bluuebunny/crossref_metadata_2025 huggingface dataset:
Testing for human impacts in the mismatch of living and dead ostracode assemblages at nested spatial scales in subtropical lakes from the Bahamian archipelago
Authors: Michelson Andrew V. , Kidwell Susan M. , Park Boush Lisa E. , Ash Jeanine L.
Published: August 2018

Naturally time-averaged accumulations of skeletal remains—death assemblages—provide reliable, albeit temporally coarse, information on the species composition and structure of communities in diverse settings, and their mismatch with local living communities usually signals recent human-driven ecological change. Here, we present the first test of live–dead mismatch as an indicator of human stress using ostracodes. On three islands along a gradient of human population density in the Bahamas, we compared the similarity of living and death assemblages in 10 lakes with relatively low levels of human stress to live–dead similarity in 11 physically comparable lakes subject to industrial, agricultural, or other human activities currently or in the past. We find that live–dead agreement in pristine lakes is consistently excellent, boding well for using death assemblages in modern-day and paleolimnological biodiversity assessments. In most comparison of physically similar paired lakes, sample-level live–dead mismatch in both taxonomic composition and species’ rank abundance is on average significantly greater in the stressed lakes; live–dead agreement is not lower in all samples from stressed lakes, but is more variable. When samples are pooled for lake-level and island-level comparisons, stressed lakes still yield lower live–dead agreement, but the significance of the difference with pristine lakes decreases—species that occur dead-only (or alive-only) in one sample are likely to occur alive (or dead) in other samples. Interisland differences in live–dead agreement are congruent with, but not significantly correlated with, differences in human population density. This situation arises from heterogeneity in the timing and magnitudes of stresses and in the extent of poststress recovery. Live–dead mismatch in ostracode assemblages thus may be a reliable indicator of human impact at the sample level with the potential to be a widely applicable tool for identifying impacted habitats and, perhaps, monitoring the progress of their recovery.
Millennial-scale Asian monsoon variability during the late Marine Isotope Stage 6 from Hulu Cave, China
Authors: Wang Quan , Wang Yongjin , Shao Qingfeng , Liang Yijia , Zhang Zhenqiu , Kong Xinggong
Published: August 2018

A precisely 230Th-dated stalagmite δ13C profile from Hulu Cave, China, is presented to characterize the frequency and pattern of millennial-scale Asian monsoon (AM) variability from 160.6 to 132.5 ka. Evidence for an antiphased relationship of the δ13C and δ18O on the millennial scale suggests that the δ13C is indicative of the local hydrological cycle associated with changes in AM strength. Owing to the δ13C responding to AM changes more sensitively than the δ18O, we could identify 15 strong AM events that correlate to cold intervals recorded in Antarctic ice cores within 230Th dating uncertainty. This result supports a dynamic link of AM strength and southern hemispheric climates via the cross-equatorial airflows. Power spectrum analysis shows a predominant periodicity of 1.5–2.5 ka for the δ13C profile, similar to the Dansgaard-Oeschger frequency during the last glacial period. Moreover, the AM events are characterized by rapid transitions at the onset, suggesting that the observed millennial-scale AM variability is likely forced by northern high-latitude climates via north–south shifts of the Intertropical Convergence Zone associated with the bipolar seesaw mechanism. As evidence for a common mechanism for ice age terminations, a strong AM event (~134 ka) surrounding Termination II is analogous to the Bølling-Allerød warming interval.
Warriors and States: Military labour in southern India, circa 1750–1800
Authors: VARTAVARIAN MESROB
Published: August 2018

The consolidation of numerous regional polities in the aftermath of Mughal imperial decline presented favourable socioeconomic opportunities for South Asian service communities. Protracted armed conflicts in southern India allowed a variety of mercenaries, soldiers, and war bands to accumulate resources in exchange for mobilizing manpower on behalf of states with weak standing armies. This article focuses on British imperial efforts to obtain sufficient quantities of military labour during its struggle with the Mysore sultanate. As the sultanate assumed an increasingly hostile attitude towards independent warrior power, local strongmen sought more amenable arrangements with alternate entities. The British East India Company received crucial support from autonomous warrior groups during its southern wars of conquest. Warriors in turn utilized British resources to consolidate local sovereignties. Thus, the initial British intrusion into peninsular Indian society further fragmented the political landscape by patronizing petty military entrepreneurs.
Selective role for the COMT polymorphism in a trans-diagnostic compulsivity phenotype
Authors: Chamberlain Samuel R. , Grant Jon E.
Published: August 2018

Background

Impulsivity and compulsivity are central to understanding a range of psychiatric disorders but also to understanding the spectrum of normative human behavior. It was recently shown that separable latent phenotypes of impulsivity and compulsivity could be fractionated. The possible genetic contributions to these latent phenotypes have yet to be elicited. The catechol-o-methyl transferase (COMT) Val158Met polymorphism (rs4680) regulates cortical dopamine degradation and is a key area of interest in this context.

Methods

COMT Val158Met polymorphism status was obtained from a random subset (n = 258) of young adults from an established cohort, for whom latent phenotype scores were previously reported. Differences in latent phenotype scores were explored between COMT groups using analysis of variance (ANOVA) and post-hoc t tests.

Results

The Val-Val subgroup exhibited significantly elevated compulsivity scores compared to both other groups. Impulsivity scores did not differ significantly as a function of COMT Val158Met polymorphism status.

