The white rot basidiomycete Gelatoporia subvermispora produces fatty aldehydes that enable fungal manganese peroxidases to degrade recalcitrant lignin structures.

The ability of some white rot basidiomycetes to remove lignin selectively from wood indicates that low molecular weight oxidants have a role in ligninolysis. These oxidants are likely free radicals generated by fungal peroxidases from compounds in the biodegrading wood. Past work supports a role for manganese peroxidases (MnPs) in the production of ligninolytic oxidants from fungal membrane lipids. However, the fatty acid alkylperoxyl radicals initially formed during this process are not reactive enough to attack the major structures in lignin. Here, we evaluate the hypothesis that the peroxidation of fatty aldehydes might provide a source of more reactive acylperoxyl radicals. We found that Gelatoporia subvermispora produced trans-2-nonenal, trans-2-octenal, and n-hexanal (a likely metabolite of trans-2,4-decadienal) during the incipient decay of aspen wood. Fungal fatty aldehydes supported the in vitro oxidation by MnPs of a nonphenolic lignin model dimer, and also of the monomeric model veratryl alcohol. Experiments with the latter compound showed that the reactions were partially inhibited by oxalate, the chelator that white rot fungi employ to detach Mn3+ from the MnP active site, but nevertheless proceeded at its physiological concentration of 1 mM. The addition of catalase was inhibitory, which suggests that the standard MnP catalytic cycle is involved in the oxidation of aldehydes. MnP oxidized trans-2-nonenal quantitatively to trans-2-nonenoic acid with the consumption of one O2 equivalent. The data suggest that when Mn3+ remains associated with MnP, it can oxidize aldehydes to their acyl radicals, and the latter subsequently add O2 to become ligninolytic acylperoxyl radicals.IMPORTANCEThe biodegradation of lignin by white rot fungi is essential for the natural recycling of plant biomass and has useful applications in lignocellulose bioprocessing. Although fungal peroxidases have a key role in ligninolysis, past work indicates that biodegradation is initiated by smaller, as yet unidentified oxidants that can infiltrate the substrate. Here, we present evidence that the peroxidase-catalyzed oxidation of naturally occurring fungal aldehydes may provide a source of ligninolytic free radical oxidants.

Examining the Effect of Freezing Temperatures on the Survival Rate of Micro-Encapsulated Probiotic Lactobacillus acidophilus LA5 Using the Flash Freeze-Drying (FFD) Strategy.

This work proposes a novel drying method suitable for probiotic bacteria, called flash freeze-drying (FFD), which consists of a cyclic variation in pressure (up-down) in a very short time and is applied during primary drying. The effects of three FFD temperatures (-25 °C, -15 °C, and -3 °C) on the bacterial survival and water activity of Lactobacillus acidophilus LA5 (LA), previously microencapsulated with calcium alginate and chitosan, were evaluated. The total process time was 900 min, which is 68.75% less than the usual freeze-drying (FD) time of 2880 min. After FFD, LA treated at -25 °C reached a cell viability of 89.94%, which is 2.74% higher than that obtained by FD, as well as a water activity of 0.0522, which is 55% significantly lower than that observed using FD. Likewise, this freezing temperature showed 64.72% cell viability at the end of storage (28 days/20 °C/34% relative humidity). With the experimental data, a useful mathematical model was developed to obtain the optimal FFD operating parameters to achieve the target water content in the final drying.

The Impact of Sibling Relationships on Behavioral and Sexual Health among Latino Sexual Minority Men.

