julilili42/papers huggingface dataset:
Impact of serum and dialysates obtained from chronic hemodialysis patients maintained on high cut‐off membranes on inflammation profile in human THP‐1 monocytes
2016-09-26

Abstract Introduction: Patients with chronic kidney disease maintained on intermittent hemodialysis suffer from systemic chronic inflammation which is causally associated with high mortality. Inflammation mediators of 15–45 kDa range cannot be effectively removed by conventional dialysis membranes. In this study, we tested the influence of serum and dialysates obtained from patients maintained on High cut‐off or High flux membranes on the inflammation profile of THP‐1 monocytes. Methods: THP‐1 monocytes were treated with serum or dialysates obtained from patients maintained on High cut‐off and High flux membranes within a randomized crossover pilot trial. Serum‐treated cells were subjected to qPCR analyses with TaqMan probes specific for IL6, TNFa, osteopontin and osteocalcin, and transcriptional screening with Inflammatory Array. Apoptosis assay was performed flow cytometrically with 7‐AAD and Annexin V staining. Findings: Treatment of the cells with High cut‐off serum led to significant reduction of TNFa and IL‐6 expression as well as inflammation‐related osteopontin and osteocalcin as compared to High flux membrane treatment. As a complementary finding, treatment with High cut‐off dialysates induced a pro‐apoptotic phenotype in the cells as demonstrated by a significantly increased percentage of 7‐AAD and Annexin V positivity. Global screening of serum‐treated cells revealed noticeably decreased inflammation profile under High cut‐off serum as compared to High flux treatment. Discussion: Taken together, these data demonstrate that High cut‐off ‐membranes eliminate a spectrum of mediators from serum into the dialysate that possess proinflammatory properties and may impair cellular viability.
Lipoprotein immunoproteomics question the potential of Staphylococcus aureus TLR2 agonists as vaccine antigens
2016-09-26

Toll‐like receptor 2 (TLR2) is regarded as the major innate immunity sensor in infections caused by the Gram‐positive bacterial pathogen Staphylococcus aureus . However, previous studies on the roles of TLR2 in S. aureus infections have been elusive and in part contradictory. It has remained particularly unclear if bacterial lipoproteins, the major TLR2 ligands, could serve as antigens with intrinsic adjuvant property for the development of protective vaccines. The study by Vu et al. published in this issue of Proteomics analyzed the antibody and T‐cell responses in human sera against major S. aureus lipoproteins. Notably, even lipoproteins released to culture filtrates at similar levels as established immunodominant antigens elicited only very weak or no detectable antibody and T‐cell responses, indicating that the potent TLR2‐stimulating capacity of S. aureus lipoproteins does not promote and may rather impair robust immune responses so lipoprpteins. Among several potential explanations it is tempting to speculate that the role of TLR2 in S. aureus infections may be more complex and more ambiguous than previously thought. The study of Vu et al. may thus provoke more detailed investigations on the roles of lipoproteins and TLR2 in innate and adaptive immunity against bacterial pathogens.
Use of laser capture microdissection coupled mass spectrometry to analyze the choroidal proteome relevant to AMD
2016-09-26

Purpose : Age-related macular degeneration (AMD) is a sight-threatening disorder of the central retina. Emerging evidence suggests that the loss of choroidal vasculature may be the initial insult leading to the dysfunction of photoreceptors, but the underlying molecular mechanisms are still to be elucidated. We performed a systematic analysis of the human choroidal proteome to gain insights into underlying disease processes. Methods : Human post-mortem eyes from six donors were removed and fixed with cross-linking (10% buffered formalin) fixative. Laser capture microdissection was used to isolate minute amounts of the regions of interest from cresyl violet stained sections for subsequent proteomics analysis. Catapulted tissue patches were directly collected in CapSure® caps and subjected to alternating cycles of ambient to high pressure (up to 35,000 psi), in order to facilitate enzymatic digestions of samples. Mass spectrometry analysis was conducted after trypsinization of the samples. Photoreceptor outer segments were also isolated along with choroidal samples serving as controls to detect abundant proteins also present outside the choroid. LC-MS/MS analysis was performed an Orbitrap Fusion mass spectrometer. All acquired spectra were analyzed using the MaxQuant software. Results : Formalin fixation gave satisfactory results in preserving tissue morphology and protein identification. Hundred eighty-four proteins were identified both in choroidal and in retinal samples, while thirty proteins were specific to choroid. As expected, most of the choroid-specific proteins are constituents of the extracellular matrix (e.g. Heparan Sulfate Proteoglycan 2, lamininins) and also collagens with known AMD risk variants in the corresponding genes (COL4A3, COL8A1). Besides, melanocyte-specific proteins (e.g. Transmembrane Glycoprotein NMB) were also characteristic for the choroid. Conclusions : The combination of LCM and mass spectrometric technologies may be effective in detecting protein profiles within the choroid specific to age-related changes and to certain pathologies. Using high-pressure assisted sample preparation not only abridged processing, but vastly improved protein identification offering great analytical depth. This strategy can contribute to a better understanding of the role of choroid in the pathomechanism of AMD. This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
Atypical Self-Focus Effect on Interoceptive Accuracy in Anorexia Nervosa
2016-09-27