Conclusions

These results suggest that the COMT polymorphism, and by implication cortical dopamine degradation, influences the expression of a trans-diagnostic compulsivity phenotype, even accounting for possible confounding effects of impulsivity.
Longitudinal Changes in Resting State Connectivity and White Matter Integrity in Adolescents With Sports-Related Concussion
Authors: Murdaugh Donna L. , King Tricia Z. , Sun Binjian , Jones Richard A. , Ono Kim E. , Reisner Andrew , Burns Thomas G.
Published: August 2018

Objectives: The aim of this study was to investigate alterations in functional connectivity, white matter integrity, and cognitive abilities due to sports-related concussion (SRC) in adolescents using a prospective longitudinal design. Methods: We assessed male high school football players (ages 14–18) with (n=16) and without (n=12) SRC using complementary resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI) along with cognitive performance using the Immediate Post-Concussive Assessment and Cognitive Testing (ImPACT). We assessed both changes at the acute phase (<7 days post-SRC) and at 21 days later, as well as, differences between athletes with SRC and age- and team-matched control athletes. Results: The results revealed rs-fMRI hyperconnectivity within posterior brain regions (e.g., precuneus and cerebellum), and hypoconnectivity in more anterior areas (e.g., inferior and middle frontal gyri) when comparing SRC group to control group acutely. Performance on the ImPACT (visual/verbal memory composites) was correlated with resting state network connectivity at both time points. DTI results revealed altered diffusion in the SRC group along a segment of the corticospinal tract and the superior longitudinal fasciculus in the acute phase of SRC. No differences between the SRC group and control group were seen at follow-up imaging. Conclusions: Acute effects of SRC are associated with both hyperconnectivity and hypoconnectivity, with disruption of white matter integrity. In addition, acute memory performance was most sensitive to these changes. After 21 days, adolescents with SRC returned to baseline performance, although chronic hyperconnectivity of these regions could place these adolescents at greater risk for secondary neuropathological changes, necessitating future follow-up. (JINS, 2018, 24, 781–792)
Akute Herzinsuffizienz
Authors: Arrigo Mattia , Ruschitzka Frank , Flammer Andreas J.
Published: August 2018

Zusammenfassung. Akute Herzinsuffizienz (AHF) ist eine lebensbedrohliche Erkrankung, die eine sofortige Behandlung erfordert. Die initiale Therapie sollte die klinische Präsentation, die pathophysiologischen Mechanismen, die auslösenden Faktoren und die zugrundeliegende Herzpathologie berücksichtigen. Besondere Aufmerksamkeit sollte der Polymorbidität und der Vermeidung potentieller iatrogener Schäden gewidmet werden. Patientenpräferenzen, Langzeitoptionen und ethische Fragen sollten frühzeitig in den Behandlungsplan integriert werden. Die Prognose von AHF-Patienten ist ernst, und die kritischste Zeitspanne stellen die ersten drei Monate direkt nach der Spitalentlassung dar. Daher ist es für die Verbesserung der Prognose von AHF-Patienten unerlässlich, die persistierende subklinische systemische Stauung zu vermeiden, den Einsatz von krankheitsmodifizierenden Herzinsuffizienz-Therapien zu optimieren und optimale Versorgungsübergänge nach der Spitalentlassung sicherzustellen.
Schlaf und Kognition bei Kindern und Jugendlichen
Authors: Prehn-Kristensen Alexander , Göder Robert
Published: August 2018

Zusammenfassung. In diesem Überblicksartikel beschäftigen wir uns mit einer der wichtigsten Aufgaben des Schlafs, nämlich der Förderung kognitiver Prozesse bei Kindern und Jugendlichen. Bislang wurde überwiegend bei älteren Kindern und Jugendlichen beschrieben, dass der Schlaf die kognitive Leistungsfähigkeit auf komplexe Weise beeinflusst. Schon bei sehr jungen Kindern wurde nachgewiesen, dass der Schlaf eine fördernde Funktion in vielen Bereichen des Langzeitgedächtnisses aufweist. Hierzu gehören das Faktenwissen (deklaratives Gedächtnis) sowie das Erlernen von Sprache und das Lernen aus Belohnung. Hingegen fördert Schlaf bei Kindern die Konsolidierung motorischer Fertigkeiten nur unter bestimmten Voraussetzungen. Klinische Implikationen ergeben sich aus den Beobachtungen der Folgen von Schlafmangel bei Kindern und Jugendlichen aufgrund des frühen Schulbeginns, aber auch aus Untersuchungen von verschiedenen Störungsbildern wie der Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS), dem Schlafapnoesyndrom und anderen Schlafstörungen. Nur teilweise wurde bisher gezeigt, dass eine Behandlung der Störungen des Schlafs auch zu verbesserten Kognitions- oder Gedächtnisleistungen führt. Dies bleibt eine Herausforderung zukünftiger Forschungsanstrengungen.
Profitieren psychisch erkrankte Eltern und psychisch belastete Kinder von einer gemeinsamen Eltern-Kind-Behandlung?
Authors: Fritz Lisa-Marina , Domin Sabine , Thies Annekatrin , Yang Julia , Stolle Martin , Fricke Christian , Petermann Franz
Published: August 2018

