Population dynamics of potentially harmful haplotypes: a pedigree analysis.

BACKGROUND: The identification of low-frequency haplotypes, never observed in homozygous state in a population, is considered informative on the presence of potentially harmful alleles (candidate alleles), putatively involved in inbreeding depression. Although identification of candidate alleles is challenging, studies analyzing the dynamics of potentially harmful alleles are lacking. A pedigree of the highly endangered Gochu Asturcelta pig breed, including 471 individuals belonging to 51 different families with at least 5 offspring each, was genotyped using the Axiom PigHDv1 Array (658,692 SNPs). Analyses were carried out on four different cohorts defined according to pedigree depth and at the whole population (WP) level. RESULTS: The 4,470 Linkage Blocks (LB) identified in the Base Population (10 individuals), gathered a total of 16,981 alleles in the WP. Up to 5,466 (32%) haplotypes were statistically considered candidate alleles, 3,995 of them (73%) having one copy only. The number of alleles and candidate alleles varied across cohorts according to sample size. Up to 4,610 of the alleles identified in the WP (27% of the total) were present in one cohort only. Parentage analysis identified a total of 67,742 parent-offspring incompatibilities. The number of mismatches varied according to family size. Parent-offspring inconsistencies were identified in 98.2% of the candidate alleles and 100% of the LB in which they were located. Segregation analyses informed that most potential candidate alleles appeared de novo in the pedigree. Only 17 candidate alleles were identified in the boar, sow, and paternal and maternal grandparents and were considered segregants. CONCLUSIONS: Our results suggest that neither mutation nor recombination are the major forces causing the apparition of candidate alleles. Their occurrence is more likely caused by Allele-Drop-In events due to SNP calling errors. New alleles appear when wrongly called SNPs are used to construct haplotypes. The presence of candidate alleles in either parents or grandparents of the carrier individuals does not ensure that they are true alleles. Minimum Allele Frequency thresholds may remove informative alleles. Only fully segregant candidate alleles should be considered potentially harmful alleles. A set of 16 candidate genes, potentially involved in inbreeding depression, is described.

Long-Term Effects of a 6-Week Power-Based Resistance Training and Fast Walking Interval Training Program on Physical Function, Muscle Power, Disability, and Frailty in Pre-Frail and Frail Older Adults.

INTRODUCTION: Concurrent training has been shown to be a beneficial approach to improve overall health status in older adults. However, little is known about the adaptations of this type of training in the long term (i.e., after cessation of exercise), even less in older people affected by frailty syndrome. Therefore, this study aimed (i) to assess the effects of a 6-week concurrent training program composed of power-oriented resistance training and fast walking interval training on physical function, muscle power, disability in activities of daily living and frailty in pre-frail and frail older people, and (ii) to assess the effects of a 6-month detraining period on these outcomes. METHODS: A total of 59 pre-frail and frail older adults (>75 years old; Frailty Phenotype >1) were allocated into intervention (INT; n = 32; 81.8 years; 21 women) or control (CON; n = 27; 82.5 years; 19 women) groups. Primary outcomes of this study were Short Physical Performance Battery (SPPB), relative sit-to-stand (STS) power, Barthel index, Lawton scale and Frailty Phenotype. Assessments were performed at baseline (PRE), after the concurrent training programme (POST) and after 6 months of follow-up (DET) in both groups. Mixed model repeated measures ANOVA with Bonferroni's post hoc tests was used. RESULTS: Immediately after the intervention (∆ = POST-PRE), INT improved SPPB (∆ = 3.0 points; p < 0.001), relative STS power (∆ = 0.87 W·kg-1; p < 0.001) and reduced their frailty levels (∆ = -1.42 criteria; p < 0.001), while no changes were observed in CON. After 6 months of detraining (∆ = DET-PRE), INT showed higher SPPB (∆ = 2.2 points; p < 0.001), higher relative STS power (∆ = 0.73 W·kg-1; p < 0.001) and lower frailty (∆ = -1.24 criteria; p < 0.001) values than those reported at baseline, which were significantly different than those reported by CON. Both, Barthel index and Lawton scale values were not modified during the study in either group. CONCLUSIONS: The 6-week concurrent training program improved physical function, muscle power and reduced frailty in pre-frail and frail older people and these improvements were maintained above baseline levels after 6 months of detraining. However, due to the individual variability found, future studies of long-term responders versus non-responders in frail populations are required.

Power-oriented resistance training combined with high-intensity interval training in pre-frail and frail older people: comparison between traditional and cluster training set configurations on the force-velocity relationship, physical function and frailty.