<b>Background</b>: Interoceptive abilities are known to be affected in anorexia nervosa (AN). Previous studies could show that private self-focus can enhance interoceptive accuracy (IAcc) in healthy participants. As body dissatisfaction is high in AN, confrontation with bodily features such as the own face might have a directly opposed effect in AN. Whether patients with AN can benefit from self-focus in their IAcc and whether this pattern changes over the time-course of cognitive behavioral therapy was investigated in this study. <b>Methods</b>: Fifteen patients with AN from the Psychosomatic Clinic in Windach were assessed three times in the time course of a standardized cognitive-behavioral therapy. They were compared to 15 controls, recruited from Ulm University and tested in a comparable setting. Both groups performed the heartbeat perception task assessing IAcc under two conditions either enhancing ("Self") or decreasing ("Other") self-focused attention. Furthermore, body dissatisfaction was assessed by a subscale of the Eating Disorder (ED) Inventory 2. <b>Results</b>: Patients with AN scored higher in IAcc when watching others' faces as compared to one's own face while performing the heartbeat perception task. The opposite pattern was observed in controls. IAcc remained reduced in AN as compared to controls in the time-course of cognitive-behavioral therapy, while body-dissatisfaction improved in AN. High body dissatisfaction was related to poorer IAcc in the "Self" condition. <b>Conclusions</b>: Our findings suggest that using self-focused attention reduces IAcc in AN while the opposite pattern was observed in controls. Confronting anorexic patients with bodily features might increase body-related avoidance and therefore decrease IAcc. The current study introduces a new perspective concerning the role of interoceptive processes in AN and generates further questions regarding the therapeutic utility of methods targeting self-focus in the treatment of AN.
Monoclonal antibodies for the treatment of Ebola virus disease
2016-09-27

To date, the management of patients with suspected or confirmed Ebolavirus disease (EVD) depends on quarantine, symptomatic management and supportive care, as there are no approved vaccines or treatments available for human use. However, accelerated by the recent large outbreak in West Africa, significant progress has been made towards vaccine development but also towards specific treatment with convalescent plasma and monoclonal antibodies. Areas covered: We describe recent developments in monoclonal antibody treatment for EVD, encompassing mAb114 and the MB-003, ZMAb, ZMappTM and MIL-77E cocktails. Expert opinion: Preventive measures, are, and will remain essential to curb EVD outbreaks; even more so with vaccine development progressing. However, research for treatment options must not be neglected. Small-scale animal and individual human case studies show that monoclonal antibodies (mAbs) can be effective for EVD treatment; thus justifying exploration in clinical trials. Potential limitations are that high doses may be needed to yield clinical efficacy; epitope mutations might reduce efficacy; and constant evolution of (outbreak-specific) mAb mixtures might be required. Interim advice based on the clinical experience to date is that treatment of patients with mAbs is sensible, provided those could be made available in the necessary amounts in time.
The effect of the severity of obstructive sleep apnea syndrome on telomere length
2016-09-27

