bluuebunny/crossref_metadata_2025 huggingface dataset:
PEMANFAATAN GOOGLE CLASSROOM SEBAGAI MEDIA PEMBELAJARAN DARING DIMASA PANDEMI COVID 19 DI PRODI INFORMATIKA UNIVERSITAS BATURAJA
Authors: Muris Anggraeni Agustin
Published: June 2021

Abstrak : Saat ini, media internet menjadi peran yang sangat penting untuk dikembangkan dalam kehidupan kita sehari-hari terutama dibidang pendidikan. Oleh karena itu, bidang pendidikan perlu menggunakan teknologi informasi dalam proses pembelajaran di kampus. Google Classroom, adalah salah satu akses gratis yang memudahkan dosen dalam proses pembelajaran jarak jauh atau e-learning. Lebih jauh, platform ini menawarkan banyak sekali keuntungan bagi penggunanya. Selain itu, platform ini dikenal sebagai alat yang mudah digunakan oleh pengguna smartphone atau laptop, serta mampu menciptakan peluang yang sama bagi semua mahasiswa dan mendorong mahasiswa untuk belajar lebih banyak tentang media internet. Penelitian ini menggunakan paradigma interpretif, dengan pendekatan kualitatif dan metode studi kasus untuk menemukan pemanfaatan Google Classroom oleh dosen Universitas Baturaja  khususnya di Program Studi Informatika Fakultas Teknik dan Komputer, Peran media baru di bidang pendidikan ini menghasilkan proses yang begitu mudah untuk dilakukan dan membuat dosen dapat lebih mudah untuk mengelola tugas kelas dengan cepat dan memberikan umpan balik kepada mahasiswa secara efektif.

 

Kata Kunci: Google Classroom, Media Pembelajaran, Media Internet
Irritable bowel syndrome: what's new? (UEG Week Virtual 2020 materials review)
Authors: Gaus O. V. , Livzan M. A.
Published: June 2021

Irritable bowel syndrome is a very urgent problem in modern gastroenterology. A deeper understanding of the ethology and pathogenesis, thevariety of drugs for the treatment of IBS gives hope for the possibility of effective control over the disease in the near future. The article provides a briefoverview of the latest advances in the study of irritable bowel syndrome, which were reported at the next UEG Week Virtual 2020, held in October 2020.
USULAN PERBAIKAN AREA KERJA MENGGUNAKAN METODE 5S GUNA TAHAP AWAL PENERAPAN LEAN MANUFACTURING (STUDI KASUS PT. XYZ)
Authors: Priyanto Dika , Prakoso Indro
Published: June 2021

PT. XYZ is a company engaged in wood processing. The product produced is plywood according to customer demand. After observing the production floor, several problems were found, namely that there was unused equipment in the work area. This equipment is equipment that is damaged or is not used. Besides, the cleanliness of the production floor is also poorly maintained where there is still dirt and dust. This study aims to identify problems related to waste on the production floor and design and propose the 5S method to create an effective work environment. The method used in this study uses the 5S concept approach (Seiri, Seiton, Seiso, Seiketsu, Shitsuke). 5S assessment is carried out using the audit checklist and evaluation checklist. The audit checklist and evaluation checklist are filled out by an auditor who knows clearly how the actual conditions on the production floor are. Data were collected in five work areas, namely rotary, press dryer, repair, assembling, and packing. The results of this study can be concluded that 1) problems on the production floor of PT XYZ include: there is no written procedure for elimination, there is no label on the work area, there is no regular cleaning, employees do not understand 5s, there are no procedures and 5s standards, there is no audit regarding 5s, there is no visual management system and standard procedures regarding 5s, lots of garbage scattered, dirty work surfaces and difficult to clean, everyone is not involved in 5s activities; 2) The results of the 5S assessment before improvement were 37.78% in the bad category. After planning the implementation of the improvement, the score rose to 80% in the good category
Biofabrication of Prevascularised Hypertrophic Cartilage Microtissues for Bone Tissue Engineering
Authors: Nulty Jessica , Burdis Ross , Kelly Daniel J.
Published: June 2021

Bone tissue engineering (TE) has the potential to transform the treatment of challenging musculoskeletal pathologies. To date, clinical translation of many traditional TE strategies has been impaired by poor vascularisation of the implant. Addressing such challenges has motivated research into developmentally inspired TE strategies, whereby implants mimicking earlier stages of a tissue’s development are engineered in vitro and then implanted in vivo to fully mature into the adult tissue. The goal of this study was to engineer in vitro tissues mimicking the immediate developmental precursor to long bones, specifically a vascularised hypertrophic cartilage template, and to then assess the capacity of such a construct to support endochondral bone formation in vivo. To this end, we first developed a method for the generation of large numbers of hypertrophic cartilage microtissues using a microwell system, and encapsulated these microtissues into a fibrin-based hydrogel capable of supporting vasculogenesis by human umbilical vein endothelial cells (HUVECs). The microwells supported the formation of bone marrow derived stem/stromal cell (BMSC) aggregates and their differentiation toward a hypertrophic cartilage phenotype over 5 weeks of cultivation, as evident by the development of a matrix rich in sulphated glycosaminoglycan (sGAG), collagen types I, II, and X, and calcium. Prevascularisation of these microtissues, undertaken in vitro 1 week prior to implantation, enhanced their capacity to mineralise, with significantly higher levels of mineralised tissue observed within such implants after 4 weeks in vivo within an ectopic murine model for bone formation. It is also possible to integrate such microtissues into 3D bioprinting systems, thereby enabling the bioprinting of scaled-up, patient-specific prevascularised implants. Taken together, these results demonstrate the development of an effective strategy for prevascularising a tissue engineered construct comprised of multiple individual microtissue “building blocks,” which could potentially be used in the treatment of challenging bone defects.
TDP-43 Mutation Affects Stress Granule Dynamics in Differentiated NSC-34 Motoneuron-Like Cells
Authors: Ding Qiao , Chaplin Justin , Morris Matthew J. , Hilliard Massimo A. , Wolvetang Ernst , Ng Dominic C. H. , Noakes Peter G.
Published: June 2021

