bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging functional connectivity differences in newborn infants vulnerable to autism spectrum disorders
Authors: Ciarrusta Judit , Dimitrova Ralica , Batalle Dafnis , O’Muircheartaigh Jonathan , Cordero-Grande Lucilio , Price Anthony , Hughes Emer , Kangas Johanna , Perry Emily , Javed Ayesha , Demilew Jill , Hajnal Joseph , Edwards Anthony David , Murphy Declan , Arichi Tomoki , McAlonan Grainne
Published: May 2020

Studies in animal models of autism spectrum disorders (ASD) suggest atypical early neural activity is a core vulnerability mechanism which alters functional connectivity and predisposes to dysmaturation of neural circuits. However, underlying biological changes associated to ASD in humans remain unclear. Results from functional connectivity studies of individuals diagnosed with ASD are highly heterogeneous, in part because of complex life-long secondary and/or compensatory events. To minimize these confounds and examine primary vulnerability mechanisms, we need to investigate very early brain development. Here, we tested the hypothesis that brain functional connectivity is altered in neonates who are vulnerable to this condition due to a family history of ASD. We acquired high temporal resolution multiband resting state functional magnetic resonance imaging (fMRI) in newborn infants with and without a first-degree relative with ASD. Differences in local functional connectivity were quantified using regional homogeneity (ReHo) analysis and long-range connectivity was assessed using distance correlation analysis. Neonates who have a first-degree relative with ASD had significantly higher ReHo within multiple resting state networks in comparison to age matched controls; there were no differences in long range connectivity. Atypical local functional activity may constitute a biomarker of vulnerability, that might precede disruptions in long range connectivity reported in older individuals diagnosed with ASD.
Rodent models of post-traumatic stress disorder: behavioral assessment
Authors: Verbitsky Alexander , Dopfel David , Zhang Nanyin
Published: May 2020

Although the etiology and expression of psychiatric disorders are complex, mammals show biologically preserved behavioral and neurobiological responses to valent stimuli which underlie the use of rodent models of post-traumatic stress disorder (PTSD). PTSD is a complex phenotype that is difficult to model in rodents because it is diagnosed by patient interview and influenced by both environmental and genetic factors. However, given that PTSD results from traumatic experiences, rodent models can simulate stress induction and disorder development. By manipulating stress type, intensity, duration, and frequency, preclinical models reflect core PTSD phenotypes, measured through various behavioral assays. Paradigms precipitate the disorder by applying physical, social, and psychological stressors individually or in combination. This review discusses the methods used to trigger and evaluate PTSD-like phenotypes. It highlights studies employing each stress model and evaluates their translational efficacies against DSM-5, validity criteria, and criteria proposed by Yehuda and Antelman’s commentary in 1993. This is intended to aid in paradigm selection by informing readers about rodent models, their benefits to the clinical community, challenges associated with the translational models, and opportunities for future work. To inform PTSD model validity and relevance to human psychopathology, we propose that models incorporate behavioral test batteries, individual differences, sex differences, strain and stock differences, early life stress effects, biomarkers, stringent success criteria for drug development, Research Domain Criteria, technological advances, and cross-species comparisons. We conclude that, despite the challenges, animal studies will be pivotal to advances in understanding PTSD and the neurobiology of stress.
Functional neural correlates of psychopathy: a meta-analysis of MRI data
Authors: Deming Philip , Koenigs Michael
Published: May 2020

Neuroimaging studies over the last two decades have begun to specify the neurobiological correlates of psychopathy, a personality disorder that is strongly related to criminal offending and recidivism. Despite the accumulation of neuroimaging studies of psychopathy, a clear and comprehensive picture of the disorder’s neural correlates has yet to emerge. The current study is a meta-analysis of functional MRI studies of psychopathy. Multilevel kernel density analysis was used to identify consistent findings across 25 studies (460 foci) of task-related brain activity. Psychopathy was associated with increased task-related activity predominantly in midline cortical regions overlapping with the default mode network (dorsomedial prefrontal cortex, posterior cingulate, and precuneus) as well as medial temporal lobe (including amygdala). Psychopathy was related to decreased task-related activity in a region of the dorsal anterior cingulate cortex overlapping with the salience network. These findings challenge predominant theories of amygdala hypoactivity and highlight the potential role of hyperactivity in medial default mode network regions and hypoactivity in a key node of the salience network during task performance in psychopathy.
Early assessment of KRAS mutation in cfDNA correlates with risk of progression and death in advanced non-small-cell lung cancer
Authors: Zulato Elisabetta , Attili Ilaria , Pavan Alberto , Nardo Giorgia , Del Bianco Paola , Boscolo Bragadin Andrea , Verza Martina , Pasqualini Lorenza , Pasello Giulia , Fassan Matteo , Calabrese Fiorella , Guarneri Valentina , Amadori Alberto , Conte PierFranco , Indraccolo Stefano , Bonanno Laura
Published: May 2020

Background

Liquid biopsy has the potential to monitor biological effects of treatment. KRAS represents the most commonly mutated oncogene in Caucasian non-small-cell lung cancer (NSCLC). The aim of this study was to explore association of dynamic plasma KRAS genotyping with outcome in advanced NSCLC patients.

Methods

Advanced NSCLC patients were prospectively enrolled. Plasma samples were collected at baseline (T1), after 3 or 4 weeks, according to treatment schedule (T2) and at first radiological restaging (T3). Patients carrying KRAS mutation in tissue were analysed in plasma with droplet digital PCR. Semi-quantitative index of fractional abundance of mutated allele (MAFA) was used.

