bluuebunny/crossref_metadata_2025 huggingface dataset:
Viral Diseases that Affect Donkeys and Mules
Authors: Câmara Rebeca Jéssica Falcão , Bueno Bruna Lopes , Resende Cláudia Fideles , Balasuriya Udeni B. R. , Sakamoto Sidnei Miyoshi , Reis Jenner Karlisson Pimenta dos
Published: November 2020

Donkeys (Equus asinus) and mules represent approximately 50% of the entire domestic equine herd in the world and play an essential role in the lives of thousands of people, primarily in developing countries. Despite their importance, donkeys are currently a neglected and threatened species due to abandonment, indiscriminate slaughter, and a lack of proper sanitary management. Specific knowledge about infectious viral diseases that affect this group of Equidae is still limited. In many cases, donkeys and mules are treated like horses, with the physiological differences between these species usually not taken into account. Most infectious diseases that affect the Equidae family are exclusive to the family, and they have a tremendous economic impact on the equine industry. However, some viruses may cross the species barrier and affect humans, representing an imminent risk to public health. Nevertheless, even with such importance, most studies are conducted on horses (Equus caballus), and there is little comparative information on infection in donkeys and mules. Therefore, the objective of this article is to provide a brief update on viruses that affect donkeys and mules, thereby compromising their performance and well-being. These diseases may put them at risk of extinction in some parts of the world due to neglect and the precarious conditions they live in and may ultimately endanger other species’ health and humans.
Biochemical and Histopathological Alterations in Different Tissues of Rats Due to Repeated Oral Dose Toxicity of Cymoxanil
Authors: Ahmed Mohamed S. , Massoud Ahmed H. , Derbalah Aly S. , Al-Brakati Ashraf , Al-Abdawani Mohsin A. , Eltahir Hatim A. , Yanai Tokuma , Elmahallawy Ehab Kotb
Published: November 2020

Evaluating potential adverse health impacts caused by pesticides is an important parameter in human toxicity. This study focuses on the importance of subchronic toxicity assessment of cymoxanil fungicide in rats with special reference to target biochemical enzymes and histopathological changes in different tissues. In this regard, a 21-day toxicity study with repeated cymoxanil oral doses was conducted. It has been shown that low doses (0.5 mg/kg) were less effective than medium (1 mg/kg) and high (2 mg/kg) doses. Moreover, high dose dose-treated rats showed piecemeal necrosis in the liver, interstitial nephritis and tubular degeneration in the kidneys, interstitial pneumonia and type II pneumocyte hyperplasia in the lungs, gliosis, spongiosis, and malacia in the brain, and testicular edema and degeneration in the testes. Cymoxanil significantly increased AST, ALT, and ALP in serum and liver, indicating tissue necrosis and possible leakage of these enzymes into the bloodstream. Creatinine levels increased, indicating renal damage. Similarly, significant inhibition was recorded in brain acetylcholinesterase, indicating that both synaptic transmission and nerve conduction were affected. Importantly, these histopathological and biochemical alterations were dose-dependent. Taken together, our study reported interesting biochemical and histopathological alterations in different rat tissues following repeated toxicity with oral doses of cymoxanil. Our study suggests future studies on different pesticides at different concentrations that would help urge governments to create more restrictive regulations concerning these compounds’ levels.
Molecular Characterization of the Burkholderia cenocepacia dcw Operon and FtsZ Interactors as New Targets for Novel Antimicrobial Design
Authors: Trespidi Gabriele , Scoffone Viola Camilla , Barbieri Giulia , Riccardi Giovanna , De Rossi Edda , Buroni Silvia
Published: November 2020

The worldwide spread of antimicrobial resistance highlights the need of new druggable cellular targets. The increasing knowledge of bacterial cell division suggested the potentiality of this pathway as a pool of alternative drug targets, mainly based on the essentiality of these proteins, as well as on the divergence from their eukaryotic counterparts. People suffering from cystic fibrosis are particularly challenged by the lack of antibiotic alternatives. Among the opportunistic pathogens that colonize the lungs of these patients, Burkholderia cenocepacia is a well-known multi-drug resistant bacterium, particularly difficult to treat. Here we describe the organization of its division cell wall (dcw) cluster: we found that 15 genes of the dcw operon can be transcribed as a polycistronic mRNA from mraZ to ftsZ and that its transcription is under the control of a strong promoter regulated by MraZ. B. cenocepacia J2315 FtsZ was also shown to interact with the other components of the divisome machinery, with a few differences respect to other bacteria, such as the direct interaction with FtsQ. Using an in vitro sedimentation assay, we validated the role of SulA as FtsZ inhibitor, and the roles of FtsA and ZipA as tethers of FtsZ polymers. Together our results pave the way for future antimicrobial design based on the divisome as pool of antibiotic cellular targets.
Berberis microphylla G. Forst (Calafate) Berry Extract Reduces Oxidative Stress and Lipid Peroxidation of Human LDL
Authors: Olivares-Caro Lia , Radojkovic Claudia , Chau Si Yen , Nova Daniela , Bustamante Luis , Neira Jose Yamil , Perez Andy J. , Mardones Claudia
Published: November 2020

