bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnesium hydroxide as a novel herbage spray supplement for Iactating cows and ewes
Authors: Parkins J.J. , Fishwick G.
Published: November 2021

Pasture dusting with fine particle grade calcined magnesite (16kg Mg/ha) is an effective means for the prevention of hypomagnesaemia and clinical tetany in dairy cows, but almost double that rate was recommended for practical use as both leaf adherence and spreading distribution may be inefficient, (Todd and Morrison, 1964). Magnesium hydroxide powder has been demonstrated to have a significantly higher apparent magnesium availability and increased urine magnesium output for wether sheep than some granular calcined magnesites (Hemingwayet al., 1997). Very fine particle size (0.95 ˂10μm) Mg hydroxide suspension (‘Neutramag 40’, Britmag Ltd, Hartlepool TS24 0BY) is available (405g dry matter (DM)/kg, 168g Mg/kg liquid suspension with S.G. of 1.3). The objective of the work was to examine the apparent availability and also the effectiveness of varying rates of application of this material in providing supplemental magnesium to grazing ruminants in spring.
Responses in dry matter intakes and plasma phosphorus concentrations in ewes given phosphorus sources of contrasting rumen solubility
Authors: Parkins J.J. , Hemingway R.G.
Published: November 2021

Full rumination and feed dry matter (DM) intake require adequate recirculation of soluble phosphorus (P) and nitrogen (as urea) via saliva. Both decrease following periods of inadequate dietary intake, which may be prolonged for P with adults. Earlier studies, using 23 μm mesh nylon bags in cannulated cows, showed that rumen solubility coefficients of P in granular mono-calcium phosphate (MCP), powdered di-calcium phosphate (DCP) and granular defluorinated phosphate (DFP) were respectively 0.85, 0.14 and 0.03. This communication describes their relative ability to enhance plasma P and voluntary DM intake by ewes after lambing following development of aphosphorosis when given a low P diet (LP) throughout pregnancy (Parkins et al. 1998).
A comparison between ARC (1965) and AFRC (1991) phosphorus requirements for ewes
Authors: Parkins J.J. , Hemingway R.G. , Adam C.L.
Published: November 2021

Beef cows given a diet severely inadequate in phosphorus (P) from 16 weeks before calving maintained appetite until 3-6 weeks after calving when plasma P concentrations were below 1.0 mmol/1 (Bass et al. 1981). The objective of this experiment was to compare the adequacy of ARC (1965) and AFRC (1991) dietary P inputs for ewes in relation to dry matter (DM) intake, plasma P concentration and early lamb growth.

Blackface ewes (˃ 3 lambings, n=87, mean liveweight (LW) 53.9, s.d. 5.1kg)) were mated to Border Leicester rams and then randomly allocated to three equal groups according to LW and expected lambing date.
Effects of dietary supplemental baker's yeast (Saccharomyces cerevisiae) and niacin on milk yield and milk composition of dairy cows
Authors: Tasdemir A.R. , Gorgulu M.
Published: November 2021

In the last twenty years, some probiotics, such as Aspergillus oryzae or A. niger (Pioneer, 1989), yeast culture (Saccharomyces cerevisiae) (Wallace, 1994) and some microbial growth promoters (e.g. thiamine, niacin) (Shield, 1981), were used as feed additives in order to improve rumen conditions and cellulose digestion in the rumen and milk yield of dairy cows. The present study was planned to determine whether dietary supplemental baker's yeast and niacin would have individual and/or synergistic effects on milk yield and milk composition of dairy cows under our experimental conditions.
Effect of caustic-treated linseed on the composition of cow's milk
Authors: Kirkland R M , Scaife J.R. , Goodwill M.
Published: November 2021

In ruminant diets, whole oilseeds are potential sources of polyunsaturated fatty acids (PUFA), which, because they are protected by the intact seed pericarp, may escape rumen biohydrogenation (Murphy et. al., 1990). Some seed coats are highly resistant to microbial and enzymic digestion and seed lipids may therefore be poorly degraded. Mild chemical treatment of oilseeds with sodium hydroxide has been suggested as a way to allow only limited ruminal lipid digestion but more extensive intestinal digestion of seed lipids (Aldrich et. al., 1997). Such treatments may allow the manipulation of milk composition by strategic use of selected oilseeds. Linseed is rich in C18:3n-3, an essential component of a healthy human diet which is normally only present at low levels in cows milk. This study evaluated the effect of inclusion of caustic-treated linseed in dairy cow rations on the protein, fat and fatty acid composition of milk
Effect of lipid supplementation on digestion of nutrients in steers
Authors: Choi N.J. , Enser M. , Wood J.D. , Scollan N.D.
Published: November 2021

Lipids are commonly used in ruminant diets to increase the energy density of the ration and increasingly to manipulate the fatty acid (FA) composition of the final product (meat or milk). However, lipids may have negative effects on rumen function and in particular on the extent of carbohydrate digestion, which is accompanied by alterations in volatile fatty acid proportions, towards less acetate and more propionate. These alternations are more pronounced for lipids high in polyunsaturated fatty acids particularly linolenic acid (18:3n-3; found in linseed). However, there is some evidence to suggest that the opposite is true for longer chain C20 FAs, found in fish oil (Doreau and Chilliard, 1996). This experiment has examined the impact of lipid sources differing in their FA composition (saturated compared polyunsaturated FA) on digestion of nutrients in the rumen and small intestine.
Milk production response of lactating dairy cows to dietary fat from three sources
Authors: Reynolds C.K. , Phipps R. H. , Jones A. K. , Beever D.E.
Published: November 2021

