Recruitment Capacity Research Articles

ITAlian partnership for psychosis prevention (ITAPP): Improving the mental health of young people.

The European impact of the clinical high risk for psychosis (CHR-P) paradigm is constrained by the lack of critical mass (detection) to power prognostic and preventive interventions. An ITAlian partnership for psychosis prevention (ITAPP) was created across CHR-P centers, which were surveyed to describe: (a) service, catchment area, and outreach; (b) service users; and (c) interventions and outcomes. Descriptive statistics and Kaplan-Meier failure function complemented the analyses. The ITAPP included five CHR-P clinical academic centers established from 2007 to 2018, serving about 13million inhabitants, with a recruitment capacity of 277 CHR-P individuals (mean age: 18.7years, SD: 4.8, range: 12-39years; 53.1% females; 85.7% meeting attenuated psychotic symptoms; 85.8% without any substance abuse). All centers were multidisciplinary and included adolescents and young adults (transitional) primarily recruited through healthcare services. The comprehensive assessment of at-risk mental state was the most widely used instrument, while the duration of follow-up, type of outreach, and preventive interventions were heterogeneous. Across 205 CHR-P individuals with follow up (663.7days±551.7), the cumulative risk of psychosis increased from 8.7% (95% CI 5.3-14.1) at 1year to 15.9% (95% CI 10.6-23.3) at 2years, 21.8% (95% CI 14.9-31.3) at 3years, 34.8% (95% CI 24.5-47.9) at 4years, and 51.9% (95% CI 36.3-69.6) at 5years. The ITAPP is one of the few CHR-P clinical research partnerships in Europe for fostering detection, prognosis, and preventive care, as well as for translating research innovations into practice.

Protective CD4+ Th1 cell-mediated immunity is reliant upon execution of effector function prior to the establishment of the pathogen niche.

Intracellular infection with the parasite Leishmania major features a state of concomitant immunity in which CD4+ T helper 1 (Th1) cell-mediated immunity against reinfection coincides with a chronic but sub-clinical primary infection. In this setting, the rapidity of the Th1 response at a secondary site of challenge in the skin represents the best correlate of parasite elimination and has been associated with a reversal in Leishmania-mediated modulation of monocytic host cells. Remarkably, the degree to which Th1 cells are absolutely reliant upon the time at which they interact with infected monocytes to mediate their protective effect has not been defined. In the present work, we report that CXCR3-dependent recruitment of Ly6C+ Th1 effector (Th1EFF) cells is indispensable for concomitant immunity and acute (<4 days post-infection) Th1EFF cell-phagocyte interactions are critical to prevent the establishment of a permissive pathogen niche, as evidenced by altered recruitment, gene expression and functional capacity of innate and adaptive immune cells at the site of secondary challenge. Surprisingly, provision of Th1EFF cells after establishment of the pathogen niche, even when Th1 cells were provided in large quantities, abrogated protection, Th1EFF cell accumulation and IFN-γ production, and iNOS production by inflammatory monocytes. These findings indicate that protective Th1 immunity is critically dependent on activation of permissive phagocytic host cells by preactivated Th1EFF cells at the time of infection.

Limits to post-fire vegetation recovery under climate change.

Record-breaking fire seasons in many regions across the globe raise important questions about plant community responses to shifting fire regimes (i.e., changing fire frequency, severity and seasonality). Here, we examine the impacts of climate-driven shifts in fire regimes on vegetation communities, and likely responses to fire coinciding with severe drought, heatwaves and/or insect outbreaks. We present scenario-based conceptual models on how overlapping disturbance events and shifting fire regimes interact differently to limit post-fire resprouting and recruitment capacity. We demonstrate that, although many communities will remain resilient to changing fire regimes in the short-term, longer-term changes to vegetation structure, demography and species composition are likely, with a range of subsequent effects on ecosystem function. Resprouting species are likely to be most resilient to changing fire regimes. However, even these species are susceptible if exposed to repeated short-interval fire in combination with other stressors. Post-fire recruitment is highly vulnerable to increased fire frequency, particularly as climatic limitations on propagule availability intensify. Prediction of community responses to fire under climate change will be greatly improved by addressing knowledge gaps on how overlapping disturbances and climate change-induced shifts in fire regime affect post-fire resprouting, recruitment, growth rates, and species-level adaptation capacity.

