bluuebunny/crossref_metadata_2025 huggingface dataset:
Der Riot als Vorbote und Symptom einer Krise: Zu den Ausschreitungen während des G20-Gipfels 2018 in Hamburg
Authors: Uhlmann Sarah
Published: January 2019

Während des G20-Gipfels in Hamburg kam es zu immensen Ausschreitungen, die zahlreiche Diskussionen in der Presse nach sich zogen. In diesen stand häufig die Straffälligkeit der RandaliererInnen im Vordergrund. Eine weitergehende politische oder wissenschaftliche Einordnung der Geschehnisse suchte man vergebens. Dieses Defizit ist auch dem Umstand geschuldet, dass die hiesige Soziale Bewegungs- und Protestforschung kaum Forschungsansätze zur Analyse von Ausschreitungen anbietet. Der vorliegende Artikel versteht Riots als ein gesellschaftliches Phänomen und bemüht sich daher um ein tiefergehendes Verständnis, indem sowohl ideelle und psychosoziale als auch sozialstrukturelle Ursachen beleuchtet werden. Die Ausschreitungen werden mithilfe von politökonomischen Arbeiten wie die von Joshua Clover als ein Krisenphänomen gedeutet, wobei sich die Eruption selbst nur aus einer relationalen Perspektive begreifen lässt. Das Ausmaß in Hamburg war nur möglich, weil die heterogenen Protestgruppierungen beim Anblick der geteilten Gegnerschaft zur Polizei eine Koalition bildeten, in der die üblichen Grenzen zwischen den unterschiedlichen politischen Spektren aber auch sozialen Schichten kurzzeitig aufgehoben wurden und so eine schwer kontrollierbare Protestmasse entstand.
Datenfusion in der sozialwissenschaftlichen Wahlforschung – Begründeter Verzicht oder ungenutzte Chance? Theoretische Vorüberlegungen, Verfahrensüberblick und ein erster Erfahrungsbericht
Authors: Bacher Johann , Prandner Dimitri
Published: January 2019

Datenarchive stellen umfangreiches Individualdatenmaterial in hoher Qualität zur Verfügung. Theoretisch böte sich damit die Möglichkeit für eine Datenfusion: Auf Ebene der Befragten wird ein neuer Datensatz erzeugt, der Variablen aus unterschiedlichen Datensätzen enthält. Dieses Potential wird in den Sozialwissenschaften aber kaum genutzt. Es existieren nur wenige Ausnahmen, in denen das Verfahren der Datenfusion zur Anwendung kommt.Der Beitrag geht daher der Frage nach, ob dieser Verzicht begründet ist oder ob dadurch Chancen ungenutzt bleiben. Zur Beantwortung wird zunächst ein formales Modell entwickelt, das aufzeigt, unter welchen Bedingungen eine Datenfusion zu einer Verbesserung oder Verschlechterung der Datenqualität führen kann. Daran anschließend wird ein Überblick zu den Techniken der Datenfusion gegeben, bevor anhand eines konkreten Beispiels aus der Wahlforschung die Frage untersucht wird, ob Datenfusion mit einem der derzeit verfügbaren Standardstatistikpaketen möglich ist und zu welchen Ergebnissen sie führt.
Comparing the Triarchic and Five-Factor Trait Models: Relations With Psychopathy and Other Clinical Criteria in an Incarcerated Offender Sample
Authors: Brislin Sarah J. , Cernohorsky Peter , Patrick Christopher J. , Drislane Laura E. , Caruso Maria , Giulini Paolo , Sica Claudio
Published: January 2019

This study compared how normative personality dimensions of the Five-Factor Model (FFM) and neurobehavioral traits of the triarchic model relate to psychopathic tendencies and clinical outcomes in an incarcerated sample of 277 Italian male offenders. Associations between triarchic model traits, measured using the TriPM and the FFM dimensions, measured using the NEO-FFI, were consistent with prior studies. Scores on the TriPM, particularly the Disinhibition scale, were associated with substance abuse and self-harm behavior over and above the presence of psychopathy, and beyond the personality dimensions indexed by the NEO-FFI. By contrast, the Neuroticism and Extraversion scales showed incremental validity, over and above psychopathy and TriPM scores, in predicting depressive tendencies. Lastly, both NEO-FFI and TriPM scales contributed to prediction of staff ratings of behavior in prison and prognosis for release, above and beyond psychopathy. These findings highlight potential advantages of the FFM and triarchic trait models for predicting clinical outcomes.
Representation of Auditory Motion Directions and Sound Source Locations in the Human Planum Temporale
Authors: Battal Ceren , Rezk Mohamed , Mattioni Stefania , Vadlamudi Jyothirmayi , Collignon Olivier
Published: January 2019

The ability to compute the location and direction of sounds is a crucial perceptual skill to efficiently interact with dynamic environments. How the human brain implements spatial hearing is, however, poorly understood. In our study, we used fMRI to characterize the brain activity of male and female humans listening to sounds moving left, right, up, and down as well as static sounds. Whole-brain univariate results contrasting moving and static sounds varying in their location revealed a robust functional preference for auditory motion in bilateral human planum temporale (hPT). Using independently localized hPT, we show that this region contains information about auditory motion directions and, to a lesser extent, sound source locations. Moreover, hPT showed an axis of motion organization reminiscent of the functional organization of the middle-temporal cortex (hMT+/V5) for vision. Importantly, whereas motion direction and location rely on partially shared pattern geometries in hPT, as demonstrated by successful cross-condition decoding, the responses elicited by static and moving sounds were, however, significantly distinct. Altogether, our results demonstrate that the hPT codes for auditory motion and location but that the underlying neural computation linked to motion processing is more reliable and partially distinct from the one supporting sound source location.

