bluuebunny/crossref_metadata_2025 huggingface dataset:
Ryegrass production in Wairarapa, New Zealand: is biological control of Argentine stem weevil important?
Authors: Mcneill M.R. , Hume D.E. , Ashby R. , Ashby M. , Brandon P. , Guscott P. , Tosswill B. , Barton R.
Published: April 2021

To investigate the interaction between Argentine stem weevil (Listronotus bonariensis), its parasitoid Microctonus hyperodae, fungal endophyte (Neotyphodium lolii) and its grass host, four endophyte-ryegrass (Lolium perenne) treatments were established on four farms in Wairarapa in autumn 2003. A diploid ryegrass contained either wild-type or AR1 endophyte or was endophytefree, while a tetraploid ryegrass contained AR1 endophyte. Wild-type, AR1 and endophyte-free ryegrasses average 52%, 91% and 2% endophyte-infected tillers for the 3 years of measurement. Moderate increases over time in the proportion of wild-type infected tillers indicated selection pressures favoured endophyte-infected tillers. Endophyte-free tiller populations were 11% lower than AR1 or wild-type but not significantly so. L. bonariensis populations were highest in endophyte-free and wild-type pastures and 80% lower in AR1 pastures. Mean rates of parasitism in L. bonariensis were lower in spring (9%) than autumn (35%), tended to be higher in wild-type than in AR1 diploid ryegrass, and only had a weak relationship with percent endophyte-infection. Keywords: endophyte, Neotyphodium lolii, Lolium perenne, dry matter yields, plant persistence, Listronotus bonariensis, Microctonus hyperodae
Variable performance of bird cherry-oat aphid on Neotyphodium-infected tall fescue from Tunisia
Authors: Clement S.L. , Elberson L.R. , Waldron B.L. , Quisenberry S.S.
Published: April 2021

The extent of Neotyphodium based resistance in wild fescue to bird cherry-oat aphid (Rhopalosiphum padi) was determined by quantifying densities of this aphid on a series of Neotyphodiuminfected (E+) and uninfected (E-) tall fescue entries. Little or no aphid survival was observed on E+ 'Kentucky 31' tall fescue and three E+ wild tall fescue accessions (16079, 15978, 16075) from Tunisia; however, three E+ Tunisia accessions (16036, 16044, 16085) supported populations of R. padi. These results suggest that wild tall fescue from Tunisia harbour diverse Neotyphodium endophytes. They also support earlier observations by entomologists that the magnitude of insect (including aphids) resistance in E+ grasses varies with the host genotype and Neotyphodium strain involved in the interaction. Keywords: Neotyphodium endophyte, tall fescue, Rhopalosiphum padi, host plant resistance
Cereal leaf beetle: is performance affected by grass endophytes?
Authors: Clement S.L. , Elberson L.R. , Miller T. , Kynaston M. , Phillips T.D.
Published: April 2021

Cereal leaf beetle (CLB), Oulema melanopus (L.) (Coleoptera: Chrysomelidae), a long known pest of small grains in Europe, was first recorded in North America (Michigan) in 1962.
Dynamics of peripheral blood flow for endophyte-naive cattle fed toxic tall fescue seed
Authors: Aiken G.E. , Kirch B.H. , Strickland J.R.
Published: April 2021

Doppler ultrasonography was used to measure blood flow dynamics in the caudal artery of heifers that were fed diets with either endophyte-infected (E+) or non-infected (E+) tall fescue (Festuca arundinacea Schreb.) seed. Heifers were assigned to six pens and during an adjustment period were fed alfalfa hay for 5 d, and then the hay plus a concentrate with E- tall fescue seed for 9 d. An 11-d experimental period followed with three pens being changed to hay plus concentrate with E+ seed. Caudal artery area in E+ heifers had declined by 4 h from the initial feeding of the E+ diet before stabilising at the lower level between 4 and 28 h. Heart rates followed a similar trend. Blood flow rate was lower in E+ heifers from 28 h onwards. Results indicated that vasoconstriction can occur in cattle within 28 h from initial consumption of toxic fescue. Keywords: tall fescue, fescue toxicosis, cattle, vasoconstriction
Effect of perennial ryegrass endophyte and a feed additive on some physiological parameters and intake of young ewes in winter
Authors: Henry M.L.E. , Hazelton M. , Reed K.F.M. , Cummins L.J. , Leury B.J.
Published: April 2021

Young merino ewes were offered a pelleted ration containing approx 15% perennial ryegrass seed, either infected or not infected with wild endophyte. Each group was split so that 10 ewes received the toxin deactivation product, ElitoxÂ®. Groups were fed indoors on treatment for 4 weeks in winter (average daily temperature, 11.5ÂºC). Analysis for endophyte toxins indicated intakes of 63 Î¼g/kg LW/day ergovaline and 23 Î¼g/kg LW/day lolitrem B. Increases in respiration rate and rectal temperature were obvious after 1 week. Respiration rate more than doubled for ewes ingesting toxin-containing wild endophyte. Differences were greater with observations taken at 9 pm, compared with those taken at 9 am. The intake and liveweight gain of ewes ingesting endophyte increased relative to those on the endophyte-free diet. Administration of ElitoxÂ®, resulted in a significant interaction: respiration rate and intake increased in the absence of endophyte, but decreased in its presence. Keywords: Merino sheep, perennial ryegrass, lolitrem B, ergovaline, ElitoxÂ®, intake, respiration rate, faecal moisture
Soil recovery following landslides at Whatawhata Research Station, Waikato, New Zealand: preliminary results
Authors: Noyes A.M. , Balks M.R. , Moon V.G. , Lowe D.J.
Published: April 2021

