Standardising clinical outcomes measures for adult clinical trials in Fabry disease: A global Delphi consensus.

BACKGROUND: Recent years have witnessed a considerable increase in clinical trials of new investigational agents for Fabry disease (FD). Several trials investigating different agents are currently in progress; however, lack of standardisation results in challenges to interpretation and comparison. To facilitate the standardisation of investigational programs, we have developed a common framework for future clinical trials in FD. METHODS AND FINDINGS: A broad consensus regarding clinical outcomes and ways to measure them was obtained via the Delphi methodology. 35 FD clinical experts from 4 continents, representing 3389 FD patients, participated in 3 rounds of Delphi procedure. The aim was to reach a consensus regarding clinical trial design, best treatment comparator, clinical outcomes, measurement of those clinical outcomes and inclusion and exclusion criteria. Consensus results of this initiative included: the selection of the adaptative clinical trial as the ideal study design and agalsidase beta as ideal comparator treatment due to its longstanding use in FD. Renal and cardiac outcomes, such as glomerular filtration rate, proteinuria and left ventricular mass index, were prioritised, whereas neurological outcomes including cerebrovascular and white matter lesions were dismissed as a primary or secondary outcome measure. Besides, there was a consensus regarding the importance of patient-related outcomes such as general quality of life, pain, and gastrointestinal symptoms. Also, unity about lysoGb3 and Gb3 tissue deposits as useful surrogate markers of the disease was obtained. The group recognised that cardiac T1 mapping still has potential but requires further development before its widespread introduction in clinical trials. Finally, patients with end-stage renal disease or renal transplant should be excluded unless a particular group for them is created inside the clinical trial. CONCLUSION: This consensus will help to shape the future of clinical trials in FD. We note that the FDA has, coincidentally, recently published draft guidelines on clinical trials in FD and welcome this contribution.

Evaluation of the amount of nanoparticles emitted in LASER additive manufacture/welding.

Objectives: The objective of this study was the evaluation of the professional exposure to nanoparticles during tasks performed in workstations for production of metallic parts by laser welding additive manufacturing. Materials and methods: The study was developed in an installed additive manufacturing machine, having controlled temperature and humidity in an industrial unit where metal parts were being produced using stainless steel powders of granulometry of 10 to 35 µm. Results and discussion: Monitoring of airborne nanoparticles emission was made using adequate equipment, which showed considerable number of nanoparticles over the baseline, having the same composition as the steel powder used. Conclusion: It is concluded that the values of professional exposure to nanoparticles are high in these workstations and that the nanoparticles to which the workers are exposed are small in size (around 15 nm), thus having a strong capacity for alveolar penetration and, consequently, with a strong possibility of passing to the bloodstream, accumulating in the body.

Collagen type IV-related nephropathies in Portugal: pathogenic COL4A3 and COL4A4 mutations and clinical characterization of 25 families.

Pathogenic mutations in genes COL4A3/COL4A4 are responsible for autosomal Alport syndrome (AS) and thin basement membrane nephropathy (TBMN). We used Sanger sequencing to analyze all exons and splice site regions of COL4A3/COL4A4, in 40 unrelated Portuguese probands with clinical suspicion of AS/TBMN. To assess genotype-phenotype correlations, we compared clinically relevant phenotypes/outcomes between homozygous/compound heterozygous and apparently heterozygous patients. Seventeen novel and four reportedly pathogenic COL4A3/COL4A4 mutations were identified in 62.5% (25/40) of the probands. Regardless of the mutated gene, all patients with ARAS manifested chronic renal failure (CRF) and hearing loss, whereas a minority of the apparently heterozygous patients had CRF or extrarenal symptoms. CRF was diagnosed at a significantly younger age in patients with ARAS. In our families, the occurrence of COL4A3/COL4A4 mutations was higher, while the prevalence of XLAS was lower than expected. Overall, a pathogenic COL4A3/COL4A4/COL4A5 mutation was identified in >50% of patients with fewer than three of the standard diagnostic criteria of AS. With such a population background, simultaneous next-generation sequencing of all three genes may be recommended as the most expedite approach to diagnose collagen IV-related glomerular basement membrane nephropathies.

Collagen type IV-related nephropathies in Portugal: pathogenic COL4A5 mutations and clinical characterization of 22 families.

