bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of Weather Systems in Controlling Mass Balance in the Southern Alps of New Zealand
Authors: Cullen Nicolas J. , Gibson Peter B. , Mölg Thomas , Conway Jonathan P. , Sirguey Pascal , Kingston Daniel G.
Published: March 2019

The recent advance of some fast‐responding glaciers in New Zealand demonstrates that regional variability in atmospheric circulation can counteract the effects of global warming. Until recently, a key challenge in quantifying how weather systems influence glaciers has been the lack of observational data from high‐elevation sites in the Southern Alps. Using high‐quality meteorological and glaciological observations from Brewster Glacier over four summers and two winters, a physically based mass balance model is used to resolve daily ablation and solid precipitation. Composite analysis confirms ablation is largely controlled by changes in meridional airflow, with high ablation associated with north to northwest airflow, while low ablation is associated with south to southwest airflow. The largest snowfall events in the cool season also occur during northwesterly airflow, highlighting the importance of seasonality (i.e., whether an event occurs in the ablation or accumulation period) for mass balance. Application of a synoptic weather typing approach commonly used for the New Zealand region, known broadly as Kidson weather types, revealed that three established regimes (trough, zonal, and blocking) are less effective in resolving variability in ablation and snowfall than a simple procedure that groups weather types using geostrophic flow direction. The frequency of four weather types can explain approximately 40% of the variance in mass balance over a 42‐year period. This highlights that future regional variability or trends in large‐scale circulation and their seasonality, superimposed on background warming, will be important in shaping glacier mass balance in the coming decades.
Phase I trial of isatuximab monotherapy in the treatment of refractory multiple myeloma
Authors: Martin Thomas , Strickland Stephen , Glenn Martha , Charpentier Eric , Guillemin Hélène , Hsu Karl , Mikhael Joseph
Published: March 2019

This phase I dose-escalation/expansion study evaluated isatuximab (anti-CD38 monoclonal antibody) monotherapy in patients with relapsed/refractory multiple myeloma (RRMM). Patients progressing on or after standard therapy received intravenous isatuximab (weekly [QW] or every 2 weeks [Q2W]). The primary objective was to determine the maximum tolerated dose (MTD) of isatuximab. Overall, 84 patients received ≥ 1 dose of isatuximab. The MTD was not reached; no cumulative adverse reactions were noted. The most frequent adverse events were infusion reactions (IRs), occurring in 37/73 patients (51%) following introduction of mandatory prophylaxis. IRs were mostly grade 1/2, occurred predominantly during Cycle 1, and led to treatment discontinuation in two patients. CD38 receptor occupancy reached a plateau of 80% with isatuximab 20 mg/kg (highest dose tested) and was associated with clinical response. In patients receiving isatuximab ≥ 10 mg/kg, overall response rate (ORR) was 23.8% (15/63), including one complete response. In high-risk patients treated with isatuximab 10 mg/kg (QW or Q2W), ORR was 16.7% (3/18). Median (range) duration of response at doses ≥ 10 mg/kg was 25 (8–30) weeks among high-risk patients versus 36 (6–85) weeks for other patients. In conclusion, isatuximab demonstrated a manageable safety profile and clinical activity in patients with RRMM.
Spontaneous formation and relaxation of spin domains in antiferromagnetic spin-1 condensates
Authors: Jiménez-García K. , Invernizzi A. , Evrard B. , Frapolli C. , Dalibard J. , Gerbier F.
Published: March 2019

Many-body systems at low temperatures generally organize themselves into ordered phases, whose nature and symmetries are captured by an order parameter. This order parameter is spatially uniform in the simplest cases, for example the macroscopic magnetization of a ferromagnetic material. Non-uniform situations also exist in nature, for instance in antiferromagnetic materials, where the magnetization alternates in space, or in the so-called stripe phases emerging for itinerant electrons in strongly correlated materials. Understanding such inhomogeneously ordered states is of central importance in many-body physics. Here we study experimentally the magnetic ordering of itinerant spin-1 bosons in inhomegeneous spin domains at nano-Kelvin temperatures. We demonstrate that spin domains form spontaneously, that is purely because of the antiferromagnetic interactions between the atoms and in the absence of external magnetic forces, after a phase separation transition. Furthermore, we explore how the equilibrium domain configuration emerges from an initial state prepared far from equilibrium.
Specialized dendritic cells induce tumor-promoting IL-10+IL-17+ FoxP3neg regulatory CD4+ T cells in pancreatic carcinoma
Authors: Barilla Rocky M. , Diskin Brian , Caso Raul Caso , Lee Ki Buom , Mohan Navyatha , Buttar Chandan , Adam Salma , Sekendiz Zennur , Wang Junjie , Salas Ruben D. , Cassini Marcelo F. , Karlen Jason , Sundberg Belen , Akbar Hashem , Levchenko Dmitry , Gakhal Inderdeep , Gutierrez Johana , Wang Wei , Hundeyin Mautin , Torres-Hernandez Alejandro , Leinwand Joshua , Kurz Emma , Rossi Juan A. Kochen , Mishra Ankita , Liria Miguel , Sanchez Gustavo , Panta Jyoti , Loke P’ng , Aykut Berk , Miller George
Published: March 2019