Zusammenfassung. Es wird überprüft, ob die Teilnahme am Gruppenprogramm SEEK (Seelische Erkrankungen, Eltern und Kinder) für psychisch erkrankte Eltern im Rahmen einer stationären Eltern-Kind-Behandlung kurz- und längerfristige additive Behandlungseffekte erbringt hinsichtlich psychischer Symptome der Eltern (erfasst mit der Hopkins-Symptom-Checkliste-25; HSCL-25), der elterlichen Stressbelastung (erfasst mit dem Eltern-Belastungs-Inventar; EBI) sowie psychischer und körperlicher Symptome des Kindes (erfasst mit der Child Behavior Checklist; CBCL). Die Vergleichsgruppe (n = 11), die das übliche Behandlungsprogramm durchlief, und die Interventionsgruppe (n = 15), die zusätzlich an SEEK teilnahm, werden zu drei Messzeitpunkten (t1 bei Aufnahme, t2 bei Entlassung und t3 sechs Monate nach Entlassung) miteinander verglichen. Additive Effekte des Gruppenprogramms können bei dieser Untersuchung im umfangreichen stationären Behandlungssetting nicht belegt werden. Beide Gruppen erscheinen (mit Ausnahme zweier CBCL-Skalen im t1-t2-Vergleich) vergleichbar bezüglich ihres Behandlungserfolgs. Es zeigen sich sowohl kurzfristige Effekte als auch längerfristig stabile Effekte der stationären Eltern-Kind-Behandlung im 6-Monats-Follow-Up.
Lateral Rheology Differences in the Lithosphere and Dynamics as Revealed by Magnetotelluric Imaging at the Northern Tibetan Plateau
Authors: Xiao Qibin , Yu Guo , Shao Guihang , Li Man , Wang Jijun
Published: August 2018

Differences in topography and surface deformation in the northern Tibetan Plateau may reflect variable rheology in the lithosphere. Whether middle to lower crustal flow exists below the region between the eastern Kunlun Shan range and the Qaidam Basin remains debated. We provide electrical resistivity images of three new magnetotelluric (MT) profiles across the Qiman Tagh and the western Qaidam Basin. The new models reveal low‐resistivity anomalies below the Qaidam Basin in the lower crust and generally high‐resistivity crust in the Qiman Tagh range. A low‐resistivity anomaly at the uppermost‐mantle level is imaged below the Qiman Tagh range in the profile close to the Altyn Tagh Fault. This anomaly is possibly connected with partial melting in the lower portion of the thickened Songpan‐Ganzi crust close to the southern end of the study area; the minimum requirements for the low‐resistivity anomaly below the Qiman Tagh are 0.05 wt% water content or 0.02 melt fraction, which may greatly decrease the effective viscosity in the uppermost‐mantle rocks and allow flowing. Consequently, we propose that the crustal flow is not mature below the Kunlun Shan range south of the Qaidam Basin because no continuous and stable low‐resistivity anomaly was imaged at this level. The uppermost‐mantle low‐resistivity anomaly below the Qiman Tagh is a passage that allows the continuous northward transfer of materials in the interior of the plateau. This low‐resistivity channel shallows northward and reaches the lower crust of the southwestern Qaidam Basin.
Are STEREO Single Hits Dust Impacts?
Authors: Kellogg P. J. , Goetz K. , Monson S. J.
Published: August 2018

A certain type of impulsive signal in the Solar Terrestrial Relations Observatory (STEREO) electric field data has been identified as impacts of small dust, nanodust, entrained by the solar wind and accelerated to solar wind speeds, so that their speed compensates, in the emitted cloud, for their small size. It is argued here that these signals, called single hit signals, are not due to nanodust nor to dust impacts at all, as they have some characteristics which are not compatible with random hits by interplanetary and interstellar dust. The major observational data for the flux of nanodust are then in question. Another cause of these signals, however, is not given, and their cause is unknown.
The Vortex State in Geologic Materials: A Micromagnetic Perspective
Authors: Lascu Ioan , Einsle Joshua F. , Ball Matthew R. , Harrison Richard J.
Published: August 2018

A wide variety of Earth and planetary materials are very good recorders of paleomagnetic information. However, most magnetic grains in these materials are not in the stable single domain grain size range but are larger and in nonuniform vortex magnetization states. We provide a detailed account of vortex phenomena in geologic materials by simulating first‐order reversal curves (FORCs) via finite‐element micromagnetic modeling of magnetite nanoparticles with realistic morphologies. The particles have been reconstructed from focused ion beam nanotomography of magnetite‐bearing obsidian and accommodate single and multiple vortex structures. Single vortex (SV) grains have fingerprints with contributions to both the transient and transient‐free zones of FORC diagrams. A fundamental feature of the SV fingerprint is a central ridge, representing a distribution of negative saturation vortex annihilation fields. SV irreversible events at multiple field values along different FORC branches determine the asymmetry in the upper and lower lobes of generic bulk FORC diagrams of natural materials with grains predominantly in the vortex state. Multivortex (MV) FORC signatures are modeled here for the first time. MV grains contribute mostly to the transient‐free zone of a FORC diagram, averaging out to create a broad central peak. The intensity of the central peak is higher than that of the lobes, implying that MV particles are more abundant than SV particles in geologic materials with vortex state fingerprints. The abundance of MV particles, as well as their single domain‐like properties point to MV grains being the main natural remanent magnetization carriers in geologic materials.
Geothermal Heating in the Panama Basin: 1. Hydrography of the Basin
Authors: Banyte D. , Morales Maqueda M. , Hobbs R. , Smeed D. A. , Megann A. , Recalde S.
Published: August 2018

