Miracle-dz/UniFAR-FTUs huggingface dataset:
Inoculation- and nitrate-induced CLE peptides of soybean control NARK-dependent nodule formation.

Systemic autoregulation of nodulation in legumes involves a root-derived signal (Q) that is perceived by a CLAVATA1-like leucine-rich repeat receptor kinase (e.g. GmNARK). Perception of Q triggers the production of a shoot-derived inhibitor that prevents further nodule development. We have identified three candidate CLE peptide-encoding genes (GmRIC1, GmRIC2, and GmNIC1) in soybean (Glycine max) that respond to Bradyrhizobium japonicum inoculation or nitrate treatment. Ectopic overexpression of all three CLE peptide genes in transgenic roots inhibited nodulation in a GmNARK-dependent manner. The peptides share a high degree of amino acid similarity in a 12-amino-acid C-terminal domain, deemed to represent the functional ligand of GmNARK. GmRIC1 was expressed early (12 h) in response to Bradyrhizobium-sp. -produced nodulation factor while GmRIC2 was induced later (48 to 72 h) but was more persistent during later nodule development. Neither GmRIC1 nor GmRIC2 were induced by nitrate. In contrast, GmNIC1 was strongly induced by nitrate (2 mM) treatment but not by Bradyrhizobium sp. inoculation and, unlike the other two GmCLE peptides, functioned locally to inhibit nodulation. Grafting demonstrated a requirement for root GmNARK activity for nitrate regulation of nodulation whereas Bradyrhizobium sp. -induced regulation was contingent on GmNARK function in the shoot.
The N‐terminus of histone H2B, but not that of histone H3 or its phosphorylation, is essential for chromosome condensation

We have studied the role of individual histone N‐termini and the phosphorylation of histone H3 in chromosome condensation. Nucleosomes, reconstituted with histone octamers containing different combinations of recombinant full‐length and tailless histones, were used as competitors for chromosome assembly in Xenopus egg extracts. Nucleosomes reconstituted with intact octamers inhibited chromosome condensation as efficiently as the native ones, while tailless nucleosomes were unable to affect this process. Importantly, the addition to the extract of particles containing only intact histone H2B strongly interfered with chromosome formation while such an effect was not observed with particles lacking the N‐terminal tail of H2B. This demonstrates that the inhibition effect observed in the presence of competitor nucleosomes is mainly due to the N‐terminus of this histone, which, therefore, is essential for chromosome condensation. Nucleosomes in which all histones but H3 were tailless did not impede chromosome formation. In addition, when competitor nucleosome particles were reconstituted with full‐length H2A, H2B and H4 and histone H3 mutated at the phosphorylable serine 10 or serine 28, their inhibiting efficiency was identical to that of the native particles. Hence, the tail of H3, whether intact or phosphorylated, is not important for chromosome condensation. A novel hypothesis, termed ‘the ready production label’ was suggested to explain the role of histone H3 phosphorylation during cell division.
Recruitment of the NineTeen Complex to the activated spliceosome requires AtPRMT5

Significance Protein arginine methyltransferase 5 (PRMT5) is involved in various developmental processes by globally regulating pre-mRNA splicing of diverse genes, but the underlying mechanism remains elusive. Here we demonstrate for the first time, to our knowledge, that Arabidopsis PRMT5 promotes the recruitment of the NineTeen Complex and splicing factors in the catalytic reactions to the spliceosome, thus promoting global pre-mRNA splicing. Our findings uncover a key molecular mechanism for PRMT5 in the regulation of pre-mRNA splicing, which fills a major gap in understanding of the role for PRMT5 in spliceosome assembly. Due to the conservation of PRMT5 in plants and animals, our finding is likely a fundamental molecular mechanism applicable to all eukaryotes, thereby shedding light on PRMT5 functions and spliceosome activation in animals. Protein arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), is involved in a multitude of biological processes in eukaryotes. Symmetric arginine dimethylation mediated by PRMT5 modulates constitutive and alternative pre-mRNA splicing of diverse genes to regulate normal growth and development in multiple species; however, the underlying molecular mechanism remains largely unknown. A genetic screen for suppressors of an Arabidopsis symmetric arginine dimethyltransferase mutant, atprmt5, identified two gain-of-function alleles of pre-mRNA processing factor 8 gene (prp8-8 and prp8-9), the highly conserved core component of the U5 small nuclear ribonucleoprotein (snRNP) and the spliceosome. These two atprmt5 prp8 double mutants showed suppression of the developmental and splicing alterations of atprmt5 mutants. In atprmt5 mutants, the NineTeen complex failed to be assembled into the U5 snRNP to form an activated spliceosome; this phenotype was restored in the atprmt5 prp8-8 double mutants. We also found that loss of symmetric arginine dimethylation of Sm proteins prevents recruitment of the NineTeen complex and initiation of spliceosome activation. Together, our findings demonstrate that symmetric arginine dimethylation has important functions in spliceosome assembly and activation, and uncover a key molecular mechanism for arginine methylation in pre-mRNA splicing that impacts diverse developmental processes.
Male phenotype and ejaculate quality in the zebra finch Taeniopygia guttata