Aging is associated with an increase in the prevalence of obstructive sleep apnea syndrome (OSAS) as well as the shortening of telomeres. It is known that OSAS-related factors are stimuli that can contribute to the acceleration of cellular senescence. Thus, the present study aimed to compare the leukocyte telomere length (LTL) between OSAS patients and controls, as well as to verify the correlation between LTL and sleep parameters. We used DNA extracted of 928 individuals from EPISONO to measure the LTL by the quantitative real-time polymerase chain reaction. All individuals were subjected to one full-night polysomnography. LTL was significantly shorter in OSAS patients compared to controls. The results showed negative correlations between LTL and the following variables: apnea-hypopnea index, respiratory disturbance index, desaturation index and wake after sleep onset. LTL was positively correlated with sleep efficiency, total sleep time, basal, minimum and maximum oxygen saturation. Lastly, it was observed that OSAS severity was associated with shorter LTL even after adjusting for sex, age, years of schooling, body mass index, diabetes, stroke and heart attack. In conclusion, our study indicates the presence of an association between LTL and OSAS and a significant impact of severity of OSAS in telomeres shortening.
Triggering receptor expressed on myeloid cells 1 (TREM‐1) and cytokine gene variants in complicated and uncomplicated malaria
2016-09-27

Abstract Background Malaria elicits inflammatory responses, which, if not well regulated, may exert detrimental effects. When activated, triggering receptor expressed on myeloid cells 1 ( TREM ‐1) enhances inflammatory responses by increasing secretion of IL ‐8 and other Th1 cytokines. In contrast, TREM ‐like transcript 1 ( TREML ‐1) promotes anti‐inflammatory responses by binding to TREM ‐1 ligands and competing with TREM ‐1, thus antagonizing TREM ‐1 activation to reduce inflammation. Endothelial protein C receptor ( EPCR ) also mediates anti‐inflammatory responses by activating endothelial protein C ( PC ). Upon microbial stimulation, soluble forms of TREM ‐1 ( sTREM ‐1) and soluble EPCR ( sEPCR ) are released. Their plasma levels reflect the degree of inflammation and the severity of infection. Methods In a cross‐sectional study comparing patients with severe with uncomplicated malaria, sTREM ‐1, soluble TREML ‐1 ( sTREML ‐1) and sEPCR plasma levels as well as plasma levels of sEPCR derived from convalescent patients were quantified. Samples were collected on admittance of paediatric patients infected with Plasmodium falciparum to hospitals in Accra, Ghana. Distinct genetic regions of the genes encoding TREM ‐1, EPCR , interleukin ( IL )‐8 and IL ‐18 encompassing known genetic polymorphisms that influence plasma levels underwent DNA sequencing. Results Higher sTREM ‐1 levels were observed among children suffering from severe malaria compared to those with uncomplicated malaria ( P = 0.049). Low TREM ‐1 to TREML ‐1 ratios were associated with uncomplicated malaria ( P = 0.033). The TREM 1 rs2234237T variant causing the amino acid exchange Thr25Ser, which has been associated with higher TREM ‐1 plasma levels, was significantly more frequent among patients with severe malaria than in those with uncomplicated malaria ( P = 0.036). Low levels of sEPCR were observed in severe and uncomplicated malaria, while variant genotypes of IL 8, IL 18 and EPCR did not show any association. Conclusion Higher plasma levels of sTREM ‐1 alone or relative to sTREML ‐1 during malaria predispose to the phenotype of severe malaria. Carriage of the TREM 1 rs2234237T allele appears to be a risk factor for the development of severe malaria.
Early Vocabulary in Relation to Gender, Bilingualism, Type, and Duration of Childcare
2016-09-27

This study investigates the predictive value of child-related and environmental characteristics for early lexical development. The German productive vocabulary of 51 2-year-olds (27 girls), assessed via parental report, was analyzed taking children's gender, the type of early care they experienced, and their mono- versus bilingual language composition into consideration. The children were from an educationally homogeneous group of families and state-regulated daycare facilities with high structural quality. All investigated subgroups exhibited German vocabulary size within the expected normative range. Gender differences in vocabulary composition, but not in size, were observed. There were no general differences in vocabulary size or composition between the 2 care groups. An interaction between the predictors gender and care arrangement showed that girls without regular daycare experience before the age of 2 years had a somewhat larger vocabulary than all other investigated subgroups of children. The vocabulary size of the 2-year-old children in daycare correlated positively with the duration of their daycare experience prior to testing. The small subgroup of bilingual children investigated exhibited slightly lower but still normative German expressive vocabulary size and a different vocabulary composition compared to the monolingual children. This study expands current knowledge about relevant predictors of early vocabulary. It shows that in the absence of educational disadvantages the duration of early daycare experience of high structural quality is positively associated with vocabulary size but also points to the fact that environmental characteristics, such as type of care, might affect boys' and girls' early vocabulary in different ways.
Plasmodium falciparum infection in febrile Congolese children: prevalence of clinical malaria 10 years after introduction of artemisinin‐combination therapies
2016-09-27

