bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of expanded diagnostic criteria for avoidant/restrictive food intake disorder on clinical comparisons with anorexia nervosa
Authors: Becker Kendra R. , Keshishian Ani C. , Liebman Rachel E. , Coniglio Kathryn A. , Wang Shirley B. , Franko Debra L. , Eddy Kamryn T. , Thomas Jennifer J.
Published: December 2018

Objective

Avoidant/restrictive food intake disorder (ARFID) and anorexia nervosa (AN) are restrictive eating disorders. There is a proposal before the American Psychiatric Association to broaden the current DSM‐5 criteria for ARFID, which currently require dietary intake that is inadequate to support energy or nutritional needs. We compared the clinical presentations of ARFID and AN in an outpatient sample to determine how a more inclusive definition of ARFID, heterogeneous for age and weight status, is distinct from AN.

Methods

As part of standard care, 138 individuals with AN or ARFID completed an online assessment battery and agreed to include their responses in research.

Results

Individuals with ARFID were younger, reported earlier age of onset, and had higher percent median BMI (%mBMI) than those with AN (all ps < .001). Individuals with ARFID scored lower on measures of eating pathology, depression, anxiety, and clinical impairment (all ps < .05), but did not differ from those with AN on restrictive eating (p = .52), and scored higher on food neophobia (p < .001).

Discussion

Allowing psychosocial impairment to be sufficient for an ARFID diagnosis resulted in a clinical picture of ARFID such that %mBMI was higher (and in the normal range) compared with AN. Differences in gender distribution, age, and age of onset remained consistent with previous research. Both groups reported similar levels of dietary restriction, although ARFID can be distinguished by relatively higher levels of food neophobia. Currently available measures of eating pathology may capture certain ARFID symptoms, but highlight the need for measures of impairment relative to ARFID.
Transcriptional regulation of the endocannabinoid system in a rat model of binge‐eating behavior reveals a selective modulation of the hypothalamic fatty acid amide hydrolase gene
Authors: Pucci Mariangela , Micioni Di Bonaventura Maria Vittoria , Zaplatic Elizabeta , Bellia Fabio , Maccarrone Mauro , Cifani Carlo , D'Addario Claudio
Published: December 2018

Objective

Binge‐eating episodes are recurrent and are defining features of several eating disorders. Thus binge‐eating episodes might influence eating disorder development of which exact underlying mechanisms are still largely unknown.

Methods

Here we focused on the transcriptional regulation of the endocannabinoid system, a potent regulator of feeding behavior, in relevant rat brain regions, using a rat model in which a history of intermittent food restriction and a frustration stress induce binge‐like palatable food consumption.

Results

We observed a selective down‐regulation of fatty acid amide hydrolase (faah) gene expression in the hypothalamus of rats showing the binge‐eating behavior with a consistent reduction in histone 3 acetylation at lysine 4 of the gene promoter. No relevant changes were detected for any other endocannabinoid system components in any brain regions under study, as well as for the other epigenetic mechanisms investigated (DNA methylation and histone 3 lysine 27 methylation) at the faah gene promoter.

Discussion

Our findings suggest that faah transcriptional regulation is a potential biomarker of binge‐eating episodes, with a relevant role in the homeostatic regulation of food intake.
Activation of integrated stress response pathway regulates IL‐1β production through posttranscriptional and translational reprogramming in macrophages
Authors: Naz Saima , Battu Srikanth , Khan Rafiq Ahmad , Afroz Sumbul , Giddaluru Jeevan , Vishwakarma Sandeep Kumar , Satti Vishnupriya , Habeeb Md Aejaz , Khan Aleem Ahmed , Khan Nooruddin
Published: December 2018

Immune cells sense and programme its cellular machinery appropriately to the environmental changes through the activation of cytoprotective adaptive pathway so‐called the “integrated stress response (ISR)”. However, the mechanisms implicated in ISR‐induced protective responses are poorly understood. Here, we show that ISR activation by arsenite (Ar) results in suppression of IL‐1β production in macrophages and inhibition of DSS‐induced colitis in a murine model through a novel posttranscriptional and translation regulatory (PTR) mechanism. Ar triggers PTR events through eIF2α‐phosphorylation, which results in the attenuation of active polysome formation leading to the accumulation of translationally stalled IL‐1β mRNAs. Translationally stalled IL‐1β mRNAs recruit RNA‐binding proteins (TIA‐1/TIAR), resulting in the formation of RBP‐RNA complexes known as stress granules (SGs). The SGs bound IL‐1β mRNAs might undergo degradation through induction of autophagy. Also, we show that Ar posttranslationally impairs processing and secretion of IL‐1β by diminishing inflammasome activation. Altogether, this study unveils a novel mechanism of IL‐1β regulation and further suggests that pharmacological activation of cytoprotective ISR pathway might provide an effective therapeutic intervention against inflammatory diseases.
ID2 and ID3 are indispensable for Th1 cell differentiation during influenza virus infection in mice
Authors: Han Xiaojuan , Liu Hongtao , Huang Huarong , Liu Xinyuan , Jia Baoqian , Gao George Fu , Zhang Fuping
Published: December 2018

