bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomics of osmoregulatory responses in threespine stickleback gills
Authors: Li Johnathon , Kültz Dietmar
Published: March 2020

The gill proteome of threespine sticklebacks (Gasterosteus aculeatus) differs greatly in populations that inhabit diverse environments characterized by different temperature, salinity, food availability, parasites, and other parameters. To assess the contribution of a specific environmental parameter to such differences it is necessary to isolate its effects from those of other parameters. In this study the effect of environmental salinity on the gill proteome ofG. aculeatuswas isolated in controlled mesocosm experiments. Salinity-dependent changes in the gill proteome were analyzed by LC/MSMS data-independent acquisition (DIA) and Skyline. Relative abundances of 1691 proteins representing the molecular phenotype of stickleback gills were quantified using previously developed MSMS spectral and assay libraries in combination with DIA quantitative proteomics. General stress responses were distinguished from osmoregulatory protein abundance changes by their consistent occurrence during both hypo- and hyper-osmotic salinity stress in six separate mesocosm experiments. If the abundance of a protein was consistently regulated in opposite directions by hyper- versus hypo-osmotic salinity stress, then it was considered an osmoregulatory protein. In contrast, if protein abundance was consistently increased irrespective of whether salinity was increased or decreased, then it was considered a general stress response protein. KEGG pathway analysis revealed that the salivary secretion, inositol phosphate metabolism, valine, leucine and isoleucine degradation, citrate cycle, oxidative phosphorylation, and corresponding endocrine and extracellular signaling pathways contain most of the osmoregulatory gill proteins whose abundance is directly proportional to environmental salinity. Most proteins that were inversely correlated with salinity map to KEGG pathways that represent proteostasis, immunity, and related intracellular signaling processes. General stress response proteins represent fatty and amino acid degradation, purine metabolism, focal adhesion, mRNA surveillance, phagosome, endocytosis, and associated intracellular signaling KEGG pathways. These results demonstrate thatG. aculeatusresponds to salinity changes by adjusting osmoregulatory mechanisms that are distinct from transient general stress responses to control compatible osmolyte synthesis, transepithelial ion transport, and oxidative energy metabolism. Furthermore, this study establishes salinity as a key factor for causing the regulation of numerous proteins and KEGG pathways with established functions in proteostasis, immunity, and tissue remodeling. We conclude that the corresponding osmoregulatory gill proteins and KEGG pathways represent molecular phenotypes that promote transepithelial ion transport, cellular osmoregulation, and gill epithelial remodeling to adjust gill function to environmental salinity.
Sorry, we’re open: Golden Open Access and inequality in the natural sciences
Authors: Gray Russell J
Published: March 2020

Global Open Access (GOA) journals make research more accessible and therefore more citable; however, the publication fees associated with GOA journals can be costly and therefore not a viable option for many researchers seeking high-impact publication outlets. In this study, I collect metadata from 237 open-access natural science journals and analyze them in terms of Article Processing Charges (APC), Impact Factor (IF), Eigen Factor (EF), citability, and country of publisher. The results of this study provide evidence that with IF, EF, and citability all increase as APC increases, and each of these metrics are higher in publishers from developed countries in comparison to developing countries. Implications of these trends are discussed in regards to natural sciences and inequality within the global scientific community.
A high-coverage Neandertal genome from Chagyrskaya Cave
Authors: Mafessoni Fabrizio , Grote Steffi , de Filippo Cesare , Slon Viviane , Kolobova Kseniya A. , Viola Bence , Markin Sergey V. , Chintalapati Manjusha , Peyrégne Stephane , Skov Laurits , Skoglund Pontus , Krivoshapkin Andrey I. , Derevianko Anatoly P. , Meyer Matthias , Kelso Janet , Peter Benjamin , Prüfer Kay , Pääbo Svante
Published: March 2020

We sequenced the genome of a Neandertal from Chagyrskaya Cave in the Altai Mountains, Russia, to 27-fold genomic coverage. We estimate that this individual lived ~80,000 years ago and was more closely related to Neandertals in western Eurasia (1,2) than to Neandertals who lived earlier in Denisova Cave (3), which is located about 100 km away. About 12.9% of theChagyrskayagenome is spanned by homozygous regions that are between 2.5 and 10 centiMorgans (cM) long. This is consistent with that Siberian Neandertals lived in relatively isolated populations of less than 60 individuals. In contrast, a Neandertal from Europe, a Denisovan from the Altai Mountains and ancient modern humans seem to have lived in populations of larger sizes. The availability of three Neandertal genomes of high quality allows a first view of genetic features that were unique to Neandertals and that are likely to have been at high frequency among them. We find that genes highly expressed in the striatum in the basal ganglia of the brain carry more amino acid-changing substitutions than genes expressed elsewhere in the brain, suggesting that the striatum may have evolved unique functions in Neandertals.
Hypoxic response regulators RHY-1 and EGL-9/PHD promote longevity through a VHL-1 independent transcriptional response
Authors: Kruempel Joseph , Miller Hillary A. , Schaller Megan L. , Fretz Abrielle , Howington Marshall , Sarker Marjana , Huang Shijiao , Leiser Scott F.
Published: March 2020

