Functional Longevity Research Articles

On the Relationship Among Linear Type Traits and Functional Longevity in the Italian Mediterranean Buffalo Using a Weibull Proportional Hazards Model

Weibull proportional hazards model was used to identify the non-genetic effects that affect length of productive life (LPL) of the Italian Mediterranean Buffalo (IMB). Data were provided by the Italian National Association of Buffalo Breeders (ANASB) and included records of reproductive, productive, and linear type traits from 59,943 buffalo with first calving from 2002 to 2019. Data were divided into 4 geographical regions to determine if the relationship between the investigated effects and LPL varied by region. LPL was defined as the number of days from the first calving to culling for those buffaloes that were culled (uncensored) or to the date of the last test-day for those that are still alive (censored). The Weibull model included time-dependent effects of herd-year-season of calving, parity and stage of lactation, production as within-herd deviations, as well as time-independent effects of age at first calving, year of birth, type of reproduction (natural mating vs artificial insemination), classifier and ten linear type traits. The average duration of productive life was 1,604 days. Both year of birth and production level had a significant effect on culling risk. Moreover, culling risk decreased linearly across parities. The reference point for age at first calving relative to other classes was set at 35 months. A significant relationship between linear type traits and relative culling risk was also observed, being highest for buffaloes with the lowest linear scores. The results show that the Weibull model provides consistent and robust risk estimates. Therefore, this model would be recommended for future implementation of the first genetic evaluation of LPL in the Italian Mediterranean Buffalo.

Comparison of blood parameters in two genetically different groups of horses for functional longevity in show jumping.

In order to find early selection criteria to improve the longevity of show jumping horses, a specific protocol was designed. Before entering competition, young horses selected from extreme stallions for longevity were measured for many traits, including blood parameters. Blood samples were taken from 952 horses aged 2-4years old, sired by two groups of stallions: one with unfavorable (U) and the other with favorable (F) extreme estimated breeding values for functional longevity. These breeding values were previously calculated from data on 202,320 horses that participated in show jumping competitions between 1985 and 2022. Functional longevity was defined as time spent in competition, adjusted for the level of performance. The 59 measured parameters included hematology, proteins, cytokines, liver and kidney function, bone and joint health, oxidative stress and endocrinology. Heritability was estimated using a mixed model that accounted for the effect of age, sex, estimated weight, visit (place and date of collection), and animal random additive value with 10,280 horses in pedigree. A Partial Least Square logistic regression was performed to predict the sire group. Age, sex and estimated weight significantly affected 36, 19 and 16 variables, respectively. The visit had a significant effect on all variables. Heritability estimates were high, with 75% higher than 0.20% and 30% higher than 0.50. The most heritable traits included mean corpuscular volume (0.92, se 0.11), mean corpuscular hemoglobin (0.90, se 0.11), white blood cells (0.55, se 0.13), total alkaline phosphatase (0.68, se 0.12) and percentage of γ-globulin (0.57, se 0.12). The logistic regression that predicted the group of sires favorable for longevity identified 16 significant variables. Key findings included: lower mean corpuscular hemoglobin (p-value < 0.001), lower mean corpuscular volume (p-value < 0.001), lower number of white blood cells (p-value < 0.01), higher percentage of intestinal and bone alkaline phosphatase (p-value < 0.01) for a lower total alkaline phosphatase (p-value < 0.01), higher percentage of α2-globulin (p-value < 0.001) and lower percentage of β1-globulin (p-value < 0.01). Blood parameters measured at rest in young horses may be predictive of their genetic value for functional longevity in show jumping.

Predictors of outcome following two-stage revision total knee arthroplasty.

Two stage revision arthroplasty remains the gold standard for peri-prosthetic joint infections of the knee. However, the functional outcomes of revision surgeries and the factors governing them require further investigation. The purpose of this study was to (a) evaluate impact of early and late stage I surgery and interval between stage I and stage II; (b) understand the impact of infecting organism and resistance; (c) to estimate long term survivorship and causes of failure. A retrospective review of 86 patients, who underwent two stage revision for prosthetic joint infections of the knee, was performed. Time between onset of symptoms to stage I (T1), and T1 to re-implantation (T2), along with microbiological studies, were analysed for their impact on functional outcomes, failure modalities and survivorship. In this study, the mean KSS-Knee improved from 64.0 ± 10.0 pre-operatively to 76.9 ± 10.4, and 77.2 ± 10.1 at the 5 and 10 year follow up respectively. The KSS-Function improved from 44.4 ± 8.8 pre-operatively to 72.2 ± 9.5 and 79.8 ± 8.1 at 5 and 10 year follow-up respectively. This study also found that T1 and T2 remained critical factors in determining functional outcome and longevity of the implant and a delay in these intervals was a significant predictor of failure. Gram negative, poly-microbial infections and organisms with methicillin and vancomycin resistance demonstrated lower survivorship (p-value, 0.001 at 5, 10 and 12 years). Re-infections occurred in 4 cases while 9 cases failed due to aseptic causes. Two-stage revision arthroplasty produced good functional outcomes when the infection was caused by single sensitive organism that did not exhibit high resistance to antibiotics. Stage I performed within 4 weeks and the subsequent re-implantation procedure undertaken within 6 weeks demonstrated better outcomes.