Amyotrophic Lateral Sclerosis (ALS) is characterized by degeneration of motor neurons in the brain and spinal cord. Cytoplasmic inclusions of TDP-43 are frequently reported in motor neurons of ALS patients. TDP-43 has also been shown to associate with stress granules (SGs), a complex of proteins and mRNAs formed in response to stress stimuli that temporarily sequester mRNA translation. The effect of pathogenic TDP-43 mutations within glycine-rich regions (where the majority of ALS-causing TDP-43 mutations occur) on SG dynamics in motor neurons is poorly understood. To address this issue, we generated murine NSC-34 cell lines that stably over-express wild type TDP-43 (TDP-43WT) or mutant forms (ALS-causing TDP-43 mutations TDP-43A315Tor TDP-43M337V). We then differentiated these NSC-34 lines into motoneuron-like cells and evaluated SG formation and disassembly kinetics in response to oxidative or osmotic stress treatment. Wild type and mutant TDP-43 appeared to be largely retained in the nucleus following exposure to arsenite-induced oxidative stress. Upon arsenite removal, mutant TDP-43 clearly accumulated within HuR positive SGs in the cytoplasm, whereas TDP-43WTremained mostly within the nucleus. 24 h following arsenite removal, all SGs were disassembled in both wild type and mutant TDP-43 expressing cells. By contrast, we observed significant differences in the dynamics of mutant TDP-43 association with SGs in response to hyperosmotic stress. Specifically, in response to sorbitol treatment, TDP-43WTremained in the nucleus, whereas mutant TDP-43 relocalized to HuR positive SGs in the cytoplasm following exposure to sorbitol stress, resulting in a significant increase in TDP-43 SG numbers. These SGs remained assembled for 24 h following removal of sorbitol. Our data reveal that under certain stress conditions the rates of SG formation and disassembly is modulated by TDP-43 mutations associated with ALS, and suggest that this may be an early event in the seeding of insoluble cytoplasmic inclusions observed in ALS.
Sulfation of Glycosaminoglycans Modulates the Cell Cycle of Embryonic Mouse Spinal Cord Neural Stem Cells
Authors: Schaberg Elena , Theocharidis Ursula , May Marcus , Lessmann Katrin , Schroeder Timm , Faissner Andreas
Published: June 2021

In the developing spinal cord neural stem and progenitor cells (NSPCs) secrete and are surrounded by extracellular matrix (ECM) molecules that influence their lineage decisions. The chondroitin sulfate proteoglycan (CSPG) DSD-1-PG is an isoform of receptor protein tyrosine phosphatase-beta/zeta (RPTPβ/ζ), a trans-membrane receptor expressed by NSPCs. The chondroitin sulfate glycosaminoglycan chains are sulfated at distinct positions by sulfotransferases, thereby generating the distinct DSD-1-epitope that is recognized by the monoclonal antibody (mAb) 473HD. We detected the epitope, the critical enzymes and RPTPβ/ζ in the developing spinal cord. To obtain insight into potential biological functions, we exposed spinal cord NSPCs to sodium chlorate. The reagent suppresses the sulfation of glycosaminoglycans, thereby erasing any sulfation code expressed by the glycosaminoglycan polymers. When NSPCs were treated with chlorate and cultivated in the presence of FGF2, their proliferation rate was clearly reduced, while NSPCs exposed to EGF were less affected. Time-lapse video microscopy and subsequent single-cell tracking revealed that pedigrees of NSPCs cultivated with FGF2 were strongly disrupted when sulfation was suppressed. Furthermore, the NSPCs displayed a protracted cell cycle length. We conclude that the inhibition of sulfation with sodium chlorate interferes with the FGF2-dependent cell cycle progression in spinal cord NSPCs.
Netrin 1-Mediated Role of the Substantia Nigra Pars Compacta and Ventral Tegmental Area in the Guidance of the Medial Habenular Axons
Authors: Company Verónica , Andreu-Cervera Abraham , Madrigal M. Pilar , Andrés Belén , Almagro-García Francisca , Chédotal Alain , López-Bendito Guillermina , Martinez Salvador , Echevarría Diego , Moreno-Bravo Juan A. , Puelles Eduardo
Published: June 2021

The fasciculus retroflexus is an important fascicle that mediates reward-related behaviors and is associated with different psychiatric diseases. It is the main habenular efference and constitutes a link between forebrain regions, the midbrain, and the rostral hindbrain. The proper functional organization of habenular circuitry requires complex molecular programs to control the wiring of the habenula during development. However, the mechanisms guiding the habenular axons toward their targets remain mostly unknown. Here, we demonstrate the role of the mesodiencephalic dopaminergic neurons (substantia nigra pars compacta and ventral tegmental area) as an intermediate target for the correct medial habenular axons navigation along the anteroposterior axis. These neuronal populations are distributed along the anteroposterior trajectory of these axons in the mesodiencephalic basal plate. Using in vitro and in vivo experiments, we determined that this navigation is the result of netrin 1 attraction generated by the mesodiencephalic dopaminergic neurons. This attraction is mediated by the receptor deleted in colorectal cancer (DCC), which is strongly expressed in the medial habenular axons. The increment in our knowledge on the fasciculus retroflexus trajectory guidance mechanisms opens the possibility of analyzing if its alteration in mental health patients could account for some of their symptoms.
Aldose Reductase B1 in Pig Seminal Plasma: Identification, Localization in Reproductive Tissues, and Relationship With Quality and Sperm Preservation
Authors: Mateo-Otero Yentel , Viñolas-Vergés Estel , Llavanera Marc , Ribas-Maynou Jordi , Roca Jordi , Yeste Marc , Barranco Isabel
Published: June 2021