Invasive Sun Coral Species Challenges Decommissioning of Structures Offshore Brazil

This article, written by JPT Technology Editor Chris Carpenter, contains highlights of paper OTC 30656, “Decommissioning of Subsea Structures in Brazil: Effect of Invasive Species and Genome Sequence of the Azooxanthellate Coral Tubastraea sp.,” by João Humberto Guandalini Batista, SPE, Repsol; Mauro Rebelo, Universidade Federal do Rio de Janeiro; and Giordano Soares-Souza, SENAI CETIQT, prepared for the 2020 Offshore Technology Conference, originally scheduled to be held in Houston, 4–7 May. The paper has not been peer reviewed. Copyright 2020 Offshore Technology Conference. Reproduced by permission. Decommissioning of offshore assets in Brazil is subject to high levels of uncertainty because of Tubastraea, an invasive species of sun coral. This species has a high capacity for dispersion and recruitment and has been associated with the replacement of native species in rocky shores, exerting a serious effect on native biodiversity. The complete paper explores the biology of the invasive species, aiming to identify methods to eliminate or diminish its spread. The authors write that data generated in this study will foster the development of effective technologies in coral-species management, whether species are invasive or threatened. Introduction Originally from the Coral Triangle in the Pacific Ocean—a highly diverse region with hundreds of coral species—Tubastraea was first observed in the Campos Basin in the 1980s. Tubastraea sp. have high fecundity and growth rates with the ability to reproduce asexually, establishing very dense populations. This fast reproduction allows larvae to outcompete native species in both natural and artificial substrates in the sea. Sun coral is extremely resistant to environmental change. It has been found in shallow waters, sometimes exposed to air, showing tolerance even to short periods of desiccation. Recently, new species have been identified in Brazilian waters, heightening concern over the proliferation of sun coral. In the past, the common understanding was that subspecies coccinea and tagusensis were those found in Brazilian waters. However, recent studies dedicated to the research of the Tubastraea genus raised suspicion of the presence of diaphana and aurea, with the possible occurrence of hybrids as well. The preference of Tubastraea is to live in structures that are static or mostly motionless, such as production platforms, subsea structures, and drilling rigs. This trait has made sun coral a major challenge for the local oil and gas industry. While in the Campos Basin, the main objective is to decrease dispersion of already bioencrusted production units and subsea structures, in the Santos Basin, the goal is to avoid colonization in structures in operation or those scheduled to be installed soon. To further complicate matters, drilling and intervention vessels and rigs are contracted to service both basins. They work in dynamic-positioning mode, stationary around the production units and subsea structures for lengths of time that exceed the reproduction cycle time of the sun coral, allowing larval dispersion.

Effector function prior to establishment of the phagosomal pathogen niche is required for protective CD4+ T cell-mediated immunity against Leishmania

Abstract Leishmania is an appealing model organism to study CD4+ T cell-mediated protective immunity against phagosomal pathogens which features localized primary and secondary infection sites with defined innate and adaptive responses. Upon secondary challenge of chronic L. major-infected C57Bl/6 mice, rapid CD4+T effector (TEFF) function via IFN-g-mediated activation of infected monocytes is associated with optimal immunity. However, the requirement for immediate effector function has yet to be demonstrated. Thus, we isolated time as a variable in the delivery of CD4+ TEFF effector function. We adoptively transferred (AT) chronic mouse-derived Ly6C+CD4+TEFFs into naïve recipients immediately (D0) or 4 days (D4) post-L. major challenge. In this time window Leishmania establishes an intracellular niche but does not proliferate. At day 21 post-challenge, D4 AT resulted in a total loss of the parasite control mediated by D0 transfer. To address whether parasite niche establishment modulated Th1 TEFF cell recruitment, we employed intravital imaging. Ag-sp T cells were present in the infected dermis at significantly lower numbers following D4 vs D0 transfer at 4 days post-T cell transfer, indicating a recruitment deficit. Rapid CD4+ Th1 effector function was required for circulating Th1 TEFF cells to capitalize on an early recruitment window associated with cxcl9 and cxcl10 expression and to prevent parasite niche establishment through altered cell recruitment, gene expression, and functional capacity of both innate and adaptive immune cells. Thus, acute TEFF cell availability is required to prevent host immunomodulation by Leishmania and is a key consideration for vaccination against phagosomal pathogens reliant on Th1 immunity.