Calafate (Berberis microphylla G. Forst) is a Patagonian barberry very rich in phenolic compounds. Our aim was to demonstrate, through in vitro models, that a comprehensive characterized calafate extract has a protective role against oxidative processes associated to cardiovascular disease development. Fifty-three phenolic compounds (17 of them not previously reported in calafate), were tentatively identified by Ultra-Liquid Chromatography with Diode Array Detector, coupled to Quadrupole-Time of Fly Mass Spectrometry (UHPLC-DAD-QTOF). Fatty acids profile and metals content were studied for the first time, by Gas Chromatography Mass Spectrometry (GC-MS) and Total X-ray Fluorescence (TXRF), respectively. Linolenic and linoleic acid, and Cu, Zn, and Mn were the main relevant compounds from these groups. The bioactivity of calafate extract associated to the cardiovascular protection was evaluated using Human Umbilical Vein Endothelial Cells (HUVECs) and human low density lipoproteins (LDL) to measure oxidative stress and lipid peroxidation. The results showed that calafate extract reduced intracellular Reactive Oxygen Species (ROS) production (51%) and completely inhibited LDL oxidation and malondialdehyde (MDA) formation. These findings demonstrated the potential of the relevant mix of compounds found in calafate extract on lipoperoxidation and suggest a promising protective effect for reducing the incidence of cardiovascular disease.
Does Herbal and/or Zinc Dietary Supplementation Improve the Antioxidant and Mineral Status of Lambs with Parasite Infection?
Authors: Čobanová Klaudia , Váradyová Zora , Grešáková Ľubomíra , Kucková Katarína , Mravčáková Dominika , Várady Marián
Published: November 2020

This study was conducted to evaluate the effect of feed supplementation with a medicinal herbs mixture (Hmix) and organic zinc (Zn), alone or in combination, on the antioxidant responses and mineral status of lambs infected with the gastrointestinal nematode parasite Haemonchus contortus. A total of 24 experimentally infected lambs were randomly allocated to 1 of 4 dietary treatments (n = 6). The diets included an unsupplemented control diet (CON) and the CON further supplemented with Hmix, Zn, or both Hmix + Zn. Antioxidant enzymes activities, lipid peroxidation, total antioxidant capacity (TAC) and microelement (Zn, Cu, Fe, Mn) concentrations were analyzed in serum, liver, kidney, and intestinal mucosa. Zinc treatment elevated the superoxide dismutase activities in the duodenal mucosa and ileal TAC. Intake of Hmix resulted in higher kidney and ileal catalase activity and also influenced the TAC of the liver and intestinal mucosa. The inclusion of Hmix or Zn alone into the diet increased glutathione peroxidase activity in the blood, liver and duodenal mucosa. Tissue mineral uptake was not affected by herbal supplementation. Organic Zn intake increased the serum and liver Zn levels and influenced the Cu concentration in duodenal mucosa. Dietary supplementation with Hmix and/or Zn might promote the antioxidant status of lambs infected with Haemonchus spp.
Predicting and Modeling Wildfire Propagation Areas with BAT and Maximum-State PageRank
Authors: Yeh Wei-Chang , Kuo Chia-Chen
Published: November 2020

The nature and characteristics of free-burning wildland fires have significant economic, safety, and environmental impacts. Additionally, the increase in global warming has led to an increase in the number and severity of wildfires. Hence, there is an increasing need for accurately calculating the probability of wildfire propagation in certain areas. In this study, we firstly demonstrate that the landscapes of wildfire propagation can be represented as a scale-free network, where the wildfire is modeled as the scale-free network whose degree follows the power law. By establishing the state-related concepts and modifying the Binary-Addition-Tree (BAT) together with the PageRank, we propose a new methodology to serve as a reliable tool in predicting the probability of wildfire propagation in certain areas. Furthermore, we demonstrate that the proposed maximum-state PageRank used in the methodology can be implemented separately as a fast, simple, and effective tool in identifying the areas that require immediate protection. The proposed methodology and maximum-state PageRank are validated in the example generated from the Barabási-Albert model in the study.
A Low-Cost Secure IoT Mechanism for Monitoring and Controlling Polygeneration Microgrids
Authors: Martínez-Martínez Josué , Aponte-Roa Diego , Vergara-Laurens Idalides , Weaver Wayne W.
Published: November 2020

The use of Internet-connected devices at homes has increased to monitor energy consumption. Furthermore, renewable energy sources have also increased, reducing electricity bills. However, the high cost of the equipment limits the use of these technologies. This paper presents a low-cost secured-distributed Internet of Things (IoT) system to monitor and control devices connected in a polygeneration microgrid, as a combined power system for local loads with renewable sources. The proposed mechanism includes a Wireless Sensor Actuator Networked Control System that links network nodes using the IEEE 802.15.4 standard. The Internet communication enables the monitor and control of devices using a mobile application to increase the efficiency. In addition, security mechanisms are implemented at several levels including the authentication, encryption, and decryption of the transmitted data. Furthermore, a firewall and a network intrusion detection-and-prevention program are implemented to increase the system protection against cyber-attack. The feasibility of the proposed solution was demonstrated using a DC microgrid test bench consisting of a diverse range of renewable energy sources and loads.
Impacts on Metabolism and Gill Physiology of Darter Species (Etheostoma spp.) That Are Attributed to Wastewater Effluent in the Grand River
Authors: Hodgson Rhiannon , Bragg Leslie , Dhiyebi Hadi A. , Servos Mark R. , Craig Paul M.
Published: November 2020

