bluuebunny/crossref_metadata_2025 huggingface dataset:
Biogeochemical Consequences of Nonvertical Methane Transport in Sediment Offshore Northwestern Svalbard
Authors: Treude T. , Krause S. , Steinle L. , Burwicz E. , Hamdan L. J. , Niemann H. , Feseker T. , Liebetrau V. , Krastel S. , Berndt C.
Published: March 2020

A site at the gas hydrate stability limit was investigated offshore northwestern Svalbard to study methane transport in sediment. The site was characterized by chemosynthetic communities (sulfur bacteria mats, tubeworms) and gas venting. Sediments were sampled with in situ porewater collectors and by gravity coring followed by analyses of porewater constituents, sediment and carbonate geochemistry, and microbial activity, taxonomy, and lipid biomarkers. Sulfide and alkalinity concentrations showed concentration maxima in near‐surface sediments at the bacterial mat and deeper maxima at the gas vent site. Sediments at the periphery of the chemosynthetic field were characterized by two sulfate‐methane transition zones (SMTZs) at ~204 and 45 cm depth, where activity maxima of microbial anaerobic oxidation of methane (AOM) with sulfate were found. Amplicon sequencing and lipid biomarker indicate that AOM at the SMTZs was mediated by ANME‐1 archaea. A 1D numerical transport reaction model suggests that the deeper SMTZ‐1 formed on centennial scale by vertical advection of methane, while the shallower SMTZ‐2 could only be reproduced by nonvertical methane injections starting on decadal scale. Model results were supported by age distribution of authigenic carbonates, showing youngest carbonates within SMTZ‐2. We propose that nonvertical methane injection was induced by increasing blockage of vertical transport or formation of sediment fractures. Our study further suggests that the methanotrophic response to the nonvertical methane injection was commensurate with new methane supply. This finding provides new information about for the response time and efficiency of the benthic methane filter in environments with fluctuating methane transport.
Biofilm Growth in Two Streams Draining Mountainous Permafrost Catchments in NE Greenland
Authors: Pastor A. , Wu N. , Skovsholt L. J. , Riis T.
Published: March 2020

The objective of this study was to evaluate how stream water nutrient concentrations influence biofilm accrual in streams draining mountainous permafrost headwaters. We selected six stream locations in the Zackenberg area (NE Greenland, 74°N) subjected to a gradient in the areal contribution of different geomorphological units in the watersheds and channel stability. We used nutrient diffusing substrates to evaluate biofilm growth (autotrophic and total biomass). We found elevated stream nitrate concentrations in samples from upstream reaches draining larger areas of solifluction sheets and bare rock and with higher channel instability. Nitrate had the highest standardized effect on autotrophic biofilm growth on control disks. However, stream biofilm growth was not nutrient limited as shown by the absence of an increase in biofilm biomass as a response to the experimental nutrient additions. The response to nutrient additions via diffusing substrates depended on the altitude gradient. Overall, our results showed stream nitrogen availability to be one of the main drivers of algal biofilm accrual in high‐Arctic streams, suggesting that the predicted changes in nutrient exports induced by climate change will have strong impacts on the biogeochemistry and ecological functioning of high‐Arctic streams.
Debates—Does Information Theory Provide a New Paradigm for Earth Science? Causality, Interaction, and Feedback
Authors: Goodwell Allison E. , Jiang Peishi , Ruddell Benjamin L. , Kumar Praveen
Published: March 2020

The concept of causal interactions between components is an integral part of hydrology and Earth system sciences. Modelers, decision makers, scientists, and other water resources stakeholders all utilize some notion of cause‐and‐effect to understand processes, make decisions, and infer how systems react to change. However, there are different perspectives on the meaning of causality in complex systems and, further, different frameworks and methodologies with which to detect causal interactions. We propose here that information theory (IT) provides a compelling framework for the detection of causality and discuss approaches for several levels of analyses that capture interactions that range from pairwise to multivariate in nature. We illustrate these types of analyses with an example based on weather station time series variables, in which variables may interact pairwise or jointly and on short to long time scales. In general, many unsolved or even unanticipated questions in the hydrologic sciences could benefit from this perspective.
Lactobacillus paracasei-derived extracellular vesicles attenuate the intestinal inflammatory response by augmenting the endoplasmic reticulum stress pathway
Authors: Choi Ji Hyun , Moon Chang Mo , Shin Tae-Seop , Kim Eun Kyoung , McDowell Andrea , Jo Min-Kyung , Joo Yang Hee , Kim Seong-Eun , Jung Hye-Kyung , Shim Ki-Nam , Jung Sung-Ae , Kim Yoon-Keun
Published: March 2020

