bluuebunny/crossref_metadata_2025 huggingface dataset:
The potential of neurofilaments analysis using dry-blood and plasma spots
Authors: Lombardi Vittoria , Carassiti Daniele , Giovannoni Gavin , Lu Ching-Hua , Adiutori Rocco , Malaspina Andrea
Published: January 2020

The lack of biomarkers for an early diagnosis of neurodegenerative disorders (NDs) has hampered the development of therapeutics whose effect would be enhanced by a timely intervention. Neurofilaments light chain (Nf-L), an integral part of the axonal structure, has emerged as a robust fluid biomarker for fatal neurodegenerative disorders like amyotrophic lateral sclerosis (ALS). To facilitate large-scale studies into early-stage neurodegeneration, reduce costs of samples collection/processing and cold-chain storage, we describe the measurement of Nf-L in blood fractions obtained from dry blood spots (DBS) and dry plasma spots (DPS), two filter paper-based remote blood collection tools. To test the feasibility of using this approach, Nf-L analysis in DBS/DPS is compared to that in plasma obtained from the same blood sample, looking at Nf-L discriminatory power in the clinical stratification of ALS compared to healthy controls. With the best pre-analytical treatment for total protein recovery and using highly sensitive immunoassays, we report the detection of different Nf-L levels in DBS elute compared to reference plasma and DPS from the same blood samples. However, Nf-L measurement in DBS elutes provides a very good discrimination of ALS from healthy controls which is comparable to that obtained using plasma Nf-L assays. With the available immunodetection methods, we show that Nf-L measurement based on DPS microsampling is similar to that in plasma. The filter-paper biophysical characteristics and the interference of high haemoglobin concentration released by erythrocyte lysis is likely to perturb Nf-L detection in DBS elute. Further studies into DBS-based Nf-L detection and its analytical optimization are needed to make this method suitable for routine Nf-L blood analyses in neurodegeneration.
Excessive cholecalciferol supplementation increases kidney dysfunction associated with intrarenal artery calcification in obese insulin-resistant mice
Authors: Almeida Youri E. , Fessel Melissa R. , do Carmo Luciana Simão , Jorgetti Vanda , Farias-Silva Elisângela , Pescatore Luciana Alves , Gamarra Lionel F. , Andrade Maria Claudina , Simplicio-Filho Antonio , Mangueira Cristóvão Luis Pitangueiras , Rangel Érika B. , Liberman Marcel
Published: January 2020

Diabetes mellitus accelerates vascular calcification (VC) and increases the risk of end-stage renal disease (ESRD). Nevertheless, the impact of VC in renal disease progression in type 2 diabetes mellitus (T2DM) is poorly understood. We addressed the effect of VC and mechanisms involved in renal dysfunction in a murine model of insulin resistance and obesity (ob/ob), comparing with their healthy littermates (C57BL/6). We analyzed VC and renal function in both mouse strains after challenging them with Vitamin D3 (VitD3). Although VitD3 similarly increased serum calcium and induced bone disease in both strains, 24-hour urine volume and creatinine pronouncedly decreased only in ob/ob mice. Moreover, ob/ob increased urinary albumin/creatinine ratio (ACR), indicating kidney dysfunction. In parallel, ob/ob developed extensive intrarenal VC after VitD3. Coincidently with increased intrarenal vascular mineralization, our results demonstrated that Bone Morphogenetic Protein-2 (BMP-2) was highly expressed in these arteries exclusively in ob/ob. These data depict a greater susceptibility of ob/ob mice to develop renal disease after VitD3 in comparison to paired C57BL/6. In conclusion, this study unfolds novel mechanisms of progressive renal dysfunction in diabetes mellitus (DM) after VitD3in vivo associated with increased intrarenal VC and highlights possible harmful effects of long-term supplementation of VitD3 in this population.
Antioxidant Activities of an Exopolysaccharide (DeinoPol) Produced by the Extreme Radiation-Resistant Bacterium Deinococcus radiodurans
Authors: Lin Shun Mei , Baek Chan Yu , Jung Jong-Hyun , Kim Woo Sik , Song Ha-Yeon , Lee Ji Hee , Ji Hyun Jung , Zhi Yong , Kang Bo Sun , Bahn Yong-Sun , Seo Ho Seong , Lim Sangyong
Published: January 2020

Deinococcus radiodurans shows extreme resistance to a range of remarkable environmental stresses. Deinococcal exopolysaccharide (DeinoPol) is a component of the cell wall, but its role in stress resistance has not yet been well-described. In this study, we isolated and characterized DeinoPol from Deinococcus radiodurans R1 strain and investigated its application as an antioxidant agent. Bioinformatic analysis indicated that dra0033, encoding an ExoP-like protein, was involved in DeinoPol biosynthesis, and dra0033 mutation significantly decreased survival rates in response to stresses. Purified DeinoPol consists of different monosaccharides and has a molecular weight of approximately 80 to 100 kDa. DeinoPol also demonstrates highly protective effects on human keratinocytes in response to stress-induced apoptosis by effectively scavenging ROS. Taken together, these findings indicate that DeinoPol is the first reported deinococcal exopolysaccharide that might be used in cosmetics and pharmaceuticals as a safe and attractive radical scavenger.
Melanoma cell-derived exosomes in plasma of melanoma patients suppress functions of immune effector cells
Authors: Sharma Priyanka , Diergaarde Brenda , Ferrone Soldano , Kirkwood John M. , Whiteside Theresa L.
Published: January 2020

