Candidate markers for enhanced host response to PRRS have scarce adverse effects on pigs' growth and production.

BACKGROUND: Porcine Reproductive and Respiratory Syndrome (PRRS) is one of the most challenging viral diseases that cause substantial economic losses in the pig industry worldwide. The clinical signs of PRRS depend on, among others, the immunomodulatory properties of the PRRS virus strain, farm health status, herd immunity, and host genetics. The high virulence and mutation rate of PRRS virus limit the efficacy of vaccination programs. In recent years, several candidate genetic markers associated with PRRS resilience have been identified, and selective breeding was suggested as an additional approach to control PRRS under field conditions. Even so, it is essential to investigate the effects of these genetic markers on pigs' productivity. Our study aimed to assess the association between seven previously reported candidate genetic markers for host response to PRRS (rs80800372 in GBP1, rs340943904 in GBP5, rs322187731 in GBP6, rs1107556229 in CD163, rs338508371 in SGK1, rs80928141 in TAP1, and a 275-bp insertion in the promoter of MX1) and production traits in pigs under non-challenging conditions. RESULTS: About 600 high-health Duroc pigs were genotyped for the selected genetic markers and their effects on production traits (live body weight, carcass weight, backfat thickness, intramuscular fat content and composition) were assessed using a linear model. The genetic markers GBP5_rs340943904, GBP6_rs322187731, CD163_rs1107556229, and the 275-bp insertion at the promoter of MX1 showed no relevant associations with growth and carcass traits at slaughter. Regarding GBP1_rs80800372 (WUR1000125), the favourable G allele for PRRS resilience displayed significant additive effects on backfat thickness (+ 1.18 ± 0.42 mm; p = 0.005) and lean content (-1.72 ± 0.56%; p ≤ 0.01) at slaughter. In addition, the genetic markers SGK1_rs338508371 and TAP1_rs8092814 were associated with the palmitoleic content in gluteus medius, without affecting the total of the monounsaturated fatty acids. CONCLUSIONS: Our results indicate that genetic markers for PRRS resilience have no relevant effects on growth and carcass traits in pigs reared under non-challenging conditions, except for GBP1_rs80800372 where the favourable allele for PRRS response has a negative impact on lean content. Therefore, since the effects of GBP1_rs80800372 were attributed to the causal variant GBP5_rs340943904, it seems beneficial to select pigs for the genetic marker at GBP5 instead of GBP1. Overall, pigs might be selected for enhanced PRRS resilience without compromising their overall productivity.

AFM-IR of Electrohydrodynamically Printed PbS Quantum Dots: Quantifying Ligand Exchange at the Nanoscale.

Colloidal quantum dots (cQDs), semiconductor materials with widely tunable properties, can be printed in submicrometer patterns through electrohydrodynamic printing, avoiding aggressive photolithography steps. Postprinting ligand exchange determines the final optoelectronic properties of the cQD structures. However, achieving a complete bulk exchange is challenging, and the conventional vibrational analysis lacks the required spatial resolution. Infrared nanospectroscopy enables quantitative analysis of vibrational signals and structural topography on the nanometer scale upon ligand substitution on lead sulfide cQDs. A solution of ethanedithiol led to rapid (∼60 s) exchange of ≤90% of the ligands, in structures up to ∼750 nm thick. Prolonged exposures (>1 h) caused the degradation of the microstructures, with a systematic removal of cQDs regulated by surface:bulk ratios and solvent interactions. This study establishes a method for the development of devices through a combination of tunable photoactive materials, additive manufacturing of microstructures, and their quantitative nanometer-scale analysis.

Sequence variants associated with resilient responses in growing pigs.