Feeding fat to increase metabolisable energy content of lactation rations for dairy cows is now a common practice. It generally increases milk yield but decreases milk protein concentration. In North America whole oil seeds (cotton seeds, soya beans, sunflower seeds, etc.) containing high levels of linoleic acid are often fed as a fat source in a total mixed ration (TMR). Rape seed has also been fed and provides higher levels of oleic acid, but rape seed must be processed to be digested. Historically dietary fats for dairy cows have been rendered inert in the rumen to minimise negative effects on fibre digestion. In North America it is now recognised that unsaturated fats fed as whole oil seeds in a TMR do not have deleterious effects on digestion or intake, but these rations typically do not contain grass. Therefore our objective was to determine the intake and lactation response to feeding whole oil seeds (cotton seed and rape seed) in a grass silage-based ration and compare the response to that obtained using a rumen protected fat source as a positive control.
Monolithically-integrated 3D printed coaxial bandpass filters and RF diplexers: single-band and dual-band
Authors: Zhao Kunchen , Psychogiou Dimitra
Published: November 2021

The manuscript reports on additively-manufactured (AM) coaxial-resonator-based bandpass filters (BPFs) and RF diplexers. A monolithic integration concept using stereolithography apparatus (SLA) is proposed and discussed in detail. Coupled-resonator-based synthesis alongside full-electromagnetic-based design methods is used for the design of the monolithic filters and RF diplexers. In particular, the paper discusses a new external coupling mechanism for dual-band BPFs that allow to independently control the coupling in each of the BPF passbands. Furthermore, a novel coaxial transmission line-type T-junction is proposed for the design of single- and dual-band RF diplexers. For practical validation purposes, multiple BPF and RF diplexer prototypes were designed, manufactured and tested at S- and C-band demonstrating the applicability of the proposed concept to low-cost, low-loss and low-weight RF components with complex geometrical features.
Improving the Scientific Understanding of the Paradox of Irrigation Efficiency: An Integrated Modeling Approach to Assessing Basin‐Scale Irrigation Efficiency
Authors: Xiong Rui , Zheng Yi , Han Feng , Tian Yong
Published: November 2021

Irrigation is vital for the sustainability of water‐limited agricultural areas. However, higher irrigation efficiency (IE) rarely reduces irrigation water consumption, a paradox well noted in the real world. Resolving this paradox requires rigorous assessment of basin‐scale IE, which remains rare. This study holistically analyzed basin‐scale IE using the Zhangye Basin (ZB), a typical agricultural area in arid northwestern China, as the testbed. A new basin‐scale IE index was proposed that factors in irrigation return flow and groundwater's direct contributions to crop evapotranspiration. A novel approach was also developed to calculate this new index based on integrated ecohydrological modeling. The major study findings for the ZB include the following. First, return flow accounts for approximately 13% of irrigation water, which creates a difference of 0.1 between the new basin‐scale IE index and a traditional field‐scale index. Second, although basin‐scale IE has notable interannual fluctuation, its multiyear average shows stability, which may be dependent on the basin's physical characteristics. Third, basin‐scale IE reflects large spatial heterogeneity and is influenced by the intensity of surface water‐groundwater interaction. Finally, under the projected future climate, return flow in the ZB will be enhanced by 3.2% per decade, and basin‐scale IE shows an increasing trend. Overall, rigorous evaluation of basin‐scale IE is critical to making heterogeneous policies and developing adaptive management strategies under the changing climate. The integrated modeling approach developed in this study provides a methodological foundation for overcoming misunderstandings about the IE paradox and benefits the reform of the current IE policy agenda.
Occurrences of Regional Strong Es Irregularities and Corresponding Scintillations Characterized Using a High‐Temporal‐Resolution GNSS Network
Authors: Sun Wenjie , Hu Lianhuan , Yang Yuyan , Zhao Xiukuan , Yang Sipeng , Xie Haiyong , Li Yi , Liu Libo , Ning Baiqi , Li Guozhu
Published: November 2021

Strong sporadic E (Es) irregularities over China are investigated based on high‐temporal‐resolution total electron content (TEC) derived from two crossed chains of Beidou geostationary satellite (BD‐GEO) TEC receivers along 110°E and 23°N, respectively. The high resolution rate of TEC index (HR‐ROTI) calculated at an interval of 30 s, is proposed to characterize small‐scale strong Es irregularity structures. Based on the HR‐ROTI measurements and the typical drift velocity of Es 60 m/s, the scale sizes of strong Es irregularity structures were revealed to be mainly ∼7 km. The structures were mostly quasi‐periodically separated with distances of 7–16 km. Through a further statistical analysis of strong Es irregularity structures along the two chains, it was found that the Es irregularity structures predominantly occur during local summer at middle and low latitudes, with the occurrence rate peaking at ∼30°N. On average approximately 2–5 small‐scale strong Es irregularity structures may be embedded in one larger‐scale structure. Unlike the equatorial and low‐latitude F‐region irregularities which cause scintillations under most conditions, the strong Es irregularity characterized by HR‐ROTI caused scintillation with relatively low occurrence rates of 37% and 12% at middle and low latitudes, respectively.
Moho Changes Beneath the Northeastern Tibetan Plateau Revealed by Multiple Geodetic Datasets
Authors: Zhang Guoqing , Shen Wenbin , Fu Guangyu , Li Zhangjun , Zhu Yiqing , Wang Ying
Published: November 2021