OBJECTIVES: To analyse the force-velocity relationship changes in response to two different training programmes differing in the set configuration (cluster vs. traditional), and their impact on physical function and frailty in pre-frail and frail older adults. METHODS: 43 pre-frail and frail (Frailty Phenotype ≥ 1 criteria) older adults (81.4 ± 5.1 years) participated in this study. Participants were assigned to cluster (CT; n = 10; 10-s intra-set rest), traditional (TT; n = 13; no intra-set rest) or control (CON; n = 20) groups. Force-velocity relationship (F0, V0 and Pmax), physical function (Short Physical Performance Battery, SPPB) and frailty (Frailty Phenotype, FP) were assessed at baseline and after the training programme. RESULTS: Both CT and TT groups showed similar improvements in Pmax after training (CT = + 36.7 ± 34.2 W; TT = + 33.8 ± 44.6 W; both p < 0.01). V0 was improved by both CT (+ 0.08 ± 0.06 m s-1; p < 0.01), and TT (+ 0.07 ± 0.15 m s-1, p > 0.05). F0 remained unchanged in CT (+ 68.6 ± 224.2 N, p > 0.05) but increased in TT (+ 125.4 ± 226.8 N, p < 0.05). Finally, SPPB improved in both training conditions (CT = + 2.3 ± 1.3 points; TT = + 3.0 ± 1.2 points; both p < 0.05) and in the CON group (+ 0.9 ± 1.4 points, p < 0.05). CT and TT reduced their FP (CT = - 1.1 criteria; TT = - 1.6 criteria; both p < 0.01), while no changes were observed in the CON group (- 0.2 criteria, p = 0.38). CONCLUSIONS: Both training methods were equally effective for improving Pmax, physical function and reducing frailty in pre-frail and frail older people. TT may be effective for improving both force and velocity parameters, while CT may be effective for improving velocity parameters alone, although further research is required to confirm these findings.

Comparing assembly strategies for third-generation sequencing technologies across different genomes.

The recent advent of long-read sequencing technologies, such as Pacific Biosciences (PacBio) and Oxford Nanopore technology (ONT), has led to substantial accuracy and computational cost improvements. However, de novo whole-genome assembly still presents significant challenges related to the computational cost and the quality of the results. Accordingly, sequencing accuracy and throughput continue to improve, and many tools are constantly emerging. Therefore, selecting the correct sequencing platform, the proper sequencing depth and the assembly tools are necessary to perform high-quality assembly. This paper evaluates the primary assembly reconstruction from recent hybrid and non-hybrid pipelines on different genomes. We find that using PacBio high-fidelity long-read (HiFi) plays an essential role in haplotype construction with respect to ONT reads. However, we observe a substantial improvement in the correctness of the assembly from high-fidelity ONT datasets and combining it with HiFi or short-reads.

A Conserved Second Sphere Residue Tunes Copper Site Reactivity in Lytic Polysaccharide Monooxygenases.

Lytic polysaccharide monooxygenases (LPMOs) are powerful monocopper enzymes that can activate strong C-H bonds through a mechanism that remains largely unknown. Herein, we investigated the role of a conserved glutamine/glutamate in the second coordination sphere. Mutation of the Gln in NcAA9C to Glu, Asp, or Asn showed that the nature and distance of the headgroup to the copper fine-tune LPMO functionality and copper reactivity. The presence of Glu or Asp close to the copper lowered the reduction potential and decreased the ratio between the reduction and reoxidation rates by up to 500-fold. All mutants showed increased enzyme inactivation, likely due to changes in the confinement of radical intermediates, and displayed changes in a protective hole-hopping pathway. Electron paramagnetic resonance (EPR) and X-ray absorption spectroscopic (XAS) studies gave virtually identical results for all NcAA9C variants, showing that the mutations do not directly perturb the Cu(II) ligand field. DFT calculations indicated that the higher experimental reoxidation rate observed for the Glu mutant could be reconciled if this residue is protonated. Further, for the glutamic acid form, we identified a Cu(III)-hydroxide species formed in a single step on the H2O2 splitting path. This is in contrast to the Cu(II)-hydroxide and hydroxyl intermediates, which are predicted for the WT and the unprotonated glutamate variant. These results show that this second sphere residue is a crucial determinant of the catalytic functioning of the copper-binding histidine brace and provide insights that may help in understanding LPMOs and LPMO-inspired synthetic catalysts.

Temporal trends in the cost and use of first-line treatments for infantile epileptic spasms syndrome.