The current work aimed to identify genomic regions and candidate genes associated with resilience in pigs. In previous work, we proposed the body weight deviation from the expected growth curve (ΔBW) and the increase of the positive acute-phase protein haptoglobin (ΔHP) after a vaccine challenge as resilience indicators which may be improved through selective breeding in pigs. Individuals with steady growth rate and minor activation of haptoglobin (high ΔBW and low ΔHP values) were considered resilient. In contrast, pigs with perturbed growth rate and high activation of haptoglobin (low ΔBW and high ΔHP values) were considered susceptible. Both ∆BW and ∆HP were simultaneously considered to select the most resilient (N = 40) and susceptible (N = 40) pigs. A genome-wide association study was carried out for the pigs' response classification to the challenge test using whole-genome sequence data (7,760,720 variants). Eleven associated genomic regions were identified, harbouring relevant candidate genes related to the immune response (such as pro- and anti-inflammatory responses) and growth pathways. These associated genomic regions harboured 41 potential functional mutations (frameshift, splice donor, splice acceptor, start loss and stop loss/gain) in candidate genes. Overall, this study advances our knowledge about the genetic determinism of resilience, highlighting its polygenic nature and strong relationship with immunity and growth.

Evidence of a second-order phase transition in the six-dimensional Ising spin glass in a field.

The very existence of a phase transition for spin glasses in an external magnetic field is controversial, even in high dimensions. We carry out massive simulations of the Ising spin-glass in a field, in six dimensions (which, according to classical-but not generally accepted-field-theoretical studies, is the upper critical dimension). We obtain results compatible with a second-order phase transition and estimate its critical exponents for the simulated lattice sizes. The detailed analysis performed by other authors of the replica symmetric Hamiltonian, under the hypothesis of critical behavior, predicts that the ratio of the renormalized coupling constants remain bounded as the correlation length grows. Our numerical results are in agreement with this expectation.

Do NPM1 and FLT3-ITD mutations modify prognosis in patients treated with non-intensive regimens?

FLT3-ITD and NPM1 mutations are key to defining the genetic risk profile of acute myeloid leukemia (AML). We aimed to assess the prognostic features of the FLT3-ITD and NPM1 mutations in old and/or unfit individuals with AML treated with non-intensive therapies in the era before azacitidine-venetoclax approbation. The results of various non-intensive regimens were also compared. We conducted a retrospective analysis that included patients treated with different non-intensive regimens, between 2007 and 2020 from PETHEMA AML registry. We compiled 707 patients with a median age of 74 years and median follow-up time of 37.7 months. FLT3-ITD patients (N = 98) showed a non-significant difference in overall survival (OS) compared to FLT3-ITD negative-patients (N = 608) (P = 0.17, median OS was 5 vs 7.3 months respectively). NPM1-mutated patients (N = 144) also showed a non-significant difference with NPM1 wild type (N = 519) patients (P = 0.25, median OS 7.2 vs 6.8 respectively). In the Cox regression analysis neither NPM1 nor FLT3-ITD nor age were significant prognostic variables for OS prediction. Abnormal karyotype and a high leukocyte count showed a statistically significant deleterious effect. Azacitidine also showed better survival compared to FLUGA (low dose cytarabine plus fludarabine). NPM1 and FLT3-ITD seem to lack prognostic value in older/unfit AML patients treated with non-intensive regimens other than azacitidine-venetoclax combination.

Charge density waves tuned by biaxial tensile stress.

The precise arrangement and nature of atoms drive electronic phase transitions in condensed matter. To explore this tenuous link, we developed a true biaxial mechanical deformation device working at cryogenic temperatures, compatible with x-ray diffraction and transport measurements, well adapted to layered samples. Here we show that a slight deformation of TbTe3 can have a dramatic influence on its Charge Density Wave (CDW), with an orientational transition from c to a driven by the a/c parameter, a tiny coexistence region near a = c, and without space group change. The CDW transition temperature Tc displays a linear dependence with a / c - 1 while the gap saturates out of the coexistence region. This behaviour is well accounted for within a tight-binding model. Our results question the relationship between gap and Tc in RTe3 systems. This method opens a new route towards the study of coexisting or competing electronic orders in condensed matter.

Erratum: Large-scale kinetic roughening behavior of coffee-ring fronts [Phys. Rev. E 106, 044801 (2022)].