Abstract Objectives To investigate the proportion of malaria infection in febrile children consulting a paediatric hospital in Brazzaville, to determine the prevalence of submicroscopic malaria infection, to characterise Plasmodium falciparum infection and compare the prevalence of uncomplicated P. falciparum malaria according to haemoglobin profiles. Methods Blood samples were collected from children aged &lt;10 years with an axillary temperature ≥37.5 °C consulting the paediatric ward of Marien Ngouabi Hospital in Brazzaville. Parasite density was determined and all samples were screened for P. falciparum by nested polymerase chain reaction ( PCR ) using the P. falciparum msp‐2 marker to detect submicroscopic infections and characterise P. falciparum infection. Sickle cell trait was screened by PCR . Results A total of 229 children with fever were recruited, of whom 10% were diagnosed with uncomplicated malaria and 21% with submicroscopic infection. The mean parasite density in children with uncomplicated malaria was 42 824 parasites/μl of blood. The multiplicity of infection ( MOI ) was 1.59 in children with uncomplicated malaria and 1.69 in children with submicroscopic infection. The mean haemoglobin level was 10.1 ± 1.7 for children with uncomplicated malaria and 12.0 ± 8.6 for children with submicroscopic infection. About 13% of the children harboured the sickle cell trait (Hb AS ); the rest had normal haemoglobin (Hb AA ). No difference in prevalence of uncomplicated malaria and submicroscopic infection, parasite density, haemoglobin level, MOI and P. falciparum genetic diversity was observed according to haemoglobin type. Conclusion The low prevalence of uncomplicated malaria in febrile Congolese children indicates the necessity to investigate carefully other causes of fever.
Deficiency of the adaptor protein SLy1 results in a natural killer cell ribosomopathy affecting tumor clearance
2016-09-27

Individuals with robust natural killer (NK) cell function incur lower rates of malignancies. To expand our understanding of genetic factors contributing to this phenomenon, we analyzed NK cells from cancer resistant and susceptible strains of mice. We identified a correlation between NK levels of the X-chromosome-located adaptor protein SLy1 and immunologic susceptibility to cancer. Unlike the case for T or B lymphocytes, where SLy1 shuttles between the cytoplasm and nucleus to facilitate signal transduction, in NK cells SLy1 functions as a ribosomal protein and is located solely in the cytoplasm. In its absence, ribosomal instability results in p53-mediated NK cell senescence and decreased clearance of malignancies. NK defects are reversible under inflammatory conditions and viral clearance is not impacted by SLy1 deficiency. Our work defines a previously unappreciated X-linked ribosomopathy that results in a specific and subtle NK cell dysfunction leading to immunologic susceptibility to cancer.
IL‐1β, IL‐18, and eicosanoids promote neutrophil recruitment to pore‐induced intracellular traps following pyroptosis
2016-09-28

Inflammasomes activate caspase‐1, initiating a lytic form of programmed cell death termed pyroptosis, which is an important innate immune defense mechanism against intracellular infections. We recently demonstrated in a mouse infection model of pyroptosis that instead of releasing bacteria into the extracellular space, bacteria remain trapped within the pyroptotic cell corpse, termed the pore‐induced intracellular trap (PIT). This trapping mediates efferocytosis of the PIT and associated bacteria by neutrophils; bacteria are subsequently killed via neutrophil ROS. Using this pyroptosis model, we now show that the pro‐inflammatory cytokines IL‐1β and IL‐18 and inflammatory lipid mediators termed eicosanoids are required for effective clearance of bacteria downstream of pyroptosis. We further show that IL‐1β, IL‐18, and eicosanoids affect this in part by mediating neutrophil recruitment to the PIT. This is in addition to our prior findings that complement is also important to attract neutrophils. Thus, the PIT initiates a robust and coordinated innate immune response involving multiple mediators that attract neutrophils to efferocytose the PIT and its entrapped bacteria.
Geographic variation in coal tit song across continents and reduced species recognition between Central European and Mediterranean populations
2016-09-28

