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Large-scale mining of low-grade ores is energy-intensive and generates vast wastes. It has limited suitability for production of specialist metals that are required in relatively small quantities. An approach that limits environmental impact by restricting mining to high-grade deposits requires the investigation of small ore deposits as alternative sources of metals. The return on investment from small deposits is incompatible with the expensive surveys needed to secure investment and the high costs of managing risk. But increasing energy and transport costs may create space in the market for small-deposit mining with highly-competitive technological solutions. It can be argued that small-deposit mining is ethical because it must involve cooperation between mining companies and local residents who share a collective expectation and responsibility for their quality of life. However, small-deposit mining tends to be a limited, short-term initiative, which requires consideration of the extended ‘afterlife’ of mines. This manuscript is the culmination of five years of cross-sector dialogue and stakeholder engagement activities. It debates what constitutes a small deposit and describes the interactions between mining and manufacturing, investment, environment and society. It reaches the conclusion that technological innovations will support the re-emergence of small deposit mining as an important part of a diverse raw materials production sector. We do not suggest a return to past approaches, to mining of small, high-grade deposits, but a consideration of alternative narratives of localised, community-orientated mining processes, thus giving social, economic and environmental context to the needs of the present day.

Abstract During recent decades, changes in lifestyle have led to widespread nutritional obesity and its related complications. Remodelling adipose tissue as a therapeutic goal for obesity and its complications has attracted much attention and continues to be actively explored. The endothelium lines all blood vessels and is close to all cells, including adipocytes. The endothelium has been suggested to act as a paracrine organ. We explore the role of endothelial insulin-like growth factor-1 receptor (IGF-1R), as a paracrine modulator of white adipose phenotype. We show that a reduction in endothelial IGF-1R expression in the presence of high-fat feeding in male mice leads to depot-specific beneficial white adipose tissue remodelling, increases whole-body energy expenditure and enhances insulin sensitivity via a non-cell-autonomous paracrine mechanism. We demonstrate that increased endothelial malonate may be contributory and that malonate prodrugs have potentially therapeutically relevant properties in the treatment of obesity-related metabolic disease.

Abstract Feeling a texture typically involves sliding the fingers of a hand across that surface or rubbing the surface between the thumb and another digit. Texture signals appear to be integrated across the digits of a hand with perceived roughness at one finger swayed in the direction of texture touched by another finger of the same hand. To date, one study has reported similar integrative effects when the pairs of digits belong to different hands. This contrasts with observations from studies of tactile detection and tactile attention where the patterns of interactions between the digits depend on whether the digits belong to the same hand or not. The present experiments revisit the question of hand identity on multidigit roughness perception using two interval forced choice (2IFC) discrimination and single interval absolute magnitude estimation (AME). Pairs of tactile gratings were actively touched using the thumb and index fingers from the same or different hands. Attention was directed towards roughness at the thumb and index finger sensations were to be ignored. For both discrimination and ratings tasks, roughness perceived at the thumb varied with the textures touched by the index finger suggesting integration of roughness cues from the two digits. This integration occurred despite differences in the two tasks such as working memory requirements. Notably, roughness signals were integrated when originating in pairs of digits on the same hand but not when from different hands. These findings add to a body of evidence based on experiments using different stimuli and tasks, suggesting that hand identity affects interactions across the digits.

Abstract The pathways involved in the pathophysiology of fetal growth restriction (FGR) and small for gestational age (SGA) are incompletely understood. We conduct a systematic review to identify metabolomic signatures in maternal and newborn tissues and body fluids samples associated with FGR/SGA. Here, we report that 825 non-duplicated metabolites were significantly altered across the 48 included studies using 10 different human biological samples, of which only 56 (17 amino acids, 12 acylcarnitines, 11 glycerophosphocholines, six fatty acids, two hydroxy acids, and eight other metabolites) were significantly and consistently up- or down-regulated in more than one study. Three amino acid metabolism-related pathways and one related with lipid metabolism are significantly associated with FGR and/or SGA: biosynthesis of unsaturated fatty acids in umbilical cord blood, and phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine biosynthesis, and phenylalanine metabolism in newborn dried blood spot. Significantly enriched metabolic pathways were not identified in the remaining biological samples. Whether these metabolites are in the causal pathways or are biomarkers of fetal nutritional deficiency needs to be explored in large, well-phenotyped cohorts.

Abstract We examined how resistance exercise (RE), cycling exercise and disuse atrophy affect myosin heavy chain (MyHC) protein fragmentation. The 1boutRE study involved younger men (n = 8; 5 ± 2 years of RE experience) performing a lower body RE bout with vastus lateralis (VL) biopsies being obtained prior to and acutely following exercise. With the 10weekRT study, VL biopsies were obtained in 36 younger adults before and 24 h after their first/naïve RE bout. Participants also engaged in 10 weeks of resistance training and donated VL biopsies before and 24 h after their last RE bout. VL biopsies were also examined in an acute cycling study (n = 7) and a study involving 2 weeks of leg immobilization (n = 20). In the 1boutRE study, fragmentation of all MyHC isoforms (MyHCTotal) increased 3 h post‐RE (∼200%, P = 0.018) and returned to pre‐exercise levels by 6 h post‐RE. Interestingly, a greater magnitude increase in MyHC type IIa versus I isoform fragmentation occurred 3 h post‐RE (8.6 ± 6.3‐fold vs. 2.1 ± 0.7‐fold, P = 0.018). In 10weekRT participants, the first/naïve and last RE bouts increased MyHCTotal fragmentation 24 h post‐RE (+65% and +36%, P