OBJECTIVE: To describe the temporal trends in the cost and use of adrenocorticotropic hormone (ACTH), oral prednisolone, and vigabatrin, the first-line treatments for infantile epileptic spasms syndrome (IESS). METHODS: Retrospective observational study using the MarketScan Commercial database from 2006 to 2020. We identified patients with IESS diagnosed between birth and 18 months of age who received at least one of the first-line treatments within 60 days of diagnosis. Costs were adjusted for inflation using the Gross Domestic Product Implicit Price Deflator. RESULTS: A total of 1131 patients received at least one first-line treatment (median [p25 -p75 ] age: 6.3 [4.5-8.3] months, 55% male), of whom 592 patients received ACTH, 363 patients received oral prednisolone, and 355 patients received vigabatrin. After adjusting for inflation, the median average wholesale price of a 14-day course of treatment increased for ACTH from $3718 in 2006 to $100 457 in 2020, ~2700% (by a factor of 27), whereas it decreased for oral prednisolone from $169 in 2006 to $89 in 2020, ~50% (by a factor of 0.5), and increased for vigabatrin from $1206 in 2009 (first year with data on vigabatrin used for IESS) to $4102 in 2020, ~340% (by a factor of 3.4). During the first 60 days after diagnosis, inpatient admission days and costs where higher for ACTH than for oral prednisolone and vigabatrin-5.0 (3.0-8.3) days vs 2.0 (0.0-5.0) days vs 2.0 (0.0-6.0) days, p < .0001; and $32 828 ($14 711-$67 216) vs $16 227 ($0-$35 829) vs $17 844 ($0-$47 642), p < .0001. ACTH use decreased from representing 78% of first-line treatments in 2006 to 18% in 2020 (p < .0001). Sensitivity analyses confirmed the robustness of the results. SIGNIFICANCE: The gap between the cost of ACTH and the cost of oral prednisolone or vigabatrin has widened markedly from 2006 to 2020, whereas the relative proportion of ACTH use has decreased.

Load and muscle group size influence the ergogenic effect of acute caffeine intake in muscular strength, power and endurance.

INTRODUCTION: Although acute caffeine intake seems to improve muscular strength-power-endurance performance, there is scarce evidence evaluating upper vs lower-body exercises at different loads. Thus, this study aimed to examine the effects of acute caffeine intake on upper and lower-body muscular strength, power and endurance performance at different loads. METHODS: Twenty resistance-trained athletes (male/female: 10/10; age: 23 ± 4 years; body mass: 70.6 ± 15.1) participated in a double-blind, placebo-controlled, cross-over and randomized study. Participants were provided with either 3 mg/kg of body mass of caffeine or maltodextrin (placebo). Sixty minutes after ingestion, they performed muscular strength and power assessment for bench press and back squat exercise at 25%, 50%, 75% and 90% 1-repetition-maximum (1RM), performing 3, 2, 1 and 1 repetitions respectively, followed by muscular endurance assessment for both exercises at 65% and 85% 1RM performing until task failure. Isometric handgrip, isometric mid-thigh pull and vertical jump tests were also performed. RESULTS: In muscular strength and power, compared to placebo, caffeine improved mean velocity (P = 0.045; pη2 = 0.101), mean power (P = 0.049; pη2 = 0.189) and rate of force development (RFD, P = 0.032; pη2 = 0.216), particularly in back squat exercise at 75% and 90% 1RM where mean velocity increased by 5-7% (P = 0.48-0.038; g = 0.348-1.413), mean power by 6-8% (P = 0.050-0.032; g = 0.547-0.818) and RFD by 17-97% (P = 0.042-0.046; g = 1.436-1.196). No differences were found in bench press exercise. In muscular endurance, caffeine improved the number of repetitions in all exercises and loads (P = 0.003; pη2 = 0.206), but only in back squat exercise at 85% 1RM, caffeine increased mean and peak velocity (8-9%, P = 0.006-0.004; g = 2.029-2.075), mean and peak power (10-13%, P = 0.006-0.003; g = 0.888-1.151) and force peak (3%, P = 0.009; g = 0.247). CONCLUSIONS: Acute caffeine intake (3 mg/kg) improved muscular strength, power and endurance performance, revealing a more pronounced effect at high-loads (≥ 75% 1RM) and in lower-body (back squat) than in upper-body exercise (bench press) according to muscle group size.

Approaching autozygosity in a small pedigree of Gochu Asturcelta pigs.

