bluuebunny/crossref_metadata_2025 huggingface dataset:
El aprendizaje en tiempos de contingencia
Authors: Pacheco González María de Lourdes , Ramírez Ramírez Laura Patricia
Published: June 2021

Si bien la educación a distancia no es nueva, la contingencia provocada por el COVID-19 llevó a que profesores y estudiantes de la Universidad Autónoma de Aguascalientes dejaran las aulas y recurrieran a la modalidad educativa en línea, para continuar con los cursos. Pero ¿cómo ha sido esta experiencia para los jóvenes bachilleres y universitarios? Ante esta pregunta es que se formuló una encuesta para conocer la experiencia de los estudiantes; los resultados dan cuenta de que a pesar del tránsito a una experiencia en línea ha sido buena, de que ha permitido desarrollar habilidades y actitudes nuevas, así como el desplegar su capacidad de autoaprendizaje, los estudiantes siguen prefiriendo el modelo presencial, donde el trato con los compañeros y con los profesores les permiten comparar opiniones y así modificar o mantener las propias. Esta experiencia ha de llevar a presentar cursos híbridos, donde tanto profesores como estudiantes den lo mejor de sí.
Cover and Credits
Authors: Mallary Kevin J.
Published: June 2021

Cover and journal credits pages for Volume 5, Number 2.
Perrin n-Dimensional Relations
Authors: VİEİRA Renata , MANGUEİRA Milena , ALVES Francisco Regis , CRUZ CATARİNO Paula Maria Machado
Published: June 2021

This work aims, to perform a complexity in the Perrin sequence, to present the two-dimensional, three-dimensional, and n-dimensional recurrence relations of this sequence. Thus, from the one-dimensional relationship of this sequence, we will discuss the increase of its dimensionality and the insertion of imaginary units in the Perrin sequence, which is a recursive sequence of third order and presents large similarities with the Padovan sequence, differing only its initial values. Moreover, we will present a relationship between the Perrin numbers and the Padovan numbers, which will be used to perform the complexity of this sequence.
Potencial imunomodulador de extrato etanólico de Momordica charantia L. em leite de vacas mastíticas
Authors: Cunha Carolina Ferrari Luz , Marchi Patrícia Gelli Feres de , Messias Cassio Toledo , Cotrim Aron Carlos de Melo , Fujimori Mahmi , Amorim Sara Lucena de , Araújo Danielle Saldanha de Souza
Published: June 2021

A bovinocultura de leite é um importante setor da economia brasileira. Infelizmente, diversos fatores afetam a qualidade e a quantidade de leite produzido em unidades leiteiras, dentre eles a mastite. A mastite é uma doença caracterizada por inflamações nas glândulas mamárias, tendo diversas causas. O controle da mastite é feito a partir de manejo preventivo e uso de antibiótico intramamário. O uso frequente de antibióticos pode causar resistência, dificultando tratamentos posteriores. Portanto, estudos de fitoterápicos no controle da mastite vem se tornando mais frequente e com resultados promissores. Diversas plantas e extratos naturais já foram testados no controle da mastite. A planta estudada em questão é chamada de Momordica charantia L., conhecida popularmente como melão de São Caetano. Tal planta já demostrou inúmeros efeitos medicinais para diferentes finalidades. O objetivo deste trabalho consiste em analisar o potencial imunomodulador de Momordica charantia sobre células de leite de vacas mastíticas. Foram coletadas 20 amostras de leite, sendo dez de vacas sadias e dez de vacas com mastite clínica. Posteriormente, foram realizadas analises quanto a viabilidade celular, liberação de ânion superóxido, dosagem da enzima superóxido dismutase, fagocitose e atividade microbicida. Nas amostras que continham extrato observou-se uma diminuição do ânion superóxido e da enzima superóxido dismutase provavelmente devido ao mecanismo de escape das bactérias, e um aumento na atividade microbicida e na fagocitose sugerindo que o extrato de Momordica charantia seja um potencial imunomodulador contra a mastite bovina.
Osteogenesis and biofilms formation on titanium surfaces submitted to oxygen plasma immersion ion implantation
Authors: Tini Italo Rigotti Pereira , Araújo Juliani Caroline Ribeiro de , Gonçalves Thais Fernanda , Oliveira Rogerio de Moraes , Reis Danieli Aparecida Pereira , Reis Adriano Gonçalves dos , Vasconcellos Luana Marotta Reis de
Published: June 2021

The objectives of this study were to characterize titanium (Ti) surfaces treated by ion implantation by immersion in oxygen plasma (O-PIII) at different temperatures, correlating these implanted layers with therapeutic effects and with osteogenesis, as well as the formation of monotypic biofilms microbial. The groups were divided into: a) Ti (pre-treatment) b) Ti O-PIII at 400 ° C. c) Ti O-PIII at 500 ° C. d) Ti O-PIII at 600 ° C. The properties and surface characteristics were evaluated according to the roughness, texture, corrosion resistance, formation of new phases and the identification of chemical compounds present. Cellular analyzes investigated cell interaction, viability, total protein content, alkaline phosphatase and quantification of mineralized nodules using MG-63 cells. The formation of monotypic microbial biofilms, including P. aeruginosa, S. aureus, S. mutans and C. albicans were evaluated. The increase in surface roughness, corrosion resistance and oxygen content, leading to the formation of TiO2-rutile with more intense peaks and in greater numbers according to the increase in the substrate temperature, ionic implanted Ti samples was observed. There was also a significant increase in cell viability, total protein production, alkaline phosphatase activity and formation of mineralization nodules for the group treated with O-PIII at 600ºC compared to other groups, in addition to a reduction of microorganisms in the groups treated with O- PIII. Therefore, treatment with O-PIII at 600ºC in Ti grade IV showed favorable results for its use.
THE EFFECT OF UTILIZING YOUTUBE VIDEO IN IMPROVING MATHEMATIC COMMUNICATION SKILLS IN BASIC TEACHER EDUCATION
Authors: Ruqoyyah Siti , Arga Hana Sakura Putu , Wulandari Medita Ayu
Published: June 2021