The effluent from municipal wastewater treatment plants is a major point source of contamination in Canadian waterways. The improvement of effluent quality to reduce contaminants, such as pharmaceuticals and personal care products, before being released into the environment is necessary to reduce the impacts on organisms that live in the river downstream. Here, we aimed to characterize the metabolic and gill physiological responses of rainbow (Etheostoma caeruleum), fantail (Etheostoma flabellare), and greenside (Etheostoma blennioides) darters to the effluent in the Grand River from the recently upgraded Waterloo municipal wastewater treatment plant. The routine metabolism of darters was not affected by effluent exposure, but some species had increased maximum metabolic rates, leading to an increased aerobic scope. The rainbow darter aerobic scope increased by 2.2 times and the fantail darter aerobic scope increased by 2.7 times compared to the reference site. Gill samples from effluent-exposed rainbow darters and greenside darters showed evidence of more pathologies and variations in morphology. These results suggest that darters can metabolically adjust to effluent-contaminated water and may also be adapting to the urban and agricultural inputs. The modification and damage to the gills provide a useful water quality indicator but does not necessarily reflect how well acclimated the species is to the environment due to a lack of evidence of poor fish health.
Charging Platform of Chess-Pad Configuration for Unmanned Aerial Vehicle (UAV)
Authors: Al-Obaidi Mohammed Rameez , Wan Hasan Wan Zuha , Mustafa Mohd Amrallah , Azis Norhafiz
Published: November 2020

The authors of this study designed and optimized a charging landing pad system that mitigates the landing accuracy issues of unmanned aerial vehicles (UAVs). The study looks at the charging process, energy conversion during periodic landing on a unique platform, and an onboard and on-ground scheme design procedure. The circuit is fixed on the UAV platform and comprises six integrated bridge rectifier diodes to alter the four connection pin terminals’ charge polarity. The inclusion of a current indicator shows the flow of charge during successful docking. The charging platform consists of square conductive copper plates of specific dimensions that provide positive and negative polarity in a chess form to ensure the contact of various polarities. This design considers two power supply options: a solar panel and a standard mains supply. The contact point coordinate probability when landing is the crucial aspect of this design. A first version of the proposed system was implemented to measure its effectiveness for commercial drones. This system provides an automated recharge station with reliable performance. Numerical experiments showed that the system’s energy conversion remains efficient regardless of drone orientation over the platform or the environment’s nature.
Data-Driven Health Assessment in Flight Control System
Authors: Chen Jie , Zhao Yuyang , Wu Chentao , Xu Qingshan
Published: November 2020

The aircraft critical system’s health state will affect flight safety dramatically, such as flight control system, and its health state awareness or assessment is very important to avoid flight accident. A data-driven health assessment based on fuzzy comprehensive evaluation and rough set reduction is proposed for flight control system. Through the working principle and failure mode analysis, the system’s characteristic parameters are constructed to represent health state, and then the comprehensive health index construction is proposed to quantify health state. In the end, case calculation based on some aircraft’s flight data is presented to show the effectiveness of the proposed method.
Design of a Multichannel Pulser/Receiver and Optimized Damping Resistor for High-Frequency Transducer Applied to SAM System
Authors: Bui Ngoc Thang , Nguyen Thi My Tien , Dinh Tran Thanh Nam , Bui Quoc Cuong , Vo Tan Hung , Phan Duc Tri , Park Sumin , Choi Jaeyeop , Kang Yeon-Hee , Kim Byung-Gak , Oh Junghwan
Published: November 2020

Scanning acoustic microcopy (SAM) is widely used in biomedical and industrial applications in dermatology, ophthalmology, intravascular imaging, and small animal images, owing to SAM’s ability to photograph small structures with a good spatial resolution. One of the most important devices of this system is the pulser/receiver (P/R) (PRN-300, Ohlabs Corporation, Nam-gu Busan, Republic of Korea), which generates pulses to trigger a high-frequency transducer. This article presents the design of a pulse generator to excite high-frequency transducers with four channels. The characteristics of the pulses, such as time and frequency, can be reconfigured by using a high-speed field programmable gate array (FPGA). The configuration software was developed for communicating with the P/R device via a USB connector for easy, feasible pulse selection and real-time pulse management. Besides that, during the design and implementation of the hardware, we optimized the damping resistor value to reduce the overshoot and undershoot part of the signal, ensuring the best effect on the transducer signal. The test results show that unipolar pulses worked with transducers with frequencies over 100 MHz. The SAM systems can work simultaneously with multiple transducers, and the resulting images have different resolutions of regions.
Biomechanical Adaptations in Kayakers of Different Competitive Levels and the Relationship with the Kayak Elements
Authors: Abelleira-Lamela Tomás , Vaquero-Cristóbal Raquel , Esparza-Ros Francisco , Marcos-Pardo Pablo Jorge
Published: November 2020

A paddler’s characteristics can condition the placement of the elements of the boat. The aim of this study was to analyze the differences among kayakers from different skill levels on their sagittal spine position, hamstring extensibility and anthropometric variables; and to determine which variables could be used to determine the arrangement of the elements in the kayak. Thirty-four male sprint kayakers (8 Olympic-level, 13 from the U-23 national team and 13 amateurs) participated in this study. Anthropometric variables, following the protocol of the International Society for the Advancement of Kinanthropometry (ISAK); hamstring extensibility, with active and passive straight leg raise test; sagittal spine position in standing position and in the kayak, and the arrangement of the elements of the boat were measured. The groups with a high skill level showed a lower pelvic tilt in attack position in the kayak than amateurs (p ≤ 0.001). The U-23 group had a lower hamstring extensibility than amateurs (p = 0.053–0.013). The distance from the footrest to the different parts of the seat were dependent on the iliospinale measurement (R = 0.896–0.912). In conclusion, there were differences among groups on the sagittal spine position and hamstring extensibility. In addition, the placement of the boat elements was dependent on anthropometric variables, but not on hamstring extensibility or sagittal spine position.
Heat and Ozone Pollution Waves in Central and South Europe—Characteristics, Weather Types, and Association with Mortality
Authors: Hertig Elke , Russo Ana , Trigo Ricardo M.
Published: November 2020