Relationships Between Annual and Perennial Seagrass (Ruppia sinensis) Populations and Their Sediment Geochemical Characteristics in the Yellow River Delta

Annual and perennial populations commonly occur for the same submerged aquatic angiosperm species, yet relationships between population types and sediment characteristics are poorly understood. In the current study two Ruppia sinensis habitats with annual and perennial populations were surveyed in the Yellow River Delta (YRD). Biomass and seasonal seed bank size were used to evaluate population status and potential recruitment capacity. Sediment geochemical parameters including moisture, sulfide, Chl a, carbohydrate, OM, TOC, TN, and TP were measured to compare sediment nutrient composition and variability. The results revealed a higher biomass and larger seed bank in the annual R. sinensis population compared with the perennial population. The P levels in sediments between the two R. sinensis populations were similar; while the N level in the sediment of the annual population was significantly higher than the perennial population, which might support the recruitment of vegetative shoots when a large amount of seeds germinated during wet periods. The annual population exhibited greater resilience after habitat desiccation, with the population recovering rapidly once water appeared. The results of this study add to the knowledge of R. sinensis populations and their sediment geochemical characteristics, and can be used as a reference for Ruppia population conservation and management.

Silk‐Inspired In Situ Hydrogel with Anti‐Tumor Immunity Enhanced Photodynamic Therapy for Melanoma and Infected Wound Healing

AbstractEasy cancer recurrence and wound infections have been clinical challenges after surgical treatment of melanoma. Herein, a silk‐inspired in situ gelation system containing methacrylated silk fibroin (SF) and chlorine e6 for improved cancer therapy with enhanced wound healing is developed. Favored by the macrophage recruitment capacity of the SF hydrogel, promising antitumor immune responses can be turned “on” via near infrared irradiation in a controllable manner to achieve combination therapy with photodynamic therapy to significantly suppress melanoma recurrence. Moreover, the effective photodynamic antibacterial activity of this bioactive system with the capacity of light‐controllable modulating macrophage phenotype promotes remarkable tissue ingrowth with hair follicle regeneration for Staphylococcus aureus infected wound healing. Thus, this multifunctional silk‐based hydrogel system, as a desirable wound dressing, provides a new platform for promising melanoma therapy and skin regeneration.

Factors driving availability of COVID-19 convalescent plasma: Insights from a demand, production, and supply model.

BackgroundCOVID‐19 Convalescent Plasma (CCP) is a promising treatment for COVID‐19. Blood collectors have rapidly scaled up collection and distribution programs.MethodsWe developed a detailed simulation model of CCP donor recruitment, collection, production, and distribution processes. We ran our model using varying epidemic trajectories from 11 U.S. states and with key input parameters drawn from wide ranges of plausible values to identify key drivers of ability to scale collections capacity and meet demand for CCP.ResultsUtilization of available CCP collections capacity followed increases in COVID‐19 hospital discharges with a lag. Utilization never exceeded 75% of available capacity in most simulations. Demand was met for most of the simulation period in most simulations, but a substantial portion of demand went unmet during early, sharp increases in hospitalizations. For epidemic trajectories that included multiple epidemic peaks, second wave demand could generally be met due to stockpiles established during the decline from an earlier peak. Apheresis machine capacity (number of machines) and probability that COVID‐19 recovered individuals are willing to donate were the most important supply‐side drivers of ability to meet demand. Recruitment capacity was important in states with early peaks.ConclusionsEpidemic trajectory was the most important determinant of ability to meet demand for CCP, although our simulations revealed several contributing operational drivers of CCP program success.

Therapeutic depletion of CCR8+ tumor-infiltrating regulatory T cells elicits antitumor immunity and synergizes with anti-PD-1 therapy

BackgroundModulation and depletion strategies of regulatory T cells (Tregs) constitute valid approaches in antitumor immunotherapy but suffer from severe adverse effects due to their lack of selectivity for the tumor-infiltrating...

Microvascular Reactivity Measured by Dynamic Near-infrared Spectroscopy Following Induction of General Anesthesia in Healthy Patients: Observation of Age-related Change.