Comparative analysis of different filling materials in deciduous teeth

Dental caries in pediatric patients presents a significant challenge in maintaining oral health, making the choice of filling materials for deciduous teeth crucial for long-term success. Various restorative materials, including composite resins, glass ionomer cements (GICs), and resin-modified glass ionomers (RMGICs), have been used, each with distinct properties regarding durability, biocompatibility, and aesthetic outcomes. Composite resins are well-regarded for their ability to closely match the natural color of teeth, making them ideal for anterior restorations. However, they are technique-sensitive and may not provide sufficient durability in posterior regions subjected to high stress. Glass ionomer cements, known for their ease of placement and fluoride release, offer functional benefits in high-caries-risk patients, despite their lower aesthetic quality and susceptibility to wear over time. Resin-modified glass ionomers attempt to combine the strengths of both composites and GICs by improving durability and aesthetics while maintaining the fluoride-releasing property. The safety and biocompatibility of these materials also play a pivotal role in pediatric dentistry. While composite resins may release small amounts of bisphenol A (BPA), which has raised concerns about its potential health risks, GICs and RMGICs are generally considered safer due to their simpler chemical composition and fluoride release. In terms of functional longevity, composite resins offer better wear resistance compared to GICs, though resin-modified glass ionomers provide a compromise with improved strength and ease of use. Ultimately, the choice of restorative material should consider the specific clinical circumstances, including the child’s caries risk, tooth location, and the balance between aesthetic and functional needs. No single material is universally ideal for all cases, and a tailored approach is necessary to optimize outcomes in pediatric dental restorations.

Milk productivity and the concentration of ketones in the blood of Kostroma cows of different LEP genotypes

Relevance. Currently, scientists are searching for genes associated not only with an increased level of dairy productivity, but also with the preservation of functional longevity and health of cows, with a high level of realization of their genetic potential, as well as with the distinctive quality of dairy products. The available data allow us to consider the leptin gene (LEP) as one of the candidate genes of milk productivity.Methods. The research was conducted in 2022–2023 on cows of the Kostroma breed (n = 107) bred in the Kostroma region. In cows in the postpartum period, the content of ketone bodies in the blood and genotypes were determined by the R25C locus of the LEP gene. The animals were divided into groups depending on the concentration of ketone bodies in the blood: 1st – 0–1.2 mmol/l, 2nd – above 1.2 mmol/l.Results. The presence of a predisposition of highly productive cows to ketosis (р &lt; 0.05) was established. The largest number of ketone bodies in the blood was determined in animals of the 2nd group with the LEPCT genotype. However, despite such a small difference, the difference in the frequency distribution of LEP alleles in groups 1 and 2 turned out to be statistically significant (χ2 = 63.48, р &lt; 0.001). When testing the hypothesis of a significant dependence of the level of milk productivity on the concentration of ketone bodies in the blood of carriers of the CC genotype, a statistically significant rho value was obtained among cows with the CC genotype, at the level of 0.37 (р = 0.038). The rank correlation between milk yield and ketone body content in carriers of LEPCT and LEPTT genotypes was low and unreliable (р &gt; 0.05). The tendency towards a close relationship between the level of ketone bodies and the fat content in the milk of cows of the TT genotype due to its low concentration in the sample requires further confirmation in a larger sample of cows with this genotype of the leptin gene.