Air pollution and hot temperatures present two major health risks, especially for vulnerable groups such as children, the elderly, and people with pre-existing conditions. Episodes of high ozone concentrations and heat waves have been registered throughout Europe and are expected to continue to grow due to climate change. Here, several different heat and ozone wave definitions were applied to characterize the wave-type extremes for two climatically different regions, i.e., Portugal (South Europe) and Bavaria (Central Europe), and their impacts were evaluated considering each type of hazard independently but also when they occur simultaneously. Heat and ozone waves were analyzed with respect to the underlying atmospheric circulation patterns and in terms of their association with human mortality. Heat waves were identified as the most frequent wave type and, despite different climate settings, a comparable exposure to heat and ozone waves was found in Central and South Europe. Waves were associated with in-situ built-up as well as with advection of air masses. However, in Bavaria waves showed the strongest connection with autochthonous weather conditions, while for Portugal, the strongest relationship appeared for eastern and north-eastern inflow. The most severe events, as measured by excess mortality, were always associated to compound heat-ozone waves.
Degradation of Preservatives with the Formation of Off-Odor Volatile Compounds—The Case of Strawberry-Flavored Bottled Water
Authors: Sokołowska Barbara , Połaska Marzena , Dekowska Agnieszka , Woźniak Łukasz , Roszko Marek
Published: November 2020

Foods preserved with sorbic acid or its salts can undergo spoilage with the formation of chemicals characterized by odors of plastic, hydrocarbons, or kerosene. 1,3-pentadiene, which is formed through the decarboxylation of sorbic acid or its salts, is one such compound. Numerous species of molds and yeasts have been reported as capable of degrading sorbic acid. This work is aimed to identify the off-odor compounds in samples of strawberry-flavored water preserved with potassium sorbate and sodium benzoate. In addition, the mold isolated from this drink was evaluated for the ability to form undesirable compounds, and the results revealed the presence of 1,4-pentadiene and benzaldehyde in the tested samples. The mold isolated from the samples was identified as Penicillium corylophilum. During its 5-day incubation at 25 °C in a liquid medium, potassium sorbate added at a final concentration of 200 and 400 mg/L was completely assimilated by the growing mycelium and converted into 1,4-pentadiene. The concentration of the latter was determined as 46.5 and 92.6 mg/L, respectively. The decrease in the concentration of sodium benzoate exceeded 53% in the broth spiked at 200 mg/L and 23% at 400 mg/L, resulting in the formation of benzaldehyde.
Reference Values for Handgrip Strength in the Basque Country Elderly Population
Authors: Río Xabier , Larrinaga-Undabarrena Arkaitz , Coca Aitor , Guerra-Balic Myriam
Published: November 2020

Strength training is currently the most recommended primary therapeutic strategy to prevent and reverse the decline of muscle mass, strength, and functional deterioration associated with age. The aim is to provide reference values of handgrip strength (HGS) in the Basque Country population and compare the values with other populations. A total of 1869 subjects from the health-promoting programme for adults and older adults run by the Bilbao City Council were assessed using HGS with a digital dynamometer and anthropometric data measured by Tanita to obtain the mean values according to age distribution. From the 1869 subjects, 87.5% were women and 12.5% men. The HGS was higher among men than women, 32.4 ± 6.6 versus 20.1 ± 4.7 kg, respectively, p < 0.001 at all ages. Weak HGS cut-off points by age groups ranged from 31.0 to 23.8 and from 18.9 to 12.4 in men and women, respectively. The sample data were compared (d, t, and α) with those of other populations in all age groups (group > 60 years at 95% df, p < 0.05). A health-promoting programme appears to be effective in the general population in obtaining better values in the HGS test as age increases.
Extracellular Vesicles and Post-Translational Protein Deimination Signatures in Mollusca—The Blue Mussel (Mytilus edulis), Soft Shell Clam (Mya arenaria), Eastern Oyster (Crassostrea virginica) and Atlantic Jacknife Clam (Ensis leei)
Authors: Bowden Timothy J. , Kraev Igor , Lange Sigrun
Published: November 2020

Oysters and clams are important for food security and of commercial value worldwide. They are affected by anthropogenic changes and opportunistic pathogens and can be indicators of changes in ocean environments. Therefore, studies into biomarker discovery are of considerable value. This study aimed at assessing extracellular vesicle (EV) signatures and post-translational protein deimination profiles of hemolymph from four commercially valuable Mollusca species, the blue mussel (Mytilus edulis), soft shell clam (Mya arenaria), Eastern oyster (Crassostrea virginica), and Atlantic jacknife clam (Ensis leei). EVs form part of cellular communication by transporting protein and genetic cargo and play roles in immunity and host–pathogen interactions. Protein deimination is a post-translational modification caused by peptidylarginine deiminases (PADs), and can facilitate protein moonlighting in health and disease. The current study identified hemolymph-EV profiles in the four Mollusca species, revealing some species differences. Deiminated protein candidates differed in hemolymph between the species, with some common targets between all four species (e.g., histone H3 and H4, actin, and GAPDH), while other hits were species-specific; in blue mussel these included heavy metal binding protein, heat shock proteins 60 and 90, 2-phospho-D-glycerate hydrolyase, GTP cyclohydrolase feedback regulatory protein, sodium/potassium-transporting ATPase, and fibrinogen domain containing protein. In soft shell clam specific deimination hits included dynein, MCM3-associated protein, and SCRN. In Eastern oyster specific deimination hits included muscle LIM protein, beta-1,3-glucan-binding protein, myosin heavy chain, thaumatin-like protein, vWFA domain-containing protein, BTB domain-containing protein, amylase, and beta-catenin. Deiminated proteins specific to Atlantic jackknife clam included nacre c1q domain-containing protein and PDZ domain-containing protein In addition, some proteins were common as deiminated targets between two or three of the Bivalvia species under study (e.g., EP protein, C1q domain containing protein, histone H2B, tubulin, elongation factor 1-alpha, dominin, extracellular superoxide dismutase). Protein interaction network analysis for the deiminated protein hits revealed major pathways relevant for immunity and metabolism, providing novel insights into post-translational regulation via deimination. The study contributes to EV characterization in diverse taxa and understanding of roles for PAD-mediated regulation of immune and metabolic pathways throughout phylogeny.
Chemical Composition of Sour Beer Resulting from Supplementation the Fermentation Medium with Magnesium and Zinc Ions
Authors: Ciosek Aneta , Fulara Katarzyna , Hrabia Olga , Satora Paweł , Poreda Aleksander
Published: November 2020

