julilili42/papers huggingface dataset:
Multiple cytosolic and transmembrane determinants are required for the trafficking of SCAMP1 via an ER–Golgi–TGN–PM pathway
2010-12-24

Summary How polytopic plasma membrane (PM) proteins reach their destination in plant cells remains elusive. Using transgenic tobacco BY‐2 cells, we previously showed that the rice secretory carrier membrane protein 1 (SCAMP1), an integral membrane protein with four transmembrane domains (TMDs), is localized to the PM and trans ‐Golgi network (TGN). Here, we study the transport pathway and sorting signals of SCAMP1 by following its transient expression in tobacco BY‐2 protoplasts and show that SCAMP1 reaches the PM via an endoplasmic reticulum (ER)–Golgi–TGN–PM pathway. Loss‐of‐function and gain‐of‐function analysis of various green fluorescent protein (GFP) fusions with SCAMP1 mutations further demonstrates that: (i) the cytosolic N‐terminus of SCAMP1 contains an ER export signal; (ii) the transmembrane domain 2 (TMD2) and TMD3 of SCAMP1 are essential for Golgi export; (iii) SCAMP1 TMD1 is essential for TGN‐to‐PM targeting; (iv) the predicted topology of SCAMP1 and its various mutants remain identical as demonstrated by protease protection assay. Therefore, both the cytosolic N‐terminus and TMD sequences of SCAMP1 play integral roles in mediating its transport to the PM via an ER–Golgi–TGN pathway.
Do Depressed Patients Lose Their Sense of Humor
2010-12-24

&lt;i&gt;Background:&lt;/i&gt; Humor is an important coping mechanism and can improve mood. However, it is unclear whether depressed patients are able to enjoy funny material, e.g. jokes, and make use of their sense of humor for coping with adverse situations. This study aims at investigating the influence of depression on various aspects of humor abilities such as sense of humor, appraisal of funny material and exhilaration. &lt;i&gt;Sampling and Methods:&lt;/i&gt; Nineteen patients with major depression and 18 healthy controls were examined with standardized self-assessment questionnaires to study potential group differences in humor type preferences, state and trait cheerfulness, seriousness and bad mood as well as humor coping. &lt;i&gt;Results:&lt;/i&gt; Patients and controls did not differ in their humor type preferences and the degree to which humorous stimuli were rated as being funny. The readiness to react to funny stimuli with exhilaration was significantly less pronounced in the patient group. The patients’ tendency to use humor as a coping strategy was significantly lower than in the control group. &lt;i&gt;Conclusion:&lt;/i&gt; The susceptibility to humorous material seems to be unaffected by the disorder. Introducing means to promote humor behavior might therefore be beneficial to depressed patients. Study limitations were that only self-rating instruments were used and that the medication was inhomogeneous.
The nitrogen interaction network in Synechococcus WH5701, a cyanobacterium with two PipX and two PII-like proteins
2010-12-24

Nitrogen regulation involves the formation of different types of protein complexes between signal transducers and their transcriptional or metabolic targets. In oxygenic phototrophs, the signal integrator P II activates the enzyme N -acetyl- l -glutamate kinase (NAGK) by complex formation. P II also interacts with PipX, a protein with a tudor-like domain that mediates contacts with P II and with the transcriptional regulator NtcA, to which it binds to increase its activity. Here, we use a combination of in silico , yeast two-hybrid and in vitro approaches to investigate the nitrogen regulation network of Synechococcus WH5701, a marine cyanobacterium with two P II (GlnB_A and GlnB_B) and two PipX (PipX_I and PipX_II) proteins. Our results indicate that GlnB_A is functionally equivalent to the canonical P II protein from Synechococcus elongatus . GlnB_A interacted with PipX and NAGK proteins and stimulated NAGK activity, counteracting arginine inhibition. GlnB_B had only a slight stimulatory effect on NAGK activity, but its potential to bind effectors and form heterotrimers in Synechococcus WH5701 indicates additional regulatory functions. PipX_II, and less evidently PipX_I, specifically interacted with GlnB_A and NtcA, supporting a role for both Synechococcus WH5701 PipX proteins in partner swapping with GlnB_A and NtcA.
Photodegradation of P3HT−A Systematic Study of Environmental Factors
2010-12-27