HIF-1-mediated adaptation to changes in oxygen availability is a critical aspect of healthy physiology. HIF is regulated by a conserved mechanism whereby EGLN/PHD family members hydroxylate HIF in an oxygen-dependent manner, targeting it for ubiquitination by Von-Hippel-Lindau (VHL) family members, leading to its proteasomal degradation. The activity of the onlyC. elegansPHD family member, EGL-9, is also regulated by a hydrogen sulfide sensing cysteine-synthetase-like protein, CYSL-1, which is, in turn, regulated by RHY-1/acyltransferase. Over the last decade multiple seminal studies have established a role for the hypoxic response in regulating longevity, with mutations invhl-1substantially extendingC. eleganslifespan through a HIF-1-dependent mechanism. However, studies on other components of the hypoxic signaling pathway that similarly stabilize HIF-1 have shown more mixed results, suggesting that mutations inegl-9andrhy-1frequently fail to extend lifespan. Here, we show thategl-9andrhy-1mutants suppress the long-lived phenotype ofvhl-1mutants. We also show that RNAi ofrhy-1extends lifespan of wild-type worms while decreasing lifespan ofvhl-1mutant worms. We further identify VHL-1-independent gene expression changes mediated by EGL-9 and RHY-1 and find that a subset of these genes contributes to longevity regulation. The resulting data suggest that changes in HIF-1 activity derived by interactions with EGL-9 likely contribute greatly to its role in regulation of longevity.
Dopamine D1 receptor signalling in dyskinetic Parkinsonian rats revealed by fiber photometry using FRET-based biosensors
Authors: Jones-Tabah Jace , Mohammad Hanan , Hadj-Youssef Shadi , Kim Lucy , Martin Ryan D. , Benaliouad Faïza , Tanny Jason C. , Clarke Paul B.S. , Hébert Terence E.
Published: March 2020

Like many G protein-coupled receptors (GPCRs), the signalling pathways regulated by the dopamine D1 receptor (D1R) are dynamic, cell-type specific, and can change in response to disease or drug exposures. In striatal neurons, the D1R activates cAMP/protein kinase A (PKA) signalling. However, in Parkinson’s disease (PD), alterations in this pathway lead to activation of extracellular regulated kinases (ERK1/2), contributing to L-DOPA-induced dyskinesia (LID). In order to detect D1R activationin vivoand to study the progressive dysregulation of D1R signalling in PD and LID, we developed ratiometric fiber-photometry with Förster resonance energy transfer (FRET) biosensors and optically detected PKA and ERK1/2 signalling in freely moving rats. We show that in Parkinsonian animals, D1R signalling through PKA and ERK1/2 is sensitized, but that following chronic treatment with L-DOPA, these pathways become partially desensitized while concurrently D1R activation leads to greater induction of dyskinesia.
Multi-Channel Whole-Head OPM-MEG: Helmet Design and a Comparison with a Conventional System
Authors: Hill Ryan M. , Boto Elena , Rea Molly , Holmes Niall , Leggett James , Coles Laurence A. , Papastavrou Manolis , Everton Sarah , Hunt Benjamin A.E. , Sims Dominic , Osborne James , Shah Vishal , Bowtell Richard , Brookes Matthew J.
Published: March 2020

Magnetoencephalography (MEG) is a powerful technique for functional neuroimaging, offering a non-invasive window on brain electrophysiology. MEG systems have traditionally been based on cryogenic sensors which detect the small extracranial magnetic fields generated by synchronised current in neuronal assemblies, however such systems have fundamental limitations. In recent years quantum-enabled devices, called optically-pumped magnetometers (OPMs), have promised to lift those restrictions, offering an adaptable, motion-robust MEG device, with improved data quality, at reduced cost. However, OPM-MEG remains a nascent technology, and whilst viable systems exist, most employ small numbers of sensors sited above targeted brain regions. Here, building on previous work, we construct a wearable OPM-MEG system with ‘whole-head’ coverage based upon commercially available OPMs, and test its capabilities to measure alpha, beta and gamma oscillations. We design two methods for OPM mounting; a flexible (EEG-like) cap and rigid (additively-manufactured) helmet. Whilst both designs allow for high quality data to be collected, we argue that the rigid helmet offers a more robust option with significant advantages for reconstruction of field data into 3D images of changes in neuronal current. Using repeat measurements in two participants, we show signal detection for our device to be highly robust. Moreover, via application of source-space modelling, we show that, despite having 5 times fewer sensors, our system exhibits comparable performance to an established cryogenic MEG device. While significant challenges still remain, these developments provide further evidence that OPM-MEG is likely to facilitate a step change for functional neuroimaging.