This research investigates soil recovery following landslides at the Whatawhata Research Station 20 km west of Hamilton. Six landslides were studied, ranging in age from pre-1953 to 2014. The landslides were divided into four zones: shear zones (mean of 25% of landslide area), intact accumulation zones (20%), transition zones (40%), and re-deposition zones (15%), along with a control. Soils were well-developed in the control and intact accumulation zones and least recovered in the shear and re-deposition zones. Mean A horizon depths ranged from 2 cm in the shear and re-deposition zones to 7 cm in the transition zone, 17 cm in the intact accumulation zone, and 20 cm in the control. Mean soil carbon contents were lower (P
The effects of hillslope forage crop grazing in winter on soil erosion
Authors: Penny V.M. , Almond P.C. , Laurenson S. , Klik A.
Published: April 2021

Farming intensification has led to a greater use of forage crops to feed cows over winter. This farming practice is now commonly taking place on rolling to steep land in areas where stock are wintered off-farm, such as Southland and South Otago. While the impacts of forage crop grazing on soil physical properties such as compaction, and overland flow of nutrients, sediment and pathogens have been studied, there is a lack of understanding of how this practice influences soil transport. This study used a novel technique to quantify the rate soil is pushed downslope by the hooves of cows while grazing kale, and found a linear relationship between soil transport and slope for slope gradients of less than 0.25. The steep slope of the linear relationship, which defines the soil transport coefficient, indicates rapid downslope soil movement relative to slope gradient. As a consequence, soil erosion on convex sites occurs at rates that likely exceed soil production rates. The formation of stock tracks on slopes greater than 0.25 caused greater uncertainty in soil transport rates, and more research is required to determine the effect of track formation on soil movement. Keywords: winter cropping, brassica, forage crops, erosion, soil creep
An assessment of current fertiliser practices in New Zealand hill country
Authors: Edmeades D.C. , Mcbride R.M. , Gray M.
Published: April 2021

In the last decade major reviews on the phosphorus (P), potassium (K) and sulphur (S) nutrient requirements of clover-based pastures in New Zealand have been completed. This has resulted in adjustments to the P, K and S pasture production functions and some changes to the critical levels for soil tests, and modifications to our interpretation of some soil tests such as Organic S and Reserve K. Applying this new information to New Zealand's hill country pastoral soils, using case studies, suggests that there is considerable unrealized potential to increase productivity. Keywords: critical levels, economics, fertiliser, pasture, phosphorus, potassium, soil fertility, soil tests, sulphur
Capability of ground fertiliser placement when spread from fixed wing aircraft
Authors: Chok S.E. , Grafton M.C.E. , Yule I.J. , Manning M.J.
Published: April 2021

Aerial topdressing using differential rate application technology improves fertiliser spreading on hill country farms. However, the system's ability to place fertiliser accurately and precisely within an area needs to be determined. Accuracy was determined by comparing measured and intended application rates. Precision was indicated by the coefficient of variation (CV), which is the standard deviation of the measured application rate over the mean of this rate. Two trials were carried out, where aircraft deposited fertiliser at two application rates and fertiliser was captured using cone-shaped collectors. The average measured application rate for both trials was less than the intended rate. The CV ranged from 35 to 57%, and was lower than CV's from pilot-operated hopper systems (78%). A one-way analysis of variance test found the difference between measured application rate in the high and low application zone was statistically significant. The results indicate work is required to improve the accuracy and precision of the differential rate system, however, the system shows promise. Keywords: differential rate application technology, aerial spreading, fertiliser placement
Impacts of grazing management on hill country pastures: principles and practices
Authors: King Mcg , Rennie G.M. , Devantier B. , Hoogendoorn C.J.
Published: April 2021

Management of the balance of animal demand and feed supply is the result of a complex set of decisions. These decisions interact and are also variably affected by external drivers, including environmental. In particular, both pasture quantity and quality can be optimised by using appropriate grazing management, including stocking rate, livestock class, etc. In essence: apply sufficient grazing pressure at the appropriate time to maintain pasture covers at a level where the development of grass inflorescences is limited and pasture quality is maximised. The optimal grazing management strategy, however, may be different for each paddock and will change through the season. At a whole-farm scale, grazing management will be a set of trade-offs. Understanding the underlying ecological principles that drive the outcome of these grazing management decisions on pasture performance will have the greatest potential to drive the profitability and sustainability of hill country farms. Keywords: Grazing management, pasture performance, pasture quality, hill country
Improved extension practices for sheep and beef farmers
Authors: Gray D.I. , Sewell A.M. , Hartnett M. , Wood B.A. , Kemp P.D. , Blair H.T. , Kenyon P.R. , Morris S.T.
Published: April 2021