This research is motivated by the low mathematical communication skills of prospective elementary school teacher students. The purpose of this study is to see the achievement and improvement of students' mathematical communication skills using YouTube videos and those using conventional learning. This study used a quasi-experimental method with a non-equivalent pretest and posttest control group design. The population in this study were all students of second semester elementary school teacher candidates at one of the private tertiary institutions in Cimahi City. While the sample in this study were 60 students of second semester elementary school teacher candidates. The instrument used in this study was a test of mathematical communication skills. The results showed: 1) achievement and improvement of mathematical communication skills using YouTube videos was better than conventional learning; 2) Students can be confident, active and motivated in learning mathematics with YouTube videos.
Group Theoretic proof of infinitude of primes.
Authors: Haque Nazrul
Published: June 2021

A short proof using group theoretical idea.
Effects of Teaching Gardening on Science Students' Attitudes Towards Entrepreneurial Skills Acquisition
Authors:   University of Jos, Nigeria, Charity Dimlong , Ozoji Bernadette Ebele ,   Department of Science and Technology Education, University of Jos, Nigeria, Osasebor Florence Osaze ,   Department of Science and Technology Education, University of Jos, Nigeria, Umar Suleiman Ibn ,   Department of Science and Technology Education, University of Jos, Nigeria
Published: June 2021

This study investigated the effects of teaching gardening on science students' attitudes towards entrepreneurial skills acquisition in Jos South, Plateau State, Nigeria. The study employed the non-randomized pre-test-post-test non-equivalent control group design. A sample of 75 senior secondary school students from two intact classes, randomly assigned to an experimental group (n=38) and a control group (n=37) was used for the study. An Entrepreneurial Attitude Orientation Scale was used to collect data for analysis. The findings indicated that the experimental group exposed to gardening activities showed positive attitudes towards acquiring entrepreneurial skills unlike the control group. However, gender was found not to be a significant factor in students' attitudes towards entrepreneurial skills acquisition. It was concluded that teaching gardening has a significant effect on students' attitudes towards entrepreneurial skills acquisition. It is recommended that students should be taught gardening to enhance their attitudes towards entrepreneurial skills acquisition for self-reliance, among others.
Inhibiting of TACC3 Promotes Cell Proliferation, Cell Invasion and the EMT Pathway in Breast Cancer
Authors: Huo Qin , Chen Siqi , Li Zhenwei , Wang Juan , Li Jiaying , Xie Ni
Published: June 2021

Accumulating evidences indicate that transforming acidic coiled-coil 3 (TACC3) is a tumor-related gene, was highly expressed in a variety of human cancers, which is involved in cancer development. However, the potential role of TACC3 in breast cancer remains largely unknown. In the present study, we found that TACC3 was highly-expressed in breast cancer tissues, and its level was positively correlated with the clinical features of breast cancer patients. Specifically, TACC3 expression was significantly associated with the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status, nodal status, the scarff-bloom-richardson (SBR) grade, nottingham prognostic index (NPI), age, subtypes, and triple-negative and basal-like status, suggesting that TACC3 may be a potential diagnostic indicator of breast cancer. Furthermore, functional studies have shown that inhibition of TACC3 can significantly promote the cell proliferation and viability of breast cancer cells. Moreover, TACC3 knockdown suppressed the expression of E-cadherin, but increased the expression of N-cadherin, Snail, ZEB1, and TWIST, which indicate that TACC3 may impact the migration of breast cancer cells in vitro. Taken together, these findings indicate that TACC3 may serve as a prognostic and therapeutic indicator of breast cancer.
Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Potential Therapeutic Strategy for Acute Kidney Injury
Authors: Li Jia-Kun , Yang Cheng , Su Ying , Luo Jing-Chao , Luo Ming-Hao , Huang Dan-Lei , Tu Guo-Wei , Luo Zhe
Published: June 2021

Acute kidney injury (AKI) is a common and potential life-threatening disease in patients admitted to hospital, affecting 10%–15% of all hospitalizations and around 50% of patients in the intensive care unit. Severe, recurrent, and uncontrolled AKI may progress to chronic kidney disease or end-stage renal disease. AKI thus requires more efficient, specific therapies, rather than just supportive therapy. Mesenchymal stem cells (MSCs) are considered to be promising cells for cellular therapy because of their ease of harvesting, low immunogenicity, and ability to expand in vitro. Recent research indicated that the main therapeutic effects of MSCs were mediated by MSC-derived extracellular vesicles (MSC-EVs). Furthermore, compared with MSCs, MSC-EVs have lower immunogenicity, easier storage, no tumorigenesis, and the potential to be artificially modified. We reviewed the therapeutic mechanism of MSCs and MSC-EVs in AKI, and considered recent research on how to improve the efficacy of MSC-EVs in AKI. We also summarized and analyzed the potential and limitations of EVs for the treatment of AKI to provide ideas for future clinical trials and the clinical application of MSC-EVs in AKI.
The Emerging Role of Mast Cells in Response to Fungal Infection
Authors: Yu Miao , Song Xiao-ting , Liu Bo , Luan Ting-ting , Liao Shuang-lu , Zhao Zuo-tao
Published: June 2021