Green modifications for rendering cotton fabric with antibacterial, anti-mite, and mosquito-repellent functions using single natural eugenol

Cotton fabrics are widely used in everyday life; however, increasing their versatility through green modifications remains a challenge. The current mainstream approach merely physically attaches the additives onto the fibers, resulting in low binding affinity. In this study, novel cotton fabrics (Cotton-Si-EU) with long-lasting antibacterial, anti-mite, and mosquito-repellent properties were facilely fabricated in a green procedure. In contrast to conventional coating and physical addition methods, the eugenol graft modification ensured the safety, environmental friendliness and long-lasting functionality of the Cotton-Si-EU. In addition, Cotton-Si-EU fabrics retained the softness, comfort, breathability, and moisture absorption originating from the cotton fabric. Cotton-Si-EU also showed over 99.99% antibacterial, 73% anti-mite, and 75% mosquito repellent rates, simultaneously destroying microorganisms and insects through oxidative stress, inhibiting enzyme activity, affecting cell structure, and other mechanisms. More importantly, after 50 washing cycles, the fabrics still exhibited durable antibacterial properties higher than the AAA requirements, indicating high functional longevity. In addition, good cytocompatibility, hemocompatibility, and negligible skin irritation demonstrated excellent biological safety. Therefore, this study is of great significance in providing a reference for modifying cotton fabrics using an infinite number of natural products after screening, which will broaden the application scope and improve the safety level of functional cotton fabrics.

Responses of selected plasma metabolites to a 2-day nutritional challenge of goats divergently selected for functional longevity

Understanding the extent to which genetics × environment plays a role in shaping individual strategies to environmental challenges is of considerable interest for future selection of more resilient animals. Accordingly, the objective of this study was to evaluate the metabolic responses to a nutritional challenge of goats divergently selected for functional longevity based on plasma metabolites and the repeatability of these responses across 2 experimental farms and years. We carried out 6 different experimental trials from years 2018 to 2022 (4 trials on site Bourges (2018-21) and 2 trials (2021-22) on site Grignon) in which 267 first kidding goats, daughters of Alpine bucks divergently selected for functional longevity, longevity plus (n = 137), and longevity minus (n = 130), were exposed to a 2-d nutritional challenge in early lactation. The experiments consisted of a 5 or 7-d control period (pre-challenge) on a standard lactation diet followed by a 2-d nutritional challenge with straw-only feeding and then a 7 or 10-d recovery period on a standard lactation diet, for site Bourges and Grignon, respectively. During the challenge plasma metabolite composition was recorded daily. Linear mixed-effects models were used to analyze all traits, considering the individual as a random effect and the 2x2 treatments (i.e., genetic line and year nested in site) and litter size as fixed effects. The linear mixed-effects model using a piecewise arrangement was used to analyze the response/recovery profiles to the nutritional challenge. Random parameters estimated for each individual, using the mixed-effects models without the fixed effects of genetic line, were used in a Sparse Partial Least Square Discriminant Analysis (sPLS-DA) to compare the goat metabolism response to the challenge on a multivariate scale. The plasma metabolites, glucose, β-hydroxybutyrate (BHB), and nonesterified fatty acids (NEFA), and urea concentrations responded to the 2-d nutritional challenge. Selection for functional longevity did not affect plasma glucose, NEFA, BHB, and urea response/recoveries to a 2-d nutritional challenge. However, site, trial, and litter size affected these responses. Moreover, the plasma metabolites seem not to fully recover to prechallenge levels after the recovery phase. The sPLS-DA analysis did not discriminate between the 2 longevity lines. We observed meaningful between-individuals' variability in plasma BHB, especially on the prechallenge and rate of response and rate of recovery from the 2-d nutritional challenge (CV = 26.2%, 36.1%, and 41.2%, repeatability = 0.749, 0.322, and 0.741, respectively). Plasma NEFA recovery from challenge also demonstrated high between-individuals' variability (CV = 16.4%, repeatability = 0.323). Selection for functional longevity did not affect plasma metabolites responses to a 2-d nutritional challenge in dairy goats. Plasma NEFA and BHB response/recovery presented high between-individuals' variability, indicating individual adaptative characteristics to nutritional challenges not related to the environmental conditions but to inherent individual characteristics.