Aldose reductase B1 (AKR1B1), a NADPH-dependent enzyme that belongs to the aldo-keto reductase protein superfamily, has been reported to be involved in both male and female reproductive physiology. The objectives of this study were: (1) to evaluate the concentration of SP-AKR1B1 in pig ejaculate fractions; (2) to describe the immunohistochemical localization of AKR1B1 alongside the boar genital tract; (3) to evaluate the relationship between SP-AKR1B1 and sperm quality/functionality parameters. Ejaculates from seven boars (one ejaculate per boar) were collected in separate portions [the first 10 mL of the sperm rich fraction (SRF-P1), the rest of the SRF (SRF-P2), and the post-SRF (PSRF)], and the concentration of SP-AKR1B1 was assessed using an enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry and immunoblotting targeting was conducted in the reproductive tissues of these boars. Additionally, the entire ejaculates of 14 boars (one ejaculate per boar) were collected and split into three separate aliquots for: (i) SP-AKR1B1 quantification; (ii) assessment of sperm concentration and morphology; and (iii) evaluation of sperm quality and functionality parameters upon ejaculate collection (0 h) and after 72 h of liquid storage at 17°C. Concentration of AKR1B1 in the SP of SRF-P1 (458.2 ± 116.33 ng/mL) was lower (P < 0.05) than that of SRF-P2 (1105.0 ± 229.80 ng/mL) and PSRF (1342.4 ± 260.18 ng/mL). Monomeric and dimeric AKR1B1 forms were expressed alongside the reproductive tissues, except in the bulbourethral glands. No relationship between SP-AKR1B1 and sperm quality/functionality parameters was observed either at 0 h or after 72 h of storage at 17°C. In conclusion, AKR1B1 is expressed in the reproductive organs of boars (except bulbourethral glands) and a higher concentration is found in the PSRF suggesting that seminal vesicles would be the main secretory source. However, this enzyme does not appear to be related to sperm quality/functionality or to the sperm ability to withstand liquid storage at 17°C.
Incremental Values of T1 Mapping in the Prediction of Sudden Cardiac Death Risk in Hypertrophic Cardiomyopathy: A Comparison With Two Guidelines
Authors: Qin Le , Min Jiehua , Chen Chihua , Zhu Lan , Gu Shengjia , Zhou Mi , Yang Wenjie , Yan Fuhua
Published: June 2021

Background: MRI native T1 mapping and extracellular volume fraction (ECV) are quantitative values that could reflect various myocardial tissue characterization. The role of these parameters in predicting the risk of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) is still poorly understood.

Aim: This study aims to investigate the ability of native T1 mapping and ECV values to predict major adverse cardiovascular events (MACE) in HCM, and its incremental values over the 2014 European Society of Cardiology (ESC) and enhanced American College of Cardiology/American Heart Association (ACC/AHA) guidelines.

Methods: Between July 2016 and October 2020, HCM patients and healthy individuals with sex and age matched who underwent cardiac MRI were prospectively enrolled. The native T1 and ECV parameters were measured. The SCD risk was evaluated by the 2014 ESC guidelines and enhanced ACC/AHA guidelines. MACE included cardiac death, transplantation, heart failure admission, and implantable cardioverter-defibrillator implantation.

Results: A total of 203 HCM patients (54.2 ± 14.9 years) and 101 healthy individuals (53.2 ± 14.7 years) were evaluated. During a median follow-up of 15 months, 25 patients (12.3%) had MACE. In multivariate Cox regression analysis, global native T1 mapping (hazard ratio (HR): 1.446; 95% confidence interval (CI): 1.195–1.749; P < 0.001) and non-sustained ventricular tachycardia (NSVT) (HR: 4.949; 95% CI, 2.033–12.047; P < 0.001) were independently associated with MACE. Ten of 86 patients (11.6%) with low SCD risk assessed by the two guidelines had MACE. In this subgroup of patients, multivariate Cox regression analysis showed that global native T1 mapping was independently associated with MACE (HR: 1.532; 95% CI: 1.221–1.922; P < 0.001). In 85 patients with conflicting results assessed by the two guidelines, end-stage systolic dysfunction was independently associated with MACE (HR: 7.942, 95% CI: 1.322–47.707, P = 0.023). In 32 patients with high SCD risk assessed by the two guidelines, NSVT was independently associated with MACE (HR: 9.779, 95% CI: 1.953–48.964, P = 0.006).