Melanoma patients’ plasma contains exosomes produced by malignant and normal cells. Plasma exosomes were isolated and separated by immunocapture into two fractions: melanoma cell-derived exosomes (MTEX) and normal cell-derived exosomes (non-MTEX). Immunosuppressive effects of MTEX on primary human immune cells were evaluated. Exosomes were isolated from plasma of 12 melanoma patients and six healthy donors (HDs). Expression levels of 19 immunoregulatory proteins in MTEX, non-MTEX and HDs exosomes were evaluated by on-bead flow cytometry. Functional/phenotypic changes induced in CD8+ T or natural killer (NK) cells by MTEX or non-MTEX were compared. Plasma protein levels were higher in patients than HDs (P < 0.0009). In patients, MTEX accounted for 23–66% of total exosomes. MTEX were enriched in immunosuppressive proteins (P = 0.03). MTEX, but not HDs exosomes, inhibited CD69 expression (P ≤ 0.0008), induced apoptosis (P ≤ 0.0009) and suppressed proliferation (P ≤ 0.002) in CD8+ T cells and downregulated NKG2D expression in NK cells (P = 0.001). Non-MTEX were enriched in immunostimulatory proteins (P = 0.002) and were only weakly immunosuppressive. Elevated MTEX/total exosome ratios and, surprisingly, non-MTEX ability to induce apoptosis of CD8+ T cells emerged as positive correlates of disease stage. MTEX emerge as the major mechanism of tumor-induced immune suppression and as an underestimated barrier to successful melanoma immunotherapy.
Antagonistic interplay between pH and food resources affects copepod traits and performance in a year-round upwelling system
Authors: Aguilera Victor M. , Vargas Cristian A. , Dam Hans G.
Published: January 2020

Linking pH/pCO2 natural variation to phenotypic traits and performance of foundational species provides essential information for assessing and predicting the impact of ocean acidification (OA) on marine ecosystems. Yet, evidence of such linkage for copepods, the most abundant metazoans in the oceans, remains scarce, particularly for naturally corrosive Eastern Boundary Upwelling systems (EBUs). This study assessed the relationship between pH levels and traits (body and egg size) and performance (ingestion rate (IR) and egg reproduction rate (EPR)) of the numerically dominant neritic copepod Acartia tonsa, in a year-round upwelling system of the northern (23° S) Humboldt EBUs. The study revealed decreases in chlorophyll (Chl) ingestion rate, egg production rate and egg size with decreasing pH as well as egg production efficiency, but the opposite for copepod body size. Further, ingestion rate increased hyperbolically with Chl, and saturated at ~1 µg Chl. L−1. Food resources categorized as high (H, >1 µg L−1) and low (L, <1 µg L−1) levels, and pH-values categorized as equivalent to present day (≤400 µatm pCO2, pH > 7.89) and future (>400 µatm pCO2, pH < 7.89) were used to compare our observations to values globally employed to experimentally test copepod sensitivity to OA. A comparison (PERMANOVA) test with Chl/pH (2*2) design showed that partially overlapping OA levels expected for the year 2100 in other ocean regions, low-pH conditions in this system negatively impacted traits and performance associated with copepod fitness. However, interacting antagonistically with pH, food resource (Chl) maintained copepod production in spite of low pH levels. Thus, the deleterious effects of ocean acidification are modulated by resource availability in this system.
Pharmacogenomics of poor drug metabolism in Greyhounds: Cytochrome P450 (CYP) 2B11 genetic variation, breed distribution, and functional characterization
Authors: Martinez Stephanie E. , Andresen Marie C. , Zhu Zhaohui , Papageorgiou Ioannis , Court Michael H.
Published: January 2020

Greyhounds recover more slowly from certain injectable anesthetics than other dog breeds. Previous studies implicate cytochrome P450 (CYP) 2B11 as an important clearance mechanism for these drugs and suggest Greyhounds are deficient in CYP2B11. However, noCYP2B11gene mutations have been identified that explain this deficiency in Greyhounds. The objectives of this study were to provide additional evidence for CYP2B11 deficiency in Greyhounds, determine the mechanisms underlying this deficiency, and identifyCYP2B11mutations that contribute to this phenotype in Greyhounds. Greyhound livers metabolized CYP2B11 substrates slower, possessed lower CYP2B11 protein abundance, but had similar or higher mRNA expression than other breeds. Gene resequencing identified threeCYP2B11haplotypes, H1 (reference), H2, and H3 that were differentiated by mutations in the gene 3′-untranslated region (3′-UTR). Compared with 63 other dog breeds, Greyhounds had the highestCYP2B11-H3 allele frequency, whileCYP2B11-H2 was widely distributed across most breeds. Using 3′-UTR luciferase reporter constructs,CYP2B11-H3 showed markedly lower gene expression (over 70%) compared toCYP2B11-H1 whileCYP2B11-H2 expression was intermediate. Truncated mRNA transcripts were observed inCYP2B11-H2 andCYP2B11-H3 but notCYP2B11-H1 transfected cells. Our results implicateCYP2B113′-UTR mutations as a cause of decreased CYP2B11 enzyme expression in Greyhounds through reduced translational efficiency.
Micro-CT screening of old shell collections helps to understand the distribution of viviparity in the highly diversified clausiliid clade of land snails
Authors: Sulikowska-Drozd Anna , Duda Piotr , Janiszewska Katarzyna
Published: January 2020