Alport syndrome (AS) is caused by pathogenic mutations in the genes encoding α3, α4 or α5 chains of collagen IV (COL4A3/COL4A4/COL4A5), resulting in hematuria, chronic renal failure (CRF), sensorineural hearing loss (SNHL) and ocular abnormalities. Mutations in the X-linked COL4A5 gene have been identified in 85% of the families (XLAS). In this study, 22 of 60 probands (37%) of unrelated Portuguese families, with clinical diagnosis of AS and no evidence of autosomal inheritance, had pathogenic COL4A5 mutations detected by Sanger sequencing and/or multiplex-ligation probe amplification, of which 12 (57%) are novel. Males had more severe and earlier renal and extrarenal complications, but microscopic hematuria was a constant finding irrespective of gender. Nonsense and splice site mutations, as well as small and large deletions, were associated with younger age of onset of SNHL in males, and with higher risk of CRF and SNHL in females. Pathogenic COL4A3 or COL4A4 mutations were subsequently identified in more than half of the families without a pathogenic mutation in COL4A5. The lower than expected prevalence of XLAS in Portuguese families warrants the use of next-generation sequencing for simultaneous COL4A3/COL4A4/COL4A5 analysis, as first-tier approach to the genetic diagnosis of collagen type IV-related nephropathies.

Cellulose Acetate and Polycaprolactone Fibre Coatings on Medical-Grade Metal Substrates for Controlled Drug Release.

This study explores a method that has the potential to be cost effective in inhibiting biofilm formation on metallic prostheses, thereby preventing rejection or the requirement for replacement. A cost-effective metal alloy used in biomedical implants was chosen as the substrate, and ibuprofen (Ibu), a well-known anti-inflammatory drug, was selected for drug release tests for its widespread availability and accessibility. Multilayer coatings consisting of cellulose acetate (CA), polycaprolactone (PCL), and chitosan (CHI), with or without ibuprofen (Ibu) content, were applied onto medical-grade stainless steel (SS-316 type) through electrospinning, electrospray, or blow spinning. The adhesion of the CA, PCL, and layered CA/PCL membranes, with thicknesses ranging from 20 to 100 µm, to SS substrates varied between 0.15 N and 0.22 N without CHI, which increased to 0.21 and 0.74 N, respectively, when a CHI interlayer was introduced by electrospraying between the SS and the coatings. Although drug release in a simulated body fluid (SBF) medium is predominantly governed by diffusion-driven mechanisms in all single- and multilayer coatings, a delayed release was noted in CA coatings containing Ibu when overlaid with a PCL coating produced by blow spinning. This suggests avenues for further investigations into combinations of multilayer coatings, both with and without drug-imbued layers.

Identifying strategic opportunities through the development of a roadmap for additive manufacturing: The example of Portugal.

Additive Manufacturing (AM) demonstrates significant potential with rapid growth and widespread industrial adoption. To support the integration and innovation of AM technologies, the development of guidance tools and support methods are crucial, and a technological roadmap can assist in this effort. Despite its widespread use in production processes, the need for further research on the potential impact of AM remains significant. The full impact of AM is still uncertain and lacks consensus, highlighting the need for increased knowledge and investment from the scientific community and organizations. While the benefits of AM are recognized, the challenges of its adoption are not entirely known. AM will bring changes in the way organizations create, distribute, and derive value. Thus, in this article, a roadmap for AM is proposed and presented as a tool to map technological knowledge on the implementation and evolution of AM and serve as a strategic guide for organizations. The methodology for its elaboration involves three phases: planning and preparation, roadmap development, and review and update. Through a literature review, database and project consultation, and questionnaires to Portuguese companies that use AM in their production process it was possible to characterize the AM technology and through the visual format, based on a time horizon, summarize in a common framework all the information about the current and future state of AM in Portugal. The results of this study show that research and development initiatives are essential to promote the evolution of knowledge of the AM technology. Throughout this study and with the development of the roadmap it is anticipated that in the near future the AM will be widely used for prototyping and manufacturing of components and may be used for direct production in the short to medium term. It was also found that the main obstacles to the implementation of AM are the economic/productivity factors and the shortage of professionals with knowledge and skills in the area.

Spatial and directional characterization of wire and arc additive manufactured aluminum alloy using phased array ultrasonic backscattering method.

