 Standard Deviations, 95% CI: 0.37 to 0.45, p=5.42×10−92), with no associated changes in CAD risks. There were no associations with biomarkers of kidney function. The effects of both e2e2 and e2e3 were minimal on falls, muscle mass, grip strength or frailty. In conclusion, e2e3 has protective effects on some health outcomes, but the effects of e2e2 are not similar, complicating the potential usefulness of e2 as a target for anti-aging intervention.
Epigenomic translocation of H3K4me3 broad domains over oncogenes following hijacking of super-enhancers
Authors: Mikulasova Aneta , Kent Daniel , Trevisan-Herraz Marco , Karataraki Nefeli , Fung Kent T.M. , Ashby Cody , Cieslak Agata , Yaccoby Shmuel , van Rhee Frits , Zangari Maurizio , Thanendrarajan Sharmilan , Schinke Carolina , Morgan Gareth J. , Asnafi Vahid , Spicuglia Salvatore , Brackley Chris A. , Corcoran Anne E. , Hambleton Sophie , Walker Brian A. , Rico Daniel , Russell Lisa J.
Published: February 2020

Chromosomal translocations are important drivers of haematological malignancies whereby proto-oncogenes are activated by juxtaposition with enhancers, often calledenhancer hijacking. We analysed the epigenomic consequences of rearrangements between the super-enhancers of the immunoglobulin heavy locus (IGH)and proto-oncogeneCCND1that are common in B-cell malignancies. By integrating BLUEPRINT epigenomic data with DNA breakpoint detection, we characterised the normal chromatin landscape of the humanIGHlocus and its dynamics after pathological genomic rearrangement. We detected an H3K4me3 broad domain (BD) within theIGHlocus of healthy B cells that was absent in samples withIGH-CCND1translocations. The appearance of H3K4me3-BD overCCND1in the latter was associated with overexpression and extensive chromatin accessibility of its gene body. We observed similar cancer-specific H3K4me3-BDs associated with hijacking of super-enhancers of other common oncogenes in B-cell (MAF,MYCandFGFR3/NSD2) and T-cell malignancies (LMO2, TLX3andTAL1). Our analysis suggests that H3K4me3-BDs can be created by super-enhancers and supports the new concept ofepigenomic translocation, where the relocation of H3K4me3-BDs from cell identity genes to oncogenes accompanies the translocation of super-enhancers.
Regulated unbinding of ZAP70 at the T cell receptor by kinetic avidity
Authors: Goyette Jesse , Depoil David , Yang Zhengmin , Isaacson Samuel A. , Allard Jun , van der Merwe P. Anton , Gaus Katharina , Dustin Michael L , Dushek Omer
Published: February 2020

Protein-protein binding domains are critical in signalling networks. Src homology 2 (SH2) domains are binding domains that interact with sequences containing phosphorylated tyrosines. A subset of SH2 domain-containing proteins have tandem domains, which are thought to enhance binding affinity and specificity. However, a trade-off exists between long-lived binding and the ability to rapidly reverse signalling, which is a critical requirement of noise filtering mechanisms such as kinetic proofreading. Here, we use modelling to show that the unbinding rate of tandem, but not single, SH2 domains can be accelerated by phosphatases when tandem domains bind by a kinetic, but not a static, avidity mode. We use surface plasmon resonance to show that ZAP70, a tandem SH2 domain-containing kinase, binds kinetically to biphosphorylated peptides from the T cell antigen receptor (TCR) and that the unbinding rate can be accelerated by the phosphatase CD45. An important functional prediction of regulated unbinding is that the intracellular ZAP70/TCR half-life in T cells will be correlated to the extracellular TCR/antigen half-life and we show that this is the case in both cell lines and primary T cells. The work highlights that binding by kinetic avidity breaks the trade-off between signal fidelity (requiring long half-life) and signal reversibility (requiring short half-life), which is a key requirement for T cell antigen discriminated mediated by kinetic proofreading.
The irradiated brain microenvironment supports glioma stemness and survival via astrocyte-derived Transglutaminase 2
Authors: Berg Tracy J. , Marques Carolina , Pantazopoulou Vasiliki , Johansson Elinn , von Stedingk Kristoffer , Lindgren David , Pietras Elin J. , Bergström Tobias , Swartling Fredrik J. , Governa Valeria , Bengzon Johan , Belting Mattias , Axelson Håkan , Squatrito Massimo , Pietras Alexander
Published: February 2020