Current zoological research may benefit in many ways from the study of old collections of shells. These collections may provide materials for the verification of broad zoogeographical and ecological hypotheses on the reproduction of molluscs, as they include records from many areas where sampling is currently impossible or very difficult due to political circumstances. In the present paper we present data on viviparous and embryo-retention reproductive modes in clausiliid land snails (subfamily Phaedusinae) acquired from specimens collected since the nineteenth century in the Pontic, Hyrcanian, and East and Southeast Asian regions. X-ray imaging (micro-CT) enabled relatively quick screening of more than 1,000 individuals classified within 141 taxa, among which we discovered 205 shells containing embryos or eggs. Gravid individuals were found to belong to 55 species, representing, for some of these species, the first indication of brooding reproductive strategy.
Assessing police topological efficiency in a major sting operation on the dark web
Authors: da Cunha Bruno Requião , MacCarron Pádraig , Passold Jean Fernando , dos Santos Luiz Walmocyr , Oliveira Kleber A. , Gleeson James P.
Published: January 2020

The networked nature of criminals using the dark web is poorly understood and infrequently studied, mostly due to a lack of data. Rarer still are studies on the topological effectiveness of police interventions. Between 2014 and 2016, the Brazilian Federal Police raided a child pornography ring acting inside the dark web. With these data, we build a topic-view network and compare network disruption strategies with the real police work. Only 7.4% of the forum users share relevant content, and the topological features of this core differ markedly from other clandestine networks. Approximately 60% of the core users need to be targeted to fully break the network connectivity, while the real effect of the arrests was similar to random failure. Despite this topological robustness, the overall “viewership network” was still well disrupted by the arrests, because only 10 users contributed to almost 1/3 of the total post views and 8 of these were apprehended. Moreover, the users who were arrested provided a total of 60% of the viewed content. These results indicate that for similar online systems, aiming at the users that concentrate the views may lead to more efficient police interventions than focusing on the overall connectivity.
New data from Monoplacophora and a carefully-curated dataset resolve molluscan relationships
Authors: Kocot Kevin M. , Poustka Albert J. , Stöger Isabella , Halanych Kenneth M. , Schrödl Michael
Published: January 2020

Relationships among the major lineages of Mollusca have long been debated. Morphological studies have considered the rarely collected Monoplacophora (Tryblidia) to have several plesiomorphic molluscan traits. The phylogenetic position of this group is contentious as morphologists have generally placed this clade as the sister taxon of the rest of Conchifera whereas earlier molecular studies supported a clade of Monoplacophora + Polyplacophora (Serialia) and phylogenomic studies have generally recovered a clade of Monoplacophora + Cephalopoda. Phylogenomic studies have also strongly supported a clade including Gastropoda, Bivalvia, and Scaphopoda, but relationships among these taxa have been inconsistent. In order to resolve conchiferan relationships and improve understanding of early molluscan evolution, we carefully curated a high-quality data matrix and conducted phylogenomic analyses with broad taxon sampling including newly sequenced genomic data from the monoplacophoranLaevipilina antarctica. Whereas a partitioned maximum likelihood (ML) analysis using site-homogeneous models recovered Monoplacophora sister to Cephalopoda with moderate support, both ML and Bayesian inference (BI) analyses using mixture models recovered Monoplacophora sister to all other conchiferans with strong support. A supertree approach also recovered Monoplacophora as the sister taxon of a clade composed of the rest of Conchifera. Gastropoda was recovered as the sister taxon of Scaphopoda in most analyses, which was strongly supported when mixture models were used. A molecular clock based on our BI topology dates diversification of Mollusca to ~546 MYA (+/− 6 MYA) and Conchifera to ~540 MYA (+/− 9 MYA), generally consistent with previous work employing nuclear housekeeping genes. These results provide important resolution of conchiferan mollusc phylogeny and offer new insights into ancestral character states of major mollusc clades.
Direct PtSn Alloy Formation by Pt Electrodeposition on Sn Surface
Authors: Schwämmlein Jan N. , Torres Paulette A. Loichet , Gasteiger Hubert A. , El-Sayed Hany A.
Published: January 2020

Electrochemical deposition is a viable approach to develop novel catalyst structures, such as Pt thin films on conductive support materials. Most studies, reaching out to control electrochemical deposition of Pt to monolayer quantities focus on noble metal substrates (e.g., Au). In contrast, conductive oxides, such as antimony doped tin oxide (ATO), are considered as support material for different applications, e.g., as fuel cell catalysts. Herein, we investigate the deposition process of Pt on Sn, used as a model system for the electrochemical deposition of Pt on non-noble metal oxide supports. Doing so, we shade some light on the differences of a metallic Sn surface and surface oxide species in electrochemical deposition processes. With respect to a borate buffer solution, containing K2PtCl4 as Pt precursor, we report for the first time that surface oxides have the capability to fully inhibit the electrochemical deposition of Pt. Furthermore, direct alloying of the deposited Pt with the Sn support during the electrodeposition process yielded a catalyst with a high activity for the oxidation of CO.
Aedes aegypti insecticide resistance underlies the success (and failure) of Wolbachia population replacement
Authors: Garcia Gabriela A. , Hoffmann Ary A. , Maciel-de-Freitas Rafael , Villela Daniel A. M.
Published: January 2020

