Pharmacological inhibition of RAS overcomes FLT3 inhibitor resistance in FLT3-ITD+ AML through AP-1 and RUNX1.

AML is characterized by mutations in genes associated with growth regulation such as internal tandem duplications (ITD) in the receptor kinase FLT3. Inhibitors targeting FLT3 (FLT3i) are being used to treat patients with FLT3-ITD+ but most relapse and become resistant. To elucidate the resistance mechanism, we compared the gene regulatory networks (GRNs) of leukemic cells from patients before and after relapse, which revealed that the GRNs of drug-responsive patients were altered by rewiring their AP-1-RUNX1 axis. Moreover, FLT3i induces the upregulation of signaling genes, and we show that multiple cytokines, including interleukin-3 (IL-3), can overcome FLT3 inhibition and send cells back into cycle. FLT3i leads to loss of AP-1 and RUNX1 chromatin binding, which is counteracted by IL-3. However, cytokine-mediated drug resistance can be overcome by a pan-RAS inhibitor. We show that cytokines instruct AML growth via the transcriptional regulators AP-1 and RUNX1 and that pan-RAS drugs bypass this barrier.

The Influence of Cathode Degradation Products on the Anode Interface in Lithium-Ion Batteries.

Degradation of cathode materials in lithium-ion batteries results in the presence of transition metal ions in the electrolyte, and these ions are known to play a major role in capacity fade and cell failure. Yet, while it is known that transition metal ions migrate from the metal oxide cathode and deposit on the graphite anode, their specific influence on anode reactions and structures, such as the solid electrolyte interphase (SEI), is still quite poorly understood due to the complexity in studying this interface in operational cells. In this work we combine operando electrochemical atomic force microscopy (EC-AFM), electrochemical quartz crystal microbalance (EQCM), and electrochemical impedance spectroscopy (EIS) measurements to probe the influence of a range of transition metal ions on the morphological, mechanical, chemical, and electrical properties of the SEI. By adding representative concentrations of Ni2+, Mn2+, and Co2+ ions into a commercially relevant battery electrolyte, the impacts of each on the formation and stability of the anode interface layer is revealed; all are shown to pose a threat to battery performance and stability. Mn2+, in particular, is shown to induce a thick, soft, and unstable SEI layer, which is known to cause severe degradation of batteries, while Co2+ and Ni2+ significantly impact interfacial conductivity. When transition metal ions are mixed, SEI degradation is amplified, suggesting a synergistic effect on the cell stability. Hence, by uncovering the roles these cathode degradation products play in operational batteries, we have provided a foundation upon which strategies to mitigate or eliminate these degradation products can be developed.

Leukemic stem cells activate lineage inappropriate signalling pathways to promote their growth.

Acute Myeloid Leukemia (AML) is caused by multiple mutations which dysregulate growth and differentiation of myeloid cells. Cells adopt different gene regulatory networks specific to individual mutations, maintaining a rapidly proliferating blast cell population with fatal consequences for the patient if not treated. The most common treatment option is still chemotherapy which targets such cells. However, patients harbour a population of quiescent leukemic stem cells (LSCs) which can emerge from quiescence to trigger relapse after therapy. The processes that allow such cells to re-grow remain unknown. Here, we examine the well characterised t(8;21) AML sub-type as a model to address this question. Using four primary AML samples and a novel t(8;21) patient-derived xenograft model, we show that t(8;21) LSCs aberrantly activate the VEGF and IL-5 signalling pathways. Both pathways operate within a regulatory circuit consisting of the driver oncoprotein RUNX1::ETO and an AP-1/GATA2 axis allowing LSCs to re-enter the cell cycle while preserving self-renewal capacity.

Gene regulatory network analysis predicts cooperating transcription factor regulons required for FLT3-ITD+ AML growth.

Acute myeloid leukemia (AML) is a heterogeneous disease caused by different mutations. Previously, we showed that each mutational subtype develops its specific gene regulatory network (GRN) with transcription factors interacting within multiple gene modules, many of which are transcription factor genes themselves. Here, we hypothesize that highly connected nodes within such networks comprise crucial regulators of AML maintenance. We test this hypothesis using FLT3-ITD-mutated AML as a model and conduct an shRNA drop-out screen informed by this analysis. We show that AML-specific GRNs predict crucial regulatory modules required for AML growth. Furthermore, our work shows that all modules are highly connected and regulate each other. The careful multi-omic analysis of the role of one (RUNX1) module by shRNA and chemical inhibition shows that this transcription factor and its target genes stabilize the GRN of FLT3-ITD+ AML and that its removal leads to GRN collapse and cell death.