Mast cells (MCs) have been considered as the core effector cells of allergic diseases. However, there are evidence suggesting that MCs are involved in the mechanisms of fungal infection. MCs are mostly located in the border between host and environment and thus may have easy contact with the external environmental pathogens. These cells express receptors which can recognize pathogen-associated molecular patterns such as Toll-like receptors (TLR2/4) and C-type Lectins receptors (Dectin-1/2). Currently, more and more data indicate that MCs can be interacted with some fungi (Candida albicans, Aspergillus fumigatus and Sporothrix schenckii). It is demonstrated that MCs can enhance immunity through triggered degranulation, secretion of cytokines and chemokines, neutrophil recruitment, or provision of extracellular DNA traps in response to the stimulation by fungi. In contrast, the involvement of MCs in some immune responses may lead to more severe symptoms, such as intestinal barrier function loss, development of allergic bronchial pulmonary aspergillosis and increased area of inflammatory in S. schenckii infection. This suggests that MCs and their relevant signaling pathways are potential treatment regimens to prevent the clinically unwanted consequences. However, it is not yet possible to make definitive statements about the role of MCs during fungal infection and/or pathomechanisms of fungal diseases. In our article, we aim to review the function of MCs in fungal infections from molecular mechanism to signaling pathways, and illustrate the role of MCs in some common host-fungi interactions.
Glucocorticoid Therapy in Inflammatory Bowel Disease: Mechanisms and Clinical Practice
Authors: Bruscoli Stefano , Febo Marta , Riccardi Carlo , Migliorati Graziella
Published: June 2021

Inflammatory bowel disease (IBD) comprises ulcerative colitis (UC) and Crohn’s disease (CD). IBD etiopathology is multifactorial and involves alteration of immune cells and chronic activation of the inflammatory cascade against yet unknown environmental factors that trigger the disease. IBD therapy aims at improving the quality of life and reducing the risk of disease-related complications to avoid the need for surgery. There is no specific cure for IBDs, and the focus of therapy is supportive measures and use of anti-inflammatory and immunosuppressive drugs. Glucocorticoids (GCs) are powerful anti-inflammatory and immunomodulatory agents used to treat many acute and chronic inflammatory diseases. GCs remain basic treatment for moderate-to-severe IBD, but their use is limited by several important adverse drug effects. Topical administration of a second-generation of GCs, such as budesonide and beclomethasone dipropionate (BDP), represents a valid alternative to use of older, systemic GCs. Administration of second-generation GCs shows promisingly high topical activity and less systemic toxicity, but maintenance therapy with these new GCs in IBD patients is associated with multiple adverse effects. In this review, we make a comparative analysis of the efficacy of first-generation and second-generation GCs in IBD treatment. Unraveling GC biology at the molecular level to uncouple their clinical benefits from detrimental effects is important. One approach is to consider new GC mediators, such as glucocorticoid-induced leucine zipper, which may have similar anti-inflammatory properties, but avoids the side effects of GCs. This in-depth analysis can help to improve the development and the clinical outcomes of GC therapies in IBD.
Relative Abundance of Floating Plastic Debris and Neuston in the Eastern North Pacific Ocean
Authors: Egger Matthias , Quiros Lauren , Leone Giulia , Ferrari Francesco , Boerger Christiana M. , Tishler Michelle
Published: June 2021

Despite an increasing research conducted on ocean plastic pollution over the last decade, there are still large knowledge gaps in our current understanding of how floating plastic debris accumulating in subtropical oceanic gyres may harm the surface-associated pelagic community known as neuston. Removing floating plastic debris from the surface ocean can minimize potentially adverse effects of plastic pollution on the neuston, as well as prevent the formation of large quantities of secondary micro- and nanoplastics. However, due to the scarcity of observational data from remote and difficult to access offshore waters, neuston dynamics in subtropical oceanic gyres and thus the potential impacts of plastic pollution as well as of cleanup activities on the neuston remain uncertain. Here, we provide rare observational data of the relative distribution of floating plastic debris (0.05–5 cm in size) and members of the neuston in the eastern North Pacific Ocean. Our results reveal that the dominant neustonic species co-occurring with high concentrations of floating plastic debris in the North Pacific Garbage Patch (NPGP) such as Porpita porpita, Halobates spp., pteropods, isopods, heteropods, and crabs depict either a low atmospheric drag due to physical attributes or a potential plastic-associated fitness benefit such as increased surface area for oviposition and structure for habitat. We further observe relatively higher plastic to organism ratios inside the NPGP for most target species compared to waters outside the NPGP. The findings presented here provide a first observational baseline to develop ecological models that can help evaluate the long-term risks of plastic pollution and of offshore cleanup activities for neuston in the eastern North Pacific Ocean. We further suggest that offshore mitigation strategies aiming at removing floating plastic debris from the ocean surface need to evaluate both, the direct impact of neuston bycatch during plastic removal on neuston population dynamics, as well as the potential benefits of reducing the negative effects of plastic pollution on the neuston.
Mechanical Properties of WC-Si3N4 Composites With Ultrafine Porous Boron Nitride Nanofiber Additive
Authors: Cao Ting , Li Xiaoqiang , Li Jingmao , Huang Yang , Qu Shengguan , Yang Chao , Liang Liang , Song Tao
Published: June 2021