Innovation is critical for maintaining New Zealand's competitive advantage in agriculture and central to this is farmer learning and practice change. Despite the importance of farmer learning, limited research has been undertaken in New Zealand. In this study, an extension programme was developed based upon educational theory and research and then evaluated over a 3 years to identify the factors that were important for farmer learning and practice change. This paper provides a brief overview of findings of a 3 year interdisciplinary study conducted at Massey University with 23 farmers that investigated the critical factors that support farmers' learning. The five critical success factors and the seven educational principles identified from this study provide guidelines for how science should interact with farmers to foster effective innovation. These findings are also applicable to other extension approaches such discussion groups, monitor farms and sustainable farming fund initiatives where farmers work with scientists and/or rural professionals. Keywords: farmer learning, extension, practice change, herb pastures, innovation, community of practice
From there to where? Past, present and future soil fertility management on hill country farms
Authors: Roberts A.H.C. , White M.D.
Published: April 2021

This review paper discusses aspects of hill country science-based soil fertility management advice given to farmers in the past on the use of fertiliser, principally superphosphate, on hill country farms. This shows that both pasture quantity and quality are improved with the application of the nutrients phosphorus (P) and sulphur (S) in superphosphate and that an unseen benefit of this is the increased food supply to soil biological organisms which also flourish under this management. The large potential for nitrogen (N) fertiliser application is explored and demonstrated. New thinking and technologies are allowing farmers to differentially apply variable rates and types of fertiliser nutrients by air to better match the growth potentials of contrasting hill country zones and so ensure that the investment in fertiliser will give the best financial returns possible. Keywords: soil fertility, hill country, differential application, variable rate
Study of Relief Conditions, Assessment of Climatic and Agro-climatic Indicators of the Lands of the Karabakh Plain, Suitable for Growing Grain Crops
Authors: Osmanova S.
Published: April 2021

Collected and analyzed empirical data on soil, ecological (agroecological), climatic and relief conditions of the Karabakh plain. The study of climatic and relief factors affecting the yield of grain crops was carried out on the basis of both literary sources and our own research.
Çocuklar Bakımından Uzlaştırma: Farklı Yararlar Arasında Bir Denge Arayışı
Authors: BAYTEMİR KONTACI Burcu
Published: April 2021

Çocuklar bakımından uzlaştırma, günümüzde gerek dünyada gerek Türkiye’de gittikçe öne çıkan bir ceza ve ceza muhakemesi hukuku kurumudur. Bu bağlamda, anılan kurum kapsamına giren suç tiplerinin giderek çeşitlendiği ve zaman içinde daha ciddi suçların bu kapsamda ele alındığı görülmektedir. Buna bağlı olarak da, çocuklar bakımından uzlaştırmaya tâbi olan dosyaların sayısı hızla artmakta ve uzlaştırma kurumu, adalet sistemi içinde daha görünür hâle gelmektedir. Buna karşın, çocuklar bakımından uzlaştırma uygulamasından beklenen yararların sağlanabilmesi için, öncelikle bu yararların neler olduğunun açıkça tespit edilmesi ve hangi hukuki kurum ve kurallar aracılığıyla hayata geçirilebileceğinin belirlenmesi gerekmektedir. Bu çalışmada, çocuklar bakımından uzlaştırmadan beklenen üç farklı yarar kategorisi olduğu ve başarılı bir uzlaştırma uygulamasının da, ancak bu yararlar arasında makul bir denge kurulmasıyla mümkün olabileceği ileri sürülmektedir. Bu bağlamda, çalışmada benimsenen yarar kategorileri; adalet sistemi bakımından “alternatif çözüm yöntemi”, uzlaştırmanın tarafları bakımından “onarıcı adalet” ve çocuklar bakımından da “çocuğun yüksek yararı” olarak belirlenmiş bulunmaktadır. Çalışmada, her üç yarar kategorisi ayrıntılı bir biçimde tanımlanmakta ve Türk Hukuku’ndaki mevcut durumun analizi yapılarak, sorunlu olduğu düşünülen alanlara işaret edilmekte ve somut çözüm önerilerinde bulunulmaktadır.
Cytological, Histological and Molecular Characterization of Two Isolates of Cucumber Mosaic Virus (CMV) in Egypt
Authors: Wagih Elsayed E. , Zalat Mohamed M. , Kawanna Maha Adel
Published: April 2021

Two isolates of Cucumber mosaic virus (CMV), CMV-wild tobacco (from Alexandria governorate) and CMV-cucumber (from Kafr El-Sheikh governorate) were investigated in this study. Cytological studies on epidermal strips of Nicotiana glutinosa leaves separately infected with each isolate revealed the presence of viral crystalline inclusion bodies within the infected cells. Electron microscopy of ultrathin sections of CMV infected N. glutinosa leaves showed significant alterations in the shape and internal structure of chloroplasts. The cell wall had serrated edges in infected cells but was more severe in cells infected with CMV-wild tobacco isolate compared to those infected with CMV-cucumber isolate. CMV-cucumber isolate was partially purified from systemically infected leaves of N. glutinosa. The ratio A260/ 280 was 1.0 and the concentration of the virus in the preparation was estimated using an extinction coefficient of E260nm0.1%, 1cm = 5. Yield of purified virus was about 2.8 mg/100 g fresh weight of infected N. glutinosa leaves. Electron microscopy of the purified preparation of CMV showed the presence of numerous spherical particles with a mean particle diameter of 28 nm. Amplified real-time reverse transcription-polymerase chain reaction (qRT-PCR) product of coat protein gene of each isolate was purified and sequenced. Sequences of both isolates had been submitted to GenBank Database and ware assigned accession number (LT669766) for CMV-cucumber isolate and (LT706517) for CMV-wild tobacco isolate. The sequences were edited using Chromas Pro. Version 1.34 software and compared with previously subgrouping of 27 isolates of the virus retrieved from the GenBank database. Both CMV-wild tobacco and CMV-cucumber isolates were closely related to the isolate with the accession number AJ585086 with a similarity of 97.07% and 98.54%, respectively, suggesting that the two isolates belong to subgroup II. According to the available literature, this is the first report in Egypt where CMV isolates belonging to subgroup II have been obtained
FEATURES OF FORMATION OF ZONES WITH SPECIAL CONDITIONS USE OF RAILWAY TRANSPORT INFRASTRUCTURE TERRITORIES IN CONDITIONS OF INFORMATION UNCERTAINTY IN CATALOGING THE INFLUENCE OF NATURAL FACTORS
Authors:   Moscow State University of Geodesy and Cartography (MIIGAiK), Portnov Aleksey M. , Zharnikov Valeriy B. ,   Siberian State University of Geosystems and Technologies, Gurkov Sergey V. ,   LLC "MosOblTransProekt", Fominykh Maksim V. ,   LLC "MosOblTransProekt"
Published: April 2021