Physical effectiveness of corn silage fractions stratified with the Penn State Particle Separator for lactating dairy cows.

This study evaluated the physical effectiveness of whole-plant corn silage (CS) particles stratified with the Penn State Particle Separator, composed of 19- and 8-mm-diameter sieves and a pan, for lactating dairy cows. Eight Holstein cows (27.6 ± 2.8 kg/d of milk, 611 ± 74 kg body weight; 152 ± 83 d in milk) were assigned to two 4 × 4 Latin squares (22-d periods, 16-d adaptation), where one square was formed with rumen-cannulated cows. Three CS particle fractions were manually isolated using the 8- and 19-mm diameter sieves and re-ensiled in 200-L drums. The 4 experimental diets were (% dry matter): (1) CON (control): 17% forage neutral detergent fiber (NDF) from CS (basal roughage), 31.5% starch, and 31.9% NDF; (2) PSPan: 17% forage NDF from CS + 9% NDF from CS particles <8 mm, 25.9% starch, and 37.9% NDF; (3) PS8: 17% forage NDF from CS + 9% NDF from CS particles 8 to 19 mm, 25.5% starch, and 38.3% NDF; and (4) PS19: 17% forage NDF from CS + 9% NDF from CS particles >19 mm, 24.9% starch, and 38.8% NDF. Cows fed PS8 had greater dry matter intake and energy-corrected milk yield (22.4 and 26.9 kg/d, respectively) than cows fed CON (20.8 and 24.7 kg/d) and PS19 (21.2 and 24.8 kg/d), but no difference was detected between PSPan (21.6 and 25.8 kg/d) and other treatments. Milk fat concentration was greater for PS8 than CON, with intermediate values for PSPan and PS19. Milk fat yield was greater for cows fed PS8 than CON and PS19, and cows fed PSPan secreted more fat than CON cows but were not different from cows fed the other 2 diets. Cows fed CON had a lower meal frequency than cows fed PSPan, shorter meal and rumination times than PS8, and greater meal size and lower rates of rumination and chewing than the other 3 diets. Total chewing per unit of NDF was higher for PS8 than PSPan, although neither treatment differed from CON or PS19. Cows fed PS19 had higher refusal of feed particles >19 mm than cows fed CON and PSPan. The refusal of dietary NDF and undigested NDF in favor of starch were all greater for PS19 than on the other treatments. Cows fed PS19 had a greater proportion of the swallowed bolus and rumen digesta with particles >19 mm than the other 3 diets. Cows fed CON had the lowest ruminal pH and greatest lactate concentration relative to the other 3 diets. Plasma lipopolysaccharide was higher for cows fed CON and PSPan than for cows fed PS8 and PS19, and serum d-lactate tended to be lower on PSPan than for CON and PS8. In summary, the inclusion of CS fractions in a low-forage fiber diet (CON) reduced signs of ruminal acidosis. Compared with CS NDF <8 and >19 mm, CS NDF with 8- to 19-mm length promoted better rumen health and performance of dairy cows. These results highlight the importance of adjusting CS harvest and formulating dairy diets based on the proportion of particles retained between the 8- and 19-mm sieves.

Gene regulatory network analysis predicts cooperating transcription factor regulons required for FLT3-ITD+ AML growth.

AML is a heterogenous disease caused by different mutations. We have previously shown that each mutational sub-type develops its specific gene regulatory network (GRN) with transcription factors interacting with multiple gene modules, many of which are transcription factor genes themselves. Here we hypothesized that highly connected nodes within such networks comprise crucial regulators of AML maintenance. We tested this hypothesis using FLT3-ITD mutated AML as a model and conducted an shRNA drop-out screen informed by this analysis. We show that AML-specific GRNs predict identifying crucial regulatory modules required for AML but not normal cellular growth. Furthermore, our work shows that all modules are highly connected and regulate each other. The careful multi-omic analysis of the role of one (RUNX1) module by shRNA and chemical inhibition shows that this transcription factor and its target genes stabilize the GRN of FLT3-ITD AML and that its removal leads to GRN collapse and cell death.

