Multifactorial Induction of an Orphan PKS-NRPS Gene Cluster in Aspergillus terreus

SummaryMining the genome of the pathogenic fungus Aspergillus terreus revealed the presence of an orphan polyketide-nonribosomal-peptide synthetase (PKS-NRPS) gene cluster. Induced expression of the transcriptional activator gene adjacent to the PKS-NRPS gene was not sufficient for the activation of the silent pathway. Monitoring gene expression, metabolic profiling, and using a lacZ reporter strain allowed for the systematic investigation of physiological conditions that eventually led to the discovery of isoflavipucine and dihydroisoflavipucine. Phytotoxin formation is only activated in the presence of certain amino acids, stimulated at alkaline pH, but strictly repressed in the presence of glucose. Global carbon catabolite repression by CreA cannot be abolished by positive-acting factors such as PacC and overrides the pathway activator. Gene inactivation and stable isotope labeling experiments unveiled the molecular basis for flavipucine/fruit rot toxin biosynthesis

4-Amino-8-cyclo­pent­yloxy-7-meth­oxy-2H-chromen-2-one monohydrate

The asymmetric unit of the title compound, C15H17NO4·H2O, contains two organic mol­ecules with marginal differences between them and two water molecules. The chromine rings in both mol­ecules are essentially planar, with maximum deviations of 0.012 (2) and 0.060 (2) Å. The five-membered cyclo­pentane rings adopt envelope conformations in both mol­ecules. In the crystal, the components are linked by N—H⋯O, O—H⋯O and C—H⋯O hydrogen bonds, resulting in a three-dimensional network

Treatment Effect of CT-Guided Periradicular Injections in Context of Different Contrast Agent Distribution Patterns

Acutely manifesting radicular pain syndromes associated with degenerations of the lower spine are frequent ailments with a high rate of recurrence. Part of the conservative management are periradicular infiltrations of analgesics and steroids. The purpose of this study is to evaluate the dependence of the clinical efficacy of CT-guided periradicular injections on the pattern of contrast distribution and to identify the best distribution pattern that is associated with the most effective pain relief. Using a prospective study design, 161 patients were included in this study, ensuring ethical standards. Statistical analysis was performed, with the level of statistical significance set at p = 0.05. A total of 37.9% of patients experienced significant but not long-lasting (four weeks on average) complete pain relief. A total of 44.1% of patients experienced prolonged, subjectively satisfying pain relief of more than four weeks to three months. A total of 18% of patients had complete and sustained relief for more than six months. A significant correlation exists between circumferential, large area contrast distribution including the zone of action between the disc and affected nerve root contrast distribution pattern with excellent pain relief. Our results support the value of CT-guided contrast injection for achieving a good efficacy, and, if necessary, indicative repositioning of the needle to ensure a circumferential distribution pattern of corticosteroids for the sufficient treatment of radicular pain in degenerative spine disease

Assessment of a Reliable Fractional Anisotropy Cutoff in Tractography of the Corticospinal Tract for Neurosurgical Patients

Background: Tractography has become a standard technique for planning neurosurgical operations in the past decades. This technique relies on diffusion magnetic resonance imaging. The cutoff value for the fractional anisotropy (FA) has an important role in avoiding false-positive and false-negative results. However, there is a wide variation in FA cutoff values. Methods: We analyzed a prospective cohort of 14 patients (six males and eight females, 50.1 ± 4.0 years old) with intracerebral tumors that were mostly gliomas. Magnetic resonance imaging (MRI) was obtained within 7 days before and within 7 days after surgery with T1 and diffusion tensor image (DTI) sequences. We, then, reconstructed the corticospinal tract (CST) in all patients and extracted the FA values within the resulting volume. Results: The mean FA in all CSTs was 0.4406 ± 0.0003 with the fifth percentile at 0.1454. FA values in right-hemispheric CSTs were lower (p < 0.0001). Postoperatively, the FA values were more condensed around their mean (p < 0.0001). The analysis of infiltrated or compressed CSTs revealed a lower fifth percentile (0.1407 ± 0.0109 versus 0.1763 ± 0.0040, p = 0.0036). Conclusion: An FA cutoff value of 0.15 appears to be reasonable for neurosurgical patients and may shorten the tractography workflow. However, infiltrated fiber bundles must trigger vigilance and may require lower cutoffs

Antibiotic-producing symbionts dynamically transition between plant pathogenicity and insect-defensive mutualism

Pathogenic and mutualistic bacteria associated with eukaryotic hosts often lack distinctive genomic features, suggesting regular transitions between these lifestyles. Here we present evidence supporting a dynamic transition from plant pathogenicity to insect-defensive mutualism in symbiotic Burkholderia gladioli bacteria. In a group of herbivorous beetles, these symbionts protect the vulnerable egg stage against detrimental microbes. The production of a blend of antibiotics by B. gladioli, including toxoflavin, caryoynencin and two new antimicrobial compounds, the macrolide lagriene and the isothiocyanate sinapigladioside, likely mediate this defensive role. In addition to vertical transmission, these insect symbionts can be exchanged via the host plant and retain the ability to initiate systemic plant infection at the expense of the plant’s fitness. Our findings provide a paradigm for the transition between pathogenic and mutualistic lifestyles and shed light on the evolution and chemical ecology of this defensive mutualism

Histogram Analysis of Diffusion Weighted Imaging in Low-Grade Gliomas: in vivo Characterization of Tumor Architecture and Corresponding Neuropathology