The Panama Basin serves as a laboratory to investigate abyssal water upwelling. The basin has only a single abyssal water inflow pathway through the narrow Ecuador Trench. The estimated critical inflow through the Trench reaches 0.34 ± 0.07 m/s, resulting in an abyssal water volume inflow of 0.29 ± 0.07 Sv. The same trench carries the return flow of basin waters that starts just 200 m above the bottom and is approximately 400‐m deeper than the depth of the next possible deep water exchange pathway at the Carnegie Ridge Saddle. The curvature of temperature‐salinity diagrams is used to differentiate the effect of geothermal heating on the deep Panama Basin waters that was found to reach as high as 2,200‐m depth, which is about 500 m above the upper boundary of the abyssal water layer.
Geothermal Heating in the Panama Basin. Part II: Abyssal Water Mass Transformation
Authors: Banyte D. , Morales Maqueda M. , Smeed D. A. , Megann A. , Hobbs R. , Recalde S.
Published: August 2018

Diabatic upwelling of abyssal waters is investigated in the Panama Basin employing the water mass transformation framework of Walin (). We find that, in large areas of the basin, the bottom boundary layer is very weakly stratified and extends hundreds of meters above the sea floor. Within the weakly stratified bottom boundary layer, neutral density layers intercept the bottom of the basin. The area of these density layer incrops increases gradually as the abyssal waters become lighter. Large incrop areas are associated with strong diabatic upwelling of abyssal water, geothermal heating being the largest buoyancy source. While a significant amount of water mass transformation is due to extreme turbulence downstream of the Ecuador Trench, the only abyssal water inflow passage, water mass transformation across the upper boundary of abyssal water layer is accomplished almost entirely by geothermal heating.
Single capillary oximetry and tissue ultrastructural sensing by dual-band dual-scan inverse spectroscopic optical coherence tomography
Authors: Liu Rongrong , Winkelmann James A. , Spicer Graham , Zhu Yunxiao , Eid Aya , Ameer Guillermo A. , Backman Vadim , Yi Ji
Published: August 2018

Measuring capillary oxygenation and the surrounding ultrastructure can allow one to monitor a microvascular niche and better understand crucial biological mechanisms. However, capillary oximetry and pericapillary ultrastructure are challenging to measure in vivo. Here we demonstrate a novel optical imaging system, dual-band dual-scan inverse spectroscopic optical coherence tomography (D2-ISOCT), that, for the first time, can simultaneously obtain the following metrics in vivo using endogenous contrast: (1) capillary-level oxygen saturation and arteriolar-level blood flow rates, oxygen delivery rates, and oxygen metabolic rates; (2) spatial characteristics of tissue structures at length scales down to 30 nm; and (3) morphological images up to 2 mm in depth. To illustrate the capabilities of D2-ISOCT, we monitored alterations to capillaries and the surrounding pericapillary tissue (tissue between the capillaries) in the healing response of a mouse ear wound model. The obtained microvascular and ultrastructural metrics corroborated well with each other, showing the promise of D2-ISOCT for becoming a powerful new non-invasive imaging tool.
Optical metasurfaces: new generation building blocks for multi-functional optics
Authors: Neshev Dragomir , Aharonovich Igor
Published: August 2018

Optical metasurfaces (OMs) have emerged as promising candidates to solve the bottleneck of bulky optical elements. OMs offer a fundamentally new method of light manipulation based on scattering from resonant nanostructures rather than conventional refraction and propagation, thus offering efficient phase, polarization, and emission control. This perspective highlights state of the art OMs and provides a roadmap for future applications, including active generation, manipulation and detection of light for quantum technologies, holography and sensing.
The genetic risk of Alzheimer’s disease beyond APOE ε4: systematic review of Alzheimer’s genetic risk scores
Authors: Stocker Hannah , Möllers Tobias , Perna Laura , Brenner Hermann
Published: August 2018

The ε4 allele of Apolipoprotein E (APOE) is the strongest known genetic risk factor of Alzheimer’s disease (AD) but does not account for the entirety of genetic risk. Genetic risk scores (GRSs) incorporating additional genetic variants have been developed to determine the genetic risk for AD, yet there is no systematic review assessing the contribution of GRSs for AD beyond the effect of APOE ε4. The purpose of this systematic PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses)-based review was to summarize original research studies that have developed and validated a GRS for AD utilizing associated single nucleotide polymorphisms (SNPs). The PubMed and Web of Science databases were searched on April 6, 2018 and screening was completed on 2018 citations by two independent reviewers. Eighteen studies published between 2010 and 2018 were included in the review. All GRSs expressed significant associations or discrimination capability of AD when compared to clinically normal controls; however, GRS prediction of MCI to AD conversion was mixed. APOE ε4 status was more predictive of AD than the GRSs, although the GRSs did add to AD prediction accuracy beyond APOE ε4. GRSs might contribute to identifying genetic risk of AD beyond APOE. However, additional studies are warranted to assess the performance of GRSs in independent longitudinal cohorts.
Real-time in vivo two-photon imaging study reveals decreased cerebro-vascular volume and increased blood-brain barrier permeability in chronically stressed mice
Authors: Lee Sohee , Kang Bok-Man , Kim Jae Hwan , Min Jiwoong , Kim Hyung Seok , Ryu Hyunwoo , Park Hyejin , Bae Sungjun , Oh Daehwan , Choi Myunghwan , Suh Minah
Published: August 2018

