Miracle-dz/UniFAR-FTUs huggingface dataset:
Pathogenic LRRK2 Mutations Do Not Alter Gene Expression in Cell Model Systems or Human Brain Tissue

Point mutations in LRRK2 cause autosomal dominant Parkinson's disease. Despite extensive efforts to determine the mechanism of cell death in patients with LRRK2 mutations, the aetiology of LRRK2 PD is not well understood. To examine possible alterations in gene expression linked to the presence of LRRK2 mutations, we carried out a case versus control analysis of global gene expression in three systems: fibroblasts isolated from LRRK2 mutation carriers and healthy, non-mutation carrying controls; brain tissue from G2019S mutation carriers and controls; and HEK293 inducible LRRK2 wild type and mutant cell lines. No significant alteration in gene expression was found in these systems following correction for multiple testing. These data suggest that any alterations in basal gene expression in fibroblasts or cell lines containing mutations in LRRK2 are likely to be quantitatively small. This work suggests that LRRK2 is unlikely to play a direct role in modulation of gene expression, although it remains possible that this protein can influence mRNA expression under pathogenic cicumstances.
Poultry rearing on perforated plastic floors and the effect on air quality, growth performance, and carcass injuries ‐ Experiment 2: Heat stress situation

ABSTRACT Previously, we reported the effect of rearing conditions (plastic floors and air quality) on carcass injury development of broiler chickens at thermal comfort. In this study, the same rearing conditions were tested at thermal stress. The birds were reared in 2 climatic chambers, and the experiment followed a completely randomized design with one factor, flooring material: wood shaving or perforated plastic. The birds were divided into 16 experimental pens, being 8 females and 8 males. The studied parameters were the same as the previous study (ammonia concentration, carbon dioxide, performance, carcass yield, and variability, and scores of hygiene, gait and chest, and hocks and footpad lesions). Higher ammonia (15 ppm vs. 4 ppm) and carbon dioxide (1,000 ppm vs. 850 ppm) concentration was seen at d 42 for the wood shavings floor as compared to the perforated plastic floor, respectively. Regarding gender, males had better performance than females at 42 d of age on both floor types. Males reared on wood shavings showed a higher meat production (29.049 kg/m2) than females (24.700 kg/m2). There were observed breast lesion incidences of 10.4% (score 1) in males reared on the plastic floor, as well higher incidence of hock injury and footpad dermatitis. Chickens reared on plastic flooring showed better hygiene than chickens reared on wood shavings. Our findings revealed that the use of perforated plastic flooring in a heat stress situation can improve the air quality (less CO2 and NH3 concentration) and bird cleanliness. On the other hand, chickens are more susceptible to develop lesions in the breast, hock, and footpad. We conclude that the use of plastic flooring in heat stress conditions needs more attention, since chickens are more susceptible to develop lesions on the carcass, being a source of pain, impairing bird wellbeing and causing losses in meat production.
Induction of Monozygotic Twinning by Ascorbic Acid in Tobacco

Embryo development in plants initiates following the transverse division of a zygote into an apical, proembryo cell and a basal cell that gives rise to the suspensor. Although mutants affected in embryo development through changes in cell division have been described, little is known about the control of the first zygotic division that gives rise to the proembryo. Ascorbic acid (Asc) promotes cell division by inducing G1 to S progression but its role in embryo development has not been examined. In this study, we show that the level of dehydroascorbate reductase (DHAR) expression, which recycles Asc and regulates Asc pool size, affects the rate of monozygotic twinning and polycotyly. DHAR-induced twinning resulted from altered cell polarity and longitudinal instead of transverse cell division that generated embryos of equal size. Direct injection of Asc into ovaries phenocopied DHAR-induced twinning. Twinning induced by Asc was developmentally limited to the first two days after pollination whereas polycotyly was induced when the level of Asc was elevated just prior to cotyledon initiation. This work describes the first example of gene-directed monozygotic twinning and shows that Asc regulates cell polarity during embryo development.
Oxygen and Heterotrophy Affect Calcification of the Scleractinian Coral Galaxea fascicularis

