bluuebunny/crossref_metadata_2025 huggingface dataset:
Value, confidence, deliberation: a functional partition of the medial prefrontal cortex demonstrated across rating and choice tasks
Authors: Clairis N. , Pessiglione M.
Published: September 2020

Deciding about courses of action involves minimizing costs and maximizing benefits. Decision neuroscience studies have implicated both the ventral and dorsal medial prefrontal cortex (vmPFC and dmPFC) in signaling goal value and action cost, but the precise functional role of these regions is still a matter of debate. Here, we suggest a more general functional partition that applies not only to decisions but also to judgments about goal value (expected reward) and action cost (expected effort). In this conceptual framework, cognitive representations related to options (reward value and effort cost) are dissociated from metacognitive representations (confidence and deliberation) related to solving the task (providing a judgment or making a choice). Thus, we used an original approach with the goal of identifying consistencies across several preference tasks, from likeability ratings to binary decisions involving both attribute integration and option comparison. FMRI results confirmed the vmPFC as a generic valuation system, its activity increasing with reward value and decreasing with effort cost. In contrast, more dorsal regions were not concerned with the valuation of options but with metacognitive variables, confidence level being reflected in mPFC activity and deliberation time in dmPFC activity. Thus, there was a dissociation between the effort attached to choice options (represented in the vmPFC) and the effort invested in deliberation (represented in the dmPFC), the latter being expressed in pupil dilation. More generally, assessing commonalities across preference tasks might help reaching a unified view of the neural mechanisms underlying the cost/benefit tradeoffs that drive human behavior.
Perceptual rivalry with vibrotactile stimuli
Authors: Darki Farzaneh , Rankin James
Published: September 2020

In perceptual rivalry, ambiguous sensory information leads to dynamic changes in the perceptual interpretation of fixed stimuli. This phenomenon occurs when participants receive sensory stimuli that support two or more distinct interpretations; this results in spontaneous alternations between possible perceptual interpretations. Perceptual rivalry has been widely studied across different sensory modalities including vision, audition and, to a limited extent, in the tactile domain. Common features of perceptual rivalry across various ambiguous visual and auditory paradigms characterise the randomness of switching times and their dependence on input strength manipulations (Levelt’s propositions). It is still unclear whether general characteristics of perceptual rivalry are preserved with tactile stimuli. This study aims to introduce a simple tactile stimulus capable of generating perceptual rivalry and explores whether general features of perceptual rivalry from other modalities extend to the tactile domain.
DeepInsight-FS: Selecting features for non-image data using convolutional neural network
Authors: Sharma Alok , Lysenko Artem , Boroevich Keith A , Vans Edwin , Tsunoda Tatsuhiko
Published: September 2020

Identifying smaller element or gene subsets from biological or other data types is an essential step in discovering underlying mechanisms. Statistical machine learning methods have played a key role in revealing gene subsets. However, growing data complexity is pushing the limits of these techniques. A review of the recent literature shows that arranging elements by similarity in image-form for a convolutional neural network (CNN) improves classification performance over treating them individually. Expanding on this, here we show a pipeline, DeepInsight-FS, to uncover gene subsets of clinical relevance. DeepInsight-FS converts non-image samples into image-form and performs element selection via CNN. To our knowledge, this is the first approach to employ CNN for element or gene selection on non-image data. A real world application of DeepInsight-FS to publicly available cancer data identified gene sets with significant overlap to several cancer-associated pathways suggesting the potential of this method to discover biomedically meaningful connections.
Anterior Nucleus of Thalamus Gates Progression of Mesial Temporal Seizures by Modulating Thalamocortical Synchrony
Authors: Chaitanya Ganne , Ilyas Adeel , Toth Emilia , Pizarro Diana , Riley Kristen , Pati Sandipan
Published: September 2020

The anterior nucleus of the thalamus (ANT) mediates cortical-subcortical interactions between the limbic system and is hypothesized to facilitate the early organization of temporal lobe seizures. We set out to investigate the dynamic changes in synchronization parameters between the seizure onset zone (SOZ) and ANT during seizure stages (pre-onset to post-termination) in seven patients (n=26 seizures) with drug-resistant nonlesional temporal lobe epilepsy. Using local field potentials recorded directly from the limbic system and the ANT during stereoelectroencephalography, we confirm that the onset of mesial temporal lobe seizure is associated with increased thalamocortical network excitability and phase-amplitude coupling. The increase in thalamocortical phase synchronization preceded seizure onset, thereby suggesting that the early organization of temporal lobe seizures involves the integration of the ANT within the epileptic network. Towards seizure termination, there is a significant decrease in thalamic excitability, thalamocortical synchronization, and decoupling, thereby suggesting a breakdown in thalamocortical connectivity. A higher disease burden is significantly correlated with increased synchronization between the ANT and epileptic networks. Collectively, the results elucidate mechanistic insights and provide the temporal architecture of thalamocortical interactions that can be targeted in the rational designing of closed-loop seizure abortive interventions.