Pre-exposure prophylaxis (PrEP) is a highly effective method for preventing HIV acquisition and plays a crucial role in the Ending the HIV Epidemic in the US initiative. However, there are various barriers that hinder the access and uptake of PrEP among Latino sexual minority men (SMM) at individual, interpersonal, and cultural levels. While the significance of cultural factors in designing and implementing HIV prevention programs for Latino populations has been consistently emphasized in the literature and prioritized by the Centers for Disease Control and Prevention, few studies have directly integrated these cultural factors into their programs. Our study aimed to investigate the potential influence of siblings in promoting the utilization of PrEP for HIV prevention, an area that has received limited attention. We conducted interviews with 31 pairs of siblings between December 2020 and January 2021, which were held in either English or Spanish and lasted approximately 45-60 min. The data were analyzed using a deductive thematic content analysis approach. The interviews revealed several key themes and categories, including: (1) Sibling support for coming out; (2) Types of support that siblings provide to each other for behavior change; (3) Sibling support for PrEP; and (4) The impact of the study interview on the quality of the sibling relationships. Our findings indicated that siblings were willing to provide support for PrEP in various ways, ranging from emotional support for brothers who may be concerned about potential rejection to practical support such as transportation or financial assistance. These results have significant implications for the design of HIV prevention interventions for Latinos. Incorporating siblings or other extended family members into these interventions can facilitate communication between siblings and their brothers, ultimately encouraging the use of PrEP or similar prevention methods. By considering the unique dynamics and support systems within Latino communities, researchers can develop more effective strategies to promote HIV prevention and support the well-being of Latino SMM.

Exploring Psychosocial Distress in Caregivers of Children and Youth With Special Health Care Needs.

PURPOSE: Caring for a child or youth with special health care needs (CYSHCN) can be overwhelming. Parents and caregivers may experience psychosocial distress, such as depression, frustration, and hopelessness. The purpose of the current study was to gain further insight into families' perspectives on the psychosocial impacts of caring for CYSHCN to identify gaps in health care systems and strengthen systems of support. METHOD: A qualitative descriptive design was used in 16 parents and caregivers. Colaizzi's method of analysis and semi-structured interviews were used. RESULTS: Six themes emerged from this study: (1) Stigma and Isolation, (2) Religion as a Coping Mechanism, (3) Financial Challenges, (4) Bearing the Burden, (5) Familial Denial, and (6) System-Related Concerns. CONCLUSION: Psychiatric-mental health nurses (PMHNs) are in a pivotal position to use their knowledge, skills, and experiences to guide families. PMHNs can also engage communities and enhance mental health promotion to break the stigma associated with having a CYSHCN. [Journal of Psychosocial Nursing and Mental Health Services, xx(xx), xx-xx.].

The contribution of brain volume to explain autonomous imbalance during recovery from acute stress in batterers.

AIM: Many authors have suggested that intimate partner violence (IPV) perpetrators present an imbalance between both branches of the autonomous nervous system when coping with acute stress. Concretely, there is a predominance of the sympathetic branches over the parasympathetic ones when recovering from stress. This imbalance can be explained by their tendency toward anger rumination, and more concretely, by their focus on thoughts of revenge during this period. Unfortunately, there is a gap in the scientific literature in terms of using magnetic resonance imaging (MRI) techniques to assess which brain structures would explain this tendency of IPV perpetrators when coping with acute stress. METHOD: The main objective of this study was to assess whether the gray matter volume (GMV) of relevant brain structures, signaled in previous scientific literature, moderates the association between thoughts of revenge and sympathetic activation during the recovery period, based on skin conductance levels (SCL) after being exposed to stress, in a group of IPV perpetrators (n = 58) and non-violent men (n = 61). RESULTS: This study highlighted that the GMV of the left nucleus accumbens, right lobules of the cerebellum, and inferior temporal gyrus in IPV perpetrators moderated the association between thoughts of revenge and SCL during the recovery period. Accordingly, the higher the thoughts of revenge, the higher the sympathetic predominance (or higher SCL levels), especially among IPV perpetrators with the lowest GMV of these brain structures. Nonetheless, those variables were unrelated in the control group. CONCLUSIONS: Our study highlights the involvement of certain brain structures and how they explain the tendency of some IPV perpetrators to ruminate anger or, more precisely, to focus on thoughts of revenge when they recover from acute stress. These results reinforce the need to incorporate neuroimaging techniques during screening processes to properly understand how IPV perpetrators deal with stress, which in turn helps target their needs and design concrete intervention modules.

Effects of digital transformation on firm performance: The role of IT capabilities and digital orientation.

