Boredom due to being over- or under-challenged in mathematics: A latent profile analysis.

BACKGROUND: Recent research on boredom suggests that it can emerge in situations characterized by over- and under-challenge. In learning contexts, this implies that high boredom may be experienced both by low- and high-achieving students. AIMS: This research aimed to explore the existence and prevalence of boredom due to being over- and under-challenged in mathematics, for which empirical evidence is lacking. SAMPLE: We employed a sample of 1.407 students (fifth to ninth graders) from all three secondary school tracks (lower, middle and upper) in Bavaria (Germany). METHODS: Boredom was assessed via self-report and achievement via a standardized mathematics test. We used latent profile analysis to identify groups characterized by different levels of boredom and achievement, and we additionally examined gender and school track as group membership predictors. RESULTS: Results revealed four distinct groups, of which two showed considerably high boredom. One was coupled with low achievement on the test (i.e. 'over-challenged group', 13% of the total sample), and one was coupled with high achievement (i.e. 'under-challenged group', 21%). Furthermore, we found a low boredom and high achievement (i.e. 'well-off group', 27%) and a relatively low boredom low achievement group (i.e. 'indifferent group', 39%). Girls were overrepresented in the over-challenged group, and students from the upper school track were underrepresented in the under-challenged group. CONCLUSION: Our research emphasizes the need to openly discuss and further investigate boredom due to being over- and under-challenged.

RNase 7 Promotes Sensing of Self-DNA by Human Keratinocytes and Activates an Antiviral Immune Response.

RNase 7 is one of the major antimicrobial peptides (AMPs) secreted by keratinocytes. The AMPs human beta defensin 2 and LL-37 promote the toll-like receptor 9-mediated activation of human plasmacytoid dendritic cells (pDCs) by human self-DNA; however, whether keratinocytes respond in a similar way has not yet been addressed. Keratinocytes express several receptors for the detection of cytosolic DNA. Here, we investigated the activation of keratinocytes by RNase 7 in combination with human DNA. The stimulation of keratinocytes with RNase 7 and human DNA induced a strong increase in the production of IP-10. Of note, the stimulation of keratinocytes with human beta defensin 2 and LL-37 in combination with DNA failed to induce the production of IP-10. The production of IP-10 was mediated by the induction of the type I interferon IFN-ß and was significantly downregulated by blocking of the interferon-α/ß receptor and inhibition of stimulator of IFN genes. In addition, the pretreatment of keratinocytes with RNase 7 and DNA significantly reduced the herpes simplex virus-1 infection of human keratinocytes. This study demonstrates that RNase 7 functions as an alarmin by converting self-DNA into a danger signal that directly activates an antiviral immune response in human keratinocytes without the involvement of plasmacytoid dendritic cells.

RNase 7 Strongly Promotes TLR9-Mediated DNA Sensing by Human Plasmacytoid Dendritic Cells.

Plasmacytoid dendritic cells (pDCs) were described to accumulate in the skin of patients with psoriasis and to be recruited into the dermis upon allergen challenge in atopic dermatitis. Activation of pDCs in the skin has been identified as an important initiator of psoriasis development. Ribonuclease (RNase) 7 is one of the major antimicrobial peptides secreted by keratinocytes and is expressed in significantly higher amounts in lesional skin of patients with atopic dermatitis or psoriasis than in healthy individuals. The skin-derived antimicrobial peptides human ß-defensin 2 and LL-37 indirectly stimulate the activity of skin pDCs, but to our knowledge, an immunomodulatory potential of RNase 7 has not yet been reported. We show here that RNase 7 enables human pDCs to recognize self-DNA and promotes their rapid sensing of bacterial DNA. This very fast innate immune response was sufficient to up-regulate the expression of several antiviral IFN-stimulated genes in human peripheral blood mononuclear cells and to inhibit an infection of primary human keratinocytes with herpes simplex virus 1. RNase 7 was a markedly stronger trigger for IFN-α expression in human pDCs than the other antimicrobial peptides. Our data indicate that RNase 7 exhibits potent immunomodulatory functions and supports the efficient recognition of microbial infections by human skin-infiltrating pDCs.