Highlights

Anterior nucleus of thalamus is coactivated at the onset of temporal lobe seizures

Increase thalamocortical synchronization and excitability is observed at seizure onset

Seizure termination is characterized by a breakdown in thalamocortical connectivity

Increased seizure burden affects thalamocortical synchronization
Cardiac overexpression of microRNA-7 is associated with adverse cardiac remodeling
Authors: Gupta Manveen K , Sahu Anita , Wang Xi , Martelli Elizabeth E. , Stenson Kate , Witherow Conner , Naga Prasad Sathyamangla V.
Published: September 2020

Role of microRNA-7 (miRNA-7) in targeting Epidermal growth factor receptor (EGFR/ERBB) family is known in dividing cancer cells while less is known about its role in terminally differentiated cardiac cells. We generated transgenic (Tg) mice with cardiomyocyte-specific overexpression of miRNA-7 to determine its role in regulating cardiac function. Despite similar survival, expression of miRNA-7 results in cardiac dilation as measured by echocardiography, instead of age-based cardiac hypertrophy observed in littermate controls. In contrast to the classical adaptive hypertrophy in response to TAC, miRNA-7 Tg mice directly undergo cardiac dilation post-TAC that is associated with increased fibrosis. Interestingly, significant loss in ERBB2 expression was observed in cardiomyocytes with no changes in ERBB1 (EGFR). Gene ontology and cellular component analysis using the cardiac proteomics data showed significant reduction in mitochondrial membrane integrity reflecting the differential enrichment/loss of proteins in miRNA-7 Tg mice compared to littermate controls. Consistently, electron microscopy showed that miRNA-7 Tg hearts had disorganized and rounded mitochondrial morphology indicating mitochondrial dysfunction. These findings show that expression of miRNA-7 uniquely results in cardiac dilation instead of adaptive hypertrophic response to cardiac stress providing insights on adverse remodeling in physiology and pathology.
YY1 cistrome analysis uncovers an essential requirement of the YY1:BRD4-PFKP regulatory axis for promoting tumorigenesis of castration-resistant prostate cancer
Authors: Xu Chenxi , Tsai Yi-Hsuan , Galbo Phillip , Gong Weida , Storey Aaron J. , Xu Yuemei , Byrum Stephanie D. , Whang Young E. , Parker Joel S. , Mackintosh Samuel G. , Edmondson Ricky D. , Tackett Alan J. , Huang Jiaoti , Zheng Deyou , Earp H. Shelton , Wang Gang Greg , Cai Ling
Published: September 2020

Castration-resistant prostate cancer (CRPC) is a terminal disease, demanding a better understanding of its pathogenesis. Targeted therapy needs to be developed for CRPC due to its heterogeneity and resistance to current treatments. Here, through cistrome study of YY1, a transcription factor significantly overexpressed during prostate cancer progression, we identify a YY1-PFKP axis to be essential for CRPC tumorigenesis. Depletion of YY1 in independent CRPC models dramatically reduced tumor cell growthin vitroand delayed oncogenic progressionin vivo. Importantly, YY1 functions as a master regulator of prostate tumor metabolism including the Warburg effect and mitochondria respiration. Loss-of-function and rescue studies further reveals a mechanistic underpinning in which YY1 directly binds and trans-activatesPFKP, a gene encoding the rate-limiting enzyme for glycolysis, significantly contributing to the YY1-enforced oncogenic phenotypes such as enhanced tumor cell glycolysis and malignant growth. Additionally, a vast majority of gene-regulatory element in advanced prostate cancer cells are bound by YY1, lending a support for its role as a master regulator of prostate cancer progression. YY1 interactome studies point to bromodomain-containing coactivators in prostate cancer, which act as functional partners of YY1 to potentiate YY1-related target gene activation. Altogether, this study unveils an unexplored YY1:BRD4-PFKP oncogenic axis operating in advanced prostate cancer with implications for therapy.
Identification of trans-AT polyketide clusters in two marine bacteria reveals cryptic similarities between distinct symbiosis factors
Authors: Kačar Dina , Cañedo Librada M , Rodríguez Pilar , Gonzalez Elena , Galán Beatriz , Schleissner Carmen , Leopold-Messer Stefan , Piel Jörn , Cuevas Carmen , de la Calle Fernando , García José L.
Published: September 2020

Glutaramide-containing polyketides are known as potent antitumoral and antimetastatic agents. However, the associated gene clusters have only been identified and studied in a fewStreptomycesproducers and soleBurkholderia gladiolisymbiont. The new glutaramide-family polyketides, denominated sesbanimides D, E and F along with the previously known sesbanimide A and C, were isolated from two marine alphaproteobacteriaStappia indicaPHM037 andLabrenzia aggregataPHM038. Structures of the isolated compounds were elucidated based on 1D and 2D homo and heteronuclear NMR analyses and ESI-MS spectrometry. All compounds exhibited strong antitumor activity in lung, breast and colorectal cancer cell lines. Subsequent whole genome sequencing and genome mining revealed the presence of thetrans-AT PKS gene cluster responsible for the sesbanimide biosynthesis, described assbncluster, and the sesbanimide modular assembly is proposed. Interestingly, numerous homologous orphan gene clusters were localized in distantly related bacteria and used as comparative genomic assets for a more global characterization ofsbnlike-clusters. Strikingly, the modular architecture of downstream mixed type PKS/NRPS, SbnQ, revealed high similarity to PedH in pederin and Lab13 in labrenzin gene clusters, although those clusters are responsible for the production of structurally completely different molecules. The unexpected presence of SbnQ homologs in unrelated polyketide gene clusters across phylogenetically distant bacteria, raises intriguing questions about the evolutionary relationship between glutaramide-like and pederin-like pathways, as well as the functionality of their synthetic products.

