bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mediators of Inflammation-Driven Expansion, Trafficking, and Function of Tumor-Infiltrating MDSCs
Authors: Tannenbaum Charles S. , Rayman Patricia A. , Pavicic Paul G. , Kim Jin Sub , Wei Wei , Polefko Alexandra , Wallace Wesley , Rini Brian I. , Morris-Stiff Gareth , Allende Daniela S. , Hamilton Thomas , Finke James H. , Diaz-Montero C. Marcela 
Published: August 2019

AbstractMyeloid-derived suppressor cells (MDSC) are induced by and accumulate within many histologically distinct solid tumors, where they promote disease by secreting angiogenic and immunosuppressive molecules. Although IL1β can drive the generation, accumulation, and functional capacity of MDSCs, the specific IL1β-induced inflammatory mediators contributing to these activities remain incompletely defined. Here, we identified IL1β-induced molecules that expand, mobilize, and modulate the accumulation and angiogenic and immunosuppressive potencies of polymorphonuclear (PMN)-MDSCs. Unlike parental CT26 tumors, which recruited primarily monocytic (M)-MDSCs by constitutively expressing GM-CSF– and CCR2-directed chemokines, IL1β-transfected CT26 produced higher G-CSF, multiple CXC chemokines, and vascular adhesion molecules required for mediating infiltration of PMN-MDSCs with increased angiogenic and immunosuppressive properties. Conversely, CT26 tumors transfected with IL1β-inducible molecules could mobilize PMN-MDSCs, but because they lacked the ability to upregulate IL1β-inducible CXCR2-directed chemokines or vascular adhesion molecules, additional PMN-MDSCs could not infiltrate tumors. IL1β-expressing CT26 increased angiogenic and immunosuppressive factors of tumor-infiltrating MDSCs, as did CT26 tumors individually transfected with G-CSF, Bv8, CXCL1, or CXCL5, demonstrating that mediators downstream of IL1β could also modulate MDSC functional activity. Translational relevance was indicated by the finding that the same growth factors, cytokines, chemokines, and adhesion molecules responsible for the mobilization and recruitment of PMN-MDSCs into inflammatory CT26 murine tumors were also coordinately upregulated with increasing IL1β expression in human renal cell carcinoma tumors. These studies demonstrated that IL1β stimulated the components of a multifaceted inflammatory program that produces, mobilizes, chemoattracts, activates, and mediates the infiltration of PMN-MDSCs into inflammatory tumors to promote tumor progression.
Possible Involvement of Nitric Oxide in the Antipruritic Effect of Metformin on Chloroquine-Induced Scratching in Mice
Authors: Haddadi Nazgol-Sadat , Shakiba Saeed , Afshari Khashayar , Haj-Mirzaian Arvin , Vesaghati Sara , Gharagozlou Saber , Foroumadi Roham , Shafaroodi Hamed , Ostadhadi Sattar , Dehpour Ahmad Reza 
Published: August 2019