Chronic stress disrupts brain homeostasis and adversely affects the cerebro-vascular system. Even though the effects of chronic stress on brain system have been extensively studied, there are few in vivo dynamic studies on the effects of chronic stress on the cerebro-vascular system. In this study, the effects of chronic stress on cerebral vasculature and BBB permeability were studied using in vivo two-photon (2p) microscopic imaging with an injection of fluorescence-conjugated dextran. Our real-time 2p imaging results showed that chronic stress reduced the vessel diameter and reconstructed vascular volume, regardless of vessel type and branching order. BBB permeability was investigated with two different size of tracers. Stressed animals exhibited a greater BBB permeability to 40-kDa dextran, but not to 70-kDa dextran, which is suggestive of weakened vascular integrity following stress. Molecular analysis revealed significantly higher VEGFa mRNA expression and a reduction in claudin-5. In summary, chronic stress decreases the size of cerebral vessels and increases BBB permeability. These results may suggest that the sustained decrease in cerebro-vascular volume due to chronic stress leads to a hypoxic condition that causes molecular changes such as VEGF and claudin-5, which eventually impairs the function of BBB.
PirVP genes causing AHPND identified in a new Vibrio species (Vibrio punensis) within the commensal Orientalis clade
Authors: Restrepo Leda , Bayot Bonny , Arciniegas Sebastián , Bajaña Leandro , Betancourt Irma , Panchana Fanny , Reyes Muñoz Alejandro
Published: August 2018

Acute hepatopancreatic necrosis disease (AHPND) has extended rapidly, causing alarming shrimp mortalities. Initially, the only known causative agent wasVibrio parahaemolyticuscarrying a plasmid coding for the mortal toxinsPirVP. Recently, it has been found that the plasmid and hence the disease, could be transferred among members of theHarveyiclade. The current study performs a genomic characterization of an isolate capable of developing AHPND in shrimp. Mortality studies and molecular and histopathological analyses showed the infection capacity of the strain. Multilocus sequence analysis placed the bacteria as a member of theOrientalisclade, well known for containing commensal and even probiotic bacteria used in the shrimp industry. Further whole genome comparative analyses, includingVibriospecies from theOrientalisclade, and phylogenomic metrics (TETRA, ANI and DDH) showed that the isolate belongs to a previously unidentified species, now namedVibrio punensis sp. nov. strain BA55. Our findings show that the gene transfer capacity ofVibriospecies goes beyond the clade classification, demonstrating a new pathogenic capacity to a previously known commensal clade. The presence of these genes in a differentVibrioclade may contribute to the knowledge of theVibriopathogenesis and has major implications for the spread of emerging diseases.
OncomiR-10b hijacks the small molecule inhibitor linifanib in human cancers
Authors: Monroig-Bosque Paloma del C. , Shah Maitri Y. , Fu Xiao , Fuentes-Mattei Enrique , Ling Hui , Ivan Cristina , Nouraee Nazila , Huang Beibei , Chen Lu , Pileczki Valentina , Redis Roxana S. , Jung Eun-Jung , Zhang Xinna , Lehrer Michael , Nagvekar Rahul , Mafra Ana Carolina P. , Monroig-Bosque Maria del Mar , Irimie Alexandra , Rivera Carlos , Dan Dumitru Calin , Berindan-Neagoe Ioana , Nikonowicz Edward P. , Zhang Shuxing , Calin George A.
Published: August 2018

The pervasive role of microRNAs (miRNAs) in cancer pathobiology drives the introduction of new drug development approaches such as miRNA inhibition. In order to advance miRNA-therapeutics, meticulous screening strategies addressing specific tumor targets are needed. Small molecule inhibitors represent an attractive goal for these strategies. In this study, we devised a strategy to screen for small molecule inhibitors that specifically inhibit, directly or indirectly, miR-10b (SMIRs) which is overexpressed in metastatic tumors. We found that the multi-tyrosine kinase inhibitor linifanib could significantly inhibit miR-10b and reverse its oncogenic function in breast cancer and liver cancer both in vitro and in vivo. In addition, we showed that the efficacy of linifanib to inhibit tyrosine kinases was reduced by high miR-10b levels. When the level of miR-10b is high, it can “hijack” the linifanib and reduce its kinase inhibitory effects in cancer resulting in reduced anti-tumor efficacy. In conclusion, our study describes an effective strategy to screen for small molecule inhibitors of miRNAs. We further propose that miR-10b expression levels, due to the newly described “hijacking” effect, may be used as a biomarker to select patients for linifanib treatment.
ALS-causing mutations in profilin-1 alter its conformational dynamics: A computational approach to explain propensity for aggregation
Authors: Kiaei Mahmoud , Balasubramaniam Meenakshisundaram , Govind Kumar Vivek , Shmookler Reis Robert J. , Moradi Mahmoud , Varughese Kottayil I.
Published: August 2018