Significance

Glutaramide-containing polyketides are still a largely understudied group of polyketides, produced mainly by the generaStreptomyces, with a great potential for antitumor drug production. Here, we describe genomes of two cultivable marine bacteria,Stappia indicaPHM037 andLabrenzia aggregataPHM038, producers of the cytotoxic glutaramide-family polyketides sesbanimide A and C with chemical elucidation of newly identified analogs D, E and F. Genome mining revealedtrans-AT PKS gene cluster responsible for sesbanimide biosynthesis. Although there are numerous homologous gene clusters present in remarkably different bacteria, this is the first time that the biosynthesis product has been reported. The comparative genome analysis reveals stunning, cryptic evolutionary relationship between sesbanimides, glutaramides fromStreptomycesspp. and the pederin-family gene clusters.
Graph representation forecasting of patient’s medical conditions: towards a digital twin
Authors: Barbiero Pietro , Viñas Torné Ramon , Lió Pietro
Published: September 2020

Abstract

Objective

Modern medicine needs to shift from a wait and react, curative discipline to a preventative, interdisciplinary science aiming at providing personalised, systemic and precise treatment plans to patients. The aim of this work is to present how the integration of machine learning approaches with mechanistic computational modelling could yield a reliable infrastructure to run probabilistic simulations where the entire organism is considered as a whole.

Methods

We propose a general framework that composes advanced AI approaches and integrates mathematical modelling in order to provide a panoramic view over current and future physiological conditions. The proposed architecture is based on a graph neural network (GNNs) forecasting clinically relevant endpoints (such as blood pressure) and a generative adversarial network (GANs) providing a proof of concept of transcriptomic integrability.

Results

We show the results of the investigation of pathological effects of overexpression of ACE2 across different signalling pathways in multiple tissues on cardiovascular functions. We provide a proof of concept of integrating a large set of composable clinical models using molecular data to drive local and global clinical parameters and derive future trajectories representing the evolution of the physiological state of the patient.

Significance

We argue that the graph representation of a computational patient has potential to solve important technological challenges in integrating multiscale computational modelling with AI. We believe that this work represents a step forward towards a healthcare digital twin.
Shared residual risk of childhood undernutrition indicators in Malawi. An application of shared spatial component model
Authors: Ngwira Alfred
Published: September 2020

Many studies have looked at the residual risk of the specific child undenutrition indicators. This study aimed at mapping the shared risk of two of the undernutrition indicators. The shared spatial component model was fitted to two of the child undernutrition indicators using 5066 child records of the 2015 Malawi demographic health survey data. The spatial components were modelled by the convolution prior, with the structured components being assigned the conditional autoregressive distribution. The southern region is at the greatest risk of having stunting and wasting, wasting and underweight, as compared to the central and northern region. The shared risk of stunting and underweight is randomly distributed. Interventions to reduce the shared risk of child undernutrition should focus on the southern region and a little bit in the central region, and attention should be on addressing the issue of overpopulation and effects of climate change.
Msp1/ATAD1 restores mitochondrial function in Zellweger Spectrum Disease
Authors: Nuebel Esther , Morgan Jeffrey T , Fogarty Sarah , Winter Jacob M , Lettlova Sandra , Berg Jordan A , Chen Yu-Chan , Kidwell Chelsea U , Maschek J Alan , Clowers Katie J , Argyriou Catherine , Chen Lingxiao , Wittig Ilka , Cox James E , Roh-Johnson Minna , Braverman Nancy , Steinberg Steven J , Gygi Steven P , Rutter Jared
Published: September 2020

Peroxisomal Biogenesis Disorders (PBDs) are a class of inherited metabolic disorders with profound neurological and other phenotypes. The most severe PBDs are caused by mutations in peroxin genes, which result in nonfunctional peroxisomes typically through impaired protein import. In order to better understand the molecular causes of Zellweger Spectrum Disease (ZSD) -the most severe PBDs -, we investigated the fate of peroxisomal mRNAs and proteins in ZSD model systems. We found that loss of peroxisomal import has no effect on peroxin mRNA expression or translational efficiency. Instead, peroxin proteins—still produced at high levels— aberrantly accumulate on the mitochondrial membrane, impairing respiration and ATP generation. Finally, we rescued mitochondrial function in fibroblasts derived from human patients with ZSD by overexpressing ATAD1, an AAA-ATPase that functions in mitochondrial quality control. These findings might provide a new focus of PBD therapies in supporting quality control pathways that protect mitochondrial function.
Design of Biologically Active Binary Protein 2D Materials
Authors: Ben-Sasson Ariel J. , Watson Joseph , Sheffler William , Johnson Matthew Camp , Bittleston Alice , Somasundaram Logeshwaran , Decarreau Justin , Jiao Fang , Chen Jiajun , Drabek Andrew A. , Jarrett Sanchez M. , Kollman Justin M. , Blacklow Stephen C. , De Yoreo James J , Ruohola-Baker Hannele , Derivery Emmanuel , Baker David
Published: September 2020