The drivers and the specification of CD4+ T cell differentiation in the tumor microenvironment and their contributions to tumor immunity or tolerance are incompletely understood. Using models of pancreatic ductal adenocarcinoma (PDA), we show that a distinct subset of tumor-infiltrating dendritic cells (DC) promotes PDA growth by directing a unique TH-program. Specifically, CD11b+CD103− DC predominate in PDA, express high IL-23 and TGF-β, and induce FoxP3neg tumor-promoting IL-10+IL-17+IFNγ+ regulatory CD4+ T cells. The balance between this distinctive TH program and canonical FoxP3+ TREGS is unaffected by pattern recognition receptor ligation and is modulated by DC expression of retinoic acid. This TH-signature is mimicked in human PDA where it is associated with immune-tolerance and diminished patient survival. Our data suggest that CD11b+CD103− DC promote CD4+ T cell tolerance in PDA which may underscore its resistance to immunotherapy.
Enhanced Dopamine in Prodromal Schizophrenia (EDiPS): a new animal model of relevance to schizophrenia
Authors: Petty Alice , Cui Xiaoying , Tesiram Yasvir , Kirik Deniz , Howes Oliver , Eyles Darryl
Published: March 2019

One of the most robust neurochemical abnormalities reported in patients living with schizophrenia is an increase in dopamine (DA) synthesis and release in the dorsal striatum (DS). Importantly, it appears that this increase progresses as a patient transitions from a prodromal stage to the clinical diagnosis of schizophrenia. Here we have recreated this pathophysiology in an animal model by increasing the capacity for DA synthesis preferentially within the DS. To achieve this we administer a genetic construct containing the rate-limiting enzymes in DA synthesis—tyrosine hydroxylase (TH), and GTP cyclohydrolase 1 (GCH1) (packaged within an adeno-associated virus)—into the substantia nigra pars compacta (SNpc) of adolescent animals. We refer to this model as “Enhanced Dopamine in Prodromal Schizophrenia” (EDiPS). We first confirmed that the TH enzyme is preferentially increased in the DS. As adults, EDiPS animals release significantly more DA in the DS following a low dose of amphetamine (AMPH), have increased AMPH-induced hyperlocomotion and show deficits in pre-pulse inhibition (PPI). The glutamatergic response to AMPH is also altered, again in the DS. EDiPS represents an ideal experimental platform to (a) understand how a preferential increase in DA synthesis capacity in the DS relates to “positive” symptoms in schizophrenia; (b) understand how manipulation of DS DA may influence other neurotransmitter systems shown to be altered in patients with schizophrenia; (c) allow researchers to follow an “at risk”-like disease course from adolescence to adulthood; and (d) ultimately allow trials of putative prophylactic agents to prevent disease onset in vulnerable populations.
The First Definite Lambeosaurine Bone From the Liscomb Bonebed of the Upper Cretaceous Prince Creek Formation, Alaska, United States
Authors: Takasaki Ryuji , Fiorillo Anthony R. , Kobayashi Yoshitsugu , Tykoski Ronald S. , McCarthy Paul J.
Published: March 2019

The Prince Creek Formation of Alaska, a rock unit that represents lower coastal plain and delta deposits, is one of the most important formations in the world for understanding vertebrate ecology in the Arctic during the Cretaceous. Here we report on an isolated cranial material, supraoccipital, of a lambeosaurine hadrosaurid from the Liscomb Bonebed of the Prince Creek Formation. The lambeosaurine supraoccipital has well-developed squamosal bosses and a short sutural surface with the exoccipital-opisthotic complex, and is similar to lambeosaurine supraoccipitals from the Dinosaur Park Formation in having anteriorly positioned squamosal bosses. Affinities with Canadian lambeosaurines elucidate more extensive faunal exchange between the Arctic and lower paleolatitudes which was previously suggested by the presence of Edmontosaurus, Pachyrhinosaurus, tyrannosaurids, and troodontids in both regions. The presence of one lambeosaurine and nine hadrosaurine supraoccipitals in the Liscomb Bonebed suggests hadrosaurine dominated faunal structure as in the Careless Creek Quarry of the USA that was also deposited under a near-shore environment. It differs from the lambeosaurine dominant structures of localities in Russia and China interpreted as inland environments. This may suggest that lambeosaurines had less preference for near-shore environments than hadrosaurines in both Arctic and lower paleolatitudes.
Monocytes/Macrophages play a pathogenic role in IL-23 mediated psoriasis-like skin inflammation
Authors: Wang Yibing , Edelmayer Rebecca , Wetter Joe , Salte Katherine , Gauvin Donna , Leys Laura , Paulsboe Stephanie , Su Zhi , Weinberg Isaac , Namovic Marian , Gauld Stephen B. , Honore Prisca , Scott Victoria E. , McGaraughty Steve
Published: March 2019

Psoriasis is an immune-mediated inflammatory skin disease that affects millions worldwide. Studying immune cells involved in psoriasis pathogenesis is essential to identify effective and safe therapeutics for the disease. Using human psoriasis skin, activated macrophages were observed in both lesional and non-lesional skin, but were elevated in lesional skin. Activation of the IL-23/IL-17 pathway is integral to the development of psoriasis. To further characterize the monocyte/macrophage (Mon/Mac) population when the IL-23 pathway is activated, a murine model of intradermal injection of IL-23 was used. Flow cytometry revealed that Mon/Mac cells were the dominant immune population, particularly late in the model, highlighted by strong presence of Ly6ChiMHC IIhi cells. The Mon/Mac cells were also shown to have high expression for TNFα but not IL-17A. Prophylactic dosing of a CSF-1R inhibitor to deplete Mon/Mac cells significantly reduced several inflammatory mediators from the skin tissue suggesting a pathogenic role for Mon/Mac. Treatment dosing of the inhibitor produced a less robust effect. Mon/Mac cells were also differentiated by levels of Ki67 and TNFα expression. These data point to an important contribution of Mon/Mac cells in IL-23 related skin inflammation and suggest that these cells are a significant player in the underlying pathophysiology of psoriasis.
Increase of genetic diversity indicates ecological opportunities in recurrent-fire landscapes for wall lizards
Authors: Ferreira Diana , Pinho Catarina , Brito José Carlos , Santos Xavier
Published: March 2019