Conclusion: The global native T1 mapping could provide incremental values and serve as potential supplements to the current guidelines in the prediction of MACE.
The Ins and Outs of Water in Olivine-Hosted Melt Inclusions: Hygrometer vs. Speedometer
Authors: Barth Anna , Plank Terry
Published: June 2021

The amount of water dissolved in magmas at depth beneath volcanoes is fundamental to a wide range of magmatic and eruptive processes due to water’s dominant control on magma generation, viscosity, and buoyancy. Since magmas degas most of their initial water content upon ascent and eruption, the primary record of magmatic water evolution exists within melt inclusions trapped inside crystals, especially olivine. However, the discovery of rapid H+ diffusion through olivine has called into question the fidelity of the melt inclusion water record. How compromised is the vast existing and growing dataset of melt inclusion water contents? What are the circumstances favorable for recording primary or pre-eruptive water concentration? Even if inclusions are compromised, diffusive water loss can be exploited to constrain magma decompression rates, a critical parameter that affects conduit processes. Here, we outline the current understanding of factors controlling water loss: the olivine/melt partition coefficient, the diffusive transport of water through olivine, the distance between inclusion and crystal rim, the melt inclusion size, and the exterior magma’s water evolution. We combine these parameters into a regime diagram that can be used to guide when melt inclusions may be used as hygrometers and when they are better suited to act as magma speedometers. We develop diagnostic tools to recognize where and when water loss has occurred in a magma’s ascent history, and we outline quantitative tools that may be used to restore the primary and/or pre-eruptive water content. The intent of this paper is to guide researchers in the interpretation of existing melt inclusion data, and to aid in the design of new studies that maximize the valuable information that melt inclusions may convey on the evolution of water in magmas prior to eruption.
What Is an L-Cell and How Do We Study the Secretory Mechanisms of the L-Cell?
Authors: Kuhre Rune E. , Deacon Carolyn F. , Holst Jens J. , Petersen Natalia
Published: June 2021

Synthetic glucagon-like peptide-1 (GLP-1) analogues are effective anti-obesity and anti-diabetes drugs. The beneficial actions of GLP-1 go far beyond insulin secretion and appetite, and include cardiovascular benefits and possibly also beneficial effects in neurodegenerative diseases. Considerable reserves of GLP-1 are stored in intestinal endocrine cells that potentially might be mobilized by pharmacological means to improve the body’s metabolic state. In recognition of this, the interest in understanding basic L-cell physiology and the mechanisms controlling GLP-1 secretion, has increased considerably. With a view to home in on what an L-cell is, we here present an overview of available data on L-cell development, L-cell peptide expression profiles, peptide production and secretory patterns of L-cells from different parts of the gut. We conclude that L-cells differ markedly depending on their anatomical location, and that the traditional definition of L-cells as a homogeneous population of cells that only produce GLP-1, GLP-2, glicentin and oxyntomodulin is no longer tenable. We suggest to sub-classify L-cells based on their differential peptide contents as well as their differential expression of nutrient sensors, which ultimately determine the secretory responses to different stimuli. A second purpose of this review is to describe and discuss the most frequently used experimental models for functional L-cell studies, highlighting their benefits and limitations. We conclude that no experimental model is perfect and that a comprehensive understanding must be built on results from a combination of models.
The Multiple Roles of B Cells in the Pathogenesis of Sjögren’s Syndrome
Authors: Du Wenhan , Han Man , Zhu Xiaoxia , Xiao Fan , Huang Enyu , Che Nan , Tang Xiaopo , Zou Hejian , Jiang Quan , Lu Liwei
Published: June 2021

Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease characterized by lymphocytic infiltration and tissue destruction of exocrine glands such as salivary glands. Although the formation of ectopic lymphoid tissue in exocrine glands and overproduction of autoantibodies by autoreactive B cells highlight the critical involvement of B cells in disease development, the precise roles of various B cell subsets in pSS pathogenesis remain partially understood. Current studies have identified several novel B cell subsets with multiple functions in pSS, among which autoreactive age-associated B cells, and plasma cells with augmented autoantibody production contribute to the disease progression. In addition, tissue-resident Fc Receptor-Like 4 (FcRL4)+ B cell subset with enhanced pro-inflammatory cytokine production serves as a key driver in pSS patients with mucosa-associated lymphoid tissue (MALT)-lymphomas. Recently, regulatory B (Breg) cells with impaired immunosuppressive functions are found negatively correlated with T follicular helper (Tfh) cells in pSS patients. Further studies have revealed a pivotal role of Breg cells in constraining Tfh response in autoimmune pathogenesis. This review provides an overview of recent advances in the identification of pathogenic B cell subsets and Breg cells, as well as new development of B-cell targeted therapies in pSS patients.
Disease Outbreak in a Keystone Grazer Population Brings Hope to the Recovery of Macroalgal Forests in a Barren Dominated Island
Authors: Gizzi Francesca , Monteiro João Gama , Silva Rodrigo , Schäfer Susanne , Castro Nuno , Almeida Silvia , Chebaane Sahar , Bernal-Ibáñez Alejandro , Henriques Filipe , Gestoso Ignacio , Canning-Clode João
Published: June 2021