Organisations undertake profound changes to fit in a rapidly evolving digital setting. However, although the IT capabilities of the organisational members play a critical role in this, the mechanism driving IT capabilities towards enhanced firm performance is not fully understood. A theoretical model to analyse the role of digital orientation and digital transformation in this relationship is introduced and tested on a set of 246 firms through the Partial Least Squares-Structural Equation Modeling method (PLS-SEM). This research contributes to the literature by introducing the social aspect to the study of technology management, delving also into the antecedents of digital transformation. Results confirm a positive effect of IT capabilities on firm performance through the development of a digital orientation and the digital transformation of the organisation.

Weakened sympathetic response and lower parasympathetic activity in intimate partner violence perpetrators when empathizing: Influence of autonomous activation in affective approach and prosocial behavior.

The autonomic nervous system (ANS) functioning has been proposed as a relevant method to characterize the therapeutic needs of intimate partner violence (IPV) perpetrators. Nevertheless, research has neglected the influence of the ANS on socio-affective functions in this population. The aim of the present study was to analyze the psychophysiological activity of IPV perpetrators (n = 52) compared to controls (n = 46) following an empathic induction task, performed through negative emotion-eliciting videos. We employed two general ANS markers (heart rate [HR] and respiratory rate [RR]), two sympathetic-related indexes (pre-ejection period [PEP] and skin conductance level [SCL]) and a parasympathetic biomarker (respiratory sinus arrhythmia [RSA]). Additionally, we explored the impact of psychophysiological activity on prosocial behavior using Hare's donation procedure. Compared to controls, IPV perpetrators reported lower HR and SCL following the task, as well as longer PEP, suggesting an attenuated sympathetic response to others' distress. No differences in the RSA response pattern were found, however, IPV perpetrators displayed lower overall RSA levels throughout the protocol, indicative of reduced parasympathetic activity. Besides, while no differences in prosocial performance were observed, greater sympathetic responses and overall parasympathetic activity predicted increased donations across the sample. Thus, a high sympathetic and parasympathetic activity might influence the occurrence of prosocial behavior. The present study provides further evidence supporting that IPV perpetrators cope differently with others' negative emotions. In line with this biopsychosocial perspective, insights are gained on the emotional processing of IPV perpetrators which, in turn, could contribute to improve IPV psychotherapeutic programs.

The role of intimate partner violence perpetrators' resting state functional connectivity in treatment compliance and recidivism.

To expand the scientific literature on how resting state functional connectivity (rsFC) magnetic resonance imaging (MRI) (or the measurement of the strength of the coactivation of two brain regions over a sustained period of time) can be used to explain treatment compliance and recidivism among intimate partner violence (IPV) perpetrators. Therefore, our first aim was to assess whether men convicted of IPV (n = 53) presented different rsFC patterns from a control group of non-violent (n = 47) men. We also analyzed if the rsFC of IPV perpetrators before staring the intervention program could explain treatment compliance and recidivism one year after the intervention ended. The rsFC was measured by applying a whole brain analysis during a resting period, which lasted 45 min. IPV perpetrators showed higher rsFC in the occipital brain areas compared to controls. Furthermore, there was a positive association between the occipital pole (OP) and temporal lobes (ITG) and a negative association between the occipital (e.g., occipital fusiform gyrus, visual network) and both the parietal lobe regions (e.g., supramarginal gyrus, parietal operculum cortex, lingual gyrus) and the putamen in IPV perpetrators. This pattern was the opposite in the control group. The positive association between many of these occipital regions and the parietal, frontal, and temporal regions explained treatment compliance. Conversely, treatment compliance was also explained by a reduced rsFC between the rostral prefrontal cortex and the frontal gyrus and both the occipital and temporal gyrus, and between the temporal and the occipital and cerebellum areas and the sensorimotor superior networks. Last, the enhanced rsFC between the occipital regions and both the cerebellum and temporal gyrus predicted recidivism. Our results highlight that there are specific rsFC patterns that can distinguish IPV perpetrators from controls. These rsFC patterns could be useful to explain treatment compliance and recidivism among IPV perpetrators.

Reversal of biological age in multiple rat organs by young porcine plasma fraction.