Results

KRAS-mutated cohort included 58 patients, and overall 73 treatments (N = 39 chemotherapy and N = 34 immune checkpoint inhibitors) were followed with longitudinal liquid biopsy. Sensitivity of KRAS detection in plasma at baseline was 48.3% (95% confidence interval (CI): 35.0–61.8). KRAS mutation at T2 was associated with increased probability of experiencing progressive disease as best radiological response (adjusted odds ratio: 7.3; 95% CI: 2.1–25.0, p = 0.0016). Increased MAFA (T1–T2) predicted shorter progression-free survival (adjusted hazard ratio (HR): 2.1; 95% CI: 1.2–3.8, p = 0.0142) and overall survival (adjusted HR: 3.2; 95% CI: 1.2–8.4, p = 0.0168).

Conclusions

Longitudinal analysis of plasma KRAS mutations correlated with outcome: its early assessment during treatment has great potentialities for monitoring treatment outcome in NSCLC patients.
Nine-factor-based immunohistochemistry classifier predicts recurrence for early-stage hepatocellular carcinoma after curative resection
Authors: Liu Wei-Ren , Tian Meng-Xin , Tang Zheng , Fang Yuan , Zhou Yu-Fu , Song Shu-Shu , Jiang Xi-Fei , Wang Han , Tao Chen-Yang , Zhou Pei-Yun , Qu Wei-Feng , Ding Zhen-Bin , Peng Yuan-Fei , Zhou Jian , Fan Jia , Shi Ying-Hong
Published: May 2020

Background

Immunoscore have shown a promising prognostic value in many cancers. We aimed to establish and validate an immune classifier to predict survival after curative resection of hepatocellular carcinoma (HCC) patients who have undergone curative resection.

Methods

The immunohistochemistry (IHC) classifier assay was performed on 664 patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A HCC. A nine-feature-based HCC-IHC classifier was then constructed by the least absolute shrinkage and selection operator method. The associations between the HCC-IHC classifier and patient outcomes were assessed. Herein, a nomogram was generated from the Cox regression coefficients and evaluated by decision curve analysis.

Results

We constructed an HCC-IHC classifier based on nine features; significant differences were found between the low-HCC-IHC classifier patients and high-HCC-IHC classifier patients in the training cohort in the 5-year relapse-free survival rates (46.7% vs. 26.7%, respectively; P < 0.001). The HCC-IHC classifier-based nomogram presented better accuracy than traditional staging systems.

Conclusions

In conclusion, the HCC-IHC classifier could effectively predict recurrence in early-stage HCC patients and supplemented the prognostic value of the BCLC staging system. The HCC-IHC classifier may facilitate patient decision-making and individualise the management of postoperative patients with early-stage HCC.
Isolation, Characterization and Genomic Analysis of a Novel Bacteriophage VB_EcoS-Golestan Infecting Multidrug-Resistant Escherichia coli Isolated from Urinary Tract Infection
Authors: Yazdi Mahsa , Bouzari Majid , Ghaemi Ezzat Allah , Shahin Khashayar
Published: May 2020

Escherichia coli (E. coli) is one of the most common uropathogenic bacteria. The emergence of multi-drug resistance among these bacteria resulted in a worldwide public health problem which requires alternative treatment approaches such as phage therapy. In this study, phage VB_EcoS-Golestan, a member of Siphoviridae family, with high lytic ability against E. coli isolates, was isolated from wastewater. Its burst size was large and about 100 plaque-forming units/infected cell, rapid adsorption time, and high resistance to a broad range of pH and temperatures. Bioinformatics analysis of the genomic sequence suggests that VB_EcoS-Golestan is a new phage closely related to Escherichia phages in the Kagunavirus genus, Guernseyvirinae subfamily of Siphoviridae. The genome size was 44829 bp bp that encodes 78 putative ORFs, no tRNAs, 7 potential promoter sequences and 13 Rho-factor-independent terminators. No lysogenic mediated genes were detected in VB_EcoS-Golestan genome. Overall VB_EcoS-Golestan might be used as a potential treatment approach for controlling E. coli mediated urinary tract infection, however, further studies are essential to ensure its safety.
Dopaminergic Plasticity in the Bilateral Hippocampus Following Threat Reversal in Humans
Authors: Lissemore Jennifer I. , Nagano-Saito Atsuko , Smart Kelly , Gravel Paul , Leyton Marco , Benkelfat Chawki
Published: May 2020

When a cue no longer predicts a threat, a diminished ability to extinguish or reverse this association is thought to increase risk for stress-related disorders. Despite the clear clinical relevance, the mediating neurochemical mechanisms of threat reversal have received relatively little study. One neurotransmitter implicated in rodent research of changing associations with threat is dopamine. To study whether dopamine is involved in threat reversal in humans, we used high-resolution positron emission tomography (PET) coupled with 18F-fallypride. Twelve healthy volunteers (6 F/6 M) underwent three PET scans: (i) at baseline, (ii) following threat conditioning (the response to a cue associated with electric wrist shock), and (iii) following threat reversal (the response to the same cue now associated with safety). We observed moderate evidence of reduced dopamine D2/3 receptor availability, consistent with greater dopamine release, in the bilateral anterior hippocampus following threat reversal, in response to a safety cue that was previously associated with threat, as compared to both baseline and during exposure to the same cue prior to threat reversal. These findings offer the first preliminary evidence that the response to a previously threatening cue that has since become associated with safety involves dopaminergic neurotransmission within the hippocampus in healthy humans.
Advances in biocultural geography of olive tree (Olea europaea L.) landscapes by merging biological and historical assays
Authors: Russo Giuseppe , Beritognolo Isacco , Bufacchi Marina , Stanzione Vitale , Pisanelli Andrea , Ciolfi Marco , Lauteri Marco , Brush Stephen B.
Published: May 2020