HIGHLIGHTS

A 49-channel whole-head OPM-MEG system is constructed

System evaluated via repeat measurements of alpha, beta and gamma oscillations

Two OPM-helmet designs are contrasted, a flexible (EEG-like) cap and a rigid helmet

The rigid helmet offers significant advantages for a viable OPM-MEG device

49-channel OPM-MEG offers performance comparable to established cryogenic devices
Maternal cannabis vapor exposure causes long-term alterations in emotional reactivity, social behavior, and behavioral flexibility in offspring
Authors: Weimar Halle V. , Wright Hayden R. , Warrick Collin R. , Brown Amanda M. , Lugo Janelle M. , Freels Timothy G. , McLaughlin Ryan J.
Published: March 2020

The use of cannabis during pregnancy is a growing public health concern. As more states implement legislation permitting recreational cannabis use, there is an urgent need to better understand its impact on fetal neurodevelopment and its long-term effects in exposed offspring. Studies examining effects of prenatal cannabis exposure typically employ injections of synthetic cannabinoids or isolated cannabis constituents that may not accurately model cannabis use in human populations. To address this limitation, we have developed a novel e-cigarette technology-based system to deliver vaporized cannabis extracts to pregnant Long Evans rats. We used this model to determine effects of prenatal cannabis exposure on emotional, social, and cognitive endpoints of male and female offspring during early development and into adulthood. Dams were exposed to cannabis vapor (CANTHC: 400 mg/ml), vehicle vapor (VEH), or no vapor (AIR) twice daily during mating and gestation. Offspring exposed to CANTHCand VEH showed reduced weight gain relative to AIR offspring prior to weaning. CANTHCoffspring made more isolation-induced ultrasonic vocalizations (USVs) on postnatal day 6 (P6) relative to VEH-exposed offspring, which is indicative of increased emotional reactivity. Male CANTHCoffspring engaged in fewer social investigation behaviors than VEH-exposed male offspring during a social play test on P26. In adulthood, CANTHC-exposed offspring spent less time exploring the open arms of the elevated plus maze and exhibited dose-dependent deficits in behavioral flexibility in an attentional set-shifting task relative to AIR controls. These data collectively indicate that prenatal cannabis exposure causes enduring effects on the behavioral profile of offspring.
A ‘one-two punch’ therapy strategy to target chemoresistance in estrogen receptor positive breast cancer
Authors: Chi Feng , Liu Jiayi , Brady Samuel W. , Cosgrove Patrick A. , Nath Aritro , McQuerry Jasmine A. , Majumdar Sumana , Moos Philip J. , Chang Jeffrey T. , Kahn Michael , Bild Andrea H.
Published: March 2020

Background

Cancer cell phenotypes evolve over the course of a tumor’s treatment. The phenotypes that emerge and disappear over time will be specific to each drug regimen and type of cancer. Chemotherapy remains one of the most common and effective treatments for metastatic breast cancer patients; however, resistance to chemotherapy inevitably emerges. Cancer chemotherapy treatment regimens are not designed to target emerging chemo-resistance, despite its clear importance in progressive cancer. This study focuses on finding sequential treatment strategies that target acquired chemo-resistant states and optimize response to chemotherapy.

Methods

In this study, we used heterogeneous tumor samples from patients to identify subclones resistant to chemotherapy. Using flow cytometry for stem cell markers and DNA sequencing to define subclonal population changes, we measured the enrichment of cancer stem cell-like (CSL) phenotypes in subclones that survive chemotherapy. We then analyzed breast cancer patient tumor organoids and cell line acquisition of CSL traits following chemotherapy, as well as the ability of different drugs to reverse acquired resistance, using flow cytometry, mammosphere assays, and single cell RNA-sequencing analysis.

Results

We show that in progressive estrogen receptor positive (ER+) metastatic breast cancer patients, resistant tumor subclones that emerge following chemotherapy have increased CSL abundance. Further, in vitro organoid growth of ER+ patient cancer cells also shows that chemotherapy treatment leads to increased abundance of ALDH+/CD44+ CSL cells. Chemotherapy induced CSL abundance is blocked by treatment with a pan-HDAC inhibitor, belinostat. Further, belinostat treatment diminished both mammosphere formation and size following chemotherapy, also indicating a decrease in progenitor CSL traits. HDAC inhibitors specific to class IIa (HDAC4, HDAC5) and IIb (HDAC6) were shown to primarily reverse the chemo-resistant CSL state. Single-cell RNA sequencing analysis with patient samples showed that HDAC targets and MYC signaling were promoted by chemotherapy and inhibited upon HDAC inhibitor treatment.

Conclusion

These findings indicate that HDAC inhibition can block chemotherapy-induced drug resistant phenotypes with ‘one-two punch’ strategy in refractory breast cancer cells.
Lgr5-mediated restraint of β-catenin is essential for B-lymphopoiesis and leukemia-initiation
Authors: Cosgun Kadriye Nehir , Robinson Mark E. , Deb Gauri , Yang Xin , Xiao Gang , Sadras Teresa , Lee Jaewoong , Chan Lai N. , Kume Kohei , Mangolini Maurizio , Winchester Janet , Chen Zhengshan , Yang Lu , Geng Huimin , Izraeli Shai , Song Joo , Chan Wing-Chung , Polson Andrew G. , Jumaa Hassan , Clevers Hans , Müschen Markus
Published: March 2020