BACKGROUND: In spite of the availability of single nucleotide polymorphism (SNP) array data, differentiation between observed homozygosity and that caused by mating between relatives (autozygosity) introduces major difficulties. Homozygosity estimators show large variation due to different causes, namely, Mendelian sampling, population structure, and differences among chromosomes. Therefore, the ascertainment of how inbreeding is reflected in the genome is still an issue. The aim of this research was to study the usefulness of genomic information for the assessment of genetic diversity in the highly endangered Gochu Asturcelta pig breed. Pedigree depth varied from 0 (founders) to 4 equivalent discrete generations (t). Four homozygosity parameters (runs of homozygosity, FROH; heterozygosity-rich regions, FHRR; Li and Horvitz's, FLH; and Yang and colleague's FYAN) were computed for each individual, adjusted for the variability in the base population (BP; six individuals) and further jackknifed over autosomes. Individual increases in homozygosity (depending on t) and increases in pairwise homozygosity (i.e., increase in the parents' mean) were computed for each individual in the pedigree, and effective population size (Ne) was computed for five subpopulations (cohorts). Genealogical parameters (individual inbreeding, individual increase in inbreeding, and Ne) were used for comparisons. RESULTS: The mean F was 0.120 ± 0.074 and the mean BP-adjusted homozygosity ranged from 0.099 ± 0.081 (FLH) to 0.152 ± 0.075 (FYAN). After jackknifing, the mean values were slightly lower. The increase in pairwise homozygosity tended to be twofold higher than the corresponding individual increase in homozygosity values. When compared with genealogical estimates, estimates of Ne obtained using FYAN tended to have low root-mean-squared errors. However, Ne estimates based on increases in pairwise homozygosity using both FROH and FHRR estimates of genomic inbreeding had lower root-mean-squared errors. CONCLUSIONS: Parameters characterizing homozygosity may not accurately depict losses of variability in small populations in which breeding policy prohibits matings between close relatives. After BP adjustment, the performance of FROH and FHRR was highly consistent. Assuming that an increase in homozygosity depends only on pedigree depth can lead to underestimating it in populations with shallow pedigrees. An increase in pairwise homozygosity computed from either FROH or FHRR is a promising approach for characterizing autozygosity.

Residual effects of 12 weeks of power-oriented resistance training plus high-intensity interval training on muscle dysfunction, systemic oxidative damage, and antioxidant capacity after 10 months of training cessation in older people with COPD.

OBJECTIVE: This study aimed to assess the residual effects of a 12-week concurrent training program (power training + high-intensity interval training) in older adults with chronic obstructive pulmonary disease (COPD). METHODS: A total of 21 older adults with COPD [intervention (INT), n = 8; control (CON), n = 13; 76.9 ± 6.8 years] were assessed at baseline and 10 months after the completion of the intervention by the short physical performance battery (SPPB), health-related quality of life (EQ-5D-5L), vastus lateralis muscle thickness (MT), peak pulmonary oxygen uptake (peak VO2 ) and peak work rate (Wpeak ), early and late isometric rate of force development (RFD), leg and chest press maximum muscle power (LPmax and CPmax ), and systemic oxidative damage and antioxidant capacity. RESULTS: Compared to baseline, after 10 months of detraining, the INT group presented increased SPPB (∆ = 1.0 point), health-related quality of life (∆ = 0.07 points), early RFD (∆ = 834 N∙s-1 ), LPmax (∆ = 62.2 W), and CPmax (∆ = 16.0 W) (all p < 0.05). In addition, a positive effect was noted in INT compared to CON regarding MT and Wpeak (both p < 0.05). No between-group differences were reported in peak VO2 , late RFD, systemic oxidative damage, and antioxidant capacity from baseline to 10 months after the completion of the intervention (all p > 0.05). CONCLUSIONS: Twelve weeks of concurrent training were enough to ensure improved physical function, health-related quality of life, early RFD and maximum muscle power and to preserve MT and Wpeak but not peak VO2 , late RFD, systemic oxidative damage and antioxidant capacity in the subsequent 10 months of detraining in older adults with COPD.

Genomic Analysis Enlightens Agaricales Lifestyle Evolution and Increasing Peroxidase Diversity.