Railway transport and its infrastructure operate as a sophisticated technological complex, charac-terized by a convergence of industrial, social and environmental norms and requirements. In order to comply with them, along the right-of-way for the railway tracks themselves, protected zones are formed with a limited regime of land use, defined, according to modern standards of urban develop-ment, as zones with special conditions for the use of territories (ZSCUT). The formation of such zones that represent the subject of cadastral engineers' activities is a composition of technological processes that are determined by spatial data, the volume and content of which is determined by the type and complexity of the object-the property complex, in this case represented by a railway section with the corresponding infrastructure. The ambiguity of regulatory requirements for the establishment of these zones on complex sections of the route determines the need to use additional data, in particular, de-scribing geological and other natural factors. This aspect allows us to consider the situation as infor-mation-uncertain, which is noted in the title of this work, and in its content to assess the safe function-ing of railway transport on the basis of information (cartographic) modeling of the parameters of the required zone. Taking into account the complexity of solving the problem of boundaries ZSCUT de-termination, the results of the presented study include: assessment of the adequacy of regulatory data for establishing such zones, new opportunities for cartographic modeling in their formation and moni-toring, recommendations for improving the regulatory framework.
SHAPED CHARGES WITH THIN AND ULTRA-THIN FACINGS
Authors: Minin Vladilen F. , Minin Igor V. ,   Siberian State University of Geosystems and Technologies, Minin Oleg V. ,   Siberian State University of Geosystems and Technologies
Published: April 2021

The aim of the research is to study the formation of cumulative jets in charges with cumulative facings with a wall thickness of the order of the thickness of the jet-forming layer in classical charges. Based on mathematical modeling and experiments, it is shown that in such charges, the detonation products of explosives can play the role of an additional body that affects the axial velocity of the lin-ing throwing and leads to a collapse angle of more than 180 degrees. In this process, the mass of the jet is greater than the mass of the pestle. For the first time, corrugations were experimentally detected on the surface of the lining during its explosive compression. Corrugations may occur on the surface of the lining, leading to instability of the cumulative jet formation process. As a result of the study, it was found that the minimum wall thickness of the cladding is mainly determined by the instability of its surface (the appearance of corrugations on its surface).
DISADVANTAGES OF HEIGHT ACCURACY REGULATION IN SP 121.13330.2019 "AERODROMES", ACTUALIZED EDITION SNiP 32-03–96
Authors:   Yugra State University, Poberezhny Anatoliy A.
Published: April 2021

Based on the requirements of the current regulatory and technical documents governing the ful-fillment of engineering and geodetic surveys for construction, the disadvantages of standardizing the accuracy of heights in SP 121.13330.2019 "Aerodromes", actualized edition SNiP 32-03–96 are con-sidered. Attention is drawn to the ambiguity of the given norms for the accuracy of heights, which leads to their free interpretation when calculating the accuracy of the alignment base, the internal alignment network, layout work, and control geodetic measurements. Doubts are expressed to their validity. To illustrate the application of the established accuracy standards, there is given an example of calculating the accuracy of high-altitude layout works and control geodetic measurements, internal high-altitude layout networks and a grid base when constructing structural layers of artificial founda-tions and aerodrome coatings using the "negligible influence" method and taking into account the ac-curacy of technological processes. Here are suggestions on improving the quality of standardization of the accuracy of heights for the construction of airdromes.
LA AGROINDUSTRIA DEL BANANO EN LA COSTA SUR ECUATORIANA: UNA MIRADA CRÍTICA DESDE LA COREMÁTICA
Authors:   Universidad Andina Simón Bolívar (UASB- E), Z Giannina , León Efraín ,   Universidad Nacional Autónoma de México
Published: April 2021