Socioeconomic and climatic factors are modifying fire regimes with an increase of fire frequency and extension. Unfortunately, the effects of recurrent fires on biological processes that ultimately affect the genetic diversity of animal populations are mostly unknown. We examined genetic patterns of diversity in the wall lizardPodarcis guadarramaein northern Portugal, one of the European regions with the highest percentage of burnt land. This species is a small saxicolous lizard as it inhabits natural outcrops and artificial stone walls, likely in recurrent-fire landscapes. We genotyped nine microsatellites from ten populations selected according to a gradient in fire recurrence, and compared genetic diversity indexes and demographic patterns among them. At the population level, we hypothesize that a high level of mortality and population bottlenecks are expected to reduce genetic heterozygosity in sampled localities affected by recurrent fires. Alternatively, genetic signatures are expected to be absent whether fire did not cause high mortality. Regardless of levels of mortality, we expect a gain in genetic diversity whether recurrent fires facilitate lizard dispersal and migration due to the increased quality of the habitat for wall lizards. At the regional level, we examine whether a recurrent fire regime may disrupt the spatial structure of populations. Our results showed an increase in genetic diversity in recurrently burnt populations, and a decline in longer-unburnt populations. We did not detect bottleneck effects in repeatedly-burnt populations. High genetic diversity in recurrent fire populations suggests a high dispersion rate between adjacent metapopulations and perhaps immigration from outside the fire boundary. At the regional level, lizard populations show low differentiation and weak genetic structure, suggesting no effects of fire. This study confirms field-based censuses showing that recurrent-fire regimes give ecological opportunities to wall lizards that benefit from habitat openness.
Effect of fluoride mouthrinses and stannous ions on the erosion protective properties of the in situ pellicle
Authors: Kensche A. , Buschbeck E. , König B. , Koch M. , Kirsch J. , Hannig C. , Hannig M.
Published: March 2019

The particular feature of this study is the investigation of effects of pure fluoride- or stannous ions based mouthrinses on the erosion protective properties and the ultrastructure of the in situ pellicle (12 volunteers). Experimental solutions were prepared either from 500 ppm NaF, SMFP, AmF or SnF2 or 1563 ppm SnCl2, respectively. After 1 min of in situ pellicle formation on bovine enamel slabs, rinses with one of the preparations were performed for 1 min and intraoral specimens’ exposure was continued for 28 min. Native enamel slabs and rinses with bidestilled water served as controls. After oral exposure, slabs were incubated in HCl (pH 2; 2.3; 3) for 120 s and kinetics of calcium- and phosphate release were measured photometrically; representative samples were analysed by TEM and EDX. All mouthrinses reduced mineral loss compared to the native 30-min pellicle. The effect was pH-dependent and significant at all pH values only for the tin-containing mouthrinses. No significant differences were observed between the SnF2- and the SnCl2-containing solutions. TEM/EDX confirmed ultrastructural pellicle modifications. SnF2 appears to be the most effective type of fluoride to prevent erosive enamel demineralisation. The observed effects primarily have to be attributed to the stannous ions’ content.
Clinical Scenarios of the Application of Electrical Impedance Tomography in Paediatric Intensive Care
Authors: Davies Patrick , Yasin Samra , Gates Simon , Bird David , Silvestre Catarina
Published: March 2019

EIT is a radiation-free functional modality that enables bedside imaging and monitoring of lung function and expansion. Clinical interest in this method has been driven by the need for bedside monitoring of the dynamics of the lungs and the effects of ventilatory manoeuvres, including changes in ventilator settings, suctioning, chest drains, positioning and physiotherapy. We aimed to describe the use of Electrical Impedance Tomography (EIT) as a clinical tool in a tertiary Paediatric Intensive Care unit. Children requiring intensive care with a variety of clinical conditions had an electrode belt with 16 electrodes wrapped around the chest, which sequentially applied a small alternating current from each electrode pair. The signal gives information on both real time, regional, global, and relative data. With the correct application, and understanding of the monitor, much clinical information can be gained, with potentially significant patient benefit. We present the clinical use of EIT in six conditions: Asthma, Ventilation weaning and expansion recoil, Sequential Lobar Collapse, Targeted Physiotherapy, Pleural Effusion assessment, and PEEP optimisation. Screenshots and analyses are offered displaying the pragmatic use of this technology. Electrical Impedance Tomography is a clinically useful tool on the Paediatric Intensive Care unit. It allows monitoring of a patient’s respiratory function in ways which are not possible through any other means. An understanding of respiratory physiology will allow use of this information to improve patient outcomes.
Optimal control of the transport of Bose-Einstein condensates with atom chips
Authors: Amri S. , Corgier R. , Sugny D. , Rasel E. M. , Gaaloul N. , Charron E.
Published: March 2019

Using Optimal Control Theory (OCT), we design fast ramps for the controlled transport of Bose-Einstein condensates with atom chips’ magnetic traps. These ramps are engineered in the context of precision atom interferometry experiments and support transport over large distances, typically of the order of 1 mm, i.e. about 1,000 times the size of the atomic clouds, yet with durations not exceeding 200 ms. We show that with such transport durations of the order of the trap period, one can recover the ground state of the final trap at the end of the transport. The performance of the OCT procedure is compared to that of a Shortcut-To-Adiabaticity (STA) protocol and the respective advantages/disadvantages of the OCT treatment over the STA one are discussed.
Source, Spatial Distribution and Pollution Assessment of Pb, Zn, Cu, and Pb, Isotopes in urban soils of Ahvaz City, a semi-arid metropolis in southwest Iran
Authors: Nazarpour Ahad , Watts Michael J. , Madhani Ayoub , Elahi Somayeh
Published: March 2019