Upon productive immunoglobulin gene rearrangement, expression of a functional pre-B cell receptor (pre-BCR) initiates positive selection of pre-B cells, clonal expansion and self-renewal1-2. Studying mechanisms driving this first wave of B-lymphopoiesis, we identified the G-protein coupled receptor Lgr5 as an essential initiator of positive selection. Lgr5 was extensively studied as determinant of stem cell populations in multiple tissues3-6, but not in B-cells. While undetectable throughout the hematopoietic system, positively selected pre-B cells were marked with a sharp peak of Lgr5 expression. Conditional deletion ofLgr5preceding the pre-BCR checkpoint induced negative selection and complete abortion of B-cell development. Proteomic studies ofLgr5-ablation revealed massive (>250-fold) accumulation of β-catenin and suppression of MYC.Lgr5-deficient pre-B cells fully recovered by concurrent β-catenin-deletion, demonstrating a central role of Lgr5-mediated restraint of β-catenin at the pre-BCR checkpoint. In other cell types, β-catenin/TCF4 complexes drive transcriptional activation of MYC7-9. Instead of TCF4, proximity-based interactome studies in pre-B cells identified the B-lymphoid transcription factors IKZF1 and IKZF310-11as β-catenin-binding partners, which had the opposite effect and caused transcriptional repression ofMYC. On positively selected pre-B cells, Lgr5 prevented accumulation of β-catenin and formation of complexes with IKZF1 and IKZF3, which relieved transcriptional repression of MYC. Activating β-catenin-mutations are common throughout all main types of cancer7-8, but were conspicuously absent in pre-B leukemia (B-ALL). Like pre-B cells, B-ALL cells were uniquely sensitive to genetic and pharmacological β-catenin hyperactivation, which recapitulated the effects ofLgr5-deletion and compromised colony formation and leukemia-initiation. A new LGR5 antibody-drug conjugate targeted leukemia-initiating cells in patient-derived B-ALL and achieved long-term disease-control. Likewise, small molecule hyperactivation of β-catenin selectively killed B-ALL but not other cell types. Hence, Lgr5-mediated restraint of β-catenin activation is essential for B-lymphopoiesis and revealed an unexpected vulnerability that can be leveraged for the treatment of drug-resistant B-ALL.
Mutant p53 suppresses innate immune signaling to promote tumorigenesis
Authors: Ghosh Monisankar , Saha Suchandrima , Bettke Julie , Nagar Rachana , Parrales Alejandro , Iwakuma Tomoo , van der Velden Adrianus W. M. , Martinez Luis A.
Published: March 2020

Mutations in the p53 tumor suppressor occur very frequently in human cancer. Often, such mutations lead to the constitutive overproduction of mutant p53 (mtp53) proteins, which can exert a cancer-promoting gain-of-function (GOF). We have identified a novel mechanism by which mtp53 controls both cell-autonomous and non-cell autonomous signaling to promote cancer cell survival and suppress tumor immune surveillance. Mtp53 interferes with the function of the cytoplasmic DNA sensing machinery, cGAS-STING-TBK1-IRF3, that controls the activation of the innate immune response. We find that mtp53, but not wildtype p53, binds to TANK binding protein kinase (TBK1) and inhibits both its basal and agonist-induced activity. The association of mtp53 with TBK1 prevents the formation of a trimeric complex between TBK1-STING-IRF3, which is required for activation, nuclear translocation and transcriptional activity of IRF3. Mtp53 knockdown restores TBK1 activity, resulting in the transcriptional induction of IRF3 target genes and IRF3-dependent apoptosis. Furthermore, inactivation of innate immune signaling by mtp53 alters cytokine production resulting in immune evasion. Restored TBK1 signaling was sufficient to bypass mtp53 and reactivate cell-autonomous and non-cell autonomous tumor control. Thus, overriding mtp53’s inhibition of this cytosolic DNA sensing pathway may ultimately lead to restored immune cell function and cancer cell eradication.
IRF8 Governs Tumor-Associated Macrophage Control of T Cell Exhaustion
Authors: Nixon Briana G. , Kuo Fengshen , Liu Ming , Capistrano Kristelle , Do Mytrang , Franklin Ruth A. , Wu Xiaodi , Kansler Emily R. , Srivastava Raghvendra M. , Purohit Tanaya A. , Sanchez Alejandro , Vuong Lynda , Krishna Chirag , Morse Herbert C. , Hsieh James J. , Chan Timothy A. , Murphy Kenneth M. , Moon James J. , Hakimi A. Ari , Li Ming O.
Published: March 2020

Tumor progression is associated with overstimulation of cytotoxic T lymphocytes (CTLs), resulting in a dysfunctional state of exhaustion. How T cell exhaustion is elicited in the tumor remains poorly understood. Here we show that tumor-associated macrophages (TAMs) present cancer cell antigen and induce CTL exhaustion through a gene expression program dependent on the transcription factor interferon regulatory factor-8 (IRF8). In a transgenic model of murine breast cancer, CTL priming was supported by IRF8-dependent dendritic cells; yet, CTL exhaustion required TAM expression of IRF8, and its ablation suppressed tumor growth. An analysis of the highly immune-infiltrated human renal cell carcinoma tumors revealed abundant TAMs that expressed IRF8 and were enriched for an IRF8 gene expression signature. The IRF8 signature co-segregated with T cell exhaustion markers and was negatively associated with long-term patient survival. Thus, CTL exhaustion is promoted by TAMs via IRF8, and this crosstalk may be disrupted in TAM-targeted therapies.
Selective packaging of mitochondrial proteins into extracellular vesicles prevents the release of mitochondrial DAMPs
Authors: Todkar Kiran , Chikhi Lilia , Desjardins Véronique , El-Mortada Firas , Pépin Geneviève , Germain Marc
Published: March 2020