As actors of global carbon cycle, Agaricomycetes (Basidiomycota) have developed complex enzymatic machineries that allow them to decompose all plant polymers, including lignin. Among them, saprotrophic Agaricales are characterized by an unparalleled diversity of habitats and lifestyles. Comparative analysis of 52 Agaricomycetes genomes (14 of them sequenced de novo) reveals that Agaricales possess a large diversity of hydrolytic and oxidative enzymes for lignocellulose decay. Based on the gene families with the predicted highest evolutionary rates-namely cellulose-binding CBM1, glycoside hydrolase GH43, lytic polysaccharide monooxygenase AA9, class-II peroxidases, glucose-methanol-choline oxidase/dehydrogenases, laccases, and unspecific peroxygenases-we reconstructed the lifestyles of the ancestors that led to the extant lignocellulose-decomposing Agaricomycetes. The changes in the enzymatic toolkit of ancestral Agaricales are correlated with the evolution of their ability to grow not only on wood but also on leaf litter and decayed wood, with grass-litter decomposers as the most recent eco-physiological group. In this context, the above families were analyzed in detail in connection with lifestyle diversity. Peroxidases appear as a central component of the enzymatic toolkit of saprotrophic Agaricomycetes, consistent with their essential role in lignin degradation and high evolutionary rates. This includes not only expansions/losses in peroxidase genes common to other basidiomycetes but also the widespread presence in Agaricales (and Russulales) of new peroxidases types not found in wood-rotting Polyporales, and other Agaricomycetes orders. Therefore, we analyzed the peroxidase evolution in Agaricomycetes by ancestral-sequence reconstruction revealing several major evolutionary pathways and mapped the appearance of the different enzyme types in a time-calibrated species tree.

Nitric oxide signalling in roots is required for MYB72-dependent systemic resistance induced by Trichoderma volatile compounds in Arabidopsis.

Volatile compounds (VCs) of Trichoderma fungi trigger induced systemic resistance (ISR) in Arabidopsis that is effective against a broad spectrum of pathogens. The root-specific transcription factor MYB72 is an early regulator of ISR and also controls the activation of iron-deficiency responses. Nitric oxide (NO) is involved in the regulation of MYB72-dependent iron-deficiency responses in Arabidopsis roots, but the role of NO in the regulation of MYB72 and ISR by Trichoderma VCs remains unexplored. Using in vitro bioassays, we applied Trichoderma VCs to Arabidopsis seedlings. Plant perception of Trichoderma VCs triggered a burst of NO in Arabidopsis roots. By suppressing this burst using an NO scavenger, we show the involvement of NO in Trichoderma VCs-mediated regulation of MYB72 expression. Using an NO scavenger and the Arabidopsis lines myb72 and nia1nia2 in in planta bioassays, we demonstrate that NO signalling is required in the roots for activation of Trichoderma VCs-mediated ISR against the leaf pathogen Botrytis cinerea. Analysis of the defence-related genes PR1 and PDF1.2 points to the involvement of root NO in priming leaves for enhanced defence. Our results support a key role of root NO signalling in the regulation of MYB72 expression during the activation of ISR by Trichoderma VCs.

Small mammals (Insectivora, Rodentia, Lagomorpha) from the Early Pleistocene hominin-bearing site of Dmanisi (Georgia).

Small mammals (insectivores, rodents, and lagomorphs) from Dmanisi are here reviewed for the first time and used as a tool for paleoenvironmental proxies. The small mammal faunal list is composed of shrews (Beremendia fissidens, cf. Beremendia minor, Crocidura kornfeldi), hamsters (Cricetulus sp., Allocricetus bursae), gerbils (Parameriones aff. obeidiyensis), murids (Apodemus cf. atavus), arvicolids (Mimomys pliocaenicus, Mimomys aff. pusillus), and pikas (Ochotona sp.). A paleoenvironmental reconstruction based on the habitat weighting method has been applied to the rodent assemblage. According to this method, the most common elements indicate an open-dry habitat (36.5%), followed by water edge (25.7%) and rocky (21.0%) elements. Open-wet (15.5%) and woodland elements (1.3%) are rare. Therefore, the habitat occupied by the hominids of Dmanisi was characterized by the prevalence of arid conditions, from steppe or semi-desert to open Mediterranean forest, with stony or rocky substrate and bushy areas. The presence of permanent aquatic environments is also documented. From a biogeographic point of view, the small mammal community from Dmanisi is composed mainly by Western or Central Asian elements, with a poor representation of European elements (Mimomys, Apodemus). It is concluded that Dmanisi hominins most possibly had ecological requirements which were different from those of the Early Pleistocene hominins from Western Europe, which settled on wetter habitats. It could be also possible that Dmanisi hominins entered Southern Caucasus at an interglacial phase before the deposition of the Dmanisi site.

Unusual pseudocapacitive lithium-ion storage on defective Co3O4nanosheets.

