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A group of Amazonian harvestmen is recognized and described as Amazochroma gen. nov. This taxon includes Discocyrtus carvalhoi Mello-Leitão, 1941 (type species), the only species of Discocyrtus previously thought to occur in Amazonia, and Amazochroma pedroi gen. et sp. nov., described here from the Brazilian states of Acre and Rondônia. New records are added for Amazochroma carvalhoi gen. et comb. nov, expanding its distribution from the Brazilian state of Mato Grosso northwards also to Pará and Amazonas in Brazil and additionally French Guiana and Suriname. Diagnostic features of Amazochroma gen. nov. include: trichromatic pattern of legs, dry marks on the dorsal scutum and base of legs and diastema in the row of macrosetae C of the penis ventral plate. A morphological maximum parsimony analysis (1022 scorings; 16 taxa; 64 characters) is performed to test whether Amazochroma gen. nov. is a member of Discocyrtus and if the traditional allocation of Discocyrtus in Pachylinae is defendable. A clade is retrieved containing three groups: Amazochroma carvalhoi gen. et comb. nov, here described as a new subfamily of Gonyleptidae - Roeweriinae subfam. nov. Discocyrtanus Roewer, 1929 and Roeweria Mello-Leitão, 1923 are accordingly here transferred from Pachylinae to Roeweriinae subfam. nov.
The species of the subgenus Conocetus Desbrochers des Loges, 1875 are reviewed and Polydrusus (Conocetus) transjordanus sp. nov. is described. Upon examination of the holotype of Polydrusus bardus Gyllenhal, 1834, it was observed that the species hitherto determined sensu auctorum as P. bardus was a misidentification. The specimen in question was therefore unnamed and is thus newly described as Polydrusus (Conocetus) crinipes sp. nov. Polydrusus femoratus (Stierlin, 1888) is a junior synonym of P. angustus (Lucas, 1854). Polydrusus gracilicornis Kiesenwetter, 1864, P. cylindrithorax (Desbrochers des Loges, 1900) and P. quadraticollis (Desbrochers des Loges, 1902) are proposed as junior synonyms of P. bardus. Polydrusus zurcheri (Schilsky, 1912) is proposed as a junior synonym of P. grandiceps (Desbrochers des Loges, 1875). Polydrusus kahri Kirsch, 1865 is transferred from subgenus Conocetus to Denticonocetus subgen. nov., with P. siculus Desbrochers des Loges, 1872 and P. vodozi Desbrochers des Loges, 1903 both recognized as new junior synonyms of P. kahri. The lectotypes of P. gracilicornis, P. zurcheri, P. marcidus Kiesenwetter, 1864, P. gracilis (Stierlin, 1888), P. rhodiacus (Schilsky, 1912) and P. grandiceps are designated. A key, figures, label data and distribution maps are provided for all species, except for P. longus (Stierlin, 1884), for which no specimens were available for examination, and whose placement in the subgenus Conocetus remains uncertain (thus categorized as incertae sedis). Polydrusus angustus is recorded for the first time for Italy, P. rhodiacus for mainland Turkey and P. festae (Solari, 1925) for Greece.
Regulation of the antiapoptotic protein cFLIP by the glucocorticoid Dexamethasone in ALL cells
(2018)
We recently reported that the Smac mimetic BV6 and glucocorticoids, e.g. Dexamethasone (Dexa), synergize to induce cell death in acute lymphoblastic leukemia (ALL) in vitro and in vivo. Here, we discover that this synergism involves Dexa-stimulated downregulation of cellular FLICE-like inhibitory protein (cFLIP) in ALL cells. Dexa rapidly decreases cFLIPL protein levels, which is further enhanced by addition of BV6. While attenuating the activation of non-canonical nuclear factor-kappaB (NF-κB) signaling by BV6, Dexa suppresses cFLIPL protein but not mRNA levels pointing to a transcription-independent downregulation of cFLIPL by Dexa. Analysis of protein degradation pathways indicates that Dexa causes cFLIPL depletion independently of proteasomal, lysosomal or caspase pathways, as inhibitors of the proteasome, lysosomal enzymes or caspases all failed to protect from Dexa-mediated loss of cFLIPL protein. Also, Dexa alone or in combination with BV6 does not affect overall activity of the proteasome. Importantly, overexpression of cFLIPL to an extent that is no longer subject to Dexa-imposed downregulation rescues Dexa/BV6-mediated cell death. Vice versa, knockdown of cFLIP increases BV6-mediated cell death, thus mimicking the effect of Dexa. Altogether, these data demonstrate that Dexa-mediated downregulation of cFLIPL protein promotes Dexa/BV6-mediated cell death, thereby providing novel insights into the synergistic antitumor activity of this combination treatment.