El espacio agroindustrial bananero se ha estructurado en el marco de una matriz de poder social, económico, político y militar, construida bajo el paraguas de un proyecto de poder global representado por las trasnacionales y que se imbrican con el poder local desde inicios del siglo XX. El objetivo de la investigación consistió en mirar críticamente, con ayuda de la coremática, a los modelos espaciales estructurados por la agroindustria del banano en la costa sur ecuatoriana. La investigación se enmarca en la geografía crítica, utilizando las categorías espacio social y territorio, constituyéndose éstas en puentes articuladores y de diálogo con otras disciplinas, permitiendo reflexionar y analizar las formas y estructuras del espacio en torno al agronegocio del banano. Para identificar y representar las formas y estructuras espaciales elementales (o coremas) configuradas por el mercado bananero se utilizó la geohistoria como herramienta teórico – metodológica debido a que articula espacio- tiempo y sociedad. Los coremas no responden a escalas cartográficas convencionales, pero permiten la representación del movimiento espacio-tiempo-sociedad y su análisis desde la totalidad, complejidad y dialéctica. Los corotipos sociohistóricos que se identificaron son: (1) efecto andino y de divisoria de aguas, (2) orbital de propiedad de centro y periferia, (3) mercado orbital y de redes jerárquicas, (4) efecto de complementación y diferencia portuaria y (5) efecto de comercialización y distribución; estructuras elementales que definen el modelo de organización del espacio de la costa sur en torno a la agroindustria del banano.
Volume of Surgical Freedom: The Most Applicable Anatomical Measurement for Surgical Assessment and 3-Dimensional Modeling
Authors: Houlihan Lena Mary , Naughton David , Preul Mark C.
Published: April 2021

Surgical freedom is the most important metric at the disposal of the surgeon. The volume of surgical freedom (VSF) is a new methodology that produces an optimal qualitative and quantitative representation of an access corridor and provides the surgeon with an anatomical, spatially accurate, and clinically applicable metric. In this study, illustrative dissection examples were completed using two of the most common surgical approaches, the pterional craniotomy and the supraorbital craniotomy. The VSF methodology models the surgical corridor as a cone with an irregular base. The measurement data are fitted to the cone model, and from these fitted data, the volume of the cone is calculated as a volumetric measurement of the surgical corridor. A normalized VSF compensates for inaccurate measurements that may occur as a result of dependence on probe length during data acquisition and provides a fixed reference metric that is applicable across studies. The VSF compensates for multiple inaccuracies in the practical and mathematical methods currently used for quantitative assessment, thereby enabling the production of 3-dimensional models of the surgical corridor. The VSF is therefore an improved standard for assessment of surgical freedom.
Rapid Prototyping of 3D Biochips for Cell Motility Studies Using Two-Photon Polymerization
Authors: Sala Federico , Ficorella Carlotta , Martínez Vázquez Rebeca , Eichholz Hannah Marie , Käs Josef A. , Osellame Roberto
Published: April 2021

The study of cellular migration dynamics and strategies plays a relevant role in the understanding of both physiological and pathological processes. An important example could be the link between cancer cell motility and tumor evolution into metastatic stage. These strategies can be strongly influenced by the extracellular environment and the consequent mechanical constrains. In this framework, the possibility to study the behavior of single cells when subject to specific topological constraints could be an important tool in the hands of biologists. Two-photon polymerization is a sub-micrometric additive manufacturing technique that allows the fabrication of 3D structures in biocompatible resins, enabling the realization of ad hoc biochips for cell motility analyses, providing different types of mechanical stimuli. In our work, we present a new strategy for the realization of multilayer microfluidic lab-on-a-chip constructs for the study of cell motility which guarantees complete optical accessibility and the possibility to freely shape the migration area, to tailor it to the requirements of the specific cell type or experiment. The device includes a series of micro-constrictions that induce different types of mechanical stress on the cells during their migration. We show the realization of different possible geometries, in order to prove the versatility of the technique. As a proof of concept, we present the use of one of these devices for the study of the motility of murine neuronal cancer cells under high physical confinement, highlighting their peculiar migration mechanisms.
DAND5 Inactivation Enhances Cardiac Differentiation in Mouse Embryonic Stem Cells
Authors: Inácio José Manuel , von Gilsa Lopes João , Silva Ana Mafalda , Cristo Fernando , Marques Sara , Futschik Matthias E. , Belo José António
Published: April 2021

Deciphering the clues of a regenerative mechanism for the mammalian adult heart would save millions of lives in the near future. Heart failure due to cardiomyocyte loss is still one of the significant health burdens worldwide. Here, we show the potential of a single molecule, DAND5, in mouse pluripotent stem cell-derived cardiomyocytes specification and proliferation.Dand5loss-of-function generated the double of cardiac beating foci compared to the wild-type cells. The early formation of cardiac progenitor cells and the increased proliferative capacity ofDand5KO mESC-derived cardiomyocytes contribute to the observed higher number of derived cardiac cells. Transcriptional profiling sequencing and quantitative RT-PCR assays showed an upregulation of early cardiac gene networks governing cardiomyocyte differentiation, cell cycling, and cardiac regenerative pathways but reduced levels of genes involved in cardiomyocyte maturation. These findings prompt DAND5 as a key driver for the generation and expansion of pluripotent stem cell-derived cardiomyocytes systems with further clinical application purposes.
Acceleration of Translational Mesenchymal Stromal Cell Therapy Through Consistent Quality GMP Manufacturing
Authors: Jayaraman Premkumar , Lim Ryan , Ng Jacqueline , Vemuri Mohan C.
Published: April 2021

