julilili42/papers huggingface dataset:
Involvement of MicroRNAs in the Aging-Related Decline of CD28 Expression by Human T Cells
2018-06-18

Loss of CD28 is a characteristic feature of T cell aging, but the underlying mechanisms of this loss are elusive. As differential expression of microRNAs (miRNAs) has been described between CD28+ and CD28- T cells, we hypothesized that altered miRNA expression contributes to the age-associated downregulation of CD28. To avoid the confounding effects of age-associated changes in the proportions of T cells at various differentiation stages <i>in vivo</i>, an experimental model system was used to study changes over time in the expression of miRNA associated with the loss of CD28 expression in monoclonal T cell populations at a lower or higher number of population doublings (PDs). This approach allows identification of age-associated miRNA expression changes in a longitudinal model. Results were validated in <i>ex vivo</i> samples. The cumulative number of PDs but not the age of the donor of the T cell clone was correlated with decreased expression of CD28. Principal component analysis of 252 expressed miRNAs showed clustering based on low and high PDs, irrespective of the age of the clone donor. Increased expression of miR-9-5p and miR-34a-5p was seen in clones at higher PDs, and miR-9-5p expression inversely correlated with CD28 expression in <i>ex vivo</i> sorted T-cells from healthy subjects. We then examined the involvement of miR-9-5p, miR-34a-5p, and the members of the miR-23a~24-2 cluster, in which all are predicted to bind to the 3'UTR of CD28, in the IL-15-induced loss of CD28 in T cells. Culture of fresh naive CD28+ T cells in the presence of IL-15 resulted in a gradual loss of CD28 expression, while the expression of miR-9-5p, miR-34a-5p, and members of the miR-23a~24-2 cluster increased. Binding of miR-9-5p, miR-34a-5p, miR-24-3p, and miR-27- 3p to the 3'UTR of CD28 was studied using luciferase reporter constructs. Functional binding to the 3'UTR was shown for miR-24-3p and miR-27a-3p. Our results indicate involvement of defined miRNAs in T cells in relation to specific characteristics of T cell aging, i.e., PD and CD28 expression.
Investigating the Influence of Simultaneous– Versus Sequential–Text-Picture Presentation on Text-Picture Integration
2018-06-18

This study investigated whether text-picture integration is facilitated when text and pictures are presented simultaneously instead of sequentially. Participants memorized general and specific sentences and pictures. It was expected that due to text-picture integration, participants should falsely recognize specific versions of the sentences and pictures even after having studied only their general versions before. Sentences and pictures were presented simultaneously or sequentially with the picture either preceding or following the corresponding sentence. Contrary to expectations, text-picture integration was only observed for picture recognition and was not influenced by temporal contiguity. Findings are explained by the use of simple materials that did not sufficiently tax working-memory capacity to allow for any benefit of a simultaneous text-picture presentation to occur.
Student misbehavior and teacher well-being: Testing the mediating role of the teacher-student relationship
2018-06-19

Asked about major job stressors, teachers consistently name classroom disturbances or disciplinary problems. Furthermore, student misbehavior has been linked to reduced occupational well-being. However, there is a pressing need to uncover the psychological processes explaining this association. In their model of teacher well-being, Spilt, Koomen, and Thijs (2011) suggested the teacher-student relationship as a mediator. To test this assumption, the present study used longitudinal data from N = 222 teachers who rated student misbehavior in their classroom, the teacher-student relationship, and their well-being in terms of emotional exhaustion and work enthusiasm. In addition, the teachers' students (N = 4111) were asked about behavior problems in their class. The results revealed links between teacher-rated student misbehavior, increased exhaustion, and decreased enthusiasm. Student-rated misbehavior was correlated with teacher well-being to a lesser extent. Furthermore, the teacher-student relationship was positively associated with teacher well-being and mediated the link between teacher-perceived misbehavior and enthusiasm.
Greenland Ice Sheet: Higher Nonlinearity of Ice Flow Significantly Reduces Estimated Basal Motion
2018-06-19