Olive tree is a vector of cultural heritage in Mediterranean. This study explored the biocultural geography of extra virgin olive oil (EVOO) from the cultivar Ogliarola campana in Campania region, Italy. Here, the rich cultural elements related to olive tree and oil represent a suitable case study for a biocultural analysis. We joined analytical techniques, based on stable isotopes and trace elements of EVOOs, with humanistic analyses, based on toponymy and historical data. In order to provide a science-based assessment of the terroir concept, we set up a new method of data analysis that inputs heterogeneous data from analytical and anthropic variables and outputs an original global evaluation score, named terroir score, as a measure of biocultural distinctiveness of the production areas. The analysis highlighted two distinct cultural sub-regions in the production area of Ogliarola campana: a continental cluster in the inner area of Irpinia and a coastal one around Salerno province. Finally, a biocultural map displays the diversity of heterogeneous variables and may support science-based decision making for territory valorisation. This novel biocultural analysis is a promising approach to substantiate the terroir concept with science-based elements and appears suitable to characterize local agri-food products with old tradition and historical data.
Rational identification and characterisation of peptide ligands for targeting polysialic acid
Authors: Shastry Divya G. , Irudayanathan Flaviyan Jerome , Williams Asher , Koffas Mattheos , Linhardt Robert J. , Nangia Shikha , Karande Pankaj
Published: May 2020

The alpha-2,8-linked form of the polysaccharide polysialic acid (PSA) has widespread implications in physiological and pathological processes, ranging from neurological development to disease progression. Though the high electronegativity and excluded volume of PSA often promotes interference of biomolecular interactions, PSA-binding ligands have important implications for both biological processes and biotechnological applications. As such, the design, identification, and characterisation of novel ligands towards PSA is critical for expanding knowledge of PSA interactions and achieving selective glycan targeting. Here, we report on a rational approach for the identification of alpha-2,8-PSA-binding peptides, involving design from the endogenous ligand Siglec-11 and multi-platform characterisation of peptide binding. Microarray-based examination of peptides revealed charge and sequence characteristics influencing peptide affinity to PSA, and carbohydrate–peptide binding was further quantified with a novel fluorescence anisotropy assay. PSA-binding peptides exhibited specific binding to polymeric SA, as well as different degrees of selective binding in various conditions, including competition with PSA of alternating 2,8/9-linkages and screening with PSA-expressing cells. A computational study of Siglec-11 and Siglec-11-derived peptides offered synergistic insight into ligand binding. These results demonstrate the potential of PSA-binding peptides for selective targeting and highlight the importance of the approaches described herein for the study of carbohydrate interactions.
Adaptive defence-related changes in the metabolome of Sorghum bicolor cells in response to lipopolysaccharides of the pathogen Burkholderia andropogonis
Authors: Mareya Charity R. , Tugizimana Fidele , Di Lorenzo Flaviana , Silipo Alba , Piater Lizelle A. , Molinaro Antonio , Dubery Ian A.
Published: May 2020

Plant cell suspension culture systems are valuable for the study of complex biological systems such as inducible defence responses and aspects of plant innate immunity. Perturbations to the cellular metabolome can be investigated using metabolomic approaches in order to reveal the underlying metabolic mechanism of cellular responses. Lipopolysaccharides from the sorghum pathogen,Burkholderia andropogonis(LPSB.a.), were purified, chemically characterised and structurally elucidated. The lipid A moiety consists of tetra- and penta-acylated 1,4’-bis-phosphorylated disaccharide backbone decorated by aminoarabinose residues, while the O-polysaccharide chain consists of linear trisaccharide repeating units of [→2)-α-Rha3CMe-(1 → 3)-α-Rha-(1 → 3)-α-Rha-(1 → ]. The effect of LPSB.a.in triggering metabolic reprogramming inSorghum bicolorcells were investigated using untargeted metabolomics with liquid chromatography coupled to mass spectrometry detection. Cells were treated with LPSB.a.and the metabolic changes monitored over a 30 h time period. Alterations in the levels of phytohormones (jasmonates, zeatins, traumatic-, azelaic- and abscisic acid), which marked the onset of defence responses and accumulation of defence-related metabolites, were observed. Phenylpropanoids and indole alkaloids as well as oxylipins that included di- and trihydroxyoctadecedienoic acids were identified as signatory biomarkers, with marked secretion into the extracellular milieu. The study demonstrated that sorghum cells recognise LPSB.a.as a ‘microbe-associated molecular pattern’, perturbing normal cellular homeostasis. The molecular features of the altered metabolome were associated with phytohormone-responsive metabolomic reconfiguration of primary and secondary metabolites originating from various metabolic pathways, in support of defence and immunity.
Molecular analysis of the massive GSH transport mechanism mediated by the human Multidrug Resistant Protein 1/ABCC1
Authors: Nasr Rachad , Lorendeau Doriane , Khonkarn Ruttiros , Dury Lauriane , Pérès Basile , Boumendjel Ahcène , Cortay Jean-Claude , Falson Pierre , Chaptal Vincent , Baubichon-Cortay Hélène
Published: May 2020