Background: The purpose of this study was to investigate the effect of general anesthesia on microvascular reactivity and tissue oxygen saturation (StO2) using near-infrared spectroscopy in conjunction with vascular occlusion tests (VOT). Age-related changes of microvascular reactivity, that is, the capacity of capillary recruitment, were examined.Methods: This prospective observational study was performed on 60 patients without comorbidities who underwent elective surgery under general anesthesia. Baseline StO2 on thenar eminence, hemodynamics, and laboratory profile were monitored before (T0) and 30 min after general anesthesia (T1). During VOT, occlusion slope representing oxygen consumption of muscle and recovery slope representing microvascular reactivity were also collected at T0 and T1.Results: Baseline StO2 and minimum / maximum StO2 during VOT increased under general anesthesia. Occlusion slope decreased while the recovery slope increased under general anesthesia. To observe aging effect, Receiver operating characteristic analysis was performed and age less than 65 years old showed a fair performance in predicting the increase of microvascular reactivity after the induction of anesthesia (AUC 0.733, 95% CI 0.594-0.845, P= 0.003). For age-related analyses, 27 patients of younger group (< 65 years) and 26 patients of older group (≥ 65 years) were divided. Recovery slope significantly increased under general anesthesia in younger group (2.44 [1.91-2.81] % ∙ sec-1 at T0 and 3.59 [2.58-3.51] % ∙ sec-1 at T1, P <0.001), but not in older group (2.61 [2.21-3.20] % ∙ sec-1 at T0, 2.63 [1.90-3.60] % ∙ sec-1 at T1, P = 0.949).Conclusions: General anesthesia could improve StO2 through increase of microvascular reactivity and decrease of tissue metabolism. However, microvascular reactivity to capillary recruitment under general anesthesia significantly improves in younger patients, not in older patients.

Evaluation of patient involvement strategies in health technology assessment in Spain: the viewpoint of HTA researchers.

The Spanish Network of Agencies for Assessing National Health System Technologies and Performance (RedETS) defined a patient involvement (PI) framework for health technology assessment (HTA) activities in 2016. The aim of this study is to evaluate the process and impact of those PI initiatives that were implemented in the first year following the publication of this new framework. A survey was sent to those HTA researchers who implemented PI in RedETS projects. Responses were reviewed by two authors. An adapted thematic analysis was performed and the results were later discussed by all authors. Six responses from six agencies/units were analyzed. The objectives of PI initiatives were the following: inclusion of patient perspectives, preferences and values; elicitation of important health outcomes measures; and barriers, facilitators, or suggestions for implementation. Different methods were used for PI: surveys, focus groups, in depth interviews, and participation in an expert panel. Five main themes emerged: (i) challenges with the recruitment process, (ii) needs identified, (iii) impact of PI, (iv) lessons learned, and (v) suggestions for the future. PI initiatives within the RedETS framework were tailored to each HTA project, its specific goals and the individual needs and resources of each HTA agency. The results also pointed out how PI has a relevant impact that has enriched RedETS products providing key information on experiences, values, and preferences of patients, contributions that benefit the HTA and the process of drawing up recommendations. The main challenges were related to recruitment processes and capacity building.

L-Arginine Modulates Neonatal Leukocyte Recruitment in a Gestational Age-Dependent Manner.

(1) Background: L-arginine is a complex modulator of immune functions, and its levels are known to decrease under septic conditions. L-arginine may suppress leukocyte recruitment in vivo; however, little is known about the gestational age-specific effects of L-arginine on leukocyte recruitment in preterm infants. We now asked whether L-arginine alters leukocyte recruitment in preterm and term neonates. (2) Methods: Leukocytes were isolated from preterm (28 + 0 to 32 + 6 weeks of gestation) and term (>37 weeks of gestation) newborns as well as from healthy adults. After incubation with 10 µg/mL L-arginine, we assessed leukocyte rolling and adhesion in dynamic microflow chamber experiments and leukocyte transmigration in fluorescence assays. In addition, we measured the expression of inducible nitric oxide synthase (iNOS) and Arginase 1 (Arg-1) in neutrophils by flow cytometry. (3) Results: Leukocyte rolling, adhesion, and transmigration increased with gestational age. Leukocyte rolling, adhesion, and transmigration were decreased by L-arginine in term-born infants and adults. Preterm leukocytes showed no change in recruitment upon L-arginine exposure. Leukocyte adhesion after L-arginine exposure reached similar levels among all groups. In line, the expression of iNOS and Arg-1 was similar in all three age groups. (4) Conclusion: L-arginine dampens the ex vivo recruitment capacity of leukocytes from term-born infants, whereas no effect was seen in premature infants. As levels of iNOS and Arg-1 in neutrophils remain ontogenetically unchanged, the anti-inflammatory effect of L-arginine on the leukocyte recruitment cascade needs further investigation. These results add to the controversial debate of L-arginine supplementation in premature infants in sepsis.