The influence of environmental factors on the degradation process of P3HT film has been investigated quantitatively. The decay kinetics of the polymer absorption during variation of intensity and spectral distribution of the incident light, oxygen concentration, humidity level as well as temperature are monitored using infrared and UV/vis absorption spectroscopy. Additionally, the oxygen diffusion into the polymer film has been investigated using fluorescence spectroscopy under the same experimental conditions. The degradation process is light initiated with a strong increase of the effectiveness toward the ultraviolet region of the spectrum. The observed photo oxidation is not oxygen diffusion limited although an activation energy of 26 kJmol−1 was observed for both degradation and oxygen diffusion. The observed kinetics, especially its dependence on wavelength of the incident light, point to a radical-based degradation process in the solid state rather than a singlet oxygen-based mechanism as it is observed in the liquid phase. Furthermore the presence of humidity strongly affects the degradation process although water itself does not decompose the polymer. Changing the structure of the polymer from regioregular to regiorandom significantly accelerates the degradation, probably due to the higher triplet yield of the regiorandom polymer.
Red Cards
2010-12-27

A popular soccer myth states that teams affected by a sending-off perform better than they would have performed without it. Based on economic theory, the authors analyze the course of soccer matches using data from the German Bundesliga from 1999 to 2009. The results show that sending-offs against home teams have a negative impact on their performance. However, for guest teams, the impact depends on the time remaining after the sending-off and can be positive if the sending-off occurs late in the game. Thus, the “ten do it better” myth seems to hold for guest teams to a certain extent.
Intradermal Vaccinations With RNA Coding for TAA Generate CD8+ and CD4+ Immune Responses and Induce Clinical Benefit in Vaccinated Patients
2010-12-28

The aim of this phase I/II nonrandomized trial was to assess feasibility, safety as well as immunological and clinical responses of a mRNA-based vaccination in patients with stage IV renal cell cancer using granulocyte-macrophage colony stimulating factor (GM-CSF) as adjuvant. Intradermal injections of in vitro transcribed naked mRNA, which was generated using plasmids coding for the tumor-associated antigens mucin 1(MUC1), carcinoembryonic (CEA), human epidermal growth factor receptor 2 (Her-2/neu), telomerase, survivin, and melanoma-associated antigen 1 (MAGE-A1) were performed in 30 enrolled patients. In the first 14 patients (cohort A) vaccinations were administered on days 0, 14, 28, and 42 (20 μg/antigen) while in the consecutive 16 patients (cohort B) an intensified protocol consisting of injections at days 0-3, 7-10, 28, and 42 (50 μg/antigen) was used. In both cohorts, after this induction period, vaccinations were repeated monthly until tumor progression analyzed by Response Evaluation Criteria In Solid Tumors criteria (RECIST). Vaccinations were well tolerated with no severe side effects and induced clinical responses [six stable diseases (SD) and one partial response in cohort A and nine SD in cohort B]. In cohort A, 35.7% survived 4 years (median survival 24 months) compared to 31.25% in cohort B (median survival 29 months). Induction of CD4(+) and CD8(+) T cell responses was shown for several tumor-associated antigens (TAA) using interferon-γ (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) and Cr-release assays.
Heart rate variability as a measure of cardiac autonomic function in anorexia nervosa: A review of the literature
2010-12-28

Abstract Objective Patients with anorexia nervosa (AN) exhibit a wide range of autonomic system disturbances; these patients have also high mortality risk due to cardio‐vascular complications. Origin and pathogenesis of such changes are not absolutely clear. Methods Relevant publications were drawn from PUBMED using the keywords ‘anorexia nervosa’ AND ‘autonomic’. Fifty two abstracts were identified and screened for papers that measured the state of autonomic regulation by means of analysis of heart rate variability either during 24‐hour electrocardiography (ECG) monitoring or during a short‐term laboratory test. Studies selected were analysed for the number of patients included, the presence and quality of control groups, gender, age and body mass index (BMI) of patients, type of AN as well as methods used to determine heart rate variability (HRV). Results Twenty papers on HRV in patients with anorexia were identified and analysed, revealing three distinct positions regarding changes of autonomic nervous system (ANS) functions in patients with AN. The majority of papers identified parasympathetic/sympathetic imbalance with parasympathetic dominance and decreased sympathetic modulation; others could not replicate these findings, but instead described sympathetic dominance; finally a group of papers could not identify any autonomic differences in comparison to control samples. We conclude that in its current state of analysis HRV may not be suitable for routine assessment of ANS function in AN patients but rather remains a research tool. Copyright © 2010 John Wiley &amp; Sons, Ltd and Eating Disorders Association.
Synthesis and Molecular Modeling of Novel Tetrahydro-β-carboline Derivatives with Phosphodiesterase 5 Inhibitory and Anticancer Properties
2010-12-28