Pores, grains, or textures can collectively cause microstructural inhomogeneity and anisotropy in metallic materials fabricated by additive manufacturing. In this study, a phased array ultrasonic method is developed to characterize the inhomogeneity and anisotropy of wire and arc additively manufactured components by performing both beams focusing and steering. Two backscattering features, i.e., the integrated backscattering intensity and the root mean square of the backscattering signals, are employed to quantify the microstructural inhomogeneity and anisotropy, respectively. An experimental investigation is performed using an aluminum sample fabricated by wire and arc additive manufacturing. The ultrasonic measurements, performed on wire and arc additive manufactured 2319 aluminum alloy, show that the sample is inhomogeneous and weakly anisotropic. Metallography, electron backscatter diffraction, and X-ray computed tomography are used to verify the ultrasonic results. An ultrasonic scattering model is used to identify the influence of grains on the backscattering coefficient. Compared with a wrought aluminum alloy, the complex microstructure in additively manufactured material significantly influence the backscattering coefficient, and the presence of pores cannot be neglected in ultrasonic-based nondestructive evaluation for wire and arc additive manufactured metals.

Electrospray Deposition of PEDOT:PSS on Carbon Yarn Electrodes for Solid-State Flexible Supercapacitors.

The increasing demand for flexible electronic devices has risen due to the high interest in electronic textiles (e-textiles). Consequently, the urge to power e-textiles has sparked enormous interest in flexible energy storage devices. One-dimensional (1D) configuration supercapacitors are the most promising technology for textile applications, but often their production involves complex synthesis techniques and expensive materials. This work unveils the use of the novel electrospray deposition (ESD) technique for the deposition of poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonate) (PEDOT:PSS). This deposition methodology on conductive carbon yarns creates flexible electrodes with a high surface area. The deposition conditions of PEDOT:PSS were optimized, and their influence on the electrochemical performance of a 1D symmetric supercapacitor with a cellulose-based gel as an electrolyte and a separator was evaluated. The tests herein reported show that these capacitors exhibited a high specific capacitance of 72 mF g-1, an excellent cyclability of more than 85% capacitance retention after 1500 cycles, and an outstanding capability of bending.

Recycling of Reinforced Glass Fibers Waste: Current Status.

In this paper, a review of the current status and future perspectives for reinforced glass fiber waste is undertaken, as well as an evaluation of the management hierarchy for these end-of-life materials. Waste levels are expected to increase in the coming years, but an improvement of collection routes is still necessary. The recycling processes for these materials are presented. The associated advantages and disadvantages, as well as the corresponding mechanical characteristics, are described. Although mechanical shredding is currently the most used process, there is a potential for thermal processes to be more competitive than others due to the fiber quality after the recycling process. However, the energy requirements of each of the processes are not yet well explained, which compromises the determination of the economic value of the recycled fibers when included in other products, as well as the process feasibility. Nevertheless, the work of some authors that successfully integrated recycled glass fibers into other elements with increased mechanical properties is evaluated. Future recommendations for the recycling of glass fiber and its commercialization are made.

Microstructure and mechanical properties of dissimilar NiTi and 304 stainless steel joints produced by ultrasonic welding.

Superelastic NiTi alloy and 304 stainless steel (304 SS) were joined with a Cu interlayer by ultrasonic spot welding (USW) using different welding energy inputs. The surface morphology, interfacial microstructure, mechanical properties, and fracture mechanisms of the dissimilar NiTi/304 SS USWed joints were studied. The results showed that the surface oxidation intensified with increasing ultrasonic welding energy due to mutual rubbing between tools and sheets. The weld interface microstructure exhibited voids or unbonded zones at low energy inputs, while an intimate contact was established at the joining interface when applying a higher energy input of 750 J. With increasing energy input to 750 J, the weld interface shows two interfaces due to the behavior of plastic flow of Cu interlayer. The lap-shear load of the joints first increased, achieving a maximum value of ∼690 N at an energy input of 750 J, and then decreased with further increase in welding energy. Interfacial failure was observed at NiTi/Cu interface at all energy inputs, and no intermetallic compounds were found on the fracture surfaces of both the NiTi/Cu and Cu/304 SS interfaces.

Effect of dietary buriti oil on the quality, fatty acid profile and sensorial attributes of lamb meat.