Young blood plasma is known to confer beneficial effects on various organs in mice and rats. However, it was not known whether plasma from young adult pigs rejuvenates old rat tissues at the epigenetic level; whether it alters the epigenetic clock, which is a highly accurate molecular biomarker of aging. To address this question, we developed and validated six different epigenetic clocks for rat tissues that are based on DNA methylation values derived from n = 613 tissue samples. As indicated by their respective names, the rat pan-tissue clock can be applied to DNA methylation profiles from all rat tissues, while the rat brain, liver, and blood clocks apply to the corresponding tissue types. We also developed two epigenetic clocks that apply to both human and rat tissues by adding n = 1366 human tissue samples to the training data. We employed these six rat clocks to investigate the rejuvenation effects of a porcine plasma fraction treatment in different rat tissues. The treatment more than halved the epigenetic ages of blood, heart, and liver tissue. A less pronounced, but statistically significant, rejuvenation effect could be observed in the hypothalamus. The treatment was accompanied by progressive improvement in the function of these organs as ascertained through numerous biochemical/physiological biomarkers, behavioral responses encompassing cognitive functions. An immunoglobulin G (IgG) N-glycosylation pattern shift from pro- to anti-inflammatory also indicated reversal of glycan aging. Overall, this study demonstrates that a young porcine plasma-derived treatment markedly reverses aging in rats according to epigenetic clocks, IgG glycans, and other biomarkers of aging.

Development of an International Virtual Multidisciplinary Tumor Board for Breast Cancer in Mongolia.

INTRODUCTION: Breast cancer is the most diagnosed cancer among Mongolian women and mortality rates are high. We describe a virtual multi-institutional and multidisciplinary tumor board (MTB) for breast cancer created to assist the National Cancer Center of Mongolia. MATERIALS AND METHODS: A virtual MTB for breast cancer was conducted with participation of two United States and 1 Mongolian cancer centers. A standardized template for presentations was developed. Recommendations were summarized and shared with participants. Collected data included patient demographics, tumor characteristics, stage, imaging and treatments performed, and recommendations. Questions were categorized as treatment, diagnosis, or palliative questions. RESULTS: Fifteen patients were evaluated. Median age was 39 y. 86.7% of breast cancers were invasive ductal cancers and 13.3% were metaplastic carcinomas. 53.3% were estrogen and progesterone receptor positive (ER+/PR+), 60% were HER2+, 13.3% were triple negative, and 26.7% were recurrent. 40% of patients were evaluated with mammography. 6% received positron emission tomography scans for metastatic evaluation. 66.7% of surgical patients received neoadjuvant chemotherapy. Herceptin was administered to 55.6% of patients with Her2+ cancers. Modified radical mastectomy was most commonly performed and reconstruction was rare. Sentinel lymph node biopsy was not performed. 66.7% of ER+/PR+ patients received endocrine therapy. 6.7% of patients received radiation. 75% of MTB questions pertained to treatment. Recommendations were related to systemic therapy (40%), surgical management (33.3%), pathology (13.3%), and imaging (13.3%). CONCLUSIONS: This study illustrates the development of an international, virtual, multi-institutional breast cancer MTB and provides insight into challenges and potential interventions to improve breast cancer care in Mongolia.

Three-dimensional blueprinting of molecular patterns in liquid crystalline polymers.

Exploiting the interplay of anisotropic diamagnetic susceptibility of liquid crystalline monomers and site selective photopolymerization enables the fabrication of 3D freeforms with highly refined microstructures. Utilizing chain transfer agents in the mesogenic inks presents a pathway for broadly tuning the mechanical properties of liquid crystalline polymers and their response to stimuli. In particular, the combination of 1,4-benzenedimethanethiol and tetrabromomethane is shown to enable voxelated blueprinting of molecular order, while allowing for a modulation of the crosslink density and the mechanical properties. The formulation of these monomers allows for the resolution of the voxels to approach the limits set by the coherence lengths defined by the anchoring from surfaces. These compositions demonstrate the expected thermotropic responses while allowing for their functionalization with photochromic switches to elicit photomechanical responses. Actuation strains are shown to outstrip that accomplished with prior systems that did not access chain transfer agents to modulate the structure of the macromolecular network. Test cases of this system are shown to create freeform actuators that exploit the refined director patterns during high-resolution printing. These include topological defects, hierarchically-structured light responsive grippers, and biomimetic flyers whose flight dynamics can be actively modulated via irradiation with light.