WC-10 wt.% Si3N4 composites toughened with ultrafine porous boron nitride nanofiber (0, 0.01, 0.05, 0.1, and 0.15 wt.%) were prepared for the first time by spark plasma sintering. Compared with the WC-Si3N4 composite sintered in the same condition, the obtained WC-10 wt.% Si3N4 composites with ultrafine porous boron nitride were found to possess better hardness and fracture toughness. In addition, the Si3N4 phase in the UPBNNF toughened composites did not exhibit traditional catastrophic fracture as indicated in most investigations. In this study, the phenomena are discussed, and a probable mechanism is elucidated. It is deduced that the approach could be extended to materials with a feature of internal liquid phase during the sintering process and could improve hardness and fracture toughness.
Disrupted Network Topology Contributed to Spatial Navigation Impairment in Patients With Mild Cognitive Impairment
Authors: Li Weiping , Zhao Hui , Qing Zhao , Nedelska Zuzana , Wu Sichu , Lu Jiaming , Wu Wenbo , Yin Zhenyu , Hort Jakub , Xu Yun , Zhang Bing
Published: June 2021

Impairment in spatial navigation (SN) and structural network topology is not limited to patients with Alzheimer’s disease (AD) dementia and can be detected earlier in patients with mild cognitive impairment (MCI). We recruited 32 MCI patients (65.91 ± 11.33 years old) and 28 normal cognition patients (NC; 69.68 ± 10.79 years old), all of whom underwent a computer-based battery of SN tests evaluating egocentric, allocentric, and mixed SN strategies and diffusion-weighted and T1-weighted Magnetic Resonance Imaging (MRI). To evaluate the topological features of the structural connectivity network, we calculated its measures such as the global efficiency, local efficiency, clustering coefficient, and shortest path length with GRETNA. We determined the correlation between SN accuracy and network topological properties. Compared to NC, MCI subjects demonstrated a lower egocentric navigation accuracy. Compared with NC, MCI subjects showed significantly decreased clustering coefficients in the left middle frontal gyrus, right rectus, right superior parietal gyrus, and right inferior parietal gyrus and decreased shortest path length in the left paracentral lobule. We observed significant positive correlations of the shortest path length in the left paracentral lobule with both the mixed allocentric–egocentric and the allocentric accuracy measured by the average total errors. A decreased clustering coefficient in the right inferior parietal gyrus was associated with a larger allocentric navigation error. White matter hyperintensities (WMH) did not affect the correlation between network properties and SN accuracy. This study demonstrated that structural connectivity network abnormalities, especially in the frontal and parietal gyri, are associated with a lower SN accuracy, independently of WMH, providing a new insight into the brain mechanisms associated with SN impairment in MCI.
Amyloid β and Amyloid Precursor Protein Synergistically Suppress Large-Conductance Calcium-Activated Potassium Channel in Cortical Neurons
Authors: Yamamoto Kenji , Yamamoto Ryo , Kato Nobuo
Published: June 2021

Intracellular amyloid β (Aβ) injection suppresses the large-conductance calcium-dependent potassium (BK) channel in cortical pyramidal cells from wild-type (WT) mice. In 3xTg Alzheimer’s disease (AD) model mice, intraneuronal Aβ is genetically programed to accumulate, which suppresses the BK channel. However, the mode of BK channel suppression remained unclarified. The present report revealed that only one (11A1) of the three anti-Aβ-oligomer antibodies that we examined, but not anti-monomer-Aβ-antibodies, was effective in recovering BK channel activity in 3xTg neurons. Antibodies against amyloid precursor protein (APP) were also found to be effective, suggesting that APP plays an essential part in this Aβ-oligomer-induced BK channel suppression in 3xTg neurons. In WT neurons, by contrast, APP suppressed BK channels by itself, which suggests that either APP or Aβ is sufficient to block BK channels, thus pointing to a different co-operativity of Aβ and APP in WT and 3xTg neurons. To clarify this difference, we relied on our previous finding that the scaffold protein Homer1a reverses the BK channel blockade in both WT and 3xTg neurons. In cortical neurons from 3xTg mice that bear Homer1a knockout (4xTg mice), neither anti-APP antibodies nor 11A1, but only the 6E10 antibody that binds both APP and Aβ, rescued the BK channel suppression. Given that Homer1a expression is activity dependent and 3xTg neurons are hyperexcitable, Homer1a is likely to be expressed sufficiently in 3xTg neurons, thereby alleviating the suppressive influence of APP and Aβ on BK channel. A unique way that APP modifies Aβ toxicity is thus proposed.
Second Language Learning in Older Adults: Effects on Brain Structure and Predictors of Learning Success
Authors: Nilsson Jonna , Berggren Rasmus , Garzón Benjamín , Lebedev Alexander V. , Lövdén Martin
Published: June 2021