The emergence of plant pathogens is often associated with waves of unique evolutionary and epidemiological events. Xanthomonas hortorum pv. gardneri is one of the major pathogens causing bacterial spot disease of tomatoes. After its first report in the 1950s, there were no formal reports on this pathogen until the 1990s, despite active global research on the pathogens that cause tomato and pepper bacterial spot disease. Given the recently documented global distribution of X. hortorum pv. gardneri, our objective was to examine genomic diversification associated with its emergence. We sequenced the genomes of X. hortorum pv. gardneri strains collected in eight countries to examine global population structure and pathways of emergence using phylodynamic analysis. We found that strains isolated post-1990 group by region of collection and show minimal impact of recombination on genetic variation. A period of rapid geographic expansion in X. hortorum pv. gardneri is associated with acquisition of a large plasmid conferring copper tolerance by horizontal transfer and coincides with the burgeoning hybrid tomato seed industry through the 1980s. The ancestry of X. hortorum pv. gardneri is consistent with introduction to hybrid tomato seed production and dissemination during the rapid increase in trade of hybrid seeds. [Figure: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Abstract Cryptic fungal pathogens pose disease management challenges due to their morphological resemblance to known pathogens. Here, we investigated the genomes and phenotypes of 53 globally distributed isolates of Aspergillus section Nidulantes fungi and found 30 clinical isolates—including four isolated from COVID-19 patients—were A. latus, a cryptic pathogen that originated via allodiploid hybridization. Notably, all A. latus isolates were misidentified. A. latus hybrids likely originated via a single hybridization event during the Miocene and harbor substantial genetic diversity. Transcriptome profiling of a clinical isolate revealed that both parental subgenomes are actively expressed and respond to environmental stimuli. Characterizing infection-relevant traits—such as drug resistance and growth under oxidative stress—revealed distinct phenotypic profiles among A. latus hybrids compared to parental and closely related species. Moreover, we identified four features that could aid A. latus taxonomic identification. Together, these findings deepen our understanding of the origin of cryptic pathogens.

Abstract While total RNA concentrations putatively represent ribosome content, there is a need to homologize various quantification approaches. Thus, total RNA concentrations ([RNA]) provided through UV–Vis spectroscopy (UV), fluorometry‐only (Fluor), and fluorometry‐based microfluidic chip electrophoresis (MFGE) were examined in C2C12 myotubes and mouse skeletal muscle to determine if values aligned with [18S + 28S rRNA] (i.e., criterion ribosome metric). A novel antibody cocktail (termed RiboAb) was also tested and compared to [18S + 28S rRNA] in these models. In myotubes, 24‐h IGF‐1 treatments increased [18S + 28S rRNA] (~2.0‐fold) and [RNA] based on UV (~1.9‐fold), Fluor (~2.3 fold), and MFGE (~2.1‐fold). In C57BL/6 mice, 10 days of mechanical overload (MOV) elevated plantaris [18S + 28S rRNA] (~1.7‐fold) and [RNA] according to UV (~1.5‐fold), Fluor (~1.6‐fold), and MFGE (~1.8‐fold). Myotube and mouse plantaris RiboAb levels were significantly higher with IGF‐1 treatments and MOV, respectively, versus controls (1.3‐fold and 1.7‐fold, respectively), and values correlated with [18S + 28S rRNA] (r = 0.637 and r = 0.853, respectively, p ≤ 0.005). UV, Fluor, and MFGE [RNA] are seemingly valid surrogates of cell/tissue ribosome content, although each method has advantages (e.g., ease of use) and disadvantages (e.g., magnitudes of bias) discussed herein. Finally, the RiboAb cocktail may also represent ribosome content, although this should be further explored in other models.

Abstract MicroRNAs (miRNAs) are small, noncoding RNAs that play a critical role in regulating gene expression post‐transcriptionally. They are involved in various developmental and physiological processes, and their dysregulation is linked to various diseases. Skeletal muscle‐specific miRNAs, including miR‐1, play a crucial role in the development and maintenance of skeletal muscle. It has been demonstrated that the expression of miR‐1 decreases by approximately 50% in response to hypertrophic stimuli, suggesting its potential involvement in muscle hypertrophy. In our study, we hypothesize that reduction of miR‐1 levels is necessary for skeletal muscle growth due to its interaction to essential pro‐growth genes. Promoting a smaller reduction of miR‐1 levels, we observed a blunted hypertrophic response in mice undergoing a murine model of muscle hypertrophy. In addition, our results suggest that miR‐1 inhibits the expression of Itm2a, a membrane‐related protein, as potential miR‐1‐related candidate for skeletal muscle hypertrophy. While the exact mechanism in muscle hypertrophy has not been identified, our results suggest that miR‐1‐regulated membrane proteins are important for skeletal muscle hypertrophy.

ObjectiveTo describe the ocular findings, chronology of disease, and serum leptospiral titers in a group of horses, mules, and donkeys following an outbreak of leptospirosis.MethodsFifty Equidae in central North Carolina had ophthalmic examinations and serum leptospiral microscopic agglutination test (MAT) titers performed every 3–6 months for 24 months followed by a final examination at 34 months.ResultsThroughout the nearly three-year study period, 17 horses (34%; 17/49 horses) developed signs of uveitis; 20 eyes (20/34; 58.8%) of these 17 horses were visual at the initial examination, but only four eyes (11.8%) remained visual at the final examination. Serum titers (serogroups Pomona and Bratislava) in horses with uveitis were significantly elevated compared to Equidae without uveitis (p 1:800) but never developed uveitis. Water sources in the pasture were found to have high levels of leptospira.ConclusionApproximately 1/3 of horses on a farm exposed to Leptospira developed uveitis and blindness. Serum titers to L. Pomona and L. Bratislava were significantly elevated in horses with uveitis. However, despite exposure, some horses, even with very high serum titers, never developed ocular disease. These data indicates that further research is warranted to investigate the genetic and immunological aspects of the pathogenesis and susceptibility of leptospiral-associated uveitis.

Nitric oxide (NO) is a ubiquitous signaling molecule known to modulate various physiological processes, with specific implications in skeletal muscle and broader applications in exercise performance. This review focuses on the modulation of skeletal muscle function, mitochondrial adaptation and function, redox state by NO, and the effect of nitrate supplementation on exercise performance. In skeletal muscle function, NO is believed to increase the maximal shortening velocity and peak power output of muscle fibers. However, its effect on submaximal contraction is still undetermined. In mitochondria, NO may stimulate biogenesis and affect respiratory efficiency. NO also plays a role in the redox state within the skeletal muscle, partially through its interaction with respiratory chain enzymes and transcriptional regulators of antioxidant production. Nitrate supplementation leads to an increased bioavailability of NO in skeletal muscle. Thus, nitrate supplementation has been investigated for its ability to impact performance outcomes in endurance and resistance exercise. The effect of nitrate supplementation on endurance exercise is currently indecisive, although evidence indicates that it may extend the time to exhaustion in endurance exercise. Alternatively, the effect of nitrate supplementation on resistance exercise performance has been less studied. Limited research indicates that nitrate supplementation may improve repetitions to failure. Further research is needed to investigate the influence of training status, age, sex, and duration of supplementation to further elucidate the impact of nitrate supplementation on exercise performance.