The tumor microenvironment plays an essential role in supporting glioma stemness and radioresistance, and following radiotherapy, recurrent gliomas form in an irradiated microenvironment. Here, we found that astrocytes, when pre-irradiated, increased stemness and survival of co-cultured glioma cells. Tumor-naïve brains increased reactive astrocytes in response to radiation, and mice subjected to radiation prior to implantation of glioma cells developed more aggressive tumors. We identified extracellular matrix derived from irradiated astrocytes as a major driver of this phenotype, and astrocyte-derived transglutaminase 2 (TGM2) as a promoter of glioma stemness and radioresistance. TGM2 levels were increased after radiation in vivo and in recurrent human glioma, and TGM2 inhibitors abrogated glioma stemness and survival. These data suggest that irradiation of the brain results in the formation of a tumor-supportive microenvironment. Therapeutic targeting of radiation-induced, astrocyte-derived extracellular matrix proteins may enhance the efficacy of standard of care radiotherapy by reducing stemness in glioma.
A screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis
Authors: Coelho Rowena Alves , Joffe Luna Sobrino , Alves Gabriela Machado , Figueiredo-Carvalho Maria Helena Galdino , Brito-Santos Fábio , Amaral Ana Claudia Fernandes , Rodrigues Marcio L. , Almeida-Paes Rodrigo
Published: February 2020

Chromoblastomycosis (CBM) is a chronic subcutaneous mycosis caused by traumatic implantation of many species of black fungi. Due to the refractoriness of some cases and common recurrence of CBM, a more effective and less time-consuming treatment is mandatory. The aim of this study was to identify compounds within vitroantifungal activity in the Pathogen Box® compound collection against different CBM agents. Synergism of these compounds with drugs currently used to treat CBM was also assessed. An initial screening of the drugs present in this collection at 1μM was performed with aFonsecaea pedrosoiclinical strain according to the EUCAST protocol. The compounds with activity against this fungus were also tested against other seven etiologic agents of CBM (Cladophialophora carrionii,Phialophora verrucosa,Exophiala jeanselmei,Exophiala dermatitidis,Fonsecaea monophora,Fonsecaea nubica, andRhinocladiella similis) at concentrations ranging from 0.039 to 10 μM. The analysis of potential synergism of these compounds with itraconazole and terbinafine was performed by the checkerboard method. Eight compounds inhibited more than 60% of theF. pedrosoigrowth: difenoconazole, bitertanol, iodoquinol, azoxytrobin, MMV688179, MMV021013, trifloxystrobin, and auranofin. Iodoquinol produced the lowest MIC values (1.25 - 2.5μM) and MMV688179 showed MICs that were higher than all compounds tested (5 - >10μM). When auranofin and itraconazole were tested in combination, a synergistic interaction (FICI = 0.37) was observed against theC. carrioniiisolate. In summary, auranofin, iodoquinol, and MMV021013 were identified as promising compounds to be tested in CBM models of infection.
Thousands of novel unannotated proteins expand the MHC I immunopeptidome in cancer
Authors: Ouspenskaia Tamara , Law Travis , Clauser Karl R. , Klaeger Susan , Sarkizova Siranush , Aguet François , Li Bo , Christian Elena , Knisbacher Binyamin A. , Le Phuong M. , Hartigan Christina R. , Keshishian Hasmik , Apffel Annie , Oliveira Giacomo , Zhang Wandi , Chow Yuen Ting , Ji Zhe , Jungreis Irwin , Shukla Sachet A. , Bachireddy Pavan , Kellis Manolis , Getz Gad , Hacohen Nir , Keskin Derin B. , Carr Steven A. , Wu Catherine J. , Regev Aviv
Published: February 2020