Antigen‐specific Th1 cells could be a passage to the infection sites during infection to execute effector functions, such as help CD8+ T cells to localize in these sites by secretion of anti‐viral cytokines‐IFN‐γ or direct cytotoxicity of antigen‐bearing cells. However, the molecular components that modulate Th1 cell differentiation and function in response to viral infection remain incompletely understood. Here, we reported that both inhibitor of DNA binding 3(Id3) protein and inhibitor of DNA binding 2(Id2) protein promoted Th1 cell differentiation. Depletion of Id3 or Id2 led to severe defect of Th1 cell differentiation during influenza virus infection. Whereas depletion of both Id3 and Id2 in CD4+ T cells restrained Th1 cell differentiation to a greater extent, indicating that Id3 and Id2 nonredundantly regulate Th1 cell differentiation. Moreover, deletion of E‐proteins, the antagonists of Id proteins, greatly enhanced Th1 cell differentiation. Mechanistic study indicated that E‐proteins suppressed Th1 cell differentiation by directly binding to the regulatory elements of Th1 cell master regulator T‐bet and regulate T‐bet expression. Thus, our findings identified Id‐protein's importance for Th1 cells and clarified the nonredundant role of Id3 and Id2 in regulating Th1 cell differentiation, providing novel insight that Id3‐Id2‐E protein axis are essential for Th1 cell polarization.
High‐dimensional single‐cell proteomics analysis identifies immune checkpoint signatures and therapeutic targets in ulcerative colitis
Authors: Fuchs Sebastian , Sawas Nadia , Staedler Nicolas , Schubert David A. , D'Andrea Annalisa , Zeiser Robert , Piali Luca , Hruz Petr , Frei Andreas P.
Published: December 2018

Immune checkpoints are regulators of immune cells and play key roles in the modulation of immune responses. The role of checkpoints in autoimmune disease is poorly understood but likely to be central since checkpoint inhibition during cancer treatment can cause autoimmunity. We generated a high‐dimensional single‐cell proteomics data set from PBMCs of healthy individuals and patients with ulcerative colitis (UC) by mass cytometry, enabling systems‐wide analyses of immune cell frequencies and cell type‐specific expression patterns of 12 immune checkpoints. Subtle but significant changes in immune cell frequencies and checkpoint expression were observed between UC patients on different treatment regimens and between patients and healthy controls. Most strikingly, UC patients showed a reduced number of peripheral NK‐cells and those cells showed an altered phenotype including increased TIGIT expression. Based on these results, we modulated NK‐cell function ex vivo through targeting of TIGIT pathway members. In summary, we describe a pattern of changes in immune cell abundance and checkpoint expression as a basis for UC patient stratification and we show modulation of a corresponding immune cell subset through checkpoint targeting. Our approach can be used for the identification of pathogenic immune cell subsets and guide target selection in autoimmunity and chronic inflammation.
Social cure and social curse: Social identity resources and adjustment to acquired brain injury
Authors: Muldoon Orla T. , Walsh R. Stephen , Curtain Mariah , Crawley Lorraine , Kinsella Elaine L.
Published: December 2018

There is increasing evidence that identification with social groups can protect and enhance health, establishing a kind of ‘social cure’. However, for those affected by chronic or disabling conditions such as acquired brain injury (ABI), their identity may also represent a burden, a form of ‘social curse’. The present study explored the identity benefits and burdens available to 15 participants living with ABI using semi‐structured interviews. The qualitative data was then analysed systematically using thematic analysis. The findings highlight social identity changes as central to the experience of brain injury. Participants reported changes in their social networks and social group memberships after injury. Identity loss and reduced social support were described as disabling. Engagement in meaningful group activity with others affected by ABI and access to affected peers enabled new group‐based resources such as social support. In this way, group activity can be seen as a form of identity enactment that can drive social cure effects. Similarly, adaptation to life after injury was demonstrably linked to social identity processes pointing to the importance of a social cure approach to rehabilitation.
An automated food protein isolation approach on preparative scale by two‐dimensional liquid chromatography with active modulation interface
Authors: Melfi Maria Teresa , Nardiello Donatella , Natale Anna , Quinto Maurizio , Centonze Diego
Published: December 2018

In this work, an automated 2D‐LC approach for protein isolation from egg samples on preparative scale is proposed. The method is based on the use of a C18 guard column installed in a switching valve to focus the proteins coming from the first dimension column, before their elution in the second column. For the first dimension separation, a size‐exclusion column, packed with 3 μm ultrapure silica particles was used. An RP column based on core‐shell technology was used for the second dimension separation. A standard mixture of BSA, β‐lactoglobulin, and glucose oxidase, chosen as a protein model system, was used to optimize the chromatographic separation conditions. The fully automated workflow allowed to isolate, in a single‐chromatographic analysis, a protein amount of 50 μg for each peak fraction, with a total time of 15 min for the first separation and additional 30 min of the second separation for each trapped protein. The final aim was the development of proper analytical tools for protein isolation from foodstuffs to be used for the molecular identification by MS, as well as for biotherapeutic uses, allergy testing, and large‐scale investigations in biological systems.
Thermal decomposition and combustion characteristics of biomass materials using TG/DTG at different high heating rates and sizes in the air
Authors: El‐Sayed Saad A. , Ismail Mohamed A. , Mostafa Mohamed E.
Published: December 2018