Mosquitoes that carry Wolbachia endosymbionts may help control the spread of arboviral diseases, such as dengue, Zika and chikungunya. Wolbachia frequencies systematically increase only when the frequency-dependent advantage due to cytoplasmic incompatibility exceeds frequency-independent costs, which may be intrinsic to the Wolbachia and/or can be associated with the genetic background into which Wolbachia are introduced. Costs depend on field conditions such as the environmental pesticide load. Introduced mosquitoes need adequate protection against insecticides to ensure survival after release. We model how insecticide resistance of transinfected mosquitoes determines the success of local Wolbachia introductions and link our theoretical results to field data. Two Ae. aegypti laboratory strains carrying Wolbachia were released in an isolated district of Rio de Janeiro, Brazil: wMelBr (susceptible to pyrethroids) and wMelRio (resistant to pyrethroids). Our models elucidate why releases of the susceptible strain failed to result in Wolbachia establishment, while releases of the resistant strain led to Wolbachia transforming the native Ae. aegypti population. The results highlight the importance of matching insecticide resistance levels in release stocks to those in the target natural populations during Wolbachia deployment.
Computational exploration of molecular receptive fields in the olfactory bulb reveals a glomerulus-centric chemical map
Authors: Soelter Jan , Schumacher Jan , Spors Hartwig , Schmuker Michael
Published: January 2020

Progress in olfactory research is currently hampered by incomplete knowledge about chemical receptive ranges of primary receptors. Moreover, the chemical logic underlying the arrangement of computational units in the olfactory bulb has still not been resolved. We undertook a large-scale approach at characterising molecular receptive ranges (MRRs) of glomeruli in the dorsal olfactory bulb (dOB) innervated by the MOR18-2 olfactory receptor, also known as Olfr78, with human ortholog OR51E2. Guided by an iterative approach that combined biological screening and machine learning, we selected 214 odorants to characterise the response of MOR18-2 and its neighbouring glomeruli. We found that a combination of conventional physico-chemical and vibrational molecular descriptors performed best in predicting glomerular responses using nonlinear Support-Vector Regression. We also discovered several previously unknown odorants activating MOR18-2 glomeruli, and obtained detailed MRRs of MOR18-2 glomeruli and their neighbours. Our results confirm earlier findings that demonstrated tunotopy, that is, glomeruli with similar tuning curves tend to be located in spatial proximity in the dOB. In addition, our results indicate chemotopy, that is, a preference for glomeruli with similar physico-chemical MRR descriptions being located in spatial proximity. Together, these findings suggest the existence of a partial chemical map underlying glomerular arrangement in the dOB. Our methodology that combines machine learning and physiological measurements lights the way towards future high-throughput studies to deorphanise and characterise structure-activity relationships in olfaction.
Modelling photovoltaic soiling losses through optical characterization
Authors: Smestad Greg P. , Germer Thomas A. , Alrashidi Hameed , Fernández Eduardo F. , Dey Sumon , Brahma Honey , Sarmah Nabin , Ghosh Aritra , Sellami Nazmi , Hassan Ibrahim A. I. , Desouky Mai , Kasry Amal , Pesala Bala , Sundaram Senthilarasu , Almonacid Florencia , Reddy K. S. , Mallick Tapas K. , Micheli Leonardo
Published: January 2020

The accumulation of soiling on photovoltaic (PV) modules affects PV systems worldwide. Soiling consists of mineral dust, soot particles, aerosols, pollen, fungi and/or other contaminants that deposit on the surface of PV modules. Soiling absorbs, scatters, and reflects a fraction of the incoming sunlight, reducing the intensity that reaches the active part of the solar cell. Here, we report on the comparison of naturally accumulated soiling on coupons of PV glass soiled at seven locations worldwide. The spectral hemispherical transmittance was measured. It was found that natural soiling disproportionately impacts the blue and ultraviolet (UV) portions of the spectrum compared to the visible and infrared (IR). Also, the general shape of the transmittance spectra was similar at all the studied sites and could adequately be described by a modified form of the Ångström turbidity equation. In addition, the distribution of particles sizes was found to follow the IEST-STD-CC 1246E cleanliness standard. The fractional coverage of the glass surface by particles could be determined directly or indirectly and, as expected, has a linear correlation with the transmittance. It thus becomes feasible to estimate the optical consequences of the soiling of PV modules from the particle size distribution and the cleanliness value.
Assisted reproduction mediated resurrection of a feline model for Chediak-Higashi syndrome caused by a large duplication in LYST
Authors: Buckley R. M. , Grahn R. A. , Gandolfi B. , Herrick J. R. , Kittleson M. D. , Bateman H. L. , Newsom J. , Swanson W. F. , Prieur D. J. , Lyons L. A.
Published: January 2020

Chediak-Higashi Syndrome (CHS) is a well-characterized, autosomal recessively inherited lysosomal disease caused by mutations inlysosomal trafficking regulator(LYST). The feline model for CHS was originally maintained for ~20 years. However, the colonies were disbanded and the CHS cat model was lost to the research community before the causative mutation was identified. To resurrect the cat model, semen was collected and cryopreserved from a lone, fertile,  CHS carrier male. Using cryopreserved semen, laparoscopic oviductal artificial insemination was performed on three queens, two queens produced 11 viable kittens. To identify the causative mutation, a fibroblast cell line, derived from an affected cat from the original colony, was whole genome sequenced. Visual inspection of the sequence data identified a candidate causal variant as a ~20 kb tandem duplication withinLYST, spanning exons 30 through to 38 (NM_001290242.1:c.8347-2422_9548 + 1749dup). PCR genotyping of the produced offspring demonstrated three individuals inherited the mutant allele from the CHS carrier male. This study demonstrated the successful use of cryopreservation and assisted reproduction to maintain and resurrect biomedical models and has defined the variant causing Chediak-Higashi syndrome in the domestic cat.
Single-cell adhesion force kinetics of cell populations from combined label-free optical biosensor and robotic fluidic force microscopy
Authors: Sztilkovics Milan , Gerecsei Tamas , Peter Beatrix , Saftics Andras , Kurunczi Sandor , Szekacs Inna , Szabo Balint , Horvath Robert
Published: January 2020