A Meta-analysis of Cognitive Functioning in Intimate Partner Violence Perpetrators.

Numerous psychologists have shown interest in applying neuropsychological tests to study intimate partner violence (IPV) perpetrators and gain a further understanding of the underlying nature of this type of violence. However, up until now, no meta-analysis has drawn on all the available scientific literature to calculate whether consistent differences exist between the neuropsychological performance of IPV perpetrators and other samples of men (non-violent men, IPV perpetrators with drug misuse, and other men with criminal history). The aim of this study was to carry out this calculation and also measure whether neuropsychological performance explained IPV perpetration. We conducted a meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. After initially identifying 7243 sources, we eventually included a total of 25 publications. The number of studies included for effect size calculation in each cognitive domain ranged from two to nine. Taking solely into account studies comparing IPV perpetrators with non-violent men, our findings indicate that both IPV perpetrators who misuse drugs and those who do not exhibit worse neuropsychological functioning compared to non-violent men. These differences range from moderate to large for working memory, switching attention, cognitive flexibility, planning abilities, and phonemic fluency. However, while low functioning in response IQ was only observed in IPV perpetrators without drug misuse, continuous attention performance only differed in IPV perpetrators with drug misuse. It should be noted that most conclusions were consistent. In addition, the comparison between IPV perpetrator subsamples and other types of criminal convictions only revealed differences in switching attention, with IPV perpetrators presenting worse abilities than the rest of the subsamples. Finally, we also found some support for significant associations between neuropsychological performance and both physical and psychological IPV perpetration. This meta-analysis is a significant contribution that will help inform future clinical strategies for the early detection of cognitive needs. It will also guide the implementation of new or complementary intervention programs.

Depolymerisation of Kraft Lignin by Tailor-Made Alkaliphilic Fungal Laccases.

Lignins released in the black liquors of kraft pulp mills are an underutilised source of aromatics. Due to their phenol oxidase activity, laccases from ligninolytic fungi are suitable biocatalysts to depolymerise kraft lignins, which are characterised by their elevated phenolic content. However, the alkaline conditions necessary to solubilise kraft lignins make it difficult to use fungal laccases whose activity is inherently acidic. We recently developed through enzyme-directed evolution high-redox potential laccases active and stable at pH 10. Here, the ability of these tailor-made alkaliphilic fungal laccases to oxidise, demethylate, and depolymerise eucalyptus kraft lignin at pH 10 is evidenced by the increment in the content of phenolic hydroxyl and carbonyl groups, the methanol released, and the appearance of lower molecular weight moieties after laccase treatment. Nonetheless, in a second assay carried out with higher enzyme and lignin concentrations, these changes were accompanied by a strong increase in the molecular weight and content of ß-O-4 and ß-5 linkages of the main lignin fraction, indicating that repolymerisation of the oxidised products prevails in one-pot reactions. To prevent it, we finally conducted the enzymatic reaction in a bench-scale reactor coupled to a membrane separation system and were able to prove the depolymerisation of kraft lignin by high-redox alkaliphilic laccase.

MicroRNAs Associated with Disability Progression and Clinical Activity in Multiple Sclerosis Patients Treated with Glatiramer Acetate.