Proteins that assemble into ordered two-dimensional arrays such as S-layers1,2and designed analogues3–5have intrigued bioengineers,6,7but with the exception of a single lattice formed through non-rigid template streptavidin linkers,8they are constituted from just one protein component. For modulating assembly dynamics and incorporating more complex functionality, materials composed of two components would have considerable advantages.9–12Here we describe a computational method to generate de-novo binary 2D non-covalent co-assemblies by designing rigid asymmetric interfaces between two distinct protein dihedral building-blocks. The designed array components are soluble at mM concentrations, but when combined at nM concentrations, rapidly assemble into nearly-crystalline micrometer-scale p6m arrays nearly identical to the computational design model in vitro and in cells without the need of a two-dimensional support. Because the material is designed from the ground up, the components can be readily functionalized, and their symmetry reconfigured, enabling formation of ligand arrays with distinguishable surfaces to drive extensive receptor clustering, downstream protein recruitment, and signaling. Using quantitative microscopy we show that arrays assembled on living cells have component stoichiometry and likely structure similar to arrays formed in vitro, suggesting that our material can impose order onto fundamentally disordered substrates like cell membranes. We find further that in sharp contrast to previously characterized cell surface receptor binding assemblies such as antibodies and nanocages, which are rapidly endocytosed, large arrays assembled at the cell surface suppress endocytosis in a tunable manner, with potential therapeutic relevance for extending receptor engagement and immune evasion. Our work paves the way towards synthetic cell biology, where a new generation of multi-protein macroscale materials is designed to modulate cell responses and reshape synthetic and living systems.

One Sentence Summary

Co-assembling binary 2D protein crystals enables robust formation of complex large scale ordered biologically active materials
Life cycle process dependencies of positive-sense RNA viruses suggest strategies for inhibiting productive cellular infection
Authors: Chhajer Harsh , Rizvi Vaseef A. , Roy Rahul
Published: September 2020

Life cycle processes of positive-strand (+)RNA viruses are broadly conserved across families, yet they employ different life cycle strategies to grow in the cell. Using a generalized dynamical model for intracellular (+)ssRNA virus growth, we decipher these life cycle determinants and their dependencies for several viruses and parse the effect of viral mutations and host cell permissivity. We show that Poliovirus employs rapid replication and virus assembly whereas Japanese Encephalitis virus leverages its higher rate of translation and efficient cellular reorganization compared to Hepatitis C virus. Stochastic simulations of the model demonstrate infection extinction if all seeding viral RNA degrade before establishing robust replication. The probability of productive cellular infection is affected by virus-host processes, defined by early life cycle events and viral seeding. Synergy among these parameters in limiting infection suggests new avenues for inhibiting viral infections by targeting early life cycle bottlenecks.
Genomic stability of Self-inactivating Rabies
Authors: Ciabatti Ernesto , González-Rueda Ana , de Malmazet Daniel , Lee Hassal , Morgese Fabio , Tripodi Marco
Published: September 2020

Transsynaptic viral vectors provide means to gain genetic access to neurons based on synaptic connectivity and are essential tools for the dissection of neural circuit function. Among them, the retrograde monosynaptic ΔG-Rabies has been widely used in neuroscience research. A recently developed engineered version of the ΔG-Rabies, the non-toxic self-inactivating (SiR) virus, represents the first tool for open-ended genetic manipulation of neural circuits. However, the high mutational rate of the rabies virus poses a risk that mutations targeting the key genetic regulatory element in the SiR genome could emerge and revert it to a canonical ΔG-Rabies. Such revertant mutations have recently been identified in a SiR batch. To address the origin, incidence and relevance of these mutations, we investigated the genomic stability of SiRin vitroandin vivo. We found that “revertant” mutations are rare and accumulate only when SiR is extensively amplifiedin vitro, particularly in suboptimal production cell lines that have insufficient levels of TEV protease activity. Moreover, we confirmed that SiR-CRE, unlike canonical ΔG-Rab-CRE or revertant-SiR-CRE, is non-toxic and that revertant mutations do not emergein vivoduring long-term experiments.

Highlights

Revertant mutations are rare and do not accumulate when SiR is produced in high-TEVp expressing production cell lines

SiR is non-toxicin vivo

Revertant SiR mutations do not accumulate duringin vivoexperiments
A critical role for B cells in cancer immune surveillance
Authors: Rawat Kavita , Tewari Anita , Jakubzick Claudia V.
Published: September 2020

It is commonly believed that B cells play no role in cancer immune surveillance. However, this conclusion is based on studies using only a single B cell-deficient mouse strain, muMT mice, which does not show increased tumorigenesis compared with wild-type (WT) mice. In this study, we demonstrate a critical role for B cells in anti-tumor immunity and identify the cellular mechanisms that make muMT mice a special case. First, we replicate previous findings using a melanoma model in muMT mice. Then, we show that in muMT mice, B-cell deficiency is compensated for by a significant increase in another potent anti-tumor cell type, Type-1 interferon (IFN I)-producing plasmacytoid DCs (pDCs), resulting in normative anti-tumor responses. Depleting pDCs in muMT mice resulted in a significant increase in tumor size and burden. Conversely, adoptive transfer of antibodies from naïve WT serum into pDC-depleted muMT mice significantly decreased the tumor load to WT levels. Additionally, a B cell antibody repertoire-deficient mouse strain, IghelMD4 mice, showed a 3-fold increase in tumors relative to WT mice. Overall, these findings indicate the need for a diverse antibody repertoire for early neoplastic cell recognition and the critical role B cells play in anti-cancer immunity.
Professionalization of crisis management: A case study of local‐level crisis communicators in Sweden
Authors: Deverell Edward
Published: September 2020

