bluuebunny/crossref_metadata_2025 huggingface dataset:
Desempenho dos municípios da região metropolitana do Rio de Janeiro nas hospitalizações por Covid-19. Estudo baseado no SIVEP-Gripe
Authors: Kawa Helia , Correia Dayse Mary da Silva , Kazniakowski Arthur Willkomm , Andrade Beatriz Nayra Dias de , Arêas Cínthia Melo , Silva Jessyca Martins Lima da , Freitas Juliana Vianna de , Dall’Orto Lara Toretta Campo , Marinho Larissa dos Santos Sebould , Silva Marina Soares de Almeida e , Gardengui Melissa Corrêa Leal , Lessa Micael Paes , Costa Sarah Melo da , Costa Sarah Pientznauer Ozório , Rosa Maria Luiza Garcia
Published: January 2021

Introdução: a preocupação quanto à capacidade de atendimento em saúde, principalmente hospitalar, aumenta com o recrudescimento da epidemia do Covid-19. Objetivo: analisar dados do SIVEP-Gripe de 18 municípios da região metropolitana do Rio de Janeiro, de pacientes internados por SRAG em hospitais públicos e privados. Métodos: é um estudo epidemiológico ecológico e de coorte histórica com o município e o paciente como unidades de análise, no período de março a novembro de 2020. Foram estimadas as razões de chances para sinais e sintomas, fatores de risco, se hospital público ou privado, internação em UTI e óbitos. Empregou-se o teste do qui-quadrado de Pearson (p<0,05). Resultados: somente Niterói internou >90% dos seus residentes. Pelo menos 25% dos hospitais, públicos e privados, internaram somente um paciente levando à dificuldade de aprendizado. Os hospitais públicos apresentaram maior chance de terem internado pacientes mais velhos, de cor de pele preta ou parda, com dispneia, desconforto respiratório e baixa saturação de oxigênio, doença hepática e imunossupressão, condições de maior risco para resultados negativos.  A chance de um paciente ter passado por uma UTI em um hospital público foi cerca da metade do hospital privado e a de morte foi cerca do triplo. Conclusão: os municípios estudados, exceto Niterói, não estão preparados para dar suporte a seus residentes na pandemia de Covid-19. Verificou-se discrepância no atendimento dos hospitais públicos e privados, assim como falhas na atenção básica levando a um maior risco de resultados desfavoráveis e  um elevado número de óbitos nas unidades hospitalares públicas.
Lesões na Prática do Surfe
Authors: Arana Leandro Pickersgill , Afonso Max dos Santos
Published: January 2021

A prática de surfe tem tido um grande destaque em todo o mundo. Seus adeptos têm aumentado de forma considerável, tornando-o o esporte náutico mais praticado atualmente. Por ser um esporte que requer grande esforço físico e mudanças bruscas de postura seus atletas estão sempre em grande risco de desenvolver lesões. Assim o objetivo desse estudo foi elencar as lesões que mais acometem os praticantes do surfe, bem como a conduta dos atletas para evitarem tais lesões e ainda compreender a importância do fisioterapeuta na prevenção e tratamento de lesões esportivas. A metodologia utilizada nesta pesquisa foi uma revisão de literatura, onde foram realizadas buscas literárias sobre este assunto em bases de dados eletrônica como Google Acadêmico, Scientific Eletronic Library Online (Scielo), PubMed, com o propósito de analisar e sintetizar as informações encontradas. Através deste estudo foi possível verificar as principais características das lesões que acometem os atletas do surfe. Sendo assim, é de grande valia o entendimento do gestual esportivo dessa modalidade e as condutas a serem tomadas com o intuito de minimizar o risco de lesões e visando os benefícios que promovam analgesia, melhora da flexibilidade, da força muscular, do condicionamento físico e cardiorrespiratório, constatando então que, o planejamento de um programa de prevenção de lesões com atletas do surfe, pode ser considerado um excelente método para redução de lesões.
Caracterização de compostos voláteis e compostos bioativos da polpa e geleia de cagaita por microextração em fase sólida no modo headspace e espectrometria de massa por paper spray
Authors: Rodrigues Daiane Batista , Mendonça Henrique de Oliveira Prata , Nogueira Laiza Andrade , Paula Ana Cardoso Clemente Filha Ferreira de , Melo Angelita Cristine de , Reina Luisa Del Carmen Barrett , Silva Mauro Ramalho , Araújo Raquel Linhares Bello de , Augusti Rodinei , Melo Júlio Onésio Ferreira
Published: January 2021

A cagaiteira (Eugenia dysenterica) pertencente à família Myrtaceae, é uma árvore nativa do Cerrado brasileiro, o seu fruto é muito frágil, apresentando casca fina e polpa suculenta, é consumido na forma processada como geleia para prolongar a vida útil. O presente trabalho teve como objetivo elaborar geleia de cagaita e avaliar a alteração de compostos bioativos e compostos voláteis em relação à polpa in natura. A análise de espectrometria de massa por paper spray nos modos positivos e negativos permitiu a identificação de 27 compostos, dentre elas, ácidos orgânicos, açúcares, antocianinas, ácidos hidroxicinâmicos, ácidos hidroxibenzóicos e flavonoides, indicando que a produção de geleia pode ser uma técnica para conservação de compostos fenólicos com suas respectivas qualidades sensoriais como cor e sabor. Na análise de voláteis por microextração em fase sólida no modo headspace, foram detectados no total de 33 compostos, principalmente das classes de monoterpenos, de sesquiterpenos e de ésteresindicando que a produção da geleia pode conservar o aroma característico do fruto. Na caracterização dos compostos voláteis da polpa de cagaita, o 3-careno foi o monoterpeno majoritário encontrado. Enquanto no processamento da geleia houve produção do furaldeído, produto obtido como consequência natural do aquecimento.
Key drivers of microbial abundance, activity, and diversity in karst spring waters across an altitudinal gradient in Slovenia
Authors: Opalički Slabe M , Danevčič T , Hug K , Fillinger L , Mandić-Mulec I , Griebler C , Brancelj A
Published: January 2021