Lactobacillus paracasei is a major probiotic and is well known for its anti-inflammatory properties. Thus, we investigated the effects of L. paracasei-derived extracellular vesicles (LpEVs) on LPS-induced inflammation in HT29 human colorectal cancer cells and dextran sulfate sodium (DSS)-induced colitis in C57BL/6 mice. ER stress inhibitors (salubrinal or 4-PBA) or CHOP siRNA were utilized to investigate the relationship between LpEV-induced endoplasmic reticulum (ER) stress and the inhibitory effect of LpEVs against LPS-induced inflammation. DSS (2%) was administered to male C57BL/6 mice to induce inflammatory bowel disease, and disease activity was measured by determining colon length, disease activity index, and survival ratio. In in vitro experiments, LpEVs reduced the expression of the LPS-induced pro-inflammatory cytokines IL-1α, IL-1β, IL-2, and TNFα and increased the expression of the anti-inflammatory cytokines IL-10 and TGFβ. LpEVs reduced LPS-induced inflammation in HT29 cells and decreased the activation of inflammation-associated proteins, such as COX-2, iNOS and NFκB, as well as nitric oxide. In in vivo mouse experiments, the oral administration of LpEVs also protected against DSS-induced colitis by reducing weight loss, maintaining colon length, and decreasing the disease activity index (DAI). In addition, LpEVs induced the expression of endoplasmic reticulum (ER) stress-associated proteins, while the inhibition of these proteins blocked the anti-inflammatory effects of LpEVs in LPS-treated HT29 cells, restoring the pro-inflammatory effects of LPS. This study found that LpEVs attenuate LPS-induced inflammation in the intestine through ER stress activation. Our results suggest that LpEVs have a significant effect in maintaining colorectal homeostasis in inflammation-mediated pathogenesis.
ZBTB7A prevents RUNX1-RUNX1T1-dependent clonal expansion of human hematopoietic stem and progenitor cells
Authors: Redondo Monte Enric , Wilding Anja , Leubolt Georg , Kerbs Paul , Bagnoli Johannes W. , Hartmann Luise , Hiddemann Wolfgang , Chen-Wichmann Linping , Krebs Stefan , Blum Helmut , Cusan Monica , Vick Binje , Jeremias Irmela , Enard Wolfgang , Theurich Sebastian , Wichmann Christian , Greif Philipp A.
Published: March 2020

ZBTB7A is frequently mutated in acute myeloid leukemia (AML) with t(8;21) translocation. However, the oncogenic collaboration between mutated ZBTB7A and the RUNX1–RUNX1T1 fusion gene in AML t(8;21) remains unclear. Here, we investigate the role of ZBTB7A and its mutations in the context of normal and malignant hematopoiesis. We demonstrate that clinically relevant ZBTB7A mutations in AML t(8;21) lead to loss of function and result in perturbed myeloid differentiation with block of the granulocytic lineage in favor of monocytic commitment. In addition, loss of ZBTB7A increases glycolysis and hence sensitizes leukemic blasts to metabolic inhibition with 2-deoxy-d-glucose. We observed that ectopic expression of wild-type ZBTB7A prevents RUNX1-RUNX1T1-mediated clonal expansion of human CD34+ cells, whereas the outgrowth of progenitors is enabled by ZBTB7A mutation. Finally, ZBTB7A expression in t(8;21) cells lead to a cell cycle arrest that could be mimicked by inhibition of glycolysis. Our findings suggest that loss of ZBTB7A may facilitate the onset of AML t(8;21), and that RUNX1-RUNX1T1-rearranged leukemia might be treated with glycolytic inhibitors.
Gastric cancer: genome damaged by bugs
Authors: Zhao Yanan , Zhang Jinglin , Cheng Alfred S. L. , Yu Jun , To Ka Fai , Kang Wei
Published: March 2020

Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. The role of the microorganisms in gastric tumorigenesis attracts much attention in recent years. These microorganisms include bacteria, virus, and fungi. Among them,Helicobacter pylori(H. pylori) infection is by far the most important risk factor for GC development, with special reference to the early-onset cases.H. pyloritargets multiple cellular components by utilizing various virulence factors to modulate the host proliferation, apoptosis, migration, and inflammatory response. Epstein–Barr virus (EBV) serves as another major risk factor in gastric carcinogenesis. The virus protein, EBER noncoding RNA, and EBV miRNAs contribute to the tumorigenesis by modulating host genome methylation and gene expression. In this review, we summarized the related reports about the colonized microorganism in the stomach and discussed their specific roles in gastric tumorigenesis. Meanwhile, we highlighted the therapeutic significance of eradicating the microorganisms in GC treatment.
Enhanced DNA-repair capacity and resistance to chemically induced carcinogenesis upon deletion of the phosphatase regulator NIPP1
Authors: Verbinnen Iris , Boens Shannah , Ferreira Monica , Szekér Kathelijne , Van Wijk Louise , Van Eynde Aleyde , Bollen Mathieu
Published: March 2020

Nuclear Inhibitor of PP1 (NIPP1) is a conserved regulatory subunit of protein phosphatase PP1. The selective deletion of NIPP1 in mouse liver parenchymal cells or skin epidermal cells culminates in a late-onset hyperproliferation of a subset of resident progenitor cells. Although a hyperplastic phenotype is usually tumor promoting, we show here that the absence of NIPP1 conferred a strong resistance to chemically induced hepatocellular or skin carcinoma. The ablation of NIPP1 did not affect the metabolism of the administered mutagens (diethylnitrosamine or 7,12-dimethylbenz[a]anthracene), but reduced the conversion of mutagen-induced covalent DNA modifications into cancer-initiating mutations. This reduced sensitivity to mutagens correlated with an enhanced DNA-damage response and an augmented expression of rate-limiting DNA-repair proteins (MGMT in liver, XPD and XPG in skin), hinting at an increased DNA-repair capacity. Our data identify NIPP1 as a repressor of DNA repair and as a promising target for novel cancer prevention and treatment therapies.
Disruptive and avoidable: GDPR challenges to secondary research uses of data
Authors: Peloquin David , DiMaio Michael , Bierer Barbara , Barnes Mark
Published: March 2020