Macroalgal forests play a key role in shallow temperate rocky reefs worldwide, supporting communities with high productivity and providing several ecosystem services. Sea urchin grazing has been increasingly influencing spatial and temporal variation in algae distributions and it has become the main cause for the loss of these habitats in many coastal areas, causing a phase shift from macroalgae habitats to barren grounds. The low productive barrens often establish as alternative stable states and only a major reduction in sea urchin density can trigger the recovery of macroalgal forests. The present study aims to assess if the 2018 disease outbreak, responsible for a strong reduction in the sea urchinDiadema africanumdensities in Madeira Island, was able to trigger a reverse shift from barren grounds into macroalgae-dominated state. By assessing the diversity and abundance of benthic sessile organisms, macroinvertebrates and fishes before, during and after that particular mass mortality event, we evaluate changes in benthic assemblages and relate them to variations in grazer and herbivore densities. Our results revealed a clear shift from barren state to a macroalgae habitat, with barrens characterized by bare substrate, sessile invertebrate and Crustose Coralline Algae (CCA) disappearing after the mortality event. Overall variations in benthic assemblages was best explained by four taxa (among grazers and herbivores species). However, it was the 2018 demise ofD. africanumand its density reduction that most contributed to the reverse shift from a long stable barren state to a richer benthic assemblage with higher abundance of macroalgae. Despite this recent increase in macroalgae dominated habitats, their stability and persistence in Madeira Island is fragile, since it was triggered by an unpredictable disease outbreak and depends on howD. africanumpopulations will recover. With no control mechanisms, local urchin populations can easily reach the tipping point needed to promote a new shift into barren states. New conservation measures and active restoration are likely required to maintain and promote the local stability of macroalgal forests.
Assessment of Mosquito Collection Methods for Dengue Surveillance
Authors: Garjito Triwibowo Ambar , Susanti Lulus , Mujiyono Mujiyono , Prihatin Mega Tyas , Susilo Dwi , Nugroho Sidiq Setyo , Mujiyanto Mujiyanto , Wigati Raden Ajeng , Satoto Tri Baskoro Tunggul , Manguin Sylvie , Gavotte Laurent , Frutos Roger
Published: June 2021

Several methods exist to collect and assess the abundance of dengue vector mosquitoes, i.e., morning adult collection, pupal collection, ovitraps, human landing, and larval collection. Several of these methods are officially implemented to monitor mosquito density and make decisions on treatments for dengue control. This monitoring is also constrained by the need to conduct this assessment on a “one point/one day” process, meaning that once the threshold of 100 households is reached, the assessment is made, and the collectors teams move to another place, thus preventing the use of long-term sampling methods. This diversity of methods might be a source of variability and lack of statistical significance. There is also a lack of published data regarding the efficacy of these methods. Furthermore, theStegomyiaindices are shown to be not reliable for assessing the risk of dengue outbreaks. A mosquito survey was, thus, conducted in 39 locations corresponding to 15 dengue endemic provinces in Indonesia by using the different adult and larval collection methods recommended nationwide. A total of 44,675 mosquitoes were collected. The single larva method was the most efficient. Out of a total of 89 dengue-positive pools, the most frequently encountered virus was DENV2, which made up half of the positive samples, followed by DENV3 and DENV1, respectively. Factor analysis of mixed data showed that no correlation could be found between any methods and the presence of dengue virus in mosquitoes. Moreover, no correlation could be found between any methods and the incidence of dengue. There was no consistency in the efficacy of a given method from one site to another. There was no correlation between any of the parameters considered, i.e., method, incidence of dengue, location, and the presence of dengue virus in mosquitoes.
Blocking Protein Phosphatase 1 [PP1] Prevents Loss of Tether Elasticity in Anaphase Crane-Fly Spermatocytes
Authors: Forer Arthur , Adil Aisha , Berns Michael W.
Published: June 2021

In normal anaphase cells, telomeres of each separating chromosome pair are connected to each other by tethers. Tethers are elastic at the start of anaphase: arm fragments cut from anaphase chromosomes in early anaphase move across the equator to the oppositely-moving chromosome, telomere moving toward telomere. Tethers become inelastic later in anaphase as the tethers become longer: arm fragments no longer move to their partners. When early anaphase cells are treated with Calyculin A (CalA), an inhibitor of protein phosphatases 1 (PP1) and 2A (PP2A), at the end of anaphase chromosomes move backward from the poles, with telomeres moving toward partner telomeres. Experiments described herein show that in cells treated with CalA, backwards movements are stopped in a variety of ways, by cutting the tethers of backwards moving chromosomes, by severing arms of backwards moving chromosomes, by severing arms before the chromosomes reach the poles, and by cutting the telomere toward which a chromosome is moving backwards. Measurements of arm-fragment velocities show that CalA prevents tethers from becoming inelastic as they lengthen. Since treatment with CalA causes tethers to remain elastic throughout anaphase and since inhibitors of PP2A do not cause the backwards movements, PP1 activity during anaphase causes the tethers to become inelastic.
Synthetic Peptides Derived From Lycosa Erythrognatha Venom: Interaction With Phospholipid Membranes and Activity Against Resistant Bacteria
Authors: Reis Pablo V. M. , Lima Vinícius M. , Souza Kelton R. , Cardoso Gabriele A. , Melo-Braga Marcella N. , Santos Daniel M. , Verly Rodrigo M. , Pimenta Adriano M. C. , Santos Vera Lúcia dos , de Lima Maria Elena
Published: June 2021

Superbugs are a public health problem, increasing the need of new drugs and strategies to combat them. Our group has previously identified LyeTxI, an antimicrobial peptide isolated from Lycosa erythrognatha spider venom. From LyeTxI, we synthesized and characterized a derived peptide named LyeTxI-b, which has shown significant in vitro and in vivo activity. In this work, we elucidate the interaction of LyeTxI-b with artificial membranes as well as its effects on resistant strains of bacteria in planktonic conditions or biofilms. Isothermal titration calorimetry revealed that LyeTxI-b interacts more rapidly and with higher intensity with artificial vesicles, showing higher affinity to anionic vesicles, when compared to synthetic LyeTxI. In calcein experiments, LyeTxI-b caused greater levels of vesicle cleavage. Both peptides showed antibacterial activity at concentrations of μmol L−1 against 12 different clinically isolated strains, in planktonic conditions, in a concentration-dependent manner. Furthermore, both peptides elicited a dose-dependent production of reactive oxygen species in methicillin-resistant Staphylococcus aureus. In S. aureus biofilm assay, LyeTxI-b was more potent than LyeTxI. However, none of these peptides reduced Escherichia coli biofilms. Our results show LyeTxI-b as a promising drug against clinically resistant strains, being a template for developing new antibiotics.
First Encounters: Effects of the Microbiota on Neonatal Brain Development
Authors: Gars Aviva , Ronczkowski Nicole M. , Chassaing Benoit , Castillo-Ruiz Alexandra , Forger Nancy G.
Published: June 2021