New derivatives based upon the tetrahydro-β-carboline-hydantoin and tetrahydro-β-carboline-piperazinedione scaffolds were synthesized. All compounds were evaluated for their ability to inhibit PDE5 in vitro, and numerous compounds with IC(50) values in the low nanomolar range were identified including compounds derived from l-tryptophan. Compounds with high potency versus PDE5 were then evaluated for inhibitory activity against other PDEs to assess isozyme selectivity. Compound 5R,11aS-5-(3,4-dichlorophenyl)-2-ethyl-5,6,11,11a-tetrahydro-1H-imidazo[1',5':1,6]pyrido[3,4-b]indole-1,3(2H)dione 14 showed a selectivity index of >200 for cGMP hydrolysis by PDE5 versus PDE11. Meanwhile, 6R,12aR-6-(2,4-dichlorophenyl)-2-ethyl-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4dione 45 demonstrated strong potency for inhibition of PDE11 with an IC(50) value of 11 nM, representing the most potent PDE11 inhibitor thus far reported. Docking experiments differentiated between active and inactive analogues and revealing the conformational, steric, and lipophilic necessities for potent PDE5 inhibition. Many derivatives, including potent PDE5 inhibitors, were able to inhibit the growth of the MDA-MB-231 breast tumor cell line with low micromolar potency.
Special Issue: Portals for life sciences—Providing intuitive access to bioinformatic tools
2010-12-28

Abstract The topic ‘Portals for life sciences’ includes various research fields, on the one hand many different topics out of life sciences, e.g. mass spectrometry, on the other hand portal technologies and different aspects of computer science, such as usability of user interfaces and security of systems. The main aspect about portals is to simplify the user's interaction with computational resources that are concerted to a supported application domain. Copyright © 2010 John Wiley &amp; Sons, Ltd.
Identification of a Napsamycin Biosynthesis Gene Cluster by Genome Mining
2010-12-29

Abstract Napsamycins are potent inhibitors of bacterial translocase I, an essential enzyme in peptidoglycan biosynthesis, and are classified as uridylpeptide antibiotics. They comprise an N ‐methyl diaminobutyric acid, an ureido group, a methionine and two non‐proteinogenic aromatic amino acid residues in a peptide backbone that is linked to a 5′‐amino‐3′‐deoxyuridine by an unusual enamide bond. The napsamycin gene cluster was identified in Streptomyces sp. DSM5940 by using PCR probes from a putative uridylpeptide biosynthetic cluster found in S. roseosporus NRRL15998 by genome mining. Annotation revealed 29 hypothetical genes encoding for resistance, regulation and biosynthesis of the napsamycins. Analysis of the gene cluster indicated that the peptide core structure is assembled by a nonlinear non‐ribosomal peptide synthetase (NRPS)‐like mechanism that involves several discrete single or didomain proteins. Some genes could be assigned, for example, to the synthesis of the N ‐methyl diaminobutyric acid, to the generation of m ‐tyrosine and to the reduction of the uracil moiety. The heterologous expression of the gene cluster in Streptomyces coelicolor M1154 resulted in the production of napsamycins and mureidomycins as demonstrated by LC‐ESI‐MS and MS/MS analysis. The napsamycin gene cluster provides a molecular basis for the detailed study of the biosynthesis of this class of structurally unusual compounds.
Haematological and biochemical reference intervals for infants and children in Gabon
2010-12-29

Summary Objectives To establish reference intervals for major haematological and biochemical parameters in Gabonese infants and children. Methods The reference sample population consisted of 226 healthy infants (4–9 weeks of age) and 185 healthy children (18–60 months of age). Basic red cell parameters as well as total and differential white blood cell counts were performed. Clinical chemistry parameters consisted of glutamate–pyruvic transaminase and creatinine, and total bilirubin was measured in children. Statistical analysis was based on the guidelines of the Clinical and Laboratory Standards Institute. Nonparametric methods were used to determine 95% reference limits and their 90% confidence intervals. Results Compared to European populations, values for several red cell parameters (haemoglobin, haematocrit, red blood cell count, mean corpuscular volume) were lower and platelet counts were higher. Eosinophils were higher in the older age group, most likely caused by intestinal helminths. Conclusions The study confirms the importance of establishing reference limits for local populations. The reference ranges could be used as a benchmark for similar populations in Central Africa.
Fenamates as TRP channel blockers: mefenamic acid selectively blocks TRPM3
2010-12-30