The advent of the European Union’s General Data Protection Regulation (GDPR) has posed several significant difficulties for the secondary research uses of data and associated biospecimens and has led to widespread unease within the international biobanking and databanking community. This disruption of research using personal data and associated biospecimens has gone largely unremarked in the professional literature, including in a recent account of GDPR’s relationship to biobanking practices published in this journal, which instead advocated even more stringent, and in our view, unnecessary restrictions on research uses of banked data and materials. In this article, we describe challenges that GDPR has posed for biobanks and databanks and for researchers who use those banked resources for secondary research. We discuss the limitations inherent in the few pathways that GDPR makes available for secondary research, given that such pathways rely upon complex and varied laws of individual European Union member states. We advocate mitigation of these difficulties through regulatory guidance in order to allow important scientific research to continue.
Nr2e3 is a genetic modifier that rescues retinal degeneration and promotes homeostasis in multiple models of retinitis pigmentosa
Authors: Li Sujun , Datta Shyamtanu , Brabbit Emily , Love Zoe , Woytowicz Victoria , Flattery Kyle , Capri Jessica , Yao Katie , Wu Siqi , Imboden Michael , Upadhyay Arun , Arumugham Rasappa , Thoreson Wallace B. , DeAngelis Margaret M. , Haider Neena B.
Published: March 2020

Recent advances in viral vector engineering, as well as an increased understanding of the cellular and molecular mechanism of retinal diseases, have led to the development of novel gene therapy approaches. Furthermore, ease of accessibility and ocular immune privilege makes the retina an ideal target for gene therapies. In this study, the nuclear hormone receptor gene Nr2e3 was evaluated for efficacy as broad-spectrum therapy to attenuate early to intermediate stages of retinal degeneration in five unique mouse models of retinitis pigmentosa (RP). RP is a group of heterogenic inherited retinal diseases associated with over 150 gene mutations, affecting over 1.5 million individuals worldwide. RP varies in age of onset, severity, and rate of progression. In addition, ~40% of RP patients cannot be genetically diagnosed, confounding the ability to develop personalized RP therapies. Remarkably, Nr2e3 administered therapy resulted in reduced retinal degeneration as observed by increase in photoreceptor cells, improved electroretinogram, and a dramatic molecular reset of key transcription factors and associated gene networks. These therapeutic effects improved retinal homeostasis in diseased tissue. Results of this study provide evidence that Nr2e3 can serve as a broad-spectrum therapy to treat multiple forms of RP.
Single-cell analysis of human ovarian cortex identifies distinct cell populations but no oogonial stem cells
Authors: Wagner Magdalena , Yoshihara Masahito , Douagi Iyadh , Damdimopoulos Anastasios , Panula Sarita , Petropoulos Sophie , Lu Haojiang , Pettersson Karin , Palm Kerstin , Katayama Shintaro , Hovatta Outi , Kere Juha , Lanner Fredrik , Damdimopoulou Pauliina
Published: March 2020

The human ovary orchestrates sex hormone production and undergoes monthly structural changes to release mature oocytes. The outer lining of the ovary (cortex) has a key role in defining fertility in women as it harbors the ovarian reserve. It has been postulated that putative oogonial stem cells exist in the ovarian cortex and that these can be captured by DDX4 antibody isolation. Here, we report single-cell transcriptomes and cell surface antigen profiles of over 24,000 cells from high quality ovarian cortex samples from 21 patients. Our data identify transcriptional profiles of six main cell types; oocytes, granulosa cells, immune cells, endothelial cells, perivascular cells, and stromal cells. Cells captured by DDX4 antibody are perivascular cells, not oogonial stem cells. Our data do not support the existence of germline stem cells in adult human ovaries, thereby reinforcing the dogma of a limited ovarian reserve.
The special considerations of gene therapy for mitochondrial diseases
Authors: Slone Jesse , Huang Taosheng
Published: March 2020

The recent success of gene therapy across multiple clinical trials has inspired a great deal of hope regarding the treatment of previously intractable genetic diseases. This optimism has been extended to the prospect of gene therapy for mitochondrial disorders, which are not only particularly severe but also difficult to treat. However, this hope must be tempered by the reality of the mitochondrial organelle, which possesses specific biological properties that complicate genetic manipulation. In this perspective, we will discuss some of these complicating factors, including the unique pathways used to express and import mitochondrial proteins. We will also present some ways in which these challenges can be overcome by genetic manipulation strategies tailored specifically for mitochondrial diseases.
Advancing electrodeionization with conductive ionomer binders that immobilize ion-exchange resin particles into porous wafer substrates
Authors: Palakkal Varada Menon , Valentino Lauren , Lei Qi , Kole Subarna , Lin Yupo J. , Arges Christopher G.
Published: March 2020