The Moho interface depths and variations provide important references to understanding the outward growth and expansion mechanisms of the Tibetan Plateau, which have drawn much attention. Here, we constrain the Moho variations beneath the northeastern Tibetan Plateau (NETP) by using multiple geodetic data and climate models. Hydrological and tectonic gravitational signals are identified from multisource data and removed from the satellite gravity observations. Moreover, the mass variation rate, resulting from vertical Moho changes is calculated. The result shows that the mass variation rate due to the Moho changes is 1.3 ± 0.6 mm/yr (equivalent water height) within the NETP, which corresponds to a Moho uplift rate of 2.7 ± 1.3 mm/yr. Additionally, we calculate the tectonic Earth surface uplift rate from GPS and leveling observations with loading and GIA (glacier isostatic adjustment) influence corrected, which gives an uplift rate of 2.2 ± 0.1 mm/yr and is similar with the Moho uplift rate. Our results indicate that the crust in the NETP is uplifted with a slight decrease in crustal thickness. Combined with the lithospheric structure from seismological tomography studies, we suggest that the crustal uplift of the NETP is mainly caused by isostatic adjustment since the delamination of the thickened lithosphere.
Dilatancy Toughening of Shear Cracks and Implications for Slow Rupture Propagation
Authors: Brantut Nicolas
Published: November 2021

Dilatancy associated with fault slip produces a transient pore pressure drop which increases frictional strength. This effect is analyzed in a steadily propagating rupture model that includes frictional weakening, slip‐dependent fault dilation and fluid flow. Dilatancy is shown to increase the stress intensity factor required to propagate the rupture tip. With increasing rupture speed, an undrained (strengthened) region develops near the tip and extends beyond the frictionally weakened zone. Away from the undrained region, pore fluid diffusion gradually recharges the fault and strength returns to the drained, weakened value. For sufficiently large rupture dimensions, the dilation‐induced strength increase near the tip is equivalent to an increase in toughness that is proportional to the square root of the rupture speed. In general, dilation has the effect of increasing the stress required for rupture growth by decreasing the stress drop along the crack. Thermal pressurization has the potential to compensate for the dilatant strengthening effect, at the expense of an increased heating rate, which might lead to premature frictional melting. Using reasonable laboratory parameters, the dilatancy‐toughening effect leads to rupture dynamics that is quantitatively consistent with the dynamics of observed slow slip events in subduction zones.
2016 Monsoon Convection and Its Place in the Large‐Scale Circulation Using Doppler Radars
Authors: Doyle A. J. , Stein T. H. M. , Turner A. G.
Published: November 2021

Convective cloud development during the Indian monsoon helps moisten the atmospheric environment and drive the monsoon trough northwards each year, bringing a large amount of India's annual rainfall. Therefore, an increased understanding of how monsoon convection develops from observations will help inform model development. In this study, 139 days of India Meteorological Department Doppler weather radar data is analyzed for seven sites across India during the 2016 monsoon season. Convective cell‐top heights (CTHs) are objectively identified through the season, and compared with near‐surface (at 2 km height) reflectivity. These variables are analyzed over three time scales of variability during the monsoon: monsoon progression on a month‐by‐month basis, active‐break periods and the diurnal cycle. We find a modal maximum in CTH around 6–8 km for all sites. Cell‐averaged reflectivity increases with CTH, at first sharply, then less sharply above the freezing level. Bhopal and Mumbai exhibit lower CTH for monsoon break periods compared to active periods. A clear diurnal cycle in CTH is seen at all sites except Mumbai. For south‐eastern India, the phase of the diurnal cycle depends on whether the surface is land or ocean, with the frequency of oceanic cells typically exhibiting an earlier morning peak compared to land, consistent with the diurnal cycle of precipitation. Our findings confirm that Indian monsoon convective regimes are partly regulated by the large‐scale synoptic environment within which they are embedded. This demonstrates the excellent potential for weather radars to improve understanding of convection in tropical regions.
Life Cycle of Shallow Marine Cumulus Clouds From Geostationary Satellite Observations
Authors: Seelig Torsten , Deneke Hartwig , Quaas Johannes , Tesche Matthias
Published: November 2021

An analysis of the life cycle of shallow marine cumulus clouds is presented based on geostationary observations by the Spinning Enhanced Visible and InfraRed Imager aboard Meteosat Second Generation (MSG‐SEVIRI). Trajectories of about 250,000 individual shallow marine cumulus clouds have been derived by applying Particle Image Velocimetry to the Satellite Application Facility on Climate Monitoring CLoud property dAtAset using SEVIRI for a region in the trade wind zone centered around the Canary Islands in August 2015. The temporal evolution of the physical properties of these clouds allows to characterize cloud development and to infer the distribution of cloud life time and cloud extent. In the derived data set, the life time distribution follows a double power law with most clouds existing on a time scale of tens of minutes. The cloud physical properties, available during daytime, are analyzed along the cloud tracks. Relative time series of cloud extent, cloud water path, cloud droplet effective radius at cloud top, cloud optical thickness, and cloud droplet number concentration for clouds in two temporal ranges reveal conditions that can be attributed to long‐lasting clouds. Clouds of a certain horizontal extent and cloud top height as well as cloud droplet radius show longer life times if they are optically more dense, i.e., have a higher droplet number concentration. Furthermore, the investigation of the content of liquid cloud water regarding cloud life time and cloud extent shows that small short‐living clouds significantly contribute to cloud radiative effects.
Interplay Between Crustal‐Scale Thrusting, High Metamorphic Heating Rates, and the Development of Inverted Thermal‐Metamorphic Gradients: Numerical Models and Examples From the Caledonides of Northern Scotland
Authors: Thigpen J. Ryan , Ashley Kyle T. , Mako Calvin , Law Richard D. , Spencer Brandon
Published: November 2021