We tested the idea that female preference for relatively attractive extra-pair males arises because the morphological and behavioural features that females find attractive covary with ejaculate features: Sheldon’s (Proc. R. Soc. Lond. B 257 25─30 (1994)) phenotype-linked fertility insurance hypothesis. Two phenotypic traits that female zebra finches find attractive in males are song rate and symmetry of chest band plumage, but we found neither of these to be significantly related to any of the following ejaculate features: number of sperm, percentage of live sperm, absolute number of sperm, sperm length or sperm swimming velocity. Furthermore, and surprisingly, we did not find the predicted negative relationship between male song rate and fluctuating asymmetry of chest band plumage. Because most ejaculate features (except sperm numbers in rested males) show low levels of repeatability, it is unlikely that female zebra finches could reliably obtain a better quality ejaculate by choosing to copulate with a more attractive male. There was thus no evidence for the phenotype-linked fertility insurance hypothesis. Nor did we obtain evidence for the more general fertility insurance hypothesis: we found that female zebra finches paired to a vasectomized male, and hence receiving no sperm, were no more likely to seek an extra-pair copulation than females paired to an intact male.
Reductions in health-related quality of life in patients with ankylosing spondylitis and improvements with etanercept therapy.

OBJECTIVE To assess the impact of ankylosing spondylitis (AS) on patient health-related quality of life (HRQOL) relative to both the general US and chronically-ill populations, and to evaluate whether etanercept therapy can reverse impairments in HRQOL due to AS. METHODS Two AS patient populations were evaluated: patients with AS from a US clinical trial who were randomized to receive either etanercept (n = 20) or placebo (n = 20) for 16 weeks, and placebo-treated patients from a multinational sample who subsequently received etanercept (n = 129) during a 48-week, open-label extension study. A sample from the US general population and patients with other medical conditions derived from the National Survey of Functional Health Status were used as comparators to evaluate the relative impact of active AS on HRQOL, as measured by the Short Form 36 (SF-36) questionnaire. RESULTS At baseline, patients with AS in both the US and multinational samples had significantly lower scores than the US general population on all 8 SF-36 scales. Compared with patients with other medical conditions, patients with AS had the lowest scores in the physical domains--Physical Functioning, Role Physical, and Bodily Pain. Impairments in SF-36 scores for psychosocial domains, such as Social Functioning, Role Emotional, and Mental Health, were somewhat less pronounced in patients with AS. Treatment with etanercept significantly improved the HRQOL of patients with AS on all 8 SF-36 scales, especially in the same physical domains that showed the greatest impairments prior to treatment (Physical Functioning, Role Physical, and Bodily Pain). CONCLUSION Patients with active AS despite conventional therapy have significantly reduced HRQOL across a wide range of domains. These reductions are most pronounced in the physical domains and exceed those seen in many other chronic diseases. Etanercept therapy significantly improves patient HRQOL, indicating that decrements in HRQOL due to AS may be at least partly reversible.
North Carolina macular dystrophy (MCDR1) locus: a fine resolution genetic map and haplotype analysis.