Studies of extinction typically focus on unintended losses of biodiversity and culture. This study, however, examines an attempt to induce extinction of a parasite: human hookworm (Necator americanus and Ancylostoma duodenale). Our interdisciplinary approach integrates medical history and epidemiology using records created by the Jamaica Hookworm Commission of 1919–1936. We show that the attempt to induce the extinction of hookworms was driven by its perceived effects on labour productivity and consequent status as an ideological and economic threat. We use spatial epidemiology to describe the relationships between parasites, environments and the working conditions of plantation labourers. Using data from 330 locations across Jamaica in which 169,380 individuals were tested for hookworm infection we show that the prevalence of hookworm infection was higher in districts surrounding plantations. Prevalence decreased with the temperature of the coldest month, increased with the amount of rainfall in the driest month, and increased with vegetation quantity (normalised difference vegetation index). Worm burden (and thus pathology) varied greatly between individuals, even those living together; hookworm infection varied between environments, socioeconomic conditions and individuals. Nevertheless, the conditions of labour shaped the distribution of hookworms. Plantations both spread and problematised hookworms, driving efforts to bring it to extinction.

Patients with osteosarcoma (OS), a debilitating pediatric bone malignancy, have limited treatment options to combat aggressive disease. OS thrives on insulin growth factor (IGF)-mediated signaling that can facilitate cell proliferation. Previous efforts to target IGF-1R signaling were mostly unsuccessful, likely due to compensatory signaling through alternative splicing of the insulin receptor (IR) to the proliferative IR-A isoform. Here, we leverage splice-switching oligonucleotides (SSOs) to mitigate IR splicing toward the IR-B isoform. We show that SSOs can modulate cancer cell hallmarks and anoikis-resistant growth. Furthermore, we engineered the SSO sequence in an U7 snRNA packaged in an adeno-associated virus (AAV) to test the feasibility of viral vector-mediated gene therapy delivery. We noted modest increases in IR-B isoform levels after virus transduction, which prompted us to investigate the role of combinatorial treatments with dalotuzumab, an anti-IGF-1R monoclonal antibody. After observing additive impacts on phosphoprotein phosphorylation and anoikis-resistant growth with the dalotuzumab and SSO combination, we treated OS cells with dalotuzumab and the AAVrh74.U7 snRNA IR virus, which significantly slowed OS cell proliferation. While these viruses require further optimization, we highlight the potential for SSO therapy and viral vector delivery, as it may offer new treatment avenues for OS patients and be translated to other cancers.

Objective The purpose of this study was to examine the acute effects of a multi-ingredient, low calorie dietary supplement (MIDS, XTEND® Healthy Hydration) on 5-kilometer (5-km) time trial performance and blood electrolyte concentrations compared to a carbohydrate-electrolyte beverage (CE, GATORADE® Thirst Quencher) and distilled water (W).Methods During visit 1 (V1), participants (10 men and 10 women, 20–35 years old, BMI ≤ 29 kg/m2, recreationally active) reported to the laboratory whereby the following tests were performed: i) height and weight measurements, ii) body composition analysis, iii) treadmill testing to measure maximal aerobic capacity, and iv) 5-km time trial familiarization. The second visit (V2) was one week after V1 in the morning (0600 – 0900) and participants arrived 12–14 h fasted (no food or drink). The first battery of assessments (V2-T1) included nude body mass, urine specific gravity (USG), a profile of mood states (POMS) questionnaire, and the completion of a visual analogue scale (VAS) questionnaire to quantify cramping. Then heart rate (HR), blood pressure (BP), total body hydration (via bioelectrical impedance spectroscopy [BIS]) were examined. Finally, a measurement of blood markers via finger stick was performed. Participants consumed a randomized beverage (16 fl. oz. of MIDS, 16 fl. oz. of W, or 16 fl. oz. of CE) within 3 min followed by a 45-min rest. Following the rest period, a second battery (V2-T2) was performed whereby participants’ USG was assessed and they completed the POMS and VAS questionnaires, and HR, BP, and blood markers were measured. The participants then performed a 5-km treadmill time trial. Immediately following the 5-km time trial, participants completed a third testing battery (V2-T3) that began with blood markers, HR and BP assessments, followed by nude body weight assessment, and the POMS and VAS questionnaires. After 60 min, a fourth battery (V2-T4) was performed that included HR, BP, and blood markers. After sitting quietly for another 60 min a fifth battery assessment was performed (V2-T5) that included participants’ USG, POMS and VAS questionnaires, HR, BP, blood markers, and total body hydration. Visits 3 (V3) and 4 (V4) followed the same protocol except a different randomized drink (16 oz. of CE, MIDS, or W) was consumed; all of which were separated by approximately one week.Results No differences occurred between conditions for 5-km time trial completion, indirect calorimetry outcomes during 5-km time trials, USG, or nude mass measurements (p > 0.05 for all relevant statistical tests). However, blood potassium and the sodium/potassium ratio displayed significant interactions (p

Comensal Bacteroidota (Bacteroidota) and Enterobacteriacea are often linked to gut inflammation. However, the causes for variability of pro-inflammatory surface antigens that affect gut commensal/opportunistic dualism in Bacteroidota remain unclear. By using the classical lipopolysaccharide/O-antigen ‘rfb operon’ in Enterobacteriaceae as a surface antigen model (5-rfb-gene-cluster rfbABCDX), and a recent rfbA-typing strategy for strain classification, we characterized the integrity and conservancy of the entire rfb operon in Bacteroidota. Through exploratory analysis of complete genomes and metagenomes, we discovered that most Bacteroidota have the rfb operon fragmented into nonrandom patterns of gene-singlets and doublets/triplets, termed ‘rfb-gene-clusters’, or rfb-‘minioperons’ if predicted as transcriptional. To reflect global operon integrity, contiguity, duplication, and fragmentation principles, we propose a six-category (infra/supra-numerary) cataloging system and a Global Operon Profiling System for bacteria. Mechanistically, genomic sequence analyses revealed that operon fragmentation is driven by intra-operon insertions of predominantly Bacteroides-DNA (thetaiotaomicron/fragilis) and likely natural selection in gut-wall specific micro-niches or micropathologies. Bacteroides-insertions, also detected in other antigenic operons (fimbriae), but not in operons deemed essential (ribosomal), could explain why Bacteroidota have fewer KEGG-pathways despite large genomes. DNA insertions, overrepresenting DNA-exchange-avid (Bacteroides) species, impact our interpretation of functional metagenomics data by inflating by inflating gene-based pathway inference and by overestimating ‘extra-species’ abundance. Of disease relevance, Bacteroidota species isolated from cavitating/cavernous fistulous tract (CavFT) microlesions in Crohn’s Disease have supra-numerary fragmented operons, stimulate TNF-alpha from macrophages with low potency, and do not induce hyperacute peritonitis in mice compared to CavFT Enterobacteriaceae. The impact of ‘foreign-DNA’ insertions on pro-inflammatory operons, metagenomics, and commensalism/opportunism requires further studies to elucidate their potential for novel diagnostics and therapeutics, and to elucidate the role of co-existing pathobionts in Crohn’s disease microlesions.