This study applies an institutional profession perspective on a significant crisis management actor in an aim to deepen the understanding of collaborative crisis management work and practices. The study argues that a professions perspective holds a key to approaching interagency gaps in status and influence, which tend to affect collaborative crisis management negatively. Empirically the study is based on 19 interviews with local crisis communicators in Sweden. Findings indicate that, in terms of internal collaboration, limited knowledge among organizational members about the role and skills of crisis communicators require communicators to spend time and resources on ‘promoting’ their competence within the organization. Regarding inter‐organizational collaboration, the study shows that the closer a communication officer works to the spatial place of the crisis and to the rescue service, the higher the status of the communication officer. Interestingly enough, relations seem to go both ways as emergency service personnel can also be empowered by becoming more skillful communicators.
Autophagy‐Sirt3 axis decelerates hematopoietic aging
Authors: Fang Yixuan , An Ni , Zhu Lingjiang , Gu Yue , Qian Jiawei , Jiang Gaoyue , Zhao Ruijin , Wei Wen , Xu Li , Zhang Gaochuan , Yao Xingyun , Yuan Na , Zhang Suping , Zhao Yun , Wang Jianrong
Published: September 2020

Autophagy suppresses mitochondrial metabolism to preserve hematopoietic stem cells (HSCs) in mice. However, the mechanism by which autophagy regulates hematopoietic aging, in particular in humans, has largely been unexplored. Here, we demonstrate that reduction of autophagy in both hematopoietic cells and their stem cells is associated with aged hematopoiesis in human population. Mechanistically, autophagy delays hematopoietic aging by activating the downstream expression of Sirt3, a key mitochondrial protein capable of rejuvenating blood. Sirt3 is the most abundant Sirtuin family member in HSC‐enriched population, though it declines as the capacity for autophagy deteriorates with aging. Activation of autophagy upregulates Sirt3 in wild‐type mice, whereas in autophagy‐defective mice, Sirt3 expression is crippled in the entire hematopoietic hierarchy, but forced expression of Sirt3 in HSC‐enriched cells reduces oxidative stress and prevents accelerated hematopoietic aging from autophagy defect. Importantly, the upregulation of Sirt3 by manipulation of autophagy is validated in human HSC‐enriched cells. Thus, our results identify an autophagy‐Sirt3 axis in regulating hematopoietic aging and suggest a possible interventional solution to human blood rejuvenation via activation of the axis.
Relationships of reproductive performance indicators in black rhinoceros (Diceros bicornis michaeli) with plant available moisture, plant available nutrients and woody cover
Authors: Okita‐Ouma Benson , van Langevelde Frank , Heitkönig Ignas M. A. , Maina Peter , van Wieren Sip E. , Prins Herbert H. T.
Published: September 2020

Plant available moisture and plant available nutrients in soils influence forage quality and availability and subsequently affect reproductive performance in herbivores. However, the relationship of soil moisture, soil nutrients and woody forage with reproductive performance indicators is not well understood in mega‐browsers yet these three are important in selecting suitable areas for conservation of mega‐browsers. Here, the eastern black rhinoceros (Diceros bicornis michaeli), a mega‐browser, was studied in seven geographically distinct populations in Kenya to understand the relationships between its reproductive performance indicators and plant available moisture, plant available nutrients and woody cover. Reproductive parameters showed a complex relationship with plant available moisture and plant available nutrients. We found an increase in the predicted yearly percentage of females calving as plant available nutrients decreased in areas of high levels of plant available moisture but no relationship with plant available nutrients in areas of low plant available moisture. Age at first calving was earlier, inter‐calving interval was longer and yearly percentage of females calving was higher at higher woody cover. Woody plant cover contributes positively to black rhino reproduction performance indicators, whereas plant available moisture and plant available nutrients add to the selection of conservation areas, in more subtle ways.
The pathogenic role of circulating Hashimoto's Thyroiditis‐derived TPO‐positive IgG on fetal loss in naïve mice
Authors: Borodina Elena , Katz Itai , Antonelli Alessandro , Gzgzyan Alexander M. , Dzhemlikhanova Liailia Kh , Ostrinski Yuri , Niauri Dariko , Khizroeva Jamilya , Bitsadze Victoria , Makatsariya Alexander , Tincani Angela , Nalli Cecilia , Churilov Leonid P. , Shovman Ora , Halpert Gilad , Blank Miri , Shoenfeld Yehuda , Amital Howard
Published: September 2020

Problem

Antibody‐mediated autoimmune diseases, such as autoimmune thyroid diseases (ATD), systemic lupus erythematosus (SLE), and antiphospholipid syndrome (APS), often are associated with recurrent fetal loss. One of the ATD is Hashimoto's thyroiditis which recently showed association with complications of pregnancy with increased levels of circulating autoantibodies reactive with epitopes on thyroid tissue such as thyroid peroxidase (anti‐TPO). In retrospective study of sera analyses in patients with Hashimoto's thyroiditis, all patients had mainly elevated circulating anti‐TPO autoantibodies.

Aim

We assessed the potential of human anti‐TPO highly positive IgG, derived from patients with Hashimoto's thyroiditis sera associated with complications of pregnancy, to cause directly complications of pregnancy in murine model.

Method of study

Naïve ICR female mice, infused intravenously with 100 μg of anti‐TPO‐positive IgG, showed increased fetal loss and embryo small for date (P < .001) in comparison with mice passively transferred with commercial IgG or PBS. Moreover, we observed embryos small for date in the mice passively transferred with anti‐TPO‐positive IgG, exemplified by reduced weight of embryos and placentae (P = .001). Histopathological examination revealed delay in fetal development in 50% cases of anti‐TPO‐positive IgG‐treated mice. Importantly, pathological changes in the transition zone, state of glycogen cells, and significant structural changes in the labyrinth part of placenta were observed in all anti‐TPO‐positive IgG samples.