This corrects the article DOI: 10.1103/PhysRevE.106.044801.

APOBEC2 safeguards skeletal muscle cell fate through binding chromatin and regulating transcription of non-muscle genes during myoblast differentiation.

The apolipoprotein B messenger RNA editing enzyme, catalytic polypeptide (APOBEC) family is composed of nucleic acid editors with roles ranging from antibody diversification to RNA editing. APOBEC2, a member of this family with an evolutionarily conserved nucleic acid-binding cytidine deaminase domain, has neither an established substrate nor function. Using a cellular model of muscle differentiation where APOBEC2 is inducibly expressed, we confirmed that APOBEC2 does not have the attributed molecular functions of the APOBEC family, such as RNA editing, DNA demethylation, and DNA mutation. Instead, we found that during muscle differentiation APOBEC2 occupied a specific motif within promoter regions; its removal from those regions resulted in transcriptional changes. Mechanistically, these changes reflect the direct interaction of APOBEC2 with histone deacetylase (HDAC) transcriptional corepressor complexes. We also found that APOBEC2 could bind DNA directly, in a sequence-specific fashion, suggesting that it functions as a recruiter of HDAC to specific genes whose promoters it occupies. These genes are normally suppressed during muscle cell differentiation, and their suppression may contribute to the safeguarding of muscle cell fate. Altogether, our results reveal a unique role for APOBEC2 within the APOBEC family.

Biosynthesis of Strained Amino Acids by a PLP-Dependent Enzyme through Cryptic Halogenation.

Amino acids (AAs) are modular building blocks which nature uses to synthesize both macromolecules, such as proteins, and small molecule natural products, such as alkaloids and non-ribosomal peptides. While the 20 main proteinogenic AAs display relatively limited side chain diversity, a wide range of non-canonical amino acids (ncAAs) exist that are not used by the ribosome for protein synthesis, but contain a broad array of structural features and functional groups. In this communication, we report the discovery of the biosynthetic pathway for a new ncAA, pazamine, which contains a cyclopropane ring formed in two steps. In the first step, a chlorine is added onto the C4 position of lysine by a radical halogenase, PazA. The cyclopropane ring is then formed in the next step by a pyridoxal-5'-phosphate-dependent enzyme, PazB, via an SN2-like attack at C4 to eliminate chloride. Genetic studies of this pathway in the native host, Pseudomonas azotoformans, show that pazamine potentially inhibits ethylene biosynthesis in growing plants based on alterations in the root phenotype of Arabidopsis thaliana seedlings. We further show that PazB can be utilized to make an alternative cyclobutane-containing AA. These discoveries may lead to advances in biocatalytic production of specialty chemicals and agricultural biotechnology.

Cryopreservation of seeds of Neonotonia wightii Wight and Arn: a strategy for conservation, dormancy breaking and preservation of nutritional status.

BACKGROUND: N. wightii (Leguminosae) is valued as a cover crop and as a potential source of protein in food insecure countries. However, plantlet establishment is limited by physical dormancy. Our previous work has shown that exposure of N. wightii seeds to cryogenic temperatures is able to overcome physical dormancy. OBJECTIVE: The current study is an extension of that work where the field performance and nutritional composition of plants regenerated from N. wightii seeds was investigated. RESULTS: It was evident that plants regenerated from cryopreserved seeds displayed faster growth rates than those from control seeds. In addition, cryopreservation did not alter the nutritional profile of plants produced from cryo-stored seeds. CONCLUSION: Collectively, the results indicate that cryopreservation serves as a suitable strategy for the preservation of seeds of N. wightii with the added benefit of also serving as a dormancy breaking mechanism upon retrieval from cryogenic temperatures. Doi.org/10.54680/fr23510110712.

Universal interface fluctuations in the contact process.