The bioavailability of minerals, such as zinc and magnesium, has a significant impact on the fermentation process. These metal ions are known to influence the growth and metabolic activity of yeast, but there are few reports on their effects on lactic acid bacteria (LAB) metabolism during sour brewing. This study aimed to evaluate the influence of magnesium and zinc ions on the metabolism of Lactobacillus brevis WLP672 during the fermentation of brewers’ wort. We carried out lactic acid fermentations using wort with different mineral compositions: without supplementation; supplemented with magnesium at 60 mg/L and 120 mg/L; and supplemented with zinc at 0.4 mg/L and 2 mg/L. The concentration of organic acids, pH of the wort and carbohydrate use was determined during fermentation, while aroma compounds, real extract and ethanol were measured after the mixed fermentation. The addition of magnesium ions resulted in the pH of the fermenting wort decreasing more quickly, an increase in the level of L-lactic acid (after 48 h of fermentation) and increased concentrations of some volatile compounds. While zinc supplementation had a negative impact on the L. brevis strain, resulting in a decrease in the L-lactic acid content and a higher pH in the beer. We conclude that zinc supplementation is not recommended in sour beer production using L. brevis WLP672.
Ovariopexy—Before and after Endometriosis Surgery
Authors: Dhanawat Juhi , Pape Julian , Freytag Damaris , Maass Nicolai , Alkatout Ibrahim
Published: November 2020

Endometriosis surgery is often very challenging. Key to complete resection of endometriosis is access to the retroperitoneum. Endometriosis can involve the ureter and uterine vessels, and ovary on the lateral pelvic wall makes retroperitoneal access difficult. Primary and post-surgical adhesions prevalence in endometriosis is very high. Ovariopexy, transposition of ovaries temporarily, is done for better surgical access and to reduce postoperative adhesions. We concluded that although limited evidence, ovariopexy is an excellent tool to aid endometriosis surgery and prevent postoperative adhesions. It is cost effective, simple and complication rate almost nil. More robust trials are required to substantiate evidence for its impact on preventing postoperative adhesions and its effect on fertility. In this review, we describe our technique of ovariopexy supplemented with a video, with the aim to put light on this useful and important technique, which is beneficial both for surgeons and patients.
Lectin-Like Transcript 1 (LLT1) Checkpoint: A Novel Independent Prognostic Factor in HPV-Negative Oropharyngeal Squamous Cell Carcinoma
Authors: Sanchez-Canteli Mario , Hermida-Prado Francisco , Sordo-Bahamonde Christian , Montoro-Jiménez Irene , Pozo-Agundo Esperanza , Allonca Eva , Vallina-Álvarez Aitana , Álvarez-Marcos César , Gonzalez Segundo , García-Pedrero Juana M. , Rodrigo Juan P.
Published: November 2020

Lectin-like transcript 1 (LLT1) expression by tumor cells contributes to immune evasion, thereby emerging as a natural killer (NK) cell-mediated immunotherapeutic target. This study is the first to investigate LLT1 expression (encoded by CLEC2D gene) in head and neck cancers to ascertain its impact on patient prognosis. LLT1 expression was analyzed by immunohistochemistry in a homogeneous cohort of human papillomavirus (HPV)-negative oropharyngeal squamous cell carcinomas (OPSCC), and correlated with clinical data. Results were further validated using transcriptomic data from the TCGA database. Tumoral LLT1 expression was detected in 190/221 (86%) OPSCC specimens, whereas normal pharyngeal epithelium was negative. Patients harboring LLT1-positive tumors showed significantly lower disease-specific (DSS) and overall survival (OS) (p = 0.049 and p = 0.036, respectively, log-rank test). High density of LLT1-positive tumor-infiltrating lymphocytes (TIL) was also frequently detected in 160 (73%) OPSCC samples, and significantly associated with better DSS and OS (p < 0.001 and p = 0.007, respectively). Multivariate Cox analysis further revealed that tumoral LLT1 expression and infiltration of LLT1-positive TIL were independent prognostic factors for DSS and OS. CLEC2D mRNA levels are also significantly increased in primary tumors compared to normal tissue. Strikingly, the prognostic impact of CLEC2D mRNA levels varied depending on HPV status in OPSCC, and among distinct cancer types. CLEC2D expression was significantly correlated with NK cell infiltration using the MCP-counter model. These findings uncover LLT1/CLEC2D as an independent prognostic factor in HPV-negative OPSCC, and a potential novel target for immunotherapy.
Pupil Dilation during Reward Anticipation Is Correlated to Depressive Symptom Load in Patients with Major Depressive Disorder
Authors: Schneider Max , Elbau Immanuel G. , Nantawisarakul Teachawidd , Pöhlchen Dorothee , Brückl Tanja , BeCOME Working Group  , Czisch Michael , Saemann Philipp G. , Lee Michael D. , Binder Elisabeth B. , Spoormaker Victor I.
Published: November 2020