Most cells constitutively secrete mitochondrial DNA and proteins in extracellular vesicles (EVs), small vesicles that allow the transfer of material between cells. While under pro-inflammatory conditions, this mitochondrial content can further enhance inflammation, its role in the absence of inflammation remains elusive. Here, we demonstrate that cells actively prevent the packaging of pro-inflammatory, oxidized mitochondrial proteins into EVs. Importantly, the distinction between material to be included into EVs and damaged mitochondrial content to be excluded was dependent on their selective targeting to one of two distinct Mitochondria-Derived Vesicles (MDVs) pathways, MDVs being small vesicles carrying material between mitochondria and other organelles. Sorting nexin 9 (Snx9)-dependent MDVs were required to target mitochondrial proteins into EVs, while the Parkinson’s disease related protein Parkin blocked this process by targeting damaged mitochondrial content to lysosomes. Our results thus provide important insight into the interplay between mitochondrial quality control mechanisms and mitochondria driven immune responses.
A mechanism to prevent transformation of the Whi3 mnemon into a prion
Authors: Lau Yasmin , Parfenova Iuliia , Saarikangas Juha , Nichols Richard A. , Barral Yves , Caudron Fabrice
Published: March 2020

In response to deceptive courtship, budding yeast cells escape pheromone induced cell cycle arrest through coalescence of the G1/S inhibitor Whi3 into a dominant inactive super-assembly. Strikingly, Whi3 super-assemblies remain stable over many cell cycles in the mother cells and are not passed on to the daughter cells. Thereby, Whi3 coalescence encodes memory, conferring to it the property of a mnemon (Whi3mnem), a protein which conformational change maintain a trait that is permanent in the mother cell but is not inherited by daughter cells. Mnemons share structural features with prions, which are self-templating protein conformations that are inherited by daughter cells. Yet, how the maintenance and asymmetric inheritance of Whi3mnemare achieved is unknown. Here, we report that Whi3mnemis closely associated with endoplasmic reticulum (ER) membranes and retained in the mother cell by the presence of lateral membrane diffusion barriers at the bud neck. Strikingly, barrier defects made Whi3mnempropagate in a mitotically stable manner, like a prion. Alike Whi3mnem, transformation of Whi3 into a prion required its poly-glutamine prion-like domain. Thus, we propose that Whi3mnemis in a self-templating state, lending temporal stability to the memory that it encodes, while its anchorage into the compartmentalized membranes of the ER ensures its confinement in the mother cell and prevents its infectious propagation. These results suggest that confined self-templating super-assembly is a powerful mechanism for the long-term encoding of information.
Optimization of mouse embryonic stem cell culture for organoid and chimeric mice production
Authors: Martin-Lemaitre Cécilie , Alcheikh Yara , Naumann Ronald , Honigmann Alf
Published: March 2020

In vitrostem cell culture is demanding in terms of manpower and media supplements. In recent years, new protocols have been developed to expand pluripotent embryonic stem cells in suspension culture, which greatly simplifies cell handling and scalability. However, it is still unclear how suspension culture protocols with different supplements affect pluripotency, cell homogeneity and cell differentiation compared to established adherent culture methods. Here we tested four different culture conditions for mouse embryonic stem cells (mESC) and quantified chimerism and germ line transmission as well asin vitrodifferentiation into three-dimensional neuro-epithelia. We found that suspension culture supplemented with CHIR99021/LIF offers the best compromise between culturing effort, robust pluripotency and cell homogeneity. Our work provides a guideline for simplifying mESC culture and should encourage more cell biology labs to use stem cell-based organoids as model systems.
Carbon ion dosimetry on a fluorescent nuclear track detector using widefield microscopy
Authors: Walsh Dietrich W.M. , Liew Hans , Schlegel Julian , Mairani Andrea , Abdollahi Amir , Niklas Martin
Published: March 2020

Fluorescent nuclear track detectors (FNTD) are solid-state dosimeters used in a wide range of dosimetric and biomedical applications in research worldwide. FNTDs are a core but currently underutilized dosimetry tool in the field of radiation biology which are inherently capable of visualizing the tracks of ions used in hadron therapy. The ions that traverse the FNTD deposit their energy according to their linear energy transfer (LET) and transform colour centres to form trackspots around their trajectory. These trackspots have fluorescent properties which can be visualized by fluorescence microscopy enabling a well-defined dosimetric readout with a spatial component indicating the trajectory of individual ions. The current method used to analyse the FNTDs is laser scanning confocal microscopy (LSM). LSM enables a precise localization of track spots in x, y and z however due to the scanning of the laser spot across the sample, requires a long time for large samples. This body of work conclusively shows for the first time that the readout of the trackspots present after 0.5 Gy carbon ion irradiation in the FNTD can be captured with a widefield microscope (WF). The WF readout of the FNTD is a factor ∼10 faster, for an area 2.97 times the size making the method nearly a factor 19 faster in track acquisition than LSM. The dramatic decrease in image acquisition time in WF presents an alternative to LSM in FNTD workflows which are limited by time, such as biomedical sensors which combine FNTDs with live cell imaging.
Surgery and Radioactive Iodine Therapeutic Strategy for Patients Greater than 60 Years of Age with Differentiated Thyroid Cancer
Authors: Tang Tao , Zhang Wei , Zhi Jingtai , Ruan Xianhui , Hu Linfei , Chen Xiaoyu , Wang Zhaohui , Zheng Xiangqian , Gao Ming
Published: March 2020

Purpose

The purpose of the current study was to determine whether older patients with differentiated thyroid cancer (DTC) who received surgical treatment had a better cause-specific survival (CSS) than patients who were recommended surgery, but declined, and whether patients who underwent post-operative RAI-131 therapy had an impact on CSS based on TNM staging and number of lymph node metastases for all total or near-total thyroidectomy patients.