Thermogravimetric (TGA) analysis was used to study the thermal decomposition and oxidation, combustion characteristics, and kinetics of cotton stalks and sugarcane bagasse powder of various particle sizes under air from room temperature to 1000 °C at heating rates 25, 50, and 75 °C/min. It was observed that all the samples followed a two‐stage reaction mechanism between 200 and 1000 °C clearly indicating regions of volatile oxidation and char combustion during thermal decomposition and oxidation. It was also found that heating rate, particle size, lignocellulosic composition, and gas flow types affect the thermal decomposition mechanism and kinetic parameter values of both materials. The kinetic parameters were determined using simple Distributed Activation Energy Model (DAEM) and three methods of model‐free kinetics. It was found that average activation energy (Eav) for cotton stalks and bagasse for both bulk and different particle sizes ranged between 34–118 kJ/mol and 87–187 kJ/mol, respectively. Results also showed that the values of kinetic parameters obtained from all methods are in a good agreement and can be successfully used to understand the degradation mechanism of solid‐state reaction of these biomass materials. Finally, a comparison between the thermal pyrolysis characteristics of both materials under inert (nitrogen) and air at a heating rate of 10 °C/min is presented and discussed. © 2018 American Institute of Chemical Engineers Environ Prog, 38:e13124, 2019
Basal cell carcinomas developing independently from BAP1‐tumor predisposition syndrome in a patient with bilateral uveal melanoma
Authors: Melzer Charlotte , Sharma Amit , Peters Sophia , Aretz Stefan , Biswas Arijit , Holz Frank G. , Loeffler Karin U. , Herwig‐Carl Martina C.
Published: December 2018

Basal cell carcinomas (BCC) have been recently included into the spectrum of BAP1‐tumor predisposition syndrome (TPDS). Uveal melanoma (UM) is also a tumor often observed in patients with this hereditary tumor syndrome, in particular bilateral UM is highly suspicious for BAP1‐TPDS although no patient has been reported yet. Based on our index patient with BAP1‐TPDS with bilateral UM (choroid OD, oculus dexter; iris OS, oculus sinister), several BCCs and thyroid cancer as well as a family history for cancer, this paper analyzes hints and pitfalls to diagnose this syndrome clinically and histologically. A previously undescribed germline variant, namely a heterozygous deletion of a single nucleotide on position 2001 (c.2001delG;p.[Thr668Profs*24] in exon 16 of the BAP1 gene), was identified. Structural changes in the C‐terminal of the BAP1 protein were observed by in silico analysis. While the excised iris melanoma showed loss of BAP1 nuclear staining by immunohistochemical staining, the BCCs of our patient (and in the control group, n = 13) were BAP1 positive. Genetic analysis of the BCC of the ocular adnexae confirmed a remaining intact BAP1 copy. The constellation of (bilateral) UM in combination with BCC should raise suspicion for a BAP1‐TPDS. As our BCCs probably developed independently from the BAP1‐TPDS and UMs frequently show loss of nuclear BAP1 staining, genetic analysis is mandatory to diagnose this syndrome.
Role of miRNAs in immune responses and immunotherapy in cancer
Authors: Cortez Maria Angelica , Anfossi Simone , Ramapriyan Rishab , Menon Hari , Atalar Semra Cemre , Aliru Maureen , Welsh James , Calin George A.
Published: December 2018

In the past decade, the study of mechanisms of cancer immunity has seen a prominent boom, which paralleled the increased amount of research on the clinical efficacy of immune checkpoint blockade in several lethal types of cancers. This conspicuous effort has led to the development of successful immunotherapy treatment strategies, whose medical impact has been recognized by the awarding of 2018 Nobel Prize in Physiology or Medicine to the two pioneers of check point inhibitor research, Tasuku Honjo and James Allison. Despite these promising achievements, the differences in the clinical response rate in different cancer patients and the high risk of toxicity of immune‐based therapies represent crucial challenges. More remarkably, the causes responsible for different outcome (success vs failure) in patients with tumor having same histotype and clinical characteristics remain mostly unknown. MicroRNAs (miRNAs), small regulatory noncoding RNA molecules representing the most studied component of the dark matter of the human genome, are involved in the regulation of many pathways of cancer and immune cells. Therefore, understanding the role of miRNAs in controlling cancer immunity is necessary, as it can contribute to reveal mechanisms that can be modulated to improve the success of immunetherapy in cancer patients. Here, we discuss the latest findings on immune pathways regulated by miRNAs in cancer, miRNA‐mediated regulation of immune cells in the tumor microenvironment, and miRNAs as potential target for immunotherapies.
Non‐leukemic pediatric mixed phenotype acute leukemia/lymphoma: Genomic characterization and clinical outcome in a prospective trial for pediatric lymphoblastic lymphoma
Authors: Martin‐Guerrero Idoia , Salaverria Itziar , Burkhardt Birgit , Chassagne‐Clement Catherine , Szczepanowski Monika , Bens Susanne , Klapper Wolfram , Zimmermann Martin , Kabickova Edita , Bertrand Yves , Reiter Alfred , Siebert Reiner , Oschlies Ilske
Published: December 2018

Rare cases of hematological precursor neoplasms fulfill the diagnostic criteria of mixed phenotype acute leukemia (MPAL), characterized by expression patterns of at least two hematopoietic lineages, for which a highly aggressive behavior was reported. We present a series of 11 pediatric non‐leukemic MPAL identified among 146 precursor lymphoblastic lymphomas included in the prospective trial Euro‐LBL 02. Paraffin‐embedded biopsies of 10 cases were suitable for molecular analyses using OncoScan assay (n = 7), fluorescence in situ hybridization (FISH; n = 7) or both (n = 5). Except for one case with biallelic KMT2A (MLL) breaks, all cases analyzed by FISH lacked the most common translocations defining molecular subsets of lymphoblastic leukemia/lymphomas. Two non‐leukemic B‐myeloid MPALs showed the typical genomic profile of hyperdiploid precursor B‐cell lymphoblastic leukemia with gains of chromosomes 4, 6, 10, 14, 18, and 21. One B‐T MPAL showed typical aberrations of T‐cell lymphoblastic lymphoma, such as copy number neutral loss of heterozygosity (CNN‐LOH) at 9p targeting a 9p21.3 deletion of CDKN2A and 11q12.2‐qter affecting the ATM gene. ATM was also mutated in a T‐myeloid MPAL case with additional loss at 7q21.2‐q36.3 and mutation of NRAS, two alterations common in myeloid disorders. No recurrent regions of CNN‐LOH were observed. The outcome under treatment was good with all patients being alive in first complete remission after treatment according to a protocol for precursor lymphoblastic lymphoma (follow‐up 3‐10 years, median: 4.9 years). In summary, the present series of non‐leukemic MPALs widely lacked recurrently reported translocations in lymphoid/myeloid neoplasias and showed heterogeneous spectrum of chromosomal imbalances.
Spinal IL‐36γ/IL‐36R participates in the maintenance of chronic inflammatory pain through astroglial JNK pathway
Authors: Li Qian , Liu Shenbin , Li Lingling , Ji Xiaoli , Wang Min , Zhou Junmei
Published: December 2018