Abstract In times of warming in polar regions, the prediction of ice sheet discharge is of utmost importance to society, because of its impact on sea level rise. In simulations the flow rate of ice is usually implemented as proportional to the differential stress to the power of the exponent n = 3. This exponent influences the softness of the modeled ice, as higher values would produce faster flow under equal stress. We show that the stress exponent, which best fits the observed state of the Greenland Ice Sheet, equals n = 4. Our results, which are not dependent on a possible basal sliding component of flow, indicate that most of the interior northern ice sheet is currently frozen to bedrock, except for the large ice streams and marginal ice.
Phosphorylation Modulates the Subcellular Localization of SOX11
2018-06-19

SOX11 is a key Transcription Factor (TF) in the regulation of embryonic and adult neurogenesis, whose mutation has recently been linked to an intellectual disability syndrome in humans. SOX11's transient activity during neurogenesis is critical to ensure the precise execution of the neurogenic program. Here, we report that SOX11 displays differential subcellular localizations during the course of neurogenesis. Western-Blot analysis of embryonic mouse brain lysates indicated that SOX11 is post-translationally modified by phosphorylation. Using Mass Spectrometry, we found 10 serine residues in the SOX11 protein that are putatively phosphorylated. Systematic analysis of phospho-mutant SOX11 resulted in the identification of the S30 residue, whose phosphorylation promotes nuclear over cytoplasmic localization of SOX11. Collectively, these findings uncover phosphorylation as a novel layer of regulation of the intellectual disability gene Sox11.
Feasibility study for a glutamate driven subretinal prosthesis: local subretinal application of glutamate on blind retina evoke network-mediated responses in different types of ganglion cells
2018-06-19

Objective. A feasibility study for a transmitter based subretinal prosthesis, generating visual responses in blind mouse retina is presented. Approach. Degenerated rd1 mouse retina were stimulated in subretinal configuration by local glutamate (Glu) or NMDA application via micropipettes (~1.5 μm) and thereby the outer retinal activity was recorded by calcium-imaging or the ganglion cell (GC) activity was recorded by the multi-electrode array system. The network mediated activation of GC via bipolar cells was approved by the administration of Glu receptor blockers. Main results. Data of the degenerated and blind rd1 mouse retina reveals that the outer retina is Glu sensitive and that the subretinal Glu stimulation promotes network mediated GC responses. Analysis of the spatial activity-spread indicates that the Glu induced cell activation radius in the outer retina (~12.5 μm) and postsynaptically activated GC (~40 μm) is focal to the stimulation pipette tip. Moreover, the application of NMDA in subretinal space also evoked network mediated GC responses. The Glu-activated GC were identified as ON–OFF, OFF and two ON cells types. Significance. This study evaluates the prerequisite for the function of a transmitter based implant, that after the loss of the photoreceptors, the remnant blind retinal network is Glu sensitive and functional, positively. The differential activation of ON (hyperpolarisation) and OFF (depolarisation) bipolar cells by transmitter Glu is a unique feature and of high interest for retinal implants. Therefore, the respective bipolar cell types could only be driven by glutamatergic stimulation accurately and not by electrical stimulation. The preserved functionality of the blind retina at the onset of complete blindness is motivating to continue research on a transmitter-based prosthesis. Since the artificial Glu stimulation mimics the natural retinal input, early implantation of a Glu-prosthesis might delay the devastating retinal remodelling positively, due to the neuronal-plasticity.
Independent evolution of functionally exchangeable mitochondrial outer membrane import complexes
2018-06-20

Assembly and/or insertion of a subset of mitochondrial outer membrane (MOM) proteins, including subunits of the main MOM translocase, require the fungi-specific Mim1/Mim2 complex. So far it was unclear which proteins accomplish this task in other eukaryotes. Here, we show by reciprocal complementation that the MOM protein pATOM36 of trypanosomes is a functional analogue of yeast Mim1/Mim2 complex, even though these proteins show neither sequence nor topological similarity. Expression of pATOM36 rescues almost all growth, mitochondrial biogenesis, and morphology defects in yeast cells lacking Mim1 and/or Mim2. Conversely, co-expression of Mim1 and Mim2 restores the assembly and/or insertion defects of MOM proteins in trypanosomes ablated for pATOM36. Mim1/Mim2 and pATOM36 form native-like complexes when heterologously expressed, indicating that additional proteins are not part of these structures. Our findings indicate that Mim1/Mim2 and pATOM36 are the products of convergent evolution and arose only after the ancestors of fungi and trypanosomatids diverged.
BMI-Independent Effects of Gestational Diabetes on Human Placenta
2018-06-20