Although effective antibody-based vaccines have been developed against multiple viruses, such approaches have so far failed for the human immunodeficiency virus type 1 (HIV-1). Despite the success of anti-retroviral therapy (ART) that has turned HIV-1 infection into a chronic disease and has reduced the number of new infections worldwide, a vaccine against HIV-1 is still urgently needed. We discuss here the major reasons for the failure of “classical” vaccine approaches, which are mostly due to the biological properties of the virus itself. HIV-1 has developed multiple mechanisms of immune escape, which also account for vaccine failure. So far, no vaccine candidate has been able to induce broadly neutralizing antibodies (bnAbs) against primary patient viruses from different clades. However, such antibodies were identified in a subset of patients during chronic infection and were shown to protect from infection in animal models and to reduce viremia in first clinical trials. Their detailed characterization has guided structure-based reverse vaccinology approaches to design better HIV-1 envelope (Env) immunogens. Furthermore, conserved Env epitopes have been identified, which are promising candidates in view of clinical applications. Together with new vector-based technologies, considerable progress has been achieved in recent years towards the development of an effective antibody-based HIV-1 vaccine.
The mechanisms involved in malignant transformation of mature B and T lymphocytes are still poorly understood. In a previous study, we compared gene expression profiles of the tumor cells of Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) to their normal cellular counterparts and found the basic leucine zipper protein ATF-like 3 (BATF3) to be significantly upregulated in the tumor cells of both entities. To assess the oncogenic potential of BATF3 in lymphomagenesis and to dissect the molecular interactions of BATF3 in lymphoma cells, we retrovirally transduced murine mature T and B cells with a BATF3-encoding viral vector and transplanted each population into Rag1-deficient recipients. Intriguingly, BATF3-expressing B lymphocytes readily induced B-cell lymphomas after characteristic latencies, whereas T-cell transplanted animals remained healthy throughout the observation time. Further analyses revealed a germinal center B-cell-like phenotype of most BATF3-initiated lymphomas. In a multiple myeloma cell line, BATF3 inhibited BLIMP1 expression, potentially illuminating an oncogenic action of BATF3 in B-cell lymphomagenesis. In conclusion, BATF3 overexpression induces malignant transformation of mature B cells and might serve as a potential target in B-cell lymphoma treatment.
Titanium is a biocompatible material that is frequently used for making implantable medical devices. Nanoengineering of the surface is the common method for increasing material biocompatibility, and while the nanostructured materials are well-known to represent attractive substrata for eukaryotic cells, very little information has been documented about the interaction between mammalian cells and bactericidal nanostructured surfaces. In this study, we investigated the effect of bactericidal titanium nanostructures on PC12 cell attachment and differentiation—a cell line which has become a widely used in vitro model to study neuronal differentiation. The effects of the nanostructures on the cells were then compared to effects observed when the cells were placed in contact with non-structured titanium. It was found that bactericidal nanostructured surfaces enhanced the attachment of neuron-like cells. In addition, the PC12 cells were able to differentiate on nanostructured surfaces, while the cells on non-structured surfaces were not able to do so. These promising results demonstrate the potential application of bactericidal nanostructured surfaces in biomedical applications such as cochlear and neuronal implants.