The link between functional response and longevity of Trichogramma evanescens strains indigenous to Türkiye: A comparative assessment of parameters

AbstractA previous comprehensive survey in the Mediterranean and Southeastern regions of Türkiye investigating the natural egg parasitism of lepidopteran maize pests, Sesamia spp, (Lepidoptera: Noctuidae) Ostrinia nubilalis Hbn. and Chilo partellus (Swinhoe; Lepidoptera: Crambidae) by Trichogramma evanescens Westwood (Hymenoptera: Trichogrammatidae) yielded successful establishment of laboratory cultures of six strains molecularly clustering into two main groups. In this study, the functional response and adult longevity of the strains reared and tested on a factitious host, Ephestia kuehniella Zeller (Lepidoptera: Pyralidae) were investigated to provide insights into their potential as candidate biocontrol agents under constant laboratory conditions. The functional response modelling process consisted of two main sequential steps: model selection using polynomial logistic regression and parameter estimation using an iterative maximum likelihood estimation method. The functional response of two strains showed negative linear parameters (type II): HAP068M and HAP268S. Although their attack rate did not differ, the handling time of HAP268S was longer than that of HAP068M. In contrast, four strains had positive linear and negative quadratic parameters (type III) in their functional response: HAP044S, HAP070S, HAP210S, and HAP258M. The strains exhibiting type III functional response did not differ in their handling time, while HAP044S had a higher attack coefficient than HAP070S, HAP210S, and HAP258M. The longevity of both female and male adults significantly differed between strains. More importantly, the females belonging to strains exhibiting type II functional response presented a shorter longevity, compared to those with type III functional response. Males also showed a similar trend in their longevity. This paper discusses the differences in functional response types and estimated parameters of the strains in relation to their relevance for biological control programs and reveals a link between their functional response and longevity as potential reciprocal predictors.

Functional outcomes and survivorship following aseptic revision shoulder arthroplasty

BackgroundRevision shoulder arthroplasty (SA) is a surgical procedure performed to address complications or failures of primary total SA. However, limited evidence exists regarding the functional outcomes and longevity of implants following revision. MethodsA retrospective analysis was conducted on patients who underwent revision SA for failed primary arthroplasty at a single institution between 2009 and 2021 with a minimum of 2-years follow-up. Data was collected from medical records, including type of arthroplasty (anatomic total SA [TSA], reverse total SA [RSA], or hemi-SA [HSA]), demographics and patient-specific information, functional measurements, and implant survival. Patient reported outcomes were obtained during follow-up by phone. ResultsThe mean age at index and revision surgeries was 60.5 ± 12.1 years and 64.8 ± 11.1 years, respectively, and average total follow-up was 5.5 ± 3.5 years. The average time to revision was 4.5 ± 5.2 years (range 0.01–24.5 years). Among 99 revision shoulder arthroplasty procedures, 28 were TSA/HA to TSA/HA, 51 were TSA/HA to RSA, 18 were RSA to RSA, and 2 were RSA to HA. Revision surgery significantly improved functional outcomes in forward elevation (preoperative: 79.8 ± 41.0 vs postoperative: 118.5 ± 38.3; p < 0.001), external rotation (preoperative: 27.8 ± 19.3 vs postoperative: 34.3 ± 16.2; p = 0.028), internal rotation (preoperative: glute vs postoperative: S1; p = 0.002), and forward elevation strength (preoperative: 4+/5 vs postoperative: 5/5; p = 0.002). Postoperative patient reported outcomes included: VAS pain (2.2 ± 2.9), SANE (72.6 ± 21.5), ASES (73.3 ± 20.4), and SST (7.7 ± 2.8) scores. The overall 2-, 5-, and 10-year post-revision implant survival rate was 85.48%, 83.06%, and 79.84%, respectively. Patients who had an initial RSA and were revised to RSA were at higher risk of implant failure and subsequent re-revision (RSA to RSA: 1.5 ± 2.5 years vs. TSA/HA to RSA: 2.5 ± 2.1 years vs. TSA/HA to TSA/HA: 4.0 ± 3.5 years; p = 0.0046) ConclusionRevision shoulder arthroplasty improved patient outcomes post-index arthroplasty failure. Revisions were more likely to be successful when revising from TSA/HA to RSA. Level of evidenceLevel III – retrospective comparative study.

Functional longevity of exposed geosynthetics

The time at which a geosynthetic’s performance falls below established functional thresholds is known as the geosynthetic’s functional longevity. As opposed to “durability” which commonly refers to an individual exposure environment such as UV exposure or a specific chemical exposure preceded and followed by an index test to quantify physical changes, functional longevity is the result of the synergistic effects of one or more exposure environments happening simultaneously or sequentially preceded and followed by a performance test. Therefore, functional longevity is characterized by a “suite” of durability tests and an accompanying performance test. Exposed geosynthetics, such as rolled erosion control products (RECPs) and engineered turf are the most common candidates for functional longevity characterization. In each case, exposures can include ultraviolet radiation, biodegradation, and damaging mechanical forces. These exposures inevitably degrade the geosynthetic over time. Yet, the important question is, when do the synergistic effects of the simultaneous or sequential exposures degrade the geosynthetic to the point where its performance falls below established thresholds? This question can only be answered by putting the candidate product through a relevant series of durability and performance tests. This paper describes a series of durability and performance tests being used to characterize the functional longevity of RECPs.