Profilin-1 (PFN1) is a 140-amino-acid protein with two distinct binding sites―one for actin and one for poly-L-proline (PLP). The best-described function of PFN1 is to catalyze actin elongation and polymerization. Thus far, eight DNA mutations in the PFN1 gene encoding the PFN1 protein are associated with human amyotrophic lateral sclerosis (ALS). We and others recently showed that two of these mutations (Gly118Val or G118V and Cys71Gly or C71G) cause ALS in rodents. In vitro studies suggested that Met114Thr and Thr109Met cause the protein to behave abnormally and cause neurotoxicity. The mechanism by which a single amino acid change in human PFN1 causes the degeneration of motor neurons is not known. In this study, we investigated the structural perturbations of PFN1 caused by each ALS-associated mutation. We used molecular dynamics simulations to assess how these mutations alter the secondary and tertiary structures of human PFN1. Herein, we present our in silico data and analysis on the effect of G118V and T109M mutations on PFN1 and its interactions with actin and PLP. The substitution of valine for glycine reduces the conformational flexibility of the loop region between the α-helix and β-strand and enhances the hydrophobicity of the region. Our in silico analysis of T109M indicates that this mutation alters the shape of the PLP-binding site and reduces the flexibility of this site. Simulation studies of PFN1 in its wild type (WT) and mutant forms (both G118V and T109M mutants) revealed differential fluctuation patterns and the formation of salt bridges and hydrogen bonds between critical residues that may shed light on differences between WT and mutant PFN1. In particular, we hypothesize that the flexibility of the actin- and PLP-binding sites in WT PFN1 may allow the protein to adopt slightly different conformations in its free and bound forms. These findings provide new insights into how each of these mutations in PFN1 might increase its propensity for misfolding and aggregation, leading to its dysfunction.
Graves’ orbitopathy occurs sex-independently in an autoimmune hyperthyroid mouse model
Authors: Schlüter Anke , Flögel Ulrich , Diaz-Cano Salvador , Görtz Gina-Eva , Stähr Kerstin , Oeverhaus Michael , Plöhn Svenja , Mattheis Stefan , Moeller Lars C. , Lang Stephan , Bechrakis Nikolaos E. , Banga J. Paul , Eckstein Anja , Berchner-Pfannschmidt Utta
Published: August 2018

Graves’ orbitopathy (GO) is the most common extra thyroidal complication of Graves’ disease (GD) and occurs predominantly in women but more severe in men. The reason for this effect of gender on GO is unknown. Herein we studied the manifestation of GO in both sexes of an induced mouse model in absence of additional risk factors present in patients like advanced age, genetic variabilities or smoking. Male and female mice were immunized with human TSHR A-subunit encoding plasmid. Both sexes comparably developed autoimmune hyperthyroidism characterized by TSHR stimulating autoantibodies, elevated T4 values, hyperplastic thyroids and hearts. Autoimmune mice developed inflammatory eye symptoms and proptosis, although males earlier than females. Serial in vivo1H/19F-magnetic resonance imaging revealed elevated inflammatory infiltration, increased fat volume and glycosaminoglycan deposition in orbits of both sexes but most significantly in female mice. Histologically, infiltration of T-cells, extension of brown fat and overall collagen deposition were characteristics of GO in male mice. In contrast, female mice developed predominately macrophage infiltration in muscle and connective tissue, and muscle hypertrophy. Apart from sex-dependent variabilities in pathogenesis, disease classification revealed minor sex-differences in incidence and total outcome. In conclusion, sex does not predispose for autoimmune hyperthyroidism and associated GO.
Effects of land use/cover on surface water pollution based on remote sensing and 3D-EEM fluorescence data in the Jinghe Oasis
Authors: Wang Xiaoping , Zhang Fei
Published: August 2018

The key problem in the reasonable management of water is identifying the effective radius of surface water pollution. Remote sensing and three-dimensional fluorescence technologies were used to evaluate the effects of land use/cover on surface water pollution. The PARAFAC model and self-organizing map (SOM) neural network model were selected for this study. The results showed that four fluorescence components, microbial humic-like (C1), terrestrial humic-like organic (C2, C4), and protein-like organic (C3) substances, were successfully extracted by the PARAFAC factor analysis. Thirty water sampling points were selected to build 5 buffer zones. We found that the most significant relationships between land use and fluorescence components were within a 200 m buffer, and the maximum contributions to pollution were mainly from urban and salinized land sources. The clustering of land-use types and three-dimensional fluorescence peaks by the SOM neural network method demonstrated that the three-dimensional fluorescence peaks and land-use types could be grouped into 4 clusters. Principal factor analysis was selected to extract the two main fluorescence peaks from the four clustered fluorescence peaks; this study found that the relationships between salinized land, cropland and the fluorescence peaks of C1, W2, and W7 were significant by the stepwise multiple regression method.
Effects of sustained daily latanoprost application on anterior chamber anatomy and physiology in mice
Authors: Dutca Laura M. , Rudd Danielle , Robles Victor , Galor Anat , Garvin Mona K. , Anderson Michael G.
Published: August 2018

Latanoprost is a common glaucoma medication. Here, we study longitudinal effects of sustained latanoprost treatment on intraocular pressure (IOP) in C57BL/6J mice, as well as two potential side-effects, changes in iris pigmentation and central corneal thickness (CCT). Male C57BL/6J mice were treated daily for 16 weeks with latanoprost. Control mice were treated on the same schedule with the preservative used with latanoprost, benzalkonium chloride (BAK), or handled, without ocular treatments. IOP and CCT were studied at pre-treatment, 2 “early” time points, and 2 “late” time points; slit-lamp analysis performed at a late time point; and expression of corneal and iridial candidate genes analyzed at the end of the experiment. Latanoprost lowered IOP short, but not long-term. Sustained application of BAK consistently resulted in significant corneal thinning, whereas sustained treatment with latanoprost resulted in smaller and less consistent changes. Neither treatment affected iris pigmentation, corneal matrix metalloprotease expression or iridial pigment-related genes expression. In summary, latanoprost initially lowered IOP in C57BL/6J mice, but became less effective with sustained treatment, likely due to physiological adaptation. These results identify a new resource for studying changes in responsiveness associated with long-term treatment with latanoprost and highlight detrimental effects of commonly used preservative BAK.
ADAMTS1 protease is required for a balanced immune cell repertoire and tumour inflammatory response
Authors: Rodríguez-Baena Francisco Javier , Redondo-García Silvia , Peris-Torres Carlos , Martino-Echarri Estefanía , Fernández-Rodríguez Rubén , Plaza-Calonge María del Carmen , Anderson Per , Rodríguez-Manzaneque Juan Carlos
Published: August 2018