Understanding the processes that produce high prograde metamorphic heating rates and the development of inverted metamorphic sequences in collisional thrust belts remains a fundamental challenge for tectonics and metamorphic petrology. New 2D finite element models of crustal‐scale thrusts with variable slip rates (10, 20, 35, 50 km Myr−1) are used to examine how thrust sheet emplacement contributes to these processes. In the models, average prograde heating rates of 31–118 °C Myr−1 are observed in the footwall, with maximum transient heating rates of ∼167 °C Myr−1 occurring at the highest slip rate. Also, thrust sheet emplacement produces an inverted thermal gradient in the model footwall. At slip rates of 10 km Myr−1, heating magnitudes >200 °C are observed >7 km structurally beneath the thrust plane. At slip rates of 20–50 km Myr−1, models produce thermal penetration depths of 4–5 km for similar heating magnitudes. Petrologically determined heating rates for thrust footwalls in the Scandian orogenic wedge of northern Scotland mostly yield rates consistent with model results (10–230 °C Myr−1). The model‐derived magnitude of inverted thermal gradients is also similar to those indicated in texturally determined deformation temperature transects across the Scandian orogenic wedge (100 °C–180 °C). Combined, these results indicate that high heating rates can be produced by fault slip at typical plate velocities. Additionally, this implies that crustal‐scale thrusts are likely to produce inverted metamorphic sequences in most systems, provided that P‐T conditions during slip allow for metamorphic or recrystallization processes that would preserve evidence for such features.
Temperature Loggers Capture Intraregional Variation of Inundation Timing for Intermittent Ponds
Authors: Gendreau Kerry L. , Buxton Valerie L. , Moore Chloe E. , Mims Meryl C.
Published: November 2021

Hydroperiod, or the amount of time a lentic waterbody contains water, shapes communities of aquatic organisms. Precise measurement of hydroperiod features such as inundation timing and duration can help predict community dynamics and ecosystem stability. In areas defined by high spatial and temporal variability, fine‐scale temporal variation in inundation timing and duration may drive community structure, but that variation may not be captured using common approaches including remote sensing technology. Here, we provide methods to accurately capture inundation timing by fitting hidden Markov models to measurements of daily temperature SD collected from temperature loggers. We describe a rugged housing design to protect loggers from physical damage and apply our methods to a group of intermittent ponds in southeastern Arizona, showing that initial pond inundation timing is highly variable across a small geographic scale (∼50 km2). We also compare a 1‐logger (pond only) and 2‐logger (pond + control) design and show that, although a single logger may be sufficient to capture inundation timing in most cases, a 2‐logger design can increase confidence in results. These methods are cost‐effective and show promise in capturing variation in intraregional inundation timing for a range of temporary lentic habitats that may have profound effects on aquatic communities, with implications for how these communities may respond to hydroperiod alteration from a changing climate.
Rapid nanomolding of nanotopography on flexible substrates to control muscle cell growth with enhanced maturation
Authors: Wu Cong , Chin Chriss S. M. , Huang Qingyun , Chan Ho-Yin , Yu Xinge , Roy Vellaisamy A. L. , Li Wen J.
Published: November 2021

In vivo, multiple biophysical cues provided by highly ordered connective tissues of the extracellular matrix regulate skeletal muscle cells to align in parallel with one another. However, in routine in vitro cell culture environments, these key factors are often missing, which leads to changes in cell behavior. Here, we present a simple strategy for using optical media discs with nanogrooves and other polymer-based substrates nanomolded from the discs to directly culture muscle cells to study their response to the effect of biophysical cues such as nanotopography and substrate stiffness. We extend the range of study of biophysical cues for myoblasts by showing that they can sense ripple sizes as small as a 100 nm width and a 20 nm depth for myotube alignment, which has not been reported previously. The results revealed that nanotopography and substrate stiffness regulated myoblast proliferation and morphology independently, with nanotopographical cues showing a higher effect. These biophysical cues also worked synergistically, and their individual effects on cells were additive; i.e., by comparing cells grown on different polymer-based substrates (with and without nanogrooves), the cell proliferation rate could be reduced by as much as ~29%, and the elongation rate could be increased as much as ~116%. Moreover, during myogenesis, muscle cells actively responded to nanotopography and consistently showed increases in fusion and maturation indices of ~28% and ~21%, respectively. Finally, under electrical stimulation, the contraction amplitude of well-aligned myotubes was found to be almost 3 times greater than that for the cells on a smooth surface, regardless of the substrate stiffness.
Survival by race in men with chemotherapy-naive enzalutamide- or abiraterone-treated metastatic castration-resistant prostate cancer
Authors: George Daniel J. , Ramaswamy Krishnan , Huang Ahong , Russell David , Mardekian Jack , Schultz Neil M. , Janjan Nora , Freedland Stephen J.
Published: November 2021

Background

Black men are more likely to be diagnosed with aggressive prostate cancer (PC) and die from PC than white men. However, black men with metastatic castration-resistant PC (mCRPC) had longer overall survival (OS) than white men when treated with certain agents in clinical trials. We analyzed claims data from the Veterans Health Administration (VHA) database to evaluate OS in black and white men treated with enzalutamide or abiraterone (novel hormonal therapy [NHT]) for chemotherapy-naïve mCRPC.