Patients and Methods

All DTC patients information were obtained from the SEER*Stat 8.3.6 program, and only patients ≥ 60 years or older were considered. The patients were divided into two groups (underwent surgery and surgery recommend, but not performed). Furthermore, patients were grouped as follows: T4; N1b; M1; T1-3N0-1a; specific number of lymph node metastases; and total or near-total thyroidectomy.

Results

The 120-month cause-specific survival (CSS) rate of females and males showed a gradual declining trend from 60-64 to ≥80 years of age in the group that underwent surgery. The CSS rate of females and males showed a marked downward and irregular trend with an increase in age in the recommended, but no surgery group. Univariate analysis indicated that the surgery group had a higher 120-month CSS in females in most stages and males, compared with the no surgery group. RAI-131 therapy was associated with an improved 80-month CSS in T4/N1b/M1 females (P<0.0183) and males (P<0.0011). There was no CSS difference in females or males between the T1-3N0 and T1-3N1a patients. There was no statistical difference between the two subgroups.

Conclusions

Surgical treatment should be recommended for elderly DTC patients because surgery can lead to a better CSS. High-risk patients achieve a higher benefit-to-risk ratio with RAI-131 therapy. To avoid the adverse effects associated with RAI-131 therapy, a multidisciplinary discussion should be arranged for intermediate- and low-risk patients.
Consistency of superb microvascular imaging and contrast enhanced ultrasonography in detecting intraplaque neovascularization: a meta-analysis
Authors: Yang Fang , Wang Cong
Published: March 2020

This meta-analysis aimed to identify the consistency of superb microvascular imaging(SMI) and contrast-enhanced ultrasonography(CEUS) in detecting intraplaque neovascularization(IPN). We searched PubMed, Web of Science, Cochrane Library, CISCOM, and CBM databases without language restrictions. Meta-analysis was conducted using STATA version 15.1 software. We calculated the pooled Kappa index. Ten studies that met all inclusion criteria were included in this meta-analysis. A total of 608 carotid plaques were assessed through both SMI and CEUS. The pooled summary Kappa index was 0.743(95 % CI=0.696-0.790) with statistical significance(z= 31.14, p<0.01). We found no evidence for publication bias (t=-1.21, p=0.261). Our meta-analysis indicates that SMI and CEUS display a good consistency in detecting IPN of carotid plaque, that is to say SMI ultrasound maybe a promising alternative to CEUS for detecting IPN of carotid plaque.
Experimental production of anti-membrane bound variable surface glycoglycoprotein (anti-VSGm) antibodies forin vitroandin situimmunostaining of pathogenic African trypanosomes
Authors: Okwong-Oketch Reymick , Nsubuga Julius , Ayebare Peter , Nsadha Zachary , Lubega George William , Nanteza Ann
Published: March 2020

Background

The variant surface glycoprotein (VSG) of the African trypanosomes is the major membrane protein of the plasma membrane of the bloodstream stage of the parasite. African trypanosomiasis (sleeping sickness in humans and nagana in animals) is caused by the systemic infection of the host by several sub-species of the extracellular haemoflagellate protozoa under genus Trypanosoma. As a defense barrier against the host immune response, the entire surface of the bloodstream form of trypanosome is covered with densely packed molecules of VSG that determines the antigenic phenotype of the parasite. Variant surface glycoprotein has a C-terminal domain that is highly conserved in various species of trypanosomes.

Methods

The membrane bound VSG (VSGm) protein was prepared without denaturing the homologous region and by including numerous variable antigen types fromTrypanosoma brucei bruceiparasites. The purified VSGm native trypanosome protein was used to produce anti-VSGm immune sera in rabbits. The indirect immunofluorescence assay (IFA) was used to detect trypanosomes from mice blood, artificial culture media and cattle histological sections.

Results

The resultant immune sera were able to detect different strains and species of African trypanosomes fromin vivoandin situsources after immunostaining. Anti-VSGm antibodies also demonstrated a unique property to locate trypanosomes within the histological tissues even after the trypanosome’s morphology had been distorted.

Conclusion

The produced immune sera can be utilized for immunohistochemistry to detectTrypanosoma speciesin various fluids and tissues.