Electrodeionization (EDI) is an electrically driven separations technology that employs ion-exchange membranes and resin particles. Deionization occurs under the influence of an applied electric field, facilitating continuous regeneration of the resins and supplementing ionic conductivity. While EDI is commercially used for ultrapure water production, material innovation is required for improving desalination performance and energy efficiency for treating alternative water supplies. This work reports a new class of ion-exchange resin-wafers (RWs) fabricated with ion-conductive binders that exhibit exceptional ionic conductivities—a 3–5-fold improvement over conventional RWs that contain a non-ionic polyethylene binder. Incorporation into an EDI stack (RW-EDI) resulted in an increased desalination rate and reduced energy expenditure compared to the conventional RWs. The water-splitting phenomenon was also investigated in the RW in an external experimental setup in this work. Overall, this work demonstrates that ohmic resistances can be substantially curtailed with ionomer binder RWs at dilute salt concentrations.
Author Correction: A global database for metacommunity ecology, integrating species, traits, environment and space
Authors: Jeliazkov Alienor , Mijatovic Darko , Chantepie Stéphane , Andrew Nigel , Arlettaz Raphaël , Barbaro Luc , Barsoum Nadia , Bartonova Alena , Belskaya Elena , Bonada Núria , Brind’Amour Anik , Carvalho Rodrigo , Castro Helena , Chmura Damian , Choler Philippe , Chong-Seng Karen , Cleary Daniel , Cormont Anouk , Cornwell William , de Campos Ramiro , de Voogd Nicole , Doledec Sylvain , Drew Joshua , Dziock Frank , Eallonardo Anthony , Edgar Melanie J. , Farneda Fábio , Hernandez Domingo Flores , Frenette-Dussault Cédric , Fried Guillaume , Gallardo Belinda , Gibb Heloise , Gonçalves-Souza Thiago , Higuti Janet , Humbert Jean-Yves , Krasnov Boris R. , Saux Eric Le , Lindo Zoe , Lopez-Baucells Adria , Lowe Elizabeth , Marteinsdottir Bryndis , Martens Koen , Meffert Peter , Mellado-Díaz Andres , Menz Myles H. M. , Meyer Christoph F. J. , Miranda Julia Ramos , Mouillot David , Ossola Alessandro , Pakeman Robin , Pavoine Sandrine , Pekin Burak , Pino Joan , Pocheville Arnaud , Pomati Francesco , Poschlod Peter , Prentice Honor C. , Purschke Oliver , Raevel Valerie , Reitalu Triin , Renema Willem , Ribera Ignacio , Robinson Natalie , Robroek Bjorn , Rocha Ricardo , Shieh Sen-Her , Spake Rebecca , Staniaszek-Kik Monika , Stanko Michal , Tejerina-Garro Francisco Leonardo , Braak Cajo ter , Urban Mark C. , Klink Roel van , Villéger Sébastien , Wegman Ruut , Westgate Martin J. , Wolff Jonas , Żarnowiec Jan , Zolotarev Maxim , Chase Jonathan M.
Published: March 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The unique expression profile of FAM19A1 in the mouse brain and its association with hyperactivity, long-term memory and fear acquisition
Authors: Yong Hyo Jeong , Ha Nui , Cho Eun Bee , Yun Seongsik , Kim Hyun , Hwang Jong-Ik , Seong Jae Young
Published: March 2020

Neurodevelopment and mature brain function are spatiotemporally regulated by various cytokines and chemokines. The chemokine-like neuropeptide FAM19A1 is a member of family with sequence similarity 19 (FAM19), which is predominantly expressed in the brain. Its highly conserved amino acid sequence among vertebrates suggests that FAM19A1 may play important physiological roles in neurodevelopment and brain function. Here we used a LacZ reporter gene system to map the expression pattern of the FAM19A1 gene in the mouse brain. The FAM19A1 expression was observed in several brain regions starting during embryonic brain development. As the brain matured, the FAM19A1 expression was detected in the pyramidal cells of cortical layers 2/3 and 5 and in several limbic areas, including the hippocampus and the amygdala. FAM19A1-deficient mice were used to evaluate the physiological contribution of FAM19A1 to various brain functions. In behavior analysis, FAM19A1-deficient mice exhibited several abnormal behaviors, including hyperactive locomotor behavior, long-term memory deficits and fear acquisition failure. These findings provide insight into the potential contributions of FAM19A1 to neurodevelopment and mature brain function.
Comparison Of Mechanical And Chemical Nanocellulose As Additives To Reinforce Recycled Cardboard
Authors: Sanchez-Salvador Jose Luis , Balea Ana , Monte M. Concepción , Negro Carlos , Miller Meaghan , Olson James , Blanco Angeles
Published: March 2020

Recycling cycles cause a decrease in mechanical paper properties due to cellulose fiber degradation. The use of cellulose micro/nanofibers (CMF/CNF) to reinforce paper strength has been well studied, although it has been found to have negative effects on drainage. However, the application of CMF/CNF as paper reinforcement is affected by the nanocellulose type. Thus in this study mechanical and chemical treatments in CNF production were compared. Old corrugated container (OCC) pulp used to produce recycled cartonboard was reinforced with 1) CMF from never-dried northern bleached softwood kraft pulp (NBSK) highly refined in a 16-inch low consistency refiner at 1200 rpm and 25 kW of net power; and 2) CNF from NBSK pulp treated by TEMPO-mediated oxidation and homogenization at 600 bars. CMF/CNF and OCC were pulped at the same time and handsheets formed with cationic starch (CS) as retention system. Mechanical, drainage and flocculation properties were evaluated and compared. Data were also compared with other sources of TEMPO CNF. Results show an improvement in mechanical properties, drainage and flocculation when OCC is reinforced with CMF obtained with LCR. Therefore, high fibrillation was not necessary to improve mechanical paper or cardboard properties.
Dietary prebiotics alter novel microbial dependent fecal metabolites that improve sleep
Authors: Thompson Robert S. , Vargas Fernando , Dorrestein Pieter C. , Chichlowski Maciej , Berg Brian M. , Fleshner Monika
Published: March 2020

Dietary prebiotics produce favorable changes in the commensal gut microbiome and reduce host vulnerability to stress-induced disruptions in complex behaviors such as sleep. The mechanisms for how prebiotics modulate stress physiology remain unclear; however, emerging evidence suggests that gut microbes and their metabolites may play a role. This study tested if stress and/or dietary prebiotics (Test diet) alter the fecal metabolome; and explored if these changes were related to sleep and/or gut microbial alpha diversity. Male F344 rats on either Test or Control diet were instrumented for electroencephalography biotelemetry measures of sleep/wake. After 5 weeks on diet, rats were either stressed or remained in home cages. Based on untargeted mass spectrometry and 16S rRNA gene sequencing, both stress and Test diet altered the fecal metabolome/microbiome. In addition, Test diet prevented the stress-induced reduction in microbial alpha diversity based on PD_Whole_Tree, which has been previously published. Network propagation analysis revealed that stress increased members of the neuroactive steroidal pregnane molecular family; and that Test diet reduced this effect. We also discovered links between sleep, alpha diversity, and pyrimidine, secondary bile acid, and neuroactive glucocorticoid/pregnanolone-type steroidal metabolites. These results reveal novel microbial-dependent metabolites that may modulate stress physiology and sleep.
PET imaging of medulloblastoma with an 18F-labeled tryptophan analogue in a transgenic mouse model
Authors: Xin Yangchun , Yue Xuyi , Li Hua , Li Zhiqin , Cai Hancheng , Choudhary Arabinda K. , Zhang Shaohui , Chugani Diane C. , Langhans Sigrid A.
Published: March 2020