PURPOSE We previously reported linkage of North Carolina macular dystrophy in a single isolated family to a broad region on chromosome 6q16. In order to refine the localization of the MCDR1 gene (North Carolina macular dystrophy), additional families with this disease and new markers were studied. METHODS We ascertained 10 families with the North Carolina macular dystrophy phenotype (MCDR1). These families were of various ethnic and geographic origins such as Caucasian, Mayan Indian, African-American, French, British, German, and American of European decent. Two hundred thirty-two individuals in these families underwent comprehensive ophthalmic examinations and blood was collected for genotyping. One hundred seventeen were found to be affected. Linkage simulation studies were performed. Two-point linkage, haplotype analysis, and multipoint linkage was performed using VITESSE and FASTLINK. HOMOG was used to test for genetic heterogeneity. RESULTS The clinical features were consistent with the diagnosis of North Carolina macular dystrophy in all families. Multipoint linkage analysis indicates that the MCDR1 gene is in the interval between D6D249 and D6S1671 with a maximum LOD score of 41.52. There was no evidence of genetic heterogeneity among the families studied. Families 765, 768, 772, 1193, and 1292 shared the same chromosomal haplotype in this region. CONCLUSIONS This is the largest single data set of families with the MCDR1 phenotype. The single large family from North Carolina continues to be informative for the closest flanking markers and alone supports the minimal candidate region as suggested by previous studies. There remains no evidence of genetic heterogeneity in this disease. Most of the American families appear to have descended from the same ancestral mutation. The remaining families could each represent independent origins of the mutation in the MCDR1 gene.
[Influence of temperature and humidity on the nymphal development of Rhodnius robustus].

OBJECTIVE To assess the significant differences in the nymphal development of the Rhodnius robustus Larrousse, 1927 under different temperatures and humidity conditions. This is a species found in the northern region of Brazil (states of Acre, Amazonas, and Pará), Colombia, Equator, Peru and Venezuela. METHODS Three groups of triatominae were kept under the following laboratory conditions: 33/40 (33+1 degree C and 40+/-5% of relative humidity - RH), 33/70 (33+/-1 degree C and 70+/-5% RH), and 28/70 (28+/-1 degree C and 70+/-5% RH). The incubation period of the eggs, developmental time of each stage, mortality percentage, number of bloodmeals, and the total amount of time from the egg hatching to adult ecdysis were observed. RESULTS The shortest average time of nymphal development was observed in the 28/70 group, with following averages: 14.4, 17.3, 20.3, 22.8, and 40. Significant differences were observed in the embryonic development between the groups (p<0.01). For all groups, the number of bloodmeals had a gradual increase near the adult phase, except for the 3rd instar of the 33/70 group. The smallest mortality percentages were seen in the 28/70 group. CONCLUSIONS High temperatures, regardless of the humidity, can accelerate the biological development cycle of R. robustus. However, these temperatures can impair the colonies' survival, preventing their maintenance in the laboratory.
Tumor cell lines established in vitro: an independent prognostic factor for survival in non-small-cell lung cancer.

OBJECTIVE To determine the relation between in-vitro establishment of tumor cell lines and survival in patients with non-small-cell lung cancer. DESIGN Cohort study. SETTING Single-institution tertiary care center. PATIENTS One hundred twenty-three consecutive patients with non-small-cell lung cancer from whom a viable tumor specimen could be obtained. INTERVENTION Tumor tissue was removed at the time of entry into a therapeutic protocol. The tumor tissue was processed in the laboratory for attempted cell-line establishment. Patients classified as potentially curable (stages I, II, and IIIA) were treated with surgical resection, radiation therapy, or a combination. Patients suitable for palliative therapy only (stages IIIB and IV) were treated with radiation therapy with or without chemotherapy. Chemotherapy was based on in-vitro drug sensitivity when available. Cell-line establishment was correlated to clinical outcome. MEASUREMENTS AND MAIN RESULTS Univariate analysis of survival was done using the log-rank test; multivariate analysis was done by Cox modeling step-up and step-down techniques. Cell lines were established from the tumor specimens of 25 patients (20%). Those patients experienced a median survival of 7 months compared with 18 months in patients from whom cell lines could not be established (P less than 0.001). In the 61 patients with potentially curable disease, 8 patients (13%) with cell lines established had a median survival of 8 months compared with 32 months for those without cell lines established (P = 0.001). In the 62 palliative group patients, the median survival of the 17 patients (27%) from whom tumor cell lines were established was 5 months compared with 7 months for those without cell lines (P = 0.15). Multivariate analysis in both groups showed cell-line establishment to be a significant indicator of prognosis (P less than 0.0001 for curable group; P less than 0.01 for palliative group). CONCLUSION In-vitro tumor growth is related to decreased patient survival, which in turn reflects the biologic aggressiveness of cancers giving rise to these tumor cell lines.
Hepatitis C virus-infected patients are 'spared' from the metabolic syndrome but not from insulin resistance. A comparative study of nonalcoholic fatty liver disease and hepatitis C virus-related steatosis.

