Miracle-dz/UniFAR-FTUs huggingface dataset:
Recombinant human lactoferrin induces human and mouse dendritic cell maturation via Toll‐like receptors 2 and 4

Lactoferrin, a key component of innate immunity, is a cationic monomeric 80‐kDa glycoprotein of the transferrin superfamily. Recombinant human lactoferrin, known as talactoferrin (TLF), induces a distinct functional maturation program in human dendritic cells (DCs) derived from peripheral blood monocytes. However, the receptors and molecular mechanisms involved in this induction have not been fully determined. By exploiting genome‐wide transcription profiling of immature DCs, TNF‐α‐ and IL‐1 β‐matured DCs (m‐DCs), and TLF‐matured DCs (TLF‐DCs), we have detected a set of transcripts specific for m‐DCs and one specific for TLF‐DCs. Functional network reconstruction highlighted, as expected, the association of m‐DC maturation with IL‐1β, TNF‐α, and NF‐κB, whereas TLF‐DC maturation was associated with ERK and NF‐κB. This involvement of ERK and NF‐κB transduction factors suggests direct involvement of Toll‐like receptors (TLRs) in TLF‐induced maturation. We have used MyD88 inhibition and siRNA silencing TLRs on human DCs and mouse TLR‐2‐knockout cells, to show that TLF triggers the maturation of both human and mouse DCs through TLR‐2 and TLR‐4. —Spadaro, M. , Montone, M. , Arigoni, M. , Cantarella, D. , Forni, G. , Pericle, F. , Pascolo, S. , Calogero, R. A. , Cavallo, F. Recombinant human lactoferrin induces human and mouse dendritic cell maturation via Toll‐like receptors 2 and 4. FASEB J. 28, 416–429 (2014). www.fasebj. org
Effects and side-effects of surgery for snoring and obstructive sleep apnea--a systematic review.

STUDY OBJECTIVES Many patients undergo surgery for snoring and sleep apnea, although the efficacy and safety of such procedures have not been clearly established. Our aim was systematically to review studies of the efficacy and adverse effects of surgery for snoring and obstructive sleep apnea. DESIGN Systematic review. MEASUREMENTS PubMed and Cochrane databases were searched in September 2007. Randomized controlled trials of surgery vs. sham surgery or conservative treatment in adults, with daytime sleepiness, quality of life, apnea-hypopnea index, and snoring as outcomes were included. Observational studies were also reviewed to assess adverse effects. Evidence of effect required at least two studies of medium and high quality reporting the same result. RESULTS Four studies of benefits and 45 studies of adverse effects were included. There was no significant effect on daytime sleepiness and quality of life after laser-assisted uvulopalatoplasty and radiofrequency ablation. The apnea-hypopnea index and snoring was reduced in one trial after laser-assisted uvulopalatoplasty but not in another trial. Subjective snoring was reduced in one trial after radiofrequency ablation. No trial investigating the effect of any other surgical modality met the inclusion criteria. Persistent side-effects occurred after uvulopalatopharyngoplasty and uvulopalatoplasty in about half the patients and difficulty in swallowing, globus sensation and voice changes were especially common. CONCLUSIONS Only a small number of randomized controlled trials with a limited number of patients assessing some surgical modalities for snoring or sleep apnea are available. These studies do not provide any evidence of effect from laser-assisted uvulopalatoplasty or radiofrequency ablation on daytime sleepiness, apnea reduction, quality of life or snoring. We call for research of randomized, controlled trials of surgery other than uvulopalatopharyngoplasty and uvulopalatoplasty, as they are related to a high risk of long-term side-effects, especially difficulty swallowing.
cADP-ribose potentiates cytosolic Ca2+ elevation and Ca2+ entry via L-type voltage-activated Ca2+ channels in NG108-15 neuronal cells.