Forty crossbred (Santa Ines × Dorper) male lambs were used to investigate the effect of dietary buriti oil (BOIL) intake on meat quality, fatty acid (FA) composition and sensory attributes. A completely randomized design with five BOIL intake levels (0, 12, 24, 36 and 48 g/kg DM) was used. Increasing dietary BOIL intake linearly reduced the DMI, slaughter weight, cooking loss, shear force, yellowness, 16:0, c9-18:1 FA concentrations, and the delta-9-desaturase activity index computed using c9-16:1 and 16:0 as product and substrate pair, cis-MUFA and Æ©MUFA/Æ©SFA ratio of lamb meat (P ≤ 0.05); however, increasing dietary BOIL intake quadratically increased the energy intake, lipid content and linearly increased the total FA intake, chroma, collagen, total BI, 18:0, 20:3n-6 concentration and sensory attributes of lamb meat (P ≤ 0.05), without affecting health indexes regarding fat consumption. BOIL addition at levels above 24 g/kg DM in lamb diet reduces growth, however, improves tenderness, flavor and "goat" aroma intensity and slightly changes meat FA levels, promoting better acceptance by panelists.

Immunohistochemical characterization of 13 canine renal cell carcinomas.

Canine renal cell carcinomas (RCCs) are uncommon aggressive tumors that occur mainly in middle-aged male dogs. Their histologic classification bears no relationship with prognosis, and little information is available concerning their immunohistochemical properties. In this retrospective study, formalin-fixed, paraffin-embedded tissues from 13 canine RCCs were retrieved from the archives, classified histologically, and evaluated immunohistochemically. The dogs were 7 males and 6 females (1 spayed) of 10 different breeds, averaging 8 years in age. The tumors were classified as papillary, tubulopapillary, papillary-cystic, solid, or sarcomatoid. All 13 tumors were immunohistochemically positive for uromodulin, 12 for c-KIT, 11 for vimentin, 9 for wide-spectrum-screening cytokeratins, 7 for cytokeratins AE1/AE3 and carcinoembryonic antigen, 4 for cytokeratins CAM 5.2, and 3 for CD10. All 3 solid RCCs expressed vimentin, c-KIT, and carcinoembryonic antigen and were negative for cytokeratins. All 7 papillary and tubulopapillary tumors expressed vimentin; 6 (86%), cytokeratins; and 6 (86%), c-KIT. Both papillary-cystic RCCs were positive for cytokeratins and c-KIT and negative for vimentin. These results indicate that the different histologic types of RCC have characteristic immunohistochemical profiles and that c-KIT may be involved in the pathogenesis of canine RCC.

Water Dynamics on Germinating Diaspores: Physiological Perspectives from Biophysical Measurements.

We demonstrated that classical biophysical measurements of water dynamics on germinating diaspores (seeds and other dispersal units) can improve the understanding of the germination process in a simpler, safer, and newer way. This was done using diaspores of cultivated species as a biological model. To calculate the water dynamics measurements (weighted mass, initial diffusion coefficient, velocity, and acceleration), we used the mass of diaspores recorded over germination time. Weighted mass of germinating diaspores has a similar pattern, independent of the physiological quality, species, or genetic improvement degree. However, the initial diffusion coefficient (related to imbibition per se), velocity, and acceleration (related to the whole germination metabolism) are influenced by species characters, highlighting the degree of genetic improvement and physiological quality. Changes in the inflection of velocity curves demonstrated each phase of germination sensu stricto. There is no pattern related to the number of these phases, which could range between three and six. Regression models can demonstrate initial velocity and velocity increments for each phase, giving an idea of the management of germinative metabolism. Our finds demonstrated that germination is a polyphasic process with a species-specific pattern but still set by the degree of genetic improvement and (or) physiological quality of diaspores. Among the biophysical measurements, velocity has the greatest potential to define the germination metabolism.

Current Status and Perspectives on Wire and Arc Additive Manufacturing (WAAM).

Additive manufacturing has revolutionized the manufacturing paradigm in recent years due to the possibility of creating complex shaped three-dimensional parts which can be difficult or impossible to obtain by conventional manufacturing processes. Among the different additive manufacturing techniques, wire and arc additive manufacturing (WAAM) is suitable to produce large metallic parts owing to the high deposition rates achieved, which are significantly larger than powder-bed techniques, for example. The interest in WAAM is steadily increasing, and consequently, significant research efforts are underway. This review paper aims to provide an overview of the most significant achievements in WAAM, highlighting process developments and variants to control the microstructure, mechanical properties, and defect generation in the as-built parts; the most relevant engineering materials used; the main deposition strategies adopted to minimize residual stresses and the effect of post-processing heat treatments to improve the mechanical properties of the parts. An important aspect that still hinders this technology is certification and nondestructive testing of the parts, and this is discussed. Finally, a general perspective of future advancements is presented.

The g.1170C>T polymorphism of the 5' untranslated region of the human alpha-galactosidase gene is associated with decreased enzyme expression--evidence from a family study.