In vivo positron emission tomography (PET) imaging is a key modality to evaluate disease status of brain tumors. In recent years, tremendous efforts have been made in developing PET imaging methods for pediatric brain tumors. Carbon-11 labelled tryptophan derivatives are feasible as PET imaging probes in brain tumor patients with activation of the kynurenine pathway, but the short half-life of carbon-11 limits its application. Using a transgenic mouse model for the sonic hedgehog (Shh) subgroup of medulloblastoma, here we evaluated the potential of the newly developed 1-(2-[18F]fluoroethyl)-L-tryptophan (1-L-[18F]FETrp) as a PET imaging probe for this common malignant pediatric brain tumor. 1-L-[18F]FETrp was synthesized on a PETCHEM automatic synthesizer with good chemical and radiochemical purities and enantiomeric excess values. Imaging was performed in tumor-bearing Smo/Smo medulloblastoma mice with constitutive actvation of the Smoothened (Smo) receptor using a PerkinElmer G4 PET-X-Ray scanner. Medulloblastoma showed significant and specific accumulation of 1-L-[18F]FETrp. 1-L-[18F]FETrp also showed significantly higher tumor uptake than its D-enantiomer, 1-D-[18F]FETrp. The uptake of 1-L-[18F]FETrp in the normal brain tissue was low, suggesting that 1-L-[18F]FETrp may prove a valuable PET imaging probe for the Shh subgroup of medulloblastoma and possibly other pediatric and adult brain tumors.
Serum proteomics of active tuberculosis patients and contacts reveals unique processes activated during Mycobacterium tuberculosis infection
Authors: Mateos Jesús , Estévez Olivia , González-Fernández África , Anibarro Luis , Pallarés Ángeles , Reljic Rajko , Mussá Tufária , Gomes-Maueia Cremildo , Nguilichane Artur , Gallardo José M. , Medina Isabel , Carrera Mónica
Published: March 2020

Tuberculosis (TB) is the most lethal infection among infectious diseases. The specific aim of this study was to establish panels of serum protein biomarkers representative of active TB patients and their household contacts who were either infected (LTBI) or uninfected (EMI-TB Discovery Cohort, Pontevedra Region, Spain). A TMT (Tamdem mass tags) 10plex-based quantitative proteomics study was performed in quintuplicate containing a total of 15 individual serum samples per group. Peptides were analyzed in an LC-Orbitrap Elite platform, and raw data were processed using Proteome Discoverer 2.1. A total of 418 proteins were quantified. The specific protein signature of active TB patients was characterized by an accumulation of proteins related to complement activation, inflammation and modulation of immune response and also by a decrease of a small subset of proteins, including apolipoprotein A and serotransferrin, indicating the importance of lipid transport and iron assimilation in the progression of the disease. This signature was verified by the targeted measurement of selected candidates in a second cohort (EMI-TB Verification Cohort, Maputo Region, Mozambique) by ELISA and nephelometry techniques. These findings will aid our understanding of the complex metabolic processes associated with TB progression from LTBI to active disease.
The activation of BAFF/APRIL system in spleen and lymph nodes of Plasmodium falciparum infected patients
Authors: Dechkhajorn Wilanee , Benjathummarak Surachet , Glaharn Supattra , Chaisri Urai , Viriyavejakul Parnpen , Maneerat Yaowapa
Published: March 2020

Previous studies have reported activation of the B cell-activating factor (BAFF)/a proliferation-inducing ligand (APRIL) system in T independent immunity against malaria infection. Plasmodium falciparum (P. falciparum) infected animal model is not feasible. Therefore, little is known about the occurrence of BAFF/APRIL system and changes in falciparum lymphoid tissues. This study aimed to investigate the expression of BAFF/APRIL system components in lymphoid tissues from P. falciparum infected patients. Spleen and lymph node samples from 14 patients were collected at autopsy. Normal spleens and bacterially infected tonsils served as controls. The protein and/or mRNA expression of BAFF/APRIL and their cognate receptors, BAFF-R, TACI and BCMA, were determined by immunohistochemistry and RT-qPCR, respectively. The spleens of the patients exhibited significantly higher BAFF-R protein expression than normal spleens. Although without appropriate control, BCMA protein was markedly observed only in the lymph nodes. BAFF and BCMA mRNA levels were also significantly elevated in the spleen tissues of the patients compared with normal spleens. The overall BAFF-R protein levels in the lymphoid tissues of the patients correlated positively with parasitaemia. These findings are the first to confirm that BAFF/APRIL system activation in lymphoid tissues and is positively correlated with the parasitaemia levels in falciparum malaria.
Modification of radiosensitivity by Curcumin in human pancreatic cancer cell lines
Authors: Schwarz Katharina , Dobiasch Sophie , Nguyen Lily , Schilling Daniela , Combs Stephanie E.
Published: March 2020