Hospital characteristics preferred by medical students for their residency programs: A nationwide matching data analysis.

BackgroundIn 2004, Japan introduced a mandatory 2‐year postgraduate training program for graduating medical students with a super‐rotation curriculum. A national matching system was established to determine the hospital residency programs best suited for the students. We examined the hospital characteristics preferred by applicants for residencies.MethodsA nationwide cross‐sectional study was conducted. Data on salaries, bonuses, and number of accepted ambulances were compiled from the Residency Electronic Information System. Information on the prefectural population, urban area, and number of senior residents (postgraduate years 3–5) for specialty training was extracted from data published on the web page. The ratio of the number of first‐choice applicants to recruitment capacity (matching ratio) for each program was compared between the characteristics of the hospitals and prefectures.ResultsA strong linear relationship was observed between the number of first‐choice applications and the allocated number of resident positions (correlation coefficient, .72). The matching ratio was greater in community hospitals (2.10 times compared with university hospitals; 95% confidence interval [CI], 1.75–2.53), in hospitals with higher numbers of accepted ambulance cases (1.05 times per 1000 annually; 95% CI, 1.03–1.08), and in hospitals that served a larger prefectural population (1.05 times per million; 95% CI, 1.02–1.08).ConclusionsFinancial incentives do not seem to attract residency applicants. Applicants prefer non‐university hospitals located in populous areas and those that accept larger number of ambulance cases. To recruit junior residents, an emergency department may need to have higher activity with larger numbers and variety of cases.

Obesity blunts cephalic-phase microvascular responses to food

Neurally mediated anticipatory responses, also named cephalic-phase responses, and microcirculatory regulation are two important mechanisms to maintain metabolic homeostasis. Altered cephalic-phase responses in obesity and its metabolic consequences have been proposed. There is, however, a lack of studies focusing on in vivo assessment of the microcirculation during this phase in patients with obesity. In this randomized controlled trial, we selected patients with obesity and healthy subjects after clinical and laboratory assessments. Those with obesity were randomized into two groups: experimental (cephalic-phase microvascular response stimulation – CP group, n = 13) and controls (n = 14). Healthy subjects (n = 17) were also included to form a CP control group. Skin microvascular assessment was used as a model of systemic microcirculation. Resting functional capillary density (FCD) and peak FCD during post-occlusive reactive hyperemia (PORH) were measured by dorsal finger videocapillaroscopy and expressed mainly capillary recruitment capacity. Resting red blood cell velocity (RBCV), peak RBCV during PORH (RBCVmax), and time taken to reach RBCVmax (TRBCVmax) were assessed by dynamic nailfold videocapillaroscopy and expressed the microhemodynamics. Patients with obesity (with or without stimulus) failed to show an increase on FCD during PORH post-stimulus (p = 0.221 and p = 0.307, respectively) depicting lack of capillary recruitment. In contrast, healthy subjects presented an increase in this microvascular outcome (p = 0.004). Changes in all variables of microhemodynamics occurred in both CP groups (healthy and those with obesity). During CP, we originally demonstrated an absence of capillary recruitment in subjects with obesity. These findings might contribute to the literature of microvascular impairment and metabolic conditions.

Crossbridge Recruitment Capacity of Wild-Type and Hypertrophic Cardiomyopathy-Related Mutant Troponin-T Evaluated by X-ray Diffraction and Mechanical Study of Cardiac Skinned Fibers.

X-ray diffraction and tension measurement experiments were conducted on rat left ventricular skinned fibers with or without “troponin-T treatment,” which exchanges the endogenous troponin T/I/C complex with exogenous troponin-T. These experiments were performed to observe the structural changes in troponin-T within a fiber elicited by contractile crossbridge formation and investigate the abnormality of hypertrophic cardiomyopathy-related troponin-T mutants. The intensity of the troponin reflection at 1/38.5 nm−1 was decreased significantly by ATP addition after treatment with wild-type or mutant troponin-T, indicating that crossbridge formation affected the conformation of troponin-T. In experiments on cardiac fibers treated with the hypertrophic cardiomyopathy-related mutants E244D- and K247R-troponin-T, treatment with K247R-troponin-T did not recruit contracting actomyosin to a greater extent than wild-type-troponin-T, although a similar drop in the intensity of the troponin reflection occurred. Therefore, the conformational change in K247R-troponin-T was suggested to be unable to fully recruit actomyosin interaction, which may be the cause of cardiomyopathy.