Heterotrophy is known to stimulate calcification of scleractinian corals, possibly through enhanced organic matrix synthesis and photosynthesis, and increased supply of metabolic DIC. In contrast to the positive long-term effects of heterotrophy, inhibition of calcification has been observed during feeding, which may be explained by a temporal oxygen limitation in coral tissue. To test this hypothesis, we measured the short-term effects of zooplankton feeding on light and dark calcification rates of the scleractinian coral Galaxea fascicularis (n = 4) at oxygen saturation levels ranging from 13 to 280%. Significant main and interactive effects of oxygen, heterotrophy and light on calcification rates were found (three-way factorial repeated measures ANOVA, p<0.05). Light and dark calcification rates of unfed corals were severely affected by hypoxia and hyperoxia, with optimal rates at 110% saturation. Light calcification rates of fed corals exhibited a similar trend, with highest rates at 150% saturation. In contrast, dark calcification rates of fed corals were close to zero under all oxygen saturations. We conclude that oxygen exerts a strong control over light and dark calcification rates of corals, and propose that in situ calcification rates are highly dynamic. Nevertheless, the inhibitory effect of heterotrophy on dark calcification appears to be oxygen-independent. We hypothesize that dark calcification is impaired during zooplankton feeding by a temporal decrease of the pH and aragonite saturation state of the calcifying medium, caused by increased respiration rates. This may invoke a transient reallocation of metabolic energy to soft tissue growth and organic matrix synthesis. These insights enhance our understanding of how oxygen and heterotrophy affect coral calcification, both in situ as well as in aquaculture.
A case of tumor lysis syndrome and acute renal failure associated with elotuzumab treatment in multiple myeloma

Renal dysfunction is a common comorbidity of multiple myeloma. However, tumor lysis syndrome is a rare cause of renal dysfunction in multiple myeloma. Elotuzumab is a newly US FDA-approved monoclonal antibody used in the treatment of refractory multiple myeloma. To our knowledge, elotuzumab has not been associated with a case of tumor lysis syndrome. We present the case of a patient who developed clinical tumor lysis syndrome 1 week after treatment with elotuzumab accompanied by renal failure with hyperphosphatemia, hyperkalemia, and profound hyperuricemia. His course was further complicated by significant epistaxis from the accumulation of dabigatran in acute renal failure. In spite of treatment with rasburicase and hemodiafiltration, the patient decompensated and eventually died. Risk factors for the development of tumor lysis syndrome in multiple myeloma are discussed.
Effects of in Vivo Cd8+ T Cell Depletion on Virus Replication in Rhesus Macaques Immunized with a Live, Attenuated Simian Immunodeficiency Virus Vaccine

The role of CD8+ T lymphocytes in controlling replication of live, attenuated simian immunodeficiency virus (SIV) was investigated as part of a vaccine study to examine the correlates of protection in the SIV/rhesus macaque model. Rhesus macaques immunized for >2 yr with nef-deleted SIV (SIVmac239Δnef) and protected from challenge with pathogenic SIVmac251 were treated with anti-CD8 antibody (OKT8F) to deplete CD8+ T cells in vivo. The effects of CD8 depletion on viral load were measured using a novel quantitative assay based on real-time polymerase chain reaction using molecular beacons. This assay allows simultaneous detection of both the vaccine strain and the challenge virus in the same sample, enabling direct quantification of changes in each viral population. Our results show that CD8+ T cells were depleted within 1 h after administration of OKT8F, and were reduced by as much as 99% in the peripheral blood. CD8+ T cell depletion was associated with a 1–2 log increase in SIVmac239Δnef plasma viremia. Control of SIVmac239Δnef replication was temporally associated with the recovery of CD8+ T cells between days 8 and 10. The challenge virus, SIVmac251, was not detectable in either the plasma or lymph nodes after depletion of CD8+ T cells. Overall, our results indicate that CD8+ T cells play an important role in controlling replication of live, attenuated SIV in vivo.
SepM, a Streptococcal Protease Involved in Quorum Sensing, Displays Strict Substrate Specificity