This study examined the status of toxic metal contamination of the urban industrial city of Ahvaz in Iran. Two hundred and twenty-seven surface soils from a depth horizon of 0–10 cm were collected from urban areas. In addition, 15 soil samples were collected to recognise the sources of Pb in urban topsoils in Ahvaz city. Mean concentration of Pb, Zn, Cu and As were 181 ± 167, 123 ± 118, 185 ± 167 and 6.9 ± 8.9 mg.kg−1, respectively. Results of inter-element relationship among studied toxic metals revealed that Pb, Zn and Cu may have the same anthropogenic origin, whilst As originated from different sources. The results of pollution index (PI) and Nemerow pollution index (NPI) implied that Pb, Zn, and Cu had a moderate to high level of pollution. The Pb isotopic composition analysis suggested clear anthropogenic origins of Pb including industrial emission, vehicle exhaust and dust storm with the mean contributions of 47%, 15% and 7%, respectively, by a four-end member model.
Alternative sigma factor B (σB) and catalase enzyme contribute to Staphylococcus epidermidis biofilm’s tolerance against physico-chemical disinfection
Authors: Olwal Charles Ochieng’ , Ang’ienda Paul Oyieng’ , Ochiel Daniel Otieno
Published: March 2019

Staphylococcus epidermidis is the predominant cause of recalcitrant biofilm-associated infections, which are often highly resistant to antibiotics. Thus, the use of physico-chemical agents for disinfection offers a more effective approach to the control of S. epidermidis biofilm infections. However, the underlying tolerance mechanisms employed by S. epidermidis biofilm against these physico-chemical disinfectants remain largely unknown. The expression of a σB-dependent gene, alkaline shock protein 23 (asp23) and catalase activity by S. epidermidis biofilm and planktonic cells exposed to heat (50 °C), 0.8 M sodium chloride (NaCl), 5 mM sodium hypochlorite (NaOCl) or 50 μM hydrogen peroxide (H2O2) for 60 minutes were compared. Significantly higher asp23 expression levels were observed in biofilms exposed to 50 °C, 5 mM NaOCl or 50 μM H2O2 compared to the corresponding planktonic cells (p < 0.05). Conversely, asp23 expression levels in biofilm and planktonic cells exposed to 0.8 M NaCl were not significantly different (p > 0.05). Further, biofilms exposed to 50 °C, 0.8 M NaCl, 5 mM NaOCl or 50 μM H2O2 exhibited significantly higher catalase activity than the planktonic cells (p < 0.05). These results suggest that activities of σB and catalase may be involved in the tolerance of S. epidermidis biofilm against physico-chemical disinfection.
Comparative analysis of exosome isolation methods using culture supernatant for optimum yield, purity and downstream applications
Authors: Patel Girijesh Kumar , Khan Mohammad Aslam , Zubair Haseeb , Srivastava Sanjeev Kumar , Khushman Moh’d , Singh Seema , Singh Ajay Pratap
Published: March 2019

Exosomes have received significant attention for their role in pathobiological processes and are being explored as a tool for disease diagnosis and management. Consequently, various isolation methods based on different principles have been developed for exosome isolation. Here we compared the efficacy of four kits from Invitrogen, 101Bio, Wako and iZON along with conventional ultracentrifugation-based method for exosome yield, purity and quality. Cell culture supernatant was used as an abundant source of exosomes, and exosome quantity, size-distribution, zeta-potential, marker-expression and RNA/protein quality were determined. The Invitrogen kit gave the highest yield but the preparation showed broader size-distribution likely due to microvesicle co-precipitation and had the least dispersion stability. Other preparations showed <150 nm size range and good stability. Preparation from iZON column; however, had a broader size-distribution in the lower size range suggestive of some impurities of non-vesicular aggregates. RNA quality from all preparations was comparable; however, proteins from Invitrogen method-based exosomal preparation showed polyethylene glycol (PEG) contamination in mass spectrometry. Chemical impurities from the precipitant could also be the cause of toxicity of Invitrogen method-based exosomal preparation in biological growth measurement assay. Together, these findings should serve as a guide to choose and further optimize exosome isolation methods for their desired downstream applications.
Selective manipulation of the inositol metabolic pathway for induction of salt-tolerance in indica rice variety
Authors: Mukherjee Rajeswari , Mukherjee Abhishek , Bandyopadhyay Subhendu , Mukherjee Sritama , Sengupta Sonali , Ray Sudipta , Majumder Arun Lahiri
Published: March 2019

Halophytes are rich sources of salt stress tolerance genes which have often been utilized for introduction of salt-tolerance character in salt-sensitive plants. In the present study, we overexpressed PcINO1 and PcIMT1 gene(s), earlier characterized in this laboratory from wild halophytic rice Porteresia coarctata, into IR64 indica rice either singly or in combination and assessed their role in conferring salt-tolerance. Homozygous T3/T4 transgenic plants revealed that PcINO1 transformed transgenic rice lines exhibit significantly higher tolerance upto 200 mM or higher salt concentration with negligible compromise in their growth or other physiological parameters compared to the untransformed system grown without stress. The PcIMT1-lines or the double transgenic lines (DC1) having PcINO1 and PcIMT1 introgressed together, were less efficient in such respect. Comparison of inositol and/or pinitol pool in three types of transgenic plants suggests that plants whose inositol production remains uninterrupted under stress by the functional PcINO1 protein, showed normal growth as in the wild-type plants without stress. It is conceivable that inositol itself acts as a stress-ameliorator and/or as a switch for a number of other pathways important for imparting salt-tolerance. Such selective manipulation of the inositol metabolic pathway may be one of the ways to combat salt stress in plants.
Diffraction-less propagation beyond the sub-wavelength regime: a new type of nanophotonic waveguide
Authors: Alonso-Ramos Carlos , Le Roux Xavier , Zhang Jianhao , Benedikovic Daniel , Vakarin Vladyslav , Durán-Valdeiglesias Elena , Oser Dorian , Pérez-Galacho Diego , Mazeas Florent , Labonté Laurent , Tanzilli Sébastien , Cassan Éric , Marris-Morini Delphine , Cheben Pavel , Vivien Laurent
Published: March 2019