Arthroscopic tenodesis versus tenotomy of the long head of biceps tendon in simultaneous rotator cuff repair.

INTRODUCTION: Full thickness rotator cuff tears are a common cause of shoulder pain and disability. While the role of the rotator cuff seems to be well known, the clinical significance of the biceps tendon for shoulder function has still been a subject of controversy. The aim of this study was to evaluate differences between tenodesis or tenotomy in simultaneous rotator cuff repair. METHODS: For this retrospective study 53 consecutive patients (25f/28m, Ø age 58 years) undergoing arthroscopic double row rotator cuff reconstruction and suture bridge repair were included. The LHB was treated with tenodesis (n = 24) or tenotomy (n = 29). Clinical examination was carried out for all patients after an average of 34 months (range 27­38) following arthroscopic surgery. The Constant score, level of pain, range of motion in flexion and abduction, and isometric force for the operated and healthy shoulder in flexion and abduction were recorded. RESULTS: Patients in the tenodesis and tenotomy group reached similar good result regarding the Constant score (86.6 ± 11.9 vs. 81.3 ± 12.2; P = 0.120), pain (median 0, range 0­8 vs. Median 0, range 0­10; P = 0.421), and range of motion (flexion: median 180°, range 90°­180° vs. median 180°, range 90°­180°; P = 0.833; abduction: median 180°, range 90°­180° vs. median 180°, range 120°­180°; P = 0.472). Postoperative popeye sign was found only in one patient (1.9 %). At the time of postoperative follow-up, no patient reported cramping of the biceps. Isometric forces in abduction of the tenotomy group (mean 4.7 ± 2.9 kg; maximum 5.5 ± 2.8 kg) was significant lower compared to the tenodesis group (mean 6.6 ± 3.0 kg, P = 0.019; maximum 7.7 ± 2.9 kg, P = 0.007) and compared to healthy shoulders (mean 6.1 ± 3.0 kg P = 0.004; maximum 7.4 ± 3.1 kg, P = 0.001), all other measurements were similar. CONCLUSION: According to our results arthroscopic biceps tenodesis and tenotomy are valuable procedures in simultaneous rotator cuff repair regarding function, pain, and range of motion. However, the tenotomy group showed reduced strength in abduction. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Antimicrobial peptide coating of dental implants: biocompatibility assessment of recombinant human beta defensin-2 for human cells.

PURPOSE: Artificial materials such as dental implants are at risk of bacterial contamination in the oral cavity. Human beta defensins (HBDs), small cationic antimicrobial peptides that exert a broad-spectrum antibacterial function at epithelial surfaces and within some mesenchymal tissues, could probably help to reduce such contamination. HBDs also have protective immunomodulatory effects and have been reported to promote bone remodeling. The aim of this study, therefore, was to investigate the influence of recombinant HBD-2 on the proliferation and survival of cells in culture. MATERIALS AND METHODS: Human mesenchymal stem cells (hMSCs), human osteoblasts, human keratinocytes (control), and the HeLa cancer cell line (control) were incubated with recombinant HBD-2 (1, 5, 10, or 20 µg/mL). Cell proliferation and cytotoxicity were evaluated via a water-soluble tetrazolium salt (WST-1) and lactate dehydrogenase assays, respectively. RESULTS: HBD-2 was not toxic in any tested concentration to hMSCs, osteoblasts, keratinocytes, or HeLa cells. Furthermore, proliferation of hMSCs and osteoblasts increased after treatment with HBD-2 at all tested concentrations, and keratinocyte proliferation increased when treated at 20 µg/mL. In contrast, HeLa cancer cells were not affected by HBD-2 as tested. CONCLUSIONS: HBD-2 is not only biocompatible but also promotes proliferation of hMSCs, osteoblasts, and keratinocytes in culture. Further investigation of HBD-2 functional surface coating of artificial materials is recommended.