Conclusion

The current study shows in the first time, a direct proof of concept, on the association of human TPO‐positive IgG from Hashimoto's thyroiditis patients on fetal loss induction in murine model.
Interleukin‐4‐loaded hydrogel scaffold regulates macrophages polarization to promote bone mesenchymal stem cells osteogenic differentiation via TGF‐β1/Smad pathway for repair of bone defect
Authors: Zhang Jiankang , Shi Haitao , Zhang Nian , Hu Liru , Jing Wei , Pan Jian
Published: September 2020

Objective

Tissue engineering is a promising strategy for repair of large bone defect. However, the immune system reactions to biological scaffold are increasingly being recognized as a crucial factor influencing regeneration efficacy. In this study, a bone‐bioactive hydrogel bead loaded with interleukin‐4 (IL‐4) was used to regulate macrophages polarization and accelerate bone regeneration.

Methods

IL‐4‐loaded calcium‐enriched gellan gum (Ca‐GG + IL‐4) hydrogel beads were synthesised. And the effect on cell behaviour was detected. Furthermore, the effect of the Ca‐GG + IL‐4 hydrogel bead on macrophage polarization and the effect of macrophage polarization on bone mesenchymal stem cells (BMSCs) apoptosis and osteogenic differentiation were evaluated in vitro and in vivo.

Results

BMSCs were able to survive in the hydrogel regardless of whether IL‐4 was incorporated. Immunofluorescence staining and qPCR results revealed that Ca‐GG + IL‐4 hydrogel bead could promote M2 macrophage polarization and increase transforming growth factor (TGF)‐β1 expression level, which activates the TGF‐β1/Smad signalling pathway in BMSCs and promotes osteogenic differentiation. Moreover, immunohistochemical analysis demonstrated Ca‐GG + IL‐4 hydrogel bead could promote M2 macrophage polarization and reduce cell apoptosis in vivo. In addition, micro‐CT and immunohistochemical analysis at 12 weeks post‐surgery showed that Ca‐GG + IL‐4 hydrogel bead could achieve superior bone defect repair efficacy in vivo.

Conclusions

The Ca‐GG + IL‐4 hydrogel bead effectively promoted bone defect regeneration via regulating macrophage polarization, reducing cell apoptosis and promoting BMSCs osteogenesis through TGF‐β1/Smad pathway. Therefore, it is a promising strategy for repair of bone defect.
Prevalence of pain and interference with daily activities and sleep in adults with cerebral palsy
Authors: Rodby‐Bousquet Elisabet , Alriksson‐Schmidt Ann , Jarl Johan
Published: September 2020

Aim

To analyse the prevalence of pain, pain sites, pain severity, and pain interfering with work or daily activities and sleep in adults with cerebral palsy (CP).

Method

This was a cross‐sectional study based on data from 1591 adults (16–76y, median age 25y; 879 males, 712 females; Communication Function Classification System [CFCS] levels I–V) in the Swedish Cerebral Palsy Follow‐up Program. Pain severity was rated for several body sites and pain interference with activities/work and sleep was also evaluated. Logistic regression was used to estimate the odds ratios (ORs) of the factors associated with the prevalence of pain and pain interfering with activities/work or sleep.

Results

Pain was reported in 1059 of 1591 adults; a higher proportion self‐reported pain (69.9%) compared to proxy‐reported pain (62.4%). More adults classified in CFCS level I (72.5%) reported pain compared to those in CFCS levels II to V (56.5–64.9%). Adults with severe/very severe pain had a sixfold risk of pain interfering with activity/work (OR=6.68; 95% CI 4.99–8.96) and sleep (OR=6.60; 95% CI 4.84–8.98).

Interpretation

Two‐thirds of adults with CP experienced pain, which is likely to be underreported in individuals who do not communicate efficiently or rely on proxy reports. Pain strongly interfered with activities and sleep; thus, it must be assessed and treated more effectively.

What this paper adds

Two‐thirds of adults with cerebral palsy (CP) experienced pain from a median of three body sites.

Pain is likely to be underreported in adults who do not communicate efficiently or rely on proxy reports.

Adults with CP in severe pain had a sixfold risk of pain interfering with activity/work and sleep.
Buried in the sand: Uncovering the ecological roles and importance of rays
Authors: Flowers Kathryn I. , Heithaus Michael R. , Papastamatiou Yannis P.
Published: September 2020

Rays (superorder Batoidea) are the most diverse group of elasmobranchs, and many are threatened with extinction. However, there remain areas where research on the ecology of this group is lacking, from trophic interactions to their importance to ecosystem structure and function. Such ecological insights are critical for predicting the potential consequences of changes in their population sizes. Our aim was to synthesize the existing ray ecology literature and identify key knowledge gaps in order to provide a framework for future research. Numerous studies describe ray diets, and the number of studies using biochemical methods to address ray trophic interactions is increasing. The implications of ray predator–prey interactions on population dynamics of prey and how ray foraging might influence ecosystem dynamics through bioturbation remain relatively unexplored, despite claims that rays are ecologically important because they are bioturbators and because of their potential to deplete stocks of commercially important bivalves. Therefore, to better integrate rays in our understanding of marine community dynamics, there is a need to: (i) combine behavioural data with dietary information to describe predator–prey interactions; (ii) understand how ray bioturbation affects biogeochemical cycles and infaunal communities; (iii) elucidate conditions under which rays might initiate or transmit trophic cascades through consumptive and non‐consumptive pathways; and (iv) consider anthropogenic influences on the ecological roles and importance of rays.
Interaction between and impact of IL‐6 genotype and alpha‐tocopherol levels on periodontal condition in aging individuals
Authors: Yoshihara Akihiro , Kaneko Noboru , Miyamoto Akane , Nohno Kaname
Published: September 2020

Background and Objectives

Few studies have assessed the possible interaction between and impact of IL‐6 variants and serum α‐tocopherol levels on periodontal condition in older individuals. Here, we assessed the relationship between IL‐6 variants and serum α‐tocopherol levels on periodontal condition by considering effect modification.