SIGNIFICANCE STATEMENTCompared with what we know about visual motion, little is known about how the brain implements spatial hearing. Our study reveals that motion directions and sound source locations can be reliably decoded in the human planum temporale (hPT) and that they rely on partially shared pattern geometries. Our study, therefore, sheds important new light on how computing the location or direction of sounds is implemented in the human auditory cortex by showing that those two computations rely on partially shared neural codes. Furthermore, our results show that the neural representation of moving sounds in hPT follows a “preferred axis of motion” organization, reminiscent of the coding mechanisms typically observed in the occipital middle-temporal cortex (hMT+/V5) region for computing visual motion.
Plasticity in the Link between Pain-Transmitting and Pain-Modulating Systems in Acute and Persistent Inflammation
Authors: Chen QiLiang , Heinricher Mary M.
Published: January 2019

There is strong evidence that spinoparabrachial neurons in the superficial dorsal horn contribute to persistent pain states, and that the lateral parabrachial complex (PB) conveys relevant nociceptive information to higher structures. The role of PB itself in hyperalgesia and how it recruits descending facilitation has nevertheless received significantly less attention. The current study is a first step toward delineating the functional dynamics of PB and its link to descending control in acute and persistent inflammatory pain. In lightly anesthetized rats, we recorded behavioral withdrawal evoked by mechanical stimulation of the hindpaw and, simultaneously, the activity of identified pain-modulating neurons, “ON-cells” and “OFF-cells,” in the rostral ventromedial medulla (RVM). This was done before and after the inactivation of PB, contralateral or ipsilateral to an inflamed paw [1 h, 1 d, or 5–6 d after intraplantar injection of Complete Freund's Adjuvant (CFA)]. The inactivation of contralateral, but not ipsilateral, PB interfered with nociceptive input to RVM under basal conditions, as well as in acute inflammation. By contrast, blocking ipsilateral, but not contralateral, PB in established inflammation interfered with behavioral hyperalgesia and ON-cell and OFF-cell responses. The lesioning of contralateral PB before CFA injection prevented this recruitment of ipsilateral PB in persistent inflammation. These experiments show that contralateral PB is required to initiate hyperalgesia, which is then maintained by ipsilateral PB, most likely in both cases via the engagement of pain-modulating neurons of the RVM.

SIGNIFICANCE STATEMENTThe lateral parabrachial complex (PB) relays nociceptive information to brain circuits that are important for the transmission and modulation of pain, but its specific role in persistent pain and engagement of descending control mechanisms has received relatively little attention. We show here that PB contralateral and ipsilateral to an inflammatory insult demonstrate different functions as inflammation persists, likely by engaging pain-facilitating neurons of the rostral ventromedial medulla. While the contralateral PB, the target of the major spinoparabrachial pathway, relays acute nociceptive information, the ipsilateral PB is recruited or unmasked in persistent inflammation to maintain hyperalgesia. These data point to plasticity in the PB itself or its direct and indirect connections with pain-modulating systems as central to the development and maintenance of persistent pain.
Amplification and Suppression of Traveling Waves along the Mouse Organ of Corti: Evidence for Spatial Variation in the Longitudinal Coupling of Outer Hair Cell-Generated Forces
Authors: Dewey James B. , Applegate Brian E. , Oghalai John S.
Published: January 2019

Mammalian hearing sensitivity and frequency selectivity depend on a mechanical amplification process mediated by outer hair cells (OHCs). OHCs are situated within the organ of Corti atop the basilar membrane (BM), which supports sound-evoked traveling waves. It is well established that OHCs generate force to selectively amplify BM traveling waves where they peak, and that amplification accumulates from one location to the next over this narrow cochlear region. However, recent measurements demonstrate that traveling waves along the apical surface of the organ of Corti, the reticular lamina (RL), are amplified over a much broader region. Whether OHC forces accumulate along the length of the RL traveling wave to provide a form of “global” cochlear amplification is unclear. Here we examined the spatial accumulation of RL amplification. In mice of either sex, we used tones to suppress amplification from different cochlear regions and examined the effect on RL vibrations near and far from the traveling-wave peak. We found that although OHC forces amplify the entire RL traveling wave, amplification only accumulates near the peak, over the same region where BM motion is amplified. This contradicts the notion that RL motion is involved in a global amplification mechanism and reveals that the mechanical properties of the BM and organ of Corti tune how OHC forces accumulate spatially. Restricting the spatial buildup of amplification enhances frequency selectivity by sharpening the peaks of cochlear traveling waves and constrains the number of OHCs responsible for mechanical sensitivity at each location.