In aquatic ecosystems, the biomass, activity and composition of microorganisms are determined to a large extent by local and regional environmental conditions. While karst aquifers are an important source for drinking water, the ecology of microbial communities in karst waters has hardly been studied. This study examined the regional variations and seasonal dynamics of microbial communities in pristine karst spring waters of Slovenia (Central Europe). Fifteen springs distributed across 5 eco-regions exhibiting a strong altitudinal gradient were sampled 4 times a year. Evaluation of the microbial communities included quantification of prokaryotic biomass via total cell counts and microbial activity estimated via measurements of electron transport system activity. The taxonomic structure of the bacterial communities was analysed by terminal restriction fragment length polymorphism fingerprinting. Biological measures were complemented by a set of physico-chemical parameters, including dissolved organic carbon, nutrients, major ions, temperature, electrical conductivity, pH, and dissolved oxygen. Bacterial community structure differed significantly with seasons and eco-regions, with the latter causing greater variation. While the overall power of the environmental variable tested was a moderate factor (15%) in explaining the variability in microbial community structure, catchment altitude was a key determinant. Prokaryotic cell density and microbial activity in spring water decreased with an increase in catchment altitude and were significantly positively correlated. For a better understanding of karst ecosystems and the ecosystem service of water purification, future investigation should address karst microbial communities at a higher phylogenetic and functional resolution.
Effects of seawater viscosity and temperature on the movement of the marine dinoflagellate Prorocentrum minimum
Authors: Tyrell AS , Jiang H , Fisher NS
Published: January 2021

It is important to understand how planktonic dinoflagellate movements may be affected by environmental conditions, including those potentially influenced by climate change. Because of their small size, dinoflagellates can be expected to be highly sensitive to changes in viscosity; however, there is currently little understanding of how these organisms and other algae may be regulated by seawater viscosity. Previous work that has addressed the effects of seawater viscosity on single-celled plankton considered unnaturally large viscosity changes from a biomechanical perspective, sometimes without considering temperature effects. We studied the swimming of the dinoflagellateProrocentrum minimum, a common coastal species, when exposed to environmentally relevant temperature and viscosity changes.P. minimumshowed an additive response to seawater viscosity and temperature: cold temperature and high viscosity both slowed swimming speeds. However, seawater temperature and viscosity did not affect the movement direction or linearity of swimming of the dinoflagellates. We argue that temperature-related changes in movement may be partially regulated by a mechanical response to viscosity, which increases at cold temperature. We also propose possible future directions for laboratory and modelling studies.
Selected Adipokines - Plasma Concentrations and Adipose Tissue
Expressions during 24-Hour Lipid Infusion in Healthy Men
Authors: Kopecký J , Krušinová E , Klementová M , Kazdová L , Mlejnek P , Pravenec M , Hill M , Pelikánová T
Published: January 2021

Our aim was to assess the reaction of TNFα, resistin, leptin and
adiponectin to lipid infusion. Eight healthy subjects underwent a
24-hour lasting infusion of lipid emulsion. Plasma concentrations
and expressions of selected cytokines in subcutaneous fat were
measured. TNFα plasma concentration did not change during the
first 4 hours of hypertriglyceridemia, but a significant increase
after 24 hours was detected (p<0.001 for 0; 30; 240 min vs.
24 h). Plasma concentration of resistin significantly increased at
30 min of infusion and remained elevated (p<0.01 for 0 min vs.
30; 240 min; p<0.001 for 0 min vs. 24 h). Plasma concentrations
of leptin and adiponectin did not show any significant changes.
Although the expression of resistin in the subcutaneous adipose
tissue tended to increase, the change was not significant.
Expressions of TNFα, leptin and adiponectin were unaffected. In
conclusions, our results indicate that acutely induced
hyperlipidemia could influence the secretion of TNFα and resistin.
Connexin 43 Expression in Human Hypertrophied Heart Due to Pressure and Volume Overload
Authors: Vetter C , Zweifel M , Zuppinger C , Carrel T , Martin D , Haefliger J-A , Delacrétaz E
Published: January 2021

Left ventricular hypertrophy (LVH) is due to pressure overload or mechanical stretch and is thought to be associated with remodeling of gap-junctions. We investigated whether the expression of connexin 43 (Cx43) is altered in humans in response to different degrees of LVH. The expression of Cx43 was analyzed by quantitative polymerase chain reaction, Western blot analysis and immunohistochemistry on left ventricular biopsies from patients undergoing aortic or mitral valve replacement. Three groups were analyzed: patients with aortic stenosis with severe LVH (n=9) versus only mild LVH (n=7), and patients with LVH caused by mitral regurgitation (n=5). Cx43 mRNA expression and protein expression were similar in the three groups studied. Furthermore, immunohistochemistry revealed no change in Cx43 distribution. We can conclude that when compared with mild LVH or with LVH due to volume overload, severe LVH due to chronic pressure overload is not accompanied by detectable changes of Cx43 expression or spatial distribution.
Vestibular Control of Intermediate- and Long-Term Cardiovascular
Responses to Experimental Orthostasis
Authors: Raffai G , Csekő C , Nádasy G , Monos E
Published: January 2021