Subnormal leukocyte α-galactosidase (α-Gal) activity was found during evaluation of an adolescent male with cryptogenic cerebrovascular small-vessel disease. The only molecular abnormality found was the g.1170C>T single-nucleotide polymorphism (SNP) in the 5' untranslated region of exon 1 in the α-Gal gene (GLA). Historically, this polymorphism has been considered to be biologically neutral. To test the hypothesis that the g.1170T allele might be associated with lower α-Gal expression, we genotyped GLA exon 1 and measured leukocyte and plasma α-Gal in the parents, brother and sister of the index case. The g.1170T allele co-segregated with a subnormal leukocyte α-Gal activity in the three siblings. Although plasma enzyme activities were within the normal range in all five relatives, the ranking of their values suggested a dosage effect of the g.1170T allele. Western blotting assays of leukocyte protein extracts showed that the relative expression of α-Gal in both the patient and his sister was significantly lower than in sex-matched hemizygous or homozygous controls for the g.1170C allele, either normalized to the ß-actin immunoblot expression or standardized to a known amount of recombinant human α-Gal. These family data, in combination with results from a recent GLA SNP screening study among healthy Portuguese individuals, suggest that the g.1170C>T SNP may be co-dominantly associated with a relatively decreased GLA expression at the transcription and/or translation level. Larger population studies are needed to confirm these findings and to test the hypothesis that the GLA g.1170C>T may contribute to the multifactorial risk of ischaemic small-vessel cerebrovascular disease.

Effect of single-nucleotide polymorphisms of the 5' untranslated region of the human α-galactosidase gene on enzyme activity, and their frequencies in Portuguese caucasians.

BACKGROUND: The α-galactosidase gene (GLA) has three single-nucleotide polymorphisms in the 5' untranslated region of exon 1, respectively g.1150G>A, g.1168G>A, g.1170C>T. The g.1150A allele is associated with increased plasma α-galactosidase (α-Gal) activity in hemizygotes, while the others are regarded as biologically neutral. The primary goal of this investigation was to test the hypothesis, raised by a clinical observation and results of a family study, that the g.1170T allele polymorphism is associated with lower α-Gal expression. SUBJECTS AND METHODS: Plasma and leukocyte α-Gal activities were assayed in unrelated healthy young adults of both sexes, who had been genotyped for GLA exon 1, and enzyme activity values in carriers of any of the polymorphisms were compared to those of individuals with the standard genotype; GLA exon 1 was genotyped in males who had α-Gal activity in dried blood spots lower than 2 SD below the cohort average. RESULTS AND CONCLUSIONS: Mean α-Gal leukocyte activity was ∼ 25% higher in subjects with the g.1170C or CC genotype than in those with the alternative genotypes (p < 0.05). The frequency of the g.1170T allele in subjects with low α-Gal activity in dried blood spots was 4-fold higher (p < 0.05) than in the general population. As in hemizygotes, the g.1150A heterozygote identified in this study had plasma α-Gal activity more than 2-fold above the normal mean. The g.1168A allele did not affect enzyme activity. Surprisingly, females with the standard GLA exon 1 genotype had significantly higher plasma α-Gal activity than genetically comparable males.

Cadmium tolerance of Typha domingensis Pers. (Typhaceae) as related to growth and leaf morphophysiology.

Typha domingensis (cattail) is a native macrophyte known by its capacity to tolerate several heavy metals effects and the potential use for phytoremediation. However, in despite that cadmium (Cd) is one of the most toxic pollutants; its effects in T. domingensis biology remain uninvestigated. Thus, the objective of this study was to study the tolerance of T. domingensis to cadmium contamination by evaluating its growth, Cd uptake, leaf anatomy and gas exchange. The experiment was designed using three cadmium concentrations (0, 10 and 50 µM) and ten replicates for 90 days. The cadmium uptake, growth, gas exchange, chlorophyll content and leaf anatomy were evaluated. Data was submitted to ANOVA and Scott-Knott test for P<0.05. Typha domingensis accumulates Cd proportionally to its concentration on the solution and the content of this metal was higher in roots as compared to shoots. Plants showed no significant modifications on growth parameters such as the biomass production, number of leaves, number of clones and the biomass allocation to organs. The photosynthesis, transpiration and chlorophyll content were not modified by Cd. Most anatomical traits evaluated were not modified by the metal but the stomatal density and the proportion of vascular tissues were reduced under 50 µM of Cd. In despite, the leaf anatomy showed no toxicity evidences for any Cd level. The absence of growth reduction and the stability of anatomical and physiological traits give insight about the Cd tolerance of this species. Therefore, T. domingensis is able to overcome Cd toxicity and shows potential for phytoremediation.