The microbiota plays important roles in host metabolism and immunity, and its disruption affects adult brain physiology and behavior. Although such findings have been attributed to altered neurodevelopment, few studies have actually examined microbiota effects on the developing brain. This review focuses on developmental effects of the earliest exposure to microbes. At birth, the mammalian fetus enters a world teeming with microbes which colonize all body sites in contact with the environment. Bacteria reach the gut within a few hours of birth and cause a measurable response in the intestinal epithelium. In adults, the gut microbiota signals to the brain via the vagus nerve, bacterial metabolites, hormones, and immune signaling, and work in perinatal rodents is beginning to elucidate which of these signaling pathways herald the very first encounter with gut microbes in the neonate. Neural effects of the microbiota during the first few days of life include changes in neuronal cell death, microglia, and brain cytokine levels. In addition to these effects of direct exposure of the newborn to microbes, accumulating evidence points to a role for the maternal microbiota in affecting brain development via bacterial molecules and metabolites while the offspring is still in utero. Hence, perturbations to microbial exposure perinatally, such as through C-section delivery or antibiotic treatment, alter microbiota colonization and may have long-term neural consequences. The perinatal period is critical for brain development and a close look at microbiota effects during this time promises to reveal the earliest, most primary effects of the microbiota on neurodevelopment.
Localization of the Epileptogenic Zone by Multimodal Neuroimaging and High-Frequency Oscillation
Authors: Li Xiaonan , Yu Tao , Ren Zhiwei , Wang Xueyuan , Yan Jiaqing , Chen Xin , Yan Xiaoming , Wang Wei , Xing Yue , Zhang Xianchang , Zhang Herui , Loh Horace H. , Zhang Guojun , Yang Xiaofeng
Published: June 2021

Accurate localization of the epileptogenic zone (EZ) is a key factor to obtain good surgical outcome for refractory epilepsy patients. However, no technique, so far, can precisely locate the EZ, and there are barely any reports on the combined application of multiple technologies to improve the localization accuracy of the EZ. In this study, we aimed to explore the use of a multimodal method combining PET-MRI, fluid and white matter suppression (FLAWS)—a novel MRI sequence, and high-frequency oscillation (HFO) automated analysis to delineate EZ. We retrospectively collected 15 patients with refractory epilepsy who underwent surgery and used the above three methods to detect abnormal brain areas of all patients. We compared the PET-MRI, FLAWS, and HFO results with traditional methods to evaluate their diagnostic value. The sensitivities, specificities of locating the EZ, and marking extent removed versus not removed [RatioChann(ev)] of each method were compared with surgical outcome. We also tested the possibility of using different combinations to locate the EZ. The marked areas in every patient established using each method were also compared to determine the correlations among the three methods. The results showed that PET-MRI, FLAWS, and HFOs can provide more information about potential epileptic areas than traditional methods. When detecting the EZs, the sensitivities of PET-MRI, FLAWS, and HFOs were 68.75, 53.85, and 87.50%, and the specificities were 80.00, 33.33, and 100.00%. The RatioChann(ev) of HFO-marked contacts was significantly higher in patients with good outcome than those with poor outcome (p< 0.05). When intracranial electrodes covered all the abnormal areas indicated by neuroimaging with the overlapping EZs being completely removed referred to HFO analysis, patients could reach seizure-free (p < 0.01). The periphery of the lesion marked by neuroimaging may be epileptic, but not every lesion contributes to seizures. Therefore, approaches in multimodality can detect EZ more accurately, and HFO analysis may help in defining real epileptic areas that may be missed in the neuroimaging results. The implantation of intracranial electrodes guided by non-invasive PET-MRI and FLAWS findings as well as HFO analysis would be an optimized multimodal approach for locating EZ.
Development and Validation of a Semi-Automated, Preclinical, MRI-Template Based PET Image Data Analysis Tool for Rodents
Authors: Schadt Fabian , Israel Ina , Samnick Samuel
Published: June 2021

Aim

In PET imaging, the different types of radiotracers and accumulations, as well as the diversity of disease patterns, make the analysis of molecular imaging data acquired in vivo challenging. Here, we evaluate and validate a semi-automated MRI template-based data analysis tool that allows preclinical PET images to be aligned to a self-created PET template. Based on the user-defined volume-of-interest (VOI), image data can then be evaluated using three different semi-quantitative parameters: normalized activity, standardized uptake value, and uptake ratio.

Materials and Methods

The nuclear medicine Data Processing Analysis tool (NU_DPA) was implemented in Matlab. Testing and validation of the tool was performed using two types of radiotracers in different kinds of stroke-related brain diseases in rat models. The radiotracers used are 2-[18F]fluoro-2-deoxyglucose ([18F]FDG), a metabolic tracer with symmetrical distribution in brain, and [68Ga]Ga-Fucoidan, a target-selective radioligand specifically binding to p-selectin. After manual image import, the NU_DPA tool automatically creates an averaged PET template out of the acquired PET images, to which all PET images are then aligned onto. The added MRI template-based information, resized to the lower PET resolution, defines the VOI and also allows a precise subdivision of the VOI into individual sub-regions. The aligned PET images can then be evaluated semi-quantitatively for all regions defined in the MRI atlas. In addition, a statistical analysis and evaluation of the semi-quantitative parameters can then be performed in the NU_DPA tool.