GDM, independently of BMI, altered maternal plasma NEFAs and the placental lipid profile. GDM was associated with trophoblast and whole-placenta lipoinflammation; however, this was not accompanied by elevated concentrations of inflammatory cytokines or NEFAs in neonatal cord blood.
Short‐term external counterpulsation augments cerebral blood flow and tissue oxygenation in chronic cerebrovascular occlusive disease
2018-06-20

Background and purpose External counterpulsation improves cerebral perfusion velocity in acute stroke and may stimulate collateral artery growth. However, whether (non‐acute) at‐risk patients with high‐grade carotid artery disease may benefit from counterpulsation needs to be validated. Methods Twenty‐eight patients (71 ± 6.5 years, five women) with asymptomatic unilateral chronic severe internal carotid artery stenosis (&gt;70%) or occlusion were randomized to receive 20 min active counterpulsation followed by sham treatment or vice versa. Cerebral blood flow velocity ( CBFV ) (measured bilaterally by transcranial middle cerebral artery Doppler), tissue oxygenation index ( TOI ) (measured over the bilateral prefrontal cortex by near‐infrared spectroscopy) and cerebral hemodynamic parameters, such as relative pulse slope index ( RPSI ), were monitored. Results Ipsilateral mean CBFV (Δ V mean +3.5 ± 1.2 cm/s) and tissue oxygenation (Δ TOI +2.86 ± 0.8) increased significantly during active counterpulsation compared to baseline, whilst the sham had little effect (Δ V mean +1.13 ± 1.1 cm/s; Δ TOI +1.25 ± 0.65). On contralateral sides, neither counterpulsation nor sham control had any effect on either parameter. During counterpulsation, early dynamic changes in Δ RPSI of the ipsilateral CBFV signal predicted improved tissue oxygenation during counterpulsation (odds ratio 1.179, 95% confidence interval 1.01–1.51), whilst baseline cerebrovascular reactivity to hypercapnia failed to show an association. Conclusions In patients with high‐grade carotid disease, ipsilateral cerebral oxygenation and blood flow velocity are increased by counterpulsation. This is a necessary condition for the stimulation of regenerative collateral artery growth and thus a therapeutic concept for the prevention of cerebral ischaemia. This study provides a rationale for further clinical investigations on the long‐term effects of counterpulsation on cerebral hemodynamics and collateral growth.
Cytosolic Hsp70 and Hsp40 chaperones enable the biogenesis of mitochondrial β-barrel proteins
2018-06-21

Mitochondrial β-barrel proteins are encoded in the nucleus, translated by cytosolic ribosomes, and then imported into the organelle. Recently, a detailed understanding of the intramitochondrial import pathway of β-barrel proteins was obtained. In contrast, it is still completely unclear how newly synthesized β-barrel proteins reach the mitochondrial surface in an import-competent conformation. In this study, we show that cytosolic Hsp70 chaperones and their Hsp40 cochaperones Ydj1 and Sis1 interact with newly synthesized β-barrel proteins. These interactions are highly relevant for proper biogenesis, as inhibiting the activity of the cytosolic Hsp70, preventing its docking to the mitochondrial receptor Tom70, or depleting both Ydj1 and Sis1 resulted in a significant reduction in the import of such substrates into mitochondria. Further experiments demonstrate that the interactions between β-barrel proteins and Hsp70 chaperones and their importance are conserved also in mammalian cells. Collectively, this study outlines a novel mechanism in the early events of the biogenesis of mitochondrial outer membrane β-barrel proteins.
Historic Treponema pallidum genomes from Colonial Mexico retrieved from archaeological remains
2018-06-21

Treponema pallidum infections occur worldwide causing, among other diseases, syphilis and yaws. In particular sexually transmitted syphilis is regarded as a re-emerging infectious disease with millions of new infections annually. Here we present three historic T. pallidum genomes (two from T. pallidum ssp. pallidum and one from T. pallidum ssp. pertenue) that have been reconstructed from skeletons recovered from the Convent of Santa Isabel in Mexico City, operational between the 17th and 19th century. Our analyses indicate that different T. pallidum subspecies caused similar diagnostic presentations that are normally associated with syphilis in infants, and potential evidence of a congenital infection of T. pallidum ssp. pertenue, the causative agent of yaws. This first reconstruction of T. pallidum genomes from archaeological material opens the possibility of studying its evolutionary history at a resolution previously assumed to be out of reach.
Memote: A community driven effort towards a standardized genome-scale metabolic model test suite
2018-06-21