Tumor epitopes – peptides that are presented on surface-bound MHC I proteins - provide targets for cancer immunotherapy and have been identified extensively in the annotated protein-coding regions of the genome. Motivated by the recent discovery of translated novel unannotated open reading frames (nuORFs) using ribosome profiling (Ribo-seq), we hypothesized that cancer-associated processes could generate nuORFs that can serve as a new source of tumor antigens that harbor somatic mutations or show tumor-specific expression. To identify cancer-specific nuORFs, we generated Ribo-seq profiles for 29 malignant and healthy samples, developed a sensitive analytic approach for hierarchical ORF prediction, and constructed a high-confidence database of translated nuORFs across tissues. Peptides from 3,555 unique translated nuORFs were presented on MHC I, based on analysis of an extensive dataset of MHC I-bound peptides detected by mass spectrometry, with >20-fold more nuORF peptides detected in the MHC I immunopeptidomes compared to whole proteomes. We further detected somatic mutations in nuORFs of cancer samples and identified nuORFs with tumor-specific translation in melanoma, chronic lymphocytic leukemia and glioblastoma. NuORFs thus expand the pool of MHC I-presented, tumor-specific peptides, targetable by immunotherapies.
Protein interaction mapping reveals widespread targeting of development-related host transcription factors by phytoplasma effectors
Authors: Marrero Miguel Correa , Capdevielle Sylvain , Huang Weijie , Al-Subhi Ali M. , Busscher Marco , Busscher-Lange Jacqueline , van der Wal Froukje , de Ridder Dick , van Dijk Aalt D.J. , Hogenhout Saskia A. , Immink Richard G.H.
Published: February 2020

Phytoplasmas are pathogenic bacteria that reprogram plant host development for their own benefit. Previous studies have characterized a few different phytoplasma effector proteins that destabilize specific plant transcription factors. However, these are only a small fraction of the potential effectors used by phytoplasmas; therefore, the molecular mechanisms through which phytoplasmas modulate their hosts require further investigation. To obtain further insights into the phytoplasma infection mechanisms, we generated a protein-protein interaction network between a broad set of phytoplasma effectors and a large, unbiased collection ofArabidopsis thalianatranscription factors and transcriptional regulators. We found widespread, but specific, interactions between phytoplasma effectors and host transcription factors, especially those related to host developmental processes. In particular, many unrelated effectors target specific sets of TCP transcription factors, which regulate plant development and immunity. Comparison with other host-pathogen protein interaction networks shows that phytoplasma effectors have unusual targets, indicating that phytoplasmas have evolved a unique and unusual infection strategy. This study contributes a rich and solid data source that guides further investigations of the functions of individual effectors, as demonstrated for some herein. Moreover, the dataset provides insights into the underlying molecular mechanisms of phytoplasma infection.
Solvent influence on the crystal packing of 6-aminothiocytosine
Authors: Grześkiewicz Anita M. , Ostrowska Agata , Kubicki Maciej
Published: February 2020

The crystal structures of 6-aminothiocytosine (systematic name: 4,6-diamino-1,2-dihydropyrimidine-2-thione, DAPMT, C4H6N4S), its hemihydrate (0.5H2O) and its dimethylformamide (DMF, C3H7NO) monosolvate were compared, and the influence of the type of solvent on the supramolecular motifs was analysed. In all three crystal structures, there are two symmetry-independent molecules (A and B), and these molecules are connected by three relatively short and directional hydrogen bonds to form chains of alternating A and B molecules. A further organization of these chains is dependent on the nature of the solvent molecule. In the unsolvated form, two orientations of the neighbouring chains are observed, and similar motifs – but only one per structure – can be observed in the solvated structures. These two different motifs can be connected by two different kinds of contacts, i.e. either π–π (hemihydrate) or staple-supported S...S (DMF). In the crystal structures, the O atoms of the solvent molecules are double acceptors of the same type of hydrogen bonds and bind the chains of DAPMT molecules into different motifs (dimeric or infinite chains). A Hirshfeld fingerprint analysis was used for visualization and additional interpretation of these results.
Estimation of the equivalent tourist population trough indirect methods
Authors: Fernández Melchor , Lazovski Oleg
Published: February 2020

Purpose

This proposal represents four main advantages: the immediate availability of the relevant information to the local manager; its potential application to any municipality regardless of its size; its reduced economic cost both in terms of information and calculation; and the possibility of obtaining information for very short periods (monthly or even daily) which is very important in areas where the population varies significantly throughout the year.

Design/methodology/approach

The authors present an indirect estimation method based on extrapolating the equivalent tourist population from the monthly variations in the production of solid urban waste.

Findings

It would also be desirable to compare the estimates made by using other indirect indicators such as electricity or water consumption, which could also provide relevant information on the degree of use of second homes.