Methods

Patients with mCRPC aged ≥18 years were identified in the VHA database by diagnosis codes, evidence of surgical/medical castration, and a prescription claim for enzalutamide or abiraterone after castration from April 2014–March 2017. Cox models assessed associations between race and OS. Unadjusted and multivariable analyses were performed on the entire population and subsets based on the type of therapy received (if any) after NHT.

Results

In total, 2910 patients were identified (787 black, mean 71.7 years; 2123 white, mean 74.0 years). Median follow-up was 19.0 and 18.7 months in blacks and whites, respectively. Black men had better survival versus white men: hazard ratios (95% CIs) were 0.89 (0.790–0.996; P = 0.044) and 0.67 (0.592–0.758; P < 0.0001) in the unadjusted and multivariable models, respectively. Statistically significantly longer OS was seen in black versus white men regardless of subsequent treatment, including no subsequent treatment.

Conclusions

In the VHA, black men with chemotherapy-naïve mCRPC initiating NHT may have better outcomes than similarly treated white men.
Application of long-read sequencing to elucidate complex pharmacogenomic regions: a proof of principle
Authors: van der Lee Maaike , Rowell William J. , Menafra Roberta , Guchelaar Henk-Jan , Swen Jesse J. , Anvar Seyed Yahya
Published: November 2021

The use of pharmacogenomics in clinical practice is becoming standard of care. However, due to the complex genetic makeup of pharmacogenes, not all genetic variation is currently accounted for. Here, we show the utility of long-read sequencing to resolve complex pharmacogenes by analyzing a well-characterised sample. This data consists of long reads that were processed to resolve phased haploblocks. 73% of pharmacogenes were fully covered in one phased haploblock, including 9/15 genes that are 100% complex. Variant calling accuracy in the pharmacogenes was high, with 99.8% recall and 100% precision for SNVs and 98.7% precision and 98.0% recall for Indels. For the majority of gene-drug interactions in the DPWG and CPIC guidelines, the associated genes could be fully resolved (62% and 63% respectively). Together, these findings suggest that long-read sequencing data offers promising opportunities in elucidating complex pharmacogenes and haplotype phasing while maintaining accurate variant calling.
Dystrophin and mini-dystrophin quantification by mass spectrometry in skeletal muscle for gene therapy development in Duchenne muscular dystrophy
Authors: Farrokhi Vahid , Walsh Jason , Palandra Joe , Brodfuehrer Joanne , Caiazzo Teresa , Owens Jane , Binks Michael , Neelakantan Srividya , Yong Florence , Dua Pinky , Le Guiner Caroline , Neubert Hendrik
Published: November 2021

Duchenne muscular dystrophy (DMD) is a lethal, degenerative muscle disorder caused by mutations in the DMD gene, leading to severe reduction or absence of the protein dystrophin. Gene therapy strategies that aim to increase expression of a functional dystrophin protein (mini-dystrophin) are under investigation. The ability to accurately quantify dystrophin/mini-dystrophin is essential in assessing the level of gene transduction. We demonstrated the validation and application of a novel peptide immunoaffinity liquid chromatography–tandem mass spectrometry (IA-LC-MS/MS) assay. Data showed that dystrophin expression in Becker muscular dystrophy and DMD tissues, normalized against the mean of non-dystrophic control tissues (n = 20), was 4–84.5% (mean 32%, n = 20) and 0.4–24.1% (mean 5%, n = 20), respectively. In a DMD rat model, biceps femoris tissue from dystrophin-deficient rats treated with AAV9.hCK.Hopti-Dys3978.spA, an adeno-associated virus vector containing a mini-dystrophin transgene, showed a dose-dependent increase in mini-dystrophin expression at 6 months post-dose, exceeding wildtype dystrophin levels at high doses. Validation data showed that inter- and intra-assay precision were ≤20% (≤25% at the lower limit of quantification [LLOQ]) and inter- and intra-run relative error was within ±20% (±25% at LLOQ). IA-LC-MS/MS accurately quantifies dystrophin/mini-dystrophin in human and preclinical species with sufficient sensitivity for immediate application in preclinical/clinical trials.
A new method for sampling African swine fever virus genome and its inactivation in environmental samples
Authors: Kosowska Aleksandra , Barasona Jose A. , Barroso-Arévalo Sandra , Rivera Belén , Domínguez Lucas , Sánchez-Vizcaíno Jose M.
Published: November 2021

African swine fever (ASF) is currently the most dangerous disease for the global pig industry, causing huge economic losses, due to the lack of effective vaccine or treatment. Only the early detection of ASF virus (ASFV) and proper biosecurity measures are effective to reduce the viral expansion. One of the most widely recognized risks as regards the introduction ASFV into a country is infected animals and contaminated livestock vehicles. In order to improve ASF surveillance, we have assessed the capacity for the detection and inactivation of ASFV genome by using Dry-Sponges (3 M) pre-hydrated with a new surfactant liquid. We sampled different surfaces in ASFV-contaminated facilities, including animal skins, and the results were compared to those obtained using a traditional sampling method. The surfactant liquid successfully inactivated the virus, while ASFV DNA was well preserved for the detection. This is an effective method to systematically recover ASFV DNA from different surfaces and skin, which has a key applied relevance in surveillance of vehicles transporting live animals and greatly improves animal welfare. This method provides an important basis for the detection of ASFV genome that can be assessed without the biosafety requirements of a BSL-3 laboratory at least in ASF-affected countries, which may substantially speed up the early detection of the pathogen.
A multicenter Spanish study of atropine 0.01% in childhood myopia progression
Authors: Pérez-Flores Inés , Macías-Murelaga Beatríz , Barrio-Barrio Jesús ,   Multicenter Group of Atropine Treatment for Myopia Control (GTAM), Pérez Flores Inés , Valcárcel Vizcaíno Marta , García Arias Marta , Catalán López Sara , Rodríguez Enríquez Manuel , Iglesias Álvarez María , Lorente Bulnes Betty , García-Anllo Reinoso Matías , Carnero José María , de Rojas Silva Victoria , Barrio Barrio Jesús , Macías-Murelaga Beatríz , Rodríguez Feijoo David , Rodríguez Sánchez Javier , Calvo Robles Argentina Rosario , López-Romero Moraleda Sonia , Barrajón Rodríguez Ángela , Gálvez Martínez Javier , Mesa Carina Diana Victoria , Galán Risueño Elena , Rodríguez Domingo Esther
Published: November 2021