Human mesenchymal stromal cell (hMSC) therapy has been gaining immense interest in regenerative medicine and quite recently for its immunomodulatory properties in COVID-19 treatment. Currently, the use of hMSCs for various diseases is being investigated in >900 clinical trials. Despite the huge effort, setting up consistent and robust scalable manufacturing to meet regulatory compliance across various global regions remains a nagging challenge. This is in part due to a lack of definitive consensus for quality control checkpoint assays starting from cell isolation to expansion and final release criterion of clinical grade hMSCs. In this review, we highlight the bottlenecks associated with hMSC-based therapies and propose solutions for consistent GMP manufacturing of hMSCs starting from raw materials selection, closed and modular systems of manufacturing, characterization, functional testing, quality control, and safety testing for release criteria. We also discuss the standard regulatory compliances adopted by current clinical trials to broaden our view on the expectations across different jurisdictions worldwide.
Prognostic Significance and Tumor Immune Microenvironment Heterogenicity of m5C RNA Methylation Regulators in Triple-Negative Breast Cancer
Authors: Huang Zhidong , Pan Junfan , Wang Helin , Du Xianqiang , Xu Yusheng , Wang Zhitang , Chen Debo
Published: April 2021

Purpose

The m5C RNA methylation regulators are closely related to tumor proliferation, occurrence, and metastasis. This study aimed to investigate the gene expression, clinicopathological characteristics, and prognostic value of m5C regulators in triple-negative breast cancer (TNBC) and their correlation with the tumor immune microenvironment (TIM).

Methods

The TNBC data, Luminal BC data and HER2 positive BC data set were obtained from The Cancer Genome Atlas and Gene Expression Omnibus, and 11 m5C RNA methylation regulators were analyzed. Univariate Cox regression and the least absolute shrinkage and selection operator regression models were used to develop a prognostic risk signature. The UALCAN and cBioportal databases were used to analyze the gene characteristics and gene alteration frequency of prognosis-related m5C RNA methylation regulators. Gene set enrichment analysis was used to analyze cellular pathways enriched by prognostic factors. The Tumor Immune Single Cell Hub (TISCH) and Timer online databases were used to explore the relationship between prognosis-related genes and the TIM.

Results

Most of the 11 m5C RNA methylation regulators were differentially expressed in TNBC and normal samples. The prognostic risk signature showed good reliability and an independent prognostic value. Prognosis-related gene mutations were mainly amplified. Concurrently, the NOP2/Sun domain family member 2 (NSUN2) upregulation was closely related to spliceosome, RNA degradation, cell cycle signaling pathways, and RNA polymerase. Meanwhile, NSUN6 downregulation was related to extracellular matrix receptor interaction, metabolism, and cell adhesion. Analysis of the TISCH and Timer databases showed that prognosis-related genes affected the TIM, and the subtypes of immune-infiltrating cells differed between NSUN2 and NSUN6.

Conclusion

Regulatory factors of m5C RNA methylation can predict the clinical prognostic risk of TNBC patients and affect tumor development and the TIM. Thus, they have the potential to be a novel prognostic marker of TNBC, providing clues for understanding the RNA epigenetic modification of TNBC.
The Ion-Translocating NrfD-Like Subunit of Energy-Transducing Membrane Complexes
Authors: Calisto Filipa , Pereira Manuela M.
Published: April 2021

Several energy-transducing microbial enzymes have their peripheral subunits connected to the membrane through an integral membrane protein, that interacts with quinones but does not have redox cofactors, the so-called NrfD-like subunit. The periplasmic nitrite reductase (NrfABCD) was the first complex recognized to have a membrane subunit with these characteristics and consequently provided the family's name: NrfD. Sequence analyses indicate that NrfD homologs are present in many diverse enzymes, such as polysulfide reductase (PsrABC), respiratory alternative complex III (ACIII), dimethyl sulfoxide (DMSO) reductase (DmsABC), tetrathionate reductase (TtrABC), sulfur reductase complex (SreABC), sulfite dehydrogenase (SoeABC), quinone reductase complex (QrcABCD), nine-heme cytochrome complex (NhcABCD), group-2 [NiFe] hydrogenase (Hyd-2), dissimilatory sulfite-reductase complex (DsrMKJOP), arsenate reductase (ArrC) and multiheme cytochrome c sulfite reductase (MccACD). The molecular structure of ACIII subunit C (ActC) and Psr subunit C (PsrC), NrfD-like subunits, revealed the existence of ion-conducting pathways. We performed thorough primary structural analyses and built structural models of the NrfD-like subunits. We observed that all these subunits are constituted by two structural repeats composed of four-helix bundles, possibly harboring ion-conducting pathways and containing a quinone/quinol binding site. NrfD-like subunits may be the ion-pumping module of several enzymes. Our data impact on the discussion of functional implications of the NrfD-like subunit-containing complexes, namely in their ability to transduce energy.
Clinical Identification and Characteristic Analysis of Giant Cell Myocarditis in 12 Cases
Authors: Liu Shangyu , Zheng Lihui , Shen Lishui , Wu Lingmin , Yao Yan
Published: April 2021

Aims: Giant cell myocarditis (GCM) is a rare, rapidly progressing cardiomyopathy with high mortality, if not diagnosed and treated in time. We analyzed the progression and clinical manifestations of patients with definitive diagnosis of GCM.

