Due to raising functional integration in micro fluidic, micro mechanic, micro electronic and micro optical systems the trend to scaling down the work piece sizes while increasing its complexity ...requires high precise machine accuracy. With respect to the process and geometrical parameters, most of the finishing manufacturing processes can be covered by milling and grinding operations with three or five machine axes. But whereas the available machine tools hardly achieve the required process dynamic and accuracy in all degrees of freedom, the requirements still increase. For this reason the Fraunhofer IPT has developed high precise machine tools following a compact design strategy by reducing the overall machine dimensions as far as conventional machine components such as measuring or drive systems were available. The developments of two compact machine tools exemplify the dynamic and accuracy enhancement by compact design and are described in the following.
The bengamides, sponge‐derived natural products that have been characterized as inhibitors of methionine aminopeptidases (MetAPs), have been intensively investigated as anticancer compounds. We ...embarked on a multidisciplinary project to supply bengamides by fermentation of the terrestrial myxobacterium M. virescens, decipher their biosynthesis, and optimize their properties as drug leads. The characterization of the biosynthetic pathway revealed that bacterial resistance to bengamides is conferred by Leu 154 of the myxobacterial MetAP protein, and enabled transfer of the entire gene cluster into the more suitable production host M. xanthus DK1622. A combination of semisynthesis of microbially derived bengamides and total synthesis resulted in an optimized derivative that combined high cellular potency in the nanomolar range with high metabolic stability, which translated to an improved half‐life in mice and antitumor efficacy in a melanoma mouse model.
A terrestrial dive to bengamides: Bengamides, sponge‐derived natural products, have been generated from a terrestrial source. Their biosynthesis and self‐resistance mechanism against methionine aminopeptidases was elucidated, a heterologous expression platform was established, and their pharmaceutical properties were improved by medicinal chemistry.
Long-chain polyunsaturated fatty acids (LC-PUFAs) can be produced de novo via polyketide synthase-like enzymes known as PUFA synthases, which are encoded by pfa biosynthetic gene clusters originally ...discovered from marine microorganisms. Recently similar gene clusters were detected and characterized in terrestrial myxobacteria revealing several striking differences. As the identified myxobacterial producers are difficult to handle genetically and grow very slowly we aimed to establish heterologous expression platforms for myxobacterial PUFA synthases. Here we report the heterologous expression of the pfa gene cluster from Aetherobacter fasciculatus (SBSr002) in the phylogenetically distant model host bacteria Escherichia coli and Pseudomonas putida. The latter host turned out to be the more promising PUFA producer revealing higher production rates of n-6 docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). After several rounds of genetic engineering of expression plasmids combined with metabolic engineering of P. putida, DHA production yields were eventually increased more than threefold. Additionally, we applied synthetic biology approaches to redesign and construct artificial versions of the A. fasciculatus pfa gene cluster, which to the best of our knowledge represents the first example of a polyketide-like biosynthetic gene cluster modulated and synthesized for P. putida. Combination with the engineering efforts described above led to a further increase in LC-PUFA production yields. The established production platform based on synthetic DNA now sets the stage for flexible engineering of the complex PUFA synthase.
•Engineering of a myxobacterial polyunsaturated fatty acid biosynthetic pathway.•Heterologous expression of myxobacterial PUFA synthases in Escherichia coli and Pseudomonas putida.•First synthetic polyketide synthase-like pathway expressed in P. putida.•Production enhancement by genetic and metabolic engineering.
This review presents recommended nomenclature for the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), a rapidly growing class of natural products. The ...current knowledge regarding the biosynthesis of the >20 distinct compound classes is also reviewed, and commonalities are discussed.
Implantation of the Bonebridge (MED-EL, Innsbruck, Austria), an active semi-implantable transcutaneous bone conduction hearing system, involves the risk of impression or a lesion in intracranial ...structures, such as the dura or sigmoid sinus. Therefore, determining the optimal implant position requires careful preoperative radiological planning.
The aim of this study was to provide an overview of the possibilities for preoperative radiological planning for the Bonebridge implantation and to evaluate their indications and feasibility.
A systematic literature search was conducted in the PubMed/MEDLINE database for all studies with preoperative planning or implant placement as the primary endpoint or that secondarily mention preoperative planning.
Of 558 studies, 49 fulfilled the inclusion criteria. In 18 studies, preoperative planning and floating mass transducer (FMT) placement were the primary endpoints, whereas in 31 studies, preoperative planning was described secondarily.