Bioactive coating of titanium surfaces with recombinant human ß-defensin-2 (rHußD2) may prevent bacterial colonization in orthopaedic surgery.

BACKGROUND: A promising strategy to prevent infections around orthopaedic titanium implants is to use naturally occurring cationic antimicrobial peptides (CAMPs) such as the human ß-defensin-2 as antibacterial coatings. Human antimicrobial peptides represent a part of the innate immune system and have a broad antimicrobial spectrum against bacteria, fungi, and viruses. METHODS: In the present study, titanium surfaces were functionalized by four different self-assembled monolayers (SAMs) forming methoxy silanes: (1) hexadecyltrimethoxysilane, (2) dimethoxymethyloctylsilane, (3) allyltrimethylsilane, and (4) 3-aminopropyltrimethoxysilane. In addition, calf skin type-I collagen was cross-linked to the SAM surface 3-aminopropyltrimethoxysilane by means of two different treatments: (1) N-hydroxysuccinimide and (2) glutaraldehyde. The functionalized titanium surfaces were coated with recombinant human ß-defensin-2 (rHußD2), an antimicrobial peptide, and were tested for antibacterial activity against Escherichia coli. The release of rHußD2 was quantified by means of enzyme-linked immunosorbent assay (ELISA). RESULTS: The coating of functionalized titanium surfaces with rHußD2 was successful. Recombinant HußD2 was eluted from the titanium surfaces continuously, yielding antimicrobial activity up to several hours. Antimicrobial activity with a killing rate of 100% was observed for all functionalized titanium surfaces after two hours of incubation. The dimethoxymethyloctylsilane-functionalized titanium surface delivered 0.65 µg of rHußD2 after six hours with a 60% bacterial killing rate. The silane-functionalized surfaces exhibited a faster release of antimicrobially active rHußD2 compared with collagen modifications. CONCLUSIONS: Natural antibiotics such as rHußD2 integrated into the metal surface of titanium implants may be a promising tool to prevent and control infections around orthopaedic implants.

Draft genome sequence of the marine Streptomyces sp. strain PP-C42, isolated from the Baltic Sea.

Streptomyces, a branch of aerobic Gram-positive bacteria, represents the largest genus of actinobacteria. The streptomycetes are characterized by a complex secondary metabolism and produce over two-thirds of the clinically used natural antibiotics today. Here we report the draft genome sequence of a Streptomyces strain, PP-C42, isolated from the marine environment. A subset of unique genes and gene clusters for diverse secondary metabolites as well as antimicrobial peptides could be identified from the genome, showing great promise as a source for novel bioactive compounds.

Genome sequence of Bacillus subtilis subsp. spizizenii gtP20b, isolated from the Indian ocean.

Bacillus subtilis is an aerobic spore-forming Gram-positive bacterium that is a model organism and of great industrial significance as the source of diverse novel functional molecules. Here we present, to our knowledge, the first genome sequence of Bacillus subtilis strain gtP20b isolated from the marine environment. A subset of candidate genes and gene clusters were identified, which are potentially involved in production of diverse functional molecules, like novel ribosomal and nonribosomal antimicrobial peptides. The genome sequence described in this paper is due to its high strain specificity of great importance for basic as well as applied researches on marine organisms.

Acceleration/ejection time ratio in the fetal pulmonary artery predicts fetal lung maturity.