Single-cell adhesion force plays a crucial role in biological sciences, however its in-depth investigation is hindered by the extremely low throughput and the lack of temporal resolution of present techniques. While atomic force microcopy (AFM) based methods are capable of directly measuring the detachment force values between individual cells and a substrate, their throughput is limited to few cells per day, and cannot provide the kinetic evaluation of the adhesion force over the timescale of several hours. In this study a high spatial and temporal resolution resonant waveguide grating based label-free optical biosensor was combined with robotic fluidic force microscopy to monitor the adhesion of living cancer cells. In contrast to traditional fluidic force microscopy methods with a manipulation range in the order of 300–400 micrometers, the robotic device employed here can address single cells over mm-cm scale areas. This feature significantly increased measurement throughput, and opened the way to combine the technology with the employed microplate-based, large area biosensor. After calibrating the biosensor signals with the direct force measuring technology on 30 individual cells, the kinetic evaluation of the adhesion force and energy of large cell populations was performed for the first time. We concluded that the distribution of the single-cell adhesion force and energy can be fitted by log-normal functions as cells are spreading on the surface and revealed the dynamic changes in these distributions. The present methodology opens the way for the quantitative assessment of the kinetics of single-cell adhesion force and energy with an unprecedented throughput and time resolution, in a completely non-invasive manner.
Effect of input voltage frequency on the distribution of electrical stresses on the cell surface based on single-cell dielectrophoresis analysis
Authors: Dastani Kia , Moghimi Zand Mahdi , Kavand Hanie , Javidi Reza , Hadi Amin , Valadkhani Zarrintaj , Renaud Philippe
Published: January 2020

Electroporation is defined as cell membrane permeabilization under the application of electric fields. The mechanism of hydrophilic pore formation is not yet well understood. When cells are exposed to electric fields, electrical stresses act on their surfaces. These electrical stresses play a crucial role in cell membrane structural changes, which lead to cell permeabilization. These electrical stresses depend on the dielectric properties of the cell, buffer solution, and the applied electric field characteristics. In the current study, the effect of electric field frequency on the electrical stresses distribution on the cell surface and cell deformation is numerically and experimentally investigated. As previous studies were mostly focused on the effect of electric fields on a group of cells, the present study focused on the behavior of a single cell exposed to an electric field. To accomplish this, the effect of cells on electrostatic potential distribution and electric field must be considered. To do this, Fast immersed interface method (IIM) was used to discretize the governing quasi-electrostatic equations. Numerical results confirmed the accuracy of fast IIM in satisfying the internal electrical boundary conditions on the cell surface. Finally, experimental results showed the effect of applied electric field on cell deformation at different frequencies.
Thermotolerance experiments on active and desiccated states of Ramazzottius varieornatus emphasize that tardigrades are sensitive to high temperatures
Authors: Neves Ricardo Cardoso , Hvidepil Lykke K. B. , Sørensen-Hygum Thomas L. , Stuart Robyn M. , Møbjerg Nadja
Published: January 2020

Global warming is already having harmful effects on habitats worldwide and it is therefore important to gain an understanding of how rising temperatures may affect extant animals. Here, we investigate the tolerance to high temperatures of Ramazzottius varieornatus, a tardigrade frequently found in transient freshwater habitats. Using logistic modelling on activity we evaluate the effect of 24 hour temperature exposures on active tardigrades, with or without a short acclimation period, compared to exposures of desiccated tardigrades. We estimate that the 50% mortality temperature for non-acclimated active tardigrades is 37.1 °C, with a small but significant increase to 37.6 °C following acclimation. Desiccated specimens tolerate much higher temperatures, with an estimated 50% mortality temperature of 82.7 °C following 1 hour exposures, but with a significant decrease to 63.1 °C following 24 hour exposures. Our results show that metabolically active tardigrades are vulnerable to high temperatures, yet acclimatization could provide a tolerance increase. Desiccated specimens show a much higher resilience—exposure-time is, however, a limiting factor giving tardigrades a restricted window of high temperature tolerance. Tardigrades are renowned for their ability to tolerate extreme conditions, but their endurance towards high temperatures clearly has an upper limit—high temperatures thus seem to be their Achilles heel.
Experimental and Theoretical Studies of Novel Azo Benzene Functionalized Conjugated Polymers: In-vitro Antileishmanial Activity and Bioimaging
Authors: Singh Neetika , Arish Mohd. , Kumar Prabhat , Rub Abdur , Riaz Ufana
Published: January 2020

To study the effect of insertion of azobenzene moiety on the spectral, morphological and fluorescence properties of conventional conducting polymers, the present work reports ultrasound-assisted polymerization of azobenzene with aniline, 1-naphthylamine, luminol and o-phenylenediamine. The chemical structure and polymerization was established via Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (1H-NMR) spectroscopy, while the electronic properties were explored via ultraviolet-visible (UV-vis) spectroscopy. Theoretical IR and UV spectra were computed using DFT/B3LYP method with 6–311G basis set while theoretical 1H-NMR spectra was obtained by gauge independent atomic orbital (GIAO) method. The theoretically computed spectra were found to be in close agreement with the experimental findings confirming the chemical as well as electronic structure of the synthesized polymers. Morphology was investigated by X-ray diffraction and transmission electron microscopy studies. Fluorescence studies revealed emission ranging between 530–570 nm. The polymers also revealed high singlet oxygen (1O2) generation characteristics. In-vitro antileishmanial efficacy as well as live cell imaging investigations reflected the potential application of these polymers in the treatment of leishmaniasis and its diagnosis.
Non-essentiality of canonical cell division genes in the planctomycete Planctopirus limnophila
Authors: Rivas-Marin Elena , Peeters Stijn H. , Claret Fernández Laura , Jogler Christian , van Niftrik Laura , Wiegand Sandra , Devos Damien P.
Published: January 2020