Human-machine interface for two-dimensional steering control with the auricular muscles.

Human-machine interfaces (HMIs) can be used to decode a user's motor intention to control an external device. People that suffer from motor disabilities, such as spinal cord injury, can benefit from the uses of these interfaces. While many solutions can be found in this direction, there is still room for improvement both from a decoding, hardware, and subject-motor learning perspective. Here we show, in a series of experiments with non-disabled participants, a novel decoding and training paradigm allowing naïve participants to use their auricular muscles (AM) to control two degrees of freedom with a virtual cursor. AMs are particularly interesting because they are vestigial muscles and are often preserved after neurological diseases. Our method relies on the use of surface electromyographic records and the use of contraction levels of both AMs to modulate the velocity and direction of a cursor in a two-dimensional paradigm. We used a locking mechanism to fix the current position of each axis separately to enable the user to stop the cursor at a certain location. A five-session training procedure (20-30 min per session) with a 2D center-out task was performed by five volunteers. All participants increased their success rate (Initial: 52.78 ± 5.56%; Final: 72.22 ± 6.67%; median ± median absolute deviation) and their trajectory performances throughout the training. We implemented a dual task with visual distractors to assess the mental challenge of controlling while executing another task; our results suggest that the participants could perform the task in cognitively demanding conditions (success rate of 66.67 ± 5.56%). Finally, using the Nasa Task Load Index questionnaire, we found that participants reported lower mental demand and effort in the last two sessions. To summarize, all subjects could learn to control the movement of a cursor with two degrees of freedom using their AM, with a low impact on the cognitive load. Our study is a first step in developing AM-based decoders for HMIs for people with motor disabilities, such as spinal cord injury.

Toward the Identification of Neurophysiological Biomarkers for Alzheimer's Disease in Down Syndrome: A Potential Role for Cross-Frequency Phase-Amplitude Coupling Analysis.

Cross-frequency coupling (CFC) mechanisms play a central role in brain activity. Pathophysiological mechanisms leading to many brain disorders, such as Alzheimer's disease (AD), may produce unique patterns of brain activity detectable by electroencephalography (EEG). Identifying biomarkers for AD diagnosis is also an ambition among research teams working in Down syndrome (DS), given the increased susceptibility of people with DS to develop early-onset AD (DS-AD). Here, we review accumulating evidence that altered theta-gamma phase-amplitude coupling (PAC) may be one of the earliest EEG signatures of AD, and therefore may serve as an adjuvant tool for detecting cognitive decline in DS-AD. We suggest that this field of research could potentially provide clues to the biophysical mechanisms underlying cognitive dysfunction in DS-AD and generate opportunities for identifying EEG-based biomarkers with diagnostic and prognostic utility in DS-AD.

Computer-Vision-Based Approach to Classify and Quantify Flaws in Li-Ion Electrodes.

X-ray computed tomography (X-ray CT) is a non-destructive characterization technique that in recent years has been adopted to study the microstructure of battery electrodes. However, the often manual and laborious data analysis process hinders the extraction of useful metrics that can ultimately inform the mechanisms behind cycle life degradation. This work presents a novel approach that combines two convolutional neural networks to first locate and segment each particle in a nano-CT LiNiMnCoO2 (NMC) electrode dataset, and successively classifies each particle according to the presence of flaws or cracks within its internal structure. Metrics extracted from the computer vision segmentation are validated with respect to traditional threshold-based segmentation, confirming that flawed particles are correctly identified as single entities. Successively, slices from each particle are analyzed by a pre-trained classifier to detect the presence of flaws or cracks. The models are used to quantify microstructural evolution in uncycled and cycled NMC811 electrodes, as well as the number of flawed particles in a NMC622 electrode. As a proof-of-concept, a 3-phase segmentation is also presented, whereby each individual flaw is segmented as a separate pixel label. It is anticipated that this analysis pipeline will be widely used in the field of battery research and beyond.

Disentangling water, ion and polymer dynamics in an anion exchange membrane.