<b><i>Background:</i></b> Metformin ameliorates non-histamine-mediated itch. We have recently reported that the nitric oxide (NO) pathway is involved in chloroquine (CQ)-induced scratching behavior. Here we investigated the involvement of the NO pathway in the antipruritic effect of metformin on CQ-induced itch. <b><i>Methods:</i></b> Metformin (5–200 mg/kg, given intraperitoneally [i.p.]) was injected 4 h before CQ (400 µg/site, given intradermally [i.d.]) or compound 48/80 (100 µg/site, i.d.). A nonspecific nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 1 and 10 mg/kg, i.p.), or an NO precursor, L-arginine (10 and 100 mg/kg, i.p.) was administered 30 min before injection of CQ. A neural NOS (nNOS) inhibitor, 7-nitroindazole (7-NI; 1 and 10 nmol/site, i.d.) was concurrently administered with CQ. The scratching behavior was recorded for 30 min following the injection of CQ. We studied the changes in skin and spinal nitrite levels after treatments. <b><i>Results:</i></b> Our results showed that metformin (100 and 200 mg/kg) significantly reduced the CQ-induced scratching behavior but not the compound 48/80-induced scratching behavior. L-Arginine inhibited the antipruritic effect of metformin, while L-NAME and 7-NI significantly potentiated the inhibitory effects of a subeffective dose of metformin on the CQ-induced scratching behavior. The skin but not the spinal nitrite level was significantly increased after CQ administration. The elevated cutaneous nitrite level was reversed by effective doses of either metformin or 7-NI, but not by the subeffective doses of metformin + 7-NI. <b><i>Conclusion:</i></b> Acute injection of metformin significantly inhibits CQ-induced scratching behavior. This effect is mediated through inhibition of the NO pathway, especially by inhibiting the dermal nNOS enzyme.
ЗАСТОСУВАННЯ КІБЕРФІЗИЧНИХ БІОСЕНСОРНИХ ТА ІМУНОСЕНСОРНИХ СИСТЕМ
Authors: Martsenyuk V. P. , Sverstiuk A. S. , Bihunyak T. V. , Pavlyshyn A. V. , Mochulska O. M. 
Published: August 2019

У роботі проведено огляд кіберфізичних біосенсорних та імуносенсорних систем, що є новим поколінням інформаційно-вимірювальних систем із використанням у конструкції біологічних матеріалів, які забезпечують їх високу селективність. Проведена класифікація досліджуваних систем відносно чутливих елементів і можливості використанням різних режимів фізико-хімічного перетворення вимірювальної величини. Розглянуто такі види кіберфізичних біосенсорних та імуносенсорних систем: електрохімічні; оптичні; на основі оксиду кремнію, кварцу та скла; на основі наноматеріалів; генетично кодовані або синтетичні флуоресцентні; мікробні, розроблені за допомогою синтетичної біології та генетичної інженерії. Досліджувані системи порівняно за технологією, специфічністю, порогом виявлення, тривалістю аналізу, вартістю та портативністю.
Розглянуто методи виготовлення електрохімічних кіберфізичних біосенсорних та імуносенсорних систем. Окремо представлено методи виготовлення, шляхом модифікування поверхні металевих і вуглецевих електродів із використанням біоматеріалів, таких як ферменти, антитіла або ДНК. Представлено оптичні досліджувані системи, що реалізуть свою дію за допомогою іммобілайзерів і можуть виготовлятися із золота, матеріалів на основі вуглецю, кварцу або скла. Описано найбільш важливі напрями використання кіберфізичних біосенсорних та імуносенсорних систем у лікувальних і діагностичних закладах, зокрема для моніторингу рівня глюкози в крові пацієнтів із цукровим діабетом, а також для розроблення нових лікарських засобів, біозондування та біомедицини. Зроблено висновок, що досліджувані системи з наноматеріалів на основі оксиду кремнію володіють найбільш високим потенціалом щодо застосування для біовізуалізаціі, біосенсорного аналізу та лікування онкологічнх захворювань.
Розглянуто мічені кіберфізичні біосенсорні та імуносенсорні системи з використанням генетичного кодування або синтетичної флуоресценції, що дало змогу вивчати біологічні процеси, в тому числі, різні молекулярні перетворення всередині клітин. Наведено переваги візуалізації in vivo за допомогою досліджуваних систем малих молекул з метою кращого розуміння клітинної активності та механізму дії ДНК, РНК та мікро-РНК. Описано клітинні біосенсорні та імуносенсорні системи, що можна застосовувати для моніторингу біохімічної потреби в кисні, токсичності в навколишньому середовищі, для виявлення пестицидів і важких металів, спостереженні за екологічною ефективністю при виробництві електроенергії. Зроблено висновок, що для створення високочутливих мініатюрних пристроїв потрібне розроблення різних мікро- і нано-кіберфізичних біосенсорних та імуносенсорних платформ із залученням інтегрованих технологій, які використовують електрохімічний або оптичний біоелектронні принципи з комбінацією біомолекул або біологічних матеріалів, полімерів і наноматеріалів.
ЛОГІКА ПІДГОТОВКИ ЗДОБУВАЧІВ ВИЩОЇ ОСВІТИ СТУПЕНЯ ДОКТОРА ФІЛОСОФІЇ ЗІ СПЕЦІАЛІЗАЦІЇ «МЕДИЧНА ТА БІОЛОГІЧНА ІНФОРМАТИКА І КІБЕРНЕТИКА»
Authors: Mintser O.P. , Babintseva L. Yu. 
Published: August 2019