Effect of increasing levels of fat-soluble and water-soluble vitamins on improving performance and plasma vitamin concentration in modern hybrids pig's growth and finishing phase / Efeito do aumento dos níveis de vitaminas lipossolúveis e hidrossolúveis na melhoria do desempenho e na concentração plasmática de vitaminas em suínos híbridos modernos nas fases de crescimento e terminação

The objective was to evaluate the supplementation of fat-soluble and water-soluble vitamins on the performance and plasma concentrations of vitamins in modern hybrids pigs. A total of 144 commercial hybrid castrated male, 43.531 ± 1.099kg, were used in a randomized block design with six treatments, eight replicates and three animals per pen. The experimental treatments were different vitamin supplementation levels - 0, 25, 50, 75, 100, and 125% of the recommended by Rostagno et al. (2011) for male pigs in growth I (40 to 50kg), growth II (50 to 70kg), and finishing I (70 to 90kg) phases. For growth phases I and II, a linear effect (P<0.05) due to increase in vitamin supplementation was observed on performance. For finishing phase I and total phase, a linear effect (P<0.05) was observed with increased final average weight (FAW) and improved feed conversion ratio (FCR). For average daily weight gain (ADWG) and average daily feed intake (ADFI) a quadratic effect was observed (P<0.05). A linear (P<0.05) increase in plasmatic α-tocopherol and B12 was observed with the 125%. Thus, it is concluded that the 125% vitamin supplementation improved performance of modern hybrids pigs (40 to 90kg).

Objetivou-se avaliar a suplementação de vitaminas lipossolúveis e hidrossolúveis sobre o desempenho e as concentrações plasmáticas de vitaminas em suínos híbridos modernos. Um total de 144 híbridos machos castrados, 43,531 ± 1,099kg, foram distribuídos em delineamento de blocos ao acaso, com seis tratamentos, oito repetições e três animais por baia. Os tratamentos foram diferentes níveis de vitaminas - 0, 25, 50, 75, 100 e 125% do recomendado por Rostagno et al. (2011) para suínos machos nas fases de crescimento I (40 a 50kg), crescimento II (50 a 70kg) e terminação I (70 a 90kg). Para as fases de crescimento I e II, observou-se efeito linear (P<0,05) devido ao aumento na suplementação vitamínica sobre o desempenho. Para a fase de terminação I e a fase total, observou-se efeito linear (P<0,05) com o aumento do peso médio final (PMF) e melhoria da conversão alimentar (CA). Já para as variáveis de ganho de peso médio diário (GPMD) e consumo de ração médio diário (CRMD,) observou-se efeito quadrático (P<0,05). Houve aumento linear (P<0,05) em α-tocoferol e cobalamina plasmáticos devido à suplementação de 125%. Assim, conclui-se que a suplementação com 125% de vitaminas melhorou o desempenho de suínos híbridos modernos (40 a 90kg).

An integrative insight on dormancy alleviation in diaspores of Urochloa humidicola (Rendle) Morrone & Zuloaga, a tropical grass with great economic and ecological impact.

Even though exhaustively studied, dormancy alleviation in diaspores of Urochloa humidicola (Rendle) Morrone & Zuloaga remains a mystery. To clarify this, we asked the following question: could dormancy alleviation in diaspores of this species be associated with ageing, GA/ABA balance and remaining structures of the panicoid spikelet? We answer this question using diaspores of U. humidicola cv. BRS Tupi as a biological model, a cultivar with a wide edaphoclimatic range in Neotropical areas and whose diaspores possess 'deep dormancy' when dispersed. We analysed both germination and early plant development using a split-plot model. Our findings demonstrate that dormancy alleviation in diaspores of U. humidicola is a synergic phenomenon driven by crosstalk between age, GA/ABA balance and remaining structures of the panicoid spikelet covering caryopses, since this interaction acts on the dynamics of germination and early plant development. We demonstrate that: (i) spreading germination time is a maternal survival mechanism of this species, which has repercussions for occupational aggressiveness of the species; (ii) remaining structures of the panicoid spikelet covering caryopses are the main modulator of embryo development. These structures control the after-ripening process, which is modulated by some molecular factor. We also highlight that it is necessary to review concepts about dormancy of dispersal units in this grass species.