INNOVATIVE METAL COMPLEXES AS PHOTOSTABILIZERS TO IMPROVE THE FUNCTIONAL LONGEVITY OF POLYVINYL CHLORIDE

Polyvinyl chloride (PVC) is involved in diverse applications that significantly influence our daily lives; it is industrially synthesized in various configurations in order to fulfill the target application. However, PVC is susceptible to photodegradation, yielding toxic byproducts detrimental to both the environment and human health, which diminishing its utility lifespan. Addressing this concern, current research explores the application of metal complexes as potential photostabilizers to mitigate PVC photodecomposition. The objective of this study is to investigate the effectiveness of formulated metal complexes in preventing photodegradation. Five metals, namely Cu(II), Ni(II), Cd(II), Zn(II), and Sn(II), are included. Examining parameters, such as molecular weight attenuation, the formation of alkene-laden and carbonyl fragments, and the surface morphology alterations of PVC sheets subjected to irradiation are considered. Findings indicate that these metal complexes exhibit remarkable efficacy in decreasing the photodegradation of PVC, thus presenting a promising avenue for extending its functional longevity. The polymer containing Cd(II) complex unit showed the least damage in the PVC surface due to photoirradiation, followed by other complexes

The significance of growth shells in development of symmetry, transparency, and refraction of the human lens.

Human visual function depends on the biological lens, a biconvex optical element formed by coordinated, synchronous generation of growth shells produced from ordered cells at the lens equator, the distal edge of the epithelium. Growth shells are comprised of straight (St) and S-shaped (SSh) lens fibers organized in highly symmetric, sinusoidal pattern which optimizes both the refractile, transparent structure and the unique microcirculation that regulates hydration and nutrition over the lifetime of an individual. The fiber cells are characterized by diversity in composition and age. All fiber cells remain interconnected in their growth shells throughout the life of the adult lens. As an optical element, cellular differentiation is constrained by the physical properties of light and its special development accounts for its characteristic symmetry, gradient of refractive index (GRIN), short range transparent order (SRO), and functional longevity. The complex sinusoidal structure is the basis for the lens microcirculation required for the establishment and maintenance of image formation.

Social connectedness, functional capacity, and longevity: A focus on positive relations with others

RationaleA large literature links social connectedness to health, but there is growing recognition of considerable nuance in the ways social connectedness is defined, assessed, and associated with health. ObjectiveThis study centers on positive relations with others – a measure derived from philosophical notions of the components of a “good life” – and the extent to which it predicts functional limitations and mortality using data from the national, longitudinal Mid-Life in the United States (MIDUS) study. We also assess whether these associations are independent of two common measures of social connectedness: social integration and social support. MethodsData on social connectedness came from the first wave of MIDUS (1994–1996), self-reported functional limitations were from the first (MIDUS 1) and third (MIDUS 3; 2013–2014) waves, and mortality data through 2022 were obtained from the National Death Index. ResultsLinear regression analyses showed that higher scores on positive relations with others predicted significantly less increase in functional limitations over time, and logistic regression models showed reduced probability of onset of functional limitations between MIDUS 1 and MIDUS 3 in those scoring higher on positive relations with others. Mortality was also significantly lower in those with higher scores on positive relations with others. All models adjusted for demographic and health characteristics, and all associations were robust to the inclusion of social integration and social support in the models. ConclusionsThese results show that positive relations with others, a component of a well-lived life that describes sustained investment in social relationships that are mutual and trusting, is associated with two key health outcomes in aging adults: functional limitations and longevity. That these associations are independent of social integration and social support suggests a unique role for this formulation of social connectedness in the health of aging adults.