The transporter Multidrug Resistance Protein 1 (MRP1, ABCC1) is implicated in multidrug resistant (MDR) phenotype of cancer cells. Glutathione (GSH) plays a key role in MRP1 transport activities. In addition, a ligand-stimulated GSH transport which triggers the death of cells overexpressing MRP1, by collateral sensitivity (CS), has been described. This CS could be a way to overcome the poor prognosis for patients suffering from a chemoresistant cancer. The molecular mechanism of such massive GSH transport and its connection to the other transport activities of MRP1 are unknown. In this context, we generated MRP1/MRP2 chimeras covering different regions, MRP2 being a close homolog that does not trigger CS. The one encompassing helices 16 and 17 led to the loss of CS and MDR phenotype without altering basal GSH transport. Within this region, the sole restoration of the original G1228 (D1236 in MRP2) close to the extracellular loop between the two helices fully rescued the CS (massive GSH efflux and cell death) but not the MDR phenotype. The flexibility of that loop and the binding of a CS agent like verapamil could favor a particular conformation for the massive transport of GSH, not related to other transport activities of MRP1.
On the Spontaneous Build-Up of Voltage between Dissimilar Metals Under High Relative Humidity Conditions
Authors: Lax J. Y. , Price C. , Saaroni H.
Published: May 2020

Certain metals can surprisingly build-up charge spontaneously, when exposed to high relative humidity (RH), although they need to be isolated from the ground. We have explored this phenomenon, building on former experimental knowledge and carrying out additional experiments, to identify the parameters that could enhance this charging. We used many types of metals with different characteristics under different RH and temperature conditions. While some metals were unaffected by high RH, others, like zinc and stainless steel, did acquire charge, when RH was >60%, and charged a capacitor to a voltage of 1 V. For the first time, we also performed outdoors experiments, showing this phenomenon is also valid under similar natural ambient humid conditions. If these results can be scaled up, it may lead to the development of practical applications for regions and times of high RH conditions.
An Ex Vivo Brain Slice Culture Model of Chronic Wasting Disease: Implications for Disease Pathogenesis and Therapeutic Development
Authors: Kondru Naveen , Manne Sireesha , Kokemuller Robyn , Greenlee Justin , Greenlee M. Heather West , Nichols Tracy , Kong Qingzhong , Anantharam Vellareddy , Kanthasamy Arthi , Halbur Patrick , Kanthasamy Anumantha G.
Published: May 2020

Chronic wasting disease (CWD) is a rapidly spreading prion disease of cervids, yet antemortem diagnosis, treatment, and control remain elusive. We recently developed an organotypic slice culture assay for sensitive detection of scrapie prions using ultrasensitive prion seeding. However, this model was not established for CWD prions due to their strong transmission barrier from deer (Odocoileus spp) to standard laboratory mice (Mus musculus). Therefore, we developed and characterized the ex vivo brain slice culture model for CWD, using a transgenic mouse model (Tg12) that expresses the elk (Cervus canadensis) prion protein gene (PRNP). We tested for CWD infectivity in cultured slices using sensitive seeding assays such as real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA). Slice cultures from Tg12, but not from prnp−/− mice, tested positive for CWD. Slice-generated CWD prions transmitted efficiently to Tg12 mice. Furthermore, we determined the activity of anti-prion compounds and optimized a screening protocol for the infectivity of biological samples in this CWD slice culture model. Our results demonstrate that this integrated brain slice model of CWD enables the study of pathogenic mechanisms with translational implications for controlling CWD.
First evidence of plastic fallout from the North Pacific Garbage Patch
Authors: Egger Matthias , Sulu-Gambari Fatimah , Lebreton Laurent
Published: May 2020

The infamous garbage patches on the surface of subtropical oceanic gyres are proof that plastic is polluting the ocean on an unprecedented scale. The fate of floating plastic debris ‘trapped’ in these gyres, however, remains largely unknown. Here, we provide the first evidence for the vertical transfer of plastic debris from the North Pacific Garbage Patch (NPGP) into the underlying deep sea. The numerical and mass concentrations of plastic fragments (500 µm to 5 cm in size) suspended in the water column below the NPGP follow a power law decline with water depth, reaching values <0.001 pieces/m3 and <0.1 µg/m3 in the deep sea. The plastic particles in the NPGP water column are mostly in the size range of particles that are apparently missing from the ocean surface and the polymer composition of plastic in the NPGP water column is similar to that of floating debris circulating in its surface waters (i.e. dominated by polyethylene and polypropylene). Our results further reveal a positive correlation between the amount of plastic debris at the sea surface and the depth-integrated concentrations of plastic fragments in the water column. We therefore conclude that the presence of plastics in the water column below the NPGP is the result of ‘fallout’ of small plastic fragments from its surface waters.
Radiographic analysis of adult ankle fractures using combined Danis-Weber and Lauge-Hansen classification systems
Authors: Han Shu-Man , Wu Tian-Hao , Wen Jin-Xu , Wang Yong , Cao Lei , Wu Wen-Juan , Gao Bu-Lang
Published: May 2020