The effects of cADP-ribose (cADPR), a metabolite of beta-NAD(+), on the elevation of cytoplasmic free Ca(2+) concentration ([Ca(2+)](i)) and Ca(2+) influx through voltage-activated Ca(2+) channels (VACCs) were studied in NG108-15 neuroblastomaxglioma hybrid cells. NG108-15 cells were pre-loaded with fura-2 and whole-cell patch-clamped. Application of cADPR through patch pipettes did not by itself trigger any [Ca(2+)](i) rise at the resting membrane potential. A rise in [Ca(2+)](i) was evoked upon sustained membrane depolarization, and was significantly larger in cADPR-infused cells than in non-infused cells. This potentiation in the [Ca(2+)](i) elevation was reproduced by infusion of beta-NAD(+), and was blocked by 8-bromo-cADPR and antagonized by external application of ryanodine or by pretreatment of cells with FK506. Nicotinamide inhibited beta-NAD(+)-induced, but not cADPR-elicited, potentiation. [Ca(2+)](i) increases or Ca(2+) influx, measured by Mn(2+) quenching, elicited by the same protocol of depolarization was blocked completely by nifedipine but not by omega-conotoxin. Ca(2+) influx in cADPR- or beta-NAD(+)-infused cells was steeper and greater than that in control cells, and was inhibited partly by ryanodine. In contrast, ryanodine accelerated Ca(2+) influx in non-infused cells. These results show that cADPR amplifies both depolarization-induced [Ca(2+)](i) increase and Ca(2+) influx through L-type VACCs. These results suggest that cADPR functions on ryanodine receptors as a direct agonist and also interacts with L-type VACCs as an indirect agonist, i.e. via a retrograde signal.
The Representation of Objects in the Human Occipital and Temporal Cortex

Recently, we identified, using fMRI, three bilateral regions in the ventral temporal cortex that responded preferentially to faces, houses, and chairs [Ishai, A. , Ungerleider, L. G. , Martin, A. , Schouten, J. L. , & Haxby, J. Y. (1999). Distributed representation of objects in the human ventral visual pathway. Proceedings of the National Academy of Sciences, U.S.A. , 96, 9379-9384]. Here, we report differential patterns of activation, similar to those seen in the ventral temporal cortex, in bilateral regions of the ventral occipital cortex. We also found category-related responses in the dorsal occipital cortex and in the superior temporal sulcus. Moreover, rather than activating discrete, segregated areas, each category was associated with its own differential pattern of response across a broad expanse of cortex. The distributed patterns of response were similar across tasks (passive viewing, delayed matching) and presentation formats (photographs, line drawings). We propose that the representation of objects in the ventral visual pathway, including both occipital and temporal regions, is not restricted to small, highly selective patches of cortex but, instead, is a distributed representation of information about object form. Within this distributed system, the representation of faces appears to be less extensive as compared to the representations of nonface objects.
Physical and psychological outcomes 8 months after serious gunshot injury.

BACKGROUND The purpose of this study was to determine the health status and psychological distress of gunshot injury victims 8 months after hospital discharge. METHODS Sixty patients admitted to a Level I trauma center for firearm-related injuries were interviewed during their hospitalization and again 8 months postdischarge. Health status was measured using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). Symptoms of posttraumatic stress (avoidance and intrusion) were assessed using the Impact of Event Scale. RESULTS Subjects were predominantly young (mean age, 30 years), male (92%), and African-American (95%). Mean SF-36 scores at follow-up were significantly worse than preinjury scores for all subscales (p < 0.05). Symptoms of posttraumatic stress were common; 39% of respondents reported severe intrusive thoughts and 42% reported severe avoidance behaviors. Admission Injury Severity Scores did not predict poor health status 8 months postdischarge, but intrusion symptoms were strongly associated with lower SF-36 scores. CONCLUSION Many hospitalized survivors of gunshot injuries report significant long-term declines in physical and/or mental health. Injury severity at hospital admission may not be predictive of long-term health status.
Neuroendocrine effects of Citalopram, a selective serotonin re-uptake inhibitor, during lifespan in humans