Semipermeable polymeric anion exchange membranes are essential for separation, filtration and energy conversion technologies including reverse electrodialysis systems that produce energy from salinity gradients, fuel cells to generate electrical power from the electrochemical reaction between hydrogen and oxygen, and water electrolyser systems that provide H2 fuel. Anion exchange membrane fuel cells and anion exchange membrane water electrolysers rely on the membrane to transport OH- ions between the cathode and anode in a process that involves cooperative interactions with H2O molecules and polymer dynamics. Understanding and controlling the interactions between the relaxation and diffusional processes pose a main scientific and critical membrane design challenge. Here quasi-elastic neutron scattering is applied over a wide range of timescales (100-103 ps) to disentangle the water, polymer relaxation and OH- diffusional dynamics in commercially available anion exchange membranes (Fumatech FAD-55) designed for selective anion transport across different technology platforms, using the concept of serial decoupling of relaxation and diffusional processes to analyse the data. Preliminary data are also reported for a laboratory-prepared anion exchange membrane especially designed for fuel cell applications.

Molecular Basis of Hematological Disease Caused by Inherited or Acquired RUNX1 Mutations.

The transcription factor RUNX1 is essential for correct hematopoietic development; in its absence in the germ line, blood stem cells are not formed. RUNX1 orchestrates dramatic changes in the chromatin landscape at the onset of stem cell formation, which set the stage for both stem self-renewal and further differentiation. However, once blood stem cells are formed, the mutation of the RUNX1 gene is not lethal but can lead to various hematopoietic defects and a predisposition to cancer. Here we summarize the current literature on inherited and acquired RUNX1 mutations, with a particular emphasis on mutations that alter the structure of the RUNX1 protein itself, and place these changes in the context of what is known about RUNX1 function. We also summarize which mutant RUNX1 proteins are actually expressed in cells and discuss the molecular mechanism underlying how such variants reprogram the epigenome setting stem cells on the path to malignancy.

Effects of calcium ammonium nitrate fed to dairy cows on nutrient intake and digestibility, milk quality, microbial protein synthesis, and ruminal fermentation parameters.

We evaluated the effects of supplemental calcium ammonium nitrate (CAN) fed to dairy cows on dry matter (DM) intake, nutrient digestibility, milk quality, microbial protein synthesis, and ruminal fermentation. Six multiparous Holstein cows at 106 ± 14.8 d in milk, with 551 ± 21.8 kg of body weight were used in a replicated 3 × 3 Latin square design. Experimental period lasted 21 d, with 14 d for an adaptation phase and 7 d for sampling and data collection. Cows were randomly assigned to receive the following treatments: URE, 12 g of urea/kg of DM as a control group; CAN15, 15 g of CAN/kg of DM; and CAN30, 30 g of CAN/kg of DM. Supplemental CAN reduced DM intake (URE 19.0 vs. CAN15 18.9 vs. CAN30 16.5 kg/d). No treatment effects were observed for apparent digestibility of DM, organic matter, crude protein, ether extract, and neutral detergent fiber; however, CAN supplementation linearly increased nonfiber carbohydrate digestibility. Milk yield was not affected by treatments (average = 23.1 kg/d), whereas energy-corrected milk (ECM) and 3.5% fat-corrected milk (FCM) decreased as the levels of CAN increased. Nitrate residue in milk increased linearly (URE 0.30 vs. CAN15 0.33 vs. CAN30 0.38 mg/L); however, treatments did not affect nitrite concentration (average: 0.042 mg/L). Milk fat concentration was decreased (URE 3.39 vs. CAN15 3.35 vs. CAN30 2.94%), and the proportion of saturated fatty acids was suppressed by CAN supplementation. No treatment effects were observed on the reducing power and thiobarbituric acid reactive substances of milk, whereas conjugated dienes increased linearly (URE 47.6 vs. CAN15 52.7 vs. CAN30 63.4 mmol/g of fat) with CAN supplementation. Treatments had no effect on microbial protein synthesis; however, molar proportion of ruminal acetate and acetate-to-propionate ratio increased with CAN supplementation. Based on the results observed, supplementing CAN at 30 g/kg of DM should not be recommended as an optimal dose because it lowered DM intake along with ECM and 3.5% FCM, although no major changes were observed on milk quality and ruminal fermentation.