SIGNIFICANCE STATEMENTOuter hair cells generate force to amplify traveling waves within the mammalian cochlea. This force generation is critical to the ability to detect and discriminate sounds. Nevertheless, how these forces couple to the motions of the surrounding structures and integrate along the cochlear length remains poorly understood. Here we demonstrate that outer hair cell-generated forces amplify traveling-wave motion on the organ of Corti throughout the wave's extent, but that these forces only accumulate longitudinally over a region near the wave's peak. The longitudinal coupling of outer hair cell-generated forces is therefore spatially tuned, likely by the mechanical properties of the basilar membrane and organ of Corti. Our findings provide new insight into the mechanical processes that underlie sensitive hearing.
Vitamin D testing and treatment: a narrative review of current evidence
Authors: Pilz Stefan , Zittermann Armin , Trummer Christian , Theiler-Schwetz Verena , Lerchbaum Elisabeth , Keppel Martin H , Grübler Martin R , März Winfried , Pandis Marlene
Published: January 2019

Vitamin D testing and treatment is a subject of controversial scientific discussions, and it is challenging to navigate through the expanding vitamin D literature with heterogeneous and partially opposed opinions and recommendations. In this narrative review, we aim to provide an update on vitamin D guidelines and the current evidence on the role of vitamin D for human health with its subsequent implications for patient care and public health issues. Vitamin D is critical for bone and mineral metabolism, and it is established that vitamin D deficiency can cause rickets and osteomalacia. While many guidelines recommend target serum 25-hydroxyvitamin D (25[OH]D) concentrations of ≥50 nmol/L (20 ng/mL), the minimum consensus in the scientific community is that serum 25(OH)D concentrations below 25–30 nmol/L (10–12 ng/mL) must be prevented and treated. Using this latter threshold of serum 25(OH)D concentrations, it has been documented that there is a high worldwide prevalence of vitamin D deficiency that may require public health actions such as vitamin D food fortification. On the other hand, there is also reason for concern that an exploding rate of vitamin D testing and supplementation increases costs and might potentially be harmful. In the scientific debate on vitamin D, we should consider that nutrient trials differ from drug trials and that apart from the opposed positions regarding indications for vitamin D treatment we still have to better characterize the precise role of vitamin D for human health.
Os procedimentos de determinação dos preços de transferência
Authors: Amorim José Campos
Published: January 2019

ResumoOs preços de transferência baseiam-se no princípio da plena concorrência que assenta no pressuposto de que as transações que ocorrem entre empresas relacionadas devem ser idênticas às transações ocorridas entre empresas independentes. Para calcular os preços de transferência podem ser utilizados métodos tradicionais ou métodos não tradicionais. O não cumprimento do princípio da plena concorrência pode levar a correções fiscais efetuadas pela Autoridade Tributária agravando assim o montante de imposto a entregar ao Estado.Palavras-chave: Preços de transferência, Princípio de plena concorrência, Métodos tradicionais, Métodos não tradicionais, Sociedades. ResumenLos precios de transferencia se basan en el principio de plena competencia que parte del supuesto de que las transacciones que se produzcan entre empresas relacionadas deben ser idénticas a las transacciones entre empresas independientes. Para calcular los precios de transferencia pueden utilizarse métodos tradicionales o métodos no tradicionales. El incumplimiento del principio de plena competencia puede llevar a correcciones fiscales efectuadas por la Autoridad Tributaria agravando así el importe de impuesto que debe entregarse al Estado.Palabras clave: Métodos tradicionales, Métodos no tradicionales, Precios de transferencia, Principio de la plena competencia. AbstractThe transfer pricing is based in the arm`s length principle, which is based on the assumption that transactions taking place between related companies must be identical to transactions occurred between the independent companies. Traditional or non-traditional methods can be used to calculate the transfer pricing. Failure to comply with arm`s length principle, may lead to tax corrections made by the tax administration that will increase the amount of tax due to the state.Keywords: Transfer pricing, Arm’s length principle, Traditional methods, Non-traditional methods, Companies.
Reciprocal F1 Hybrids of Two Inbred Mouse Strains Reveal Parent-of-Origin and Perinatal Diet Effects on Behavior and Expression
Authors: Oreper Daniel , Schoenrock Sarah A , McMullan Rachel , Ervin Robin , Farrington Joseph , Miller Darla R , de Villena Fernando Pardo-Manuel , Valdar William , Tarantino Lisa M
Published: January 2019

Parent-of-origin effects (POE) in mammals typically arise from maternal effects or imprinting. In some instances, such POE have been associated with psychiatric disorders, as well as with changes in a handful of animal behaviors. However, POE on complex traits such as behavior remain largely uncharacterized. Moreover, although both behavior and epigenetic effects are known to be modified by perinatal environmental exposures such as nutrient deficiency, the architecture of such environment-by-POE is mostly unexplored. To study POE and environment-by-POE, we employ a relatively neglected but especially powerful experimental system for POE-detection: reciprocal F1 hybrids (RF1s). We exposed female NOD/ShiLtJ×C57Bl/6J and C57Bl/6J×NOD/ShiLtJ mice, perinatally, to one of four different diets, then after weaning recorded a set of behaviors that model psychiatric disease. Whole-brain microarray expression data revealed an imprinting-enriched set of 15 genes subject to POE. The most-significant expression POE, on the non-imprinted gene Carmil1 (a.k.a. Lrrc16a), was validated using qPCR in the same and in a new set of mice. Several behaviors, especially locomotor behaviors, also showed POE. Bayesian mediation analysis suggested Carmil1 expression suppresses behavioral POE, and that the imprinted gene Airn suppresses POE on Carmil1 expression. A suggestive diet-by-POE was observed on percent center time in the open field test, and a significant diet-by-POE was observed on one imprinted gene, Mir341, and on 16 non-imprinted genes. The relatively small, tractable set of POE and diet-by-POE detected on behavior and expression here motivates further studies examining such effects across RF1s on multiple genetic backgrounds.
Natural Genetic Variation in Yeast Reveals That NEDD4 Is a Conserved Modifier of Mutant Polyglutamine Aggregation
Authors: Peters Theodore W , Nelson Christopher S , Gerencser Akos A , Dumas Kathleen J , Tavshanjian Brandon , Chang Kyu Chul , Lithgow Gordon J , Hughes Robert E
Published: January 2019