ABSTRACT Streptococcus mutans, a causative agent of dental caries, relies on multiple quorum-sensing (QS) pathways that coordinate the expression of factors needed for colonization in the oral cavity. S. mutans uses small peptides as QS signaling molecules that typically are secreted into the outside milieu. Competence-stimulating peptide (CSP) is one such QS signaling molecule that functions through the ComDE two-component signal transduction pathway. CSP is secreted through NlmTE, a dedicated ABC transporter that cleaves off the N-terminal leader peptide to generate a mature peptide that is 21 residues long (CSP-21). We recently identified a surface-localized protease, SepM, which further cleaves the CSP-21 peptide at the C-terminal end and removes the last 3 residues to generate CSP-18. CSP-18 is the active QS molecule that interacts with the ComD sensor kinase to activate the QS pathway. In this study, we show that SepM specifically cleaves CSP-21 between the Ala18 and Leu19 residues. We also show that SepM recognizes only Ala at position 18 and Leu at position 19, although some CSP-18 variants with a substitution at position 18 can function equally as well as the QS peptide. Furthermore, we demonstrate that SepM homologs from other streptococci are capable of processing CSP-21 to generate functional CSP-18. IMPORTANCE SepM is a membrane-associated streptococcal protease that processes competence-stimulating peptide (CSP) to generate an active quorum-sensing molecule in S. mutans. SepM belongs to the S16 family of serine proteases, and in this study, we found that SepM behaves as an endopeptidase. SepM displays strict substrate specificity and cleaves the peptide bond between the Ala and Leu residues. This is the first report of an endopeptidase that specifically cleaves these two residues.
Enhanced Direct Major Histocompatibility Complex Class I Self-Antigen Presentation Induced by Chlamydia Infection

ABSTRACT The direct major histocompatibility complex (MHC) class I antigen presentation pathway ensures intracellular peptides are displayed at the cellular surface for recognition of infected or transformed cells by CD8+ cytotoxic T lymphocytes. Chlamydia spp. are obligate intracellular bacteria and, as such, should be targeted by CD8+ T cells. It is likely that Chlamydia spp. have evolved mechanisms to avoid the CD8+ killer T cell responses by interfering with MHC class I antigen presentation. Using a model system of self-peptide presentation which allows for posttranslational control of the model protein's stability, we tested the ability of various Chlamydia species to alter direct MHC class I antigen presentation. Infection of the JY lymphoblastoid cell line limited the accumulation of a model host protein and increased presentation of the model-protein-derived peptides. Enhanced self-peptide presentation was detected only when presentation was restricted to defective ribosomal products, or DRiPs, and total MHC class I levels remained unaltered. Skewed antigen presentation was dependent on a bacterial synthesized component, as evidenced by reversal of the observed phenotype upon preventing bacterial transcription, translation, and the inhibition of bacterial lipooligosaccharide synthesis. These data suggest that Chlamydia spp. have evolved to alter the host antigen presentation machinery to favor presentation of defective and rapidly degraded forms of self-antigen, possibly as a mechanism to diminish the presentation of peptides derived from bacterial proteins.
A modified‐live porcine reproductive and respiratory syndrome virus (PRRSV)‐1 vaccine protects late‐term pregnancy gilts against heterologous PRRSV‐1 but not PRRSV‐2 challenge