Depression is a debilitating disorder with high prevalence and socioeconomic cost, but the brain-physiological processes that are altered during depressive states are not well understood. Here, we build on recent findings in macaques that indicate a direct causal relationship between pupil dilation and anterior cingulate cortex mediated arousal during anticipation of reward. We translated these findings to human subjects with concomitant pupillometry/fMRI in a sample of unmedicated participants diagnosed with major depression and healthy controls. We could show that the upregulation and maintenance of arousal in anticipation of reward was disrupted in patients in a symptom-load dependent manner. We could further show that the failure to maintain reward anticipatory arousal showed state-marker properties, as it tracked the load and impact of depressive symptoms independent of prior diagnosis status. Further, group differences of anticipatory arousal and continuous correlations with symptom load were not traceable only at the level of pupillometric responses, but were mirrored also at the neural level within salience network hubs. The upregulation and maintenance of arousal during reward anticipation is a novel translational and well-traceable process that could prove a promising gateway to a physiologically informed patient stratification and targeted interventions.
KLK4 Induces Anti-Tumor Effects in Human Xenograft Mouse Models of Orthotopic and Metastatic Prostate Cancer
Authors: Tse Brian W.-C. , Kryza Thomas , Yeh Mei-Chun , Dong Ying , Sokolowski Kamil A. , Walpole Carina , Dreyer Tobias , Felber Johanna , Harris Jonathan , Magdolen Viktor , Russell Pamela J. , Clements Judith A.
Published: November 2020

Recent reports have suggested the role of kallikrein-related peptidase 4 (KLK4) to be that of remodeling the tumor microenvironment in many cancers, including prostate cancer. Notably, these studies have suggested a pro-tumorigenic role for KLK4, especially in prostate cancer. However, these have been primarily in vitro studies, with limited in vivo studies performed to date. Herein, we employed an orthotopic inoculation xenograft model to mimic the growth of primary tumors, and an intracardiac injection to induce metastatic dissemination to determine the in vivo tumorigenic effects of KLK4 overexpressed in PC3 prostate cancer cells. Notably, we found that these KLK4-expressing cells gave rise to smaller localized tumors and decreased metastases than the parent PC-3 cells. To our knowledge, this is the first report of an anti-tumorigenic effect of KLK4, particularly in prostate cancer. These findings also provide a cautionary tale of the need for in vivo analyses to substantiate in vitro experimental data.
LNX1 Modulates Notch1 Signaling to Promote Expansion of the Glioma Stem Cell Population during Temozolomide Therapy in Glioblastoma
Authors: Baisiwala Shivani , Hall Robert R. , Saathoff Miranda R. , M. Shireman Jack , Park Cheol , Budhiraja Shreya , Goel Chirag , Warnke Louisa , Hardiman Clare , Wang Jennifer Y. , McCortney Katy , Horbinski Craig M. , Ahmed Atique U.
Published: November 2020

Glioblastoma (GBM) is the most common primary brain malignancy in adults, with a 100% recurrence rate and 21-month median survival. Our lab and others have shown that GBM contains a subpopulation of glioma stem cells (GSCs) that expand during chemotherapy and may contribute to therapeutic resistance and recurrence in GBM. To investigate the mechanism behind this expansion, we applied gene set expression analysis (GSEA) to patient-derived xenograft (PDX) cells in response to temozolomide (TMZ), the most commonly used chemotherapy against GBM. Results showed significant enrichment of cancer stem cell and cell cycle pathways (False Discovery Rate (FDR) < 0.25). The ligand of numb protein 1 (LNX1), a known regulator of Notch signaling by targeting negative regulator Numb, is strongly upregulated after TMZ therapy (p < 0.0001) and is negatively correlated with survival of GBM patients. LNX1 is also upregulated after TMZ therapy in multiple PDX lines with concomitant downregulations in Numb and upregulations in intracellular Notch1 (NICD). Overexpression of LNX1 results in Notch1 signaling activation and increased GSC populations. In contrast, knocking down LNX1 reverses these changes, causing a significant downregulation of NICD, reduction in stemness after TMZ therapy, and resulting in more prolonged median survival in a mouse model. Based on this, we propose that during anti-GBM chemotherapy, LNX1-regulated Notch1 signaling promotes stemness and contributes to therapeutic resistance.
Autoantibody Formation and Mapping of Immunogenic Epitopes against Cold-Shock-Protein YB-1 in Cancer Patients and Healthy Controls
Authors: Morgenroth Ronnie , Reichardt Charlotte , Steffen Johannes , Busse Stefan , Frank Ronald , Heidecke Harald , Mertens Peter R.
Published: November 2020