A large body of evidence suggests that the 11+ warm-up programme is effective in preventing football-related musculoskeletal injuries. However, despite considerable efforts to promote and disseminate the programme, it is unclear as to whether team head coaches are familiar with the 11+ and how they rate its feasibility. The present study aimed to gather information on awareness and usage among German amateur level football coaches. A questionnaire was administered to 7893 individuals who were in charge of youth and adult non-professional teams. Descriptive and inferential statistics were used to analyse the obtained data. A total of 1223 coaches (16%) returned the questionnaire. There was no risk of a non-response bias (p>.05). At the time of the survey, nearly half of the participants (42.6%) knew the 11+. Among the coaches who were familiar with the programme, three of four reported applying it regularly (at least once per week). Holding a license (φ = .28, p < .0001), high competitive level (Cramer-V = .13, p = .007), and coaching a youth team (φ = .1, p = .001) were associated with usage of 11+. Feasibility and suitability of the 11+ were rated similarly by aware and unaware coaches. Although a substantial share of German amateur level coaches is familiar with the 11+, more than half of the surveyed participants did not know the programme. As the non-usage does not appear to stem from a lack of rated feasibility and suitability, existing communication strategies might need to be revised.
The structural diversity of terpenoids is limited by the isoprene rule which states that all primary terpene synthase products derive from methyl-branched building blocks with five carbon atoms. With this study we discover a broad spectrum of novel terpenoids with eleven carbon atoms as byproducts of bacterial 2-methylisoborneol or 2-methylenebornane synthases. Both enzymes use 2-methyl-GPP as substrate, which is synthesized from GPP by the action of a methyltransferase. We used E. coli strains that heterologously produce different C11-terpene synthases together with the GPP methyltransferase and the mevalonate pathway enzymes. With this de novo approach, 35 different C11-terpenes could be produced. In addition to eleven known compounds, it was possible to detect 24 novel C11-terpenes which have not yet been described as terpene synthase products. Four of them, 3,4-dimethylcumene, 2-methylborneol and the two diastereomers of 2-methylcitronellol could be identified. Furthermore, we showed that an E. coli strain expressing the GPP-methyltransferase can produce the C16-terpene 6-methylfarnesol which indicates the condensation of 2-methyl-GPP and IPP to 6-methyl-FPP by the E. coli FPP-synthase. Our study demonstrates the broad range of unusual terpenes accessible by expression of GPP-methyltransferases and C11-terpene synthases in E. coli and provides an extended mechanism for C11-terpene synthases.
Aims: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk.
Methods and results: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies.
In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95–1.02) in group A, 0.98 (0.93–1.04) in group B, and 0.95 (0.89–1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07–1.23) in group A, 1.13 (1.05–1.22) in group B, and 1.12 (1.05–1.20) in group C.
Conclusions: We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.
Empiric antibiotics are often used in combination with mechanical debridement to treat patients suffering from periodontitis and to eliminate disease-associated pathogens. Until now, only a few next generation sequencing 16S rDNA amplicon based publications with rather small sample sizes studied the effect of those interventions on the subgingival microbiome. Therefore, we studied subgingival samples of 89 patients with chronic periodontitis (solely non-smokers) before and two months after therapy. Forty-seven patients received mechanical periodontal therapy only, whereas 42 patients additionally received oral administered amoxicillin plus metronidazole (500 and 400 mg, respectively; 3x/day for 7 days). Samples were sequenced with Illumina MiSeq 300 base pairs paired end technology (V3 and V4 hypervariable regions of the 16S rDNA). Inter-group differences before and after therapy of clinical variables (percentage of sites with pocket depth ≥ 5mm, percentage of sites with bleeding on probing) and microbiome variables (diversity, richness, evenness, and dissimilarity) were calculated, a principal coordinate analysis (PCoA) was conducted, and differential abundance of agglomerated ribosomal sequence variants (aRSVs) classified on genus level was calculated using a negative binomial regression model. We found statistically noticeable decreased richness, and increased dissimilarity in the antibiotic, but not in the placebo group after therapy. The PCoA revealed a clear compositional separation of microbiomes after therapy in the antibiotic group, which could not be seen in the group receiving mechanical therapy only. This difference was even more pronounced on aRSV level. Here, adjunctive antibiotics were able to induce a microbiome shift by statistically noticeably reducing aRSVs belonging to genera containing disease-associated species, e.g., Porphyromonas, Tannerella, Treponema, and Aggregatibacter, and by noticeably increasing genera containing health-associated species. Mechanical therapy alone did not statistically noticeably affect any disease-associated taxa. Despite the difference in microbiome modulation both therapies improved the tested clinical parameters after two months. These results cast doubt on the relevance of the elimination and/or reduction of disease-associated taxa as a main goal of periodontal therapy.