Author summary
Mitochondrial-Derived Compartments Facilitate Cellular Adaptation to Amino Acid Stress
Authors: Schuler Max-Hinderk , English Alyssa M. , Campbell Thane J. , Shaw Janet M. , Hughes Adam L.
Published: March 2020

Amino acids are essential building blocks of life. However, increasing evidence suggests that elevated amino acids cause cellular toxicity associated with numerous metabolic disorders. How cells cope with elevated amino acids remains poorly understood. Here, we show that a previously identified cellular structure, themitochondrial-derivedcompartment (MDC), is a dynamic, lumen-containing organelle that functions to protect cells from amino acid stress. In response to amino acid elevation, MDCs are generated from mitochondria, where they selectively sequester and remove Tom70, a surface receptor required for import of nutrient carriers of the SLC25 family. MDC formation is regulated by levels of mitochondrial carriers, and its activation by amino acids occurs simultaneously with removal of plasma membrane-localized transporters via the multi-vesicular body (MVB) pathway. Combined loss of MDC and MVB formation renders cells sensitive to elevated amino acids, suggesting these pathways operate as a coordinated network to protect cells from amino acid toxicity.
Development and validation of a transcriptional signature for the assessment of fibrosis in organs
Authors: Wang Bin , Chen Shiju , Qian Hongyan , Chen Rongjuan , He Yan , Zhang Xinwei , Xuan Jingxiu , Liu Yuan , Shi Guixiu
Published: March 2020

Background

Fibrosis in most organs has proven to be an critical factor related to high risk of morbidity and mortality, but an adequate assessment of fibrosis severity is still challenging. This study tried to evaluate fibrosis severity through a fibrosis transcriptional signature.

Methods

A fibrosis transcriptional signature was developed through an integrated analysis of multiple expression profiling datasets of human organs with fibrosis-related diseases. A fibrosis severity score for each sample was the calculated through gene set variation analysis (GSVA), and its role in evaluating fibrosis severity was then analyzed.

Results

Ten expression profiling datasets of human tissues with organ failure were integrated with robust rank aggregation method, and a fibrosis severity score consisting of 149 genes. Most of those included genes were involved in fibrogenic pathways. GSEA analysis revealed that fibrosis transcriptional signature was significantly enriched in the fibrogenic tissues. Additionally, we found that fibrosis transcriptional signature could effectively differentiate fibrosis tissues and non-fibrosis tissues.

Conclusion

This study developed an useful fibrosis transcriptional signature involved in fibrosis-related diseases. This fibrosis transcriptional signature is helpful in precisely evaluating the fibrosis severity in common organs at the transcriptional level.
Modelling the epidemic 2019-nCoV event in Italy: a preliminary note
Authors: Traini Marco Claudio , Caponi Carla , De Socio Giuseppe Vittorio
Published: March 2020

An analysis of the time evolution of the 2019-nCoV outbreak event in Italy is proposed and is based on the preliminary data at disposal (till March 11th, 2020) on one side, and on an epidemiological model recently used to describe the same epidemic event in the Wuhan region (February 2020) on the other side. The equations of the model include the description of compartments like Susceptible (S), exposed (E), infectious but not yet symptomatic (pre-symptomatic) (A), infectious with symptoms (I), hospitalized (H) and recovered (R). Further stratification includes quarantined susceptible (Sq), isolated exposed (Eq) and isolated infected (Iq) compartments. The equations are numerically solved for boundary (initial) conditions tuned on the Italian event. The rôle of quarantine is specifically emphasized and supports the strategies adopted providing a numerical description of the effects.
Sulfisoxazole does not inhibit the secretion of small extracellular vesicles
Authors: Fonseka Pamali , Chitti Sai V , Sanwlani Rahul , Mathivanan Suresh
Published: March 2020

Recently, the study by Im etal. focused on blocking the release of extracellular vesicles (EVs) by cancer cells, as a strategy to block metastasis, by deploying a drug repurposing screen. Upon screening the library of FDA approved drugs in breast cancer cellsin vitro, the authors reported the ability of the antibiotic Sulfisoxazole (SFX) in inhibiting EV biogenesis and secretion. SFX was also effective in reducing breast primary tumor burden and blocking metastasis in immunocompromised and immunocompetent mouse models. As we seek a compound to block EV biogenesis and secretion in our currentin vivostudies, we intended to use SFX and hence performedin vitrocharacterization as the first step. However, treatment of two cancer cells with SFX did not reduce the amount of EVs as reported by the authors.
The nutritional behavior of pregnant women attending antenatal classes and non-attendees
Authors: Ługowska Katarzyna , Kolanowski Wojciech
Published: March 2020

Purpose

The purpose of this study was to assess the nutritional behavior regarding the frequency of consumption of the main types of food by pregnant women attending antenatal classes in comparison to non-attendees.

Design/methodology/approach

A questionnaire survey was conducted in Poland among 200 women in the first pregnancy, 100 of whom were attending antenatal classes and 100 were non-attendees.

Findings

Women attending antenatal classes exhibited more favorable health-related nutritional behaviors in comparison with those not attending. Attendees eat more vegetables and milk products whereas non-attendees declared more processed meat and sweets consumption. Three-fourth of non-attendees and two-fourth of attendees considered their diet as good. It was also found that the level of physical activity of pregnant women attending antenatal classes was significantly higher than among those who did not attend such classes.

Research limitations/implications

A limitation of the study was that it took place in Poland and voices from women of other European countries as well as diverse ethnicities were not represented. In addition, women were interviewed only during their pregnancy, and therefore it was not possible to investigate women's nutritional behaviors after delivery.

Practical implications

This research shows clearly that attending antenatal classes may involve with a beneficial effect on the nutritional behavior of pregnant women. It is expected that once established healthy nutritional habits should be practiced further.