BACKGROUND AND PURPOSE Fenamates are N‐phenyl‐substituted anthranilic acid derivatives clinically used as non‐steroid anti‐inflammatory drugs in pain treatment. Reports describing fenamates as tools to interfere with cellular volume regulation attracted our attention based on our interest in the role of the volume‐modulated transient receptor potential (TRP) channels TRPM3 and TRPV4. EXPERIMENTAL APPROACH Firstly, we measured the blocking potencies and selectivities of fenamates on TRPM3 and TRPV4 as well as TRPC6 and TRPM2 by Ca 2+ imaging in the heterologous HEK293 cell system. Secondly, we further investigated the effects of mefenamic acid on cytosolic Ca 2+ and on the membrane voltage in single HEK293 cells that exogenously express TRPM3. Thirdly, in insulin‐secreting INS‐1E cells, which endogenously express TRPM3, we validated the effect of mefenamic acid on cytosolic Ca 2+ and insulin secretion. KEY RESULTS We identified and characterized mefenamic acid as a selective and potent TRPM3 blocker, whereas other fenamate structures non‐selectively blocked TRPM3, TRPV4, TRPC6 and TRPM2. CONCLUSIONS AND IMPLICATIONS This study reveals that mefenamic acid selectively inhibits TRPM3‐mediated calcium entry. This selectivity was further confirmed using insulin‐secreting cells. K ATP channel‐dependent increases in cytosolic Ca 2+ and insulin secretion were not blocked by mefenamic acid, but the selective stimulation of TRPM3‐dependent Ca 2+ entry and insulin secretion induced by pregnenolone sulphate were inhibited. However, the physiological regulator of TRPM3 in insulin‐secreting cells remains to be elucidated, as well as the conditions under which the inhibition of TRPM3 can impair pancreatic β‐cell function. Our results strongly suggest mefenamic acid is the most selective fenamate to interfere with TRPM3 function.
Remodeling of Articular Cartilage and Subchondral Bone After Bone Grafting and Matrix-Associated Autologous Chondrocyte Implantation for Osteochondritis Dissecans of the Knee
2010-12-30

Background: Osteochondritis dissecans (OCD) of the knee is a challenging problem. Previously, the authors implemented a novel 1-step surgical procedure for OCD treatment consisting of matrix-associated autologous chondrocyte implantation (ACI) and simultaneous bone reconstruction including the subchondral lamina. Purpose: This study presents the 2-to 5-year results after this technique, assessing correlations of clinical function and cartilage and bone remodeling processes. Study Design: Case series; Level of evidence, 4. Methods: Twenty-six patients with symptomatic condylar knee OCD (International Cartilage Repair Society OCD III/IV) were treated with matrix-associated ACI and monocortical cancellous cylinders for defect filling and subchondral bone plate reconstruction using cortical graft layers as novel subchondral lamina. Evaluations were performed with clinical rating scales and 1.5-T magnetic resonance imaging using the magnetic resonance observation of cartilage repair tissue (MOCART) score and a newly implemented subchondral lamina remodeling grade. Results: The defect size was 5.3 ± 2.3 cm 2 . The defect depth was 8.7 ± 2.4 mm. After a follow-up of 39.8 ± 12.0 months, all scores improved significantly. Nineteen patients (73%) reached good/excellent results in the Lysholm-Gillquist score (preoperatively: 53.2 ± 18.0 points; latest follow-up: 88.5 ± 9.5 points) and the Cincinnati knee rating score (preoperatively: 51.7 ± 13.0 points; latest follow-up: 84.6 ± 11.7 points) and significant improvements in the subjective International Knee Documentation Committee (IKDC) score by 27.9% (preoperatively: 50.5% ± 16.1%; latest follow-up: 78.4% ± 13.4%). The MOCART score reached 62.4 ± 18.9 points. The clinical improvement and tissue remodeling occurred simultaneously and timed; thus, the cartilage defect filling and the lamina remodeling grades correlated significantly with each other, the follow-up time, and almost all clinical scores. Conclusion: The simultaneous reconstruction of deep osteochondral defects of the knee OCD with monocortical cancellous cylinders and matrix-associated ACI is a biological, 1-step alternative to osteochondral cylinder transfer or conventional ACI that leads to good clinical and magnetic resonance imaging results after an intermediate follow-up period. The present study demonstrated simultaneous remodeling processes of articular cartilage repair tissue and subchondral lamina; this synchronization is not yet understood and deserves further investigation.
Neuronal Ca2+-Activated K+ Channels Limit Brain Infarction and Promote Survival
2010-12-30