Exploring factors influencing recruitment results of nurses recruiting diabetes patients for a randomized controlled trial.

BackgroundEffective recruitment of patients by health professionals is challenging but pivotal to the success of clinical trials. Many trials fail to include the required number of participants, which affects the power of the study, generalizability of results, and timely dissemination of positive outcomes. Existing research is inconclusive regarding factors influencing recruitment results, and most research does not focus on perceptions of recruiting health professionals themselves. Therefore, thorough evaluations of recruitment facilitators and barriers in trials are needed in order to optimize future patient recruitment in trials. We observed divergent recruitment results among nurses who recruited diabetes patients to our trial, which examined the effectiveness of an eHealth programme. Therefore, we aimed to describe nurses’ recruitment results and related shifts over time, and to qualitatively explore factors influencing nurses’ recruitment results.MethodsNurses’ recruitment results and related temporal shifts were derived from trial data (NTR6840). Based on their recruitment results, nurses were categorized as non-, low-, medium-, or high-recruiters. Subsequently, a subset of nurses per group participated in an individual semi-structured telephone interview. Interviews were analysed using NVivo software, applying an inductive coding approach.ResultsNinety-six nurses participated in our trial and recruited on average seven patients (range: 0–32). Fifteen nurses did not recruit any patients. Most patients were recruited close to recruitment onset. Nurses who did not recruit patients close to recruitment onset generally ended up recruiting no patients. Data show a relatively high number of early recruited patients that progressively declined over time. High-recruiters were generally successful throughout the entire recruitment period. Recruitment facilitators and barriers comprised organizational, study, patient, and especially recruiter characteristics. Contrary to non- and low-recruiters, medium- and high-recruiters reported more in-depth knowledge about the study and trial requirements, expressed more personal participation-related benefits and fewer barriers, and incorporated more recruitment activities, reminders, and barrier-focused coping strategies.Conclusion and implicationsTo optimize patient recruitment to clinical trials, suggested intervention targets include the continued inclusion of recruiters after initial recruitment onset and the encouragement of early recruitment success. A personalized approach may aid recruiters to become and remain successful. Primarily, it is important to provide recruiters with sufficient information on trial requirements and to address salient benefits for participation in the trial, both for themselves and for their patients. Finally, teaching recruiters skills on how to overcome barriers may further enhance motivation and recruitment capacities.

CONTRIBUTIONS OF FEVER TO THE PROMOTION OF CELLULAR ANTIMICROBIAL DEFENSES

Abstract Thermal changes impact molecular and cellular immune responses. Herein we take advantage of evolutionarily conserved mechanisms for the control of fever to define its contributions to host immune antimicrobial defenses. Our work demonstrates that discrete thermoregulatory programs provide a broader range of immunological benefits than previously anticipated. Complementing prior findings on the modulation of immune gene expression, high resolution quantitative monitoring of cell function showed predictable changes to leukocyte recruitment and pathogen killing capacity. Assessment of kinetics of leukocyte infiltration to a challenge site and changes to the distribution of cellular subsets showed changes in the efficiency of the teleost acute inflammatory response. Ex vivo characterization of cell function as well as in vivo evaluation of host-pathogen interactions pointed to enhancements in immune defenses and pathogen clearance. These have obvious positive implications for health, setting the stage for valuable applications.