Sub-wavelength grating (SWG) metamaterials have garnered a great interest for their singular capability to shape the propagation of light. However, practical SWG implementations are limited by fabrication constraints, such as minimum feature size. Here, we present a new nanophotonic waveguide grating concept that exploits phase-matching engineering to suppress diffraction effects for a period three times larger than those with SWG approaches. This long-period grating not only facilitates fabrication, but also enables a new diffraction-less regime with additional degrees of freedom to control light propagation. More specifically, the proposed phase-matching engineering enables selective diffraction suppression, providing new tools to shape propagation in the grating. We harness this flexible diffraction control to yield single-mode propagation in, otherwise, highly multimode waveguides, and to implement Bragg filters that combine highly-diffractive and diffraction-less regions to dramatically increase light rejection. Capitalizing on this new concept, we experimentally demonstrate a Si membrane Bragg filter with record rejection value exceeding 60 dB. These results demonstrate the potential of the proposed long-period grating for the engineering of diffraction in nanophotonic waveguides and pave the way for the development of a new generation of high-performance Si photonics devices.
Massive benthic litter funnelled to deep sea by flash-flood generated hyperpycnal flows
Authors: Pierdomenico Martina , Casalbore Daniele , Chiocci Francesco Latino
Published: March 2019

Marine litter is an emerging environmental threat affecting all world’s oceans including the deep seafloor, where the extent of the phenomenon is still largely unknown. We report the spatial patterns of macro-litter distribution within the Messina Strait’s channels (Central Mediterranean), focusing on the transfer mechanisms responsible for its emplacement, a key information to better understand litter distribution. Litter is patchy but pervasive on all surveyed channels, reaching densities up to ~200 items/10 m, the highest reported for the deep sea until now. Litter is often arranged in large accumulations formed by hundreds of land-sourced items, mixed to vegetal and coarse-grained debris, indicating an emplacement from sedimentary gravity flows. Such impressive amount of litter can be explained by the superposition of a very efficient source-to-sink sedimentary transport and a strong urbanization of the coastal area. These findings point out that macro-benthic litter pollution is a major, often overlooked, threat for deep-sea ecosystems. Further explorations are thus required in similar marine settings to fully understand the magnitude of the problem, since they may represent the largest litter hotspots in the deep-sea.
No signal of deleterious mutation accumulation in conserved gene sequences of extant asexual hexapods
Authors: Brandt Alexander , Bast Jens , Scheu Stefan , Meusemann Karen , Donath Alexander , Schütte Kai , Machida Ryuichiro , Kraaijeveld Ken
Published: March 2019

Loss of sex and recombination is generally assumed to impede the effectiveness of purifying selection and to result in the accumulation of slightly deleterious mutations. Empirical evidence for this has come from several studies investigating mutational load in a small number of individual genes. However, recent whole transcriptome based studies have yielded inconsistent results, hence questioning the validity of the assumption of mutational meltdown in asexual populations. Here, we study the effectiveness of purifying selection in eight asexual hexapod lineages and their sexual relatives, as present in the 1 K Insect Transcriptome Evolution (1KITE) project, covering eight hexapod groups. We analyse the accumulation of slightly deleterious nonsynonymous and synonymous point mutations in 99 single copy orthologue protein-coding loci shared among the investigated taxa. While accumulation rates of nonsynonymous mutations differed between genes and hexapod groups, we found no effect of reproductive mode on the effectiveness of purifying selection acting at nonsynonymous and synonymous sites. Although the setup of this study does not fully rule out nondetection of subtle effects, our data does not support the established consensus of asexual lineages undergoing ‘mutational meltdown’.
Analysis of α-dicarbonyl compounds and volatiles formed in Maillard reaction model systems
Authors: Cha Jiyoon , Debnath Trishna , Lee Kwang-Geun
Published: March 2019

In this study, production of three α-dicarbonyl compounds (α-DCs) including glyoxal (GO), methylglyoxal (MGO), and diacetyl (DA) as well as volatile flavor compounds was analyzed using Maillard reaction (MR) model systems. A total of 16 model systems were assembled using four amino acids and four reducing sugars, and reactions were performed at 160 °C and pH 9. Determination of α-DCs was conducted using a gas chromatography/nitrogen phosphorous detector (GC-NPD) after derivatization and liquid-liquid extraction. α-DC levels in MR model systems were 5.92 to 39.10 μg/mL of GO, 3.66 to 151.88 μg/ml of MGO, and 1.10 to 6.12 μg/mL of DA. The highest concentration of total α-DCs was found in the fructose-threonine model system and the lowest concentration in the lactose-cysteine model system. Volatile flavor compounds were analyzed using solid-phase micro-extraction (SPME) followed by GC-mass spectrometry (GC-MS). Different volatile flavor compound profiles were identified in the different MR model systems. Higher concentrations of α-DCs and volatile flavor compounds were observed in monosaccharide-amino acid MR model systems compared with disaccharide-amino acid model systems.
Preventing lung pathology and mortality in rabbit Staphylococcus aureus pneumonia models with cytotoxin-neutralizing monoclonal IgGs penetrating the epithelial lining fluid
Authors: Stulik Lukas , Rouha Harald , Labrousse Delphine , Visram Zehra Claire , Badarau Adriana , Maierhofer Barbara , Groß Karin , Weber Susanne , Kramarić Miroslava Dominis , Glojnarić Ines , Nagy Gábor , Croisier Delphine , Nagy Eszter
Published: March 2019