There are both freely available and commercial tools involving different time commitments for preoperative three-dimensional (3D) planning and intraoperative transfer. Preoperative 3D planning can increase the safety of Bonebridge implantation.
The heterologous expression of natural product biosynthetic pathways is of increasing interest in biotechnology and drug discovery. It enables the (over)production of structurally complex substances ...through transfer of the biosynthetic genes from the original producer to more amenable heterologous hosts, and provides the basis to generate novel analogs through biosynthetic engineering. Furthermore, the lateral transfer of ‘silent’ (not expressed under standard laboratory conditions) secondary metabolite pathways or metagenomic DNA into surrogate host strains is expected to yield new, potentially bioactive compounds. This review discusses recent reports on the heterologous production of natural products with emphasis on polyketide and nonribosomally biosynthesized peptide compounds.
Chemotherapy‐ and radiotherapy‐induced oral mucositis represents a therapeutic challenge frequently encountered in cancer patients. This side effect causes significant morbidity and may delay the ...treatment plan, as well as increase therapeutic expenses.
The pathogenesis of this debilitating side effect can be attributed to the direct mucosal toxicity of cytotoxic agents and ionizing radiation and to indirect mucosal damage caused by a concomitant inflammatory reaction exacerbated in the presence of neutropenia, and the emergence of bacterial, mycotic, and viral infections. The prophylactic and therapeutic armamentarium for the treatment of oral mucositis consists of locally and systemically applied nonpharmacological measures and pharmacotherapeutics.
Here, we describe the surgical technique for implanting a new, active, transcutaneous bone conduction hearing aid. The implant technology is based on a system that has been in use reliably since ...2012. The geometry of the new implant has been adapted based on experience with previously introduced implants. The surgery was feasible, standardized, and safe. Due to the optimized geometric design that improved the bone fit, it is not necessary to use specialized, detailed preoperative planning, except in challenging anatomical conditions; e.g., in young children, malformations, poor pneumatization, or after a canal wall down mastoidectomy.
Introduction and hypothesis
The high uterosacral vault suspension (HUVS) is a vaginal approach for treating apical prolapse that provides shorter operative and recovery times and is associated with ...lower morbidity rates. Success rates reported for this technique are comparable with the abdominal sacrocolpopexy (SCP); however, to date, there are no prospective randomized studies comparing HUVS to SCP. The aim of the study was to compare the anatomical objective cure rates for the apical compartment in patients undergoing either HUVS or SCP at 12 months’ follow-up.
Methods
We performed a single-center parallel randomized controlled trial in patients with severe apical defect defined as Pelvic Organ Prolapse Quantification (POP-Q) point C ≥ stage 3. Based on the center’s previous experience, a sample size of 124 patients was required to show a 20 % cure rate difference between both techniques with 80 % power and using a two-tailed 5 % level of significance. One hundred and ten patients were available for analysis; 54 were allocated to abdominal SCP and 56 to HUVS. The primary outcome was to evaluate surgical objective success defined as POP-Q point C stage<2. The Pelvic Floor Distress Inventory (PFDI-20), the Perceived Quality of Life Scale (P-QOL), and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-12) questionnaires were used for subjective assessment.
Results
The objective success rate for apical suspension at 12 months’ follow-up was 100 % for abdominal SCP and 82.5 % for HUVS (log-rank
p
0.033). Both techniques showed a significant improvement with regards to prolapse symptoms, quality of life (QOL), and sexual function. The significant improvement in postoperative questionnaires was comparable between both surgeries at 12 months’ follow-up.
Conclusions
Abdominal SCP has statistically significant better anatomical results when compared with HUVS for correcting apical defects at 12 months.
In complex hand traumas nerves and vessels are often destructed without the possibility for primary repair. For bridging defects of nerves, veins and arteries grafts are necessary. Commonly nerve and ...vein grafts from adjacent donor sites as the wrist, forearm or cubital region are harvested.
This study is a retrospective cohort study. Between 2017 and 2019, 10 patients with complex hand injuries were treated. There were 8 males and 2 females, with an average age of 39 years (range 8-63 years). In all cases grafts were used of the dorsum of the foot for reconstructing of the severed digital nerves and arteries. All donor sites could be closed primarily.
In 100% of cases nerves and veins of the dorsum of the foot showed a good size match as well as adequate length for a sufficient repair. The overall Hand Injury Severity Score (HISS) was determined with a median of 86 (range 57 to 286). In the area of the donor site no relevant complications were seen.
In complex hand injuries the dorsum of the foot is a favorable donor site for nerve and vein graft harvest.
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