Originality/value

This research is the indication of the important role of antenatal classes in developing more favorable health-related dietary behavior expressed by the participants. To our knowledge in Poland, it is the first time that the nutritional behavior of pregnant women attending and not attending antenatal classes were examined and compared. So far in Poland, the extent and type of nutritional education received by pregnant women across antenatal care has not been examined. This research can contribute to a broader recognition of nutritional knowledge and practice of pregnant women important for the health of mother and her baby.
Barriers to Total Quality Management for sustainability in Indian organizations
Authors: Kumar Vimal , Verma Pratima , Mangla Sachin Kumar , Mishra Atul , Chowdhary Dababrata , Sung Chi Hsu , Lai Kuei Kuei
Published: March 2020

Purpose

The paper aims to identify key human and operational focused barriers to the implementation of Total Quality Management (TQM). It develops a comprehensive structural relationship between various barriers to successfully implement TQM for sustainability in Indian organizations.

Design/methodology/approach

With the help of expert opinions and extant literature review, we identified the case of TQM failure companies and barriers to implement TQM effectively. Interpretive Structural Modeling (ISM) and fuzzy MICMAC techniques are employed to develop a structural model and the identified barriers are categorized based on their dependence and driving power in the various categories.

Findings

From the intensive case analysis, we identify fourteen barriers that constrain the successful implementation of TQM. The findings also provide a hierarchy of barriers in which the absence of top management involvement and ineffective leadership are the human barriers having the highest dependence.

Research limitations/implications

The critical inputs show the implementation of TQM in the firms being more proactive and well prepared in the selected five companies. The study's emphasis on barriers will help organizations in implementing TQM for better sustainability in an organizational context.

Originality/value

In the successful implementation of TQM, barriers need to be identified because failure has often eliminated the organizations from the market. Thus, TQM is the source of strength to achieve higher productivity, profitability, and sustainable business performance. The barriers must be identified to improve organizational performance to contribute to sustainable development.
Benchmarking contractors’ financial performance: case study of Singapore
Authors: Zhang Zhe , Koh Zhi Ye , Ling Florence
Published: March 2020

Purpose

This study aims to develop benchmarks of the financial performance of contractors and a decision support tool for evaluation, selection and appointment of contractors. The financial benchmarks allow contractors to know where they are relative to the best-performing contractors, and they can then take steps to improve their own performance. The decision support tool helps clients to decide which contractor should be awarded the project.

Design/methodology/approach

Financial data between 2013 and 2015 of 44 Singapore-based contractors were acquired from a Singaporean public agency. Benchmarks for Z-score and financial ratios were developed. A decision tree for evaluating contractors was constructed.

Findings

This study found that between 57% and 64% of contractors stayed in the financially healthy zone from 2013 to 2015. Ratios related to financial liabilities are relatively bad compared with international standards.

Research limitations/implications

The limitation is that the data is obtained from a cross-sectional survey of contractors’ financial performance in Singapore over a three-year period. Regarding the finding that ratios relating to financial liabilities are weak, the implication is that contractors need to reduce their financial liabilities to achieve a good solvency profile. Contractors may use the benchmarks to check their financial performances relative to that of their competitors. To reduce financial risks, project clients may use these benchmarks to examine contractors’ financial performance.

Originality/value

This study provides benchmarks for contractors and clients to examine the financial performance of contractors in Singapore. A decision tree is provided to aid clients in making decisions on which contractors to appoint.
Vulnerability of multinational corporation knowledge network facing resource loss
Authors: Su Jiafu , Bai Qun , Sindakis Stavros , Zhang Xuefeng , Yang Tao
Published: March 2020

Purpose

The vulnerability of multinational corporation (MNC) knowledge network is one of the major causes for the failure and even the death of MNCs in the fierce global market competition. Employee turnover and knowledge loss are the triggers for the MNC knowledge network vulnerability and a matter of serious concern in the evolution and development of MNC knowledge network. The purpose of this work is to propose a valid and quantitative measurement method to investigate the influence of employee loss and knowledge loss on the vulnerability of MNC knowledge network.

Design/methodology/approach

MNC knowledge network is inherently a heterogeneous network where there are mainly two types of units: employees and their knowledge. Therefore, this paper establishes a weighted super-network model for MNC knowledge network to depict its heterogeneous composition. On the basis of the weighted MNC knowledge super-network, the static and dynamic vulnerability measurement methods are further proposed to investigate and evaluate MNC knowledge network vulnerability.

Findings

A real case is given to illustrate the applicability of the proposed weighted MNC knowledge super-network model and the network vulnerability measurement methods. The results show the super-network model proposed in this paper can effectively embody the complex features of MNC knowledge network, and the vulnerability measurement methods can effectively investigate the influence of employee loss and knowledge loss on network vulnerability.

Originality/value

From the perspective of super-network, researchers and practitioners can get a more systematic and deeper understanding of the MNC knowledge network and its human and knowledge resource constitute which are vital for the evolution and development of MNC. Moreover, the MNC knowledge network vulnerability measurement methods can effectively measure and analyze the influence of resource loss on network vulnerability, which can provide a helpful decision support for monitoring and managing of MNC knowledge network vulnerability to reduce its adverse effects.