Recent advances have emphasized the relevance of studying the extracellular microenvironment given its main contribution to tissue homeostasis and disease. Within this complex scenario, we have studied the extracellular protease ADAMTS1 (a disintegrin and metalloprotease with thrombospondin motif 1), implicated in vascularization and development, with reported anti- and pro-tumorigenic activities. In this work we performed a detailed study of the vasculature and substrates in adult organs of wild type and Adamts1-deficient mice. In addition to the expected alterations of organs like kidney, heart and aorta, we found that the lack of ADAMTS1 differently affects lymphocyte and myeloid populations in the spleen and bone marrow. The study of the substrate versican also revealed its alteration in the absence of the protease. With such premises, we challenged our mice with subcutaneous B16F1 syngeneic tumours and closely evaluated the immune repertoire in the tumours but also in the distant spleen and bone marrow. Our results confirmed a pro-inflammatory landscape in the absence of ADAMTS1, correlating with tumour blockade, supporting its novel role as a modulator of the immune cell response.
Prevalence and influencing factors of overweight and obesity in a Chinese rural population: the Henan Rural Cohort Study
Authors: Liu Xiaotian , Wu Weidong , Mao Zhenxing , Huo Wenqian , Tu Runqi , Qian Xinling , Zhang Xia , Tian Zhongyan , Zhang Haiqing , Jiang Jingjing , Li Yuqian , Wang Chongjian
Published: August 2018

The study aimed to estimate prevalence and influencing factors of overweight, general obesity, and abdominal obesity in rural areas of China. A total of 39034 participants aged 18 to 79 years were enrolled from the Henan Rural Cohort Study for the cross-sectional study. The age-standardized prevalence of overweight, general obesity, and abdominal obesity were 34.97%, 16.82%, and 43.71% in the general Chinese rural adults, respectively. Gender differences were: 36.04%, 18.98%, 35.37% for men, and 34.55%, 15.42%, 49.13% for women, respectively. The subgroup analysis showed the rates of overweight, general obesity, and abdominal obesity existed considerable disparities, but were universally high in all subgroups. Further, the study found that there were statistically significant U-shaped associations between the prevalence of overweight, general obesity, and abdominal obesity and age groups. In addition, the prevalence of participants with both abnormal BMI and WC were even at approximate forty percent. Aging, married/cohabiting, higher per capita monthly income, and unhealthy lifestyle were independent influencing factors of overweight, general obesity and abdominal obesity. In conclusion, overweight and obesity were severe in rural China. There is an increased need for closely monitoring high risk factors and promoting healthy lifestyle to curb the obesity epidemic among rural population.
Vasopressin and oxytocin in sensory neurones: expression, exocytotic release and regulation by lactation
Authors: Dayanithi Govindan , Forostyak Oksana , Forostyak Serhiy , Kayano Tomohiko , Ueta Yoichi , Verkhratsky Alexei
Published: August 2018

The neurohormones arginine-vasopressin (AVP) and oxytocin (OT) synthesised in supraoptic and paraventricular nuclei of neurohypophysis regulate lactation, systemic water homeostasis and nociception. Using transgenic rats expressing AVP and OT tagged with fluorescent proteins we demonstrate that both neurohormones are expressed in sensory neurones both in vitro, in primary cultures, and in situ, in the intact ganglia; this expression was further confirmed with immunocytochemistry. Both neurohormones were expressed in nociceptive neurones immunopositive to transient receptor potential vannilloid 1 (TRPV1) channel antibodies. The AVP and OT-expressing DRG neurones responded to AVP, OT, 50 mM K+ and capsaicin with [Ca2+]i transients; responses to AVP and OT were specifically blocked by the antagonists of V1 AVP and OT receptors. Probing the extracellular incubation saline with ELISA revealed AVP and OT secretion from isolated DRGs; this secretion was inhibited by tetanus toxin (TeNT) indicating the role for vesicular release. Expression of OT, but not AVP in DRG neurones significantly increased during lactation. Together, the results indicate novel physiological roles (possibly related to nociception and mood regulation) of AVP and OT in the sensory neurones.
A microscopic Kapitza pendulum
Authors: Richards Christopher J. , Smart Thomas J. , Jones Philip H. , Cubero David
Published: August 2018

Pyotr Kapitza studied in 1951 the unusual equilibrium features of a rigid pendulum when its point of suspension is under a high-frequency vertical vibration. A sufficiently fast vibration makes the top position stable, putting the pendulum in an inverted orientation that seemingly defies gravity. Kapitza’s analytical method, based on an asymptotic separation of fast and slow variables yielding a renormalized potential, has found application in many diverse areas. Here we study Kapitza’s pendulum going beyond its typical idealizations, by explicitly considering its finite stiffness and the dissipative interaction with the surrounding medium, and using similar theoretical methods as Kapitza. The pendulum is realized at the micrometre scale using a colloidal particle suspended in water and trapped by optical tweezers. Though the strong dissipation present at this scale prevents the inverted pendulum regime, new ones appear in which the equilibrium positions are displaced to the side, and with transitions between them determined either by the driving frequency or the friction coefficient. These new regimes could be exploited in applications aimed at particle separation at small scales.
CEA: Combination-based gene set functional enrichment analysis
Authors: Sun Duanchen , Liu Yinliang , Zhang Xiang-Sun , Wu Ling-Yun
Published: August 2018