Originality/value

These advantages turn this indicator into a practical and accessible estimation tool, which can be directly applied to the planning and management of all types of services and facilities provided by municipalities.
Paleoearthquake Investigation along the Chenghai Fault Zone since ∼500 ka, Southeast Margin of the Tibetan Plateau
Authors: YANG Shuaibin , QIAO Yansong , WU Zhonghai , ZHANG Xujiao , QI Lin , HE Zexin , LIANG Ying
Published: February 2020

The Chenghai fault zone is located in the Sichuan–Yunnan rhombus block, which is surrounded by the Honghe River, Xianshuihe–Xiaojiang, and Jinsha River fault zones. As a mid‐continental active fault, it is one of the most important seismogenic fractures in the southeast margin of the Tibetan Plateau. Geological seismic study is an important supplement to the historical seismic record; therefore, identification of paleoearthquake events in this region is of great significance to reveal the pattern and mechanism of earthquake development. In this study, detailed investigation has been carried out on the earthquake traces that formed in the Quaternary sediments in the Jinsha River section of the Chenghai fault zone, and samples for dating chronology testing were also collected. Many paleoearthquake traces were discovered in the field, including earthquake fissions, dammed lake sediments and landslides, earthquake‐generated rock falls, seismic faults, and sand liquefaction veins. The collected samples were tested using optically stimulated luminescence, electron‐spin resonance, and U‐series methods. A total of 68 chronological samples were dated, combined with the results of field investigations, and 10 large paleoearthquake events were discovered in this region since 500 ka, which are at approximately 450, 400, 345, 300, 250, 190, 155, 105, 75, and 25 ka. Ten tectonic activity periods that produced multiple paleoearthquake events were identified since 500 ka. This study identifies paleoearthquake events in longer scales, larger spaces, and more extensive sediments, which provides new perspectives and new ideas for paleoearthquake research.
Phenological stages ofMediterraneanforage legumes, based on the BBCH scale
Authors: Enriquez‐Hidalgo Daniel , Cruz Trinidad , Teixeira Dayane L. , Steinfort Ursula
Published: February 2020

One of the most widespread methodologies used to describe phenological stages in plants was developed by the Biologische Bundesanstalt Bundessortenamt und Chemische Industrie (BBCH). The BBCH scale utilises a decimal‐code system that divides plant phenological stages into a binary code composed of the principal and the secondary stages. This system has been extensively used to describe the phenological stages of diverse species, but there is no phenological description that can aid researchers in defining the duration of phenological stages of annual Mediterranean forage legumes that present different growth habits. The development of a precise phenological scale for forages enables the determination of grazing management strategies to attain a desired forage yield and quality as to precisely define the timing of agronomical practices. We have adapted the BBCH decimal‐code scale forMedicago polymorpha,Trifolium alexandrinum,Trifolium subterraneum, andVicia benghalensis. The scale consists of 10 main stages with specific secondary stages. Descriptive keys with illustrations will help identify any particular phenological stage for each species. The scales presented here will aid researchers and the agricultural community in clearly defining the timing of agronomical practices, such as the appropriate time for grazing/harvest of these species.
The effect of the pine woolly aphid (Pineus pini) on survival, growth and natural selection in Scots pine (Pinus sylvestris) in Iceland
Authors: Heiðarsson Lárus , Sigurdsson Bjarni D. , Davíðsson Benjamín Ö. , Hrafnkelsdóttir Brynja , Sigurgeirsson Aðalsteinn , Skúlason Brynjar , D. Vest María , Halldorsson Guðmundur
Published: February 2020

Scots pine Pinus sylvestris was originally introduced to Iceland in the beginning of the 20th Century. Extensive plantings started in the late 1940s and, in total, 2–3 million Scots pine seedlings were planted, mainly originating from two counties in northern Norway. Part of this plant material was imported as seedlings.

Pine woolly aphid Pineus pini was introduced to Iceland before 1940, most likely on imported seedlings in 1937.

High mortality of Scots pine, concurrent with high infestation of the pine woolly aphid, was observed in Iceland during the late 1950s and 1960s and planting was discontinued.

Provenance trials with Scots pine were established in Iceland in 2004–2006. They consisted of 15 provenances from Norway, four from Finland, four from Scotland, one from Russia, one from the Austrian Alps and three first generation Scots pine provenances from Iceland, collected from survivors of the epidemic in the 1950s and 1960s. In total, there were 28 provenances.