Intraspecific variation of passerine song may influence mate choice and consequently provides a potential mechanism for premating reproductive isolation in birds. Notable geographic variation of songs is particularly common in widespread bird species, such as the coal tit Periparus ater (Aves, Passeriformes, Paridae) having a large trans-Palearctic distribution range including allopatric populations. In this study, measurement and analysis of 16 song parameters from different Western Palearctic populations showed a relatively uniform song in all continental European and the island populations of Corsica and Sardinia. Song variation among and within these populations seems so variable that there is a broad geographical overlap of acoustic parameters between populations. However, songs from northwest African and Cypriot populations had lowest minimum frequencies and were thus significantly different from continental European, Corsican and Sardinian populations. To test for intraspecific species recognition and potential acoustic isolation of different Palearctic populations, we carried out field playback experiments on Central European coal tit males with songs from populations of the Eurasian (Germany, Latvia, Russian Far East, Japan) and the Mediterranean region (northwest Africa, Cyprus, Corsica, Sardinia). Eurasian song types elicited similar strong territorial reactions in Central European coal tits as local control songs. In contrast, none of the Mediterranean songs evoked any notable reaction. Thus, there is geographic variation in coal tit song across continents that coincides with reduced species recognition between Central European and Mediterranean populations.
Hemostyptic property of chitosan: Opportunities and pitfalls
2016-09-28

Our data indicate that chitosan activates human blood coagulation and hence has good properties as a hemostyptic agent. However, inflammatory parameters were upregulated after direct contact with human blood indicating that systemic administration of chitosans should not be performed whereas the topical use of chitosan as a hemostypticum should not present any hazard with regard to adverse inflammatory reactions at the site of application.
Adiponectin and pro‐inflammatory cytokines are modulated in Vietnamese patients with type 2 diabetes mellitus
2016-09-29

Abstract Aims/Introduction Adipose tissue‐derived hormones are associated with metabolic disorders including type 2 diabetes mellitus. The present study investigated the levels of adiponectin and pro‐inflammatory cytokines including tumor necrosis factor‐α ( TNF ‐α), interleukin‐1 beta ( IL ‐1β) and IL ‐10 in Vietnamese patients with type 2 diabetes mellitus, and their correlations with clinical parameters of overweight and type 2 diabetes mellitus. Materials and Methods Based on body mass index, 73 patients with type 2 diabetes mellitus were categorized either as overweight or non‐overweight. As healthy controls, 57 overweight and non‐overweight individuals without type 2 diabetes mellitus were included. The adiponectin, TNF ‐α, IL ‐1β and IL ‐10 levels were measured in the sera samples in all study participants by enzyme‐linked immunosorbent assay and were correlated with clinical parameters. Results The adiponectin levels were lower in patients with type 2 diabetes mellitus (2.5 ± 1.5 μg/mL) compared with controls (16 ± 18.6 μg/mL; P &lt; 0.0001), and were decreased in overweight individuals compared with those who were not overweight. The TNF ‐α and IL ‐1β levels were increased, whereas the IL ‐10 levels were decreased in patients with type 2 diabetes mellitus and in overweight controls compared with non‐overweight controls ( P &lt; 0.0001). The adiponectin levels were correlated with the TNF ‐α, IL ‐1β, IL ‐10 levels, and the clinical parameters of overweight and type 2 diabetes mellitus. The quantitative insulin sensitivity check index and homeostasis model assessment insulin resistance indexes were correlated with the relative ratios of adiponectin/ TNF ‐α, adiponectin/ IL ‐1β, adiponectin/ IL ‐10, TNF ‐α/ IL ‐10 and IL ‐1β/ IL ‐10. Conclusions Adiponectin and pro‐inflammatory cytokines are associated with type 2 diabetes mellitus, and might serve as a prognostic marker and a therapeutic intervention for overweight‐related type 2 diabetes mellitus.