Staphylococcus aureus pneumonia is associated with high mortality irrespective of antibiotic susceptibility. Both MRSA and MSSA strains produce powerful cytotoxins: alpha-hemolysin(Hla) and up to five leukocidins – LukSF-PV, HlgAB, HlgCB, LukED and LukGH (LukAB) – to evade host innate defense mechanisms. Neutralizing cytotoxins has been shown to provide survival benefit in rabbit S. aureus pneumonia models. We studied the mechanisms of protection of ASN100, a combination of two human monoclonal antibodies (mAbs), ASN-1 and ASN-2, that together neutralize Hla and the five leukocidins, in rabbit MRSA and MSSA pneumonia models. Upon prophylactic passive immunization, ASN100 displayed dose-dependent increase in survival and was fully protective against all S. aureus strains tested at 5 or 20 mg/kg doses. Macroscopic and microscopic lung pathology, edema rate, and bacterial burden were evaluated 12 hours post infection and reduced by ASN100. Pharmacokinetic analysis of ASN100 in bronchoalveolar-lavage fluid from uninfected animals detected efficient penetration to lung epithelial lining fluid reaching peak levels between 24 and 48 hours post dosing that were comparable to the mAb concentration measured in serum. These data confirm that the ASN100 mAbs neutralize the powerful cytotoxins of S. aureus in the lung and prevent damage to the mucosal barrier and innate immune cells.
Heterogeneous drug tissue binding in brain regions of rats, Alzheimer’s patients and controls: impact on translational drug development
Authors: Gustafsson Sofia , Sehlin Dag , Lampa Erik , Hammarlund-Udenaes Margareta , Loryan Irena
Published: March 2019

For preclinical and clinical assessment of therapeutically relevant unbound, free, brain concentrations, the pharmacokinetic parameter fraction of unbound drug in brain (fu,brain) is commonly used to compensate total drug concentrations for nonspecific brain tissue binding (BTB). As, homogenous BTB is assumed between species and in health and disease, rat BTB is routinely used. The impact of Alzheimer’s disease (AD) on drug BTB in brain regions of interest (ROI), i.e., fu,brain,ROI, is yet unclear. This study for the first time provides insight into regional drug BTB and the validity of employing rat fu,brain,ROI as a surrogate of human BTB, by investigating five marketed drugs in post-mortem tissue from AD patients (n = 6) and age-matched controls (n = 6). Heterogeneous drug BTB was observed in all within group comparisons independent of disease and species. The findings oppose the assumption of uniform BTB, highlighting the need of case-by-case evaluation of fu,brain,ROI in translational CNS research.
Computer aided protein engineering to enhance the thermo-stability of CXCR1- T4 lysozyme complex
Authors: Wang Yang , Park Jae-Hyun , Lupala Cecylia Severin , Yun Ji-Hye , Jin Zeyu , Huang Lanqing , Li Xuanxuan , Tang Leihan , Lee Weontae , Liu Haiguang
Published: March 2019

CXCR1, a member in G-protein coupled receptor (GPCR) family, binds to chemokine interleukin-8 (IL-8) specifically and transduces signals to mediate immune and inflammatory responses. Despite the importance of CXCR1, high-resolution structure determination is hindered by the challenges in crystallization. It has been shown that properly designed mutants with enhanced thermostability, together with fusion partner proteins, can be useful to form crystals for GPCR proteins. In this study,in silicoprotein design was carried out by using homology modeling and molecular dynamics simulations. To validate the computational modeling results, the thermostability of several mutants and the wild type were measured experimentally. Both computational results and experimental data suggest that the mutant L126W has a significant improvement in the thermostability. This study demonstrated thatin silicodesign can guide protein engineering and potentially facilitate protein crystallography research.
Comparison of recombinant and urinary follicle-stimulating hormones over 2000 gonadotropin-releasing hormone antagonist cycles: a retrospective study
Authors: Pan Wei , Tu Haiting , Jin Lei , Hu Cheng , Xiong Jianwu , Pan Wulin , Yu Dongyang , Wang Renjie , Li Yuehan , Huang Weiming , Liao ShuJie
Published: March 2019

The objective of this paper was to compare the effect of recombinant follicle-stimulating hormone (rFSH) and urinary follicle-stimulating hormone (uFSH) on pregnancy rates and live birth rates with the gonadotropin-releasing hormone (GnRH) antagonist protocol in China. This retrospective study was conducted from January 2014 through August 2017. Patients treated with uFSH had significantly higher levels of luteinizing hormone (3.79 mIU/ml vs. 3.09 mIU/ml) and progesterone (0.93 ng/ml vs. 1.16 ng/ml) on the day of human chorionic gonadotropin (HCG) administration, and they also had higher pregnancy rates (24.19% vs. 22.86%). There was no significant difference in the rate of live births. In the logistic regression results of the rFSH group, the pregnancy rate was positively correlated with the level of luteinizing hormone, with an odds ratio (OR) of 1.09 (95% confidence interval [CI]: 1.00–1.18; P = 0.048). In the uFSH group, the pregnancy rate was negatively correlated with the progesterone level on the day of HCG administration, with an OR of 0.47 (95% CI: 0.27–0.77; P = 0.004). Our research concluded that uFSH performed better than rFSH in terms of pregnancy rates when it was associated with the GnRH antagonist protocol. Meanwhile, no significant differences in the rate of live births were observed between the two groups.
Streptolysin S induces mitochondrial damage and macrophage death through inhibiting degradation of glycogen synthase kinase-3β in Streptococcus pyogenes infection
Authors: Tsao Nina , Kuo Chih-Feng , Cheng Miao-Hui , Lin Wei-Chen , Lin Chiou-Feng , Lin Yee-Shin
Published: March 2019