Tryptophanyl-tRNA synthetase (WRS), a novel damage-induced cytokine, significantly increases the therapeutic effects of endometrial stem cells

Background & Aim Aminoacyl-tRNA synthetases (AARSs) are highly conserved and ubiquitously expressed enzymes that catalyze the first step of protein synthesis by covalently attaching amino acids to their corresponding tRNA to form an aminoacyl tRNA during mRNA translation in the nucleus. Importantly, in addition to their known canonical activities, several studies have recently shown that some AARS family members may have non-canonical cytokine-like functions under specific physiological conditions, such as apoptosis, cell proliferation, glucose homeostasis, and inflammatory response, and vascularization. More recently, particular attention has been focused on the non-canonical functions of the one of their family member tryptophanyl-tRNA synthetase (WRS) in inflammatory response as a cytokine, due to its rapidly secretion upon pathogen infection to activate host defense pathways. These observations have raised the possibility that in addition to its previous reported canonical functions, WRS may exert diverse biological activities as a novel secreted cytokine. Therefore, in the present study, we devoted our attention to the discovery of the previously unidentified cytokine functions of WRS that regulates multiple functions of human stem cells. However, its non-canonical functions and its underlying molecular mechanisms in stem cells still remain unknown. Methods, Results & Conclusion Indeed, we found for the first time that WRS is actively released from the site of injury in response to various damage signals both in vitro and in vivo and then acts as a potent non-enzymatic cytokine that facilitates the self-renewal, migratory, and differentiation capacities of endometrial stem cells to repair damaged tissues. Furthermore, we found that WRS, through its functional receptor cadherin-6 (CDH-6), is shown to activate major pro-survival signaling pathways, such as Akt and ERK1/2 signaling, which are implicated in diverse cellular functions, including, differentiation/pluripotency, recruitment, and self-renewal capacity of various stem cell types. Taken together, these results suggest that, in addition to its well-known canonical functions (catalyzing enzyme for protein synthesis), WRS is actively secreted in response to tissue injury and subsequently enhances the therapeutic effects of stem cells in vitro and in vivo as a novel non-enzymatic cytokine. tissue injury and subsequently enhances the therapeutic effects of stem cells in vitro and in vivo as a novel non-enzymatic cytokine.

RRNA expansion segment 27Lb modulates the factor recruitment capacity of the yeast ribosome and shapes the proteome

Fine-tuned regulation of protein biosynthesis is crucial for cellular fitness and became even more vital when cellular and organismal complexity increased during the course of evolution. In order to cope with this augmented demand for translation control, eukaryal ribosomes have gained extensions both at the ribosomal protein and rRNA levels. Here we analyze the functional role of ES27L, an rRNA expansion segment in the large ribosomal subunit of Saccharomyces cerevisiae. Deletion of the b-arm of this expansion segment, called ES27Lb, did not hamper growth during optimal conditions, thus demonstrating that this 25S rRNA segment is not inherently crucial for ribosome functioning. However, reductive stress results in retarded growth and rendered unique protein sets prone to aggregation. Lack of ES27Lb negatively affects ribosome-association of known co-translational N-terminal processing enzymes which in turn contributes to the observed protein aggregation. Likely as a compensatory response to these challenges, the truncated ribosomes showed re-adjusted translation of specific sets of mRNAs and thus fine-tune the translatome in order to re-establish proteostasis. Our study gives comprehensive insight into how a highly conserved eukaryal rRNA expansion segment defines ribosomal integrity, co-translational protein maturation events and consequently cellular fitness.

Wheat-derived arabinoxylans reduced M2-macrophage functional activity, but enhanced monocyte-recruitment capacity.

The immunomodulatory properties of non-digestible polysaccharides (NDPs) have been recognized in in vitro and in vivo studies. The latter mostly demonstrated altered frequencies and inflammatory status of immune cells as clinical parameters. Most of the NDP activity will be exerted in the intestine where they can directly interact with macrophages. The predominant macrophage phenotype in the intestine is M2-like, with M1-like macrophages arising during inflammation. Here, we investigated transcriptional and functional impact on these macrophage phenotypes by NDP-treatment (i.e. yeast-derived soluble β-glucan (yeast-βG), apple-derived RG-I (apple-RGI), shiitake-derived β-glucan (shiitake-βG) or wheat-derived arabinoxylan (wheat-AX)). Wheat-AX, and to a lesser extent shiitake-βG and apple-RGI but not yeast-βG, reduced endocytosis and antigen processing capacity of M1- and M2-like macrophages. Moreover, the NDPs, and most notably wheat-AX, strongly induced transcription and secretion of a unique set of cytokines and chemokines. Conditioned medium from wheat-AX-treated M2-like macrophages subsequently demonstrated strongly increased monocyte recruitment capacity. These findings are in line with clinically observed immunomodulatory aspects of NDPs making it tempting to speculate that clinical activity of some NDPs is mediated through enhanced chemoattraction and modifying activity of intestinal immune cells.