Pancreatic cancer is one of the most aggressive malignancies and is characterized by a low 5-year survival rate, a broad genetic diversity and a high resistance to conventional therapies. As a result, novel therapeutic agents to improve the current situation are needed urgently. Curcumin, a polyphenolic colorant derived from Curcuma longa root, showed pleiotropic influences on cellular pathways in vitro and amongst others anti-cancer properties including sensitization of tumor cells to chemo- and radiation-therapy. In this study, we evaluated the impact of Curcumin on the radiosensitivity of the established human pancreatic cancer cell lines Panc-1 and MiaPaCa-2 in vitro. In contrast to MiaPaCa-2 cells, we found a significant radiosensitization by Curcumin in the more radioresistant Panc-1 cells, possibly caused by cell cycle arrest in the most radiation-sensitive G2/M-phase at the time of irradiation. Furthermore, a significant enhancement of radiation-induced apoptosis, DNA-double-strand breaks and G2/M-arrest after curcumin treatment was observed in both cell lines. These in vitro findings suggest that especially patients with more radioresistant tumors could benefit from a radiation-concomitant, phytotherapeutic therapy with Curcumin.
Assessment of trace metal alterations in the blood, cerebrospinal fluid and tissue samples of patients with malignant brain tumors
Authors: Stojsavljević Aleksandar , Vujotić Ljiljana , Rovčanin Branislav , Borković-Mitić Slavica , Gavrović-Jankulović Marija , Manojlović Dragan
Published: March 2020

The pathogenesis of malignant brain tumors (MBTs) should be better understood due to the evident association between prolonged exposure to metals and increased risk of MBTs. The present research aimed to find trace metals that could contribute to the pathogenesis of MBTs. Essential trace elements (Mn, Co, Zn, Cu, Se) and relevant toxic metals (Al, Ni, As, Sr, Cd, Ce, Pt, Pb, U) in the serum, cell fraction (CF), cerebrospinal fluid (CSF) and cancerous tissue (CT) samples of MBT patients were analyzed. The results were compared with sex- and age-matched control groups. For the first time, this research showed that elemental profiles of serum, CF, CSF and CT samples in MBT patients were significantly altered compared to the appropriate controls, as well as that higher contents of trace elements (particularly Mn, Se, and Pb) could be involved in the pathogenesis of MBTs. However, the most noticeable change found was the elevated U content, indicating its considerable role as a major cerebral discriminator of the presence/absence of MBTs. The U/Se ratio could be considered as an appropriate blood marker in diagnostic MBT evaluation. The reported results could contribute to better understanding of the poorly understood pathogenesis of MBTs. Furthermore, the reported results could highlight a molecular basis for the pathophysiological changes caused by the hazardous effects of trace metals on brain homeostasis.
A multilayer temporal network model for STD spreading accounting for permanent and casual partners
Authors: Vajdi Aram , Juher David , Saldaña Joan , Scoglio Caterina
Published: March 2020

Sexually transmitted diseases (STD) modeling has used contact networks to study the spreading of pathogens. Recent findings have stressed the increasing role of casual partners, often enabled by online dating applications. We study the Susceptible-Infected-Susceptible (SIS) epidemic model –appropriate for STDs– over a two-layer network aimed to account for the effect of casual partners in the spreading of STDs. In this novel model, individuals have a set of steady partnerships (links in layer 1). At certain rates, every individual can switch between active and inactive states and, while active, it establishes casual partnerships with some probability with active neighbors in layer 2 (whose links can be thought as potential casual partnerships). Individuals that are not engaged in casual partnerships are classified as inactive, and the transitions between active and inactive states are independent of their infectious state. We use mean-field equations as well as stochastic simulations to derive the epidemic threshold, which decreases substantially with the addition of the second layer. Interestingly, for a given expected number of casual partnerships, which depends on the probabilities of being active, this threshold turns out to depend on the duration of casual partnerships: the longer they are, the lower the threshold.
Automatic human identification based on dental X-ray radiographs using computer vision
Authors: Heinrich Andreas , Güttler Felix V. , Schenkl Sebastian , Wagner Rebecca , Teichgräber Ulf K.-M.
Published: March 2020

A person may be identified by comparison between ante- and post-mortem dental panoramic radiographs (DPR). However, it is difficult to find reference material if the person is unknown. This is often the case when victims of crime or mass disaster are found. Computer vision can be a helpful solution to automate the finding of reference material in a large database of images. The purpose of the present study was to improve the automated identification of unknown individuals by comparison of ante- and post-mortem DPR using computer vision. The study includes 61,545 DPRs from 33,206 patients, acquired between October 2006 and June 2018. The matching process is based on the Speeded Up Robust Features (SURF) algorithm to find unique corresponding points between two DPRs (unknown person and database entry). The number of matching points found is an indicator for identification. All 43 individuals (100%) were successfully identified by comparison with the content of the feature database. The experimental setup was designed to identify unknown persons based on their DPR using an automatic algorithm system. The proposed tool is able to filter large databases with many entries of potentially matching partners. This identification method is suitable even if dental characteristics were removed or added in the past.
Anterior relapse or posterior drift after intraoral vertical ramus osteotomy
Authors: Rokutanda Satoshi , Yamada Shin-Ichi , Yanamoto Souichi , Sakamoto Hiroshi , Furukawa Kohei , Rokutanda Hiromi , Yoshimi Tomoko , Nakamura Takuya , Morita Yukiko , Yoshida Noriaki , Umeda Masahiro
Published: March 2020