Group A Streptococcus (GAS) infection is associated with a variety of human diseases. Previous studies indicate GAS infection leads to RAW264.7 cell death, but the mechanism is unclear. Here, analyzing the timing of reactive oxygen species (ROS) production and using mitochondrial ROS scavenger, we found the wild type GAS-induced RAW264.7 cell death was associated with mitochondrial ROS. The wild type GAS infection could activate glycogen synthase kinase-3β (GSK-3β). Inhibition of GSK-3β activity by lithium chloride or decreasing GSK-3β expression by lentivirus-mediated short hairpin RNA for GSK-3β could not only decrease the wild type GAS-induced mitochondrial ROS generation, mitochondria damage and cell death, but also reduced GAS intracellular replication. Streptolysin S (SLS), a GAS toxin, played the important role on GAS-induced macrophage death. Compared to the wild type GAS with its isogenic sagB mutant (SLS mutant)-infected macrophages, we found sagB mutant infection caused less mitochondrial ROS generation and cell death than those of the wild type GAS-infected ones. Furthermore, the sagB mutant, but not the wild type or the sagB-complementary mutant, could induce GSK-3β degradation via a proteasome-dependent pathway. These results suggest that a new mechanism of SLS-induced macrophage death was through inhibiting GSK-3β degradation and further enhancing mitochondrial damage.
Increased flux in acetyl-CoA synthetic pathway and TCA cycle of Kluyveromyces marxianus under respiratory conditions
Authors: Sakihama Yuri , Hidese Ryota , Hasunuma Tomohisa , Kondo Akihiko
Published: March 2019

Yeasts are extremely useful, not only for fermentation but also for a wide spectrum of fuel and chemical productions. We analyzed the overall metabolic turnover and transcript dynamics in glycolysis and the TCA cycle, revealing the difference in adaptive pyruvate metabolic response between a Crabtree-negative species,Kluyveromyces marxianus, and a Crabtree-positive species,Saccharomyces cerevisiae, during aerobic growth. Pyruvate metabolism was inclined toward ethanol production under aerobic conditions inS.cerevisiae, while increased transcript abundances of the genes involved in ethanol metabolism and those encoding pyruvate dehydrogenase were seen inK.marxianus, indicating the augmentation of acetyl-CoA synthesis. Furthermore, different metabolic turnover in the TCA cycle was observed in the two species: malate and fumarate production inS.cerevisiaewas higher than inK.marxianus, irrespective of aeration; however, fluxes of both the reductive and oxidative TCA cycles were enhanced inK.marxianusby aeration, implying both the cycles contribute to efficient electron flux without producing ethanol. Additionally, decreased hexokinase activity under aerobic conditions is expected to be important for maintenance of suitable carbon flux. These findings demonstrate differences in the key metabolic trait of yeasts employing respiration or fermentation, and provide important insight into the metabolic engineering of yeasts.
Photochemical nitrogenation of alkanes and arenes by a strongly luminescent osmium(VI) nitrido complex
Authors: Xiang Jing , Jin Xin-Xin , Su Qian-Qian , Cheng Shun-Cheung , Ko Chi-Chiu , Man Wai-Lun , Xue Minying , Wu Liangliang , Che Chi-Ming , Lau Tai-Chu
Published: March 2019

The search for a highly active nitrido complex that can transfer its nitrogen atom to inert organic molecules remains a challenge to chemists. In this regard, the use of solar energy to generate a reactive nitrido species is an appealing strategy to solve this problem. Here we report the design of a strongly luminescent osmium(VI) nitrido compound, [OsVI(N)(NO2-L)(CN)3]− (NO2-OsN) with emission quantum yield (Φ) and life time (τ) of 3.0% and 0.48 μs, respectively in dichloromethane solution. Upon irradiation with visible light, this complex readily activates the aliphatic C-H bonds of various hydrocarbons, including alkanes. The excited state of NO2-OsN can undergo ring-nitrogenation of arenes, including benzene. Photophysical and computational studies suggest that the excited state of NO2-OsN arises from O^N ligand to Os ≡ N charge transfer transitions, and as a result it possesses [Os = N•] nitridyl character and is highly electrophilic.
Why is high persistence alone a major cause of concern?
Authors: Cousins Ian T. , Ng Carla A. , Wang Zhanyun , Scheringer Martin
Published: March 2019

High persistence has important implications for chemicals regulation and management.
Enhancing the antitumor activity of tea polyphenols encapsulated in biodegradable nanogels by macromolecular self-assembly
Authors: Liu Chen , Zhang Zhong , Kong Qingjun , Zhang Runguang , Yang Xingbin
Published: March 2019

Fabrication of biodegradable TP-loaded Ly and CMC nanogels via self-assembly and the study of their controlled release and absorption process in vivo.
Gel-like ionic complexes for antimicrobial, hemostatic and adhesive properties
Authors: Jhiang Jhia-Sin , Wu Tzu-Hsien , Chou Chung-Jung , Chang Yung , Huang Chun-Jen
Published: March 2019