We study the interface representation of the contact process at its directed-percolation critical point, where the scaling properties of the interface can be related to those of the original particle model. Interestingly, such a behavior happens to be intrinsically anomalous and more complex than that described by the standard Family-Vicsek dynamic scaling Ansatz of surface kinetic roughening. We expand on a previous numerical study by Dickman and Muñoz [Phys. Rev. E 62, 7632 (2000)10.1103/PhysRevE.62.7632] to fully characterize the kinetic roughening universality class for interface dimensions d=1,2, and 3. Beyond obtaining scaling exponent values, we characterize the interface fluctuations via their probability density function (PDF) and covariance, seen to display universal properties which are qualitatively similar to those recently assessed for the Kardar-Parisi-Zhang (KPZ) and other important universality classes of kinetic roughening. Quantitatively, while for d=1 the interface covariance seems to be well described by the KPZ, Airy_{1} covariance, no such agreement occurs in terms of the fluctuation PDF or the scaling exponents.

Age-related Changes in the Adrenal Cortex: Insights and Implications.

Aging is characterized by a gradual decline in physiological function. This process affects all organs including the adrenal cortex, which normally functions to produce essential steroid hormones including mineralocorticoids, glucocorticoids, and androgens. With increasing age, features such as reduced adrenal cortex size, altered zonation, and increased myeloid immune cell infiltration substantially alter the structure and function of the adrenal cortex. Many of these hallmark features of adrenal cortex aging occur both in males and females, yet are more enhanced in males. Hormonally, a substantial reduction in adrenal androgens is a key feature of aging, which is accompanied by modest changes in aldosterone and cortisol. These hormonal changes are associated with various pathological consequences including impaired immune responses, decreased bone health, and accelerated age-related diseases. One of the most notable changes with adrenal aging is the increased incidence of adrenal tumors, which is sex dimorphic with a higher prevalence in females. Increased adrenal tumorigenesis with age is likely driven by both an increase in genetic mutations as well as remodeling of the tissue microenvironment. Novel antiaging strategies offer a promising avenue to mitigate adrenal aging and alleviate age-associated pathologies, including adrenal tumors.

Bibliometric analysis of original articles of journal Enfermería Intensiva in the period 2001-2020.

INTRODUCTION: Bibliometric analysis allow the quantitative evaluation of the characteristics of a scientific publication. OBJECTIVE: To perform a bibliometric analysis of original articles in the journal Enfermería Intensiva from 2001 to 2020. RESULTS: The journal Enfermería Intensiva has published, between 2001 and 2020, 438 works, of which 259 are original articles (59.1%). These original articles are mostly quantitative studies (76.1%), with an average of 30.5 bibliographic references (SD 13.9), 4.9 citations (SD 1.7) in the Web of Science and Scopus repertoires, and 15,489.5 visits/downloads (median 9090 and interquartile range 4567-15,260) according to information on the magazine's website. These originals have been signed by 1345 authors, which represents a collaboration index of 5.2. 78.0% of the authors are sporadic, having published only one work. Most of the articles come from authors who work in institutionally located in hospitals and university centers, and geographically in the Communities of Madrid, Cataluña, Navarra and Andalucía. CONCLUSIONS: There is little international, regional and institutional collaboration, producing the highest level of collaboration between authors from the same center. The journal has established itself in the panorama of scientific nursing research in Spain and shows bibliometric indicators similar or even superior to other publications in its environment.

Senescence-induced immune remodeling facilitates metastatic adrenal cancer in a sex-dimorphic manner.

Aging markedly increases cancer risk, yet our mechanistic understanding of how aging influences cancer initiation is limited. Here we demonstrate that the loss of ZNRF3, an inhibitor of Wnt signaling that is frequently mutated in adrenocortical carcinoma, leads to the induction of cellular senescence that remodels the tissue microenvironment and ultimately permits metastatic adrenal cancer in old animals. The effects are sexually dimorphic, with males exhibiting earlier senescence activation and a greater innate immune response, driven in part by androgens, resulting in high myeloid cell accumulation and lower incidence of malignancy. Conversely, females present a dampened immune response and increased susceptibility to metastatic cancer. Senescence-recruited myeloid cells become depleted as tumors progress, which is recapitulated in patients in whom a low myeloid signature is associated with worse outcomes. Our study uncovers a role for myeloid cells in restraining adrenal cancer with substantial prognostic value and provides a model for interrogating pleiotropic effects of cellular senescence in cancer.