This study was to analyze ankle fractures for determining the epidemiology, types, distribution, possible mechanisms and diagnosis precision. Between January 2013 and December 2017, all Chinese patients older than 16 years of age with ankle fractures excluding old ankle fractures and pathological fractures in a tertiary care hospital were analyzed by using the Danis-Weber and Lauge-Hansen classification systems. Among 3952 patients with ankle fractures, 1225 fractures (31%) were Danis-Weber type A, 1640 (42%) were type B, 751 (19%) were type C, and 336 (9%) were perpendicular compression fracture. There were 1949 fractures on the left side and 2003 on the right with no significant difference (P > 0.05). Male patients between 16 and 50 years of age and women over 50 years had a higher incidence of ankle fractures accounting for 38.4% (1517/3952) and 22.2% (800/3952), respectively. Posterior malleolar fractures, fibular fractures above the inferior tibiofibular joint and Tillaux fractures were easily missed in the diagnosis, with 38 fractures (0.96%) being missed in the diagnosis. In conclusion, young and middle-aged men and older women have a higher incidence of ankle fractures, and use of the Lauge-Hansen and Danis-Weber classification systems can better help assessing the varied and complex ankle fractures, predicting the injuries, increasing diagnostic precision and decreasing misdiagnosis rate.
Intraoperative Laser Speckle Contrast Imaging For Real-Time Visualization of Cerebral Blood Flow in Cerebrovascular Surgery: Results From Pre-Clinical Studies
Authors: Mangraviti Antonella , Volpin Francesco , Cha Jaepyeong , Cunningham Samantha I. , Raje Karan , Brooke M. Jason , Brem Henry , Olivi Alessandro , Huang Judy , Tyler Betty M. , Rege Abhishek
Published: May 2020

Cerebrovascular surgery can benefit from an intraoperative system that conducts continuous monitoring of cerebral blood flow (CBF). Such a system must be handy, non-invasive, and directly integrated into the surgical workflow. None of the currently available techniques, considered alone, meets all these criteria. Here, we introduce the SurgeON™ system: a newly developed non-invasive modular tool which transmits high-resolution Laser Speckle Contrast Imaging (LSCI) directly onto the eyepiece of the surgical microscope. In preclinical rodent and rabbit models, we show that this system enabled the detection of acute perfusion changes as well as the recording of temporal response patterns and degrees of flow changes in various microvascular settings, such as middle cerebral artery occlusion, femoral artery clipping, and complete or incomplete cortical vessel cautery. During these procedures, a real-time visualization of vasculature and CBF was available in high spatial resolution through the eyepiece as a direct overlay on the live morphological view of the surgical field. Upon comparison with indocyanine green angiography videoangiography (ICG-VA) imaging, also operable via SurgeON, we found that direct-LSCI can produce greater information than ICG-VA and that continuous display of data is advantageous for performing immediate LSCI-guided adjustments in real time.
Study on the experimental performance by electrolysis-integrated ecological floating bed for nitrogen and phosphorus removal in eutrophic water
Authors: Yan Cheng , Wang Mingxuan , Ma Tangming , Yang Shunqing , Kong Ming , Shen Jianing , Yang Liuyan , Gao Yan
Published: May 2020

The new-type electrolysis-integrated ecological floating beds (EEFBs) were set up to study their water removal ability due to the excellent water treatment capacity of electrolysis, this enhanced EEFBs were made of polyethylene filled with biochar substrate and in middle of the substrate placed the Mg-Al alloy served as anode and graphite served as cathode. The results show that removal rates of total nitrogen (TN), ammonia nitrogen (NH3-N), total phosphorus (TP) and phosphate (PO43−-P) by the EEFBs increased 53.1%, 96.5%, 76.5% and 74.5%, respectively. The electrolysis reaction was the main pathway for TN and TP removals in the EEFBs. A higher concentration of hydrogen autotrophic denitrification bacteria was recorded in the substrate of the EEFBs than that in the traditional ecological floating beds (EFBs) (p < 0.05), suggesting that the electrolysis may have enhanced the NO3−-N removal efficiency of the EEFBs by promoting the growth and reproduce of hydrogen autotrophic denitrification bacteria. The in-situ formation of Mg2+ and Al3+ ions from a sacrificial Mg-Al alloy anode, caused PO43−-P and other suspended matter flocculation, improved phosphorus removal and simultaneously reduced turbidity. Thus, electrolysis-integrated ecological floating bed has high nitrogen and phosphorus removal potential in eutrophic water.
Cyto-Feature Engineering: A Pipeline for Flow Cytometry Analysis to Uncover Immune Populations and Associations with Disease
Authors: Fox Amy , Dutt Taru S. , Karger Burton , Rojas Mauricio , Obregón-Henao Andrés , Anderson G. Brooke , Henao-Tamayo Marcela
Published: May 2020

Flow cytometers can now analyze up to 50 parameters per cell and millions of cells per sample; however, conventional methods to analyze data are subjective and time-consuming. To address these issues, we have developed a novel flow cytometry analysis pipeline to identify a plethora of cell populations efficiently. Coupled with feature engineering and immunological context, researchers can immediately extrapolate novel discoveries through easy-to-understand plots. The R-based pipeline uses Fluorescence Minus One (FMO) controls or distinct population differences to develop thresholds for positive/negative marker expression. The continuous data is transformed into binary data, capturing a positive/negative biological dichotomy often of interest in characterizing cells. Next, a filtering step refines the data from all identified cell phenotypes to populations of interest. The data can be partitioned by immune lineages and statistically correlated to other experimental measurements. The pipeline’s modularity allows customization of statistical testing, adoption of alternative initial gating steps, and incorporation of other datasets. Validation of this pipeline through manual gating of two datasets (murine splenocytes and human whole blood) confirmed its accuracy in identifying even rare subsets. Lastly, this pipeline can be applied in all disciplines utilizing flow cytometry regardless of cytometer or panel design. The code is available athttps://github.com/aef1004/cyto-feature_engineering.
On the use of DNA as a linker in antibody-drug conjugates: synthesis, stability and in vitro potency
Authors: Dovgan Igor , Ehkirch Anthony , Lehot Victor , Kuhn Isabelle , Koniev Oleksandr , Kolodych Sergii , Hentz Alexandre , Ripoll Manon , Ursuegui Sylvain , Nothisen Marc , Cianférani Sarah , Wagner Alain
Published: May 2020