Abstract Several studies have shown that neither the formal representation nor the functional requirements of genome-scale metabolic models (GEMs) are precisely defined. Without a consistent standard, comparability, reproducibility, and interoperability of models across groups and software tools cannot be guaranteed. Here, we present memote ( https://github.com/opencobra/memote ) an open-source software containing a community-maintained, standardized set of me tabolic mo del te sts. The tests cover a range of aspects from annotations to conceptual integrity and can be extended to include experimental datasets for automatic model validation. In addition to testing a model once, memote can be configured to do so automatically, i.e., while building a GEM. A comprehensive report displays the model’s performance parameters, which supports informed model development and facilitates error detection. Memote provides a measure for model quality that is consistent across reconstruction platforms and analysis software and simplifies collaboration within the community by establishing workflows for publicly hosted and version controlled models.
Approaching Perfect Light Incoupling in Perovskite and Silicon Thin Film Solar Cells by Moth Eye Surface Textures
2018-06-21

Abstract Solar cells with increased short‐circuit current density and energy conversion efficiency can be realized by integrating moth eye textures in the design of perovskite and amorphous silicon thin film solar cells. Broadband light incoupling in solar cells can be achieved by using hexagonally arranged arrays of nipples or domes with parabolically shaped surface profiles. The moth eye surface texture represents a refractive index grating that allows for an efficient incoupling of light in the solar cell while minimizing reflection losses. The light incoupling is studied for perovskite and amorphous silicon solar cells. Perovskite has a rather low refractive index of ≈2.5, while amorphous silicon exhibits a refractive index of ≈4.5 comparable to that of crystalline silicon. Due to largely different refractive indices, different device designs must be selected to allow for an efficient light incoupling in the solar cell. 3D finite‐difference time‐domain simulations are used for the optical modeling. Design guidelines are provided on how to realize perovskite and silicon thin film solar cells with high quantum efficiency and short‐circuit current by using moth eye textures.
Circularly Polarised Luminescence in Enantiopure Samarium and Europium Cryptates
2018-06-21

Abstract Circularly polarised luminescence (CPL) is a chiroptical phenomenon gaining more and more attention, as the availability of the necessary spectrometers is getting better and first applications in bioimaging or for the preparation of OLEDs (organic light emitting diodes) are coming within range. Until now most examples of distinctly CPL‐active compounds were europium and terbium complexes though theoretically the electronic structure of samarium should be as suitable as the one of terbium. This discrepancy can be accounted for by the high susceptibility of samarium to non‐radiative deactivation processes. The aim of this study was to strategically circumvent this difficulty by the use of a ligand scaffold which has already proven to efficiently suppress these processes, namely the cryptates. The prepared partly deuterated samarium and europium complexes exhibit distinct circularly polarised luminescence with dissymmetry factors up to g lum =+0.13 (Sm III ) or g lum =−0.19 (Eu III ).
Impact of Altered Mineral Metabolism on Pathological Cardiac Remodeling in Elevated Fibroblast Growth Factor 23
2018-06-21