BACKGROUND Nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis C feature steatosis and insulin resistance (IR), conditions associated with the metabolic syndrome (MS). OBJECTIVES To assess the prevalence of MS and determinants of IR in patients with NAFLD and chronic hepatitis C. METHODS Ninety-three consecutive patients with NAFLD, 97 with chronic hepatitis C virus (HCV) genotypes 1 and 2, and 182 'healthy' controls without steatosis were enrolled in the present study. The prevalence of MS was assessed by modified Adult Treatment Panel III criteria and IR by the homeostasis model assessment of insulin resistance (HOMA-IR). IR was defined as the 75th percentile of the HOMA-IR of control subjects. RESULTS While the prevalence of IR was similar in NAFLD and HCV-infected subjects (70.0% and 78.7%, respectively), the prevalence of MS was significantly higher in NAFLD patients than in HCV-infected patients (27.9% versus 4.1%) and in controls (5.6%). With multivariate analysis, IR was predicted by body mass index (OR 1.263; 95% CI 1.078 to 1.480) and triglyceridemia (OR 1.011; 95% CI 1.002 to 1.020) in NAFLD and by sex (OR for female sex 0.297; 95% CI 0.094 to 0.940) and fibrosis stage (OR 2.751; 95% CI 1.417 to 5.340) in chronic hepatitis C. CONCLUSIONS IR is independently associated with body mass index and triglyceridemia in NAFLD, sex and fibrosis in chronic HCV infection, and has a higher prevalence in NAFLD and chronic hepatitis C than in controls. However, the frequency of MS in HCVinfected patients, similar to that of controls, is significantly lower than that seen in NAFLD patients. The current diagnostic criteria of MS are more likely to 'capture' patients with NAFLD than with chronic hepatitis C, although both groups are insulin resistant.
Apoptosis and immunohistochemical bcl‐2 expression in colorectal adenomas and carcinomas: Aspects of carcinogenesis and prognostic significance

The bcl‐2 oncoprotein confers a survival advantage to cells by inhibiting programmed cell death (PCD) or apoptosis. Overexpression of bcl‐2 probably plays a role in colorectal carcinogenesis. The aims of our study were to determine bcl‐2 expression and PCD index in colorectal adenomas and carcinomas in correlation with p53 expression, Ki‐67 index, and histopathology, and to test their prognostic significance in patients with colorectal carcinomas.
Loss of Early Phase of Insulin Release in Humans Impairs Glucose Tolerance and Blunts Thermic Effect of Glucose

Loss of the early phase of insulin release has been documented in both type I (insulin-dependent) and type II (non-insulin-dependent) diabetes; however, the physiological importanceof this loss is unsettled. We created a model of loss of the early phase of insulin release in normal volunteers. Somatostatin (SRIF) was briefly infused (from −5 to 15 min) during intravenous (IVGTT) and oral (OGTT) glucose tolerance tests. The thermic response to oral glucose was determined under these conditions by indirect calorimetry. Early insulin release was totally blocked during IVGTT and OGTT by SRIF infusion. During the IVGTT, glucose tolerance was deteriorated in association with loss of the early phase of insulin release as indicated by a decrease in the K value (control 1.9 ± 0.36 vs. SRIF 1.1 ± 0.27, P < .001). Higher plasma glucose concentrations were observed during SRIF tests in the OGTT at 60, 90, 120, 150, and 180 min; total glycemic excursion was larger during the SRIF test (9473 ± 3089 mg · dl−1 · 5 h−1) when compared with the control condition (6583 ± 2329 mg dl−1 5 h−1). During the OGTT the total amount of glucose oxidized (control 56 ± 4.2 vs. SRIF 55 ± 3.4 g/5 h) was similar in both conditions, suggesting that nonoxidative pathways of glucose disposal were responsible for the deterioration in glucose tolerance. Surprisingly, we found that glucose-induced thermogenesis was reduced in association with loss of the early phase of insulin release (control 102 ± 21.3 vs. SRIF 72 ± 27.8 J/5 h, P < .001). Thus, loss of the early phase of insulin release is associated with deterioration of glucose tolerance and blunted glucose-induced thermogenesis. These data underscore the key role of the early phase of insulin release in glucose homeostasis and provide a possible mechanism that could lead eventually to obesity and diabetes.
L’Inégalité Mondiale: La Répartition des Revenus dans 141 Pays