Functional enrichment analysis is a fundamental and challenging task in bioinformatics. Most of the current enrichment analysis approaches individually evaluate functional terms and often output a list of enriched terms with high similarity and redundancy, which makes it difficult for downstream studies to extract the underlying biological interpretation. In this paper, we proposed a novel framework to assess the performance of combination-based enrichment analysis. Using this framework, we formulated the enrichment analysis as a multi-objective combinatorial optimization problem and developed the CEA (Combination-based Enrichment Analysis) method. CEA provides the whole landscape of term combinations; therefore, it is a good benchmark for evaluating the current state-of-the-art combination-based functional enrichment methods in a comprehensive manner. We tested the effectiveness of CEA on four published microarray datasets. Enriched functional terms identified by CEA not only involve crucial biological processes of related diseases, but also have much less redundancy and can serve as a preferable representation for the enriched terms found by traditional single-term-based methods. CEA has been implemented in the R package CopTea and is available at http://github.com/wulingyun/CopTea/.
Multiple polymerase gene mutations for human adaptation occurring in Asian H5N1 influenza virus clinical isolates
Authors: Arai Yasuha , Kawashita Norihito , Hotta Kozue , Hoang Phuong Vu Mai , Nguyen Hang Le Khanh , Nguyen Thach Co , Vuong Cuong Duc , Le Thanh Thi , Le Mai Thi Quynh , Soda Kosuke , Ibrahim Madiha S. , Daidoji Tomo , Takagi Tatsuya , Shioda Tatsuo , Nakaya Takaaki , Ito Toshihiro , Hasebe Futoshi , Watanabe Yohei
Published: August 2018

The role of the influenza virus polymerase complex in host range restriction has been well-studied and several host range determinants, such as the polymerase PB2-E627K and PB2-D701N mutations, have been identified. However, there may be additional, currently unknown, human adaptation polymerase mutations. Here, we used a database search of influenza virus H5N1 clade 1.1, clade 2.3.2.1 and clade 2.3.4 strains isolated from 2008–2012 in Southern China, Vietnam and Cambodia to identify polymerase adaptation mutations that had been selected in infected patients. Several of these mutations acted either alone or together to increase viral polymerase activity in human airway cells to levels similar to the PB2-D701N and PB2-E627K single mutations and to increase progeny virus yields in infected mouse lungs to levels similar to the PB2-D701N single mutation. In particular, specific mutations acted synergistically with the PB2-D701N mutation and showed synergistic effects on viral replication both in human airway cells and mice compared with the corresponding single mutations. Thus, H5N1 viruses in infected patients were able to acquire multiple polymerase mutations that acted cooperatively for human adaptation. Our findings give new insight into the human adaptation of AI viruses and help in avian influenza virus risk assessment.
The effect of male age on patterns of sexual segregation in Siberian ibex
Authors: Wang Muyang , Alves Joana , da Silva António Alves , Yang Weikang , Ruckstuhl Kathreen E.
Published: August 2018

Sexual segregation is very common in sexually size dimorphic ungulates and may be the result of different habitat preferences and/or differential social behaviours of males and females. Various hypotheses have been put forward to explain this phenomenon. In the present research, we examined sexual segregation in a quite poorly understood species, the Siberian ibex. The species presents a marked sexual size dimorphism, with adult males weighing double as much as females. We use the Sexual Segregation and Aggregation Statistics (SSAS) to analyze the sex-age patterns of sexual segregation in this species, to understand the relevance of social factors. Our results show that adult Siberian ibex males were socially segregated from females all year round, except during the rutting season. Furthermore, the degree of segregation between females and males was influenced by the age of males. Moreover, the patterns of social segregation within males also increased with male age, reaching maximum values for males of 9 years-old and older, which means male age plays an important role in the sexual segregation of this species. This study clearly shows that social factors play a key role in the sexual segregation of Siberian ibex.
Optimal multisensory integration leads to optimal time estimation
Authors: Murai Yuki , Yotsumoto Yuko
Published: August 2018

Our brain compensates sensory uncertainty by combining multisensory information derived from an event, and by integrating the current sensory signal with the prior knowledge about the statistical structure of previous events. There is growing evidence that both strategies are statistically optimal; however, how these two stages of information integration interact and shape an optimal percept remains an open question. In the present study, we investigated the perception of time as an amodal perceptual attribute. The central tendency, a phenomenon of biasing the current percept toward previous stimuli, is used to quantify and model how the prior information affects the current timing behavior. We measured the timing sensitivity and the central tendency for unisensory and multisensory stimuli with sensory uncertainty systematically manipulated by adding noise. Psychophysical results demonstrate that the central tendency increases as the uncertainty increases, and that the multisensory timing improves both the timing sensitivity and the central tendency bias compared to the unisensory timing. Computational models indicate that the optimal multisensory integration precedes the optimal integration of prior information causing the central tendency. Our findings suggest that our brain incorporates the multisensory information and prior knowledge in a statistically optimal manner to realize precise and accurate timing behavior.