Getting to grips with Resilience: Towards large-scale phenotyping of this complex trait

The capacity of animals to cope with environmental perturbations, hereafter called resilience, is an increasingly important trait. Resilience at the level of the animal is an emergent property of multiple underlying mechanisms (physiological, immunological, behavioral). This means that there is no direct measure of resilience, no easy key traits. It is a latent variable that may be inferred from multivariate measures. Further, the flexibility that resilience provides is evidenced in the rate of response to, and rate of recovery from, the environmental perturbation. Thus, it requires time-series measurements. The increasing availability of on-farm precision livestock technologies, that are capable of providing time-series measures of performance and of various physiological and health biomarkers, offer the opportunity to move toward large-scale phenotyping of resilience. There have been numerous studies putting forward methods to quantify resilience. These methods can be classified as being data-driven or concept driven. However, new candidate resilience proxies need to be validated. This is tricky to do as there is no direct measure of resilience, no easy gold standard measure. Per definition, good resilience will benefit the animal. Thus, the accumulated consequences of resilience can be used to evaluate resilience proxies. All other things being equal, it is expected that good resilience will be associated with a longer functional longevity (longevity adjusted for production level), with more reproductive cycles, and with fewer disease events. Recent examples of this approach of evaluating resilience proxies against the accumulated consequences of resilience are discussed. They show clearly that operational resilience proxies that are heritable and have been validated against the consequences of good resilience can be derived from on-farm time-series data. With the aim of deriving more nuanced phenotypes, there are an increasing number of studies that have taken up the challenge of attempting to statistically combine the information coming from multiple time-series measures. These studies show how multivariate time-series statistics can be used to derive more nuanced resilience phenotypes that capture some of the underlying mechanisms of resilience. In conclusion, the recent studies reviewed here have shown that operational and heritable resilience proxies exist, that they can form the basis for selection for resilience, and that more nuanced phenotypes are attainable which will allow selection for resilience to be tailored according to prevailing environmental challenge types.

Combined single-step evaluation of functional longevity of dairy cows including correlated traits

BackgroundFor years, multiple trait genetic evaluations have been used to increase the accuracy of estimated breeding values (EBV) using information from correlated traits. In France, accurate approximations of multiple trait evaluations were implemented for traits that are described by different models by combining the results of univariate best linear unbiased prediction (BLUP) evaluations. Functional longevity (FL) is the trait that has most benefited from this approach. Currently, with many single-step (SS) evaluations, only univariate FL evaluations can be run. The aim of this study was to implement a “combined” SS (CSS) evaluation that extends the “combined” BLUP evaluation to obtain more accurate genomic (G) EBV for FL when information from five correlated traits (somatic cell score, clinical mastitis, conception rate for heifers and cows, and udder depth) is added.ResultsGEBV obtained from univariate SS (USS) evaluations and from a CSS evaluation were compared. The correlations between these GEBV showed the benefits of including information from correlated traits. Indeed, a CSS evaluation run without any performances on FL showed that the indirect information from correlated traits to evaluate FL was substantial. USS and CSS evaluations that mimic SS evaluations with data available in 2016 were compared. For each evaluation separately, the GEBV were sorted and then split into 10 consecutive groups (deciles). Survival curves were calculated for each group, based on the observed productive life of these cows as known in 2021. Regardless of their genotyping status, the worst group of heifers based on their GEBV in 2016 was well identified in the CSS evaluation and they had a substantially shorter herd life, while those in the best heifer group had a longer herd life. The gaps between groups were more important for the genotyped than the ungenotyped heifers, which indicates better prediction of future survival.ConclusionsA CSS evaluation is an efficient tool to improve FL. It allows a proper combination of information on functional traits that influence culling. In contrast, because of the strong selection intensity on young bulls for functional traits, the benefit of such a “combined” evaluation of functional traits is more modest for these males.

Analysis of reproduction success, growth and milk trajectories and response to nutritional challenge in two Alpine goat lines selected on divergent longevity

This study aims to investigate whether the variation in reproduction success, growth, and milk trajectories is associated with different adaptive strategies in the short term (response to an acute nutritional challenge), using two Alpine goat lines. A total of 382 Alpine goats (179 low longevity (low_LGV) and 203 high longevity (high_LGV)), selected for divergent functional longevity from a commercial population, were monitored for 4 years and recorded for BW, reproduction and milking performance. Every year, an average of fifty primiparous goats were exposed to a 2-d nutritional challenge in early lactation. A polynomial model was used to analyse the lifetime trajectory of lactation and BW. A piecewise model was used to analyse the individual milk yield and responses of milk components to the nutritional challenges. The statistical analysis revealed that the two lines had a similar performance for total milk yield in the first lactation, BW at birth and at first kidding, litter size and weight, kidding interval and interval from the first insemination to conception. BW trajectories revealed that low_LGV goats had a greater BW in pregnancy but then lost more weight in early lactation compared to high_LGV goats, which showed a greater BW after kidding. Milk trajectories showed that the high_LGV goats had a higher initial milk yield, an earlier but less marked lactation peak and more persistency in milk production in late lactation than low_LGV goats. Except for milk protein content, quite similar response and recovery profiles of milk yield and milk fat content were observed during the challenge for both lines. The response to the challenge was positively correlated to the initial level of milk production in early lactation but negatively correlated with milk production decline after the peak. This finding suggests that the low_LGV goats were more adapted to allocate resources to meet an expected physiological change such as gestation and lactation. However, high_LGV goats allocate more than low_LGV goats for structural mass and may better cope with an unexpected environmental change such as nutritional deficit.