Most bacteria divide by binary fission using an FtsZ-based mechanism that relies on a multi-protein complex, the divisome. In the majority of non-spherical bacteria another multi-protein complex, the elongasome, is also required for the maintenance of cell shape. Components of these multi-protein assemblies are conserved and essential in most bacteria. Here, we provide evidence that at least three proteins of these two complexes are not essential in the FtsZ-less ovoid planctomycete bacterium Planctopirus limnophila which divides by budding. We attempted to construct P. limnophila knock-out mutants of the genes coding for the divisome proteins FtsI, FtsK, FtsW and the elongasome protein MreB. Surprisingly, ftsI, ftsW and mreB could be deleted without affecting the growth rate. On the other hand, the conserved ftsK appeared to be essential in this bacterium. In conclusion, the canonical bacterial cell division machinery is not essential in P. limnophila and this bacterium divides via budding using an unknown mechanism.
Dynamics and stability in prebiotic information integration: an RNA World model from first principles
Authors: Szilágyi András , Könnyű Balázs , Czárán Tamás
Published: January 2020

The robust coevolution of catalytically active, metabolically cooperating prebiotic RNA replicators were investigated using an RNA World model of the origin of life based on physically and chemically plausible first principles. The Metabolically Coupled Replicator System assumes RNA replicators to supply metabolically essential catalytic activities indispensable to produce nucleotide monomers for their own template replication. Using external chemicals as the resource and the necessary ribozyme activities, Watson-Crick type replication produces complementary strands burdened by high-rate point mutations (insertions, deletions, substitutions). Metabolic ribozyme activities, replicabilities and decay rates are assigned to certain sequence and/or folding (thermodynamical) properties of single-stranded RNA molecules. Short and loosely folded sequences are given replication advantage, longer and tightly folded ones are better metabolic ribozymes and more resistant to hydrolytic decay. We show that the surface-bound MCRS evolves stable and metabolically functional communities of replicators of almost equal lengths, replicabilities and ribozyme activities. Being highly resistant to the invasion of parasitic (non-functional) replicators, it is also stable in the evolutionary sense. The template replication mechanism selects for catalytic “promiscuity”: the two (complementary) strands of the same evolved replicator will often carry more than a single catalytically active motif, thus maximizing functionality in a minimum of genetic information.
Remotely-sensed planform morphologies reveal fluvial and tidal nature of meandering channels
Authors: Finotello Alvise , D’Alpaos Andrea , Bogoni Manuel , Ghinassi Massimiliano , Lanzoni Stefano
Published: January 2020

Meandering channels extensively dissect fluvial and tidal landscapes, critically controlling their morphodynamic evolution and sedimentary architecture. In spite of an apparently striking dissimilarity of the governing processes, planform dimensions of tidal and fluvial meanders consistently scale to local channel width, and previous studies were unable to identify quantitative planimetric differences between these landforms. Here we use satellite imagery, measurements of meandering patterns, and different statistical analyses applied to about 10,000 tidal and fluvial meanders worldwide to objectively disclose fingerprints of the different physical processes they are shaped by. We find that fluvial and tidal meanders can be distinguished on the exclusive basis of their remotely-sensed planforms. Moreover, we show that tidal meanders are less morphologically complex and display more spatially homogeneous characteristics compared to fluvial meanders. Based on existing theoretical, numerical, and field studies, we suggest that our empirical observations can be explained by the more regular processes carving tidal meanders, as well as by the higher lithological homogeneity of the substrates they typically cut through. Allowing one to effectively infer processes from landforms, a fundamental inverse problem in geomorphology, our results have relevant implications for the conservation and restoration of tidal environments, as well as from planetary exploration perspectives.
A high throughput zebrafish chemical screen reveals ALK5 and non-canonical androgen signalling as modulators of the pkd2−/− phenotype
Authors: Metzner A. , Griffiths J. D. , Streets A. J. , Markham E. , Philippou T. , Van Eeden F. J. M. , Ong A. C. M.
Published: January 2020

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of end-stage renal failure in humans and results from germline mutations inPKD1orPKD2. Despite the recent approval of tolvaptan, safer and more effective alternative drugs are clearly needed to slow disease progression. As a first step in drug discovery, we conducted an unbiased chemical screen on zebrafishpkd2mutant embryos using two publicly available compound libraries (Spectrum, PKIS) totalling 2,367 compounds to identify novel treatments for ADPKD. Using dorsal tail curvature as the assay readout, three major chemical classes (steroids, coumarins, flavonoids) were identified from the Spectrum library as the most promising candidates to be tested on humanPKD1cystic cells. Amongst these were an androgen, 5α−androstane 3,17-dione, detected as the strongest enhancer of thepkd2phenotype but whose effect was found to be independent of the canonical androgen receptor pathway. From the PKIS library, we identified several ALK5 kinase inhibitors as strong suppressors of thepkd2tail phenotype andin vitrocyst expansion. In summary, our results identify ALK5 and non-canonical androgen receptors as potential therapeutic targets for further evaluation in drug development for ADPKD.
Spatial-Memory Formation After Spaced Learning Involves ERKs1/2 Activation Through a Behavioral-Tagging Process
Authors: Tintorelli Ramiro , Budriesi Pablo , Villar Maria Eugenia , Marchal Paul , Lopes da Cunha Pamela , Correa Julieta , Giurfa Martin , Viola Haydée
Published: January 2020