This study aimed to evaluate the factors contributing to postoperative anterior relapse or posterior drift of the distal segment after intraoral vertical ramus osteotomy. A retrospective cohort study was conducted which included 31 patients who underwent setback surgery for mandibular prognathism by the intraoral vertical ramus osteotomy technique. Uni- and multivariate analyses were performed to determine the association of potential explanatory variables (sex, age, magnitude of setback, differences in setback magnitude between sides (right/left), duration of splint use, Angle’s classification of malocclusion, mandibular angle, and tightness of occlusion of the molars) with positional changes in the distal segment. The setback magnitude was only significant factor affecting (P = 0.015) for posterior drift, with significant posterior in setback magnitudes of less than 7.25 mm. Posterior drift after intraoral vertical ramus osteotomy is less likely if setback magnitude exceeds 7.25 mm. For setbacks less than 7.25 mm, posterior drift should either be carefully corrected postoperatively, or an alternative surgical technique should be used. The setback magnitude showed a significant association with the risk of posterior drift following intraoral vertical ramus osteotomy, and the determined cut-off value may serve as a predictor for postoperative outcomes.
Effects of engineered aluminum and nickel oxide nanoparticles on the growth and antioxidant defense systems of Nigella arvensis L.
Authors: Chahardoli Azam , Karimi Naser , Ma Xingmao , Qalekhani Farshad
Published: March 2020

The effects of different concentrations (0, 50,100, 1000 and 2500 mg/L) of engineered aluminum and nickel oxide nanoparticles (Al2O3 and NiO NPs) on plant growth, oxidative stress and antioxidant activities in the hydroponically grown tissues of Nigella arvensis L. were investigated. The plant biomass was significantly increased under 50 and 100 mg/L of Al2O3 NPs or 50 mg/L of NiO NPs treatment, but was significantly decreased at higher concentrations of these nanoparticles. Assays of several enzymatic antioxidants such as ascorbate peroxidase (APX), catalase (CAT), superoxide dismutase (SOD) and peroxidase (POD) in roots and shoots indicate a general increase of activities after exposure to 50–2,500 mg/L of Al2O3 NPs and NiO NPs. The results are corroborated by an increased 2,2-diphenyl-1-picryl hydrazyl (DPPH) scavenging activity, total antioxidant capacity, total reducing power, total iridoids content, total saponin content, and total phenolic content in treated plants by Al2O3 NPs compared to the control plants. By contrast, the antioxidant activities, formation of secondary metabolites, and other related physiological parameters such as the total antioxidant capacity, DPPH scavenging activity and total saponin content were inhibited after the concentration of NiO NPs was increased to 100 mg/L. Total phenols, saponins, iridoids and total antioxidant content and DPPH scavenging activity were increased in plants treated with 100–2,500 mg/L Al2O3 NPs. Overall, these two nanoparticles displayed different effects in the shoots and roots of plants at different concentrations, which may be due to their physico-chemical properties.
Enzymatic decontamination of paraoxon-ethyl limits long-term effects in planarians
Authors: Poirier Laetitia , Plener Laure , Daudé David , Chabrière Eric
Published: March 2020

Organophosphorus compounds (OP) are highly toxic molecules used as insecticides that inhibit cholinesterase enzymes involved in neuronal transmission. The intensive use of OP for vector control and agriculture has led to environmental pollutions responsible for severe intoxications and putative long-term effects on humans and wild animals. Many in vivo models were studied over the years to assess OP acute toxicity, but the long-term effects are poorly documented. Planarian, a freshwater flatworm having a cholinergic system, has emerged as a new original model for addressing both toxicity and developmental perturbations. We used Schmidtea mediterranea planarians to evaluate long-term effects of paraoxon-ethyl at two sublethal concentrations over three generations. Toxicity, developmental perturbations and disruption of behavior were rapidly observed and higher sensitivity to paraoxon-ethyl of next generations was noticed suggesting that low insecticide doses can induce transgenerational effects. With the view of limiting OP poisoning, SsoPox, an hyperthermostable enzyme issued from the archaea Saccharolobus solfataricus, was used to degrade paraoxon-ethyl prior to planarian exposure. The degradation products, although not lethal to the worms, were found to decrease cholinesterase activities for the last generation of planarians and to induce abnormalities albeit in lower proportion than insecticides.
Constraints on the Structure of the Shallow Crust in Central Italy from Geophysical Log Data
Authors: Montone Paola , Mariucci Maria Teresa
Published: March 2020

To better define the seismic velocities of the shallow crust in central Italy, in the area affected by the 1997 Colfiorito, 2009 L’Aquila and 2016–2018 Amatrice–Norcia seismic sequences, we selected all deep wells with available sonic logs from the Apennine belt to the related Adriatic foredeep. Sonic logs are among the most important in situ measurements of rock properties and provide a reliable image of physical conditions at depth. By analysing the wave train transit times, we inferred the P-wave velocity within depth intervals displaying homogeneous sonic log properties, and estimated the rock density by applying an empirical relationship between the sonic velocity and density in sedimentary rocks. We compared these results with the main litho-stratigraphic units in stratigraphic profiles of the wells. From the density estimates, we inferred the trends of the vertical stress magnitude in the belt, eastern front and foredeep geodynamic domains. This work is a contribution to better interpretation of physical conditions at depth and provides data that can be applied to define more complete seismological, gravity and magnetic models. We provide data uncertainties that must be considered to ensure proper use of data and to evaluate the spatial resolution of the models derived from those data.
Clinical Relevance of the serum CTLA-4 in Cats with Mammary Carcinoma
Authors: Urbano Ana Catarina , Nascimento Catarina , Soares Maria , Correia Jorge , Ferreira Fernando
Published: March 2020