Secondary lithium-ion batteries are restricted in large-scale applications including power grids and long driving electric vehicles owing to the low specific capacity of conventional intercalation anodes possessing sluggish Li-ion diffusion kinetics. Herein, we demonstrate an unusual pseudocapacitive lithium-ion storage on defective Co3O4nanosheet anodes for high-performance rechargeable batteries. Cobalt-oxide nanosheets presented here composed of various defects including vacancies, dislocations and grain boundaries. Unique 2D holey microstructure enabled efficient charge transport as well as provided room for volume expansions associated with lithiation-delithiation process. These defective anodes exhibited outstanding pseudocapacitance (up to 87%), reversible capacities (1490 mAh g-1@ 25 mA g-1), rate capability (592 mAh g-1@ 30 A g-1), stable cycling (85% after 500 cycles @ 1 A g-1) and columbic efficiency (∼100%). Exceptional Li-ion storage phenomena in defective Co3O4nanosheets is accredited to the pseudocapacitive nature of conversion reaction resulting from ultrafast Li-ion diffusion through various crystal defects. The demonstrated approach of defect-induced pseudocapacitance can also be protracted for various low-cost and/or eco-friendly transition metal-oxides for next-generation rechargeable batteries.

Neuromuscular adaptations after 12 weeks of light- vs. heavy-load power-oriented resistance training in older adults.

This study aimed to determine the specific adaptations provoked by power-oriented resistance training using light (LL-PT, 40% 1-RM) vs. heavy (HL-PT, 80% 1-RM) loads in older adults. Using a randomized within-subject study design, 45 older adults (>65 years) completed an 8-week control period (CTR) followed by 12 weeks of unilateral LL-PT vs. HL-PT on a leg press. The 1-RM, theoretical force at zero velocity (F0 ), maximal unloaded velocity (V0 ), and maximal muscle power (Pmax ) were determined through a force-velocity relationship test. Isometrically, the rate of force development (RFD) and the corresponding muscle excitation of the knee extensor muscles were assessed. In addition, muscle cross-sectional area (CSA) and architecture of two quadriceps muscles were determined. Changes after CTR, LL-PT and HL-PT were compared using linear mixed models. HL-PT provoked greater improvements in 1-RM and F0 (effect size (ES) = 0.55-0.68; p < 0.001) than those observed after LL-PT (ES = 0.27-0.47; p ≤ 0.001) (post hoc treatment effect, p ≤ 0.057). By contrast, ES of changes in V0 was greater in LL-PT compared to HL-PT (ES = 0.71, p < 0.001 vs. ES = 0.39, p < 0.001), but this difference was not statistically significant. Both power training interventions elicited a moderate increase in Pmax (ES = 0.65-0.69, p < 0.001). Only LL-PT improved early RFD (ie, ≤100 ms) and muscle excitation (ES = 0.36-0.60, p < 0.05). Increased CSA were noted after both power training programs (ES = 0.13-0.35, p < 0.035), whereas pennation angle increased only after HL-PT (ES = 0.37, p = 0.004). In conclusion, HL-PT seems to be more effective in improving the capability to generate large forces, whereas LL-PT appears to trigger greater gains in movement velocity in older adults. However, both interventions promoted similar increases in muscle power as well as muscle hypertrophy.

Peroxidase evolution in white-rot fungi follows wood lignin evolution in plants.

A comparison of sequenced Agaricomycotina genomes suggests that efficient degradation of wood lignin was associated with the appearance of secreted peroxidases with a solvent-exposed catalytic tryptophan. This hypothesis is experimentally demonstrated here by resurrecting ancestral fungal peroxidases, after sequence reconstruction from genomes of extant white-rot Polyporales, and evaluating their oxidative attack on the lignin polymer by state-of-the-art analytical techniques. Rapid stopped-flow estimation of the transient-state constants for the 2 successive one-electron transfers from lignin to the peroxide-activated enzyme (k2app and k3app ) showed a progressive increase during peroxidase evolution (up to 50-fold higher values for the rate-limiting k3app ). The above agreed with 2-dimensional NMR analyses during steady-state treatments of hardwood lignin, showing that its degradation (estimated from the normalized aromatic signals of lignin units compared with a control) and syringyl-to-guaiacyl ratio increased with the enzyme evolutionary distance from the first peroxidase ancestor. More interestingly, the stopped-flow estimations of electron transfer rates also showed how the most recent peroxidase ancestors that already incorporated the exposed tryptophan into their molecular structure (as well as the extant lignin peroxidase) were comparatively more efficient at oxidizing hardwood (angiosperm) lignin, while the most ancestral "tryptophanless" enzymes were more efficient at abstracting electrons from softwood (conifer) lignin. A time calibration of the ancestry of Polyporales peroxidases localized the appearance of the first peroxidase with a solvent-exposed catalytic tryptophan to 194 ± 70 Mya, coincident with the diversification of angiosperm plants characterized by the appearance of dimethoxylated syringyl lignin units.