Ce document: (i) donne un apercu de l'inegalite du revenu mondial, regional et national sur la base des dernieres donnees de la Banque mondiale, l'UNU-WIDER et Eurostat, (ii) examine les consequences negatives de l'inegalite croissante des revenus pour le developpement, (iii) appelle a un programme de developpement de l'ONU fonde sur l'equite, (iv) decrit la probabilite d’inegalites exacerbees au cours de la crise economique mondiale, (v) plaide pour des changements politiques urgents aux niveaux national et international pour assurer une «Reprise pour Tous», et (vi) sert de source de reference generale. L’annexe 2 presente un resume actualise des donnees sur la repartition des revenus et des inegalites dans 141 pays.
KCl and forskolin synergistically up‐regulate cholecystokinin gene expression via coordinate activation of CREB and the co‐activator CBP

Cholecystokinin (CCK) is one of the most abundant peptide transmitters in the mammalian brain. Despite the physiological significance of CCK expression in long‐term memory and psychiatric disorders, little is known about the factors that regulate the expression of CCK peptides. Here, we report that KCl and forskolin synergistically increase CCK gene transcription via protein kinase A (PKA) and extracellular signal‐regulated kinase (ERK) signalling pathways, activating cAMP response element‐binding protein (CREB) associated with the CRE(− 80) element of the CCK promoter. Whereas, CREB Ser133 phosphorylation was essential for transcriptional activation, the synergistic stimulation was not correlated to the level of Ser133 phosphorylation, indicating that recruitment and/or activation of additional downstream factors were required for maximal stimulation. Transcriptional activation was reduced by co‐expression of adenovirus 12S E1A, that inhibits binding of CREB‐binding protein (CBP) to CREB. Moreover GAL4‐CREB‐DIEDML, which mediates the phosphorylation‐independent binding of CBP, and the C‐terminal domain of CBP was synergistically activated by forskolin and KCl. Taken together the results imply that neuronal CCK gene transcription is regulated by the cumulative action of calcium and cAMP via stimulation of the PKA and ERK signalling pathways and that synergy is accomplished by the coordinate activation of CREB and CBP.
Filifactor alocis Infection and Inflammatory Responses in the Mouse Subcutaneous Chamber Model

ABSTRACT Recent microbiome studies have implicated a role for Filifactor alocis in periodontal disease. In this study, we investigated the colonization and survival properties of F. alocis in a mouse subcutaneous chamber model of infection and characterized host innate immune responses. An infection of 109 F. alocis successfully colonized all chambers; however, the infection was cleared after 72 h. F. alocis elicited a local inflammatory response with neutrophils recruited into the chambers at 2 h postinfection along with an increase in levels of the proinflammatory cytokines interleukin 1β (IL-1β), IL-6, and tumor necrosis factor (TNF). F. alocis also induced apoptosis in chamber epithelial cells and neutrophils. Consistent with resolution of infection, neutrophil numbers and cytokine levels returned to baseline by 72 h. Fluorescent in situ hybridization (FISH) and quantitative PCR demonstrated that F. alocis exited the chambers and spread to the spleen, liver, lung, and kidney. Massive neutrophil infiltration was observed in the spleen and lungs, and the recruited neutrophils were in close proximity to the infecting bacteria. Significant epithelial injury was observed in the kidneys. Infection of all tissues was resolved after 7 days. This first in vivo study of the pathogenicity of F. alocis shows that in the chamber model the organism can establish a proinflammatory, proapoptotic local infection which is rapidly resolved by the host concordant with neutrophil influx. Moreover, F. alocis can spread to, and transiently infect, remote tissues where neutrophils can also be recruited.