Представлено освітню програму та навчальний план підготовки здобувачів вищої освіти ступеня доктора філософії на третьому (освітньо-науковому) рівні за всіма формами навчання для спеціалізації «Медична та біологічна інформатика і кібернетика». Навчання в аспірантурі та поза нею відбувається відповідно до Закону України «Про вищу освіту», постанов Кабінету Міністрів України від 23.03.2016 № 261 «Про затвердження Порядку підготовки здобувачів вищої освіти ступеня доктора філософії та доктора наук у вищих навчальних закладах (наукових установах)» та від 30.12.2015 № 1187 «Про затвердження Ліцензійних умов провадження освітньої діяльності закладів освіти».
Кінцеві цілі з навчальної дисципліни «Медична та біологічна інформатика і кібернетика» спрямовані на здобуття глибинних знань зі спеціальності, за якою здобувач проводить дослідження, зокрема засвоєння основних концепцій, розуміння теоретичних і практичних проблем, оволодіння термінологією з досліджуваного наукового напряму тощо.
Відомо, що навчальний план відповідно до наказу МОН України є нормативним документом (стандартом) закладу вищої освіти. Проте освітня програма та навчальний план складено на кафедрі медичної інформатики, що є опорною в системі післядипломної медичної освіти, тому запропоновані документи можуть розглядатись як уніфікована освітня програма та навчальний план.
Epigenetic Regulation of Vascular Smooth Muscle Cells by Histone H3 Lysine 9 Dimethylation Attenuates Target Gene-Induction by Inflammatory Signaling
Authors: Harman Jennifer L. , Dobnikar Lina , Chappell Joel , Stokell Benjamin G. , Dalby Amanda , Foote Kirsty , Finigan Alison , Freire-Pritchett Paula , Taylor Annabel L. , Worssam Matthew D. , Madsen Ralitsa R. , Loche Elena , Uryga Anna , Bennett Martin R. , Jørgensen Helle F. 
Published: August 2019

Objective:
Vascular inflammation underlies cardiovascular disease. Vascular smooth muscle cells (VSMCs) upregulate selective genes, including MMPs (matrix metalloproteinases) and proinflammatory cytokines upon local inflammation, which directly contribute to vascular disease and adverse clinical outcome. Identification of factors controlling VSMC responses to inflammation is therefore of considerable therapeutic importance. Here, we determine the role of Histone H3 lysine 9 di-methylation (H3K9me2), a repressive epigenetic mark that is reduced in atherosclerotic lesions, in regulating the VSMC inflammatory response.

Approach and Results:

We used VSMC-lineage tracing to reveal reduced H3K9me2 levels in VSMCs of arteries after injury and in atherosclerotic lesions compared with control vessels. Intriguingly, chromatin immunoprecipitation showed H3K9me2 enrichment at a subset of inflammation-responsive gene promoters, including
MMP3
,
MMP9
,
MMP12
, and
IL6
, in mouse and human VSMCs. Inhibition of G9A/GLP (G9A-like protein), the primary enzymes responsible for H3K9me2, significantly potentiated inflammation-induced gene induction in vitro and in vivo without altering NFκB (nuclear factor kappa-light-chain-enhancer of activated B cell) and MAPK (mitogen-activated protein kinase) signaling. Rather, reduced G9A/GLP activity enhanced inflammation-induced binding of transcription factors NFκB-p65 and cJUN to H3K9me2 target gene promoters
MMP3
and
IL6
. Taken together, these results suggest that promoter-associated H3K9me2 directly attenuates the induction of target genes in response to inflammation in human VSMCs.