To evaluate the efficacy and safety of atropine 0.01% eye drops for myopia control in a multicentric pediatric Spanish cohort. An interventional, prospective, multicenter study was designed. Children aged between 6 and 14 years, with myopia between − 2.00 D to − 6.00 D, astigmatism < 1.50 D and documented previous annual progression greater than − 0.5 D (cycloplegic spherical equivalent, SE) were included. Once nightly atropine 0.01% eye drops in each eye were prescribed to all participants for 12 months. Age, gender, ethnicity and iris color were registered. All patients underwent the same follow-up protocol in every center: baseline visit, telephone consultation 2 weeks later and office controls at 4, 8 and 12 months. At each visit, best-corrected visual acuity, and cycloplegic autorefraction were assessed. Axial length (AL), anterior chamber depth and pupil diameter were measured on an IOL Master (Carl Zeiss Meditec, Inc, Dublin, CA). Adverse effects were registered in a specific questionnaire. Mean changes in cycloplegic SE and AL in the 12 months follow-up were analyzed. SE progression during treatment was compared with the SE progression in the year before enrollment for each patient. Correlation between SE and AL, and annual progression distribution were evaluated. Progression risk factors were analyzed by multivariate logistic regression analyses. Of the 105 recruited children, 92 completed the treatment. Mean SE and AL changes were − 0.44 ± 0.41 D and 0.27 ± 0.20 mm respectively. Mean SE progression was lower than the year before treatment (− 0.44 ± 0.41 D versus − 1.01 ± 0.38 D; p < 0.0001). An inverse correlation between SE progression and AL progression (r: − 0.42; p < 0.0001) was found. Fifty-seven patients (62%) had a SE progression less than − 0.50 D. No risk factors associated with progression could be identified in multivariate analyses. Mean pupil diameter increment at 12-months visit was 0.74 ± 1.76 mm. The adverse effects were mild and infrequent, and decreased over the time. Atropine 0.01% is effective and safe for myopia progression control in a multicentric Spanish children cohort. We believe this efficacy might be extensible to the myopic pediatric population from Western countries with similar social and demographic features. More studies about myopia progression risk factors among atropine treated patients are needed.
Understanding complex multiple sublattice magnetism in double double perovskites
Authors: Halder Anita , Das Shreya , Sanyal Prabuddha , Saha-Dasgupta Tanusri
Published: November 2021

Understanding magnetism in multiple magnetic sublattice system, driven by the interplay of varied nature of magnetic exchanges, is on one hand challenging and on other hand intriguing. Motivated by the recent synthesis of AA$$^{\prime }$$

′

BB$$^{\prime }$$

′

O$$_6$$

6

double double perovskites with multiple magnetic ions both at A- and B-sites, we investigate the mechanism of magnetic behavior in these interesting class of compounds. We find that the magnetism in such multiple sublattice compounds is governed by the interplay and delicate balance between two distinct mechanisms, (a) kinetic energy-driven multiple sublattice double exchange mechanism and (b) the conventional super-exchange mechanism. The derived spin Hamiltonian based on first-principles calculations is solved by classical Monte Carlo technique which reproduces the observed magnetic properties. Finally, the influence of off-stoichiometry, as in experimental samples, is discussed. Some of these double double perovskite compounds are found to possess large total magnetic moment and also are found to be half-metallic with reasonably high transition temperature, which raises the hope of future applications of these large magnetic moment half-metallic oxides in spintronics and memory devices.
Infrared reflectance image-guided laser photocoagulation of telangiectatic capillaries in persistent diabetic macular edema
Authors: Roh Hyeon Cheol , Lee Chaeyeon , Kang Se Woong , Choi Kyung Jun , Eun Jun Soo , Hwang Sungsoon
Published: November 2021