Material and Methods

Among the study participants, 359 who were 71 years of age underwent a dental examination, biochemical analysis, and interview. After dividing the participants into tertiles based on serum α‐tocopherol levels, we conducted Poisson regression analysis to compare the prevalence rate ratio (PRR) for periodontal disease markers with the IL‐6 genotype (rs1800796) based on each tertile adjusted by the number of teeth present (offset).

Results

The PRRs of the IL‐6 genotype for periodontal condition (probing pocket depth [PPD], clinical attachment level [CAL], and bleeding on probing [BOP]) which were adjusted by the number of teeth present (offset) were 1.17 (P < .001), 1.37 (P < .001), and 1.08 (P = .048), respectively. In addition, a significant association was found between the reciprocal number of PRRs of the IL‐6 genotype and three serum α‐tocopherol levels. The adjusted PRRs (± standard error) of the IL‐6 genotypes for PPD were 0.48 (0.12) for the first group (P < .001), 1.54 (0.04) for the second group (P < .001), and 2.11 (0.03) for the third group (P < .001); similar tendencies were seen for CAL and BOP.

Conclusion

The results of this study suggest a potential association between the IL‐6 genotype and periodontal condition in relation to serum antioxidant concentrations.
Case of “relapsing” COVID‐19 in a kidney transplant recipient
Authors: MA Becky Mingyao , Hung Ivan Fan Ngai , Chan Gary Chi Wang , Tam Anthony Raymond , Chan Samuel Shung Kay , Wong Bonnie Chun Kwan , Fukuda Kenichiro , Ohno Takanori , Yuen Kwok Yung , Chan Tak Mao
Published: September 2020

Clinical outcomes of COVID‐19 vary considerably between patients. Little was known about the clinical course and optimal management of immunosuppressed patients infected with SARS‐CoV‐2. We report a kidney transplant recipient with COVID‐19 who presented with pneumonitis and acute kidney injury (AKI). She improved after reduction of immunosuppressive treatment and had two consecutive negative reverse transcription polymerase chain reaction (RT‐PCR) tests. Her respiratory tract samples turned positive again afterwards, and she was treated with lopinavir‐ritonavir. She had satisfactory virological and clinical response after a prolonged disease course. This case illustrates the risk of relapse or persisting shedding of SARS‐CoV‐2 in immunosuppressed patients, the important role of viral load monitoring in management, the challenges in balancing the risks of COVID‐19 progression and transplant rejection, and the pharmacokinetic interaction between immunosuppressive and antiviral medications.
Treatment of tinea capitis with topical 1% encapsulated terbinafine hydrochloride gel: A pilot study
Authors: Jerasutus Suthep , Vejjabhinanta Voraphol , Prapapan Ornicha
Published: September 2020

Background/Objective

Oral antifungal agents are the mainstay of the therapy of pediatric tinea capitis. No approved topical medications for tinea capitis are found. We evaluated the therapeutic efficacy, safety, and tolerability of topical 1% encapsulated terbinafine hydrochloride gel for the treatment of pediatric tinea capitis.

Methods

An open‐label clinical trial was performed on 10 children with clinical and mycologically confirmed diagnosis of tinea capitis. Each child was prescribed topical 1% encapsulated terbinafine hydrochloride gel to be applied twice daily to the full scalp for 4 weeks. Clinical and mycological examinations were assessed 2 weeks after completion of treatment. Monitoring was performed for associated side effects during the treatment and follow‐up periods.

Results

Ten male patients were enrolled with a mean age of 10.3 years. A cure rate of 80% (n = 8) was noted 2 weeks after treatment completion. An additional 20% (n = 2) had mycological cure with incomplete, but significant clinical improvement. No significant side effects were reported.

Conclusions

This preliminary study demonstrated that topical 1% encapsulated terbinafine hydrochloride gel was an effective treatment for tinea capitis in children.
The role of solute transporters in aluminum toxicity and tolerance
Authors: Kar Debojyoti , Pradhan Ajar Anupam , Datta Sourav
Published: September 2020

The prevalence of aluminum ions (Al3+) under acidic soil conditions inhibits primary root elongation and hinders plant growth and productivity. Al3+ alters the membrane potential, displaces critical ions in the apoplast and disrupts intracellular ionic concentrations by targeting membrane‐localized solute transporters. Here, we provide an overview of how Al3+ affects the activities of several solute transporters especially in the root. High Al3+ level impairs the functions of potassium (K+), calcium (Ca2+), magnesium (Mg2+), nitrate (NO3−) and ammonium (NH4+) transporters. We further discuss the role of some key transporters in mediating Al tolerance either by exclusion or sequestration. Anion channels responsible for organic acid efflux modulate the sensitivity to Al3+. The ALUMINUM ACTIVATED MALATE TRANSPORTER (ALMT) and MULTIDRUG AND TOXIC COMPOUND EXTRUSION (MATE) family of transporters exude malate and citrate, respectively, to the rhizosphere to alleviate Al toxicity by Al exclusion. The ABC transporters, aquaporins and H+‐ATPases perform vacuolar sequestration of Al3+, leading to aluminum tolerance in plants. Targeting these solute transporters in crop plants can help generating aluminum‐tolerant crops in future.
METHYLENE BLUE REMOVAL USING COCONUT SHELL BIOCHAR SYNTHESIZED THROUGH MICROWAVE-ASSISTED PYROLYSIS
Authors: Nuryana Dwi , Alim Muhammad Fahrul Rahman , Yahayu Maizatulakmal , Ahmad Muhammad Abbas , Sulong Raja Safazliana Raja , Aziz Muhammad Fakhrul Syukri Abd , Prasetiawan Haniif , Zakaria Zainul Akmar , Kusumaningtyas Ratna Dewi
Published: September 2020