Results

Using ischemic stroke data in Wistar rats as an example, the statistical analysis of the tool should be demonstrated. In this [18F]FDG-PET experiment, three different experimental states were compared: healthy control state, ischemic stroke without electrical stimulation, ischemic stroke with electrical stimulation. Thereby, statistical data evaluation using the NU_DPA tool showed that the glucose metabolism in a photothrombotic lesion can be influenced by electrical stimulation.

Conclusion

Our NU_DPA tool allows a very flexible data evaluation of small animal PET data in vivo including statistical data evaluation. Using the radiotracers [18F]FDG and [68Ga]Ga-Fucoidan, it was shown that the semi-automatic MRI-template based data analysis of the NU_DPA tool is potentially suitable for both metabolic radiotracers as well as target-selective radiotracers.
Non-thermal Technologies for Food Processing
Authors: Jadhav Harsh Bhaskar , Annapure Uday S. , Deshmukh Rajendra R.
Published: June 2021

Food is subjected to various thermal treatments during processes to enhance its shelf-life. But these thermal treatments may result in deterioration of the nutritional and sensory qualities of food. With the change in the lifestyle of people around the globe, their food needs have changed as well. Today's consumer demand is for clean and safe food without compromising the nutritional and sensory qualities of food. This directed the attention of food professionals toward the development of non-thermal technologies that are green, safe, and environment-friendly. In non-thermal processing, food is processed at near room temperature, so there is no damage to food because heat-sensitive nutritious materials are intact in the food, contrary to thermal processing of food. These non-thermal technologies can be utilized for treating all kinds of food like fruits, vegetables, pulses, spices, meat, fish, etc. Non-thermal technologies have emerged largely in the last few decades in food sector.
Reduced PHLPP Expression Leads to EGFR-TKI Resistance in Lung Cancer by Activating PI3K-AKT and MAPK-ERK Dual Signaling
Authors: Wang Wei , Xia Xinhang , Chen Kuifei , Chen Meng , Meng Yinnan , Lv Dongqing , Yang Haihua
Published: June 2021

Background

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are effective in advanced EGFR-mutation non-small cell lung cancer (NSCLC) but the magnitude of tumor regression varies, and drug resistance is unavoidable. The pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP) levels are reduced or lost and acts as a tumor suppressor in many cancers. Here, we hypothesized that PHLPP is a key regulator of EGFR-TKI sensitivity and a potential treatment target for overcoming resistance to EGFR-TKI in lung cancer.

Methods

Cell proliferation and growth inhibition were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assay. PHLPP- knockdown stable cell lines were generated by lentivirus-mediated delivery of PHLPP shRNAs. The expression of PHLPP mRNA and protein levels was detected by real-time quantitative polymerase chain reaction (qPCR) and Western blotting. Immunohistochemical (IHC) staining was performed to detect the PHLPP expression in clinical patient tissue samples. A transcriptomic assay of genome-wide RNA expressions of PHLPP in NSCLC cell lines according to gefitinib sensitivity was obtained from Gene Expression Omnibus (GEO) database. Murine xenograft model was established to verify the function of PHLPP in gefitinib resistance in vivo.

Results

PHLPP highly expressed in gefitinib-sensitive NSCLC cell lines than gefitinib-resistant NSCLC cell lines. In gefitinib-acquired resistance cell line HCC827-GR, PHLPP expression even dramatically reduced. Knockdown of PHLPP in NSCLC cells decreased cell death induced by the EGFR-TKI, while overexpression PHLPP in gefitinib-resistance NSCLC cells can enhance or restore EGFR-TKIs sensitivity. Mechanism study indicated that PHLPP downregulation attenuates the effect of EGFR-TKI on the both AKT and ERK pathway, thereby decreasing the cell death sensitivity to EGFR inhibitors. In xenograft mice, knockdown of PHLPP decreased tumor response to gefitinib and advanced tumor cells re-growth after gefitinib treatment. In clinical, PHLPP expression were reduced in the post-relapse tumor compared to that of pre-treatment, and lower pre-treatment PHLPP levels were significantly correlated with shorter progression-free survival (PFS) in patients with EGFR-mutant lung adenocarcinoma whom treated with EGFR-TKI.

Conclusions

Our data strongly demonstrated that loss of PHLPP function was a key factor of EGFR-TKI resistance in NSCLC. Downregulated PHLPP expression activated PI3K-AKT and MAPK-ERK pathway which strengthened cell survival to EGFR-TKI. Therefore, PHLPP expression level was not only a potential biomarker to predict EGFR-TKIs sensitivity but also as a therapeutic target in EGFR-TKIs therapy, enhancing PHLPP expression may be a valuable strategy for delaying or overcoming EGFR-TKIs drug resistance.
miR-27-3p Enhances the Sensitivity of Triple-Negative Breast Cancer Cells to the Antitumor Agent Olaparib by Targeting PSEN-1, the Catalytic Subunit of Γ-Secretase
Authors: Zhao Meng , Sun Baisheng , Wang Yan , Qu Gengbao , Yang Hua , Wang Pilin
Published: June 2021