OBJECTIVE: The aim of this study was to determine whether sonographic fetal pulmonary artery flow velocity waveforms correlate with amniotic fluid biomarkers of fetal lung maturity. STUDY DESIGN: We studied women with singleton pregnancies undergoing clinically indicated amniocentesis for fetal lung maturity at Yale-New Haven Hospital. Fetal pulmonary artery flow velocity measurements, including systolic/diastolic ratio, pulsatility index, resistance index, and acceleration-time/ejection-time ratio were obtained using spectral Doppler ultrasound. Pearson's correlation coefficient was used to determine the association between fetal pulmonary artery flow velocity parameters and the lecithin/sphingomyelin ratio. RESULTS: Twenty-nine subjects met study criteria. The acceleration-time/ejection-time ratio was inversely correlated with the lecithin/sphingomyelin ratio (r = -0.76; P < or = .001). This relationship was maintained after controlling for potential confounders. Other fetal pulmonary artery flow velocity measurements were not associated with the lecithin/sphingomyelin ratio. CONCLUSION: There is an inverse correlation between the acceleration-time/ejection-time ratio in the fetal pulmonary artery and the amniotic fluid lecithin/sphingomyelin ratio. This suggests that ultrasound evaluation of fetal pulmonary artery blood flow may be a promising new noninvasive technique to evaluate fetal lung maturity.

Human beta defensin 2 promotes intestinal wound healing in vitro.

Limiting microbial threats, maintenance and re-establishment of the mucosal barrier are vital for intestinal homeostasis. Antimicrobial peptides have been recognized as essential defence molecules and decreased expression of these peptides has been attributed to chronic inflammation of the human intestinal mucosa. Recently, pluripotent properties, including stimulation of proliferation and migration have been suggested for a number of antimicrobial peptides. However, it is currently unknown, whether the human beta-defensin 2 (hBD-2) in addition to its known antimicrobial properties has further effects on healing and protection of the intestinal epithelial barrier. Caco-2 and HT-29 cells were stimulated with 0.1-10 microg/ml hBD-2 for 6-72 h. Effects on cell viability and apoptosis were monitored and proliferation was quantified by bromo-deoxyuridine incorporation. Migration was quantified in wounding assays and characterized by immunohistochemistry. Expression of mucins was determined by quantitative PCR and slot-blot analysis. Furthermore, anti-apoptotic capacities of hBD-2 were studied. Over a broad range of concentrations and stimulation periods, hBD-2 was well tolerated by IECs and did not induce apoptosis. hBD-2 significantly increased migration but not proliferation of intestinal epithelial cells. Furthermore, hBD-2 induced cell line specific the expression of mucins 2 and 3 and ameliorated TNF-related apoptosis-inducing ligand (TRAIL) induced apoptosis. In addition to its known antimicrobial properties, hBD-2 might have further protective effects on the intestinal epithelium. Results of this in vitro study suggest, that hBD-2 expression may play a dual role in vivo, i.e. in impaired intestinal barrier function observed in patients with inflammatory bowel disease.

Barrier function, epidermal differentiation, and human beta-defensin 2 expression in tinea corporis.

Tinea corporis is a superficial mycotic infection resulting in substantial epidermal changes. We determined skin barrier function, epidermal differentiation, and human-beta-defensin 2 (hBD-2) protein expression in 10 patients with tinea corporis caused by Trichophyton rubrum (T. rubrum). We found disturbed skin barrier function as shown by a significant increase in transepidermal water loss (TEWL) and specific ultrastructural changes including disturbed formation of extracellular lipid bilayers, lamellar body extrusion, and deposit of clotted material at the stratum granulosum/stratum corneum interface. Epidermal proliferation in tinea increased several fold and accordingly, proliferation and inflammation-associated keratins K6, K16, and K17 were expressed. Expression of basal keratins K5 and K14 increased, whereas differentiation-associated K10 was reduced. Reduction of the cornified envelope proteins involucrin, loricrin, and the S100 protein filaggrin was also seen. Reduced filaggrin expression correlated with reduced skin hydration; protein breakdown products of filaggrin have been shown to be important for water binding. Surprisingly, we found pronounced epidermal protein expression of hBD-2, which may be related to disturbed epidermal differentiation and inflammation. hBD-2 showed a weak, although significant, antifungal activity against T. rubrum in the turbidimetric assay and the immunohistological staining was somewhat less pronounced in areas directly underneath fungal hyphae in the stratum corneum. Together, we describe profound changes in skin barrier structure and function, epidermal proliferation, and differentiation including pronounced protein expression of hBD-2 in tinea corporis.