Here we present the synthesis and evaluation of antibody-drug conjugates (ADCs), for which antibody and drug are non-covalently connected using complementary DNA linkers. These ADCs are composed of trastuzumab, an antibody targeting HER2 receptors overexpressed on breast cancer cells, and monomethyl auristatin E (MMAE) as a drug payload. In this new ADC format, trastuzumab conjugated to a 37-mer oligonucleotide (ON) was prepared and hybridized with its complementary ON modified at 5-end with MMAE (cON-MMAE) in order to obtain trastuzumab-DNA-MMAE. As an advantage, the cON-MMAE was completely soluble in water, which decreases overall hydrophobicity of toxic payload, an important characteristic of ADCs. The stability in the human plasma of these non-engineered ON-based linkers was investigated and showed a satisfactory half-life of 5.8 days for the trastuzumab-DNA format. Finally, we investigated the in vitro cytotoxicity profile of both the DNA-linked ADC and the ON-drug conjugates and compared them with classical covalently linked ADC. Interestingly, we found increased cytotoxicity for MMAE compared to cON-MMAE and an EC50 in the nanomolar range for trastuzumab-DNA-MMAE on HER2-positive cells. Although this proved to be less potent than classically linked ADC with picomolar range EC50, the difference in cytotoxicity between naked payload and conjugated payload was significant when an ON linker was used. We also observed an interesting increase in cytotoxicity of trastuzumab-DNA-MMAE on HER2-negative cells. This was attributed to enhanced non-specific interaction triggered by the DNA strand as it could be confirmed using ligand tracer assay.
Chemical Compositions and Sources Contribution of Atmospheric Particles at a Typical Steel Industrial Urban Site
Authors: Zhang Guiqin , Ding Chun , Jiang Xiaojing , Pan Guang , Wei Xiaofeng , Sun Youmin
Published: May 2020

Online monitoring concentrations of PM at five sites were obtained from 01/01/2016 to 31/12/2016 in Laiwu, China, and PM2.5 filters were manually sampled for total 34 days at the same sites in four seasons in 2016. PM pollution sources, including soil dust, urban dust, construction dust, coal-fired power plants dust, steel plant dust and motor vehicle exhaust dust were sampled, respectively. The overall mean PM2.5/PM10 ratio (0.57) in Laiwu was at a relatively lower level compared with that in other Chinese cities, which was higher in winter, indicating fine particulate was the main contributor of atmospheric pollution in this period. NH4+ mainly existed in the form of NH4NO3 and (NH4)2SO4 during the sampling periods. Higher sulfate and NH4+ concentrations were in summer while higher nitrate concentrations prevailed in winter. The annual value of OC/EC was (5.38 ± 1.70), higher in summer and lower in winter, and the calculated SOC/OC value (%) was (43.68 ± 12.98)%. The characteristic components were Si, Fe and Ca in urban dust and soil dust; Ca, Mg, and NH4+ in construction dust; Fe, Ca and SO42− in steel dust; OC, EC and Si in motor vehicle exhaust dust; SO42−, Al and NH4+ in power plant dust. Compared with other cities at home and abroad, it was found that the concentrations of metal elements in Laiwu were significantly higher than those in foreign cities, and at a medium level in China. With the improved CRAESCMB model, the urban dust was regarded as the receptor and the source of PM2.5 and apportioned its secondary sources contributions to PM2.5. The CMB results showed the contributions of secondary sources including sulfate (17%), nitrate (17%) and SOC (13%) to PM2.5 accounted for nearly half of all sources. Therefore, more attentions should be paid on secondary sources from the primary emission sources of the motor vehicle exhaust, coal combustion sources especially.
Determination of earthquake epicentres based upon invariant quantities of GRACE strain gravity tensors
Authors: Fatolazadeh Farzam , Goïta Kalifa , Javadi Azar Rahim
Published: May 2020

Investigation of regional and temporal variations in Earth’s gravitational field that are detected by the Gravity Recovery and Climate Experiment (GRACE) twin-satellites may be useful in earthquake epicentre determinations. This study focuses on monthly spherical harmonic coefficients that were extracted from GRACE observations, which were corrected for hydrological effects to determine earthquake epicentres. For the first time, we use the concept of deformation of Earth’s gravity field to estimate invariant components of strain tensors. Four different earthquakes (Iran, China, Turkey, Nepal) were analysed that occurred between 2003 and 2015 and under different hydrological regimes. Wavelet analysis was explored as a means of refining and reconstructing tectonic signals forming the disturbance gravitational potential tensor in the GRACE gravity field models. Dilatation and maximum shear were extracted from these tensors and used to map earthquake epicentre locations. Both components reached their maxima during months of the earthquakes (respectively, 11.78 and 4.93, Bam earthquake; 61.36 and 169.10, Sichuan-Gansu border earthquake; 2415.80 and 627.93, Elazig earthquake; 98.71 and 157.37, Banepa earthquake). For the aforementioned earthquakes, we estimated their respective epicentres in the ranges: φ = 29°–29.5° λ = 58.5°–59°; φ = 32.5°–33° λ = 105.5°–106°; φ = 38.5°–39° λ = 39.5°–40°; and φ = 27.5°–28° λ = 85°–85.5°. Overall, these results agree well with values from other sources. The advance that is provided by our method compared to other research is the ability of determining earthquake epicentres with magnitudes ≤7.5 based upon GRACE observations. However, the approach is of limited use for very deep earthquakes.
Catechol inhibits epidermal growth factor-induced epithelial-to-mesenchymal transition and stem cell-like properties in hepatocellular carcinoma cells
Authors: Lim Won-Chul , Kim Hyunhee , Kim Young-Joo , Jeon Bu-Nam , Kang Hee-Bum , Ko Hyeonseok
Published: May 2020