Sustained orthostasis elicits the elevation of arterial blood
pressure (BP) via sympathetic activation in conscious Wistar rats
for at least 2 hours. We tested the hypothesis whether vestibular
apparatus plays a role in BP and heart rate (HR) control in
response to prolonged gravitational stress. BP and HR responses
to 45º head-up for either 2 or 24 hours were monitored by
telemetry. Vestibular lesions (VL) were performed by a modified
microsurgical-chemical technique. Horizontal BP and HR were not
influenced by VL preceding 2-hour tilt. VL abolished the sustained
2-hour BP response to head-up tilt (8.3±0.9 mm Hg relative to
horizontal values) while suppressed HR transiently only. VL
eliminated diurnal BP fluctuations and decreased HR in horizontal
position for 24 hours. Head-up tilt for 24 hours increased BP and
HR progressively in intact animals, raising their daily average
value by 5.6±0.7 mm Hg and 22.2±6 BPM, respectively. VL
resulted in an initial BP rise followed by progressive BP reduction
in response to long-term head-up tilt (4±2.2 mm Hg) without
eliminating the tachycardia (34.4±5.4 BPM). Thus, blockade of
labyrinthine inputs attenuates the BP responses elicited by both
intermediate and long-term gravitational stress of orthostatic
type. However, other sensory inputs derived from non-vestibular
cues (e.g. proprioceptive, visual, visceral, cutaneous etc.) seem
to be effective enough to maintain BP normal.
Rapid Reversal of Insulin-Stimulated AS160 Phosphorylation in Rat
Skeletal Muscle after Insulin Exposure
Authors: Sharma N , Arias E B , Cartee G D
Published: January 2021

Increased phosphorylation of Akt substrate of 160 kDa (AS160) is
essential to trigger the full increase in insulin-stimulated glucose
transport in skeletal muscle. The primary aim of this study was to
characterize the time course for reversal of insulin-stimulated
AS160 phosphorylation in rat skeletal muscle after insulin
removal. The time courses for reversal of insulin effects both
upstream (Akt phosphorylation) and downstream (glucose
uptake) of AS160 were also determined. Epitrochlearis muscles
were incubated in vitro using three protocols which differed with
regard to insulin exposure: No Insulin (never exposed to insulin),
Transient Insulin (30 min with 1.8 nmol/l insulin, then incubation
without insulin for 10, 20 or 40 min), or Sustained Insulin
(continuously incubated with 1.8 nmol/l insulin). After removal of
muscles from insulin, Akt and AS160 phosphorylation reversed
rapidly, each with a half-time of <10 min and essentially full
reversal by 20 min. Glucose uptake reversed more slowly (half
time between 10 and 20 min with essentially full reversal by
40 min). Removal of muscles from insulin resulted in a rapid
reversal of the increase in AS160 phosphorylation which
preceded the reversal of the increase in glucose uptake,
consistent with AS160 phosphorylation being essential for
maintenance of insulin-stimulated glucose uptake.
Polyvariance of Shoot Morphogenesis in Clones of Salix triandra (Salicaceae) Against the Background of the Periodicity of Rainstorms
Authors: Afonin A.
Published: January 2021

The article substantiates the need to study the development of one-year saplings from cuttings of almond willow (Salix triandra). Purpose of research: identification and analysis of seasonal dynamics of daily growth of shoots in S. triandra clones against the background of excessive atmospheric moisture in the form of three showers in 2020. Material and methods. Research methods: selection, structural-morphological, chronobiological. Object of research: model inbred-clone one-year population of S. triandra. The number of clones is 7; the recurrence is 6-fold. Material: growing annual shoots on one-year saplings; each sapling was formed into a single shoot. Results. Under experimental conditions, the rooting capacity of cuttings was 100%. Dimorphic root systems were formed on the mother cuttings of the excavated seedlings. The annual growth of the strongest shoots was 175 ... 215 cm. The daily growth in shoots reached peak values by June 10: the average daily growth was 3.6 cm/day, the maximum — 4.4 ... 4.9 cm/day. After June 10, the daily growth rate decreased unevenly until the end of the growing season. Some shoots completed growth before the beginning of August, and some continued growth until the middle of August. The cyclical nature of the seasonal dynamics of daily growth in the form of three peaks separated by two dips is established. The third peak is formed after the third rainstorm. Discussion and conclusions. Cyclical seasonal dynamics of daily growth of shoots is characterized by a high degree of synchronization of growth processes. Probably, all the shoots are affected by some powerful pulse synchronizer of unknown nature. It is possible that periodic showers may have a modifying effect on the mechanisms that regulate growth processes. The temporal discreteness of shoot morphogenesis is due to the full or partial realization of the seasonal cycle of shoot development. The duration of growth is due to interclonal and intraclonal differences. Probably, the duration of morphogenesis is controlled by both genetic and epigenetic factors.
Social Work and Social Media: Organizing in the Digital Age
Authors: Lee Shawyn C.
Published: January 2021