A Suite of Constitutive Promoters for Tuning Gene Expression in Plants.

The need for convenient tools to express transgenes over a large dynamic range is pervasive throughout plant synthetic biology; however, current efforts are largely limited by the heavy reliance on a small set of strong promoters, precluding more nuanced and refined engineering endeavors in planta. To address this technical gap, we characterize a suite of constitutive promoters that span a wide range of transcriptional levels and develop a GoldenGate-based plasmid toolkit named PCONS, optimized for versatile cloning and rapid testing of transgene expression at varying strengths. We demonstrate how easy access to a stepwise gradient of expression levels can be used for optimizing synthetic transcriptional systems and the production of small molecules in planta. We also systematically investigate the potential of using PCONS as an internal standard in plant biology experimental design, establishing the best practices for signal normalization in experiments. Although our library has primarily been developed for optimizing expression in N. benthamiana, we demonstrate the translatability of our promoters across distantly related species using a multiplexed reporter assay with barcoded transcripts. Our findings showcase the advantages of the PCONS library as an invaluable toolkit for plant synthetic biology.

The epidemiology of multifood allergy in the United States: A population-based study.

BACKGROUND: Immunoglobulin E (IgE)-mediated food allergies (FAs) are increasingly common among US children and adults. Not only can living with FA impose considerable physical health impacts, but it also imposes economic burden and can negatively affect quality of life. Limited data indicate that allergy to multiple foods (multi-FA) also may be common, but much remains unknown about its distribution and determinants. OBJECTIVE: To characterize the prevalence, characteristics, determinants, psychosocial burden, and distribution of multi-FA among a large, nationally representative sample of US children and adults. METHODS: A US population-based survey was administered. Estimates of multi-FA prevalence, conditional frequencies of multi-FA combinations, and associated factors were derived. Latent class analyses were conducted using 9 dichotomized indicators of specific FA prevalence, which were used to determine factors associated with latent class membership and characterize FA-related psychosocial burden within each class. RESULTS: Surveys were completed for 38,408 children and 40,443 adults. Among children and adults meeting established symptom-report criteria for FA, an estimated 40% and 48% had multi-FA, respectively. Among pediatric and adult populations with convincing FAs, the lifetime reported prevalence of physician-diagnosed atopic comorbidities increased significantly as the number of reported current convincing FAs increased, as did the proportion reporting multi-FA-related health care utilization and higher perceived psychosocial burden. Latent class analyses suggested the existence of the following 4 key latent phenotypes of multi-FA: milk and egg-dominant, seafood-dominant, peanut and tree nut-dominant, and broadly multi-food allergic. CONCLUSION: The US population-level burden of multi-FA is high among both children and adults, and data indicate the presence of 4 major phenotypes of multi-FA in both populations.

Effectiveness of interventions for academic burnout among nursing students: A systematic review.

BACKGROUND: Nursing students experience higher stress and burnout compared to students in other health professions, with a prevalence rate of as high as 20%. More recently, they have been affected by changes in nursing education due to the COVID-19 pandemic, such as requirements for social isolation and distance learning. Although there are existing studies on interventions that address academic burnout among nursing students, there is no synthesis of randomized trials on this topic. AIM: This study aimed to systematically synthesize studies of interventions for academic burnout among nursing students. METHODS: A systematic search for randomized controlled trials was performed in PubMed, CINAHL, CENTRAL, Web of Science, and Scopus. Eligibility criteria were based on study directness in relation to the Patient, Intervention, Comparison, and Outcome (PICO) question. Two review authors independently screened articles for inclusion, collected data from the included studies, and performed risk of bias assessments using the Cochrane Risk of Bias Tool 2.0. A narrative synthesis was performed. This review was registered a priori in PROSPERO (CRD42022350196). RESULTS: Six papers were included in this review. Various interventions were studied: Qigong exercises, progressive muscle relaxation, autogenic therapy and laughter therapy, didactic behavioral sessions focusing on personal and professional development, and coping skills enhancement. The effects of these interventions on academic burnout, depression, and stress among nursing students were short term and their benefits over time remain uncertain. LINKING EVIDENCE TO ACTION: Progressive muscle relaxation and cognitive behavioral interventions demonstrated short-term positive effects on academic burnout, depression, and stress among nursing students. These findings may support the development of individual-level and organizational-level initiatives for nursing students aimed to lessen or prevent academic burnout. Large-scale, high-quality studies on the effect of interventions on academic burden in various settings and cultures are needed.