Pathology Training for Cancer Diagnosis in Africa.

OBJECTIVES: In response to requests for training in cancer pathology, two virtual training courses were organized: one in English for participants in Nigeria and another in French for participants in Francophone Africa. Each course had weekly 90-minute sessions covering essential topics in cancer pathology led by global experts. METHODS: Two research questions were investigated for both courses: (1) did the participants improve their knowledge of the topics covered during the course, and (2) did the course participants appreciate the virtual training format? RESULTS: The Nigeria course enrolled 85 participants from 26 Nigerian states; the Francophone Africa course enrolled 425 participants from 18 African countries. In the pre-post technical assessment, participants increased their scores on average by 3.4% (P > .05) in the Nigeria course and by 13.1% (P < .001) in the Francophone Africa course. On the postcourse survey, 95.8% of Nigerian respondents and 96.1% of Francophone African respondents reported being satisfied or very satisfied with the virtual format. CONCLUSIONS: Virtual training is a promising tool to improve cancer diagnosis in Africa, as the experience of the courses illustrates that participants appreciate the virtual format. Continued training is required to reinforce skills and enable participants to appropriately apply new knowledge to their daily practice.

A Multiscale X-Ray Tomography Study of the Cycled-Induced Degradation in Magnesium-Sulfur Batteries.

Rechargeable Mg/S batteries have the potential to provide a compelling battery for a range of applications owing to their high capacity and gravimetric energy density, safety, and low-cost construction. However, the Mg/S energy storage is not widely developed and deployed due to technical challenges, which include short cycle lifespan and lack of suitable electrolyte. To study the microstructure degradation of Mg/S batteries, multiscale X-ray tomography, an inherently nondestructive method, is performed on dismantled Swagelok Mg/S cells comprising a graphene-sulfur cathode and a super-P separator. For the first time, 3D microstructure visualization and quantification reveal the dissolution (volume fraction decreases from 13.5% to 0.7%, surface area reduces from 2.91 to 1.74 µm2 µm-3 ) and agglomeration of sulfur particles, and the carbon binder densification after 10 cycles. Using tomography data, the image-based simulations are then performed. The results show that the insoluble polysulfides can inevitably block the Mg2+ transportation via shuttle effect. The representative volume should exceed 8200 µm3 to represent bulk cathode. This work elucidates that the Mg/S cell performance is significantly affected by microstructural degradation, and moreover demonstrates how multiscale and multimodal characterization can play an indispensable role in developing and optimizing the Mg/S electrode design.

Enzymatic effects of Pleurotus ostreatus spent substrate on whole-plant corn silage and performance of lactating goats.

Pleurotus ostreatus (oyster mushroom) synthesizes enzymes that degrade lignin, cellulose, and hemicellulose. The objectives of this study were to evaluate the effect of Pleurotus ostreatus spent substrate (POSS) on whole-plant corn silage (WPCS) chemical composition, antioxidant capacity, lignin monomers, and in vitro digestibility, as well as the performance of lactating goats fed corn silage treated with different levels of POSS. In experiment 1, 4 levels of lignocellulolytic enzymes were tested in a complete randomized design: 0, 10, 20, and 30 mg of lignocellulosic enzymes per kilogram of fresh matter, 4 replicates per treatment (vacuum-sealed bags). The bags were opened 60 d after ensiling. In experiment 2, corn silage treated with 3 enzyme levels (0, 10, or 30 mg/kg of fresh matter) was fed to lactating goats as part of the total mixed ration. Nine lactating Saanen goats (62.68 ± 7.62 kg BW; 44 ± 8 d in milk; 2.91 ± 0.81 kg of milk/day, mean ± SD) were assigned to three 3 × 3 Latin squares. Data were analyzed using the GLIMMIX procedure of SAS (version 9.4, SAS Institute Inc.), and means were compared by linear and quadratic orthogonal contrast. In experiment 1, neutral detergent fiber (NDF), acid detergent fiber (ADF), lignin, and cellulose quadratically decreased in the WPCS treated with POSS. At the nadir point, POSS decreased NDF by 14.1%, ADF by 19.5%, lignin by 9.07%, and cellulose by 22.1% compared with the untreated silage. Therefore, POSS led to a quadratic increase in in vitro dry matter digestibility of WPCS (+8.88% at the vertex) compared with the untreated silage. In experiment 2, POSS quadratically increased the in vivo total-tract ADF digestibility. Also, the concentration of polyphenols in the milk of goats linearly increased with the addition of POSS, and no differences were observed among treatments for milk yield and composition. In summary, adding 10 mg of lignocellulolytic enzymes from POSS per kilogram of fresh matter of whole-plant corn at ensiling had a more evident reduction in lignin and cellulose concentration, leading to greater in vitro digestibility, as well as greater in vivo ADF digestibility; however, milk yield was not different among treatments.