Preseason Injury Characteristics in Spanish Professional Futsal Players: The LNFS Project.

ABSTRACT: López-Segovia, M, Vivo Fernández, I, Herrero Carrasco, R, and Pareja Blanco, F. Preseason injury characteristics in Spanish professional futsal players: the National Futsal League (LFNS) project. J Strength Cond Res 36(1): 232-237, 2022-This study aimed to examine the incidence of injuries and their characteristics among professional Spanish futsal players during the preseason period and to compare injury-related variables in the context of both competition and training. Eleven futsal teams belonging to the First and Second Spanish Division and 161 players participated in the study. Characteristics of injuries, including type, location, cause and time of injury, injury recurrence, and duration of absence, were recorded. A total of 62 injuries were reported; injury rates of 9.9 (95% confidence interval [CI]: 7.0-12.5) injuries/1,000 training hours and 61.1 (95% CI: 25.7-96.5) injuries/1,000 match hours were collected. These data indicate a mean of 5.64 ± 2.66 injuries per team during the preseason period. Of these injuries, 92.1% involved the lower limbs. When data from training and competition were analyzed together, the highest incidence of injuries affected the ankle (21%), followed by the hip/groin and knee (19.4% each). The most common type of injury was muscle rupture/tear/strain (29.0%). During training, the highest percentage of injuries were located in the knee (23.9%), followed by the ankle and hip/groin (21.7% in each case), while during matches, the thigh (35.7%) followed by the ankle (21.4%) was the regions most affected. A significant relationship (p = 0.008) was observed between injury cause (without contact, with other player, with the ball, and others) and injury context (training, match). To conclude, the results of this study suggest the need for injury prevention protocols focuses on the ankle and the knee joints and muscle strain prevention.

A coumarin exudation pathway mitigates arbuscular mycorrhizal incompatibility in Arabidopsis thaliana.

KEY MESSAGE: Overexpression of genes involved in coumarin production and secretion can mitigate mycorrhizal incompatibility in nonhost Arabidopsis plants. The coumarin scopoletin, in particular, stimulates pre-penetration development and metabolism in mycorrhizal fungi. Although most plants can benefit from mutualistic associations with arbuscular mycorrhizal (AM) fungi, nonhost plant species such as the model Arabidopsis thaliana have acquired incompatibility. The transcriptional response of Arabidopsis to colonization by host-supported AM fungi switches from initial AM recognition to defense activation and plant growth antagonism. However, detailed functional information on incompatibility in nonhost-AM fungus interactions is largely missing. We studied interactions between host-sustained AM fungal networks of Rhizophagus irregularis and 18 Arabidopsis genotypes affected in nonhost penetration resistance, coumarin production and secretion, and defense (salicylic acid, jasmonic acid, and ethylene) and growth hormones (auxin, brassinosteroid, cytokinin, and gibberellin). We demonstrated that root-secreted coumarins can mitigate incompatibility by stimulating fungal metabolism and promoting initial steps of AM colonization. Moreover, we provide evidence that major molecular defenses in Arabidopsis do not operate as primary mechanisms of AM incompatibility nor of growth antagonism. Our study reveals that, although incompatible, nonhost plants can harbor hidden tools that promote initial steps of AM colonization. Moreover, it uncovered the coumarin scopoletin as a novel signal in the pre-penetration dialogue, with possible implications for the chemical communication in plant-mycorrhizal fungi associations.

Differences in microbial community response to nitrogen fertilization result in unique enzyme shifts between arbuscular and ectomycorrhizal-dominated soils.