A feature common to late onset proteinopathic disorders is an accumulation of toxic protein conformers and aggregates in affected tissues. In the search for potential drug targets, many studies used high-throughput screens to find genes that modify the cytotoxicity of misfolded proteins. A complement to this approach is to focus on strategies that use protein aggregation as a phenotypic readout to identify pathways that control aggregate formation and maintenance. Here we use natural variation between strains of budding yeast to genetically map loci that influence the aggregation of a polyglutamine-containing protein derived from a mutant form of huntingtin, the causative agent in Huntington disease. Linkage analysis of progeny derived from a cross between wild and laboratory yeast strains revealed two polymorphic loci that modify polyglutamine aggregation. One locus contains the gene RFU1 which modifies ubiquitination states of misfolded proteins targeted by the E3-ubiquitin ligase complex Rsp5. Activity of the Rsp5 complex, and the mammalian homolog NEDD4, are critical in maintaining protein homeostasis in response to proteomic stress. Our analysis also showed linkage of the aggregation phenotype to a distinct locus containing a gene encoding the Rsp5-interacting Bul2 protein. Allele-swap experiments validated the impact of both RFU1 and BUL2 on huntingtin aggregation. Furthermore, we found that the nematode Caenorhabditis elegans’ ortholog of Rsp5, wwp-1, also negatively regulates polyglutamine aggregation. Knockdown of the NEDD4 in human cells likewise altered polyglutamine aggregation. Taken together, these results implicate conserved processes involving the ubiquitin regulation network that modify protein aggregation and provide novel therapeutic targets for polyglutamine and other protein folding diseases.
Bulked-Segregant Analysis Coupled to Whole Genome Sequencing (BSA-Seq) for Rapid Gene Cloning in Maize
Authors: Klein Harry , Xiao Yuguo , Conklin Phillip A , Govindarajulu Rajanikanth , Kelly Jacob A , Scanlon Michael J , Whipple Clinton J , Bartlett Madelaine
Published: January 2019

Forward genetics remains a powerful method for revealing the genes underpinning organismal form and function, and for revealing how these genes are tied together in gene networks. In maize, forward genetics has been tremendously successful, but the size and complexity of the maize genome made identifying mutant genes an often arduous process with traditional methods. The next generation sequencing revolution has allowed for the gene cloning process to be significantly accelerated in many organisms, even when genomes are large and complex. Here, we describe a bulked-segregant analysis sequencing (BSA-Seq) protocol for cloning mutant genes in maize. Our simple strategy can be used to quickly identify a mapping interval and candidate single nucleotide polymorphisms (SNPs) from whole genome sequencing of pooled F2 individuals. We employed this strategy to identify narrow odd dwarf as an enhancer of teosinte branched1, and to identify a new allele of defective kernel1. Our method provides a quick, simple way to clone genes in maize.
Signatures of Insecticide Selection in the Genome of Drosophila melanogaster
Authors: Duneau David , Sun Haina , Revah Jonathan , San Miguel Keri , Kunerth Henry D , Caldas Ian V , Messer Philipp W , Scott Jeffrey G , Buchon Nicolas
Published: January 2019

Resistance to insecticides has evolved in multiple insect species, leading to increased application rates and even control failures. Understanding the genetic basis of insecticide resistance is fundamental for mitigating its impact on crop production and disease control. We performed a GWAS approach with the Drosophila Genetic Reference Panel (DGRP) to identify the mutations involved in resistance to two widely used classes of insecticides: organophosphates (OPs, parathion) and pyrethroids (deltamethrin). Most variation in parathion resistance was associated with mutations in the target gene Ace, while most variation in deltamethrin resistance was associated with mutations in Cyp6a23, a gene encoding a detoxification enzyme never previously associated with resistance. A “nested GWAS” further revealed the contribution of other loci: Dscam1 and trpl were implicated in resistance to parathion, but only in lines lacking Wolbachia. Cyp6a17, the paralogous gene of Cyp6a23, and CG7627, an ATP-binding cassette transporter, were implicated in deltamethrin resistance. We observed signatures of recent selective sweeps at all of these resistance loci and confirmed that the soft sweep at Ace is indeed driven by the identified resistance mutations. Analysis of allele frequencies in additional population samples revealed that most resistance mutations are segregating across the globe, but that frequencies can vary substantially among populations. Altogether, our data reveal that the widely used OP and pyrethroid insecticides imposed a strong selection pressure on natural insect populations. However, it remains unclear why, in Drosophila, resistance evolved due to changes in the target site for OPs, but due to a detoxification enzyme for pyrethroids.
Mushroom Body Specific Transcriptome Analysis Reveals Dynamic Regulation of Learning and Memory Genes After Acquisition of Long-Term Courtship Memory in Drosophila
Authors: Jones Spencer G , Nixon Kevin C J , Chubak Melissa C , Kramer Jamie M
Published: January 2019