MicroRNAs (miRNAs) are promising biomarkers in multiple sclerosis (MS). This study aims to investigate the association between a preselected list of miRNAs in serum with therapeutic response to Glatiramer Acetate (GA) and with the clinical evolution of a cohort of relapsing-remitting MS (RRMS) patients. We conducted a longitudinal study for 5 years, with cut-off points at 2 and 5 years, including 26 RRMS patients treated with GA for at least 6 months. A total of 6 miRNAs from a previous study (miR-9.5p, miR-126.3p, mir-138.5p, miR-146a.5p, miR-200c.3p, and miR-223.3p) were selected for this analysis. Clinical relapse, MRI activity, confirmed disability progression (CDP), alone or in combination (No Evidence of Disease Activity-3) (NEDA-3), and Expanded Disability Status Scale (EDSS), were studied. After multivariate regression analysis, miR-9.5p was associated with EDSS progression at 2 years (ß = 0.23; 95% CI: 0.04-0.46; p = 0.047). Besides this, mean miR-138.5p values were lower in those patients with NEDA-3 at 2 years (p = 0.033), and miR-146a.5p and miR-126.3p were higher in patients with CDP progression at 2 years (p = 0.044 and p = 0.05 respectively. These results reinforce the use of microRNAs as potential biomarkers in multiple sclerosis. We will need more studies to corroborate these data and to better understand the role of microRNAs in the pathophysiology of this disease.

Would the Siblings of Latinx Men Who Have Sex With Men Encourage Their Brothers to Use PrEP? Findings From a Feasibility and Acceptability Study.

We explored whether siblings can be engaged in PrEP promotion. We used the Information-Motivation-Behavior model to develop and conduct surveys and dyadic interviews with Latino men who have sex with men (LMSM) and their siblings (n = 31) and three sibling-only focus groups (n = 20). For LMSM, only n = 14 (45%) agreed they would benefit from taking PrEP, yet n = 22 (71%) would take PrEP to make their sibling worry less about them, and n = 23 (74%) requested a PrEP referral. For siblings, n = 20 (65%) believed PrEP would benefit their brother, and n = 19 (95%) in the focus groups said they would take PrEP to help their brother get started. Qualitative results include (1) siblings' support for PrEP use, (2) explicit conversations about sex were not necessary for discussing sexual health, and (3) siblings wanted to understand what they could do to encourage their brother to consider PrEP. We conclude siblings can be engaged in PrEP promotion.

International Liver Transplantation Society Global Census: First Look at Pediatric Liver Transplantation Activity Around the World.

BACKGROUND: Over 16 000 children under the age of 15 died worldwide in 2017 because of liver disease. Pediatric liver transplantation (PLT) is currently the standard of care for these patients. The aim of this study is to describe global PLT activity and identify variations between regions. METHODS: A survey was conducted from May 2018 to August 2019 to determine the current state of PLT. Transplant centers were categorized into quintile categories according to the year they performed their first PLT. Countries were classified according to gross national income per capita. RESULTS: One hundred eight programs from 38 countries were included (68% response rate). 10 619 PLTs were performed within the last 5 y. High-income countries performed 4992 (46.4%) PLT, followed by upper-middle- (4704 [44·3%]) and lower-middle (993 [9·4%])-income countries. The most frequently used type of grafts worldwide are living donor grafts. A higher proportion of lower-middle-income countries (68·7%) performed ≥25 living donor liver transplants over the last 5 y compared to high-income countries (36%; P = 0.019). A greater proportion of programs from high-income countries have performed ≥25 whole liver transplants (52.4% versus 6.2%; P = 0.001) and ≥25 split/reduced liver transplants (53.2% versus 6.2%; P < 0.001) compared to lower-middle-income countries. CONCLUSIONS: This study represents, to our knowledge, the most geographically comprehensive report on PLT activity and a first step toward global collaboration and data sharing for the greater good of children with liver disease; it is imperative that these centers share the lead in PLT.

Geospatial availability of breast cancer treatment modalities and hypothetical access improvement in Ghana: A nationwide survey.