A complete physical map of a wild beet (Beta procumbens) translocation in sugar beet.

Two sugar beet lines carry homologous translocations of the wild beet Beta procumbens. Long-range restriction mapping with rare cutting enzymes revealed that both translocations are different in size, however, an overlapping region of about 350 kb could be identified. Both lines are resistant to the beet cyst nematode but only TR520 carries the previously cloned resistance gene Hs1pro-1. Hence, a second gene for nematode resistance (Hs1-1) must be located within this region. A bacterial artificial chromosome (BAC) library was constructed from line TR520. The library was screened with a number of B. procumbens specific probes and 61 BAC clones were identified. Five BAC clones formed a minimal tiling path of 580 kb to cover the overlapping region between both translocations including the translocation breakpoint. The five BACs from the overlapping region and one additional BAC distal from that contig were sequenced. The total sequence length from the five BACs of the overlapping region amounted to 524 kb which is 74.35% of the total insert size of these BACs. The frequency of retrotransposon sequences ranged between 14.7 and 43.3%. A total of 133 ORFs were identified, none of these showed similarity to known disease resistance genes. Of these, 12 ORFs showed homology to genes involved in biotic stress resistance reactions or to transcription factors. This paper demonstrates how genome specific probes can be employed for cloning an alien gene introgression into a cultivated species.

Activity of human beta-defensins 2 and 3 against ESBL-producing Klebsiella strains.

OBJECTIVES: To test the bactericidal activity of human beta-defensins (hBDs) 2 and 3 against extended-spectrum beta-lactamase (ESBL)-producing Klebsiella strains. METHODS: Thirty-six Klebsiella pneumoniae and seventeen Klebsiella oxytoca ESBL-producing isolates from nosocomial infections were tested. The bactericidal activity of recombinantly synthesized hBD-2 and -3 was tested and the results were given either as lethal doses killing > or = 90% of bacteria (LD90s) or as MBCs (> or = 99.9% killing). RESULTS: Except for one intermediately susceptible strain (MBC = 25 mg/L), all other ESBL-producing strains were highly susceptible to both defensins (LD90s and MBCs < or = 12.5 mg/L). CONCLUSIONS: The results underline the high efficacy of hBD-2 and -3 against ESBL-producing Klebsiella, making both defensins attractive candidates as antimicrobial agents to combat these increasingly troublesome bacteria.

Cloning and functional analyses of a gene from sugar beet up-regulated upon cyst nematode infection.

The cDNA-AFLP technique was used to isolate sugar beet genes up-regulated upon infection with the beet cyst nematode Heterodera schachtii. Hairy root cultures were obtained from resistant plants carrying a Beta procumbens translocation as well as from a non-resistant control. mRNA was isolated from hairy root clones and sugar beet plants infected or not with the beet cyst nematode and 8000 transcript-derived fragments (TDFs) were analysed. One TDF was found to be differentially expressed in both materials and was further investigated. Real-time PCR confirmed that this TDF is specifically up-regulated in resistant sugar beet upon nematode infection and its full-length cDNA was isolated. Sequence analysis suggests that the gene encodes a 317 amino acid polypeptide of unknown function. No homology to any sequence present in the public databases could be detected. To further elucidate its function in resistance to the beet cyst nematode, the cDNA was transformed into hairy roots of susceptible sugar beet under the control of the 35S promoter and hairy root clones were inoculated with nematodes. The number of developing females was significantly reduced in 12 out of 15 clones resulting from independent transgenic events suggesting that the gene can be used for inducing cyst nematode resistance in plants.