Conclusions:
This study implicates H3K9me2 in regulating the proinflammatory VSMC phenotype. Our findings suggest that reduced H3K9me2 in disease enhance binding of NFκB and AP-1 (activator protein-1) transcription factors at specific inflammation-responsive genes to augment proinflammatory stimuli in VSMC. Therefore, H3K9me2-regulation could be targeted clinically to limit expression of MMPs and IL6, which are induced in vascular disease.
Mechanism of Enhanced MerTK-Dependent Macrophage Efferocytosis by Extracellular Vesicles
Authors: de Couto Geoffrey , Jaghatspanyan Ervin , DeBerge Matthew , Liu Weixin , Luther Kristin , Wang Yizhou , Tang Jie , Thorp Edward B. , Marbán Eduardo 
Published: August 2019

Objective:

Extracellular vesicles secreted by cardiosphere-derived cells (CDC
ev
) polarize macrophages toward a distinctive phenotype with enhanced phagocytic capacity (M
CDCev
). These changes underlie cardioprotection by CDC
ev
and by the parent CDCs, notably attenuating the no-reflow phenomenon following myocardial infarction, but the mechanisms are unclear. Here, we tested the hypothesis that M
CDCev
are especially effective at scavenging debris from dying cells (ie, efferocytosis) to attenuate irreversible damage post-myocardial infarction.

Approach and Results:

In vitro efferocytosis assays with bone marrow-derived macrophages, and in vivo transgenic rodent models of myocardial infarction, demonstrate enhanced apoptotic cell clearance with M
CDCev
. CDC
ev
exposure induces sustained MerTK expression in M
CDCev
through extracellular vesicle transfer of microRNA-26a (via suppression of
Adam17
); the cardioprotective response is lost in animals deficient in MerTK. Single-cell RNA-sequencing revealed phagocytic pathway activation in M
CDCev
, with increased expression of complement factor
C1qa
, a phagocytosis facilitator.

Conclusions:
Together, these data demonstrate that extracellular vesicle modulation of MerTK and C1qa expression leads to enhanced macrophage efferocytosis and cardioprotection.
SCF (Stem Cell Factor) and cKIT Modulate Pathological Ocular Neovascularization
Authors: Kim Koung Li , Seo Songyi , Kim Jee Taek , Kim Jaetaek , Kim Won , Yeo Yeongju , Sung Jong-Hyuk , Park Sang Gyu , Suh Wonhee 
Published: August 2019

Objective:
Aberrant neovascularization is a leading cause of blindness in several eye diseases, including age-related macular degeneration and proliferative diabetic retinopathy. The identification of key regulators of pathological ocular neovascularization has been a subject of extensive research and great therapeutic interest. Here, we explored the previously unrecognized role of cKIT and its ligand, SCF (stem cell factor), in the pathological ocular neovascularization process.

Approach and Results:

Compared with normoxia, hypoxia, a crucial driver of neovascularization, caused cKIT to be highly upregulated in endothelial cells, which significantly enhanced the angiogenic response of endothelial cells to SCF. In murine models of pathological ocular neovascularization, such as oxygen-induced retinopathy and laser-induced choroidal neovascularization models, cKIT and SCF expression was significantly increased in ocular tissues, and blockade of cKIT and SCF using
cKit
mutant mice and anti-SCF neutralizing IgG substantially suppressed pathological ocular neovascularization. Mechanistically, SCF/cKIT signaling induced neovascularization through phosphorylation of glycogen synthase kinase-3β and enhancement of the nuclear translocation of β-catenin and the transcription of β-catenin target genes related to angiogenesis. Inhibition of β-catenin-mediated transcription using chemical inhibitors blocked SCF-induced in vitro angiogenesis in hypoxia, and injection of a β-catenin agonist into
cKit
mutant mice with oxygen-induced retinopathy significantly enhanced pathological neovascularization in the retina.