It has previously been demonstrated that short-term foreign language learning can lead to structural brain changes in younger adults. Experience-dependent brain plasticity is known to be possible also in older age, but the specific effect of foreign language learning on brain structure in language-and memory-relevant regions in the old brain remains unknown. In the present study, 160 older Swedish adults (65–75 years) were randomized to complete either an entry-level Italian course or a relaxation course, both with a total duration of 11 weeks. Structural MRI scans were conducted before and after the intervention in a subset of participants to test for differential change in gray matter in the two groups in the inferior frontal gyrus, the superior temporal gyrus, and the hippocampus, and in white matter microstructure in the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), fronto-occipital fasciculus, and the hippocampal (HC) section of the cingulum. The study found no evidence for differential structural change following language training, independent of achieved vocabulary proficiency. However, hippocampal volume and associative memory ability before the intervention were found to be robust predictors of vocabulary proficiency at the end of the language course. The results suggest that having greater hippocampal volume and better associative memory ability benefits vocabulary learning in old age but that the very initial stage of foreign language learning does not trigger detectable changes in brain morphometry in old age.
Ferroptosis and Its Multifaceted Roles in Cerebral Stroke
Authors: Zhang Yongfa , Lu Xiaoyang , Tai Bai , Li Weijia , Li Tao
Published: June 2021

Ferroptosis is a unique regulated cell death defined by the intracellular iron overload and distinct biological features compared with other well-known programmed cell death. Ferroptosis can be triggered by many causes including decreased expression of glutathione (GSH), inhibition of the function of glutathione-dependent peroxidase 4 (GPX4), and system xc–, all of which finally lead to the over-accumulation of lipid peroxides in the cell. Ferroptosis has been reported to play an important role in the pathophysiological process of various cancers. In recent years, much evidence also proved that ferroptosis is involved in the progress of cerebral stroke. In this review, we summarized the characteristics of ferroptosis and the potential relationship between ferroptosis and ischemic and hemorrhagic stroke, to provide new targets and ideas for the therapy of stroke.
Dystonia Management: What to Expect From the Future? The Perspectives of Patients and Clinicians Within DystoniaNet Europe
Authors: Smit Marenka , Albanese Alberto , Benson Monika , Edwards Mark J. , Graessner Holm , Hutchinson Michael , Jech Robert , Krauss Joachim K. , Morgante Francesca , Pérez Dueñas Belen , Reilly Richard B. , Tinazzi Michele , Contarino Maria Fiorella , Tijssen Marina A. J. ,   The Collaborative Working Group
Published: June 2021

Improved care for people with dystonia presents a number of challenges. Major gaps in knowledge exist with regard to how to optimize the diagnostic process, how to leverage discoveries in pathophysiology into biomarkers, and how to develop an evidence base for current and novel treatments. These challenges are made greater by the realization of the wide spectrum of symptoms and difficulties faced by people with dystonia, which go well-beyond motor symptoms. A network of clinicians, scientists, and patients could provide resources to facilitate information exchange at different levels, share mutual experiences, and support each other's innovative projects. In the past, collaborative initiatives have been launched, including the American Dystonia Coalition, the European Cooperation in Science and Technology (COST—which however only existed for a limited time), and the Dutch DystonieNet project. The European Reference Network on Rare Neurological Diseases includes dystonia among other rare conditions affecting the central nervous system in a dedicated stream. Currently, we aim to broaden the scope of these initiatives to a comprehensive European level by further expanding the DystoniaNet network, in close collaboration with the ERN-RND. In line with the ERN-RND, the mission of DystoniaNet Europe is to improve care and quality of life for people with dystonia by, among other endeavors, facilitating access to specialized care, overcoming the disparity in education of medical professionals, and serving as a solid platform to foster international clinical and research collaborations. In this review, both professionals within the dystonia field and patients and caregivers representing Dystonia Europe highlight important unsolved issues and promising new strategies and the role that a European network can play in activating them.
Suppression of Microgliosis With the Colony-Stimulating Factor 1 Receptor Inhibitor PLX3397 Does Not Attenuate Memory Defects During Epileptogenesis in the Rat
Authors: Wyatt-Johnson Season K. , Sommer Alexandra L. , Shim Kevin Y. , Brewster Amy L.
Published: June 2021

Events of status epilepticus (SE) trigger the development of temporal lobe epilepsy (TLE), a type of focal epilepsy that is commonly drug-resistant and is highly comorbid with cognitive deficits. While SE-induced hippocampal injury, accompanied by gliosis and neuronal loss, typically disrupts cognitive functions resulting in memory defects, it is not definitively known how. Our previous studies revealed extensive hippocampal microgliosis that peaked between 2 and 3 weeks after SE and paralleled the development of cognitive impairments, suggesting a role for reactive microglia in this pathophysiology. Microglial survival and proliferation are regulated by the colony-stimulating factor 1 receptor (CSF1R). The CSF1R inhibitor PLX3397 has been shown to reduce/deplete microglial populations and improve cognitive performance in models of neurodegenerative disorders. Therefore, we hypothesized that suppression of microgliosis with PLX3397 during epileptogenesis may attenuate the hippocampal-dependent spatial learning and memory deficits in the rat pilocarpine model of SE and acquired TLE. Different groups of control and SE rats were fed standard chow (SC) or chow with PLX3397 starting immediately after SE and for 3 weeks. Novel object recognition (NOR) and Barnes maze (BM) were performed to determine memory function between 2 and 3 weeks after SE. Then microglial populations were assessed using immunohistochemistry. Control rats fed with either SC or PLX3397 performed similarly in both NOR and BM tests, differentiating novel vs. familiar objects in NOR, and rapidly learning the location of the hidden platform in BM. In contrast, both SE groups (SC and PLX3397) showed significant deficits in both NOR and BM tests compared to controls. Both PLX3397-treated control and SE groups had significantly decreased numbers of microglia in the hippocampus (60%) compared to those in SC. In parallel, we found that PLX3397 treatment also reduced SE-induced hippocampal astrogliosis. Thus, despite drastic reductions in microglial cells, memory was unaffected in the PLX3397-treated groups compared to those in SC, suggesting that remaining microglia may be sufficient to help maintain hippocampal functions. In sum, PLX3397 did not improve or worsen the memory deficits in rats that sustained pilocarpine-induced SE. Further research is required to determine whether microglia play a role in cognitive decline during epileptogenesis.
Migraine Is More Than Just Headache: Is the Link to Chronic Fatigue and Mood Disorders Simply Due to Shared Biological Systems?
Authors: Karsan Nazia , Goadsby Peter J.
Published: June 2021