While the effect of nitrogen (N) deposition on belowground carbon (C) cycling varies, emerging evidence shows that forest soils dominated by trees that associate with ectomycorrhizal fungi (ECM) store more C than soils dominated by trees that associate with arbuscular mycorrhizae (AM) with increasing N deposition. We hypothesized that this is due to unique nutrient cycling responses to N between AM and ECM-dominated soils. ECM trees primarily obtain N through fungal mining of soil organic matter subsidized by root-C. As such, we expected the largest N-induced responses of C and N cycling to occur in ECM rhizospheres and be driven by fungi. Conversely, as AM trees rely on bacterial scavengers in bulk soils to cycle N, we predicted the largest AM responses to be driven by shifts in bacteria and occur in bulk soils. To test this hypothesis, we measured microbial community composition, metatranscriptome profiles, and extracellular enzyme activity in bulk, rhizosphere, and organic horizon (OH) soils in AM and ECM-dominated soils at Bear Brook Watershed in Maine, USA. After 27 years of N fertilization, fungal community composition shifted across ECM soils, but bacterial communities shifted across AM soils. These shifts were mirrored by enhanced C relative to N mining enzyme activities in both mycorrhizal types, but this occurred in different soil fractions. In ECM stands these shifts occurred in rhizosphere soils, but in AM stands they occurred in bulk soils. Additionally, ECM OH soils exhibited the opposite response with declines in C relative to N mining. As rhizosphere soils account for only a small portion of total soil volume relative to bulk soils, coupled with declines in C to N enzyme activity in ECM OH soils, we posit that this may partly explain why ECM soils store more C than AM soils as N inputs increase.

Cost-effectiveness of adrenocorticotropic hormone versus oral steroids for infantile spasms.

OBJECTIVE: To compare the effectiveness and cost-effectiveness of adrenocorticotropic hormone (ACTH) and oral steroids as first-line treatment for infantile spasm resolution, we performed a systematic review, meta-analysis, and cost-effectiveness study. METHODS: A decision analysis model was populated with effectiveness data from a systematic review and meta-analysis of existing literature and cost data from publicly available prices. Effectiveness was defined as the probability of clinical spasm resolution 14 days after treatment initiation. RESULTS: We included 21 studies with a total of 968 patients. The effectiveness of ACTH was not statistically significantly different from that of oral steroids (.70, 95% confidence interval [CI] = .60-.79 vs. .63, 95% CI = .56-.70; p = .28). Considering only the three available randomized trials with a total of 185 patients, the odds ratio of spasm resolution at 14 days with ACTH compared to high-dose prednisolone (4-8 mg/kg/day) was .92 (95% CI = .34-2.52, p = .87). Adjusting for potential publication bias, estimates became even more favorable to high-dose prednisolone. Using US prices, the more cost-effective treatment was high-dose prednisolone, with an incremental cost-effectiveness ratio (ICER) of $333 per case of spasms resolved, followed by ACTH, with an ICER of $1 432 200 per case of spasms resolved. These results were robust to multiple sensitivity analyses and different assumptions. Prednisolone at 4-8 mg/kg/day was more cost-effective than ACTH under a wide range of assumptions. SIGNIFICANCE: For infantile spasm resolution 2 weeks after treatment initiation, current evidence does not support the preeminence of ACTH in terms of effectiveness and, especially, cost-effectiveness.

Clinical presentation of new onset refractory status epilepticus in children (the pSERG cohort).

OBJECTIVE: We aimed to characterize the clinical profile and outcomes of new onset refractory status epilepticus (NORSE) in children, and investigated the relationship between fever onset and status epilepticus (SE). METHODS: Patients with refractory SE (RSE) between June 1, 2011 and October 1, 2016 were prospectively enrolled in the pSERG (Pediatric Status Epilepticus Research Group) cohort. Cases meeting the definition of NORSE were classified as "NORSE of known etiology" or "NORSE of unknown etiology." Subgroup analysis of NORSE of unknown etiology was completed based on the presence and time of fever occurrence relative to RSE onset: fever at onset (≤24 h), previous fever (2 weeks-24 h), and without fever. RESULTS: Of 279 patients with RSE, 46 patients met the criteria for NORSE. The median age was 2.4 years, and 25 (54%) were female. Forty (87%) patients had NORSE of unknown etiology. Nineteen (48%) presented with fever at SE onset, 16 (40%) had a previous fever, and five (12%) had no fever. The patients with preceding fever had more prolonged SE and worse outcomes, and 25% recovered baseline neurological function. The patients with fever at onset were younger and had shorter SE episodes, and 89% recovered baseline function. SIGNIFICANCE: Among pediatric patients with RSE, 16% met diagnostic criteria for NORSE, including the subcategory of febrile infection-related epilepsy syndrome (FIRES). Pediatric NORSE cases may also overlap with refractory febrile SE (FSE). FIRES occurs more frequently in older children, the course is usually prolonged, and outcomes are worse, as compared to refractory FSE. Fever occurring more than 24 h before the onset of seizures differentiates a subgroup of NORSE patients with distinctive clinical characteristics and worse outcomes.