Social workers are trained to be actively involved in the lives of their clients and communities. They become seeped in the socio-cultural environments and lived realities of people negatively affected by oppression and social injustices. As such, it is easy for social workers to suffer from vicarious trauma and compassion fatigue. Complicating this reality is the effect of social media on the wellbeing of social workers. The use of devices, such as smartphones and tablets, is used regularly in education and workplace settings. Whether for strictly professional purposes, or dotted with personal use throughout the day, we are one tap away from the vast world of social media and social networking sites. The majority of Americans that have these devices access news stories on sites such as Facebook, Snapchat, and Twitter. These stories can certainly help inform us on the broader more macro issues our clients and communities face. But they can also have a profound effect on our ability to repeatedly engage with values, beliefs, and systems that are harmful and dangerous to our clients and ourselves. Because of our dependence on our devices, and the constant barrage of especially negative news stories, how can social workers continue to do their work effectively? This perspective piece considers repeated exposure to negative news stories on Facebook and its effects on social workers engaged in community organizing. Implications for further research are discussed.
Graphene-Modified Titanium Surface Enhances Local Growth Factor Adsorption and Promotes Osteogenic Differentiation of Bone Marrow Stromal Cells
Authors: Lu Jiayu , Sun Jiayue , Zou Derong , Song Jinlin , Yang Sheng
Published: January 2021

Graphene coating exhibits excellent abilities of protein adsorption and cell adhesion, which might expand the osteogenic activity of titanium implant surface to adapt to the environment of low bone mass and poor bone quality. In this paper, we designed and explored the graphene-coated titanium sheet, through the surface modification of oxygen-containing functional groups, to optimize the adsorption capacity of material by improving the electrostatic interactions, and successfully adsorbed and sustained-released a variety of osteogenic related growth factors in the autologous concentrated growth factors. Compared with the pure titanium, we observed that the bone marrow stromal cells (BMSCs) on the graphene-coated titanium with concentrated growth factors showed a flat shape and expressed osteogenic related genes and proteins, while the coating surfaces promoted and accelerated the osteogenic differentiation ability of BMSCs. The results suggested that it might be a feasible alternative to improve the osteogenesis of dental implant in the early stage.
Thy-1 (CD90)-Induced Metastatic Cancer Cell Migration and Invasion Are β3 Integrin-Dependent and Involve a Ca2+/P2X7 Receptor Signaling Axis
Authors: Brenet Marianne , Martínez Samuel , Pérez-Nuñez Ramón , Pérez Leonardo A. , Contreras Pamela , Díaz Jorge , Avalos Ana María , Schneider Pascal , Quest Andrew F. G. , Leyton Lisette
Published: January 2021

Cancer cell adhesion to the vascular endothelium is an important step in tumor metastasis. Thy-1 (CD90), a cell adhesion molecule expressed in activated endothelial cells, has been implicated in melanoma metastasis by binding to integrins present in cancer cells. However, the signaling pathway(s) triggered by this Thy-1-Integrin interaction in cancer cells remains to be defined. Our previously reported data indicate that Ca2+-dependent hemichannel opening, as well as the P2X7 receptor, are key players in Thy-1-αVβ3 Integrin-induced migration of reactive astrocytes. Thus, we investigated whether this signaling pathway is activated in MDA-MB-231 breast cancer cells and in B16F10 melanoma cells when stimulated with Thy-1. In both cancer cell types, Thy-1 induced a rapid increase in intracellular Ca2+, ATP release, as well as cell migration and invasion. Connexin and Pannexin inhibitors decreased cell migration, implicating a requirement for hemichannel opening in Thy-1-induced cell migration. In addition, cell migration and invasion were precluded when the P2X7 receptor was pharmacologically blocked. Moreover, the ability of breast cancer and melanoma cells to transmigrate through an activated endothelial monolayer was significantly decreased when the β3 Integrin was silenced in these cancer cells. Importantly, melanoma cells with silenced β3 Integrin were unable to metastasize to the lung in a preclinical mouse model. Thus, our results suggest that the Ca2+/hemichannel/ATP/P2X7 receptor-signaling axis triggered by the Thy-1-αVβ3 Integrin interaction is important for cancer cell migration, invasion and transvasation. These findings open up the possibility of therapeutically targeting the Thy-1-Integrin signaling pathway to prevent metastasis.
Metabolism of Amino Acids in Cancer
Authors: Wei Zhen , Liu Xiaoyi , Cheng Chunming , Yu Wei , Yi Ping
Published: January 2021

Metabolic reprogramming has been widely recognized as a hallmark of malignancy. The uptake and metabolism of amino acids are aberrantly upregulated in many cancers that display addiction to particular amino acids. Amino acids facilitate the survival and proliferation of cancer cells under genotoxic, oxidative, and nutritional stress. Thus, targeting amino acid metabolism is becoming a potential therapeutic strategy for cancer patients. In this review, we will systematically summarize the recent progress of amino acid metabolism in malignancy and discuss their interconnection with mammalian target of rapamycin complex 1 (mTORC1) signaling, epigenetic modification, tumor growth and immunity, and ferroptosis. Finally, we will highlight the potential therapeutic applications.
Prkaa1 Metabolically Regulates Monocyte/Macrophage Recruitment and Viability in Diet-Induced Murine Metabolic Disorders
Authors: Yang Qiuhua , Ma Qian , Xu Jiean , Liu Zhiping , Zou Jianqiu , Shen Jian , Zhou Yaqi , Da Qingen , Mao Xiaoxiao , Lu Sarah , Fulton David J. , Weintraub Neal L. , Bagi Zsolt , Hong Mei , Huo Yuqing
Published: January 2021