Migraine is a symptomatically heterogeneous condition, of which headache is just one manifestation. Migraine is a disorder of altered sensory thresholding, with hypersensitivity among sufferers to sensory input. Advances in functional neuroimaging have highlighted that several brain areas are involved even prior to pain onset. Clinically, patients can experience symptoms hours to days prior to migraine pain, which can warn of impending headache. These symptoms can include mood and cognitive change, fatigue, and neck discomfort. Some epidemiological studies have suggested that migraine is associated in a bidirectional fashion with other disorders, such as mood disorders and chronic fatigue, as well as with other pain conditions such as fibromyalgia. This review will focus on the literature surrounding alterations in fatigue, mood, and cognition in particular, in association with migraine, and the suggested links to disorders such as chronic fatigue syndrome and depression. We hypothesize that migraine should be considered a neural disorder of brain function, in which alterations in aminergic networks integrating the limbic system with the sensory and homeostatic systems occur early and persist after headache resolution and perhaps interictally. The associations with some of these other disorders may allude to the inherent sensory sensitivity of the migraine brain and shared neurobiology and neurotransmitter systems rather than true co-morbidity.
On the Use of a Multimodal Optimizer for Fitting Neuron Models. Application to the Cerebellar Granule Cell
Authors: Marín Milagros , Cruz Nicolás C. , Ortigosa Eva M. , Sáez-Lara María J. , Garrido Jesús A. , Carrillo Richard R.
Published: June 2021

This article extends a recent methodological workflow for creating realistic and computationally efficient neuron models whilst capturing essential aspects of single-neuron dynamics. We overcome the intrinsic limitations of the extant optimization methods by proposing an alternative optimization component based on multimodal algorithms. This approach can natively explore a diverse population of neuron model configurations. In contrast to methods that focus on a single global optimum, the multimodal method allows directly obtaining a set of promising solutions for a single but complex multi-feature objective function. The final sparse population of candidate solutions has to be analyzed and evaluated according to the biological plausibility and their objective to the target features by the expert. In order to illustrate the value of this approach, we base our proposal on the optimization of cerebellar granule cell (GrC) models that replicate the essential properties of the biological cell. Our results show the emerging variability of plausible sets of values that this type of neuron can adopt underlying complex spiking characteristics. Also, the set of selected cerebellar GrC models captured spiking dynamics closer to the reference model than the single model obtained with off-the-shelf parameter optimization algorithms used in our previous article. The method hereby proposed represents a valuable strategy for adjusting a varied population of realistic and simplified neuron models. It can be applied to other kinds of neuron models and biological contexts.
Temporal Characteristics of Visual Processing in Amblyopia
Authors: Hu Xia , Qin Yi , Ying Xiaoxiao , Yuan Junli , Cui Rong , Ruan Xiaowei , He Xianghang , Lu Zhong-Lin , Lu Fan , Hou Fang
Published: June 2021

Purpose

Amblyopia affects not only spatial vision but also temporal vision. In this study, we aim to investigate temporal processing deficits in amblyopia.

Methods

Twenty amblyopic patients (age: 27.0 ± 5.53 years, 15 males), and 25 normal observers (age: 25.6 ± 4.03 years, 15 males) were recruited in this study. Contrast thresholds in an orientation discrimination task in five target-mask stimulus onset asynchronies (SOA) conditions (16.7 ms, 33.4 ms, 50.0 ms, 83.4 ms, and ∞/no noise) were measured. An elaborated perceptual template model (ePTM) was fit to the behavioral data to derive the temporal profile of visual processing for each participant.

Results

There were significant threshold differences between the amblyopic and normal eyes [F(1,43) = 10.6, p = 0.002] and a significant group × SOA interaction [F(2.75,118) = 4.98, p = 0.004], suggesting different temporal processing between the two groups. The ePTM fitted the data well (χ2 test, all ps > 0.50). Compared to the normal eye, the amblyopic eye had a lower template gain (p = 0.046), and a temporal window with lower peak and broader width (all ps < 0.05). No significant correlation was found between the observed temporal deficits and visual acuity in amblyopia (ps > 0.50). Similar results were found in the anisometropic amblyopia subgroup. No significant difference was found between the fellow eyes of the monocular amblyopia and the normal eyes.