The formation and recall of long-term memory (LTM) requires neuron activity-induced gene expression. Transcriptome analysis has been used to identify genes that have altered expression after memory acquisition, however, we still have an incomplete picture of the transcriptional changes that are required for LTM formation. The complex spatial and temporal dynamics of memory formation creates significant challenges in defining memory-relevant gene expression changes. The Drosophila mushroom body (MB) is a signaling hub in the insect brain that integrates sensory information to form memories across several different experimental memory paradigms. Here, we performed transcriptome analysis in the MB at two time points after the acquisition of LTM: 1 hr and 24 hr. The MB transcriptome was compared to biologically paired whole head (WH) transcriptomes. In both, we identified more transcript level changes at 1 hr after memory acquisition (WH = 322, MB = 302) than at 24 hr (WH = 23, MB = 20). WH samples showed downregulation of developmental genes and upregulation of sensory response genes. In contrast, MB samples showed vastly different changes in transcripts involved in biological processes that are specifically related to LTM. MB-downregulated genes were highly enriched for metabolic function. MB-upregulated genes were highly enriched for known learning and memory processes, including calcium-mediated neurotransmitter release and cAMP signaling. The neuron activity inducible genes Hr38 and sr were also specifically induced in the MB. These results highlight the importance of sampling time and cell type in capturing biologically relevant transcript level changes involved in learning and memory. Our data suggests that MB cells transiently upregulate known memory-related pathways after memory acquisition and provides a critical frame of reference for further investigation into the role of MB-specific gene regulation in memory.
An Efficient Genome Editing Strategy To Generate Putative Null Mutants in Caenorhabditis elegans Using CRISPR/Cas9
Authors: Wang Han , Park Heenam , Liu Jonathan , Sternberg Paul W
Published: January 2019

Null mutants are essential for analyzing gene function. Here, we describe a simple and efficient method to generate Caenorhabditis elegans null mutants using CRISPR/Cas9 and short single stranded DNA oligo repair templates to insert a universal 43-nucleotide-long knock-in cassette (STOP-IN) into the early exons of target genes. This STOP-IN cassette has stop codons in all three reading frames and leads to frameshifts, which will generate putative null mutations regardless of the reading frame of the insertion position in exons. The STOP-IN cassette also contains an exogenous Cas9 target site that allows further genome editing and provides a unique sequence that simplifies the identification of successful insertion events via PCR. As a proof of concept, we inserted the STOP-IN cassette at a Cas9 target site in aex-2 to generate new putative null alleles by injecting preassembled Cas9 ribonucleoprotein and a short synthetic single stranded DNA repair template containing the STOP-IN cassette and two ∼35-nucleotide-long homology arms identical to the sequences flanking the Cas9 cut site. We showed that these new aex-2 alleles phenocopied an existing loss-of-function allele of aex-2. We further showed that the new aex-2 null alleles could be reverted back to the wild-type sequence by targeting the exogenous Cas9 cut site included in the STOP-IN cassette and providing a single stranded wild-type DNA repair oligo. We applied our STOP-IN method to generate new putative null mutants for 20 additional genes, including three pharyngeal muscle-specific genes (clik-1, clik-2, and clik-3), and reported a high insertion rate (46%) based on the animals we screened. We showed that null mutations of clik-2 cause recessive lethality with a severe pumping defect and clik-3 null mutants have a mild pumping defect, while clik-1 is dispensable for pumping. We expect that the knock-in method using the STOP-IN cassette will facilitate the generation of new null mutants to understand gene function in C. elegans and other genetic model organisms.
Spore Germination Requires Ferrichrome Biosynthesis and the Siderophore Transporter Str1 in Schizosaccharomyces pombe
Authors: Plante Samuel , Labbé Simon
Published: January 2019

Spore germination is a process whereby spores exit dormancy to become competent for mitotic cell division. In Schizosaccharomyces pombe, one critical step of germination is the formation of a germ tube that hatches out the spore wall in a stage called outgrowth. Here, we show that iron deficiency blocks the outgrowth of germinating spores. The siderophore synthetase Sib1 and the ornithine N5-oxygenase Sib2 participate in ferrichrome biosynthesis, whereas Str1 functions as a ferrichrome transporter. Expression profiles of sib1+, sib2+, and str1+ transcripts reveal that they are induced shortly after induction of germination and their expression remains upregulated throughout the germination program under low-iron conditions. sib1Δ sib2Δ mutant spores are unable to form a germ tube under iron-poor conditions. Supplementation with exogenous ferrichrome suppresses this phenotype when str1+ is present. Str1 localizes at the contour of swollen spores 4 hr after induction of germination. At the onset of outgrowth, localization of Str1 changes and it moves away from the mother spore to primarily localize at the periphery of the new daughter cell. Two conserved Tyr residues (Tyr553 and Tyr567) are predicted to be located in the last extracellular loop region of Str1. Results show that these amino acid residues are critical to ensure timely completion of the outgrowth phase of spores in response to exogenous ferrichrome. Taken together, the results reveal the essential requirement of ferrichrome biosynthesis to promote outgrowth, as well as the necessity to take up ferrichrome from an external source via Str1 when ferrichrome biosynthesis is blocked.
Molecular and morphological identification of Phylloderma stenops Peters, 1865 (Chiroptera, Phyllostomidae) and new records for Colombia
Authors: Martínez-Cerón Juan M. , Patiño-Castillo Edilson , Carvalho-Madrigal Sara , Díaz-Nieto Juan F.
Published: January 2019