Objective: Serotonergic system contributes to the regulation of hypothalamus-pituitary-adrenal axis. In humans, serotonergic agonists increase PRL, ACTH, and cortisol, while serotonin (5HT) influence on GH is controversial. Central 5HT activity and neuroendocrine function change during lifespan. Design: To clarify the neuroendocrine response to 5HT across lifespan, we assessed ACTH, cortisol, DHEA, PRL, and GH responses to citalopram (CT) in young adults (YA) (no.=12, 29.2±1.7 yr mean±SEM), middle aged (MA) (no.=12, 54.3±0.9 yr), and elderly (ES) (no.=12, 69.3±0.9 yr) males. All the subjects received placebo (saline iv over 120 min) or CT (20 mg iv over 120 min). Blood samples were taken every 15 min up to 240 min. Results: During placebo, ACTH, cortisol, GH, and PRL were similar in all groups while DHEA showed an age-dependent reduction from middle age (p<0.001). During CT, ACTH, and cortisol were higher than during placebo in YA (p<0.05) and even more in MA (p<0.01 vs placebo, p<0.05 vs YA); in ES, the increase of both ACTH and cortisol (p<0.05 vs placebo) was lower than in MA (p<0.05) and higher than in YA (p<0.05 for cortisol only). No changes were observed for DHEA, GH, and PRL in any group. Conclusions: Corticotrope response to CT is age-dependent in normal men, being amplified starting from middle age, suggesting precocious changes in the serotonergic neuroendocrine control during lifespan. CT is a useful tool to evaluate the age-dependent serotonergic function in humans.
Human CD1D Gene Has TATA Boxless Dual Promoters: An SP1-Binding Element Determines the Function of the Proximal Promoter1

CD1d presents lipid Ags to a specific population of NK T cells, which are involved in the host immune defense, suppression of autoimmunity, and the rejection of tumor cells. The transcriptional control mechanism that determines the regulation and the tissue distribution of CD1d remains largely unknown. After investigating 3.7 kb 5′ upstream of the coding region, we found that human gene encoding CD1d molecule (CD1D) has TATA boxless dual promoters with multiple transcription initiation sites. The proximal promoter is located within the region of −106 to +24, and the distal promoter is located within the region of −665 to −202 with the A of the translational start codon defined as +1. The longest 5′-untranslated region derived from 5′-RACE and apparently generated by the distal promoter has 272 bp in length covering the genomic sequence of the proximal promoter. The region covering the proximal promoter gave a much higher luciferase activity in Jurkat cells than in K562 cells, whereas it was in reverse for the region covering the distal promoter, indicating a cell type sp. act. of the two promoters. Transcription factor SP1 plays a crucial role in the function of the proximal promoter. The analysis of the CD1D promoter region indicates that IFN-γ, NF-IL-6, and T cell factor 1/lymphoid enhancer-binding factor 1 are most likely involved in the regulation of CD1d expression. The illustration of the dual CD1D gene promoters will help to reveal the regulatory factors that control CD1d expression and its tissue distribution for a better understanding of the cross-regulation between CD1d and NK T cells.
Thymoglobulin Induction Is Safe and Effective in Live-Donor Renal Transplantation: A Single Center Experience

Background. The relative benefit versus safety of induction therapy in live-donor renal transplant recipients is controversial. This paper presents observational data of live-donor recipients who received Thymoglobulin induction and standard maintenance immunosuppressive therapy. Methods. Review and analysis of clinic records and electronic databases of live-donor renal transplants that received Thymoglobulin induction from May 1996 through 2003. Results. Data analysis included 214 live-donor recipients (146 related, 68 unrelated) with a mean follow-up of 3.0±1.9 years. The average age of recipients was 44±13 years, with a majority being Caucasian (86%) and male (64%). Nineteen (9%) received previous transplants. No patients experienced delayed graft function and 10 (5%) developed acute rejection. Overall, predicted five-year patient survival was 96% and graft survival was 82%. The rates of CMV infection (5%), malignancy (3%), and lymphoproliferative disorder (0.5%) were low. When compared to live-donor kidney transplant recipients nationwide, the center cohort demonstrated improved five year patient (96% center versus 90% national, P=0.0326) and graft survival (82% center versus 79% national, P=0.0901), and a lower one-year acute rejection rate (2% center versus 21 % national, P<0.001). Conclusions. In this analysis, the use of Thymoglobulin in live-donor renal transplantation was associated with an absence of delayed graft function, low acute rejection rates, and high patient and graft survival without increasing the risk of infection or lymphoproliferative disorder.
Platelet Activation and Signal Transduction by Convulxin, a C-type Lectin from Crotalus durissus terrificus (Tropical Rattlesnake) Venom via the p62/GPVI Collagen Receptor*