The objective of this study was to determine the efficacy of a commercially available porcine reproductive and respiratory syndrome virus (PRRSV)-1 modified-live virus (MLV) vaccine against PRRSV-1 and PRRSV-2 challenge in late-term pregnancy gilts. Gilts were vaccinated with the PRRSV-1 MLV vaccine at 4 weeks prior to breeding and then challenged intranasally with PRRSV-1 or PRRSV-2 at 93 days of gestation. After PRRSV-1 challenge, vaccinated pregnant gilts had a significantly longer gestation period, significantly higher numbers of live-born and weaned piglets and a significantly lower number of stillborn piglets at birth compared to unvaccinated pregnant gilts. No significant improvement in reproductive performance was observed between vaccinated and unvaccinated pregnant gilts following PRRSV-2 challenge. Vaccinated pregnant gilts also exhibited a significantly improved reproductive performance after challenge with PRRSV-1 compared to vaccinated pregnant gilts following PRRSV-2 challenge. The PRRSV-1 MLV vaccine was able to reduce PRRSV-1 but not PRRSV-2 viremia in pregnant gilts. Vaccinated gilts also showed a significantly higher number of PRRSV-1-specific IFN-γ-secreting cells (IFN-γ-SC) compared to PRRSV-2-specific IFN-γ-SC. The data presented here suggest that the vaccination of pregnant gilts with a PRRSV-1 MLV vaccine provides good protection against PRRSV-1 but only limited protection against PRRSV-2 challenge in late-term pregnancy gilts based on improvement of reproductive performance, reduction in viremia and induction of IFN-γ-SC.
Romantic Relationship Quality in the Digital Age: A Study with Young Adults

Abstract Recent studies suggest that the online and offline behaviors young people display in romantic relationships are closely related. However, the differential effects of the dimensions of couple quality in the online context have not yet been explored in depth. The aim of this study was to explore online couple quality in young-adult relationships, and its association with romantic relationship satisfaction, also looking at effects of gender, age, and length of the relationship. 431 university students currently in a romantic relationship (68.2% females; mean age = 21.57) participated in this study. They completed different self-report measures to tap the online quality of their romantic relationships (online intimacy, control, jealousy, intrusiveness, cyberdating practices, and communication strategies) and level of satisfaction with those relationships. Results showed that participants more often reported online intimacy (M men = 2.49; M women = 2.38) than the negative scales of online quality (mean ranged from .43 to 1.50), and all the online quality scales decreased with age (correlations ranged from –.12 to –.30) and relationship length (correlations ranged from –.02 to –.20). Linear regression analyses indicated that online intimacy (b = .32, p = .001) and intrusiveness (b = .11, p = .035) were positively related to relationship satisfaction, while cyberdating practices (b = –.20, p = .001) and communication strategies (b = –.34, p = .001) were negatively correlated with relationship satisfaction. Moreover, gender and relationship length moderated some of these associations. Results indicate that while online quality and relationship satisfaction are related, the impact of different online quality dimensions on relationship satisfaction differs depending on a participant’s sex, age, and relationship length.
T cell responses: naive to memory and everything in between.

THE MAMMALIAN IMMUNE SYSTEM can be broadly divided into two main arms: innate and adaptive immunity. As its name implies, the cells and receptors of the innate immune system are critical for the rapid recognition of the infectious agent and initiating a proinflammatory response. While the inflammation generated by innate immune cells [neutrophils, macrophages, monocytes, natural killer (NK) cells, dendritic cells (DCs), etc.] is important in the initial containment of the infection, it also informs and directs the expansion and differentiation of adaptive immune cells. Responding to the inflammatory environment created by the innate response, cells of the adaptive arm of the immune response (B cells, T cells, and T cells) are stimulated to expand in number (proliferate) and to differentiate into cells with a range of functions appropriate for the immunological challenge. Upon elimination of the invading pathogen, the majority of adaptive cells die and leave behind an (evergrowing) array of memory cell subsets. These memory cells offer a diversity of migratory properties and functions, collectively mediating a rapid and protective immune response upon reinfection. Thus, the major advantages of an adaptive response to the host are twofold. First, it allows the host to form an immune response that is specifically tailored to the invading pathogen. Second, it forms a pool of memory cells from these specific effectors that can last for many years, capable of protecting the host against reinfection by their rapid response. This combination of specificity and memory are the mechanistic underpinnings for the clinical success of vaccination. Critical to almost all functions of the adaptive immune response is the activation and programming of T cells from their naive/resting state. Although there is much more to be learned, we now have a good basic understanding of the signals and cell types involved in the various stages of the T cell response initiated within the secondary lymphoid organs (SLOs). To provide a comprehensive overview, this review will summarize the T cell response broken down into three major stages: activation, differentiation, and memory formation. We will then assemble these components into a description of the anatomy of an immune response and its relationship to productive immune protection.
Effectiveness of the Tier 1 Program of Project P.A.T.H.S.: Findings Based on the First 2 Years of Program Implementation