Position statement The International Society of Sports Nutrition (ISSN) provides an objective and critical review of the use of a ketogenic diet in healthy exercising adults, with a focus on exercise performance and body composition. However, this review does not address the use of exogenous ketone supplements. The following points summarize the position of the ISSN:1. A ketogenic diet induces a state of nutritional ketosis, which is generally defined as serum ketone levels above 0.5 mM. While many factors can impact what amount of daily carbohydrate intake will result in these levels, a broad guideline is a daily dietary carbohydrate intake of less than 50 grams per day.2. Nutritional ketosis achieved through carbohydrate restriction and a high dietary fat intake is not intrinsically harmful and should not be confused with ketoacidosis, a life-threatening condition most commonly seen in clinical populations and metabolic dysregulation.3. A ketogenic diet has largely neutral or detrimental effects on athletic performance compared to a diet higher in carbohydrates and lower in fat, despite achieving significantly elevated levels of fat oxidation during exercise (~1.5 g/min).4. The endurance effects of a ketogenic diet may be influenced by both training status and duration of the dietary intervention, but further research is necessary to elucidate these possibilities. All studies involving elite athletes showed a performance decrement from a ketogenic diet, all lasting six weeks or less. Of the two studies lasting more than six weeks, only one reported a statistically significant benefit of a ketogenic diet.5. A ketogenic diet tends to have similar effects on maximal strength or strength gains from a resistance training program compared to a diet higher in carbohydrates. However, a minority of studies show superior effects of non-ketogenic comparators.6. When compared to a diet higher in carbohydrates and lower in fat, a ketogenic diet may cause greater losses in body weight, fat mass, and fat-free mass, but may also heighten losses of lean tissue. However, this is likely due to differences in calorie and protein intake, as well as shifts in fluid balance.7. There is insufficient evidence to determine if a ketogenic diet affects males and females differently. However, there is a strong mechanistic basis for sex differences to exist in response to a ketogenic diet.

We previously reported that the DNA alkylator and transcriptional-blocking chemotherapeutic agent trabectedin enhances oncolytic herpes simplex viroimmunotherapy in human sarcoma xenograft models, though the mechanism remained to be elucidated. Here we report trabectedin disrupts the intrinsic cellular antiviral response which increases viral transcript presence in the human tumor cells. We also extended our synergy findings to syngeneic murine sarcoma models, which are poorly susceptible to virus infection. In the absence of robust virus replication, we found trabectedin enhanced viroimmunotherapy efficacy by reducing infiltrating immunosuppressive CD4 T and myeloid cells and stimulating granzyme expression in infiltrating T and natural killer cells to cause immune-mediated tumor regressions. Thus, trabectedin enhances both the direct virus-mediated killing of tumor cells and the viral-induced activation of cytotoxic effector lymphocytes to cause tumor regressions across models. Our data provide a strong rationale for clinical translation as both mechanisms should be simultaneously active in human patients.

Abstract Limb immobilization causes rapid declines in muscle strength and mass. Given the role of the nervous system in immobilization‐induced weakness, targeted interventions may be able to preserve muscle strength, but not mass, and vice versa. The purpose of this study was to assess the effects of two distinct interventions during 1 week of knee joint immobilization on muscle strength (isometric and concentric isokinetic peak torque), mass (bioimpedance spectroscopy and ultrasonography), and neuromuscular function (transcranial magnetic stimulation and interpolated twitch technique). Thirty‐nine healthy, college‐aged adults (21 males, 18 females) were randomized into one of four groups: immobilization only (n = 9), immobilization + action observation/mental imagery (AOMI) (n = 10), immobilization + neuromuscular electrical stimulation (NMES) (n = 12), or control group (n = 8). The AOMI group performed daily video observation and mental imagery of knee extensions. The NMES group performed twice daily stimulation of the quadriceps femoris. Based on observed effect sizes, it appears that AOMI shows promise as a means of preserving voluntary strength, which may be modulated by neural adaptations. Strength increased from PRE to POST in the AOMI group, with +7.2% (Cohen's d = 1.018) increase in concentric isokinetic peak torque at 30°/s. However, NMES did not preserve muscle mass. Though preliminary, our findings highlight the specific nature of clinical interventions and suggest that muscle strength can be independently targeted during rehabilitation. This study was prospectively registered: ClinicalTrials.gov NCT05072652.

Abstract Background Bacterial spot of pepper (BSP), caused by four different Xanthomonas species, primarily X. euvesicatoria (Xe), poses a significant challenge in pepper cultivation. Host resistance is considered the most important approach for BSP control, offering long-term protection and sustainability. While breeding for resistance to BSP for many years focused on dominant R genes, introgression of recessive resistance has been a more recent focus of breeding programs. The molecular interactions underlying recessive resistance remain poorly understood. Results In this study, transcriptomic analyses were performed to elucidate defense responses triggered by Xe race P6 infection by two distinct pepper lines: the Xe-resistant line ECW50R containing bs5, a recessive resistance gene that confers resistance to all pepper Xe races, and the Xe-susceptible line ECW. The results revealed a total of 3357 upregulated and 4091 downregulated genes at 0, 1, 2, and 4 days post-inoculation (dpi), with the highest number of differentially expressed genes (DEGs) observed at 2 dpi. Pathway analysis highlighted DEGs in key pathways such as plant-pathogen interaction, MAPK signaling pathway, plant hormone signal transduction, and photosynthesis – antenna proteins, along with cysteine and methionine metabolism. Notably, upregulation of genes associated with PAMP-Triggered Immunity (PTI) was observed, including components like FLS2, Ca-dependent pathways, Rboh, and reactive oxygen species (ROS) generation. In support of these results, infiltration of ECW50R leaves with bacterial suspension of Xe led to observable hydrogen peroxide accumulation without a rapid increase in electrolyte leakage, suggestive of the absence of Effector-Triggered Immunity (ETI). Furthermore, the study confirmed that bs5 does not disrupt the effector delivery system, as evidenced by incompatible interactions between avirulence genes and their corresponding dominant resistant genes in the bs5 background. Conclusion Overall, these findings provide insights into the molecular mechanisms underlying bs5-mediated resistance in pepper against Xe and suggest a robust defense mechanism in ECW50R, primarily mediated through PTI. Given that bs5 provides early strong response for resistance, combining this resistance with other dominant resistance genes will enhance the durability of resistance to BSP.