Indonesia is the world’s second largest producer of coconut. This at the same time resulted in huge generation of coconut shell waste that need to be properly managed to prevent environmental contamination such as water, air and soil pollution. Current techniques of physical and thermal processing are time and energy consuming. This study reports on the conversion of coconut shell biomass into biochar using microwave-assisted pyrolysis (MAP). The MAP processes were carried out at different microwave power (550-650W) and   residence time (15-25 minutes). Two of the highest biochar yields were obtained at 550W with the residence times of 15 minutes (91.31 wt%, termed as S1) and 20 minutes (83.88 wt%, termed as S2), respectively. Both values were higher than biochar yield obtained using conventional pyrolysis process i.e. 30.10 wt%. Both S1 and S2 showed considerable capacity to remove 0.6875 mg.g-1 and 0.5165 mg.g-1 methylene blue which had the initial concentration of 25 mg.L-1. The adsorption efficiencies of S1 and S2 biochars were 55.00% and 41.32%, respectively. Results obtained from the FTIR, FESEM and BET analysis also supported the methylene blue removal properties of both S1 and S2, respectively. As a conclusion, coconut shell showed potential as a useful raw material to produce biochar that can be used for methylene blue removal from solution. Nevertheless, more investigation need to be carried out prior to commercialization venture of the coconut-shell based biochar.
A three-dimensional pattern recognition localization system based on a Bayesian graphical model
Authors: Alhammadi Abdulraqeb , Hashim Fazirulhisyam , A Rasid Mohd. Fadlee , Alraih Saddam
Published: September 2020

Access points in wireless local area networks are deployed in many indoor environments. Device-free wireless localization systems based on available received signal strength indicators have gained considerable attention recently because they can localize the people using commercial off-the-shelf equipment. Majority of localization algorithms consider two-dimensional models that cause low positioning accuracy. Although three-dimensional localization models are available, they possess high computational and localization errors, given their use of numerous reference points. In this work, we propose a three-dimensional indoor localization system based on a Bayesian graphical model. The proposed model has been tested through experiments based on fingerprinting technique which collects received signal strength indicators from each access point in an offline training phase and then estimates the user location in an online localization phase. Results indicate that the proposed model achieves a high localization accuracy of more than 25% using reference points fewer than that of benchmarked algorithms.
Down-regulation of PADI2 prevents proliferation and epithelial-mesenchymal transition in ovarian cancer through inhibiting JAK2/STAT3 pathway in vitro and in vivo, alone or in combination with Olaparib
Authors: Liu Lidong , Zhang Zhiwei , Zhang Guoxiang , Wang Ting , Ma Yingchun , Guo Wei
Published: September 2020

Background

Epithelial ovarian cancer (EOC) is the most lethal disease among female genital malignant tumors. Peptidylarginine deiminase type II(PADI II) has been shown to enhance a variety of cancers carcinogenesis, including ovarian cancer. The purpose of this study was to investigate the biological role of PADI2 in ovarian cancer (OC) and the relative mechanism.

Methods

Gene Expression Profiling Interactive Analysis (GEPIA) (https://gepia.pku.cn/) and ONCOMINE (https://www.oncomine.org/) were used to analyze PADI2 Gene Expression data. The survival curve for the PADI2 gene was generated by using the online Kaplan–Meier mapping site (https://www.kmplot.com/). We conducted MTT assay, cloning formation assay and EdU cell proliferation assay to detect the cell activity of PADI2 knockdown A2780 and SKOV3 ovarian cancer cells treated with Olaparib. Cell migration and invasion were observed by would healing and transwell assay. The pathway changes after the treatment of PADI2 were detected by transcriptome sequencing and western blot. The role of PADI2 combined with Olaparib treatment in vivo was studied in nude mouse model bearing ovarian cancer tumor.

Results

We investigated the role of PADI2 on EOC in vitro and in vivo. PADI2 was upregulated in ovarian cancer samples and high PADI2 expression was correlated with poor outcome. Downregulating PADI2 suppressed colony formation, proliferation, migration and invasion of A2780 and SKOV3 cells. Furthermore, downregulating PADI2 and Olaparib combination treatment attenuated the viability, migration and invasion of A2780 and SKOV3 cells. We identified differentially expressed genes in A2780-shPADI2 and SKOV3-shPADI2 cell by transcriptome sequencing analysis and verified that downregulating PADI2 and Olaparib combination treatment suppresses EMT and JAK2/STAT3 signaling pathway in A2780 and SKOV3 cells in vitro and in vivo.

Conclusions

Downregulation of PADI2 and Olaparib combination treatment attenuated the proliferation, migration and invasion of A2780 and SKOV3 cells by inhibiting the EMT through JAK2/STAT3 signaling pathway.