Ion-specific effects offer a great opportunity to construct intelligent macromolecular systems with diverse architectures, on-demand controlled release behaviors and interfacial responsiveness.
Iron(iii)-selective materials based on a catechol-bearing amide for optical sensing
Authors: Łukasik Natalia , Wagner-Wysiecka Ewa , Małachowska Aleksandra
Published: March 2019

The synthesis and ion-binding properties of a new amide L derived from 3,4-dihydroxybenzoic acid are described.
Ruthenium(ii)-catalysed direct synthesis of ketazines using secondary alcohols
Authors: Kishore Jugal , Thiyagarajan Subramanian , Gunanathan Chidambaram
Published: March 2019

Ruthenium(ii)-catalysed direct synthesis of ketazines using secondary alcohols is reported.
Commenting on the photoreactions of anthracene derivatives in the solid state
Authors: Salzillo Tommaso , Brillante Aldo
Published: March 2019

The photochemical reactions of anthracene derivatives have been reviewed by means of a micro-Raman technique, monitoring at the same time and on the very same spot, the molecular (intramolecular vibrations) and the lattice (intermolecular vibrations) transformations.
Effects of temperature and pressure on the optical and vibrational properties of thermoelectric SnSe
Authors: Efthimiopoulos Ilias , Berg Matthias , Bande Annika , Puskar Ljiljana , Ritter Eglof , Xu Wei , Marcelli Augusto , Ortolani Michele , Harms Martin , Müller Jan , Speziale Sergio , Koch-Müller Monika , Liu Yong , Zhao Li-Dong , Schade Ulrich
Published: March 2019

We have conducted a comprehensive investigation of the optical and vibrational properties of the binary semiconductor SnSe as a function of temperature and pressure by means of experimental and ab initio probes.
Systems biology approach to elucidation of contaminant biodegradation in complex samples – integration of high-resolution analytical and molecular tools
Authors: Gauchotte-Lindsay Caroline , Aspray Thomas J. , Knapp Mara , Ijaz Umer Z.
Published: March 2019

We present here a data-driven systems biology framework for the rational design of biotechnological solutions for contaminated environments with the aim of understanding the interactions and mechanisms underpinning the role of microbial communities in the biodegradation of contaminated soils.
Copper-catalyzed versatile C(sp3)–H arylation: synthetic scope and regioselectivity investigations
Authors: Zhou Jiadi , Zou Yawen , Zhou Peng , Chen Zhiwei , Li Jianjun
Published: March 2019

A mild and practical protocol is developed for the synthesis of functionalized nitrogen-containing heteroaromatics via radical C(sp2)–H or C(sp2)–halogen alkylation.
Preparation and biocompatibility of Fe50Ni50p/HAP/PEEK biocomposites with weak magnetic properties
Authors: Liu Dengyu , Zhu Zhenghou , Zhou Jia , Zhao Hui , Chen Jie , Bai Ruru , Lin Qianying , Alagarsamy Manikandan
Published: March 2019

Hydroxyapatite (HAP)/polyetheretherketone (PEEK) composites are widely used in the new generation of bone implant materials.
Effect of moderate magnetic fields on the surface tension of aqueous liquids: a reliable assessment
Authors: Hayakawa Masayuki , Vialetto Jacopo , Anyfantakis Manos , Takinoue Masahiro , Rudiuk Sergii , Morel Mathieu , Baigl Damien
Published: March 2019

A novel setup measures the effect of magnetic field intensities on the surface tension of liquids placed inside uniform fields.
Tailoring the multiphase flow pattern of gas and liquid through micro-packed bed of pillars
Authors: Márquez Nathalie , Moulijn Jacob A. , Makkee Michiel , Kreutzer Michiel T. , Castaño Pedro
Published: March 2019

We describe the co-current flow pattern of gas and liquid through micro-fabricated beds of solid and pillars under variable (i) capillary number, (ii) contact angle or wettability and (iii) pillar arrangement, i.e. modifying the distance between pillars or their size and comparing regular with more chaotic systems.
Expression profile and prognostic value of SFN in human ovarian cancer
Authors: Hu Yi , Zeng Qing , Li Chenxi , Xie Ying
Published: March 2019

Ovarian cancer is a highly lethal cancer in females. Therefore, it is necessary to explore effective biomarkers for the diagnosis and prognosis of the disease. Stratifin (SFN) is a cell cycle checkpoint protein that has been reported to be involved in oncogenesis. Our studies detected the expression of SFN in ovarian cancer by Oncomine, Human Protein Atlas database and ULCAN database. Meanwhile, we found its coexpression gene by cBioPortal online tool and validated their expression in different ovarian cancer cells by western blot and reverse transcription quantitative PCR. Then, we also investigated their prognostic values via the Kaplan–Meier plotter database in different subtypes of ovarian cancer patients. The results demonstrated that SFN was found to be increased in ten various ovarian cancer datasets, compared with healthy tissues. Additionally, up-regulation of SFN expression is associated with age and cancer grades. The higher expression of SFN in all patients with ovarian cancers is significantly correlated with worse postprogression survival. In addition, high SFN expression is associated with significantly worse overall survival in patients who received chemotherapy contains gemcitabine, taxol, taxol+platin, paclitaxel and avastin. In human ovarian carcinoma SKOV3 and A2780 cells, the expression of SFN and its coexpression gene MICB were also increased at protein and mRNA levels compared with the normal ovarian epithelial cells. Based on above results, overexpression of SFN was correlated with the prognosis in ovarian cancer. The present study might be useful for better understanding the clinical significance of SFN mRNA.