Neuronal calcium-activated potassium channels of the BK type are activated by membrane depolarization and intracellular Ca(2+) ions. It has been suggested that these channels may play a key neuroprotective role during and after brain ischemia, but this hypothesis has so far not been tested by selective BK-channel manipulations in vivo. To elucidate the in vivo contribution of neuronal BK channels in acute focal cerebral ischemia, we performed middle cerebral artery occlusion (MCAO) in mice lacking BK channels (homozygous mice lacking the BK channel alpha subunit, BK(-/-)). MCAO was performed in BK(-/-) and WT mice for 90 minutes followed by a 7-hour-reperfusion period. Coronal 1 mm thick sections were stained with 2,3,5-triphenyltetrazolium chloride to reveal the infarction area. We found that transient focal cerebral ischemia by MCAO produced larger infarct volume, more severe neurological deficits, and higher post-ischemic mortality in BK(-/-) mice compared to WT littermates. However, the regional cerebral blood flow was not significantly different between genotypes as measured by Laser Doppler (LD) flowmetry pre-ischemically, intra-ischemically, and post-ischemically, suggesting that the different impact of MCAO in BK(-/-) vs. WT was not due to vascular BK channels. Furthermore, when NMDA was injected intracerebrally in non-ischemic mice, NMDA-induced neurotoxicity was found to be larger in BK(-/-) mice compared to WT. Whole-cell patch clamp recordings from CA1 pyramidal cells in organotypic hippocampal slice cultures revealed that BK channels contribute to rapid action potential repolarization, as previously found in acute slices. When these cultures were exposed to ischemia-like conditions this induced significantly more neuronal death in BK(-/-) than in WT cultures. These results indicate that neuronal BK channels are important for protection against ischemic brain damage.
Growth Inhibition of HeLa Cells Is a Conserved Feature of High-Risk Human Papillomavirus E8^E2C Proteins and Can Also Be Achieved by an Artificial Repressor Protein
2010-12-30

ABSTRACT Infections with certain human papillomaviruses (HPV), such as type 16 (HPV16), 18, or 31, are a necessary risk factor for the development of cervical cancer. Transcript analyses of several HPV revealed that the viral E2 gene encodes both the E2 regulator protein and the E8∧E2C protein, which differ in their amino termini. Up to now, functional studies have focused on HPV31 E8∧E2C and demonstrated that it is a potent repressor of viral transcription and replication. However, recent analyses of HPV16 genomes have suggested that E8∧E2C proteins may differ in their activities. Therefore, we performed a comparative analysis of E8∧E2C proteins of HPV16, -18, and -31. All E8∧E2C proteins potently inhibited HPV E6/E7 oncogene promoters, and also displayed long-distance transcriptional-repression activities. Furthermore, the expression of all E8∧E2C proteins inhibited the growth of HeLa cells. Expression of E8∧E2C proteins rapidly increased the protein levels of the E6 and E7 targets p53 and p21, consistent with the repression of the endogenous HPV18 E6/E7 promoter. All E8∧E2C proteins induced G 1 arrest more efficiently than E2 proteins and activated senescence markers. Furthermore, we demonstrate that the 31E8 domain can be functionally replaced by the KRAB repression domain derived from KOX1. The KRAB-E2C fusion protein possesses long-distance transcriptional-repression activity and inhibits the growth of HeLa cells comparably to E8∧E2C. Taken together, our results suggest that the E8∧E2C proteins of HPV16, -18, and -31 are highly conserved transcriptional repressors that inhibit the growth of HeLa cells by repression of E6/E7 transcription but do not have proapoptotic activities.