Cold shock Y-box binding protein-1 participates in cancer cell transformation and mediates invasive cell growth. It is unknown whether an autoimmune response against cancerous human YB-1 with posttranslational protein modifications or processing develops. We performed a systematic analysis for autoantibody formation directed against conformational and linear epitopes within the protein. Full-length and truncated recombinant proteins from prokaryotic and eukaryotic cells were generated. Characterization revealed a pattern of spontaneous protein cleavage, predominantly with the prokaryotic protein. Autoantibodies against prokaryotic, but not eukaryotic full-length and cleaved human YB-1 protein fragments were detected in both, healthy volunteers and cancer patients. A mapping of immunogenic epitopes performed with truncated E. coli-derived GST-hYB-1 proteins yielded distinct residues in the protein N- and C-terminus. A peptide array with consecutive overlapping 15mers revealed six distinct antigenic regions in cancer patients, however to a lesser extent in healthy controls. Finally, a protein cleavage assay was set up with recombinant pro- and eukaryotic-derived tagged hYB-1 proteins. A distinct cleavage pattern developed, that is retarded by sera from cancer patients. Taken together, a specific autoimmune response against hYB-1 protein develops in cancer patients with autoantibodies targeting linear epitopes.
STAT3 and STAT5B Mutations in T/NK-Cell Chronic Lymphoproliferative Disorders of Large Granular Lymphocytes (LGL): Association with Disease Features
Authors: Muñoz-García Noemí , Jara-Acevedo María , Caldas Carolina , Bárcena Paloma , López Antonio , Puig Noemí , Alcoceba Miguel , Fernández Paula , Villamor Neus , Flores-Montero Juan A. , Gómez Karoll , Lemes María Angelina , Hernández Jose Carlos , Álvarez-Twose Iván , Guerra Jose Luis , González Marcos , Orfao Alberto , Almeida Julia
Published: November 2020

STAT3 and STAT5B (STAT3/STAT5B) mutations are the most common mutations in T-cell large granular lymphocytic leukemia (T-LGLL) and chronic lymphoproliferative disorders of NK cells (CLPD-NK), but their clinical impact remains unknown. We investigated the frequency and type of STAT3/STAT5B mutations in FACS-sorted populations of expanded T/NK-LGL from 100 (82 clonal; 6 oligoclonal; 12 polyclonal) patients, and its relationship with disease features. Seventeen non-LGL T-CLPD patients and 628 age-matched healthy donors were analyzed as controls. STAT3 (n = 30) and STAT5B (n = 1) mutations were detected in 28/82 clonal T/NK-LGLL patients (34%), while absent (0/18, 0%) among oligoclonal/polyclonal LGL-lymphocytosis. Mutations were found across all diagnostic subgroups: TCD8+-LGLL, 36%; CLPD-NK, 38%; TCD4+-LGLL, 7%; Tαβ+DP-LGLL, 100%; Tαβ+DN-LGLL, 50%; Tγδ+-LGLL, 44%. STAT3-mutated T-LGLL/CLPD-NK showed overall reduced (p < 0.05) blood counts of most normal leukocyte subsets, with a higher rate (vs. nonmutated LGLL) of neutropenia (p = 0.04), severe neutropenia (p = 0.02), and cases requiring treatment (p = 0.0001), together with a shorter time-to-therapy (p = 0.0001), particularly in non-Y640F STAT3-mutated patients. These findings confirm and extend on previous observations about the high prevalence of STAT3 mutations across different subtypes of LGLL, and its association with a more marked decrease of all major blood-cell subsets and a shortened time-to-therapy.
Trastuzumab Emtansine Plus Non-Pegylated Liposomal Doxorubicin in HER2-Positive Metastatic Breast Cancer (Thelma): A Single-Arm, Multicenter, Phase Ib Trial
Authors: López-Miranda Elena , Pérez-García José Manuel , Di Cosimo Serena , Brain Etienne , Ravnik Maja , Escrivá-de-Romaní Santiago , Vidal Maria , Gligorov Joseph , Borštnar Simona , Calabuig Laura , Sampayo-Cordero Miguel , Malfettone Andrea , Llombart-Cussac Antonio , Suter Thomas M. , Cortés Javier
Published: November 2020

The paper assesses the dose-limiting toxicities and the maximum tolerated dose (MTD) of trastuzumab emtansine (T-DM1) combined with non-pegylated liposomal doxorubicin (NPLD) in HER2-positive (HER2+) metastatic breast cancer (MBC). This single-arm, open-label, phase Ib trial (NCT02562378) enrolled anthracycline-naïve HER2+ MBC patients who had progressed on trastuzumab and taxanes. Patients received a maximum of 6 cycles of NPLD intravenously (IV) at various dose levels (45, 50, and 60 mg/m2) in the “3 plus 3” dose-escalation part. During expansion, they received 60 mg/m2 of NPLD every 3 weeks (Q3W) plus standard doses of T-DM1. The MTD was T-DM1 3.6 mg/kg plus NPLD 60 mg/m2 administered IV Q3W. No clinically relevant worsening of cardiac function was observed. Among all evaluable patients, the overall response rate was 40.0% (95%CI, 16.3–67.7) with a median duration of response of 6.9 months (95%CI, 4.8–9.1). Clinical benefit rate was 66.7% (95%CI, 38.4–88.2) and median progression-free survival was 7.2 months (95%CI, 4.5–9.6). No significant influence of NPLD on T-DM1 pharmacokinetics was observed. The addition of NPLD to T-DM1 is feasible but does not seem to improve the antitumor efficacy of T-DM1 in HER2+ MBC patients.
Tryptophan Fluorescence and Time-Lag Hydrolysis of Peptide Bonds during Degradation of β-Lactoglobulin by Trypsin
Authors: M. Vorob’ev Mikhail
Published: November 2020

The opening of protein globules and corresponding exposure of their internal peptide bonds, the so-called demasking effect, is required for successful hydrolysis of peptide bonds by proteases. Under the proteolytic action of trypsin on β-lactoglobulin (β-LG), the evolution of tryptophan fluorescence spectra showed that the demasking process consists of two stages with different demasking rate constants for each stage. It was found that the ratio of these constants depends on the concentration of trypsin and changes are approximately threefold when the concentration of trypsin changes in the range of 0.3–15 mg/L. Simulation of hydrolysis taking into account the demasking effect demonstrated how the apparent first-order rate constants obtained experimentally are related to the true hydrolysis rate constants and demasking parameters. The lag phase in the kinetic curves corresponding to the hydrolysis of various peptide bonds in β-LG was also analyzed. The increased lag times indicated sites that are hydrolyzed by a two-stage demasking mechanism.
Mesoporous Carbon of Carbonized Human Urine Waste: A Valuable Heterogeneous Catalyst for Chromene and Xanthene Derivative Synthesis
Authors: Siddiqui T. A. J. , Shaikh Shoyebmohamad F. , Sangale Sushil S. , Raut Siddheshwar D. , Mane Rajaram S. , Ubaidullah Mohd , Thamer Badr M. , Al-Enizi Abdullah M. , Totawar Balaji B. , Samdani Mohammad Shahzad
Published: November 2020