Epithelial-mesenchymal transition (EMT) is a major cellular process in which epithelial cells lose cell polarity and cell-cell adhesion and become motility and invasiveness by transforming into mesenchymal cells. Catechol is one of the natural compounds present in fruits and vegetables and has various pharmacological and physiological activities including anti-carcinogenic effects. However, the effects of catechol on EMT has not been reported. Epidermal growth factor (EGF) is one of the growth factors and is known to play a role in inducing EMT. The present study showed that catechol suppressed not only the morphological changes to the mesenchymal phenotype of epithelial HCC cells, but also the reduction of E-cadherin and the increment of Vimentin, which are typical hallmark of EMT. In addition, catechol suppressed EMT-related steps such as migration, invasion, anoikis resistance acquisition, and stem cell-like characterization through the EGFR-AKT-ERK signaling pathway during liver cancer metastasis. Therefore, these results suggest that catechol may be able to regulate the early metastasis of liver cancer in vitro.
Fluorescence spectroscopy and chemometrics for simultaneous monitoring of cell concentration, chlorophyll and fatty acids in Nannochloropsis oceanica
Authors: Sá Marta , Bertinetto Carlo G. , Ferrer-Ledo Narcís , Jansen Jeroen J. , Wijffels Rene , Crespo João G. , Barbosa Maria , Galinha Claudia F.
Published: May 2020

Online monitoring of algal biotechnological processes still requires development to support economic sustainability. In this work, fluorescence spectroscopy coupled with chemometric modelling is studied to monitor simultaneously several compounds of interest, such as chlorophyll and fatty acids, but also the biomass as a whole (cell concentration). Fluorescence excitation-emission matrices (EEM) were acquired in experiments where different environmental growing parameters were tested, namely light regime, temperature and nitrogen (replete or deplete medium). The prediction models developed have a high R2 for the validation data set for all five parameters monitored, specifically cell concentration (0.66), chlorophyll (0.78), and fatty acid as total (0.78), saturated (0.81) and unsaturated (0.74). Regression coefficient maps of the models show the importance of the pigment region for all outputs studied, and the protein-like fluorescence region for the cell concentration. These results demonstrate for the first time the potential of fluorescence spectroscopy for in vivo and real-time monitoring of these key performance parameters during Nannochloropsis oceanica cultivation.
Afebrile Bacteremia in Adult Emergency Department Patients with Liver Cirrhosis: Clinical Characteristics and Outcomes
Authors: Chen Hung-Yu , Hsu Yin-Chou
Published: May 2020

Cirrhotic patients with bacteremia are at an increased risk of organ failure and mortality. In addition, they can develop serious infection without fever because of their impaired immune response. Our study aimed to investigate the clinical characteristics and outcomes in afebrile bacteremic patients with liver cirrhosis. A single-center, retrospective cohort study was performed on adult patients who visited the emergency department from January 2015 to December 2018. All patients with bacteremia and diagnosis of liver cirrhosis were enrolled and classified as either afebrile or febrile. In total, 104 bacteremic patients with liver cirrhosis (afebrile: 55 patients and, febrile: 49) were included in the study. Compared with the febrile group, patients in the afebrile group showed a significantly higher rate of inappropriate antibiotics administration (43.6% vs. 20.4%,p = 0.01). They were also at an increased risk of 30-day mortality (40% vs. 18.4%,p = 0.02), intensive care unit transfer (38.2% vs. 18.4%,p = 0.03) and endotracheal intubation (27.3% vs. 10.2%,p = 0.03). The afebrile state was also an independent risk factor associated with 30-day mortality in cirrhotic patients with bacteremia. Clinicians should perform a prudent evaluation in cirrhotic patients and carefully monitor for possible signs of serious infection even in the absence of fever.
Responses of soil microbial biomass and enzyme activity to herbicides imazethapyr and flumioxazin
Authors: Pertile Mariane , Antunes Jadson Emanuel Lopes , Araujo Fabio Fernando , Mendes Lucas William , Van den Brink Paul J. , Araujo Ademir Sérgio Ferreira
Published: May 2020

The use of herbicides is important for controlling weeds in crops. However, they can present impacts on soil properties, such as biological properties. In this study, we evaluated the responses of soil microbial biomass and enzymes activity to the application of the herbicides imazethapyr and flumioxazin and their mixture in an experiment under laboratory conditions, using soils with a different history of use. Soil microbial biomass C (MBC) decreased, while microbial biomass N (MBN) was not affected after the application of the herbicides as compared to the control. Soil respiration, respiratory quotient, and dehydrogenase (DHA) activity increased significantly after the application of the herbicides compared to the control. The hydrolysis of fluorescein diacetate (FDA) was not significantly different between the control and the herbicide treatments. The principal response curve showed the largest initial effects for the flumioxazin, followed by imazethapyr and their mixture. Flumioxazin had a different influence on soil respiration and respiratory quotient than imazethapyr and their mixture. Finally, the effects of herbicides on soil microbial biomass and enzymes are short-term as we observed recovery in the biological parameters over time.
Bimetallic Implanted Plasmonic Photoanodes for TiO2 Sensitized Third Generation Solar Cells
Authors: Kaur Navdeep , Bhullar Viplove , Singh Davinder Paul , Mahajan Aman
Published: May 2020