Abstract Using a symmetry-preserving formulation of a vector $$\,\times \,$$ × vector contact interaction (SCI) and treating the proton as a quark + interacting-diquark bound state, whose structure is obtained by solving a Poincaré-covariant Faddeev equation, we provide a comprehensive, coherent set of predictions for unpolarised and polarised proton parton distribution functions (DFs): valence, glue, and four-flavour separated sea. The results enable many themes to be addressed, including: the asymmetry of antimatter in the proton; the neutron:proton structure function ratio; helicity retention in hard scattering processes; the charm quark momentum fraction; the sign and size of the polarised gluon DF; and the origin of the proton spin. In all cases where sound analyses of data are available, SCI predictions are semiquantitatively in agreement with the results. Those mismatches which exist are typically attributable to the momentum-independence of the underlying interaction. Judiciously interpreted, the SCI delivers a sound and insightful explanation of proton structure as expressed in DFs.

Abstract The 2021 Pacific Northwest heatwave was so extreme as to challenge conventional statistical and climate-model-based approaches to extreme weather attribution. However, state-of-the-art operational weather prediction systems are demonstrably able to simulate the detailed physics of the heatwave. Here, we leverage these systems to show that human influence on the climate made this event at least 8 [2–50] times more likely. At the current rate of global warming, the likelihood of such an event is doubling every 20 [10–50] years. Given the multi-decade lower-bound return-time implied by the length of the historical record, this rate of change in likelihood is highly relevant for decision makers. Further, forecast-based attribution can synthesise the conditional event-specific storyline and unconditional event-class probabilistic approaches to attribution. If developed as a routine service in forecasting centres, it could provide reliable estimates of human influence on extreme weather risk, which is critical to supporting effective adaptation planning.

A light-front holographic model is used to illustrate an algebraic scheme for constructing a representation of a hadron's zero-skewness generalised parton distribution (GPD) from its valence-quark distribution function (DF) and electromagnetic form factor, FH, without reference to deeply virtual Compton scattering data. The hadron's mass distribution gravitational form factor, AH, calculated from this GPD is harder than FH; and, for each hadron, the associated mass-density profile is more compact than the analogous charge profile, with each pion near-core density being larger than that of its proton partner. These features are independent of the scheme employed.

Background It is unclear whether chronically training close to volitional failure influences motor unit recruitment strategies during fatigue. Purpose We compared resistance training to near volitional failure vs. non-failure on individual motor unit action potential amplitude (MUAP) and surface electromyographic excitation (sEMG) during fatiguing contractions. Methods Nineteen resistance-trained adults (11 males, 8 females) underwent 5 weeks (3×/week) of either low repetitions-in-reserve (RIR; 0–1 RIR) or high RIR training (4–6 RIR). Before and after the intervention, participants performed isometric contractions of the knee extensors at 30% of maximal peak torque until exhaustion while vastus lateralis sEMG signals were recorded and later decomposed. MUAP and sEMG excitation for the vastus lateralis were quantified at the beginning, middle, and end of the fatigue assessment. Results Both training groups improved time-to-task failure (mean change = 43.3 s, 24.0%), with no significant differences between low and high RIR training groups (low RIR = 28.7%, high RIR = 19.4%). Our fatigue assessment revealed reduced isometric torque steadiness and increased MUAP amplitude and sEMG excitation during the fatiguing task, but these changes were consistent between groups. Conclusion Both low and high RIR training improved time-to-task failure, but resulted in comparable motor unit recruitment during fatiguing contractions. Our findings indicate that both low and high RIR training can be used to enhance fatiguability among previously resistance-trained adults.

IntroductionThe topoisomerase 1 (TOP1) inhibitor irinotecan is a standard-of-care agent for relapsed Ewing sarcoma (EWS), but its efficacy is limited by chemical instability, rapid clearance and reversibility, and dose-limiting toxicities, such as diarrhea. Indenoisoquinolines (IIQs) represent a new class of clinical TOP1 inhibitors designed to address these limitations.MethodsIn this study, we evaluated the preclinical efficacy of three IIQs (LMP400, LMP744, and LMP776) in relevant models of EWS. We characterized the pharmacokinetics of IIQs in orthotopic xenograft models of EWS, optimized the dosing regimen through tolerability studies, and tested the efficacy of IIQs in a panel of six molecularly heterogeneous EWS patient-derived xenograft (PDX) models. For each PDX, we conducted whole genome and RNA sequencing, and methylation analysis.ResultsWe show that IIQs potently inhibit the proliferation of EWS cells in vitro, inducing complete cell growth inhibition at nanomolar concentrations via induction of DNA damage and apoptotic cell death. LMP400 treatment induced ≥30% tumor regression in two of six PDX models, with more durable regression compared to irinotecan treatment in one of these models. RNA sequencing of PDX models identified a candidate predictive biomarker gene signature for LMP400 response. These data, along with pharmacogenomic data on IIQs in sarcoma cell lines, are available at a new interactive public website: https://discover.nci.nih.gov/rsconnect/EwingSarcomaMinerCDB/.DiscussionOur findings suggest that IIQs may be promising new agents for a subset of EWS patients.

A reaction model for γ+p→J/ψ+p photoproduction, which exposes the cc¯ content of the photon in making the transition γ→cc¯+P→J/ψ and couples the intermediate cc¯ system to the proton's valence quarks via Pomeron (P) exchange, is used to deliver a description of available data, viz. both differential and total cross sections from near threshold, where data has newly been acquired, to invariant mass W≈300GeV. The study suggests that it is premature to link existing γ+p→J/ψ+p data with, for instance, in-proton gluon distributions, the quantum chromodynamics trace anomaly, or pentaquark production. Further developments in reaction theory and higher precision data are necessary before the validity of any such connections can be assessed.