Based on revisionary work of recently collected material in Colombian museums we confirm the presence of Phylloderma stenops Peters, 1865 in 6 new localities for the country, including the first record of the species in the dry lowlands of the northern Caribbean coast, and the increase by more than 800 m of the elevational range of the species in Colombia. DNA-barcoding confirmed our morphological identification, and supported a paraphyletic composition of the cis-Andean populations. Our records exemplify the little knowledge on the ecogeographic distribution of this species and provide further evidence to consider this as a widespread but rare species.
Hepatitis C Virus Infection and Renal Disorders
Authors: Salvadori Maurizio , Tsalouchos Aris
Published: January 2019

Hepatitis C virus (HCV) infection is frequently associated with extrahepatic disorders, among which renal diseases are frequent. This article highlights the most frequent HCV-associated renal disorders, the impact of HCV infection on chronic renal disease and renal transplantation, and the role of current direct-acting antiviral therapies. HCV is associated with membranoproliferative glomerulonephritis, acceleration of end-stage renal diseases in patients with glomerulopathies, and a higher risk of death in patients affected by chronic kidney disease. Before the introduction of direct-acting antiviral drugs as treatment modality, renal transplantation was a challenging clinical problem because the drugs available until 2011 obtained a poor sustained virologic response, had several side effects, and caused acute rejection when used after transplantation. The knowledge of the viral structure and its replication allowed the discovery of new classes of direct-acting antiviral drugs that revolutionized this scenario. These new drugs are comparatively more effective and safer. Accumulating evidence suggests that it is possible to cure HCV-related glomerulonephritis, and obtain a sustained virologic response in patients with renal failure, or on dialysis, before commencing transplantation. Finally, it became possible to transplant HCV-positive kidneys into HCV-positive or HCV-negative recipients.
Influence of environmental factors on the bathymetric distribution of the flecked box crab Hepatus pudibundus (Herbst, 1785) (Crustacea: Aethroidea) in the Southeastern Brazilian coast
Authors: Bernardes Veronica Pereira , Mantelatto Fernando Luis , Silva Thiago Elias da , Sousa Aline Nonato de , Bernardo Camila Hipólito , Fransozo Adilson
Published: January 2019

Abstract: This study evaluated the relationships between environmental factors and the spatio-temporal distribution of H. pudibundus, with the hypothesis of differential occupation in coastal areas of southeastern Brazil. The samplings took place monthly in January-December 2000 period, along nine transects from 2 to 40 m of depth, in Ubatuba region, northern coast of São Paulo. We collected 1808 individuals of H. pudibundus. The highest abundance was recorded in winter in the transects 10-25 m deep. Abundance was positively correlated with organic matter content and texture sediment (phi values). With the retreat of the South Atlantic Central Water (SACW) in autumn and winter, the sediment swirls, suspending the detritivore and filter-feeding macrofauna, increasing the food availability. Sites characterized by finer sediment offer higher food availability, besides facilitating H. pudibundus burying behavior. Due to its opportunistic predatory behavior, this species feeds on a variety of organisms, including mollusks, annelids and foraminifera, which are preys more abundant in the studied area and in sediments of finer grain size.
Long-Term Safety Experience with Telotristat Ethyl Across Five Clinical Studies in Patients with Carcinoid Syndrome
Authors: Anthony Lowell B. , Kulke Matthew H. , Caplin Martyn E. , Bergsland Emily , Öberg Kjell , Pavel Marianne , Hörsch Dieter , Warner Richard R.P. , O'Dorisio Thomas M. , Dillon Joseph S. , Lapuerta Pablo , Kassler-Taub Kenneth , Jiang Wenjun
Published: January 2019

Background

Patients with neuroendocrine tumors (NETs) and carcinoid syndrome experience considerable morbidity and mortality; carcinoid syndrome may be associated with shorter survival. Carcinoid syndrome is linked to tumoral secretion of serotonin and other bioactive substances. The subsequent debilitating diarrhea and urgency to defecate pose significant health risks. In previous studies, telotristat ethyl, a tryptophan hydroxylase inhibitor, was effective and well tolerated in treating carcinoid syndrome diarrhea. We present pooled safety data from five clinical trials with telotristat ethyl in patients with carcinoid syndrome.

Subjects, Materials, and Methods

Adverse events reported during telotristat ethyl treatment were pooled from two phase II and three phase III clinical trials in 239 patients with carcinoid syndrome. Long-term safety of telotristat ethyl and causes of hospitalization and death were reviewed; overall survival was estimated.

Results

Mean (median; range) duration of exposure and follow-up was 1.3 years (1.1 years; 1 week to 5.7 years), with 309 total patient-years of exposure. Leading causes of hospitalization were gastrointestinal disorders or were related to the underlying tumor and related treatment. Survival estimates at 1, 2, and 3 years were 93%, 88%, and 77%. Nearly all deaths were due to progression or complication of the underlying disease; none were attributable to telotristat ethyl. There was one death in year 4.