Breast cancer in Ghana is a growing public health problem with increasing incidence and poor outcomes. Lack of access to comprehensive treatment in Ghana may be a contributing factor to its high mortality. The purpose of this study was to evaluate the availability of treatments nationwide and systematically identify high yield areas for targeted expansion. We conducted a cross-sectional, nationwide hospital-based survey from November 2020-October 2021. Surveys were conducted in person with trained research assistants and described hospital availability of all breast cancer treatments and personnel. All individual treatment services were reported, and hospitals were further stratified into levels of multi-modal treatment modeled after the National Comprehensive Cancer Network (NCCN) Framework treatment recommendations for low-resource settings. Level 3 included Tamoxifen and surgery (mastectomy with axillary lymph node sampling); Level 2 included Level 3 plus radiation, aromatase inhibitors, lumpectomy, and sentinel lymph node biopsy; Level 1 included Level 2 plus Her2 therapy and breast reconstruction. Hospitals were identified that could expand to these service levels based on existing services, location and personnel. The distance of the total population from treatment services before and after hypothetical expansion was determined with a geospatial analysis. Of the 328 participating hospitals (95% response rate), 9 hospitals had Level 3 care, 0 had Level 2, and 2 had Level 1. Twelve hospitals could expand to Level 3, 1 could expand to Level 2, and 1 could expand to Level 1. With expansion, the population percentage within 75km of Level 1, 2 and 3 care would increase from 42% to 50%, 0 to 6% and 44% to 67%, respectively. Multi-modal breast cancer treatment is available in Ghana, but it is not accessible to most of the population. Leveraging the knowledge of current resources and population proximity provides an opportunity to identify high-yield areas for targeted expansion.

Reversal of Biological Age in Multiple Rat Organs by Young Porcine Plasma Fraction.

Young blood plasma is known to confer beneficial effects on various organs in mice and rats. However, it was not known whether plasma from young pigs rejuvenates old rat tissues at the epigenetic level; whether it alters the epigenetic clock, which is a highly accurate molecular biomarker of aging. To address this question, we developed and validated six different epigenetic clocks for rat tissues that are based on DNA methylation values derived from n=613 tissue samples. As indicated by their respective names, the rat pan-tissue clock can be applied to DNA methylation profiles from all rat tissues, while the rat brain-, liver-, and blood clocks apply to the corresponding tissue types. We also developed two epigenetic clocks that apply to both human and rat tissues by adding n=1366 human tissue samples to the training data. We employed these six rat clocks to investigate the rejuvenation effects of a porcine plasma fraction treatment in different rat tissues. The treatment more than halved the epigenetic ages of blood, heart, and liver tissue. A less pronounced, but statistically significant, rejuvenation effect could be observed in the hypothalamus. The treatment was accompanied by progressive improvement in the function of these organs as ascertained through numerous biochemical/physiological biomarkers and behavioral responses to assess cognitive functions. An immunoglobulin G (IgG) N-glycosylation pattern shift from pro- to anti-inflammatory also indicated reversal of glycan aging. Overall, this study demonstrates that a young porcine plasma-derived treatment markedly reverses aging in rats according to epigenetic clocks, IgG glycans, and other biomarkers of aging.

Genome-wide association studies of human and rat BMI converge on synapse, epigenome, and hormone signaling networks.

A vexing observation in genome-wide association studies (GWASs) is that parallel analyses in different species may not identify orthologous genes. Here, we demonstrate that cross-species translation of GWASs can be greatly improved by an analysis of co-localization within molecular networks. Using body mass index (BMI) as an example, we show that the genes associated with BMI in humans lack significant agreement with those identified in rats. However, the networks interconnecting these genes show substantial overlap, highlighting common mechanisms including synaptic signaling, epigenetic modification, and hormonal regulation. Genetic perturbations within these networks cause abnormal BMI phenotypes in mice, too, supporting their broad conservation across mammals. Other mechanisms appear species specific, including carbohydrate biosynthesis (humans) and glycerolipid metabolism (rodents). Finally, network co-localization also identifies cross-species convergence for height/body length. This study advances a general paradigm for determining whether and how phenotypes measured in model species recapitulate human biology.

Intramolecular Diels-Alder Reaction of Cyclopropenyl Vinylarenes: Access to Benzonorcarane Derivatives.

Intramolecular Diels-Alder vinylarene reaction (IMDAV) is a [4 + 2] cycloaddition that employs styrene derivatives as conjugated dienes, whose poor reactivity arises from the required loss of aromaticity, which is recovered by a subsequent [1,3]-H shift. Herein, we describe the use of cyclopropene as a dienophile, harnessing its strain energy to drive the IMDAV reaction. Benzonorcarane scaffolds form in good yields, excellent stereoselectivity, and broad functional tolerance. Theoretical calculations and NMR studies have revealed significant mechanistic insights.