Conclusions;
Our data reveal that SCF and cKIT are promising novel therapeutic targets for treating vision-threatening ocular neovascular diseases.
Heparan Sulfate–Editing Extracellular Sulfatases Enhance VEGF Bioavailability for Ischemic Heart Repair
Authors: Korf-Klingebiel Mortimer , Reboll Marc R. , Grote Karsten , Schleiner Hauke , Wang Yong , Wu Xuekun , Klede Stefanie , Mikhed Yuliya , Nobre André , Bauersachs Johann , Klintschar Michael , Rudat Carsten , Kispert Andreas , Niessen Hans W. , Lübke Torben , Dierks Thomas , Wollert Kai C. 
Published: August 2019

Rationale:
Mechanistic insight into the inflammatory response after acute myocardial infarction may inform new molecularly targeted treatment strategies to prevent chronic heart failure.

Objective:

We identified the sulfatase SULF2 in an in silico secretome analysis in bone marrow cells from patients with acute myocardial infarction and detected increased sulfatase activity in myocardial autopsy samples. SULF2 (Sulf2 in mice) and its isoform SULF1 (Sulf1) act as endosulfatases removing 6-
O
-sulfate groups from heparan sulfate (HS) in the extracellular space, thus eliminating docking sites for HS-binding proteins. We hypothesized that the Sulfs have a role in tissue repair after myocardial infarction.

Methods and Results:

Both Sulfs were dynamically upregulated after coronary artery ligation in mice, attaining peak expression and activity levels during the first week after injury. Sulf2 was expressed by monocytes and macrophages, Sulf1 by endothelial cells and fibroblasts. Infarct border zone capillarization was impaired, scar size increased, and cardiac dysfunction more pronounced in mice with a genetic deletion of either Sulf1 or Sulf2. Studies in bone marrow-chimeric Sulf-deficient mice and Sulf-deficient cardiac endothelial cells established that inflammatory cell-derived Sulf2 and endothelial cell-autonomous Sulf1 promote angiogenesis. Mechanistically, both Sulfs reduced HS sulfation in the infarcted myocardium, thereby diminishing Vegfa (vascular endothelial growth factor A) interaction with HS. Along this line, both Sulfs rendered infarcted mouse heart explants responsive to the angiogenic effects of HS-binding Vegfa
164
but did not modulate the angiogenic effects of non-HS-binding Vegfa
120
. Treating wild-type mice systemically with the small molecule HS-antagonist surfen (bis-2-methyl-4-amino-quinolyl-6-carbamide, 1 mg/kg/day) for 7 days after myocardial infarction released Vegfa from HS, enhanced infarct border-zone capillarization, and exerted sustained beneficial effects on cardiac function and survival.

Conclusions:
These findings establish HS-editing Sulfs as critical inducers of postinfarction angiogenesis and identify HS sulfation as a therapeutic target for ischemic tissue repair.
Ritual and Rationality in Islam: A Case Study on Nail Polish
Authors: Mustafa Abdul-Rahman 
Published: August 2019