The Icelandic provenances had significantly lower P. pini infestation than all the provenances of non‐Icelandic origin, which indicates that natural selection in Scots pine in Iceland has occurred in favour of individuals less susceptible to P. pini.
Reporting assisted reproductive technology success rates on Australian and New Zealand fertility clinic websites
Authors: Goodman Lucy Kate , Prentice Lucy Rebecca , Chanati Rebecca , Farquhar Cynthia
Published: February 2020

Background

Fertility clinics commonly report their success rates online. These can be difficult to interpret as they are influenced by the way the data are presented. To improve transparency, the Reproductive Technology Accreditation Committee (RTAC) has published guidelines to support fertility clinics with their online reporting of success rates. However, it is unclear whether compliance with these guidelines will allow patients to make fair comparisons between clinics.

Aims

To illustrate the variability in patient and treatment populations that contribute to fertility clinic published rates.

Materials and Methods

Fertility clinics offering in vitro fertilisation treatment in Australia or New Zealand were assessed for compliance with six guidelines adapted from RTAC’s code of practice, for reporting success rates in the public domain. All graphs and/or tables reporting clinic success rates were assessed to illustrate the combination of outcome or treatment variables contributing to each dataset.

Results

Twenty of the 30 fertility clinic websites reported success rates. Of these only 17 reported live births. The median compliance score with RTAC guidelines was 8/8 (interquartile range: 6–8). Of 41 figures published across all websites, five reported clinical pregnancy rates as their only outcome measure. Thirty‐seven figures reported success rates ‘per embryo transfer’, two figures used ‘per egg collection’, and no figures described success rates ‘per cycle started’. Thirty‐two different combinations of reporting variables were observed.

Conclusions

Websites were broadly compliant with RTAC’s guidelines. However, considering the variability in patient and treatment groups contributing to success rate data, patients cannot be expected to make an informed decision based on clinics’ self‐reported outcomes. RTAC guidelines could be improved by providing a clear definition of success, including the appropriate use of denominators.
Allostasis and Adaptation: Biocultural Processes Integrating Lifestyle, Life History, and Blood Pressure Variation
Authors: James Gary D.
Published: February 2020

Allostasis (literally “stability through change”) is a key concept for understanding how human behavior and physiological adaptation are related. The continuous variation in arterial blood pressure is an exemplar of allostasis. The purpose of this article is to describe theoretical and methodological developments that have led to an improved biocultural understanding of arterial blood pressure responses to everyday life in humans using allostasis as a paradigm. Arterial pressure variation is directly related to lifestyle, or more specifically, the things that people do, think, and experience in their daily lives. Allostatic patterns of arterial pressure variation also change with life‐history events. Patterns are altered as people age and take on differing social roles, and patterns vary between men and women. The cumulative effects of allostasis is the development of allostatic load, or a “wearing out” of the system. Studies have linked allostatic load to the development of cardiovascular diseases (CVD). However, the rate and trajectory of allostatic load through adult life is effectively dictated by developmental and evolutionary processes that impact allostasis and will vary among populations as a consequence of developmental, heritable, environmental, and cultural differences. Allostasis is the paradigm for biocultural studies of arterial blood pressure. [allostasis, adaptation, blood pressure, life history, biocultural]
Variation of intrapartum care and cesarean rates among practitioners attending births of low‐risk, nulliparous women
Authors: Iobst Stacey E. , Storr Carla L. , Bingham Debra , Zhu Shijun , Johantgen Meg
Published: February 2020

Background

Variation in hospital cesarean birth rates across the United States is likely because of differences in practitioner practice patterns. Yet, few studies conducted in the last twenty years have examined the relationships between practitioner characteristics and the use of intrapartum interventions and cesarean birth. The objective of this study was to examine associations among practitioner characteristics and the use of amniotomy, epidural, oxytocin augmentation, and cesarean birth in low‐risk women with spontaneous onset of labor.

Methods

A secondary analysis was performed using data collected by the Consortium on Safe Labor. The sample included nulliparous term singleton vertex (NTSV) births with spontaneous onset of labor (n = 13 196) from 2002 to 2007 across eight hospitals. Generalized linear mixed models were conducted to examine outcomes.

Results

The cesarean birth rate ranged from 7.2% to 18.9% across hospitals and from 0% to 53.3% across physicians. Practice type (P < .05) and specialty type (P < .0001) were associated with physician cesarean birth rates. Compared with obstetrician/gynecologists, midwives were nearly twice as likely to use no intrapartum interventions (relative risk 1.80 [CI 95 1.45‐2.24]) and 26% less likely to use amniotomy‐epidural‐oxytocin (0.74 [0.62‐0.89]). Family practice physicians had a 21% lower likelihood of using amniotomy‐epidural‐oxytocin (0.79 [0.67‐0.94]) and a 53% lower likelihood of performing cesarean births (0.47 [0.35‐0.63]).