Myeloid cells, including monocytes/macrophages, primarily rely on glucose and lipid metabolism to provide the energy and metabolites needed for their functions and survival. AMP-activated protein kinase (AMPK, its gene is PRKA for human, Prka for rodent) is a key metabolic sensor that regulates many metabolic pathways. We studied recruitment and viability of Prkaa1-deficient myeloid cells in mice and the phenotype of these mice in the context of cardio-metabolic diseases. We found that the deficiency of Prkaa1 in myeloid cells downregulated genes for glucose and lipid metabolism, compromised glucose and lipid metabolism of macrophages, and suppressed their recruitment to adipose, liver and arterial vessel walls. The viability of macrophages in the above tissues/organs was also decreased. These cellular alterations resulted in decreases in body weight, insulin resistance, and lipid accumulation in liver of mice fed with a high fat diet, and reduced the size of atherosclerotic lesions of mice fed with a Western diet. Our results indicate that AMPKα1/PRKAA1-regulated metabolism supports monocyte recruitment and macrophage viability, contributing to the development of diet-induced metabolic disorders including diabetes and atherosclerosis.
Extracellular Vesicles From Liver Progenitor Cells Downregulates Fibroblast Metabolic Activity and Increase the Expression of Immune-Response Related Molecules
Authors: Royo Felix , Azkargorta Mikel , Lavin Jose L. , Clos-Garcia Marc , Cortazar Ana R. , Gonzalez-Lopez Monika , Barcena Laura , del Portillo Hernando A. , Yáñez-Mó María , Marcilla Antonio , Borras Francesc E. , Peinado Hector , Guerrero Isabel , Váles-Gómez Mar , Cereijo Unai , Sardon Teresa , Aransay Ana M. , Elortza Felix , Falcon-Perez Juan M.
Published: January 2021

Extracellular vesicles (EVs) mediate cell-to-cell crosstalk whose content can induce changes in acceptor cells and their microenvironment. MLP29 cells are mouse liver progenitor cells that release EVs loaded with signaling cues that could affect cell fate. In the current work, we incubated 3T3-L1 mouse fibroblasts with MLP29-derived EVs, and then analyzed changes by proteomics and transcriptomics. Results showed a general downregulation of protein and transcript expression related to proliferative and metabolic routes dependent on TGF-beta. We also observed an increase in the ERBB2 interacting protein (ERBIN) and Cxcl2, together with an induction of ribosome biogenesis and interferon-related response molecules, suggesting the activation of immune system signaling.
Apurinic/Apyrimidinic Endonuclease 1 and Tyrosyl-DNA Phosphodiesterase 1 Prevent Suicidal Covalent DNA-Protein Crosslink at Apurinic/Apyrimidinic Site
Authors: Lebedeva Natalia A. , Rechkunova Nadejda I. , Endutkin Anton V. , Lavrik Olga I.
Published: January 2021

Bifunctional 8-oxoguanine-DNA glycosylase (OGG1), a crucial DNA-repair enzyme, removes from DNA 8-oxo-7,8-dihydroguanine (8-oxoG) with following cleavage of the arising apurinic/apyrimidinic (AP) site. The major enzyme in eukaryotic cells that catalyzes the cleavage of AP sites is AP endonuclease 1 (APE1). Alternatively, AP sites can be cleaved by tyrosyl-DNA phosphodiesterase 1 (TDP1) to initiate APE1-independent repair, thus expanding the ability of the base excision repair (BER) process. Poly(ADP-ribose) polymerase 1 (PARP1) is a regulatory protein of DNA repair. PARP2 is also activated in response to DNA damage and can be regarded as the BER participant. Here we analyze PARP1 and PARP2 interactions with DNA intermediates of the initial stages of the BER process (8-oxoG and AP-site containing DNA) and their interplay with the proteins recognizing and processing these DNA structures focusing on OGG1. OGG1 as well as PARP1 and PARP2 form covalent complex with AP site-containing DNA without borohydride reduction. AP site incision by APE1 or TDP1 removal of protein adducts but not proteins’ PARylation prevent DNA-protein crosslinks.
Bearing My Heart: The Role of Extracellular Matrix on Cardiac Development, Homeostasis, and Injury Response
Authors: Silva Ana Catarina , Pereira Cassilda , Fonseca Ana Catarina R. G. , Pinto-do-Ó Perpétua , Nascimento Diana S.
Published: January 2021

The extracellular matrix (ECM) is an essential component of the heart that imparts fundamental cellular processes during organ development and homeostasis. Most cardiovascular diseases involve severe remodeling of the ECM, culminating in the formation of fibrotic tissue that is deleterious to organ function. Treatment schemes effective at managing fibrosis and promoting physiological ECM repair are not yet in reach. Of note, the composition of the cardiac ECM changes significantly in a short period after birth, concurrent with the loss of the regenerative capacity of the heart. This highlights the importance of understanding ECM composition and function headed for the development of more efficient therapies. In this review, we explore the impact of ECM alterations, throughout heart ontogeny and disease, on cardiac cells and debate available approaches to deeper insights on cell–ECM interactions, toward the design of new regenerative therapies.
Selective Inhibition of 2-Oxoglutarate and 2-Oxoadipate Dehydrogenases by the Phosphonate Analogs of Their 2-Oxo Acid Substrates
Authors: Artiukhov Artem V. , Kazantsev Alexey V. , Lukashev Nikolay V. , Bellinzoni Marco , Bunik Victoria I.
Published: January 2021