Conclusion

Based on long-term safety data, telotristat ethyl is well tolerated and has a favorable long-term safety profile in patients with carcinoid syndrome.
Exploring Biomarkers of Phosphoinositide 3-Kinase Pathway Activation in the Treatment of Hormone Receptor Positive, Human Epidermal Growth Receptor 2 Negative Advanced Breast Cancer
Authors: Kaklamani Virginia G. , Richardson Andrea L. , Arteaga Carlos L.
Published: January 2019

Resistance to endocrine therapy (ET) is common in patients with hormone receptor positive (HR+) advanced breast cancer (ABC). Consequently, new targeted treatment options are needed in the post-ET setting, with validated biomarkers to inform treatment decisions. Hyperactivation of the phosphoinositide 3-kinase (PI3K) signaling pathway is common in ABC and is implicated in resistance to ET. The most frequent mechanism of PI3K pathway activation is activating mutations or amplification of PIK3CA, which encodes the α-isoform of the catalytic subunit of PI3K. Combining buparlisib, a pan-PI3K-targeted agent, with ET demonstrated modest clinical benefits in patients with aromatase inhibitor-resistant, HR+, human epidermal growth receptor 2 negative (HER2−) ABC in two phase III trials. Importantly, greater efficacy gains were observed in individuals with PIK3CA-mutated disease versus PIK3CA-wild-type tumors. Although the challenging safety profile did not support widespread use of this treatment combination, isoform-selective PI3K inhibitors may improve tolerability. In early clinical trials, promising disease control benefits were demonstrated with the PI3K isoform-selective inhibitors alpelisib and taselisib in patients with PIK3CA-mutated HR+, HER2− ABC. Ongoing biomarker-guided phase II/III studies may provide further opportunities to identify patients most likely to benefit from treatment with PI3K inhibitors and provide insight into optimizing the therapeutic index of PI3K inhibitors. Challenges facing the implementation of routine PIK3CA mutation testing must be addressed promptly so robust and reproducible genotyping can be obtained with liquid and tumor biopsies in a timely and cost-effective manner.

Implications for Practice

The development of phosphoinositide 3-kinase (PI3K) inhibitors, especially those that selectively target isoforms, may be an effective strategy for overcoming endocrine therapy resistance in hormone receptor positive, human epidermal growth receptor 2 negative advanced breast cancer. Early-phase studies have confirmed that patients with PIK3CA mutations respond best to PI3Kα-isoform inhibition. Ongoing phase III trials will provide further data regarding the efficacy and safety of PI3K inhibitors in patients with different biomarker profiles.
S-1 plus Raltitrexed for Refractory Metastatic Colorectal Cancer: A Phase II Trial
Authors: Chen Ye , Wu Jing , Cheng Ke , Li Zhi-Ping , Luo De-Yun , Qiu Meng , Gou Hong-Feng , Yi Cheng , Li Qiu , Wang Xin , Yang Yu , Cao Dan , Shen Ya-Li , Bi Feng , Liu Ji-Yan
Published: January 2019

Lessons Learned

The upregulation of dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) are important mechanisms of resistance to 5-fluorouracil (5-FU) in metastatic colorectal cancer (mCRC) after long exposure to 5-FU. S-1 (containing a DPD inhibitor) combined with raltitrexed (a TS inhibitor) showed a moderate effect, which needs further study as a third- or later-line therapy in mCRC.

Background

5-fluorouracil (5-FU) is a fundamental drug in the treatment of metastatic colorectal cancer (mCRC). Patients with mCRC are often exposed to 5-FU and/or its analogues for a long time because of its central role in treatment regimens. The upregulation of dihydropyrimidine dehydrogenase (DPD) and/or thymidylate synthase (TS) are important mechanisms of resistance of 5-FU. To evaluate the efficacy and safety of S-1 (containing a DPD inhibitor) and raltitrexed (a TS inhibitor) for refractory mCRC, a one-center, single-arm, prospective phase II trial was conducted.

Methods

Patients who had mCRC that had progressed after treatment with fluoropyrimidine, irinotecan, and oxaliplatin and who had at least one measurable lesion were eligible for this trial. Patients received oral S-1 (80–120 mg for 14 days every 3 weeks) plus an intravenous infusion of raltitrexed (3 mg/m2 on day 1 every 3 weeks). The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity.

Results

In total, 46 patients were enrolled. Three patients did not complete the first assessment because of adverse events and unwillingness, leaving tumor response evaluation available in 43 patients. Of 43 evaluable patients, the ORR was 13.9% and disease control rate was 58.1%. In the intention-to-treat population (n = 46), the ORR was 13.0% and disease control rate was 54.3%. Median PFS and median OS were 107 days (95% confidence interval [CI], 96.3–117.7) and 373 days (95% CI, 226.2–519.8), respectively. Most of the adverse effects were mild to moderate.