Human urine is universal unused waste material that is regularly disposed of by the human body. We, for the first time, presented an economically beneficial, sustainable, and novel route to synthesize mesoporous human urine carbon (HUC)-containing heteroatoms, i.e., C, Na, Cl, N, S, and P, using a human urine waste. The as-synthesized HUC were envisaged for their structural elucidation, morphology evolution, crystal structure, functional bonding, and elemental composition analyses through various sophisticated technologies. The HUC catalyst had a moderately crystalline nature due to the graphitic phase of carbon with a particle size of 20–50 nm, which was successfully used to synthesizing chromenes, 1,8-di-oxo-octahydroxanthenes, and benzypyrazolylcoumarin and biscoumarin derivatives through a one-pot multicomponent reaction with 20 mg of catalyst in EtOH/H2O solvent. This eco-friendly and simple method offers numerous advantages such as easy purification, clean reaction, and excellent yield for organic synthesis. The HUC catalyst can be recycled ten times and reused multiple times after activation without affecting catalytic performance.
Preparation and Electrocatalysis Application of Pure Metallic Aerogel: A Review
Authors: Zhang Ran , Zhao Yan
Published: November 2020

Nanomaterials are widely used in electrocatalysts due to their quantum size effect and high utilization efficiency. There are two ways to improve the activity of nanoelectrocatalysts: increasing the number of active sites and improving the inherent activity of each catalytic site. The structure of the catalyst itself can be improved by increasing the number of exposed active sites per unit mass. The high porosity and three-dimensional network structure enable aerogels to have the characteristics of a large specific surface area, exposing many active sites and bringing structural stability through the self-supporting nature of aerogels. Thus, by adjusting the compositions of aerogels, the synergetic effect introduced by alloy elements can be utilized to further improve the single-site activity. In this review, we summarized the basic preparation strategy of aerogels and extended it to the preparation of alloys and special structure aerogels. Moreover, through the eight electrocatalysis cases, the outstanding catalytic performances and broad applicability of aerogel electrocatalysts are emphasized. Finally, we predict the future development of pure metallic aerogel electrocatalysts from the perspective of preparation to application.
Top 10 Cited Papers in the Section “Electrocatalysis”
Authors: Baglio Vincenzo
Published: November 2020

This editorial is dealing with the most cited papers published in the years 2018–2019 in the section “Electrocatalysis” of the journal Catalysts [...]
Mast Cell Functions Linking Innate Sensing to Adaptive Immunity
Authors: Katsoulis-Dimitriou Konstantinos , Kotrba Johanna , Voss Martin , Dudeck Jan , Dudeck Anne
Published: November 2020

Although mast cells (MCs) are known as key drivers of type I allergic reactions, there is increasing evidence for their critical role in host defense. MCs not only play an important role in initiating innate immune responses, but also influence the onset, kinetics, and amplitude of the adaptive arm of immunity or fine-tune the mode of the adaptive reaction. Intriguingly, MCs have been shown to affect T-cell activation by direct interaction or indirectly, by modifying the properties of antigen-presenting cells, and can even modulate lymph node-borne adaptive responses remotely from the periphery. In this review, we provide a summary of recent findings that explain how MCs act as a link between the innate and adaptive immunity, all the way from sensing inflammatory insult to orchestrating the final outcome of the immune response.
Alerting and Circadian Effects of Short-Wavelength vs. Long-Wavelength Narrow-Bandwidth Light during a Simulated Night Shift
Authors: Sunde Erlend , Pedersen Torhild , Mrdalj Jelena , Thun Eirunn , Grønli Janne , Harris Anette , Bjorvatn Bjørn , Waage Siri , Skene Debra J. , Pallesen Ståle
Published: November 2020

Light can be used to facilitate alertness, task performance and circadian adaptation during night work. Novel strategies for illumination of workplaces, using ceiling mounted LED-luminaires, allow the use of a range of different light conditions, altering intensity and spectral composition. This study (ClinicalTrials.gov Identifier NCT03203538) investigated the effects of short-wavelength narrow-bandwidth light (λmax = 455 nm) compared to long-wavelength narrow-bandwidth light (λmax = 625 nm), with similar photon density (~2.8 × 1014 photons/cm2/s) across light conditions, during a simulated night shift (23:00–06:45 h) when conducting cognitive performance tasks. Light conditions were administered by ceiling mounted LED-luminaires. Using a within-subjects repeated measurements study design, a total of 34 healthy young adults (27 females and 7 males; mean age = 21.6 years, SD = 2.0 years) participated. The results revealed significantly reduced sleepiness and improved task performance during the night shift with short-wavelength light compared to long-wavelength light. There was also a larger shift of the melatonin rhythm (phase delay) after working a night shift in short-wavelength light compared to long-wavelength light. Participants’ visual comfort was rated as better in the short-wavelength light than the long-wavelength light. Ceiling mounted LED-luminaires may be feasible to use in real workplaces, as these have the potential to provide light conditions that are favorable for alertness and performance among night workers.