Phosphonate analogs of pyruvate and 2-oxoglutarate are established specific inhibitors of cognate 2-oxo acid dehydrogenases. The present work develops application of this class of compounds to specific in vivo inhibition of 2-oxoglutarate dehydrogenase (OGDH) and its isoenzyme, 2-oxoadipate dehydrogenase (OADH). The isoenzymes-enriched preparations from the rat tissues with different expression of OADH and OGDH are used to characterize their interaction with 2-oxoglutarate (OG), 2-oxoadipate (OA) and the phosphonate analogs. Despite a 100-fold difference in the isoenzymes ratio in the heart and liver, similar Michaelis saturations by OG are inherent in the enzyme preparations from these tissues (KmOG = 0.45 ± 0.06 and 0.27 ± 0.026 mM, respectively), indicating no significant contribution of OADH to the OGDH reaction, or similar affinities of the isoenzymes to OG. However, the preparations differ in the catalysis of OADH reaction. The heart preparation, where OADH/OGDH ratio is ≈ 0.01, possesses low-affinity sites to OA (KmOA = 0.55 ± 0.07 mM). The liver preparation, where OADH/OGDH ratio is ≈ 1.6, demonstrates a biphasic saturation with OA: the low-affinity sites (Km,2OA = 0.45 ± 0.12 mM) are similar to those of the heart preparation; the high-affinity sites (Km,1OA = 0.008 ± 0.001 mM), revealed in the liver preparation only, are attributed to OADH. Phosphonate analogs of C5-C7 dicarboxylic 2-oxo acids inhibit OGDH and OADH competitively to 2-oxo substrates in all sites. The high-affinity sites for OA are affected the least by the C5 analog (succinyl phosphonate) and the most by the C7 one (adipoyl phosphonate). The opposite reactivity is inherent in both the low-affinity OA-binding sites and OG-binding sites. The C6 analog (glutaryl phosphonate) does not exhibit a significant preference to either OADH or OGDH. Structural analysis of the phosphonates binding to OADH and OGDH reveals the substitution of a tyrosine residue in OGDH for a serine residue in OADH among structural determinants of the preferential binding of the bulkier ligands to OADH. The consistent kinetic and structural results expose adipoyl phosphonate as a valuable pharmacological tool for specific in vivo inhibition of the DHTKD1-encoded OADH, a new member of mammalian family of 2-oxo acid dehydrogenases, up-regulated in some cancers and associated with diabetes and obesity.
Metabolic Profile of Four Selected Cathinones in Microsome Incubations: Identification of Phase I and II Metabolites by Liquid Chromatography High Resolution Mass Spectrometry
Authors: Lopes Beatriz T. , Caldeira Maria João , Gaspar Helena , Antunes Alexandra M. M.
Published: January 2021

Consumption of synthetic cathinones, the second largest class of new psychoactive substances (NPS) reported worldwide, represents a serious public health risk. One of the biggest challenges created by the rapid spread of NPS on the illegal drug market is the discovery of selective biomarkers for their detection in biological matrices, which is only possible through the study of their metabolic profile. The synthetic cathinones 4′-methyl-N,N-dimethylcathinone (4-MDMC), 4′-methyl-N,N-diethylcathinone (4-MDEC), 4′-chloro-α-pyrrolidinovalerophenone (4Cl-PVP), and 4′-chloroethylcathinone (4-CEC) are NPS recently seized in Europe, and, with the exception of 4-CEC, no metabolism study was reported for these cathinones. With the ultimate goal of overcoming this gap, these cathinones were incubated in vitro in human and rat liver microsomes in the presence of Phase I and II (glucuronidation) co-factors, using α-pyrrolidinovalerophenone (α-PVP) as positive control. The metabolite identification was performed by liquid chromatography coupled to tandem high resolution mass spectrometry (LC-HRMS/MS). This allowed the identification of multiple Phase I and glucuronide metabolites of the selected cathinones. Additionally, a new glucuronide conjugate, derived from the recreational drug α-PVP, was herein identified for the first time. Importantly, we have demonstrated that 4-MDMC and 4-MDEC can act as prodrugs of the controlled substances 4-MMC and 4-MEC, respectively. The metabolites herein identified are expected to play an important role not only by acting as potential selective biomarkers of the intake of the synthetic cathinones selected for this study but also to understand their potential adverse effects and link these causative agents to toxicities, thereby helping in the treatment of non-fatal intoxications.
The Safety and Efficacy of Inspiratory Muscle Training for Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention: Study Protocol for a Randomized Controlled Trial
Authors: Liu YuanHui , Dai YiNing , Liu Zhi , Zhan HuiMin , Zhu Manyu , Chen XianYuan , Zhang ShengQing , Zhang GuoLin , Xue Ling , Duan ChongYang , Chen JiYan , Guo Lan , He PengCheng , Tan Ning
Published: January 2021

Background: Uncommonly high rates of pneumonia in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) have been observed during recent years. Inspiratory muscle training (IMT) could reduce pneumonia in patients undergoing coronary artery bypass grafting and other cardiac surgeries. The relationship between IMT and AMI is unknown. Here, we describe the feasibility and potential benefit of IMT in patients at high risk for pneumonia with AMI who have undergone primary PCI.

Methods: Our study is a prospective, randomized, controlled, single-center clinical trial. A total of 60 participants will be randomized into an IMT group and control group with 30 participants in each group. Participants in the IMT group will undergo training for 15 min per session, twice a day, from 12 to 24 h after primary PCI, until 30 days post-randomization; usual care will be provided for the control group. The primary endpoint is the change in inspiratory muscle strength, the secondary endpoint included feasibility, pneumonia, major adverse cardiovascular events, length of stay, pulmonary function tests measure, and quality of life.