Conclusions

Wide variation in hospital and physician cesarean birth rates was observed in this sample of low‐risk, nulliparous women. Practitioner practice type and specialty were significantly associated with the use of intrapartum interventions. Interprofessional practitioner education could be one strategy to reduce variation of intrapartum care and cesarean birth.
Endogenous urinary glucocorticoid metabolites and mortality in prednisolone‐treated renal transplant recipients
Authors: Vulto Annet , Minović Isidor , de Vries Laura V. , Timmermans Arwin C. , van Faassen Martijn , Gomes Neto Antonio W. , Touw Daan J. , de Jong Margriet F. C. , van Beek André P. , Dullaart Robin P. F. , Navis Gerjan , Kema Ido P. , Bakker Stephan J. L.
Published: February 2020

Background

Chronic corticosteroid treatment suppresses HPA‐axis activity and might alter activity of 11β hydroxysteroid dehydrogenases (11β‐HSD). We aimed to investigate whether the endogenous glucocorticoid production and 11β‐HSD activities are altered in prednisolone‐treated renal transplant recipients (RTR) compared with healthy controls and whether this has implications for long‐term survival in RTR.

Methods

In a longitudinal cohort of 693 stable RTR and 275 healthy controls, 24‐hour urinary cortisol, cortisone, tetrahydrocorisol (THF), allotetrahydrocortisol (alloTHF), and tetrahydrocortisone (THE) were measured using liquid chromatography tandem‐mass spectrometry. Twenty‐four‐hour urinary excretion of cortisol and metabolites were used as measures of endogenous glucocorticoid production; (THF + alloTHF)/THE and cortisol/cortisone ratios were used as measures of 11β‐HSD activity.

Results

Urinary cortisol and metabolite excretion were significantly lower in RTR compared with healthy controls (P < .001), whereas (THF + alloTHF)/THE and cortisol/cortisone ratios were significantly higher (P < .001 and P = .002). Lower total urinary metabolite excretion and higher urinary (THF + alloTHF)/THE ratios were associated with increased risk of mortality, independent of age, sex, estimated glomerular filtration rate, C‐reactive protein, body surface area, and daily prednisolone dose, respectively.

Conclusions

Endogenous glucocorticoid production and 11β‐HSD activities are altered in prednisolone‐treated RTR. Decreased total urinary endogenous glucocorticoid metabolite excretion and increased urinary (THF + alloTHF)/THE ratios are associated with increased risk of mortality.
Assessing the distribution of a species‐rich group in a continental‐sized megadiverse country: Bats in Brazil
Authors: Delgado‐Jaramillo Mariana , Aguiar Ludmilla M. S. , Machado Ricardo B. , Bernard Enrico
Published: February 2020

Aim

The effective conservation and management of any given species frequently requires basic knowledge on its distribution, which is problematic for highly mobile, species‐ and ecologically‐rich groups, like bats. Moreover, to produce detailed distributions for continental‐sized, bat species‐rich countries, like Brazil, is difficult, especially considering that ~60% of the country has not a single formal bat record. Using Species Distribution Modelling (SDM), we assessed the potential distribution of >100 species of Brazilian bats.

Location

Brazil.

Methods

We (a) updated data on the distribution of 135 bat species, (b) generated SDMs for each species, (c) constructed species richness maps for Brazil, (d) determined areas of endemism and (e) identified areas harbouring threatened species.

Results

Amazonia harbours the highest bat species richness (76% of the species), followed by the Atlantic Forest (66%), Cerrado (65%) and the Caatinga (53%). Richness in 5 × 5 km grid cells varied between 23 and 117 species and 70% of Brazil's territory is predicted to have 50–90 species, and 25% >90 species. Coastal Atlantic forest, mainly in its north‐eastern region, and along its contact zone with the Caatinga biome had the highest potential richness. However, there is a severe regional sampling bias: 48% of the records available were from the Atlantic Forest and 21% were from along the Amazon River.