Conclusion

Amblyopia is less efficient in processing dynamic visual stimuli. The temporal deficits in amblyopia, represented by a flattened temporal window, are likely independent of spatial vision deficits.
Axotomy Induces Drp1-Dependent Fragmentation of Axonal Mitochondria
Authors: Kedra Joseph , Lin Shen , Pacheco Almudena , Gallo Gianluca , Smith George M.
Published: June 2021

It is well established that CNS axons fail to regenerate, undergo retrograde dieback, and form dystrophic growth cones due to both intrinsic and extrinsic factors. We sought to investigate the role of axonal mitochondria in the axonal response to injury. A viral vector (AAV) containing a mitochondrially targeted fluorescent protein (mitoDsRed) as well as fluorescently tagged LC3 (GFP-LC3), an autophagosomal marker, was injected into the primary motor cortex, to label the corticospinal tract (CST), of adult rats. The axons of the CST were then injured by dorsal column lesion at C4-C5. We found that mitochondria in injured CST axons near the injury site are fragmented and fragmentation of mitochondria persists for 2 weeks before returning to pre-injury lengths. Fragmented mitochondria have consistently been shown to be dysfunctional and detrimental to cellular health. Inhibition of Drp1, the GTPase responsible for mitochondrial fission, using a specific pharmacological inhibitor (mDivi-1) blocked fragmentation. Additionally, it was determined that there is increased mitophagy in CST axons following Spinal cord injury (SCI) based on increased colocalization of mitochondria and LC3. In vitro models revealed that mitochondrial divalent ion uptake is necessary for injury-induced mitochondrial fission, as inhibiting the mitochondrial calcium uniporter (MCU) using RU360 prevented injury-induced fission. This phenomenon was also observed in vivo. These studies indicate that following the injury, both in vivo and in vitro, axonal mitochondria undergo increased fission, which may contribute to the lack of regeneration seen in CNS neurons.
Pelvic Pain Alters Functional Connectivity Between Anterior Cingulate Cortex and Hippocampus in Both Humans and a Rat Model
Authors: Yu Wenjun , Wu Xiaoyan , Chen Yunan , Liang Zhiying , Jiang Jinxiang , Misrani Afzal , Su Yun , Peng Yigang , Chen Jian , Tang Binliang , Sun Mengyao , Long Cheng , Shen Jun , Yang Li
Published: June 2021

The anterior cingulate cortex (ACC) and hippocampus (HIPP) are two key brain regions associated with pain and pain-related affective processing. However, whether and how pelvic pain alters the neural activity and connectivity of the ACC and HIPP under baseline and during social pain, and the underlying cellular and molecular mechanisms, remain unclear. Using functional magnetic resonance imaging (fMRI) combined with electrophysiology and biochemistry, we show that pelvic pain, particularly, primary dysmenorrhea (PDM), causes an increase in the functional connectivity between ACC and HIPP in resting-state fMRI, and a smaller reduction in connectivity during social exclusion in PDM females with periovulatory phase. Similarly, model rats demonstrate significantly increased ACC-HIPP synchronization in the gamma band, associating with reduced modulation by ACC-theta on HIPP-gamma and increased levels of receptor proteins and excitation. This study brings together human fMRI and animal research and enables improved therapeutic strategies for ameliorating pain and pain-related affective processing.
Molecular and Metabolic Reprogramming: Pulling the Strings Toward Tumor Metastasis
Authors: Hipólito Ana , Martins Filipa , Mendes Cindy , Lopes-Coelho Filipa , Serpa Jacinta
Published: June 2021

Metastasis is a major hurdle to the efficient treatment of cancer, accounting for the great majority of cancer-related deaths. Although several studies have disclosed the detailed mechanisms underlying primary tumor formation, the emergence of metastatic disease remains poorly understood. This multistep process encompasses the dissemination of cancer cells to distant organs, followed by their adaptation to foreign microenvironments and establishment in secondary tumors. During the last decades, it was discovered that these events may be favored by particular metabolic patterns, which are dependent on reprogrammed signaling pathways in cancer cells while they acquire metastatic traits. In this review, we present current knowledge of molecular mechanisms that coordinate the crosstalk between metastatic signaling and cellular metabolism. The recent findings involving the contribution of crucial metabolic pathways involved in the bioenergetics and biosynthesis control in metastatic cells are summarized. Finally, we highlight new promising metabolism-based therapeutic strategies as a putative way of impairing metastasis.
Sites of Distant Metastases and Cancer-Specific Survival in Intraductal Papillary Mucinous Neoplasm With Associated Invasive Carcinoma: A Study of 1,178 Patients
Authors: Huang Xiaoyi , You Siting , Ding Guiling , Liu Xingchen , Wang Jin , Gao Yisha , Zheng Jianming
Published: June 2021

Background

To explore the impact of distant metastases on cancer-specific survival in patients with intraductal papillary mucinous neoplasm (IPMN) with associated invasive carcinoma and identify the risk factor of distant metastases in IPMN with associated invasive carcinoma.

Methods

Patients with IPMN with associated invasive carcinoma between 2010 and 2015 were retrospectively selected from the Surveillance, Epidemiology, and End Results (SEER) database. The survival analyses were assessed by Kaplan-Meier analyses and log-rank test. The impact of distant metastases was evaluated by Cox regression model and the risk factors of distant metastases were identified by logistic regression analyses, respectively.