ATFS-1 counteracts mitochondrial DNA damage by promoting repair over transcription.

The ability to balance conflicting functional demands is critical for ensuring organismal survival. The transcription and repair of the mitochondrial genome (mtDNA) requires separate enzymatic activities that can sterically compete1, suggesting a life-long trade-off between these two processes. Here in Caenorhabditis elegans, we find that the bZIP transcription factor ATFS-1/Atf5 (refs. 2,3) regulates this balance in favour of mtDNA repair by localizing to mitochondria and interfering with the assembly of the mitochondrial pre-initiation transcription complex between HMG-5/TFAM and RPOM-1/mtRNAP. ATFS-1-mediated transcriptional inhibition decreases age-dependent mtDNA molecular damage through the DNA glycosylase NTH-1/NTH1, as well as the helicase TWNK-1/TWNK, resulting in an enhancement in the functional longevity of cells and protection against decline in animal behaviour caused by targeted and severe mtDNA damage. Together, our findings reveal that ATFS-1 acts as a molecular focal point for the control of balance between genome expression and maintenance in the mitochondria.

Spatiotemporal Expression of RNA-Seq Identified Proteins at the Electrode Interface.

Implantation of electrodes in the brain can be used to record from or stimulate neural tissues to treat neurological disease and injury. However, the tissue response to implanted devices can limit their functional longevity. Recent RNA-seq datasets identify hundreds of genes associated with gliosis, neuronal function, myelination, and cellular metabolism that are spatiotemporally expressed in neural tissues following the insertion of microelectrodes. To validate mRNA as a predictor of protein expression, this study evaluates a sub-set of RNA-seq identified proteins (RSIP) at 24-hours, 1-week, and 6-weeks post-implantation using quantitative immunofluorescence methods. This study found that expression of RSIPs associated with glial activation (Glial fibrillary acidic protein (GFAP), Polypyrmidine tract binding protein-1 (Ptbp1)), neuronal structure (Neurofilament heavy chain (Nefh), Proteolipid protein-1 (Plp1), Myelin Basic Protein (MBP)), and iron metabolism (Transferrin (TF), Ferritin heavy chain-1 (Fth1)) reinforce transcriptional data. This study also provides additional context to the cellular distribution of RSIPs using a MATLAB-based approach to quantify immunofluorescence intensity within specific cell types. Ptbp1, TF, and Fth1 were found to be spatiotemporally distributed within neurons, astrocytes, microglia, and oligodendrocytes at the device interface relative to distal and contralateral tissues. The altered distribution of RSIPs relative to distal tissue is largely localized within 100µm of the device injury, which approaches the functional recording range of implanted electrodes. This study provides evidence that RNA-sequencing can be used to predict protein-level changes in cortical tissues and that RSIPs can be further investigated to identify new biomarkers of the tissue response that influence signal quality. STATEMENT OF SIGNIFICANCE: : Microelectrode arrays implanted into the brain are useful tools that can be used to study neuroscience and to treat pathological conditions in a clinical setting. The tissue response to these devices, however, can severely limit their functional longevity. Transcriptomics has deepened the understandings of the tissue response by revealing numerous genes which are differentially expressed following device insertion. This manuscript provides validation for the use of transcriptomics to characterize the tissue response by evaluating a subset of known differentially expressed genes at the protein level around implanted electrodes over time. In additional to validating mRNA-to-protein relationships at the device interface, this study has identified emerging trends in the spatiotemporal distribution of proteins involved with glial activation, neuronal remodeling, and essential iron binding proteins around implanted silicon devices. This study additionally provides a new MATLAB based methodology to quantify protein distribution within discrete cell types at the device interface which may be used as biomarkers for further study or therapeutic intervention in the future.

What Are the MSTS Scores and Complications Associated With the Use of Three-dimensional Printed, Custom-made Prostheses in Patients Who Had Resection of Tumors of the Hand and Foot?