Convulxin, a powerful platelet activator, was isolated from Crotalus durissus terrificus venom, and 20 amino acid N-terminal sequences of both subunits were determined. These indicated that convulxin belongs to the heterodimeric C-type lectin family. Neither antibodies against GPIb nor echicetin had any effect on convulxin-induced platelet aggregation showing that, in contrast to other venom C-type lectins acting on platelets, GPIb is not involved in convulxin-induced platelet activation. In addition, partially reduced/denatured convulxin only affects collagen-induced platelet aggregation. The mechanism of convulxin-induced platelet activation was examined by platelet aggregation, detection of time-dependent tyrosine phosphorylation of platelet proteins, and binding studies with 125I-convulxin. Convulxin induces signal transduction in part like collagen, involving the time-dependent tyrosine phosphorylation of Fc receptor γ chain, phospholipase Cγ2, p72SYK, c-Cbl, and p36–38. However, unlike collagen, pp125FAK and some other bands are not tyrosine-phosphorylated. Convulxin binds to a glycosylated 62-kDa membrane component in platelet lysate and to p62/GPVI immunoprecipitated by human anti-p62/GPVI antibodies. Convulxin subunits inhibit both aggregation and tyrosine phosphorylation in response to collagen. Piceatannol, a tyrosine kinase inhibitor with some specificity for p72SYK, showed differential effects on collagen and convulxin-stimulated signaling. These results suggest that convulxin uses the p62/GPVI but not the α2β1 part of the collagen signaling pathways to activate platelets. Occupation and clustering of p62/GPVI may activate Src family kinases phosphorylating Fc receptor γ chain and, by a mechanism previously described in T- and B-cells, activate p72SYK that is critical for downstream activation of platelets.
Neurophysiological evidence on perception of reward and risk: Implications for trading under time pressure

Recent neurophysiological studies reveal that risk and reward are separately encoded in the human brain, and that the encodings display different timing patterns. Therefore, we hypothesized that sensitivity of trading decisions to risk and reward parameters would differ depending on time pressure. Consistent with this prediction, we find that decisions under extreme time pressure (1s delay time, with decision to be made in next 1s interval) reflect preference for expected reward and aversion to variance and skewness. With less time pressure (3s or 5s delay before decision), variance sensitivity disappears; sensitivity to expected reward remains the same and sensitivity to skewness increases. Buying impulsiveness emerges under extreme time pressure (subjects buy at higher prices, ceteris paribus), but is fully offset when more time is available. Prospect-theoretic preferences can capture decisions under extreme price pressure (including buying impulsiveness), but classical smooth expected utility preferences (constant relative and absolute risk aversion) cannot. Because choices reveal aversion to skewness but no aversion to variance, choices under less time pressure are inconsistent with either classical preferences or prospect theory. Our findings have implications for trading platform (market microstructure) design, incentives contracts, and for program trading.
Estimating Fiscal multipliers in the Eurozone. A Nonlinear Panel Data Approach.

During the sovereign debt crisis, all euro countries have deployed \aus- terity packages", believing that they could regain the path of growth im- plementing structural reforms and cutting government spending. Such policies should have led to an initial decline in GDP followed by recov- ery and a reduction of the debt to gdp ratio. A key issue is the size of scal multipliers when the economy is in recession. We estimate a non- linear model allowing variations based on the state of the economy and we control for the macroeconomic characteristics across the Euro Area. The empirical evidence suggests that, an increase in government spending will be particularly eective to boost aggregate demand, increase private consumption and investment in the short-to-medium run, without raising the debt to gdp ratio but rather decreasing it.
Potent morphiceptin analogs: structure activity relationships and morphine-like activities.