Exposure of maize seeds to liquid nitrogen modifies the morphology and hormonal response of young plants.

BACKGROUND: Cryopreservation currently represents the most suitable strategy for the long-term conservation of plant germplasm. While much effort has focused on the development of protocols to enable successful cryostorage, there are few, if any reports, that consider the effect of cryogenic temperatures on the phytohormone status of the seed and developing seedlings. OBJECTIVE: To investigate the effect of cryopreservation on external seed coat features as well as levels of indole-3-acetic acid (IAA), abscisic acid (ABA) and 1-aminocyclopropane-1-carboxylic acid (ACC) in maize. MATERIALS AND METHODS: Two groups of seeds at 6% moisture content were compared: one was maintained at 4 degree C (control) while the other was exposed to LN within cryo-vials. RESULTS: Seeds exposed to cryogenic temperatures were characterized by the presence of large cracks in the seed coat compared with control seeds. Cryogenic exposure also resulted in a reduction in biomass and plant height. Results from the phytohormone analysis showed an initial reduction in the levels of IAA, ABA and ACC after 7 days of growth followed by sharp increase in levels relative to the control by 14 days. Whilst the roles of ABA and ethylene (and by extension, its precursor ACC) are well studied as stress response molecules, much less is known about the potentially vital role of auxins in regulating plant growth under conditions of low temperature stress. CONCLUSION: It is postulated that the interaction of all three hormones modulate crosstalk between various stress responses and recovery pathways to ameliorate the damage caused by freezing stress and enable plant survival. Given the dearth of information on phytohormones in cryobiology, more studies are needed to fully elucidate these relationships in the context of freezing stress caused by liquid nitrogen. Doi.org/10.54680/fr23610110612.

Erratum: Numerical test of the replica-symmetric Hamiltonian for correlations of the critical state of spin glasses in a field [Phys. Rev. E 105, 054106 (2022)].

This corrects the article DOI: 10.1103/PhysRevE.105.054106.

Biosynthesis of Strained Amino Acids Through a PLP-Dependent Enzyme via Cryptic Halogenation.

Amino acids (AAs) are modular and modifiable building blocks which nature uses to synthesize both macromolecules, such as proteins, and small molecule natural products, such as alkaloids and non-ribosomal peptides (NRPs). While the 20 main proteinogenic AAs display relatively limited side-chain diversity, a wide range of non-canonical amino acids (ncAAs) exist that are not used by the ribosome for protein synthesis but contain a broad array of structural features and functional groups not found in proteinogenic AAs. In this communication, we report the discovery of the biosynthetic pathway for a new ncAA, pazamine, which contains a cyclopropane ring formed in two steps. In the first step, a chlorine is added onto the C4 position of lysine by a radical halogenase PazA. The cyclopropane ring is then formed in the next step by a pyridoxal-5'-phosphate-dependent enzyme, PazB, via an SN2-like attack onto C4 to eliminate chloride. Genetic studies of this pathway in the native host, Pseudomonas azotoformans, show that pazamine and its succinylated derivative, pazamide, potentially inhibit ethylene biosynthesis in growing plants based on alterations in the root phenotype of Arabidopsis thaliana seedlings. We further show that PazB can be utilized to make an alternative cyclobutane-containing AA. These discoveries may lead to advances in biocatalytic production of specialty chemicals and agricultural biotechnology.