Emerging evidence indicates that spinal neuroinflammation contributes to the maintenance of chronic inflammatory pain. IL‐36, as a novel member of the interleukin (IL)‐1 super‐family cytokines, plays an important role in inflammatory responses. The present study aimed to investigate the role of spinal IL‐36 and IL‐36 receptor (IL‐36R) signaling in the pathology of chronic inflammatory pain. IL‐36γ and IL‐36R, but not IL‐36α and IL‐36β, were persistently upregulated in the spinal cord of mice with intraplantar injections of complete Freund's adjuvant (CFA). Intrathecal administration of both IL‐36R antagonist (IL‐36Ra) and IL‐36γ siRNA significantly attenuated CFA‐induced chronic inflammatory pain behaviors. Furthermore, CFA‐induced IL‐36γ expression was mainly observed in spinal neurons whereas IL‐36R was primarily expressed in spinal astrocytes. Additionally, the intrathecal injection of IL‐36γ was sufficient to induce pain hypersensitivity and astrocyte activation in naive mice, and these effects could be inhibited by blocking c‐Jun N‐terminal kinase (JNK) phosphorylation. In vitro experiments also demonstrated that the IL‐36γ could induce astrocytic JNK activation and inflammatory cytokines release, which was mediated by IL‐36R. Finally, intrathecal injection of IL‐36γ‐activated astrocytes in a pJNK‐dependent manner induced mechanical allodynia and thermal hyperalgesia in naive mice. Collectively, these findings reveal that the neuronal/astrocytic interaction in the spinal cord by which neuronally produced IL‐36γ activates astrocytes via IL‐36R‐mediated JNK pathway is crucial for the maintenance of chronic inflammatory pain. Thus, IL‐36γ/IL‐36R‐mediated astrocyte signaling may be a suitable therapeutic target for chronic inflammatory pain.
Interleukin‐1beta released by microglia initiates the enhanced glutamatergic activity in the spinal dorsal horn during paclitaxel‐associated acute pain syndrome
Authors: Yan Xisheng , Li Fen , Maixner Dylan W. , Yadav Ruchi , Gao Mei , Ali Mourad Wagdy , Hooks Shelley B. , Weng Han‐Rong
Published: December 2018

Patients receiving paclitaxel for cancer treatment often develop an acute pain syndrome (paclitaxel‐associated acute pain syndrome, P‐APS), which occurs immediately after paclitaxel treatment. Mechanisms underlying P‐APS remain largely unknown. We recently reported that rodents receiving paclitaxel develop acute pain and activation of spinal microglial toll like receptor 4 (TLR4) by paclitaxel penetrating into the spinal cord is a critical event in the genesis of P‐APS. Our current study dissected cellular and molecular mechanisms underlying the P‐APS. We demonstrated that bath‐perfusion of paclitaxel, at a concentration similar to that found in the cerebral spinal fluid in animals receiving i.v. paclitaxel (2 mg/kg), resulted in increased calcium activity in microglia instantly, and in astrocytes with 6 min delay. TLR4 activation in microglia by paclitaxel caused microglia to rapidly release interleukin‐1β (IL‐1β) but not tumor necrosis factor α, IL‐6, or interferon‐γ. IL‐1β release from microglia depended on capthepsin B. IL‐1β acted on astrocytes, leading to elevated calcium activity and suppressed glutamate uptake. IL‐1β also acted on neurons to increase presynaptic glutamate release and postsynaptic AMPA receptor activity in the spinal dorsal horn. Knockout of IL‐1 receptors prevented the development of acute pain induced by paclitaxel in mice. Our study indicates that IL‐1β is a crucial molecule used by microglia to alter functions in astrocytes and neurons upon activation of TLR4 in the genesis of P‐APS, and targeting the signaling pathways regulating the production and function of IL‐1β from microglia is a potential avenue for the development of analgesics for the treatment of P‐APS.
Preclinical stress originates in the rat optic nerve head during development of autoimmune optic neuritis
Authors: Stojic Aleksandar , Bojcevski Jovana , Williams Sarah K. , Bas‐Orth Carlos , Nessler Stefan , Linington Christopher , Diem Ricarda , Fairless Richard
Published: December 2018