Conclusion

S-1 combined with raltitrexed for refractory mCRC showed moderate effect, and it is worthy of further study as third- or later-line therapy in mCRC.
Revisiting seismic slope stability: intermediate or below-the-toe failure?
Authors: Qin Changbing , Chian Siau Chen , Du Saizhao
Published: January 2019

This technical note presents a novel procedure, discretisation-based kinematic analysis, to investigate the seismic slope stability at limit state. Such a procedure combines the merits of highly efficient kinematic analysis with an adaptive discretisation technique for the generation of a kinematically admissible failure mechanism for non-uniform soil slopes with varying soil strength parameters, which cannot be readily solved in conventional limit analysis. Apart from shallow toe failure, the below-the-toe and intermediate failure modes are also likely to occur, particularly for gentle slopes. Considering the latter two modes, the proposed approach is applied to a non-uniform soil slope with linearly increasing soil properties and a layered soil profile to demonstrate the adaptability of the procedure for wider applications. The upper-bound formulations of yield seismic acceleration and/or limit surcharge are derived based on the balance of work rate. Through an optimisation procedure, the least upper-bound solutions are sought under given parameters, and the critical failure mechanism can be characterised simultaneously.
Recent understanding of the oxidation and burning of magnesium alloys
Authors: Tan Qiyang , Yin Yu , Mo Ning , Zhang Mingxing , Atrens Andrej
Published: January 2019

This paper reviews the following for magnesium (Mg) alloys: (a) fundamentals of oxidation and burning; (b) influence of alloying on oxidation; (c) theoretical models for improved oxidation resistance through alloying with calcium (Ca), beryllium (Be), strontium (Sr) and rare earth elements; (d) recent research on the improved oxidation resistance of beryllium-containing magnesium alloys; and (e) the recent proposed oxide reinforcement model. The oxidation resistance of magnesium alloys is closely related to the protective incubation period, which is mainly controlled by the crack resistance of the initially formed surface oxide layer. Cracking of the initially formed surface oxide facilitates the vapor phase diffusion of magnesium and results in catastrophic oxidation and eventual burning of magnesium. According to the oxide reinforcement model, an oxide layer with increased mechanical strength and hardness (such as the (Mg,Be)O layer on beryllium-containing alloys) can better withstand the internal tensile stress arising during the oxidation process and therefore can delay oxide layer cracking and extend the oxidation incubation period. This model provides guidance on developing new oxidation-resistant magnesium alloys.
How Do People Perceive Guesthouses as a Medium-low Priced Accommodation?: Focusing on Guesthouse Operators’ Perception and Typology by Q Methodology
Authors:   The Tourism Sciences Society Of Korea, Oh Jeong-Keun
Published: January 2019

This study was to form a typology after analyzing how guesthouse operators perceive guesthouses by using Q methodology. The results of Q analyses showed that 37 operators perceived four types: accommodations for travel convenience, accommodations to revive the economy, space for communication and information sharing, and alternative accommodations of legal regulation and fostering. Type 1, accommodations for travel convenience, means that they perceived guesthouses as a convenient space for travelling. Type 2, accommodations to revive the economy, means that they perceived guesthouses as a measure for national and regional economic revival and a way to create added value. Type 3, space for communication and information sharing, means that they perceived guesthouses as communication space for cultural exchange among travelers and local residents. Type 4, alternative accommodations of legal regulation and fostering, means that they perceived guesthouses as alternative accommodations that strengthen legal regulations and both foster and support. According to the results, academic, legislative, and political suggestions and implications were found, such as detailed research on medium-low priced accommodation, strong regulation of illegal guesthouses and relaxed regulations on business operators, expanding financial support, and creating tourist clusters based on guesthouses.
Analysis of Tourism Technology Trends in Korea and the U.S. Using Patent Information: Based on Topic Modeling
Authors:   The Tourism Sciences Society Of Korea, Kim Jeong-Kyu , Jeong Chul
Published: January 2019

Most studies on the technology trends in the field of tourism have mainly focused on the cases that are currently used by the tourism industry. The purpose of this paper is to quantitatively measure and evaluate technology trends in the tourism field in Korea and the U.S. based on tourism-related patents. For this purpose, this study attempts to derive the detailed techniques used in the field of tourism using the latent Dirichlet allocation (LDA) model of topic modeling and to understand the growing and declining technologies that are currently being used in both countries. As a result of this analysis, eight technologies were identified: (1) tourism information providing systems based on location information; (2) improvements in travel bag function and design; (3) business methods related to the hospitality industry; (4) tourism information provision and experience systems based on augmented and virtual reality; (5) terminal devices and software related to tourism information provision systems; (6) improvements in the function and design of travel equipment (excluding travel bags); (7) travel recommendation and reservation systems; and (8) travel information sharing and travel record collection systems. Three of these technologies are growing in Korea (tourism information and experience systems based on augmented reality and virtual reality, travel recommendation and reservation systems, and travel information sharing and travel record collection systems) and two are declining (business methods related to the hospitality industry and terminal devices and software related to tourism information provision systems). Data for the initial research on the tourism-related technology analysis and information about the technologies to be applied in tourism in the future is provided.
An Analysis of the Relatedness Effect in Leisure Sports: Collective Versus Individual Leisure Sports
Authors:   The Tourism Sciences Society Of Korea, Lee Kyung-Yur , Lee Hoon
Published: January 2019

Who feels happier between collective and individual sports participants? The purpose of this study was to examine the impact of relatedness on subjective well-being depending on the type of leisure sports. Accordingly, 788 adults participating in leisure sports in South Korea were divided into the categories of collective and individual leisure sports participants. Relatedness in sports, leisure sports participation behavior, leisure satisfaction, and subjective well-being were analyzed. The results of this study are as follows. First, collective leisure sports participants had higher mean values in leisure satisfaction as well as subjective well-being than individual ones. Additionally, the difference was statistically significant. Second, relatedness in sports bore a statistically significant impact on both leisure satisfaction and subjective well-being, regardless of the demographic characteristics as controlled variables. The importance of relatedness in leisure sports is discussed and academic and practical implications are provided in this study.