Using a symmetry-preserving truncation of the quantum field equations describing hadron properties, parameter-free predictions are delivered for pion and kaon elastic electromagnetic form factors, FP=π,K, thereby unifying them with kindred results for nucleon elastic electromagnetic form factors. Regarding positive-charge states, the analysis stresses that the presence of scaling violations in QCD entails that Q2FP(Q2) should exhibit a single maximum on Q2>0. Locating such a maximum is both necessary and sufficient to establish the existence of scaling violations. The study predicts that, for charged π, K mesons, the Q2FP(Q2) maximum lies in the neighbourhood Q2≃5 GeV2. Foreseeable experiments will test these predictions and, providing their Q2 reach meets expectations, potentially also provide details on the momentum dependence of meson form factor scaling violation.

Chapter 14 of the Vegetable Production Handbook of Florida

Chapter 8 of the Vegetable Production Handbook of Florida

Abstract A unified set of predictions for pion and kaon elastic electromagnetic and gravitational form factors is obtained using a symmetry-preserving truncation of each relevant quantum field equation. A key part of the study is a description of salient aspects of the dressed graviton + quark vertices. The calculations reveal that each meson’s mass radius is smaller than its charge radius, matching available empirical inferences; and meson core pressures are commensurate with those in neutron stars. The analysis described herein paves the way for a direct calculation of nucleon gravitational form factors.

The ability of probiotics, comprising live microbiota, to modulate the composition of intestinal microbiomes has been connected to modulation of the central nervous system (Gut–Brain axis), neuroendocrine system (Gut–Skin axis), and immune response (Gut–Immune axis). Less information is known regarding the ability of postbiotics (cell wall components and secreted metabolites derived from live organisms) to regulate host immunity. In the present study, we tested postbiotics comprising single strains of bacteria and yeast (Lactobacillus acidophilus 16axg, Lacticaseibacillus rhamnosus 18fx, Saccharomyces cerevisiae var. boulardii 16mxg) as well as combinations of multiple strains for their ability to stimulate cytokine production by human CD14+ monocytes. We quantified cytokine gene and protein expression levels in monocytes following stimulation with postbiotics. Both heat-killed L. acidophilus and L. rhamnosus stimulated naïve monocytes without significant differences between them. Heat-killed S. boulardii stimulated less cytokine production compared to postbiotic bacteria at the same concentration. Interestingly, the addition of heat-killed yeast to heat-killed L. acidophilus and L. rhamnosus resulted in an enhancement of immune stimulation. Thus, heat-killed postbiotics have immune-modulating potential, particularly when bacteria and yeast are combined. This approach may hold promise for developing targeted interventions that can be fine-tuned to modulate host immune response with beneficial health impact.

Extramedullary erythropoiesis is not expected in healthy adult mice, but erythropoietic gene expression was elevated in lineage-depleted spleen cells from Cd47−/− mice. Expression of several genes associated with early stages of erythropoiesis was elevated in mice lacking CD47 or its signaling ligand thrombospondin-1, consistent with previous evidence that this signaling pathway inhibits expression of multipotent stem cell transcription factors in spleen. In contrast, cells expressing markers of committed erythroid progenitors were more abundant in Cd47−/− spleens but significantly depleted in Thbs1−/− spleens. Single-cell transcriptome and flow cytometry analyses indicated that loss of CD47 is associated with accumulation and increased proliferation in spleen of Ter119−CD34+ progenitors and Ter119+CD34− committed erythroid progenitors with elevated mRNA expression of Kit, Ermap, and Tfrc. Induction of committed erythroid precursors is consistent with the known function of CD47 to limit the phagocytic removal of aged erythrocytes. Conversely, loss of thrombospondin-1 delays the turnover of aged red blood cells, which may account for the suppression of committed erythroid precursors in Thbs1−/− spleens relative to basal levels in wild-type mice. In addition to defining a role for CD47 to limit extramedullary erythropoiesis, these studies reveal a thrombospondin-1-dependent basal level of extramedullary erythropoiesis in adult mouse spleen.

Consensus moderation is an approach to quality assurance where collaboration and discussion take place to agree mark allocation. This study explored sessional academics' perceptions and experiences of consensus moderation in higher education. Data from four focus groups were analysed using Foucauldian Discourse Analysis. The findings reveal four discursive constructions of consensus moderation: necessary for fairness and consistency; fraught and complicated; confusing and lacking consistency; and time demanding. Situated within the discourses of the 'vulnerable position of a sessional academic' and the 'paradox of quality assurance in a neoliberal university'. The findings highlight the need for academic development on moderation processes.

Abstract Respiratory rate (RR) is a critical vital sign used to assess pulmonary function. Currently, RR estimating instrumentation is specialized and bulky, therefore unsuitable for remote health monitoring. Previously, RR was estimated using proprietary software that extract surface electrocardiogram (ECG) waveform features obtained at several thoracic locations. However, developing a non-proprietary method that uses minimal ECG leads, generally available from mobile cardiac monitors is highly desirable. Here, we introduce an open-source and well-documented Python-based algorithm that estimates RR requiring only single-stream ECG signals. The algorithm was first developed using ECGs from awake, spontaneously breathing adult human subjects. The algorithm-estimated RRs exhibited close linear correlation to the subjects’ true RR values demonstrating an R2 of 0.9092 and root mean square error of 2.2 bpm. The algorithm robustness was then tested using ECGs generated by the ischemic hearts of anesthetized, mechanically ventilated sheep. Although the ECG waveforms during ischemia exhibited severe morphologic changes, the algorithm-determined RRs exhibited high fidelity with a resolution of 1 bpm, an absolute error of 0.07 ± 0.07 bpm, and a relative error of 0.67 ± 0.64%. This optimized Python-based RR estimation technique will likely be widely adapted for remote lung function assessment in patients with cardiopulmonary disease.

Abstract How does vision affect active touch in judgments of surface roughness? We contrasted direct (combination of visual with tactile sensory information) and indirect (vision alters the processes of active touch) effects of vision on touch. Participants judged which of 2 surfaces was rougher using their index finger to make static contact with gratings of spatial period 1580 and 1620 μm. Simultaneously, they viewed the stimulus under one of five visual conditions: No vision, Filtered vision + touch, Veridical vision + touch (where vision alone yielded roughness discrimination at chance), Congruent vision + touch, Incongruent vision + touch. Results from 32 participants showed roughness discrimination for touch with vision was better than touch alone. The visual benefit for touch was strongest in a filtered (spatially non-informative) vision condition, thus results are interpreted in terms of indirect integration. An indirect effect of vision was further indicated by a finding of visual benefit in some but not all visuo-tactile congruency conditions.