The Tier 1 Program of the Project P.A. T.H. S. (Positive Adolescent Training through Holistic Social Programmes) is a curricular-based program that attempts to promote positive youth development in Hong Kong. In the second year of the Full Implementation Phase, 20 experimental schools (N = 2,784 students) and 23 control schools (N = 3,401 students) participated in a randomized group trial. Analyses of covariance and linear mixed models, controlling for differences between the two groups in terms of Wave 1 pretest scores, personal variables, and random effect of schools, showed that participants in the experimental schools had significantly higher positive youth development levels than did participants in the control schools at post-test, based on different indicators derived from the Chinese Positive Youth Development Scale. The students in the experimental schools also displayed a lower level of delinquency, but better school adjustment than did students in the control schools. Differences between experimental and control participants were also found when students who joined the Tier 1 Program and perceived the program to be beneficial were employed as participants of the experimental schools.
Improved protocols to accelerate the assembly of DNA barcode reference libraries for freshwater zooplankton

Abstract Currently, freshwater zooplankton sampling and identification methodologies have remained virtually unchanged since they were first established in the beginning of the XX century. One major contributing factor to this slow progress is the limited success of modern genetic methodologies, such as DNA barcoding, in several of the main groups. This study demonstrates improved protocols which enable the rapid assessment of most animal taxa inhabiting any freshwater system by combining the use of light traps, careful fixation at low temperatures using ethanol, and zooplankton‐specific primers. We DNA‐barcoded 2,136 specimens from a diverse array of taxonomic assemblages (rotifers, mollusks, mites, crustaceans, insects, and fishes) from several Canadian and Mexican lakes with an average sequence success rate of 85.3%. In total, 325 Barcode Index Numbers (BINs) were detected with only three BINs (two cladocerans and one copepod) shared between Canada and Mexico, suggesting a much narrower distribution range of freshwater zooplankton than previously thought. This study is the first to broadly explore the metazoan biodiversity of freshwater systems with DNA barcodes to construct a reference library that represents the first step for future programs which aim to monitor ecosystem health, track invasive species, or improve knowledge of the ecology and distribution of freshwater zooplankton.
The impact of board size on firm performance: evidence from the UK

We examine the impact of board size on firm performance for a large sample of 2746 UK listed firms over 1981–2002. The UK provides an interesting institutional setting, because UK boards play a weak monitoring role and therefore any negative effect of large board size is likely to reflect the malfunction of the board's advisory rather than monitoring role. We find that board size has a strong negative impact on profitability, Tobin's Q and share returns. This result is robust across econometric models that control for different types of endogeneity. We find no evidence that firm characteristics that determine board size in the UK lead to a more positive board size–firm performance relation. In contrast, we find that the negative relation is strongest for large firms, which tend to have larger boards. Overall, our evidence supports the argument that problems of poor communication and decision-making undermine the effectiveness of large boards.
Population Monte Carlo schemes with reduced path degeneracy

Population Monte Carlo (PMC) algorithms are versatile adaptive tools for approximating moments of complicated distributions. A common problem of PMC algorithms is the so-called path degeneracy; the diversity in the adaptation is endangered due to the resampling step. In this paper we focus on novel population Monte Carlo schemes that present enhanced diversity, compared to the standard approach, while keeping the same implementation structure (sample generation, weighting and resampling). The new schemes combine different weighting and resampling strategies to reduce the path degeneracy and achieve a higher performance at the cost of additional low computational complexity cost. Computer simulations compare the different alternatives in a frequency estimation problem with superimposed sinusoids embedded in Gaussian noise.