This study aimed to assess detection rate of telangiectatic capillaries (TelCaps) with infrared reflectance (IR) and optical coherence tomography (OCT) images and to evaluate the clinical efficacy of IR image-guided focal laser photocoagulation of TelCaps in persistent diabetic macular edema (DME). This retrospective case series included 28 eyes of 28 patients with TelCap and persistent DME refractory to intravitreal anti-vascular endothelial growth factor or corticosteroids. The presence of TelCaps was confirmed using IR and OCT images. All patients were followed up for more than 12 months after direct focal laser photocoagulation of the TelCaps. The TelCap closure rate, changes in best-corrected visual acuity, and central subfield thickness were analyzed. On IR imaging, TelCap appeared as a characteristic hyperreflectivity within a hyporeflective spherical lesion in 85.7% of the eyes. After focal laser photocoagulation, the TelCap closure rate was 57.1% at 3 months and 71.4% at 12 months. A significant improvement in visual acuity and reduction in central subfield thickness were observed at three and 12 months after focal laser photocoagulation (all p < 0.05). The characteristic hyperreflectivity within hyporeflective lesions on the IR image in conjunction with OCT helps identify the TelCap. Our results suggest that IR imaging and OCT-guided focal laser photocoagulation of TelCaps can improve functional and anatomical outcomes in persistent DME.
Genome-wide association mapping and genomic prediction for adult stage sclerotinia stem rot resistance in Brassica napus (L) under field environments
Authors: Roy Jayanta , Shaikh T. M. , del Río Mendoza Luis , Hosain Shakil , Chapara Venkat , Rahman Mukhlesur
Published: November 2021

Sclerotinia stem rot (SSR) is a fungal disease of rapeseed/canola that causes significant seed yield losses and reduces its oil content and quality. In the present study, the reaction of 187 diverse canola genotypes to SSR was characterized at full flowering stage using the agar plug to stem inoculation method in four environments. Genome-wide association study (GWAS) using three different algorithms identified 133 significant SNPs corresponding with 123 loci for disease traits like stem lesion length (LL), lesion width (LW), and plant mortality at 14 (PM_14D) and 21 (PM_21D) days. The explained phenotypic variation of these SNPs ranged from 3.6 to 12.1%. Nineteen significant SNPs were detected in two or more environments, disease traits with at least two GWAS algorithms. The strong correlations observed between LL and other three disease traits evaluated, suggest they could be used as proxies for SSR resistance phenotyping. Sixty-nine candidate genes associated with disease resistance mechanisms were identified. Genomic prediction (GP) analysis with all the four traits employing genome-wide markers resulted in 0.41–0.64 predictive ability depending on the model specifications. The highest predictive ability for PM_21D with three models was about 0.64. From our study, the identified resistant genotypes and stable significant SNP markers will serve as a valuable resource for future SSR resistance breeding. Our study also suggests that genomic selection holds promise for accelerating canola breeding progress by enabling breeders to select SSR resistance genotypes at the early stage by reducing the need to phenotype large numbers of genotypes.
Modelling the growth, development and yield of Triticum durum Desf under the changes of climatic conditions in north-eastern Europe
Authors: Bożek Kamila S. , Żuk-Gołaszewska Krystyna , Bochenek Anna , Gołaszewski Janusz , Kalaji Hazem M.
Published: November 2021

How agricultural ecosystems adapt to climate change is one of the most important issues facing agronomists at the turn of the century. Understanding agricultural ecosystem responses requires assessing the relative shift in climatic constraints on crop production at regional scales such as the temperate zone. In this work we propose an approach to modeling the growth, development and yield of Triticum durum Desf. under the climatic conditions of north-eastern Poland. The model implements 13 non-measurable parameters, including climate conditions, agronomic factors, physiological processes, biophysical parameters, yield components and biological yield (latent variables), which are described by 33 measurable predictors as well as grain and straw yield (manifest variables). The agronomic factors latent variable was correlated with nitrogen fertilization and sowing density, and biological yield was correlated with grain yield and straw yield. An analysis of the model parameters revealed that a one unit increase in agronomic factors increased biological yield by 0.575. In turn, biological yield was most effectively determined by climate conditions (score of 60–62) and biophysical parameters (score of 60–67) in the 2nd node detectable stage and at the end of heading. The modeled configuration of latent and manifest variables was responsible for less than 70% of potential biological yield, which indicates that the growth and development of durum wheat in north-eastern Europe can be further optimized to achieve high and stable yields. The proposed model accounts for local climate conditions and physiological processes in plants, and it can be implemented to optimize agronomic practices in the cultivation of durum wheat and, consequently, to expand the area under T. durum to regions with a temperate climate.
Detection of heteroplasmy and nuclear mitochondrial pseudogenes in the Japanese spiny lobster Panulirus japonicus
Authors: Chow Seinen , Yanagimoto Takashi , Takeyama Haruko
Published: November 2021

Partial mtDNA cytochrome oxidase subunit I (COI) fragments and near entire stretch of 12S rDNA (12S) and control region (Dloop) of the Japanese spiny lobster (Panulirus japonicus) (n = 3) were amplified by PCR and used for direct nucleotide sequencing and for clone library-based nucleotide sequence analysis. Nucleotide sequences of a total of 75 clones in COI, 77 in 12S and 92 in Dloop were determined. Haplotypes of the clones matched with those obtained by direct sequencing were determined to be genuine mtDNA sequence of the individual. Phylogenetic analysis revealed several distinct groups of haplotypes in all three regions. Genuine mtDNA sequences were observed to form a group with their closely related variables, and most of these variables may be due to amplification error but a few to be heteroplasmy. Haplotypes determined as nuclear mitochondrial pseudogenes (NUMTs) formed distinct groups. Nucleotide sequence divergence (K2P distance) between genuine haplotypes and NUMTs were substantial (7.169–23.880% for COI, 1.336–23.434% for 12S, and 7.897–71.862% for Dloop). These values were comparable to or smaller than those between species of the genus Panulirus, indicating that integration of mtDNA into the nuclear genome is a continuous and dynamic process throughout pre- and post-speciation events. Double peaks in electropherograms obtained by direct nucleotide sequencing were attributed to common nucleotides shared by multiple NUMTs. Information on the heteroplasmy and NUMTs would be very important for addressing their impact on direct nucleotide sequencing and for quality control of nucleotide sequences obtained.
Identification of stress response proteins through fusion of machine learning models and statistical paradigms
Authors: Alzahrani Ebraheem , Alghamdi Wajdi , Ullah Malik Zaka , Khan Yaser Daanial
Published: November 2021