Stable Epigenetic Programming of Effector and Central Memory CD4 T Cells Occurs Within 7 Days of Antigen Exposure In Vivo.

T cell immunological memory is established within days of an infection, but little is known about the in vivo changes in gene regulatory networks accounting for their ability to respond more efficiently to secondary infections. To decipher the timing and nature of immunological memory we performed genome-wide analyses of epigenetic and transcriptional changes in a mouse model generating antigen-specific T cells. Epigenetic reprogramming for Th differentiation and memory T cell formation was already established by the peak of the T cell response after 7 days. The Th memory T cell program was associated with a gain of open chromatin regions, enriched for RUNX, ETS and T-bet motifs, which remained stable for 56 days. The epigenetic programs for both effector memory, associated with T-bet, and central memory, associated with TCF-1, were established in parallel. Memory T cell-specific regulatory elements were associated with greatly enhanced inducible Th1-biased responses during secondary exposures to antigen. Furthermore, memory T cells responded in vivo to re-exposure to antigen by rapidly reprograming the entire ETS factor gene regulatory network, by suppressing Ets1 and activating Etv6 expression. These data show that gene regulatory networks are epigenetically reprogrammed towards memory during infection, and undergo substantial changes upon re-stimulation.

Atypical electrophysiological and behavioral responses to diazepam in a leading mouse model of Down syndrome.

Mounting evidence implicates dysfunctional GABAAR-mediated neurotransmission as one of the underlying causes of learning and memory deficits observed in the Ts65Dn mouse model of Down syndrome (DS). The specific origin and nature of such dysfunction is still under investigation, which is an issue with practical consequences to preclinical and clinical research, as well as to the care of individuals with DS and anxiety disorder or those experiencing seizures in emergency room settings. Here, we investigated the effects of GABAAR positive allosteric modulation (PAM) by diazepam on brain activity, synaptic plasticity, and behavior in Ts65Dn mice. We found Ts65Dn mice to be less sensitive to diazepam, as assessed by electroencephalography, long-term potentiation, and elevated plus-maze. Still, diazepam pre-treatment displayed typical effectiveness in reducing susceptibility and severity to picrotoxin-induced seizures in Ts65Dn mice. These findings fill an important gap in the understanding of GABAergic function in a key model of DS.

Nutritional value, total dry matter losses, effluent production and pollutant potential in Brachiaria brizantha cv. Paiaguás grass / [Valor nutricional, perdas totais de matéria seca, produção e potencial poluidor de efluentes em silagem de Brachiaria brizantha cv. Paiaguás]

The objective of the present study was to evaluate losses, production and polluting potential of the effluent, nutritional value and aerobic stability of silages of Brachiaria brizantha cv. Paiaguás grass, in different particle sizes and compaction density in silage. Three theoretical particle sizes (TTP 5; 8 and 12mm) and three compaction densities (DC 550; 600 and 650kg/m3) were evaluated, distributed in a factorial design (3 x 3), with four repetitions. The highest volume of effluent was found in silages with higher compaction densities (600 and 650kg/m3) and lower TTP (5 and 8mm). The highest chemical oxygen demand and biochemical oxygen demand were registered in the treatment with TTP of 5mm and higher DC (600 and 650kg/m3). Greater in vitro digestibility of DM was verified in the silage chopped at 5 and 8mm. There was no break in aerobic stability for 216 hours. Silage with a low compaction density 550kg/m3 and processing with a theoretical particle size of 12mm reduces effluent losses. In general, the nutritional value of Paiaguás grass was not influenced by the treatments. Different particle sizes and compaction density did not change the aerobic stability of silages.(AU)