The superiority of spaced over massed learning is an established fact in the formation of long-term memories (LTM). Here we addressed the cellular processes and the temporal demands of this phenomenon using a weak spatial object recognition (wSOR) training, which induces short-term memories (STM) but not LTM. We observed SOR-LTM promotion when two identical wSOR training sessions were spaced by an inter-trial interval (ITI) ranging from 15 min to 7 h, consistently with spaced training. The promoting effect was dependent on neural activity, protein synthesis and ERKs1/2 activity in the hippocampus. Based on the “behavioral tagging” hypothesis, which postulates that learning induces a neural tag that requires proteins to induce LTM formation, we propose that retraining will mainly retag the sites initially labeled by the prior training. Thus, when weak, consecutive training sessions are experienced within an appropriate spacing, the intracellular mechanisms triggered by each session would add, thereby reaching the threshold for protein synthesis required for memory consolidation. Our results suggest in addition that ERKs1/2 kinases play a dual role in SOR-LTM formation after spaced learning, both inducing protein synthesis and setting the SOR learning-tag. Overall, our findings bring new light to the mechanisms underlying the promoting effect of spaced trials on LTM formation.
Reconsidering the prognostic significance of tumour deposit count in the TNM staging system for colorectal cancer
Authors: Wang Song , Guan Xu , Ma Mingfei , Zhuang Meng , Ma Tianyi , Liu Zheng , Chen Haipeng , Jiang Zheng , Chen Yinggang , Wang Guiyu , Wang Xishan
Published: January 2020

Although the occurrence of tumour deposits (TDs) without metastatic lymph nodes (mLNs) is classified as “N1c” in the 8th TNM staging system for colorectal cancer (CRC), the prognostic significance of the TD count is still controversial. A total of 39155 CRC patients were collected from the Surveillance, Epidemiology, and End Results (SEER) database. The potential associations between baseline characteristics and TD status were evaluated using the χ2 test. Cancer-specific survival (CSS) rates were calculated by using the Kaplan-Meier method, and CSS comparisons were performed by using the log-rank test. The results showed that TD count was an important prognostic factor and that the number of TDs was negatively correlated with the prognosis of CRC patients. We found that the prognostic value of one TD is equivalent to that of two mLNs based on the comparison of CSS rates. Accordingly, we proposed a novel N staging system by integrating the TD count into the N category with the ratio of TDs to mLNs being 1:2. There were no prognostic differences in patients with or without TDs in each novel N category. Weighing one TD as two mLNs in this novel TNM staging system is superior to the “N1c” classification in the 8th TNM staging system in evaluating the prognosis of CRC patients.
Association between leucocyte telomere length and cardiovascular disease in a large general population in the United States
Authors: Xu Cheng , Wang Zhiqi , Su Xiaoqi , Da Min , Yang Zhaocong , Duan Weiwei , Mo Xuming
Published: January 2020

Leucocyte telomere length (LTL) has been reported to be linked to ageing, cancer and cardiovascular disease (CVD). This study aimed to explore the association between LTL and CVD risk in a nationally representative sample of U.S. adults. Complex associations, including nonlinearity and interaction, were also examined. A total of 7,378 subjects from the National Health and Nutrition Examination Survey (NHANES) 1999–2002 were collected. Telomere length was detected from DNA samples and expressed as the mean T/S ratio (telomere repeats per single-copy gene). We performed multiple logistic regression models and interactive analysis to explore the associations between LTL and CVD risk by adjusting for potential confounders. We also performed a sensitivity analysis to investigate the robustness of our results. Among all participants, LTL was associated with the risk of CVD (OR = 0.79, 95% CI: 0.63~0.98, P = 0.033) in a linear manner rather than in a nonlinear manner (P = 0.874). Interaction effects of LTL with both education (P = 0.017) and hypertension (P = 0.007) were observed. Furthermore, using subgroup analyses, protective effects of LTL on CVD risk were found in females and in individuals who were college graduates or above, had serum cotinine >10 ng/ml, did not have hypertension, or had normal white blood cell levels. LTL is linearly inversely associated with CVD risk in the general population of the United States.
Aberrant expression of S-SCAM causes the loss of GABAergic synapses in hippocampal neurons
Authors: Shin Seung Min , Skaar Samantha , Danielson Eric , Lee Sang H.
Published: January 2020