Discussion: Our study is designed to evaluate the feasibility of IMT and its effectiveness in improving inspiratory muscle strength in participants with AMI who have undergone primary PCI.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04491760.
A Middle to Late Miocene Trans-Andean Portal: Geologic Record in the Tatacoa Desert
Authors: Montes C. , Silva C. A. , Bayona G. A. , Villamil R. , Stiles E. , Rodriguez-Corcho A. F. , Beltran-Triviño A. , Lamus F. , Muñoz-Granados M. D. , Pérez-Angel L. C. , Hoyos N. , Gomez S. , Galeano J. J. , Romero E. , Baquero M. , Cardenas-Rozo A. L. , von Quadt A.
Published: January 2021

Integration of several geologic lines of evidence reveals the prevalence of a lowland trans-Andean portal communicating western Amazonia and the westernmost Andes from at least middle Miocene until Pliocene times. Volcanism and crustal shortening built up relief in the southernmost Central and Eastern Cordilleras of Colombia, closing this lowland gap. Independent lines of evidence consist first, of field mapping in the Tatacoa Desert with a coverage area of ∼381 km2, 1,165 km of geological contact traces, 164 structural data points, and 3D aerial digital mapping models. This map documents the beginning of southward propagation of the southernmost tip of the Eastern Cordillera’s west-verging, fold-and-thrust belt between ∼12.2 and 13.7 Ma. Second, a compilation of new and published detrital zircon geochronology in middle Miocene strata of the Tatacoa Desert shows three distinctive age populations: middle Miocene, middle Eocene, and Jurassic; the first two sourced west of the Central Cordillera, the latter in the Magdalena Valley. Similar populations with the three distinctive peaks have now been recovered in western Amazonian middle Miocene strata. These observations, along with published molecular and fossil fish data, suggest that by Serravallian times (∼13 Ma), the Northern Andes were separated from the Central Andes at ∼3°N by a fluvial system that flowed into the Amazon Basin through the Tatacoa Desert. This paleogeographic configuration would be similar to a Western Andean, or Marañon Portal. Late Miocene flattening of the subducting Nazca slab caused the eastward migration of the Miocene volcanic arc, so that starting at ∼4 Ma, large composite volcanoes were built up along the axis of today's Central Cordillera, closing this lowland Andean portal and altering the drainage patterns to resemble a modern configuration.
Effects of Melatonin on Anterior Pituitary Plasticity: A Comparison Between Mammals and Teleosts
Authors: Ciani Elia , Haug Trude M. , Maugars Gersende , Weltzien Finn-Arne , Falcón Jack , Fontaine Romain
Published: January 2021

Melatonin is a key hormone involved in the photoperiodic signaling pathway. In both teleosts and mammals, melatonin produced in the pineal gland at night is released into the blood and cerebrospinal fluid, providing rhythmic information to the whole organism. Melatonin actsviaspecific receptors, allowing the synchronization of daily and annual physiological rhythms to environmental conditions. The pituitary gland, which produces several hormones involved in a variety of physiological processes such as growth, metabolism, stress and reproduction, is an important target of melatonin. Melatonin modulates pituitary cellular activities, adjusting the synthesis and release of the different pituitary hormones to the functional demands, which changes during the day, seasons and life stages. It is, however, not always clear whether melatonin acts directly or indirectly on the pituitary. Indeed, melatonin also acts both upstream, on brain centers that control the pituitary hormone production and release, as well as downstream, on the tissues targeted by the pituitary hormones, which provide positive and negative feedback to the pituitary gland. In this review, we describe the known pathways through which melatonin modulates anterior pituitary hormonal production, distinguishing indirect effects mediated by brain centers from direct effects on the anterior pituitary. We also highlight similarities and differences between teleosts and mammals, drawing attention to knowledge gaps, and suggesting aims for future research.
Chironomidae Morphological Types and Functional Feeding Groups as a Habitat Complexity Vestige
Authors: Antczak-Orlewska Olga , Płóciennik Mateusz , Sobczyk Robert , Okupny Daniel , Stachowicz-Rybka Renata , Rzodkiewicz Monika , Siciński Jacek , Mroczkowska Agnieszka , Krąpiec Marek , Słowiński Michał , Kittel Piotr
Published: January 2021

Chironomid (Diptera: Chironomidae) larvae play an important role in a wide range of aquatic ecosystems. The study focuses on Chironomidae trophic guilds and morphological types as indicator traits in reconstructions of habitat changes in shallow water bodies. Mentum and ventromental plates are important mouthparts whose shape depends on food type and feeding behavior. Chironomidae larvae strongly vary in the mode of life and feeding habits, representing almost every feeding group. Here we classified the mentum types into 16 groups and tested if they indicated similar past habitat changes as the Chironomidae functional feeding groups (FFGs), and tribes/subfamilies. Paleoecological data of biotic and abiotic proxies were derived from short sequences from a Late Glacial oxbow and a nearby medieval moat located in Central Poland. The study revealed that the habitat substratum structure, vegetation and physicochemical conditions are associated both with the feeding types and morphological traits. This provides a valuable tool for future reconstructions of habitat changes.
UDP-Glucose Dehydrogenases: Identification, Expression, and Function Analyses in Upland Cotton (Gossypium hirsutum)
Authors: Jia Tingting , Ge Qun , Zhang Shuya , Zhang Zhen , Liu Aiying , Fan Senmiao , Jiang Xiao , Feng Yulong , Zhang Lipeng , Niu Doudou , Huang Shen , Gong Wankui , Yuan Youlu , Shang Haihong
Published: January 2021