There are a few good options for restoring bone defects in the hand and foot. 3D-printed implants have been used in the pelvis and elsewhere, but to our knowledge, they have not been evaluated in the hand and foot. The functional outcome, complications, and longevity of 3D-printed prostheses in small bones are not well known. (1) What are the functional outcomes of patients with hand or foot tumors who were treated with tumor resection and reconstruction with a 3D-printed custom prosthesis? (2) What complications are associated with using these prostheses? (3) What is the 5-year Kaplan-Meier cumulative incidence of implant breakage and reoperation? Between January 2017 and October 2020, we treated 276 patients who had tumors of the hands or feet. Of those, we considered as potentially eligible patients who might have extensive loss in their joint that could not be fixed with a bone graft, cement, or any prostheses available on the market. Based on this, 93 patients were eligible; a further 77 were excluded because they received nonoperative treatment such as chemoradiation, resection without reconstruction, reconstruction using other materials, or ray amputation; another three were lost before the minimum study follow-up of 2 years and two had incomplete datasets, leaving 11 for analysis in this retrospective study. There were seven women and four men. The median age was 29 years (range 11 to 71 years). There were five hand tumors and six tumors of the feet. Tumor types were giant cell tumor of bone (five), chondroblastoma (two), osteosarcoma (two), neuroendocrine tumor (one), and squamous cell carcinoma (one). Margin status after resection was ≥ 1 mm. All patients were followed for a minimum of 24 months. The median follow-up time was 47 months (range 25 to 67 months). Clinical data; function according to the Musculoskeletal Tumor Society, DASH, and American Orthopedic Foot and Ankle Society scores; complications; and survivorship of implants were recorded during follow-up in the clinic, or patients with complete charts and recorded data were interviewed on the telephone by our research associates, orthopaedic oncology fellows, or the surgeons who performed the surgery. The cumulative incidence of implant breakage and reoperation was assessed using a Kaplan-Meier analysis. The median Musculoskeletal Tumor Society score was 28 of 30 (range 21 to 30). Seven of 11 patients experienced postoperative complications, primarily including hyperextension deformity and joint stiffness (three patients), joint subluxation (two), aseptic loosening (one), broken stem (one), and broken plate (one), but no infection or local recurrence occurred. Subluxations of the metacarpophalangeal and proximal interphalangeal joints in two patients' hands were caused by the design of the prosthesis without a joint or stem. These prostheses were revised to a second-generation prosthesis with joint and stem, leading to improved dexterity. The cumulative incidence of implant breakage and reoperation in the Kaplan-Meier analysis was 35% (95% CI 6% to 69%) and 29% (95% CI 3% to 66%) at 5 years, respectively. These preliminary findings suggest that 3D implants may be an option for reconstruction after resections that leave large bone and joint defects in the hand and foot. Although the functional results generally appeared to be good to excellent, complications and reoperations were frequent; thus, we believe this approach could be considered when patients have few or no alternatives other than amputation. Future studies will need to compare this approach to bone grafting or bone cementation. Level IV, therapeutic study.

Multivariate analysis of milk metabolite measures shows potential for deriving new resilience phenotypes

In a context of growing interest in breeding more resilient animals, a noninvasive indicator of resilience would be very valuable. We hypothesized that the time-course of concentrations of several milk metabolites through a short-term underfeeding challenge could reflect the variation of resilience mechanisms to such a challenge. We submitted 138 one-year-old primiparous goats, selected for extreme functional longevity (i.e., productive longevity corrected for milk yield [60 low longevity line goats and 78 high longevity line goats]), to a 2-d underfeeding challenge during early lactation. We measured the concentration of 13 milk metabolites and the activity of 1 enzyme during prechallenge, challenge, and recovery periods. Functional principal component analysis summarized the trends of milk metabolite concentration over time efficiently without preliminary assumptions concerning the shapes of the curves. We first ran a supervised prediction of the longevity line of the goats based on the milk metabolite curves. The partial least square analysis could not predict the longevity line accurately. We thus decided to explore the large overall variability of milk metabolite curves with an unsupervised clustering. The large year × facility effect on the metabolite concentrations was precorrected for. This resulted in 3 clusters of goats defined by different metabolic responses to underfeeding. The cluster that showed higher β-hydroxybutyrate, cholesterol, and triacylglycerols increase during the underfeeding challenge was associated with poorer survival compared with the other 2 clusters. These results suggest that multivariate analysis of noninvasive milk measures show potential for deriving new resilience phenotypes.