The duplication and deletion mutations of the S-SCAM/MAGI-2 gene are associated with schizophrenia and infantile spasms, respectively. S-SCAM is a unique synaptic scaffolding protein that localizes to both excitatory and GABAergic synapses. However, consequences of aberrant S-SCAM expression on GABAergic synapses is little studied. Here we report the effect of S-SCAM knockdown and overexpression on GABAergic synapses. S-SCAM knockdown in cultured hippocampal neurons caused a drastic loss of both pre- and post-synaptic components of GABAergic synapses, indicating its essential role in GABAergic synapse formation and maintenance. Surprisingly, S-SCAM overexpression also attenuated GABAergic synapses, but the effect is mediated by the loss of postsynaptic GABAA receptors, gephyrin, and neuroligin 2 and does not involve presynaptic component vesicular GABA transporters. Overexpression studies using S-SCAM mutants with various domain deletions indicated that GABAergic synapse loss correlates with their ability to increase excitatory synaptic function. Consistently, AMPA receptor antagonist CNQX or calcineurin inhibitor FK506 abolished the S-SCAM overexpression-induced loss of GABAA receptors, supporting that GABAergic synapse loss by S-SCAM overexpression is due to the activity-induced dispersal of synaptic GABAA receptors. These results suggest that abnormal S-SCAM protein levels disrupt excitation/inhibition balance in neurons, which may explain the pathogenic nature of S-SCAM copy number variations.
The Complete Mitochondrial Genome of endemic giant tarantula, Lyrognathus crotalus (Araneae: Theraphosidae) and comparative analysis
Authors: Kumar Vikas , Tyagi Kaomud , Chakraborty Rajasree , Prasad Priya , Kundu Shantanu , Tyagi Inderjeet , Chandra Kailash
Published: January 2020

The complete mitochondrial genome of Lyrognathus crotalus is sequenced, annotated and compared with other spider mitogenomes. It is 13,865 bp long and featured by 22 transfer RNA genes (tRNAs), and two ribosomal RNA genes (rRNAs), 13 protein-coding genes (PCGs), and a control region (CR). Most of the PCGs used ATN start codon except cox3, and nad4 with TTG. Comparative studies indicated the use of TTG, TTA, TTT, GTG, CTG, CTA as start codons by few PCGs. Most of the tRNAs were truncated and do not fold into the typical cloverleaf structure. Further, the motif (CATATA) was detected in CR of nine species including L. crotalus. The gene arrangement of L. crotalus compared with ancestral arthropod showed the transposition of five tRNAs and one tandem duplication random loss (TDRL) event. Five plesiomophic gene blocks (A-E) were identified, of which, four (A, B, D, E) retained in all taxa except family Salticidae. However, block C was retained in Mygalomorphae and two families of Araneomorphae (Hypochilidae and Pholcidae). Out of 146 derived gene boundaries in all taxa, 15 synapomorphic gene boundaries were identified. TreeREx analysis also revealed the transposition of trnI, which makes three derived boundaries and congruent with the result of the gene boundary mapping. Maximum likelihood and Bayesian inference showed similar topologies and congruent with morphology, and previously reported multi-gene phylogeny. However, the Gene-Order based phylogeny showed sister relationship of L. crotalus with two Araneomorphae family members (Hypochilidae and Pholcidae) and other Mygalomorphae species.
Mass Spectrometry Imaging of atherosclerosis-affine Gadofluorine following Magnetic Resonance Imaging
Authors: Lohöfer Fabian , Buchholz Rebecca , Glinzer Almut , Huber Katharina , Haas Helena , Kaissis Georgios , Feuchtinger Annette , Aichler Michaela , Sporns Peter B. , Höltke Carsten , Stölting Miriam , Schilling Franz , Botnar René M. , Kimm Melanie A. , Faber Cornelius , Walch Axel K. , Zernecke Alma , Karst Uwe , Wildgruber Moritz
Published: January 2020

Molecular imaging of atherosclerosis by Magnetic Resonance Imaging (MRI) has been impaired by a lack of validation of the specific substrate responsible for the molecular imaging signal. We therefore aimed to investigate the additive value of mass spectrometry imaging (MSI) of atherosclerosis-affine Gadofluorine P for molecular MRI of atherosclerotic plaques. Atherosclerotic Ldlr−/− mice were investigated by high-field MRI (7 T) at different time points following injection of atherosclerosis-affine Gadofluorine P as well as at different stages of atherosclerosis formation (4, 8, 16 and 20 weeks of HFD). At each imaging time point mice were immediately sacrificed after imaging and aortas were excised for mass spectrometry imaging: Matrix Assisted Laser Desorption Ionization (MALDI) Imaging and Laser Ablation – Inductively Coupled Plasma – Mass Spectrometry (LA-ICP-MS) imaging. Mass spectrometry imaging allowed to visualize the localization and measure the concentration of the MR imaging probe Gadofluorine P in plaque tissue ex vivo with high spatial resolution and thus adds novel and more target specific information to molecular MR imaging of atherosclerosis.
Long-term spatio-temporal precipitation variations in China with precipitation surface interpolated by ANUSPLIN
Authors: Guo Binbin , Zhang Jing , Meng Xianyong , Xu Tingbao , Song Yongyu
Published: January 2020

Climate changes significantly impact environmental and hydrological processes. Precipitation is one of the most significant climatic parameters and its variability and trends have great influences on environmental and socioeconomic development. We investigate the spatio-temporal variability of precipitation occurrence frequency, mean precipitation depth, PVI and total precipitation in China based on long-term precipitation series from 1961 to 2015. As China’s topography is diverse and precipitation is affected by topography strongly, ANUSPLIN can model the effect of topography on precipitation effectively is adopted to generate the precipitation interpolation surface. Mann–Kendall trend analysis and simple linear regression was adopted to examine long-term trend for these indicators. The results indicate ANUSPLIN precipitation surface is reliable and the precipitation variation show different regional and seasonal trend. For example, there is a sporadic with decreasing frequency precipitation trend in spring and a uniform with increasing frequency trend in summer in Yangtze Plain, which may affect spring ploughing and alteration of flood risk for this main rice-production areas of China. In north-western China, there is a uniform with increasing precipitation frequency and intensity trend, which is beneficial for this arid region. Our study could be helpful for other counties with similar climate types.