An auspicious way to enhance the power conversion efficiency (PCE) of third generation sensitized solar cells is to improve the light harvesting ability of TiO2 sensitizer and inhibition of back recombination reactions. In the present work, we have simultaneously comprehended both the factors using stable bimetallic Au and Ag metal nanoparticles (Mnps) embedded in TiO2 with ion implantation technique at lower fluence range; and explored them in third generation dye sensitized solar cells (DSSCs). The best performing Au-Ag implanted DSSC (Fluence- 6 × 1015 ions cm−2) revealed 87.97% enhancement in its PCE relative to unimplanted DSSC; due to plasmon induced optical and electrical effects of Mnps. Here, optimized bimetallic Au-Ag Mnps embedded in TiO2 improves light harvesting of N719 dye; due to the well matched localized surface plasmon resonance (LSPR) absorption band of Au and Ag with low and high energy absorption bands of N719 dye molecules, respectively. Furthermore, Au and Ag acts as charge separation centers in TiO2 that inhibit the recombination reactions occurring at photoanode/electrolyte interface via prolonging photo-generated electron lifetime; resulting in efficient inter-facial charge transportation in DSSCs.
Effect of Curing on Micro-Physical Performance of Polypropylene Fiber Reinforced and Silica Fume stabilized Expansive Soil Under Freezing Thawing Cycles
Authors: Tiwari Nitin , Satyam Neelima , Singh Kundan
Published: May 2020

This study presents the micro-physical investigation of polypropylene (PP) fiber-reinforced, and silica fume (SF) stabilized expansive soil (BC) subgrade. The coupling effect of soil, PP fiber, and SF has been evaluated under the freezing-thawing (F-T) cycle to assess the durability of treated BC Soil. The curing method and duration staggeringly influence the strength of SF treated BC soil; therefore, three different curing method, i.e., moisture-controlled curing (MC), gunny bag curing (GC), and water submerged curing (SC) to a period of 7, 14, and 28 days were considered. The BC soil has been reinforced with 0.25%, 0.50%, and 1.00% PP fiber and stabilized with 2%, 4%, 6% and 8% SF. The physical, chemical, and microstructural properties were determined before and after 2,4,6,8,10 F-T cycles. With the increase in SF content, the unconfined compressive strength of the expansive soil has been increased due to the formation of Calcium Silicate Hydrate (C-S-H) gel. The chemically inert, hydrophobic, non-corrosive nature, and higher tensile strength of PP fiber, it has a higher potential to reinforce the BC soil for durability under tensile failure. This research confirms the possibility of incorporating SF and PP Fiber in road work applications, with significant environmental benefits.
Age and Species Comparisons of Visual Mental Manipulation Ability as Evidence for its Development and Evolution
Authors: Pailian Hrag , Carey Susan E. , Halberda Justin , Pepperberg Irene M.
Published: May 2020

Intelligent behavior is shaped by the abilities to store and manipulate information in visual working memory. Although humans and various non-human animals demonstrate similar storage capacities, the evolution of manipulation ability remains relatively unspecified. To what extent are manipulation limits unique to humans versus shared across species? Here, we compare behavioral signatures of manipulation ability demonstrated by human adults and 6-to-8-year-old children with that of an animal separated from humans by over 300 million years of evolution: a Grey parrot (Psittacus erithacus). All groups of participants completed a variant of the “Shell Game”, which required mentally updating the locations of varying set sizes of occluded objects that swapped places a number of times. The parrot not only demonstrated above-chance performance, but also outperformed children across all conditions. Indeed, the parrot’s accuracy was comparable to (and slightly better than) human adults’ over 12/14 set-size/number-of-swaps combinations, until four items were manipulated with 3–4 swaps, where performance decreased toward that of 6- to 8-year-olds. These results suggest that manipulation of visual working memory representations is an evolutionarily ancient ability. An important next step in this research program is establishing variability across species, and identifying the evolutionary origins (analogous or homologous) of manipulation mechanisms.
Cardiogenic shock elicits acute inflammation, delayed eosinophilia, and depletion of immune cells in most severe cases
Authors: Cuinet Justine , Garbagnati Andrea , Rusca Marco , Yerly Patrick , Schneider Antoine G. , Kirsch Matthias , Liaudet Lucas
Published: May 2020

Patients with cardiogenic shock (CS) display systemic inflammation and a high rate of infections, suggesting important immune disturbances. To explore the immune response to CS, we prospectively measured, in 24 consecutive CS patients, differential white blood cell (WBC) counts and the cytokines IL-1β, IL-5, IL-6, IL-10, TNFα, IFNγ, MCP-1 and eotaxin (CCL11), at Day 1 (T1), day 3 (T2) and day 6-8 (T3). Secondary infections and their influence on cytokines and WBCs were determined. CS induced early (T1) neutrophilia and elevated levels of IL-6, IL-10 and MCP-1, correlating with shock severity. The eosinophil chemoattractant eotaxin was elevated at T1 and decreased thereafter, and a progressive rise of blood eosinophils was noted over time. Patients with the most severe shock had reduced lymphocytes and monocytes at T2 and T3. Sixty-two percent of patients developed an infection, which did not alter the profile of immune response, except from higher IL-6 levels at T2. Therefore, CS elicits an acute pro-inflammatory response, followed by a delayed increase in blood eosinophils, consistent with the development of a tissue repair response, as well as depletion of immune cells in the most severely affected patients, which might predispose to secondary infections.