Results

The median cancer-specific survival time of patients with no metastases, isolated liver, isolated lung, and multiple site metastases were 19 months, 4 months, 7 months, and 3 months, respectively. In patients with isolated liver metastases, multivariate analysis after adjustment indicated that chemotherapy (Hazard Ratio [HR]=0.351, 95% confidence interval [CI]=0.256-0.481, P<0.001) was a protective prognostic factor for cancer-specific survival (CSS) in patients with isolated liver metastases. In isolated lung metastases subgroup, old age (HR=1.715, 95% CI=1.037-2.838, P=0.036) and chemotherapy (HR=0.242, 95% CI=0.134-0.435, P<0.001) were related to CSS in multivariable Cox regression analysis(P<0.05). Tumor located in the pancreatic body/tail (HR=2.239, 95% CI=1.140-4.400, P=0.019) and chemotherapy (HR=0.191, 95% CI=0.108-0.340, P<0.001) were independent prognostic factors for CSS in patients with multiple metastases. Finally, a nomogram was constructed for cancer-specific survival and the predicted C-index was 0.780 (95% CI=0.762-0.798).

Conclusion

The liver is the most common site of distant metastases in IPMN with associated invasive carcinoma. Tumor located in the pancreatic body/tail and chemotherapy are independent prognostic factors for CSS in patients with multiple metastases. Further, tumor located in body/tail is identified as a risk factor of distant metastases.
Supplementation With Phytogenic Compounds Modulates Salivation and Salivary Physico-Chemical Composition in Cattle Fed a High-Concentrate Diet
Authors: Ricci Sara , Rivera-Chacon Raul , Petri Renee M. , Sener-Aydemir Arife , Sharma Suchitra , Reisinger Nicole , Zebeli Qendrim , Castillo-Lopez Ezequias
Published: June 2021

Saliva facilitates feed ingestion, nutrient circulation, and represents an important pH buffer for ruminants, especially for cattle fed high-concentrate diets that promote rumen acidification. This experiment evaluated the short-term effects of nine phytogenic compounds on salivation, saliva physico-chemical composition as well as ingested feed boli characteristics in cattle. A total of nine ruminally cannulated Holstein cows were used. Each compound was tested in four of these cows as part of a high-concentrate meal (2.5 kg of total mixed ration in dry matter basis for 4 h) in low or high dose, and was compared to a control meal without compound. Saliva was sampled orally (unstimulated saliva) for physico-chemical composition analysis. Composition of the ingested saliva (stimulated saliva), salivation and feed boli characteristics were assessed from ingesta collected at the cardia during the first 30 min of the meal. Analysis of unstimulated saliva showed that supplementation with capsaicin and thyme oil increased buffer capacity, while supplementation with thymol, L-menthol and gentian root decreased saliva pH. In addition, supplementing angelica root decreased saliva osmolality. Regression analysis on unstimulated saliva showed negative associations between mucins and bicarbonate as well as with phosphate when garlic oil, thyme oil or angelica root was supplemented. Analysis of stimulated saliva demonstrated that supplementation with garlic oil increased phosphate concentration, thyme oil tended to increase osmolality, capsaicin and thymol increased buffer capacity, and ginger increased phosphate content. Furthermore, salivation rate increased with ginger and thymol, and tended to increase with garlic oil, capsaicin, L-menthol and mint oil. Feed ensalivation increased with capsaicin. A positive association was found between feed bolus size and salivation rate when any of the phytogenic compounds was supplemented. Overall, our results demonstrate positive short-term effects of several phytogenic compounds on unstimulated and stimulated saliva physico-chemical properties, salivation or feed boli characteristics. Thus, the phytogenic compounds enhancing salivary physico-chemical composition have the potential to contribute to maintain or improve ruminal health in cattle fed concentrate-rich rations.
Comparison of Two Metabolic Simulators Used for Gas Exchange Verification in Cardiopulmonary Exercise Test Carts
Authors: Souren Tjeu , Rose Edward , Groepenhoff Herman
Published: June 2021

Introduction

Metabolic simulators (MS) produce simulated human breaths for the purpose of verification of cardiopulmonary exercise test (CPET) equipment. MS should produce consistent identical breaths with known CO2and O2gas concentrations over a range of breath rates and tidal volumes. Reliability of a CPET metabolic cart depends on ongoing quality control and maintenance of the device, including intermittent verification with a MS. We compared two MS devices against two standard CPET systems.

Methods

The Vacumed 17056 (Vacumetrics, Ventura, CA) and Relitech (Relitech Systems BV, Nijkerk, The Netherlands) were used with two standard metabolic carts (Vyntus CPX and Vyntus ONE, both Vyaire Medical, Mettawa, IL, United States). Tidal volume (VT) was set at 2 and 3 L and breathing frequency ranged from 20 to 80 breaths per minute for each MS. At each set point, we measured three sets of 40 breaths. Primary outcome parameters collected were VT, oxygen consumption (v.O2), carbon dioxide production (v.CO2), and respiratory exchange ratio (RER).

Results

VT, RER,v.O2, andv.CO2results as obtained from both MS were all within the limits of acceptability, at both tidal volume settings, and all ventilatory rates. No significant trends were identified for either MS device. The Relitech MS produced tidal volumes that were closer to the target VT for both CPET carts at both VT and all rates, but the results of both MS were within acceptable ranges.

Conclusion

Verification of CPET equipment using either the VM or RT metabolic simulator, producing highly accurate and predictable simulated breaths of known composition, enabling CPET laboratory managers to rely on subject test data obtained during cardiopulmonary exercise testing.