UDP-glucose dehydrogenase (UGD; EC1.1.1.22) is a NAD+-dependent enzyme that catalyzes the two-fold oxidation of UDP-glucose (UDP-Glc) to produce UDP-glucuronic acid and plays an important role in plant cell wall synthesis. A total of 42 UGD genes from four Gossypium genomes including G. hirsutum, G. arboretum, G. barbadense, and G. raimondii were identified and found that the UGD gene family has conservative evolution patterns in gene structure and protein domain. The growth of fibers can be effectively promoted after adding the UDP-Glc to the medium, and the GhUGD gene expression enhanced. In addition, the transgenic Arabidopsis lines over-expressing GH_D12G1806 had longer root lengths and higher gene expression level than the wild-type plants of Columbia-0. These results indicated that UGD may play important roles in cotton fiber development and has a guiding significance for dissecting fiber development mechanism.
Silencing of an Ubiquitin Ligase Increases Grain Width and Weight in indica Rice
Authors: Verma Ankit , Prakash Geeta , Ranjan Rajeev , Tyagi Akhilesh K. , Agarwal Pinky
Published: January 2021

Many quantitative trait loci (QTLs) have been identified by molecular genetic studies which control grain size by regulating grain width, length, and/or thickness. Grain width 2 (GW2) is one such QTL that codes for a RING-type E3 ubiquitin ligase and increases grain size by regulating grain width through ubiquitin-mediated degradation of unknown substrates. A natural variation (single-nucleotide polymorphism at the 346th position) in the functional domain-coding region of OsGW2 in japonica rice genotypes has been shown to cause an increase in grain width/weight in rice. However, this variation is absent in indica rice genotypes. In this study, we report that reduced expression of OsGW2 can alter grain size, even though natural sequence variation is not responsible for increased grain size in indica rice genotypes. OsGW2 shows high expression in seed development stages and the protein localizes to the nucleus and cytoplasm. Downregulation of OsGW2 by RNAi technology results in wider and heavier grains. Microscopic observation of grain morphology suggests that OsGW2 determines grain size by influencing both cell expansion and cell proliferation in spikelet hull. Using transcriptome analysis, upregulated genes related to grain size regulation have been identified among 1,426 differentially expressed genes in an OsGW2_RNAi transgenic line. These results reveal that OsGW2 is a negative regulator of grain size in indica rice and affects both cell number and cell size in spikelet hull.
Identification of Key Tissue-Specific, Biological Processes by Integrating Enhancer Information in Maize Gene Regulatory Networks
Authors: Fagny Maud , Kuijjer Marieke Lydia , Stam Maike , Joets Johann , Turc Olivier , Rozière Julien , Pateyron Stéphanie , Venon Anthony , Vitte Clémentine
Published: January 2021

Enhancers are key players in the spatio-temporal coordination of gene expression during numerous crucial processes, including tissue differentiation across development. Characterizing the transcription factors (TFs) and genes they connect, and the molecular functions underpinned is important to better characterize developmental processes. In plants, the recent molecular characterization of enhancers revealed their capacity to activate the expression of several target genes. Nevertheless, identifying these target genes at a genome-wide level is challenging, particularly for large-genome species, where enhancers and target genes can be hundreds of kilobases away. Therefore, the contribution of enhancers to plant regulatory networks remains poorly understood. Here, we investigate the enhancer-driven regulatory network of two maize tissues at different stages: leaves at seedling stage (V2-IST) and husks (bracts) at flowering. Using systems biology, we integrate genomic, epigenomic, and transcriptomic data to model the regulatory relationships between TFs and their potential target genes, and identify regulatory modules specific to husk and V2-IST. We show that leaves at the V2-IST stage are characterized by the response to hormones and macromolecules biogenesis and assembly, which are regulated by the BBR/BPC and AP2/ERF TF families, respectively. In contrast, husks are characterized by cell wall modification and response to abiotic stresses, which are, respectively, orchestrated by the C2C2/DOF and AP2/EREB families. Analysis of the corresponding enhancer sequences reveals that two different transposable element families (TIR transposon Mutator and MITE Pif/Harbinger) have shaped part of the regulatory network in each tissue, and that MITEs have provided potential new TF binding sites involved in husk tissue-specificity.
Transcriptome Analysis of lncRNA–mRNA Interactions in Chronic Atrophic Gastritis
Authors: Chao Yang , Jin Jingpeng , Wang Liqiang , Jin Xiya , Yang Lei , Zhang Bin
Published: January 2021

The aim of this study was to identify prognosis-related differentially expressed lncRNAs and mRNAs in chronic atrophic gastritis (CAG). By analysis of high-throughput whole-transcriptome sequencing data, the levels of lncRNAs and mRNAs between CAG and chronic non-atrophic gastritis were compared pairwisely. In total, 97,282 lncRNA transcripts and 20,307 mRNA transcripts were acquired, including 50 upregulated and 66 downregulated lncRNAs and 377 upregulated and 763 downregulated mRNAs in CAG (p < 0.05, fold change ≥ 2). Moreover, the interactions of the differentially expressed genes in CAG were investigated by gene ontology enrichment analysis, showing that the enriched genes are involved in many biological processes, such as MAP kinase activity, heat generation, and protein modification processes. Through the construction of co-expression networks of the differentially expressed genes in CAG, three critical lncRNAs nodes were identified as potential key factors in CAG. Eight mRNAs common in both the co-expression network and the protein–protein interaction network were selected via Venn analysis, including DGKA, EIF6, HKDC1, DHRS11, 1, KRT15, TESPA1, and CDHR2. Finally, the expression levels of five differentially expressed lncRNAs in CAG were confirmed by quantitative real-time polymerase chain reaction. In conclusion, this study presents novel promising biomarkers for the diagnosis of CAG.