Proteins are a vital component of cells that perform physiological functions to ensure smooth operations of bodily functions. Identification of a protein's function involves a detailed understanding of the structure of proteins. Stress proteins are essential mediators of several responses to cellular stress and are categorized based on their structural characteristics. These proteins are found to be conserved across many eukaryotic and prokaryotic linkages and demonstrate varied crucial functional activities inside a cell. The in-vivo, ex vivo, and in-vitro identification of stress proteins are a time-consuming and costly task. This study is aimed at the identification of stress protein sequences with the aid of mathematical modelling and machine learning methods to supplement the aforementioned wet lab methods. The model developed using Random Forest showed remarkable results with 91.1% accuracy while models based on neural network and support vector machine showed 87.7% and 47.0% accuracy, respectively. Based on evaluation results it was concluded that random-forest based classifier surpassed all other predictors and is suitable for use in practical applications for the identification of stress proteins. Live web server is available athttp://biopred.org/stressprotiens, while the webserver code available is athttps://github.com/abdullah5naveed/SRP_WebServer.git
Patient-derived xenograft culture-transplant system for investigation of human breast cancer metastasis
Authors: Ma Dennis , Hernandez Grace A. , Lefebvre Austin E. Y. T. , Alshetaiwi Hamad , Blake Kerrigan , Dave Kushal R. , Rauf Maha , Williams Justice W. , Davis Ryan T. , Evans Katrina T. , Longworth Aaron , Masoud Madona Y. G. , Lee Regis , Edwards Robert A. , Digman Michelle A. , Kessenbrock Kai , Lawson Devon A.
Published: November 2021

Metastasis is a fatal disease where research progress has been hindered by a lack of authentic experimental models. Here, we develop a 3D tumor sphere culture-transplant system that facilitates the growth and engineering of patient-derived xenograft (PDX) tumor cells for functional metastasis assays in vivo. Orthotopic transplantation and RNA sequencing (RNA-seq) analyses show that PDX tumor spheres maintain tumorigenic potential, and the molecular marker and global transcriptome signatures of native tumor cells. Tumor spheres display robust capacity for lentiviral engineering and dissemination in spontaneous and experimental metastasis assays in vivo. Inhibition of pathways previously reported to attenuate metastasis also inhibit metastasis after sphere culture, validating our approach for authentic investigations of metastasis. Finally, we demonstrate a new role for the metabolic enzyme NME1 in promoting breast cancer metastasis, providing proof-of-principle that our culture-transplant system can be used for authentic propagation and engineering of patient tumor cells for functional studies of metastasis.
A population-specific reference panel for improved genotype imputation in African Americans
Authors: O’Connell Jared , Yun Taedong , Moreno Meghan , Li Helen , Litterman Nadia , Kolesnikov Alexey , Noblin Elizabeth , Chang Pi-Chuan , Shastri Anjali , Dorfman Elizabeth H. , Shringarpure Suyash ,   23andMe Research Team, Aslibekyan Stella , Babalola Elizabeth , Bell Robert K. , Bielenberg Jessica , Bryc Katarzyna , Bullis Emily , Coker Daniella , Partida Gabriel Cuellar , Dhamija Devika , Das Sayantan , Elson Sarah L. , Filshtein Teresa , Fletez-Brant Kipper , Fontanillas Pierre , Freyman Will , Gandhi Pooja M. , Heilbron Karl , Hernandez Alejandro , Hicks Barry , Hinds David A. , Jewett Ethan M. , Jiang Yunxuan , Kukar Katelyn , Lin Keng-Han , Lowe Maya , McCreight Jey , McIntyre Matthew H. , Micheletti Steven J. , Mountain Joanna L. , Nandakumar Priyanka , Petrakovitz Aaron A. , Poznik G. David , Schumacher Morgan , Shelton Janie F. , Shi Jingchunzi , Tchakouté Christophe Toukam , Tran Vinh , Tung Joyce Y. , Wang Xin , Wang Wei , Weldon Catherine H. , Wilton Peter , Wong Corinna , Auton Adam , Carroll Andrew , McLean Cory Y.
Published: November 2021

There is currently a dearth of accessible whole genome sequencing (WGS) data for individuals residing in the Americas with Sub-Saharan African ancestry. We generated whole genome sequencing data at intermediate (15×) coverage for 2,294 individuals with large amounts of Sub-Saharan African ancestry, predominantly Atlantic African admixed with varying amounts of European and American ancestry. We performed extensive comparisons of variant callers, phasing algorithms, and variant filtration on these data to construct a high quality imputation panel containing data from 2,269 unrelated individuals. With the exception of the TOPMed imputation server (which notably cannot be downloaded), our panel substantially outperformed other available panels when imputing African American individuals. The raw sequencing data, variant calls and imputation panel for this cohort are all freely available via dbGaP and should prove an invaluable resource for further study of admixed African genetics.
A cysteine-triggered fluorogenic donor base on native chemical ligation for tracking H2S delivery in vivo
Authors: Li Li , Lin Zhenmei , Cheng Yongfang , Tang Yaoping , Zhang Ziqian
Published: November 2021

A fluorogenic hydrogen sulfide (H2S) donor is a fundamental molecular tool used as an exogenous source in biological studies and therapies.