Clinical and experimental studies indicate a possible link between high serum levels of fibroblast growth factor 23 (FGF23), phosphate, and parathyroid hormone (PTH), deficiency of active vitamin D (1,25D) and klotho with the development of pathological cardiac remodeling, i.e., left ventricular hypertrophy and myocardial fibrosis, but a causal link has not been established so far. Here, we investigated the cardiac phenotype in klotho hypomorphic (<i>kl/kl</i>) mice and <i>Hyp</i> mice, two mouse models of elevated FGF23 levels and klotho deficiency, but differing in parameters of mineral metabolism, by using histology, quantitative real-time PCR, immunoblot analysis, and serum and urine biochemistry. Additionally, the specific impact of calcium, phosphate, PTH, and 1,25D on hypertrophic growth of isolated neonatal rat cardiac myocytes was investigated <i>in vitro</i>. <i>Kl/kl</i> mice displayed high serum Fgf23 levels, increased relative heart weight, enhanced cross-sectional area of individual cardiac myocytes, activated cardiac Fgf23/Fgf receptor (Fgfr) 4/calcineurin/nuclear factor of activated T cell (NFAT) signaling, and induction of pro-hypertrophic NFAT target genes including <i>Rcan1, bMHC</i>, brain natriuretic peptide (<i>BNP</i>), and atrial natriuretic peptide (<i>ANP</i>) as compared to corresponding wild-type (WT) mice. Investigation of fibrosis-related molecules characteristic for pathological cardiac remodeling processes demonstrated ERK1/2 activation and enhanced expression of Tgf-β1, <i>collagen I</i>, and Mmp2 in <i>kl/kl</i> mice than in WT mice. In contrast, despite significantly elevation of serum and cardiac Fgf23, and reduced renal <i>klotho</i> expression, <i>Hyp</i> mice showed no signs of pathological cardiac remodeling. <i>Kl/kl</i> mice showed enhanced serum calcium and phosphate levels, while <i>Hyp</i> mice showed unchanged serum calcium levels, lower serum phosphate, and elevated serum iPTH concentrations compared to corresponding WT mice. In cultured cardiac myocytes, treatment with both calcium or phosphate significantly upregulated endogenous <i>Fgf23</i> mRNA expression and stimulated hypertrophic cell growth and expression of pro-hypertrophic genes. The treatment with PTH induced hypertrophic cell growth only, and stimulation with 1,25D had no significant effects. In conclusion, our data indicate that <i>Hyp</i> mice, in contrast to <i>kl/kl</i> mice appear to be protected from pathological cardiac remodeling during conditions of high FGF23 levels and klotho deficiency, which may be due, at least in part, to differences in mineral metabolism alterations, i.e., hypophosphatemia and lack of hypercalcemia.
Patient acceptance and trust in automated computer‐assisted diagnosis of melanoma with dermatofluoroscopy
2018-06-21

Summary Background and objectives Automated computer‐guided diagnostic procedures are increasingly being integrated into patient care. However, in contrast to the increasing application of automation, patient acceptance and trust in such technologies has rarely been studied. Automated diagnosis of melanoma with dermatofluoroscopy was recently approved by regulatory agencies. The objective of this study is to assess patient acceptance and trust in automated melanoma diagnosis with dermatofluoroscopy. Patients and methods We examined 140 pigmented skin lesions with dermatofluoroscopy as part of a prospective clinical study. Four weeks after their examination with dermatofluoroscopy, we contacted 100 patients with a 10‐item questionnaire addressing their acceptance and trust in this technology on a five‐point visual analogue scale. Results A “high” to “very high” level of patient acceptance and trust in dermatofluoroscopy was found in 74 % of responders. Most patients agreed that computer‐assisted diagnoses are trustworthy and may generally improve the diagnostic performance of physicians. However, all responders insisted on the interpretation of computer‐assisted diagnoses by a physician and frequently rejected the idea of computers completely replacing physicians. Conclusion Patient acceptance and trust in dermatofluoroscopy was high. Patients clearly supported the use of automated, computer‐assisted diagnostics as an adjunct to the physicians' examination.
Coding variants in NOD-like receptors: An association study on risk and survival of colorectal cancer
2018-06-21

Nod-like receptors (NLRs) are important innate pattern recognition receptors and regulators of inflammation or play a role during development. We systematically analysed 41 non-synonymous single nucleotide polymorphisms (SNPs) in 21 NLR genes in a Czech discovery cohort of sporadic colorectal cancer (CRC) (1237 cases, 787 controls) for their association with CRC risk and survival. Five SNPs were found to be associated with CRC risk and eight with survival at 5% significance level. In a replication analysis using data of two large genome-wide association studies (GWASs) from Germany (DACHS: 1798 cases and 1810 controls) and Scotland (2210 cases and 9350 controls) the associations found in the Czech discovery set were not confirmed. However, expression analysis in human gut-related tissues and immune cells revealed that the NLRs associated with CRC risk or survival in the discovery set were expressed in primary human colon or rectum cells, CRC tissue and/or cell lines, providing preliminary evidence for a potential involvement of NLRs in general in CRC development and/or progression. Most interesting was the finding that the enigmatic development-related NLRP5 (also known as MATER) was not expressed in normal colon tissue but in colon cancer tissue and cell lines. Future studies may show whether regulatory variants instead of coding variants might affect the expression of NLRs and contribute to CRC risk and survival.