Optic neuritis is a common manifestation of multiple sclerosis, an inflammatory demyelinating disease of the CNS. Although it is the presenting symptom in many cases, the initial events are currently unknown. However, in the earliest stages of autoimmune optic neuritis in rats, pathological changes are already apparent such as microglial activation and disturbances in myelin ultrastructure of the optic nerves. αB‐crystallin is a heat‐shock protein induced in cells undergoing cellular stress and has been reported to be up‐regulated in both multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. Therefore, we wished to investigate the timing and localization of its expression in autoimmune optic neuritis. Although loss of oligodendrocytes was not observed until the later disease stages accompanying immune cell infiltration and demyelination, an increase in oligodendrocyte αB‐crystallin was observed during the preclinical stages. This was most pronounced within the optic nerve head and was associated with areas of IgG deposition. Since treatment of isolated oligodendrocytes with sera from myelin oligodendrocyte glycoprotein (MOG)‐immunized animals induced an increase in αB‐crystallin expression, as did passive transfer of sera from MOG‐immunized animals to unimmunized recipients, we propose that the partially permeable blood–brain barrier of the optic nerve head may present an opportunity for blood‐borne components such as anti‐MOG antibodies to come into contact with oligodendrocytes as one of the earliest events in disease development.
Automatic brain tissue segmentation in MR images using hybrid atlas forest based on confidence‐weighted probability matrix
Authors: Xu Lijun , Liu Hong , Song Enmin , Jin Renchao , Hung Chih‐Cheng
Published: December 2018

The segmentation of specific tissues in an MR brain image for quantitative analysis can assist the disease diagnosis and medical research. Therefore, a robust and accurate method for automatic segmentation is necessary. Atlas‐based‐method is a common and effective method of automatic segmentation where an atlas refers to a pair of image consist of an intensity image and its corresponding label image. Apart from the general multi‐atlas‐based methods, which propagate labels through the single atlas then fuse them, we proposed a hybrid atlas forest based on confidence‐weighted probability matrix to consider the atlases set as a whole and treat each voxel differently. In the framework, we first register the atlas to the image space of target and calculate the confidence of voxels in the registered atlas. Then, a confidence‐weighted probability matrix is generated and it augments to the intensity image of the atlas or target for providing spatial information of the target tissue. Third, a hybrid atlas forest is trained to gather the features and correlation information among the atlases in the dataset. Finally, the segmentation of the target tissues is predicted by the trained hybrid atlas forest. The segment performance and the components efficiency of the proposed method are evaluated on the two public datasets. Based on the experiment results and quantitative comparisons, our method can gather spatial information and correlation among the atlases to obtain an accurate segmentation.
Vitamin E: Regulatory role of metabolites
Authors: Birringer Marc , Lorkowski Stefan
Published: December 2018

Vitamin E plays an important role as a lipophilic antioxidant in cellular redox homeostasis. Besides this function, numerous non‐antioxidant properties of this vitamin have been discovered in the past. DNA microarray technology revealed a complex regulatory network influenced by the different vitamin E forms (Rimbach et al., Molecules, 15, 1746 (2010); Galli et al., Free Radic. Biol. Med., 102, 16 (2017)); however, little is known about the biological activity of vitamin E metabolites. A new chapter of vitamin E research was been opened when endogenous long‐chain tocopherol metabolites were identified and their high biological activity in vitro and in vivo was recognized (Schmölz et al., World J. Biol. Chem., 7, 14 (2016); Torquato et al., J. Pharm. Biomed. Anal., 124, 399 (2016)). Just recently, it was shown that an endogenous metabolite of vitamin E inhibits 5‐lipoxygenase at nanomolar concentrations, thereby limiting inflammation (Pein et al., Nat. Commun., 9, 3834 (2018)). Furthermore, long‐chain vitamin E metabolites (LCM) exhibit hormone‐like activities similar to the lipid soluble vitamins A and D (Galli et al., Free Radic. Biol. Med., 102, 16 (2017); Schubert et al., Antioxidants, 7 (2018)). This review aims at summarizing recent findings on the regulatory activities of vitamin E metabolites, especially of LCMs. © 2018 IUBMB Life, 71(4):479–486, 2019
New paradigm of functional regulation by DNA mimic proteins: Recent updates
Authors: Wang Hao‐Ching , Chou Chia‐Cheng , Hsu Kai‐Cheng , Lee Chi‐Hua , Wang Andrew H.‐J.
Published: December 2018

For many, “DNA mimic protein” (DMP) remains an unfamiliar term. The key feature of these proteins is their DNA‐like shape and charge distribution, and they affect the activity of DNA‐binding proteins by occupying their DNA‐binding domains. Functionally, DMPs regulate mechanisms such as gene expression, restriction, and DNA repair as well as the nucleosome package. Although a few DMPs, such as phage uracil DNA glycosylase inhibitor (UGI) and overcome classical restriction (Ocr), were reported about 20 years ago, only a small number of DMPs have been studied to date. In 2014, we reviewed the functional and structural features of 16 DMPs that were known at the time. Now, seven new DMPs, namely anti‐CRISPR suppressors AcrF2, AcrF10 and AcrIIA4, human immunodeficiency virus essential factor VPR, multi‐functional inhibitor anti‐restriction nuclease (Arn), translational regulator AbbA, and putative Z‐DNA mimic MBD3, have been reported. In addition, further study of two previously known DMPs, DMP19 and SAUGI, increased our knowledge of their importance and function. Here, we discuss these updated results and address how several characteristics of the structure/sequence of DMPs (e.g. the DNA‐like charge distribution and structural D/E‐rich repeats) might someday be used to identify new DMPs using bioinformatic approach. © 2018 IUBMB Life, 71(5):539–548, 2019
Raman spectroscopy–based insight into lipid droplets presence and contents in liver sinusoidal endothelial cells and hepatocytes
Authors: Szafraniec Ewelina , Kus Edyta , Wislocka Adrianna , Kukla Bozena , Sierka Ewa , Untereiner Valérie , Sockalingum Ganesh D. , Chlopicki Stefan , Baranska Malgorzata
Published: December 2018