Methods and Result: We enrolled 12 patients diagnosed with GCM in the explanted heart during heart transplantation (HTx) or by endomyocardial biopsy (EMB) and collected information on demographic data, cardiac structure and function, arrhythmias, preliminary diagnosis, and delay of the diagnosis. Seven cases were diagnosed from biopsy samples during HTx, and five cases were diagnosed through EMB. Before the diagnosis of GCM based on pathological analysis, these patients had been incorrectly diagnosed with arrhythmogenic right ventricular cardiomyopathy (n = 5), dilated cardiomyopathy (n = 2), ventricular tachycardia (n = 2), viral myocarditis (n = 1), cardiac amyloidosis (n = 1), and ischemic cardiomyopathy (n = 1) based on clues such as symptoms, arrhythmia, and cardiac imaging. Patients diagnosed with GCM through EMB had a shorter symptom-onset-to-diagnosis time (6.6 ± 2.7 months) and milder heart damage (left ventricular ejection fraction, 47.2 ± 8.8%) than those diagnosed during HTx (11.0 ± 3.3 months, P = 0.034; 31.4 ± 10.9%, P = 0.024).

Conclusion: GCM is easily misdiagnosed as other types of myocarditis and cardiomyopathy. Pathological examination of the myocardium is the most reliable diagnostic method for GCM. Endocardial biopsy can identify patients with GCM at an earlier stage.
Systematic Understanding of Pathophysiological Mechanisms of Oxidative Stress-Related Conditions—Diabetes Mellitus, Cardiovascular Diseases, and Ischemia–Reperfusion Injury
Authors: Wang Mengxue , Liu Yun , Liang Yin , Naruse Keiji , Takahashi Ken
Published: April 2021

Reactive oxygen species (ROS) plays a role in intracellular signal transduction under physiological conditions while also playing an essential role in diseases such as hypertension, ischemic heart disease, and diabetes, as well as in the process of aging. The influence of ROS has some influence on the frequent occurrence of cardiovascular diseases (CVD) in diabetic patients. In this review, we considered the pathophysiological relationship between diabetes and CVD from the perspective of ROS. In addition, considering organ damage due to ROS elevation during ischemia–reperfusion, we discussed heart and lung injuries. Furthermore, we have focused on the transient receptor potential (TRP) channels and L-type calcium channels as molecular targets for ROS in ROS-induced tissue damages and have discussed about the pathophysiological mechanism of the injury.
Circular RNAs and Cardiovascular Regeneration
Authors: Tang Ling , Li Pengsheng , Jang Michelle , Zhu Wuqiang
Published: April 2021

circular RNAs (circRNAs) are a type of non-coding RNAs that are widely present in eukaryotic cells. They have the characteristics of stable structure, high abundance, and cell or tissue specific expression. circRNAs are single-stranded RNAs that are covalently back spliced to form closed circular loops. They may participate in gene expression and regulation through a variety of action modes. circRNAs can encode proteins or function by acting as miRNA sponges for protein translation. Since 2016, a growing number of research studies have shown that circRNAs play important role in the pathogenesis of cardiovascular disease. With the construction of circRNA database, the differential expression of circRNAs in the heart tissue samples from different species and the gradual elucidation of its mode of action in disease may become an ideal diagnosis biomarker and an effective therapeutic target. What can be expected surely has a broader application prospect. In this review, we summarize recent publications on circRNA biogenesis, expression profiles, functions, and the most recent studies of circRNAs in the field of cardiovascular diseases with special emphasis on cardiac regeneration.
Step-Down of FSH- Dosage During Ovarian Stimulation – Basic Lessons to Be Learnt From a Randomized Controlled Trial
Authors: Lawrenz Barbara , Coughlan Carol , Melado Laura , Digma Shieryl , Sibal Junard , Jean Alliza , Fatemi Human M.
Published: April 2021

A rise in serum progesterone in the late follicular phase is a well described adverse effect of ovarian stimulation for IVF/ICSI. Previous data suggest, that enhanced gonadotropin stimulation causes progesterone elevation and the incidence of premature progesterone elevation can be reduced by declining gonadotropin dosages. This randomized controlled trial (RCT) aimed to achieve a significant reduction of the progesterone level on the day of final oocyte maturation by a daily reduction of 12.5 IU rec-FSH from a follicle size of 14 mm in a GnRH-antagonist protocol. A total of 127 patients had been recruited (Control group (CG): 62 patients; Study group (SG): 65 patients). Due to drop out, data from 108 patients (CG: 55 patients; SG: 53 patients) were included into the analysis. Patients’ basic parameters, gonadotropin (Gn)-starting dose, total Gn-stimulation dosage, the number of retrieved and mature oocytes as well as in the hormonal parameters on the day of trigger (DoT) were not statistically significantly different. However, through stepwise Gn-reduction of 12.5 IU/day in the SG, there was a statistically highly significant difference in the Gn-stimulation dosage on the day of trigger (p < 0.0001) and statistically significant associations for the DoT-P4-levels with the DoT-FSH-levels for both groups (CG: p = 0.001; SG: p = 0.0045). The herein described significant associations between DoT-P4-levels and DoT-FSH-levels confirm the theory that enhanced FSH stimulation is the primary source of progesterone elevation on the day of final oocyte maturation in stimulated IVF/ICSI cycles. Given the pathophysiologic mechanism of progesterone elevation during ovarian stimulation, the use of an increased FSH step-down dosage should be studied in future RCTs, despite the fact that a step-down approach of daily 12.5 IU rec-FSH did not achieve a significantly reduced progesterone level on the DoT.