Abstract
This article examines an ongoing controversy in Islamic ritual law concerning the effect of nail polish on one’s ritual purity. Ritual law serves as the canvas on which some of the most intriguing debates on Islamic theology, rationality and legal reasoning are sketched out as rival conceptualizations of the nature of God – as a rational and merciful agent or as supra-rational being – generate rival sets of jurisprudential and legal doctrines. The study of ritual law also reveals key fault lines in contemporary Sunni Islamic legal and theological thought, particularly the ways in which scholars expressing varying degrees of sympathy with Salafism – from the South Asian Ahl-e Ḥadīth tradition, the Ahl al-Ḥadīth tradition and the Ḥanbalī tradition – create new positions in Sunni law while continuing to champion principles and precedents valorized in Salafism and making their arguments legible in Sunnism.
Clinical Veterinarians’ Perceptions about Sexes and Breeds of Dogs Involved in Aggressiveness in Montevideo, Uruguay
Authors: Ruiz Santos Paul , Belino María , Rijo Ruben , Piaggio José , Damián Juan Pablo 
Published: August 2019

Abstract
Aggression is the most common dog behavioral problem, with important implications for public health. The aim of this study was to determine the perception of veterinarian clinicians of Montevideo regarding canine aggression, the sex effect, and the main breeds involved. One hundred veterinary clinics of Montevideo city were randomly selected to complete a survey about aggressiveness in dogs. Most veterinarians opined that males are more involved than females in canine aggression and that the Pit bull, the German Shepherd, and Uruguayan Cimarron breeds were the most involved in both types of aggression considered (between canines and towards people), while the Cocker Spaniel breed was involved in aggression towards humans and the Rottweiler breed in aggression between dogs. This work highlights that both veterinarians and other experts within the community identify the Uruguayan Cimarron as being aggressive, which indicates that the behavior of this breed may be of particular concern.
Cat Demographics & Impact on Wildlife in the USA, the UK, Australia and New Zealand: Facts and Values
Authors: Rowan Andrew N. , Kartal Tamara , Hadidian John 
Published: August 2019

Abstract
The estimated populations of domestic cats in the USA, whether pets, stray or feral, vary widely and have changed significantly over the past forty to fifty years. Accurate estimates of these populations are necessary to determine appropriate policy responses to calls to control domestic cats and to determine the impact of domestic cats on wildlife populations. Domestic cat predation on wild animals is being hotly debated in Australia, New Zealand and the USA (but much less so in the UK). The paper explores some of the different policy approaches being promoted in each country and examines the status of cats in each country. For example, although there is strong movement to control cat predation in New Zealand, the country also has the highest relative (to humans) population of pet cats in the world, despite the vulnerability of native animals to predation by introduced carnivores.
Observations on the terrestrial leech Haemopis septagon Sawyer &amp; Shelley, 1976 (Annelida: Hirudinea) from the Outer Banks, North Carolina, USA, with a revision of the species
Authors: SAWYER ROY T. 
Published: August 2019

The terrestrial leech Haemopis septagon Sawyer & Shelley, 1976, is indigenous to the Great Dismal Swamp and environs of northeastern North Carolina and southeastern Virginia, USA. Ever since its discovery in 1895 at Lake Drummond in the Dismal Swamp, this elusive species has been recognized as taxonomically aberrant. For example, it is the only jawed leech in the United States with seven annuli between gonopores, and the only one with sixteen complete (5-annulate) segments, both highly conserved characters in the Hirudinidae. The discovery of two populations of H. septagon in the Albemarle Peninsula in the Outer Banks region of North Carolina afforded an opportunity to investigate the taxonomy and biology of this inadequately characterized species. Its description in this study is the first comprehensive account of the external and internal anatomy of this species since its incomplete original description in 1976. This study is also an opportunity to correct errors in the incomplete original description, and to elucidate morphological and developmental variability of taxonomic significance. Evidence is presented for the first time of a possible aquatic or semi-aquatic form of H. septagon. These Albemarle individuals were compared to the holotype from Durham County, NC, specimens from southeastern Virginia and a terrestrial leech recently reported from southern New Jersey. All of these fall within the variability demonstrated in this study for the Albemarle populations, and are accordingly recognized as the same species, H. septagon. Consequentially, Haemopis ottorum Wirchansky & Shain, 2010, is recognized as a junior synonym of Haemopis septagon.