Olaparib has been used in the treatment of triple-negative breast cancer (TNBC) with BRCA mutations. In the present study, we demonstrated the effect of miR-27-3p on the γ-secretase pathway by regulating the sensitivity of TNBC cells to olaparib. miR-27-3p, a microRNA with the potential to target PSEN-1, the catalytic subunit of γ-secretase mediating the second step of the cleavage of the Notch protein, was identified by the online tool miRDB and found to inhibit the expression of PSEN-1 by directly targeting the 3’-untranslated region (3’-UTR) of PSEN-1. The overexpression of miR-27-3p inhibited the activation of the Notch pathway via the inhibition of the cleavage of the Notch protein, mediated by γ-secretase, and, in turn, enhanced the sensitivity of TNBC cells to the antitumor agent olaparib. Transfection with PSEN-1 containing mutated targeting sites for miR-27-3p or the expression vector of the Notch protein intracellular domain (NICD) almost completely blocked the effect of miR-27-3p on the Notch pathway or the sensitivity of TNBC cells to olaparib, respectively. Therefore, our results suggest that the miR-27-3p/γ-secretase axis participates in the regulation of TNBC and that the overexpression of miR-27-3p represents a potential approach to enhancing the sensitivity of TNBC to olaparib.
Microconical Structure Formation and Field Emission From Atomically Heterogeneous Surfaces Created by Microwave Plasma–Based Low-Energy Ion Beams
Authors: Majumdar Jayashree , Bhattacharjee Sudeep
Published: June 2021

We report the formation of self-organized microconical arrays on copper surface when exposed to high flux (5.4 × 1015 cm−2 s−1) of 2 keV argon ion beams at normal incidence. The created microconical arrays are explored for field emission properties. The surface morphologies are investigated by scanning electron microscopy and atomic force microscopy. The local work function variation is analyzed by Kelvin probe force microscopy, and the argon content in the irradiated layer is measured with X-ray Photoelectron Spectroscopy. The average aspect ratio (base width/height) of microstructures for individual irradiated samples is found to increase from 0.7 to 1.5 with a decrease in ion fluence. The ion concentration is highest (3.89 %) for a fluence of 4.7 × 1018 cm−2, which asserts the formation of atomically heterogeneous surface due to subsurface ion implantation. An enhancement in the field emission properties of the argon ion–treated copper substrates at a fluence of 4.7 × 1018 cm−2 with a low turn-on voltage of 2.33 kV and with electron emission current 0.5 nA has been observed. From the Fowler–Nordheim equations, the field enhancement factor is calculated to be 5,561 for pristine copper, which gets enhanced by a factor of 2–8 times for irradiated substrates. A parametric model is considered, by taking into account the modified local work function caused due to structural undulations of the microstructures and presence of implanted argon ions, for explaining the experimental results on the field enhancement factor and emission current.
Comprehensive Analysis of Heat and Water Exchanges in the Human Lungs
Authors: Haut Benoit , Nonclercq Antoine , Buess Alexandra , Rabineau Jérémy , Rigaut Clément , Sobac Benjamin
Published: June 2021

This work presents a new mathematical model of the heat and water exchanges in the human lungs (newborn to adult). This model is based on a local description of the water and energy transports in both the lumen and the surrounding tissues, and is presented in a comprehensive, dimensionless framework with explicitly stated assumptions and a strong physiological background. The model is first used to analyze and quantify the key phenomena and dimensionless numbers governing these heat and water exchanges and then it is applied to an adult in various situations (varying atmospheric conditions, exercising…). The results highlight several interesting physiological elements. They show that the bronchial region of the lungs is able to condition the air in all the considered situations even if, sometimes, for instance when exercising, distal generations have to be involved. The model also shows that these distal generations are super-conditioners. Moreover, the results quantify the key role of the submucosal glands in mucus hydration. They also show that, during expiration, a significant cooling of the air and condensation of water occur along the respiratory tract as the vascularization of the tissues surrounding the airways is not able to maintain these tissues at body temperature during inspiration. Due to the interaction between several phenomena, it appears that the ratio of the amount of water returned to the mucosa during expiration to the amount extracted during inspiration is almost independent of the breathing conditions (around 33%). The results also show that, in acute situations, such as suffering from a pathology with airway dysfunction, when being intubated or when exercising above an intensity threshold, the heat and water exchanges in the lungs may be critical regarding mucus hydration. In proximal generations, the evaporation may overwhelm the ability of the submucosal glands to replenish the airway surface liquid with water. In some situations, the cooling of the mucosa may be very important; it can even become colder than the inspired air, due to evaporative cooling. Finally, the results show that breathing cold air can significantly increase the exchanges between the lungs and the environment, which can be critical regarding disease transmission.
Into the Labyrinth of the Lipocalin α1-Acid Glycoprotein
Authors: Ruiz Mario
Published: June 2021

α1-acid glycoprotein (AGP), also known as Orosomucoid (ORM), belongs to the Lipocalin protein family and it is well-known for being a positive acute-phase protein. AGP is mostly found in plasma, with the liver as main contributor, but it is also expressed in other tissues such as the brain or the adipose tissue. Despite the vast literature on AGP, the physiological functions of the protein remain to be elucidated. A large number of activities mostly related to protection and immune system modulation have been described. Recently created AGP-knockout models have suggested novel physiological roles of AGP, including regulation of metabolism. AGP has an outstanding ability to efficiently bind endogenous and exogenous small molecules that together with the complex and variable glycosylation patterns, determine AGP functions. This review summarizes and discusses the recent findings on AGP structure (including glycans), ligand-binding ability, regulation, and physiological functions of AGP. Moreover, this review explores possible molecular and functional connections between AGP and other members of the Lipocalin protein family.