Clinical Trial Registration:clinicaltrials.gov, identifier NCT03356964.
Does Copper Contamination Affect Soil CO2 Emissions? A Literature Review
Authors: Sereni Laura , Guenet Bertrand , Lamy Isabelle
Published: April 2021

Contaminated soils are widespread and contamination is known to impact several biotic soil processes. But it is still not clear to what extent soil contamination affects soil carbon efflux (CO2) occurring through soil microfauna respiration. Regarding the large stocks of organic carbon (Corga) stored in soils, even limited changes in the outputs fluxes may modify atmospheric CO2 concentration with important feedbacks on climate. In this study, we aimed at assessing and quantifying how soil respiration is affected by contamination. For that, we performed a quantitative review of literature focusing on 1) soil heterotrophic respiration measurements thus excluding autotrophic respiration from plants, 2) soil copper contamination, and 3) the influence of pedo-climatic parameters such as pH, clay content or the type of climate. Using a dataset of 389 data analyzed with RandomForest and linear mixed statistical models, we showed a decrease in soil CO2 emission with an increase in soil copper contamination. Specific data from ex-situ spiking experiments could be easily differentiated from the ones originated from in-situ contamination due to their sharper decrease in soil Corga mineralization. Interestingly, ex-situ spikes data provided a threshold in soil Cu contents for CO2 emissions: CO2 emission increased for inputs below 265 mgCu.kg−1 soil and decreased above this concentration. Data from long-term in-situ contaminations due to anthropogenic activities (industrialization, agriculture, … ) also displayed an impact on soil carbon mineralization, much particularly for industrial contaminations (smelter, sewage sludge, … ) with decreased in CO2 emissions when Cu contamination increased. Soil pH was identified as a significant driver of the effect of Cu on CO2 emissions, as soil C mineralization was found to be more sensitive to Cu contamination in acidic soils than in neutral or alkaline soils. Conversely the clay content and the type of climate did not significantly explain the responses in soil C mineralization. Finally, the collected data were used to propose an empirical equation quantifying how soil respiration can be affected by a Cu contamination. The decrease in soil CO2 emissions cannot be related, however, in a role of C sink as it comes together with a decrease in soil microbial biomass.
A Panel of Five-lncRNA Signature as a Potential Biomarker for Predicting Survival in Gastric and Thoracic Cancers
Authors: Shao Jiayue , Lyu Wei , Zhou Jiehao , Xu Wenhui , Wang Dandan , Liang Shanshan , Zhao Jiayin , Qin Yujing
Published: April 2021

Dysfunctional long non-coding RNAs (lncRNAs) have been found to have carcinogenic and/or tumor inhibitory effects in the development and progression of cancer, suggesting their potential as new independent biomarkers for cancer diagnosis and prognosis. The exploration of the relationship between lncRNAs and the overall survival (OS) of different cancers opens up new prospects for tumor diagnosis and treatment. In this study, we established a five-lncRNA signature and explored its prognostic efficiency in gastric cancer (GC) and several thoracic malignancies, including breast invasive carcinoma (BRCA), esophageal carcinoma, lung adenocarcinoma, lung squamous cell carcinoma (LUSC), and thymoma (THYM). Cox regression analysis and lasso regression were used to evaluate the relationship between lncRNA expression and survival in different cancer datasets from GEO and TCGA. Kaplan-Meier survival curves indicated that risk scores characterized by a five-lncRNA signature were significantly associated with the OS of GC, BRCA, LUSC, and THYM patients. Functional enrichment analysis showed that these five lncRNAs are involved in known biological pathways related to cancer pathology. In conclusion, the five-lncRNA signature can be used as a prognostic marker to promote the diagnosis and treatment of GC and thymic malignancies.
Repurposing Immunomodulatory Drugs to Combat Tuberculosis
Authors: Fatima Samreen , Bhaskar Ashima , Dwivedi Ved Prakash
Published: April 2021

Tuberculosis (TB) is an infectious disease caused by an obligate intracellular pathogen, Mycobacterium tuberculosis (M.tb) and is responsible for the maximum number of deaths due to a single infectious agent. Current therapy for TB, Directly Observed Treatment Short-course (DOTS) comprises multiple antibiotics administered in combination for 6 months, which eliminates the bacteria and prevents the emergence of drug-resistance in patients if followed as prescribed. However, due to various limitations viz., severe toxicity, low efficacy and long duration; patients struggle to comply with the prescribed therapy, which leads to the development of drug resistance (DR). The emergence of resistance to various front-line anti-TB drugs urgently require the introduction of new TB drugs, to cure DR patients and to shorten the treatment course for both drug-susceptible and resistant populations of bacteria. However, the development of a novel drug regimen involving 2-3 new and effective drugs will require approximately 20-30 years and huge expenditure, as seen during the discovery of bedaquiline and delamanid. These limitations make the field of drug-repurposing indispensable and repurposing of pre-existing drugs licensed for other diseases has tremendous scope in anti-DR-TB therapy. These repurposed drugs target multiple pathways, thus reducing the risk of development of drug resistance. In this review, we have discussed some of the repurposed drugs that have shown very promising results against TB. The list includes sulfonamides, sulfanilamide, sulfadiazine, clofazimine, linezolid, amoxicillin/clavulanic acid, carbapenems, metformin, verapamil, fluoroquinolones, statins and NSAIDs and their mechanism of action with special emphasis on their immunomodulatory effects on the host to attain both host-directed and pathogen-targeted therapy. We have also focused on the studies involving the synergistic effect of these drugs with existing TB drugs in order to translate their potential as adjunct therapies against TB.