Liver sinusoidal endothelial cells (LSECs), a type of endothelial cells with unique morphology and function, play an important role in the liver hemostasis, and LSECs dysfunction is involved in the development of nonalcoholic fatty liver disease (NAFLD). Here, we employed Raman imaging and chemometric data analysis in order to characterize the presence of lipid droplets (LDs) and their lipid content in primary murine LSECs, in comparison with hepatocytes, isolated from mice on high‐fat diet. On NAFLD development, LDs content in LSECs changed toward more unsaturated lipids, and this response was associated with an increased expression of stearylo‐CoA desaturase‐1. To the best of our knowledge, this is a first report characterizing LDs in LSECs, where their chemical composition is analyzed along the progression of NAFLD at the level of single LD using Raman imaging.
Molecular characterization of acutely and gradually heavy metal acclimated aquatic bacteria by FTIR spectroscopy
Authors: Kepenek Eda S. , Gozen Ayse G. , Severcan Feride
Published: December 2018

In the environment, bacteria can be exposed to the concentration gradient of toxic heavy metals (gradual) or sudden high concentration of them (acute). In both situations, bacteria get acclimated to toxic heavy metal concentrations. Acclimation causes metabolic and molecular changes in bacteria. In this study, we aimed to understand whether there are differences between molecular profiles of the bacteria (Brevundimonas, Gordonia and Microbacterium) which are under acute or gradual exposure to cadmium or lead by using ATR‐FTIR spectroscopy. Our results revealed the differences between the acclimation groups in membrane dynamics including changes in the structure and composition of the membrane lipids and proteins. Furthermore, protein concentrations decreased in acclimated bacterial groups. Also, a remarkable increase in exopolymer production occurred in acclimated groups. Interestingly, bacteria under acute cadmium exposure produced the significantly higher amount of exopolymer than they did under gradual exposure. On the contrary, under lead exposure gradually acclimate strains produced significantly higher amounts of exopolymer than those of acutely acclimated ones. This information can be used in bioremediation studies to obtain bacterial strains producing a higher amount of exopolymer.
Dual‐modality optical projection tomography reconstruction method from fewer views
Authors: Dou Shaobin , Liu Jinhuai , Yang Lianghuai
Published: December 2018

In optical projection tomography (OPT), for longitudinal living model studies, multiple measurements of the same sample are required at different time points. It is important to decrease both the total acquisition time and the light dose to the sample. We improved the ordered subsets expectation maximization reconstruction algorithm for OPT, which reduces the acquisition time and number of projections greatly compared with filtered back projection (FBP), and obtained satisfactory reconstructed images. Using zebrafish, in transmission and fluorescence mode, we demonstrate the capability of the method to reconstruct image from downsampled projection subsets. The result shows that the reconstruction image quality of the proposed method using 30 projections is comparable to that of FBP using 720 projections. The total acquisition procedure can be finished in a few seconds. The method also provides OPT with the remarkable capability to resist noises and artifacts.

Projection image and fused image of zebrafish.
Time‐dependent diffusion MRI to distinguish malignant from benign head and neck tumors
Authors: Iima Mami , Yamamoto Akira , Kataoka Masako , Yamada Yosuke , Omori Koichi , Feiweier Thorsten , Togashi Kaori
Published: December 2018

Background

There is growing interest in the effect of diffusion time on apparent diffusion coefficient (ADC) values in cancers; however, little evidence exists regarding its utility to differentiate malignant from benign head and neck tumors.

Purpose

To investigate the utility of ADC value changes in distinguishing between malignant and benign head and neck tumors using the different diffusion times obtained from oscillating gradient spin‐echo (OGSE) and pulsed gradient spin‐echo (PGSE) MRI sequences.

Study Type

Prospective.

Subjects

Thirty‐one consecutive patients with suspected head and neck tumors and a phantom.

Field Strength/Sequence

3T MRI with diffusion‐weighted imaging (DWI) using OGSE (effective diffusion time: 4.3 msec) and PGSE (effective diffusion time: 82.6 msec) sequences and b‐values of 0 and 700 s/mm2.

Assessment

ADC values using OGSE (ADCOGSE) and PGSE (ADCPGSE) and relative ADC value changes between ADCOGSE and ADCPGSE.

Statistical Tests

Wilcoxon test, Mann–Whitney test, and McNemar test.

Results

Relative ADC changes for each polyvinylpyrrolidone (PVP) and water in the phantom between OGSE and PGSE sequences were small (relative ADC change within 0.6%). Malignant tumors had significantly smaller ADCOGSE and ADCPGSE values than benign tumors (P < 0.001 and < 0.0001, respectively). Significantly larger relative ADC changes were observed in malignant compared with benign head and neck tumors (P < 0.0001). ADCPGSE values were significantly lower than ADCOGSE values in both malignant and benign head and neck tumors (0.97 vs. 1.28 × 10−3mm2/s: P < 0.0001 and 1.93 vs. 1.99 × 10−3mm2/s: P = 0.0056, respectively). Relative ADC change and ADCPGSE tended to have higher diagnostic performance than ADCOGSE, with area under the curve (AUC) values of 0.97, 0.96, and 0.89, respectively.

Data Conclusion

ADC values obtained using the PGSE sequence were lower than those obtained with OGSE. This difference was larger for malignant than benign tumors, suggesting differences in tissue structure (diffusion hindrance) or cell permeability, revealed by changes in diffusion time. The results underline the potential importance of reporting diffusion time for interpretation of head and neck diffusion MRI.