Main conclusions

Pantanal and Pampa are clearly under sampled, with <50% of their expected richness already assessed. Endemic and endangered bat species are in the Atlantic Forest, Cerrado and Caatinga, the most threatened biomes in Brazil. In addition to the seven nationally threatened bat species in Brazil, the situation for other species is worrisome: In a business‐as‐usual scenario, local extinctions in large portions of the country may happen before basic information gaps are filled.
Only the right noise? Effects of phonetic and visual input variability on 14‐month‐olds' minimal pair word learning
Authors: Höhle Barbara , Fritzsche Tom , Meß Katharina , Philipp Mareike , Gafos Adamantios
Published: February 2020

Seminal work by Werker and colleagues (Stager & Werker [1997] Nature, 388, 381–382) has found that 14‐month‐old infants do not show evidence for learning minimal pairs in the habituation‐switch paradigm. However, when multiple speakers produce the minimal pair in acoustically variable ways, infants' performance improves in comparison to a single speaker condition (Rost & McMurray [2009] Developmental Science, 12, 339–349). The current study further extends these results and assesses how different kinds of input variability affect 14‐month‐olds' minimal pair learning in the habituation‐switch paradigm testing German learning infants. The first two experiments investigated word learning when the labels were spoken by a single speaker versus when the labels were spoken by multiple speakers. In the third experiment we studied whether non‐acoustic variability, implemented by visual variability of the objects presented together with the labels, would also affect minimal pair learning. We found enhanced learning in the multiple speakers compared to the single speaker condition, confirming previous findings with English‐learning infants. In contrast, visual variability of the presented objects did not support learning. These findings both confirm and better delimit the beneficial role of speech‐specific variability in minimal pair learning. Finally, we review different proposals on the mechanisms via which variability confers benefits to learning and outline what may be likely principles that underlie this benefit. We highlight among these the multiplicity of acoustic cues signalling phonemic contrasts and the presence of relations among these cues. It is in these relations where we trace part of the source for the apparent paradoxical benefit of variability in learning.
Variable colour patterns indicate multidimensional, intraspecific trait variation and ecological generalization in moths
Authors: Forsman Anders , Polic Daniela , Sunde Johanna , Betzholtz Per‐Eric , Franzén Markus
Published: February 2020

Animal colour patterns long have provided information about key processes that drive the ecological and evolutionary dynamics of biological diversity. Theory and empirical evidence indicate that variation in colour patterns and other traits among individuals generally improves the performance of populations and species, for example by reducing predation risk, increasing establishment success, improving resilience to environmental change, and decreasing risk of extinction. However, little is known about whether and how variation in colour pattern among species is associated with variation in other phenotypic dimensions. To address this issue, we analysed associations of colour pattern with morphological, behavioural and life‐history traits on the basis of data for nearly 400 species of noctuid moths. We found that moths with more variable colour patterns had longer flight activity periods, more diverse habitats and a greater number of host plant species than species with less variable colour patterns. Variable coloration in adult noctuid moths therefore can be considered as indicative of broader niches and generalist diets. Colour pattern variability was not significantly associated with overwintering stage or body size (wing span), and it was independent of whether the colour pattern of the larvae was non‐variable, variable or highly variable. Colour pattern variation during the larval stage tended to increase as the duration of the flight activity period increased, but was independent of the length of the larval period, diet breadth and habitat use. The realization that information on colour pattern variation in adult moths, and possibly other organisms, offers a proxy for niche breadth and dietary generalization can inform management and conservation biology.
Alpine grassland plants grow earlier and faster but biomass remains unchanged over 35 years of climate change
Authors: Wang Hao , Liu Huiying , Cao Guangmin , Ma Zhiyuan , Li Yikang , Zhang Fawei , Zhao Xia , Zhao Xinquan , Jiang Lin , Sanders Nathan J. , Classen Aimée T. , He Jin‐Sheng
Published: February 2020

Satellite data indicate significant advancement in alpine spring phenology over decades of climate warming, but corresponding field evidence is scarce. It is also unknown whether this advancement results from an earlier shift of phenological events, or enhancement of plant growth under unchanged phenological pattern. By analyzing a 35‐year dataset of seasonal biomass dynamics of a Tibetan alpine grassland, we show that climate change promoted both earlier phenology and faster growth, without changing annual biomass production. Biomass production increased in spring due to a warming‐induced earlier onset of plant growth, but decreased in autumn due mainly to increased water stress. Plants grew faster but the fast‐growing period shortened during the mid‐growing season. These findings provide the first in situ evidence of long‐term changes in growth patterns in alpine grassland plant communities, and suggest that earlier phenology and faster growth will jointly contribute to plant growth in a warming climate.