Previous studies agree on an impact of the Atlantic multidecadal variability (AMV) on the total seasonal rainfall amounts over the Sahel. However, whether and how the AMV affects the distribution of rainfall or the timing of the West African monsoon is not well known. Here we seek to explore these impacts by analyzing daily rainfall outputs from climate model simulations with an idealized AMV forcing imposed in the North Atlantic, which is representative of the observed one. The setup follows a protocol largely consistent with the one proposed by the Component C of the Decadal Climate Prediction Project (DCPP-C). We start by evaluating model's performance in simulating precipitation, showing that models underestimate it over the Sahel, where the mean intensity is consistently smaller than observations. Conversely, models overestimate precipitation over the Guinea coast, where too many rainy days are simulated. In addition, most models underestimate the average length of the rainy season over the Sahel; some are due to a monsoon onset that is too late and others due to a cessation that is too early. In response to a persistent positive AMV pattern, models show an enhancement in total summer rainfall over continental West Africa, including the Sahel. Under a positive AMV phase, the number of wet days and the intensity of daily rainfall events are also enhanced over the Sahel. The former explains most of the changes in seasonal rainfall in the northern fringe, while the latter is more relevant in the southern region, where higher rainfall anomalies occur. This dominance is connected to the changes in the number of days per type of event; the frequency of both moderate and heavy events increases over the Sahel's northern fringe. Conversely, over the southern limit, it is mostly the frequency of heavy events which is enhanced, thus affecting the mean rainfall intensity there. Extreme rainfall events are also enhanced over the whole Sahel in response to a positive phase of the AMV. Over the Sahel, models with stronger negative biases in rainfall amounts compared to observations show weaker changes in response to AMV, suggesting that systematic biases could affect the simulated responses. The monsoon onset over the Sahel shows no clear response to AMV, while the demise tends to be delayed, and the overall length of the monsoon season enhanced between 2 and 5 d with the positive AMV pattern. The effect of AMV on the seasonality of the monsoon is more consistent to the west of 10∘ W, with all models showing a statistically significant earlier onset, later demise, and enhanced monsoon season with the positive phase of the AMV. Our results suggest a potential for the decadal prediction of changes in the intraseasonal characteristics of rainfall over the Sahel, including the occurrence of extreme events.

Abstract Exploiting crossing symmetry, the hadron scale pion valence quark distribution function is used to predict the kindred elementary valence quark fragmentation function (FF). This function defines the kernel of a quark jet fragmentation equation, which is solved to obtain the full pion FFs. After evolution to a scale typical of FF fits to data, the results for quark FFs are seen to compare favourably with such fits. However, the gluon FF is markedly different. Notably, although FF evolution equations do not themselves guarantee momentum conservation, inclusion of a gluon FF which, for four quark flavours, distributes roughly 11% of the total light-front momentum fraction, is sufficient to restore momentum conservation under evolution. Overall, significant uncertainty is attached to FFs determined via fits to data; hence, the features of the predictions described herein could potentially provide useful guidance for future such studies.

We present a case of a pseudoaneurysm of the saphenous vein graft stump, which was managed with percutaneous thrombin injection. Aneurysms of a saphenous vein coronary bypass graft are rare and aneurysms of a bypass graft stump are even rarer. To our knowledge this is the first reported case of a pseudoaneurysm of a graft stump with the use of thrombin to treat a saphenous vein graft pseudoaneurysm.

This study examined the effects of sustained, isometric forearm flexion tasks anchored to ratings of perceived exertion of 2 (RPE2FT) and 8 (RPE8FT) on the patterns of fatigue-induced changes in torque and neuromuscular responses, time to task failure (TTF), performance fatigability (% decline in maximal voluntary isometric contraction [MVIC]), and perceived factors that contributed to task termination. Twelve men (mean ± SD: age = 20.9 ± 2.2 yrs) performed MVICs before and after the tasks and completed post-test questionnaires (PTQ). Data were analyzed using polynomial regression analyses, dependent t-tests, Spearman’s rank order correlations, and Wilcoxon signed rank tests. The RPE8FT had greater (p < 0.001) performance fatigability than the RPE2FT, despite no difference (p > 0.05) in TTF. During both tasks, there were significant (p ≤ 0.05) composite linear decreases for torque, electromyographic amplitude, and neuromuscular efficiency, and substantial individual variability in the neuromuscular responses. There were no significant (p > 0.05) associations among the perceived factors and TTF or performance fatigability. Thus, there were RPE-specific differences in performance fatigability, but not TTF or the composite patterns of changes in torque and neuromuscular responses. In addition, in most cases, the individual neuromuscular, but not torque, patterns of responses were RPE-specific. Furthermore, the perceived factors assessed by the PTQ were not related to TTF or performance fatigability.

Abstract Background As the availability of genomic testing grows, variant interpretation will increasingly be performed by genomic generalists, rather than domain-specific experts. Demand is rising for laboratories to accurately classify variants in inherited cardiac condition (ICC) genes, including secondary findings. Methods We analyse evidence for inheritance patterns, allelic requirement, disease mechanism and disease-relevant variant classes for 65 ClinGen-curated ICC gene-disease pairs. We present this information for the first time in a structured dataset, CardiacG2P, and assess application in genomic variant filtering. Results For 36/65 gene-disease pairs, loss of function is not an established disease mechanism, and protein truncating variants are not known to be pathogenic. Using the CardiacG2P dataset as an initial variant filter allows for efficient variant prioritisation whilst maintaining a high sensitivity for retaining pathogenic variants compared with two other variant filtering approaches. Conclusions Access to evidence-based structured data representing disease mechanism and allelic requirement aids variant filtering and analysis and is a pre-requisite for scalable genomic testing.