Morphiceptin (Tyr-Pro-Phe-Pro-NH2), a nonenkephalin peptide, is an opioid agonist highly selective for mu opiate receptors. Chemical modification of Tyr-Pro-Phe-Pro-NH2 was carried out by substituting structurally related amino acids at residues 2, 3 and 4. The morphiceptin analogs synthesized were then examined for receptor binding activities using 125I-labeled FK 33,824 (Tyr-D-Ala-Gly-NMePhe-Met(O)-ol) as the mu-ligand and 125I-labeled D-Ala2,D-Leu5-enkephalin as the delta-ligand, and for inhibitory activities on electrically evoked smooth muscle contraction of mouse vas deferens and isolated myenteric plexus-longitudinal muscle strips of guinea-pig ileum. All of these analogs showed virtually no activity at delta opiate receptor binding sites. Methylation of the nitrogen atom of phenylalanine and the substitution at the C-terminal of L-proline by D-proline produced potent mu-agonists, the prototype analog being Tyr-Pro-NMePhe-D-Pro-NH2 (PL017). The IC50 values of morphiceptin and its analogs for mu receptor binding were correlated to the ED50 values in the guinea-pig ileum assay, suggesting that the ileum effects were mediated by mu receptor interactions. A similar correlation between mu receptor binding activity and the ED50 values in the mouse vas deferens assay suggested that morphiceptin and its analogs also acted on mu receptors in this tissue. This idea is supported by the observation that naloxone has a high pA2 value of 8.71 against PL017 in mouse vas deferens. In in vivo studies, PL017 administered centrally into the rostral portion of the 4th ventricle produced long-lasting, naloxone-reversible analgesia in rats. (ABSTRACT TRUNCATED AT 250 WORDS)
Distribution of Histopathology and Ia Positive Cells in Actively Induced and Passively Transferred Experimental Autoimmune Orchitis a

Histopathology in testes from mice with actively induced experimental orchitis (EAO) (active EAO) and those from recipients of testis-sensitized lymphocytes (passive EAO) had different distributions. In passive EAO, maximum orchitis existed in the straight tubules, rete testis, and ductus efferentes, obstruction of which led to extreme dilatation of seminiferous tubules. Unusual intralymphatic granulomata also resulted in dilated testicular lymphatics. In active EAO, maximum orchitis affected seminiferous tubules under the testicular capsule, away from the rete testes. Vasitis was common and occurred in both active and passive EAO. In normal testes, IA+ F4/80+ cells were sparse but formed a cuff around the straight tubules. After immunization with testis in adjuvant or with adjuvant alone, the number, size, and staining intensity of IA+ cells increased dramatically beginning on day 5, 7 days before disease onset. Simultaneously, epithelial cells confined to the ductus efferentes became Ia+. Although recipients of sensitized lymphocytes also developed epithelial Ia in the ductus efferentes, they did not show changes in testicular interstitial Ia+ cells. Our findings indicate that testicular autoantigens are not completely sequestered, but are accessible to and can react with passively transferred immune lymphocytes in well-defined regions of the germ cell compartment. These regions coincided to a large extent with maximum expression of periductal or epithelial Ia. Changes in Ia+ cells in the testis, which are inducible by adjuvants and precede orchitis, may account in part for the different distribution of histopathology of active EAO.
The ‘Functional Muscle-Cartilage Unit’: A Reasonable Approach to Describe a Putative Relationship between Muscle Force and Longitudinal Growth at the Forearm in Children and Adolescents?

Background: Several reports give evidence that the perichondral ossificiation of bone tubes (modeling) strongly depends on muscular forces in children and adolescents. The present analyses intend to investigate the hypothesis that muscular forces also partly determine enchondral ossification and, therefore, longitudinal growth of bone tubes. Subjects and Methods: Analyses were based on a single cross-sectional investigation with peripheral quantitative computed tomography in 296 individuals (age 5–19 years) participating in the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study. Results: Forearm length (FL) was correlated with body height in gender-related subgroups of prepubertal and pubertal individuals (rs between 0.76 and 0.86). Cross-sectional muscle area (MA) increased faster than FL and faster than cross-sectional bone area (BA) close to the distal growth plate in puberty. Close to the growth plate, longitudinal growth was faster than perichondral ossification in females. The ratio MA/BA (surrogate of pressure on the distal growth plate) was correlated with FL in prepubertal boys (r = –0.249, p = 0.043) and pubertal individuals (r = 0.153, p = 0.051). Conclusions: Results support the hypothesis that longitudinal growth precedes modeling at the distal forearm. Confounding variables such as puberty may modify the relationship between muscle forces and longitudinal growth at the forearm in boys.