Level of Evidence: 1

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2019;50:88–95.
Cytomegalovirus shedding from breastmilk and mucosal sites in healthy postpartum women: A pilot study
Authors: Azenkot Tali , Zaniello Benjamin , Green Margaret L. , Selke Stacy , Huang Meei‐li , Magaret Amalia , Wald Anna , Johnston Christine
Published: December 2018

Mother‐to‐child cytomegalovirus (CMV) breastmilk transmission can occur in the postnatal period. In a pilot study, we measured daily CMV detection by polymerase chain reaction in breastmilk, vaginal, and saliva samples from nine healthy CMV‐seropositive postpartum women for 28 days. CMV was found in seven of nine women and 171 of 253 breastmilk samples (67.6%). In four women, all breastmilk samples were positive. CMV was less frequently detected in the vagina (39 of 258, 15.1%) and saliva (53 of 258, 20.5%). Daily breastmilk, oral, and genital collection is feasible and demonstrates high variability between women. Further study of the dynamics of CMV in distinct anatomic compartments is warranted.
Global observed and modelled impacts of irrigation on surface temperature
Authors: Chen Liang , Dirmeyer Paul A.
Published: December 2018

Agricultural irrigation has significant potential for altering local climate by reducing soil albedo, increasing evapotranspiration, and enabling greater leaf area. Numerous studies using regional or global climate models have demonstrated the cooling effects of irrigation on mean and extreme temperature, especially over regions where irrigation is extensive. However, these model‐based results have not been well validated due to the limitations of observational data sets. In this study, multiple satellite‐based products, including the Moderate Resolution Imaging Spectroradiometer (MODIS) and Soil Moisture Active Passive (SMAP) data sets, are used to isolate and quantify the local impacts of irrigation on surface climate over irrigated regions, which are derived from the Global Map of Irrigation Areas (GMIA). The relationships among soil moisture, albedo, evapotranspiration, and surface temperature are explored. Strong evaporative cooling by irrigation lowers daytime surface temperature over arid and semi‐arid regions, such as California's Central Valley, the Great Plains, central Asia, and northwestern India. However, the cooling effects are less evident in areas of eastern China and the Lower Mississippi River Basin despite extensive irrigation over these regions. Results are also compared with irrigation experiments using the Community Earth System Model (CESM) to assess the model's ability to represent land–atmosphere interactions in regards to irrigation. CESM greatly underestimates the surface temperature response to irrigation. The comparison between the offline and coupled simulations suggests that the irrigation‐induced cooling can be regulated by the interactions between land surface and atmosphere, and amplified signals are found over the “hot spot” regions. Meanwhile, model resolution can also influence the magnitude of the local cooling by irrigation.
Serum 25(OH)D is associated with an altered bone turnover marker response after a hip fracture
Authors: Stewart Christopher C. , O'Hara Nathan N. , Orwig Denise , Hochberg Marc C. , Sprague Sheila , Magaziner Jay , Slobogean Gerard P.
Published: December 2018

C‐terminal telopeptide of type I collagen (CTX) and procollagen type 1 N‐terminal propeptide (P1NP) are bone turnover markers (BTMs) that are promising surrogate measures of fracture healing; however, it is unknown if their response is affected by other bone healing metabolites. Since 70% of fracture patients are reported to have insufficient serum vitamin D, we sought to determine if serum 25(OH)D levels are associated with differential changes in CTX and P1NP concentrations after hip fracture. This prospective cohort included hip fracture patients 65 years of age or older admitted to one of eight Baltimore‐area hospitals. Serum samples were collected at baseline, 2‐, 6‐, and 12‐month post‐fracture. A mixed‐effects repeated‐measures analysis was used to determine the longitudinal association between vitamin D deficiency (25(OH)D < 20 ng/ml) and CTX and P1NP. Baseline lab values were obtained for 296 participants (mean age, 80.8 years; 51% male; 55% 25(OH)D < 20 ng/ml). During the acute fracture healing period P1NP concentrations increased by 14% (95%CI: 7–21%, p < 0.01) while CTX levels did not change (p = 0.07). Both CTX and P1NP decreased below baseline at 6 and 12 months. CTX levels were higher in participants with baseline 25(OH)D < 20 ng/ml (p = 0.01). There was no association between 25(OH)D < 20 ng/ml and P1NP levels over the study duration (p = 0.33). Data from this large, longitudinal cohort support claims that CTX and P1NP concentrations change during fracture healing; however, the differential response of CTX among vitamin D deficient patients highlights important questions for its utility as a reliable surrogate marker of fracture healing. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
Genetic modification of scAAV‐equine‐BMP‐2 transduced bone‐marrow‐derived mesenchymal stem cells before and after cryopreservation: An “off‐the‐shelf” option for fracture repair
Authors: Ball Alyssa N. , Phillips Jennifer N. , McIlwraith C. Wayne , Kawcak Christopher E. , Samulski Richard J. , Goodrich Laurie R.
Published: December 2018

Optimizing the environment of complex bone healing and improving treatment of catastrophic bone fractures and segmental bone defects remains an unmet clinical need both human and equine veterinary medical orthopaedics. The objective of this study was to determine whether scAAV‐equine‐BMP‐2 transduced cells would induce osteogenesis in equine bone marrow derived mesenchymal stem cells (BMDMSCs) in vitro, and if these cells could be cryopreserved in an effort to osteogenically prime them as an “off‐the‐shelf” gene therapeutic approach for fracture repair. Our study found that transgene expression is altered by cell expansion, as would be expected by a transduction resulting in episomal transgene expression, and that osteoinductive levels could still be achieved 5 days after recovery, and protein expression would continue up to 14 days after transduction. This is the first evidence that cryopreservation of genetically modified BMDMSCs would not alter the osteoinductive potential or clinical use of allogeneic donor cells in cases of equine fracture repair. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1310–1317, 2019.
Buccal bone thickness adjacent to virtual dental implants following guided bone regeneration
Authors: Phillips Daniel J. , Swenson Dane T. , Johnson Thomas M.
Published: December 2018

Background

Crestal bone thickness is a critical determinant of peri‐implant tissue stability. This retrospective observational study sought to quantify the buccal bone thickness achieved adjacent to virtual dental implants following guided bone regeneration (GBR) surgery and evaluate the influence of patient‐ and procedure‐related variables on buccal bone thickness.