Objetivou-se avaliar perdas, produção e potencial poluidor do efluente, valor nutricional e estabilidade aeróbia de silagens do capim Brachiaria brizantha cv. Paiaguás, em diferentes tamanhos de partícula e densidade de compactação na ensilagem. Foram avaliados três tamanhos teóricos de partícula (TTP 5; 8 e 12mm) e três densidades de compactação (DC 550; 600 e 650kg/m3), distribuídos em arranjo fatorial (3 x 3), com quatro repetições. O maior volume de efluente foi verificado nas silagens com maiores densidades de compactação (600 e 650kg/m3) e menores TTP (5 e 8mm). As maiores demanda química de oxigênio e demanda bioquímica de oxigênio foram registradas no tratamento com TTP de 5mm e nas maiores DC (600 e 650kg/m3). Maior digestibilidade in vitro da MS (média de 57,2%) foi verificada na silagem picada a 5 e 8mm. Não houve quebra da estabilidade aeróbia durante 216 horas. A ensilagem com baixa densidade de compactação (550kg/m3) e o processamento com tamanho teórico de partículas 12mm reduzem as perdas por efluente. O valor nutricional da silagem de capim-paiaguás, em geral, não foi influenciado pelos tratamentos. Diferentes tamanhos de partícula e densidade de compactação não alteraram a estabilidade aeróbia das silagens.(AU)

Effect of sealing strategy on the feeding value of corn silage for growing dairy heifers.

Our objective was to compare the performance of dairy heifers fed diets based on whole-plant corn silage stored in bunker silos sealed with either standard polyethylene film (white-on-black, actual thickness 121 ± 3.1 µm) covering the top surface, held in place with rows of tires every 3 m (PE) or an oxygen barrier system comprised of an ethylene-vinyl alcohol film (actual thickness 46.7 ± 2.5 µm) lining side walls and covering the silage, protected with a woven anti-UV cover and gravel bags placed around the edges and every 3 m across the silo (OB). Whole-plant corn was mechanically harvested at 39% dry matter (DM), packed in bunker silos, and sealed with PE or OB covering methods. After 6 mo of storage, silos were opened and fed to 26 Holstein heifers (260 ± 89.1 kg of shrunk body weight) for 60 d. Heifers were blocked by initial weight (13 blocks with 2 heifers each block) and housed in individual pens. Diets contained (on a DM basis) 80% corn silage (PE or OB), 17.5% soybean meal, and 2.5% mineral mix. Dry matter intake was measured daily, whereas shrunk body weight, hip height, heart girth, and body condition score were measured at the beginning and end of the experiment. Feeding behavior was recorded on d 24 and 46, and total-tract digestibility was measured from d 26 to 30 and 48 to 52. Data of intake, feeding behavior, and digestibility were averaged by animal for the whole feeding period before the statistical analysis. Data of animal performance were analyzed as a randomized complete block design. Initial shrunk body weight was used as a covariate for analyses of intake and body measures. During feed-out, silage quality was also assessed at the top (15 cm depth from upper surface) and bottom layer (135 cm depth from upper surface) and analyzed as a split-plot design. Silage stored under the OB sealing system had less yeast, mold, and NH3-N, and more lactic acid and ethanol-soluble carbohydrates. An interaction between sealing strategy and silo layer showed that OB silage had lower values of temperature, pH, anaerobic spores, acetic acid, and DM loss, and greater in vitro DM digestibility and aerobic stability, especially in the top layer. The proportion of inedible silage was lower in OB than in PE treatment (0.82 vs. 4.00% DM). Total-tract digestibility was similar between treatments, but animals that received the OB diet had higher DM intake by approximately 9% (9.39 vs. 10.20 kg/d) due to a faster eating rate and a greater number of meals per day. Therefore, OB treatment increased the digestible energy intake by 8% (26.3 vs. 28.3 Mcal/d) and average daily gain by 12% (1.08 vs. 1.21 kg/d). Body condition score change was similar between treatments, but heifers fed OB had greater heart girth and tended to have higher hip height. In conclusion, replacing a standard PE film with an OB sealing system improved silage conservation and performance of growing dairy heifers.