Cytotoxic T lymphocyte associated antigen 4 (CTLA-4) serves an important role in breast cancer progression, which has led to the development of novel immunotherapies aimed at blocking tumor immune evasion. Although feline mammary carcinoma is increasingly recognized as a valuable cancer model, no studies on CTLA-4 function had been conducted in this species. The serum CTLA-4, TNF-α and IL-6 levels of 57 female cats with mammary carcinoma were determined by ELISA, and immunohistochemistry was performed to evaluate CTLA-4 and FoxP3 expression in tumor cells and interstitial lymphocytes. The results obtained show that serum CTLA-4 levels are increased in cats with mammary carcinoma (P = 0.022), showing an association with a number of clinicopathological features: smaller tumor size, P < 0.001; absence of tumor necrosis, P < 0.001; non-basal status, P < 0.02 and HER-2-positive status. Additionally, a strong positive correlation was found between serum CTLA-4 levels and serum TNF-α (R = 0.88, P < 0.001) and IL-6 levels (R = 0.72, P < 0.001). Concerning the CTLA-4 and FoxP3 expression, although detected in both interstitial lymphocytes and tumor cells, a positive association was found only between interstitial CTLA-4 and FoxP3 expressions (R = 0.387, P = 0.01), which is negatively associated with the serum CTLA-4 levels (P = 0.03). These findings provide a preliminary step in the characterization of immune profiles in feline mammary carcinoma, uncovering a molecular rationale for targeted therapy with CTLA-4 pathway inhibitors. Finally, by strengthening the hypothesis of an immunomodulatory role for this regulator, we further validate the utility of spontaneous feline mammary carcinoma as a model for human breast cancer.
DNA fragmentation index (DFI) as a measure of sperm quality and fertility in mice
Authors: Li Ming-Wen , Lloyd K. C. Kent
Published: March 2020

Although thousands of genetically modified mouse strains have been cryopreserved by sperm freezing, the likelihood of cryorecovery success cannot be accurately predicted using conventional sperm parameters. The objective of the present study was to assess the extent to which measurement of a sperm DNA fragmentation index (DFI) can predict sperm quality and fertility after cryopreservation. Using a modified TUNEL assay, we measured and correlated the DFI of frozen-thawed sperm from 83 unique mutant mouse strains with sperm count, motility and morphology. We observed a linear inverse correlation between sperm DFI and sperm morphology and motility. Further, sperm DFI was significantly higher from males with low sperm counts compared to males with normal sperm counts (P < 0.0001). Additionally, we found that viable embryos derived using sperm from males with high DFI (62.7 ± 7.2% for IVF and 73.3 ± 8.1% for ICSI) failed to litter after embryo transfer compared to embryos from males with low DFI (20.4 ± 7.9% for IVF and 28.1 ± 10.7 for ICSI). This study reveals that measurement of DFI provides a simple, informative and reliable measure of sperm quality and can accurately predict male mouse fertility.
A bacterial cell factory converting glucose into scyllo-inositol, a therapeutic agent for Alzheimer’s disease
Authors: Michon Christophe , Kang Choong-Min , Karpenko Sophia , Tanaka Kosei , Ishikawa Shu , Yoshida Ken-ichi
Published: March 2020

A rare stereoisomer of inositol, scyllo-inositol, is a therapeutic agent that has shown potential efficacy in preventing Alzheimer’s disease. Mycobacterium tuberculosis ino1 encoding myo-inositol-1-phosphate (MI1P) synthase (MI1PS) was introduced into Bacillus subtilis to convert glucose-6-phosphate (G6P) into MI1P. We found that inactivation of pbuE elevated intracellular concentrations of NAD+·NADH as an essential cofactor of MI1PS and was required to activate MI1PS. MI1P thus produced was dephosphorylated into myo-inositol by an intrinsic inositol monophosphatase, YktC, which was subsequently isomerized into scyllo-inositol via a previously established artificial pathway involving two inositol dehydrogenases, IolG and IolW. In addition, both glcP and glcK were overexpressed to feed more G6P and accelerate scyllo-inositol production. Consequently, a B. subtilis cell factory was demonstrated to produce 2 g L−1scyllo-inositol from 20 g L−1 glucose. This cell factory provides an inexpensive way to produce scyllo-inositol, which will help us to challenge the growing problem of Alzheimer’s disease in our aging society.
Unravelling three-dimensional adsorption geometries of PbSe nanocrystal monolayers at a liquid-air interface
Authors: Geuchies Jaco J. , Soligno Giuseppe , Geraffy Ellenor , Hendrikx Cedric P. , Overbeek Carlo van , Montanarella Federico , Slot Marlou R. , Konovalov Oleg V. , Petukhov Andrei V. , Vanmaekelbergh Daniel
Published: March 2020

The adsorption, self-organization and oriented attachment of PbSe nanocrystals (NCs) at liquid-air interfaces has led to remarkable nanocrystal superlattices with atomic order and a superimposed nanoscale geometry. Earlier studies examined the NC self-organization at the suspension/air interface with time-resolved in-situ X-ray scattering. Upon continuous evaporation of the solvent, the NC interfacial layer will finally contact the (ethylene glycol) liquid substrate on which the suspension was casted. In order to obtain structural information on the NC organization at this stage of the process, we examined the ethylene glycol/NC interface in detail for PbSe NCs of different sizes, combining in-situ grazing-incidence small-and-wide-angle X-ray scattering (GISAXS/GIWAXS), X-ray reflectivity (XRR) and analytical calculations of the adsorption geometry of these NCs. Here, we observe in-situ three characteristic adsorption geometries varying with the NC size. Based on the experimental evidence and simulations, we reveal fully three-dimensional arrangements of PbSe nanocrystals at the ethylene glycol-air interface with and without the presence of rest amounts of toluene.