Abstract We recently reported that vastus lateralis (VL) cross‐sectional area (CSA) increases after 7 weeks of resistance training (RT, 2 days/week), with declines occurring following 7 weeks of subsequent treadmill high‐intensity interval training (HIIT) (3 days/week). Herein, we examined the effects of this training paradigm on skeletal muscle proteolytic markers. VL biopsies were obtained from 11 untrained college‐aged males at baseline (PRE), after 7 weeks of RT (MID), and after 7 weeks of HIIT (POST). Tissues were analysed for proteolysis markers, and in vitro experiments were performed to provide additional insights. Atrogene mRNAs (TRIM63, FBXO32, FOXO3A) were upregulated at POST versus both PRE and MID (P 0.05). in vitro experiments recapitulated the training phenotype when stimulated with a hypertrophic stimulus (insulin‐like growth factor 1; IGF1) followed by a subsequent AMP‐activated protein kinase activator (5‐aminoimidazole‐4‐carboxamide ribonucleotide; AICAR), as demonstrated by larger myotube diameter in IGF1‐treated cells versus IGF1 followed by AICAR treatments (I+A; P = 0.017). Muscle protein synthesis (MPS) levels were also greater in IGF1‐treated versus I+A myotubes (P

The ocean remains one of the least explored places on our planet, containing myriad life that are either unknown to science or poorly understood. Given the technological challenges and limited resources available for exploring this vast space, more targeted approaches are required to scale spatiotemporal observations and monitoring of ocean life. The promise of autonomous underwater vehicles to fulfill these needs has largely been hindered by their inability to adapt their behavior in real-time based on what they are observing. To overcome this challenge, we developed Deep Search and Tracking Autonomously with Robotics (DeepSTARia), a class of tracking-by-detection algorithms that integrate machine learning models with imaging and vehicle controllers to enable autonomous underwater vehicles to make targeted visual observations of ocean life. We show that these algorithms enable new, scalable sampling strategies that build on traditional operational modes, permitting more detailed (e.g., sharper imagery, temporal resolution) autonomous observations of underwater concepts without supervision and robust long-duration object tracking to observe animal behavior. This integration is critical to scale undersea exploration and represents a significant advance toward more intelligent approaches to understanding the ocean and its inhabitants.

Summary This document provides a short summary of the T3MPO-3 study, which was published in Neurogastroenterology and Motility in September 2023. At the end of this summary, there are links to websites where you can find more information about this study. Tenapanor (IBSRELA®) is a newly available medicine in the United States. It is used to treat irritable bowel syndrome with constipation (IBS-C) in people aged 18 years and older. In 2 large clinical trials, tenapanor was shown to improve the symptoms of IBS-C. People with IBS-C often need to take long-term medicines to keep their symptoms under control. As a result, this study, called T3MPO-3 , was undertaken to investigate whether there are any possible side effects associated with the long-term use of tenapanor in adults with IBS-C. There were 312 people who had taken part in either of the original 2 trials and took part in this study, with 90 receiving tenapanor for at least 1 year. Loose or watery stool (diarrhea) was the most common side effect, and most cases were mild or moderate. No people died in any of these studies. Who is this article for? This summary may help people with irritable bowel syndrome with constipation (IBS-C) and their family members and/or caregivers better understand the long-term safety of tenapanor for treating IBS-C. Two IBS-C patient advocates coauthored this summary. Where is the T3MPO-3 study in the medicine development timeline? The T3MPO-3 study was completed in 2018. In 2019, the Food and Drug Administration (FDA) approved tenapanor in the United States to treat IBS-C in adults. • The FDA is responsible for public health in the United States and makes sure that medicines are safe and effective. The medicine development process starts with laboratory and animal testing. Once a potential medicine has been identified and proven to be safe and effective in animals, it is tested in humans in phase I, phase II, and phase III studies. T3MPO-3 was a phase III study. What were the overall results? Diarrhea was the most common side effect in the three T3MPO studies. A side effect is something (expected or unexpected) that you feel was caused by a medicine or treatment you take. Side effects were similar to those reported by researchers in previous studies. No new safety issues were found with long-term use of tenapanor .

We describe three cases of critical acute myositis with myocarditis occurring within 22 days of each other at a single institution, all within 1 month of receiving the initial cycle of the anti-PD-1 drug pembrolizumab. Analysis of T cell receptor repertoires from peripheral blood and tissues revealed a high degree of clonal expansion and public clones between cases, with several T cell clones expanded within the skeletal muscle putatively recognizing viral epitopes. All patients had recently received a COVID-19 mRNA booster vaccine prior to treatment and were positive for SARS-CoV2 Spike antibody. In conclusion, we report a series of unusually severe myositis and myocarditis following PD-1 blockade and the COVID-19 mRNA vaccination.

Signal regulatory protein-α (SIRPα, SHPS-1, CD172a) expressed on myeloid cells transmits inhibitory signals when it engages its counter-receptor CD47 on an adjacent cell. Elevated CD47 expression on some cancer cells thereby serves as an innate immune checkpoint that limits phagocytic clearance of tumor cells by macrophages and antigen presentation to T cells. Antibodies and recombinant SIRPα constructs that block the CD47-SIRPα interaction on macrophages exhibit anti-tumor activities in mouse models and are in ongoing clinical trials for treating several human cancers. Based on prior evidence that engaging SIRPα can also alter CD47 signaling in some nonmalignant cells, we compared direct effects of recombinant SIRPα-Fc and a humanized CD47 antibody that inhibits CD47-SIRPα interaction (CC-90002) on CD47 signaling in cancer stem cells derived from the MDA-MB- 231 triple-negative breast carcinoma cell line. Treatment with SIRPα-Fc significantly increased the formation of mammospheres by breast cancer stem cells as compared to CC-90002 treatment or controls. Furthermore, SIRPα-Fc treatment upregulated mRNA and protein expression of ALDH1 and altered the expression of genes involved in epithelial/mesenchymal transition pathways that are associated with a poor prognosis and enhanced metastatic activity. This indicates that SIRPα-Fc has CD47-mediated agonist activities in breast cancer stem cells affecting proliferation and metastasis pathways that differ from those of CC-90002. This SIRPα-induced CD47 signaling in breast carcinoma cells may limit the efficacy of SIRPα decoy therapeutics intended to stimulate innate antitumor immune responses.

An increase in mechanical loading, such as that which occurs during resistance exercise, induces radial growth of muscle fibers (i.e. an increase in cross-sectional area). Muscle fibers are largely composed of myofibrils, but whether radial growth is mediated by an increase in the size of the myofibrils (i.e. myofibril hypertrophy) and/or the number of myofibrils (i.e. myofibrillogenesis) is not known. Electron microscopy (EM) can provide images with the level of resolution that is needed to address this question, but the acquisition and subsequent analysis of EM images is a time- and cost-intensive process. To overcome this, we developed a novel method for visualizing myofibrils with a standard fluorescence microscope (fluorescence imaging of myofibrils with image deconvolution [FIM-ID]). Images from FIM-ID have a high degree of resolution and contrast, and these properties enabled us to develop pipelines for automated measurements of myofibril size and number. After extensively validating the automated measurements, we used both mouse and human models of increased mechanical loading to discover that the radial growth of muscle fibers is largely mediated by myofibrillogenesis. Collectively, the outcomes of this study offer insight into a fundamentally important topic in the field of muscle growth and provide future investigators with a time- and cost-effective means to study it.