Background: Low-grade gliomas (LGG) in adults are usually slow growing and frequently asymptomatic brain tumors, originating from glial cells of the central nervous system (CNS). Although regarded formally as “benign” neoplasms, they harbor the potential of malignant transformation associated with high morbidity and mortality. Their complex and unpredictable tumor biology requires a reliable and conclusive presurgical magnetic resonance imaging (MRI). A promising and emerging MRI approach in this context is histogram based apparent diffusion coefficient (ADC) profiling, which recently proofed to be capable of providing prognostic relevant information in different tumor entities. Therefore, our study investigated whether histogram profiling of ADC distinguishes grade I from grade II glioma, reflects the proliferation index Ki-67, as well as the IDH (isocitrate dehydrogenase) mutation and MGMT (methylguanine-DNA methyl-transferase) promotor methylation status. Material and Methods: Pre-treatment ADC volumes of 26 LGG patients were used for histogram-profiling. WHO-grade, Ki-67 expression, IDH mutation, and MGMT promotor methylation status were evaluated. Comparative and correlative statistics investigating the association between histogram-profiling and neuropathology were performed. Results: Almost the entire ADC profile (p25, p75, p90, mean, median) was significantly lower in grade II vs. grade I gliomas. Entropy, as second order histogram parameter of ADC volumes, was significantly higher in grade II gliomas compared with grade I gliomas. Mean, maximum value (ADCmax) and the percentiles p10, p75, and p90 of ADC histogram were significantly correlated with Ki-67 expression. Furthermore, minimum ADC value (ADCmin) was significantly associated with MGMT promotor methylation status as well as ADC entropy with IDH-1 mutation status. Conclusions: ADC histogram-profiling is a valuable radiomic approach, which helps differentiating tumor grade, estimating growth kinetics and probably prognostic relevant genetic as well as epigenetic alterations in LGG

Single-Center Experience With the Bare p48MW Low-Profile Flow Diverter and Its Hydrophilically Covered Version for Treatment of Bifurcation Aneurysms in Distal Segments of the Anterior and Posterior Circulation

Background and Purpose: Flow diversion has profoundly changed the way aneurysms are treated. However, it conventionally requires dual antiplatelet medication and has yet been considered off-label use in the posterior circulation or within peripheral vessels of the anterior circulation. Here, we report our experience with the p48MW/p48MW hydrophilic coating (HPC) in the anterior and posterior circulation. This novel low-profile flow diverter is specifically designed for treatment of small peripheral vessels, and the p48MW HPC has an anti-thrombotic polymer coating, which allows application of a single antiplatelet function medication in conditions that expectably require further surgery. Materials and Methods: Thirty-two patients were prospectively included. Twenty-six treatments were performed with one flow diverter, four required two overlapping flow diverters, one case demanded three overlapping flow diverters, and in one case, extensive dissecting aneurysm telescoping with eight flow diverters was necessary. Twenty-two complex bifurcation aneurysms were treated. Three months’ follow-up was available for 14 patients. Results: Deployment was uneventful in all cases. In four cases, undersizing was unavoidable and resulted in significant shortening of the flow diverter, which demanded implantation of further flow diverters to sufficiently treat the target aneurysm. Three flow diverters required balloon angioplasty for optimal wall approximation. All parent vessels remained patent. Available 3-month follow-up studies showed decreased influx or delayed washout in all aneurysms; none was occluded completely. There were no device-related clinical complications. Conclusions: Implantation of the p48MW/p48MW HPC is safe and effective for treatment of distally located cerebral aneurysms. Considering the reported rates of ischemic complications associated with flow diversion of complex bifurcation aneurysms, the p48MW/p48MW HPC potentially provides increased safety for complex bifurcation aneurysms in the anterior and posterior circulation

Endovascular Treatment of Intracranial Aneurysms in Small Peripheral Vessel Segments—Efficacy and Intermediate Follow-Up Results of Flow Diversion With the Silk Vista Baby Low-Profile Flow Diverter

Background and Purpose: Low-profile flow diverter stents (FDS) quite recently amended peripheral segments as targets for hemodynamic aneurysm treatment; however, reports on outcomes, especially later than 3 months, are scarce. This study therefore reports our experience with the novel silk vista baby (SVB) FDS and respective outcomes after 8 and 11 months with special respect to specific adverse events. Materials and Methods: Forty-four patients (mean age, 53 years) harboring 47 aneurysms treated with the SVB between June 2018 and December 2019 were included in our study. Clinical, procedural, and angiographic data were collected. Follow-ups were performed on average after 3, 8, and 11 months, respectively. Treatment effect was assessed using the O’Kelly Marotta (OKM) grading system. Results: Overall, angiographic follow-ups were available for 41 patients/45 aneurysms. Occlusion or significant reduction in aneurysmal perfusion (OKM: D1, B1–B3 and A2–A3) was observed in 98% of all aneurysms after 8 months. Only 2% of the treated aneurysms remained morphologically unaltered and without an apparent change in perfusion (OKM A1). Adverse events in the early post-interventional course occurred in seven patients; out of them, mRS-relevant morbidity at 90 days related to FDS treatment was observable in two patients. One death occurred in the context of severe SAH related to an acutely ruptured dissecting aneurysm of the vertebral artery. Conclusion: The SVB achieves sufficient occlusion rates of intracranial aneurysms originating from peripheral segments, which are comparable to prior established conventional FDS with acceptably low complication rates. However, alteration of a hemodynamic equilibrium in distal localizations requires special attention to prevent ischemic events