Methods

Cone‐beam computed tomography (CBCT) images acquired from patients who had undergone GBR surgery between July 1, 2012, and November 7, 2016, were used for this analysis. In all cases, the GBR procedure involved a dense polytetrafluoroethylene (dPTFE) barrier membrane and a mineralized cortical particulate freeze‐dried bone allograft (FDBA). Eighty‐four virtual dental implants were placed at planned locations using CBCT images from 84 patients, and the adjacent buccal bone thickness was measured at each site. The effects of sex, age, estimated baseline ridge width, number of missing teeth in site, site type (tooth‐bounded versus terminal position in arch), dental arch (mandibular or maxillary), arch location (anterior or posterior), smoking status, titanium reinforcement in the membrane, membrane fixation, and tenting screw use were assessed.

Results

The mean post‐GBR buccal bone thickness adjacent to virtual dental implants was 2.24 ± 1.01 mm. Fifty‐nine of 84 virtual implants (70%) exhibited buccal bone thickness > 1.9 mm. GBR sites using membrane fixation produced significantly greater virtual implant buccal bone thickness than those without membrane fixation (2.31 ± 0.96 versus 1.15 ± 1.25 mm, P = 0.012). Virtual implant buccal bone thickness also exhibited moderate correlation with estimated initial ridge width (r = 0.43, P < 0.0001). The alveolar ridge at 81 virtual implant sites (96%) was classified as good or satisfactory, meaning dental implants were actually placed at these sites, with or without additional grafting at implant placement.

Conclusions

Observations in this study suggest GBR procedures using dPTFE membranes and FDBA result in favorable ridge dimensions for dental implant placement in most cases. However, additional augmentation at implant surgery may be necessary at ≈ 30% of sites, if buccal bone thickness > 1.9 mm is intended.
Effect of Texel crossbreeding on productive traits, carcass and meat quality of Segureña lambs
Authors: Blasco Miguel , Campo María M , Balado Javier , Sañudo Carlos
Published: December 2018

BACKGROUND

The present study aimed to assess the effect of crossbreeding a local breed (Segureña, S × S) with Texel as the sire line (Texel × Segureña crossbred, T × S) on productive traits and meat quality attributes. Sixty‐eight lambs (both males and females) from each genotype, weaned at about 45 days old and intensively fed with concentrates and cereal straw ad libitum until they were 72 days old, were used to assess productive traits, and ten animals from each genotype were used to assess meat quality.

RESULTS

The crossbreeding with Texel improves productivity, with a greater weight at birth (+1 kg) and at slaughter (+3 kg) and a greater average daily gain (+29 g). T × S lambs had a better conformation, less carcass fatness, and higher content of muscle (+45 g kg−1) as opposed to a lower fat content (−50.6 g kg−1). With regard to meat quality, crossbreeding with Texel provided a meat with a higher protein content (+4 g kg−1) and a lower oleic acid content (21% less), although the differences were very scarce from a sensory point of view, and non‐existent with respect to instrumental quality.

CONCLUSION

Crossbreeding could comprise a useful tool in the production of ovine meat in local breeds, such as Segureña, within the Mediterranean Area, and, consequently, a way of increasing the profitability of the farms. © 2018 Society of Chemical Industry
Synergistic effect of natural antifungal agents for postharvest diseases of blackberry fruits
Authors: Liu Hongxia , Zhao Huifang , Lyu Lianfei , Huang Zhengjin , Fan Sufan , Wu Wenlong , Li Weilin
Published: December 2018

BACKGROUND

Blackberry postharvest diseases are caused by fungal pathogens, and treatment of fruits with edible, natural products could reduce the postharvest losses and contribute to food sustainability. Based on the hypothesis that inhibition of fungal pathogens will significantly extend the shelf‐life of food products, the effects of natural antifungal agents on fungal pathogens were tested.

RESULTS

Two pathogenic fungal isolates, Aspergillus japonicus and Gilbertella persicaria, from infected blackberry fruits were identified morphologically using scanning electron microscopy and confirmed by DNA sequence analysis. The inhibitory effects and synergistic action of natural antifungal agents against the two fungal isolates were investigated. The results obtained demonstrated that the natamycin, chitosan and ferulic acid exhibited significant antifungal activities against the tested strains based on the calculated minimum inhibitory concentration. The best antifungal activity was obtained using a combination of ferulic acid and natamycin, which generated a total synergistic effect on both tested strains with a fractional inhibitory concentration index of 0.281. Application of the selected agents on postharvest blackberry fruits reduced the rot ratio and weight loss and also increased fruit firmness. In addition, the shelf‐life of fresh blackberry fruits was extended up to 12–15 days at 4 °C and 90 ± 5% relative humidity.

CONCLUSION

The combined utilization of ferulic acid and natamycin showed synergistic antifungal activity against two pathogenic fungal isolates, and extended the shelf life of fresh blackberry fruits up to 12–15 days. © 2018 Society of Chemical Industry