Auswirkungen verschiedener Bodenbearbeitungsvarianten auf den Besiedelungsgrad von Winterroggen (Secale cereale) durch arbuskuläre Mykorrhizapilze (AMP) unter den Bedingungen des Ökologischen Landbaues

Problemstellung/Ziele:Die arbuskuläre Mykorrhiza ist eine Symbiose zwischen dem Grossteil der landwirtschaftlichen Kulturpflanzen und bodenbürtigen Pilzen. Der heterotrophe Pilz erhält Assimilate von der autotrophen Pflanze, als Gegenleistung fördert der Pilz die Nährstoffaufnahme in die Pflanze und erhöht die Resistenz gegenüber phytopathogenen Mikroorganismen, die in einer Wachstumssteigerung der Pflanze resultieren können. In zahlreichen Untersuchungen wurde festgestellt, dass mechanische Bodenbearbeitung das Besiedelungspotenzial von landwirtschaftlichen Kulturpflanzen durch arbuskuläre Mykorrhizapilze (AMP) vermindert und die Effizienz des Myzels der AMP bei der Aufnahme von Phosphor mit steigender Intensität der Bodenbearbeitung abnimmt. Ziel der Untersuchungen war, die Auswirkungen verschiedener Bodenbearbeitungsvarianten auf den Mykorrhizabesiedelungsgrad von Winterroggen unter den Bedingungen des Ökologischen Landbaues festzustellen. Hypothesen: Mit abnehmender Bodenbearbeitungsintensität (Pflug > Zweischichtenpflug > Schichtengrubber) nimmt das Kolonisationspotenzial mit AMP in den Böden zu. Dadurch erfolgt eine intensivere Kolonisation der Wurzeln der pflanzlichen Symbiosepartner. Fazit: Der arbuskulären Mykorrhiza wird im Ökologischen Landbau eine relativ grosse Bedeutung bei der Ertragsbildung durch die landwirtschaftlichen Kulturpflanzen zugemessen. Bei der Auswahl der Bodenbearbeitungsgeräte sollte deshalb auch die Ausbildung einer arbuskulären Mykorrhiza beachtet werden. Lockernde Bodenbearbeitung (Schichtengrubber) bewirkte in der Untersuchung einen höheren Mykorrhizabesiedelungsgrad von Winterroggen im Vergleich zu wendender Bodenbearbeitung (Pflug, Schichtenpflug). Vor diesem Hintergrund sollte lockernder Bodenbearbeitung auf Praxisbetrieben nach Möglichkeit der Vorzug gegeben werden

New Substituted Isocoumarins and Dihydroisocoumarins and their Cytotoxic Activities

New isocoumarins were prepared in an efficient way from 2-iodobenzoic acid derivatives and hept-1-yne in a Sonogashira reaction, followed by spontaneous cyclization. Catalytic hydrogenation gave the corresponding dihydroisocoumarins. A 4-chloroisocoumarin was prepared on an alternative pathway. Some of the new compounds showed moderate cytotoxic activities against a human leukemia cell line (HL 60)

Molecular characterization of hematopoietic stem cells after in vitro amplification on biomimetic 3D PDMS cell culture scaffolds

Hematopoietic stem cell (HSC) transplantation is successfully applied since the late 1950s. However, its efficacy can be impaired by insufficient numbers of donor HSCs. A promising strategy to overcome this hurdle is the use of an advanced ex vivo culture system that supports the proliferation and, at the same time, maintains the pluripotency of HSCs. Therefore, we have developed artificial 3D bone marrow-like scaffolds made of polydimethylsiloxane (PDMS) that model the natural HSC niche in vitro. These 3D PDMS scaffolds in combination with an optimized HSC culture medium allow the amplification of high numbers of undifferentiated HSCs. After 14 days in vitro cell culture, we performed transcriptome and proteome analysis. Ingenuity pathway analysis indicated that the 3D PDMS cell culture scaffolds altered PI3K/AKT/mTOR pathways and activated SREBP, HIF1α and FOXO signaling, leading to metabolic adaptations, as judged by ELISA, Western blot and metabolic flux analysis. These molecular signaling pathways can promote the expansion of HSCs and are involved in the maintenance of their pluripotency. Thus, we have shown that the 3D PDMS scaffolds activate key molecular signaling pathways to amplify the numbers of undifferentiated HSCs ex vivo effectively

Case Report: Three cases of suspected female genital schistosomiasis and precancerous lesions for cervical cancer in a highly endemic country—from clinical management to public health implications

Female genital schistosomiasis (FGS) is a chronic manifestation of schistosomiasis, usually caused by Schistosoma haematobium infection, which can be responsible for infertility, ectopic pregnancy, and abortion, and is associated with an increased prevalence of HIV infection. No screening programs are currently recommended for FGS. Colposcopy, the conventionally suggested diagnostic tool for FGS, is also considered a crucial screening tool for cervical cancer (CC). We performed an experimental screening via colposcopy for FGS at primary healthcare centers (PHCCs) in the Boeny region of Madagascar, allowing for the detection of patients with both FGS signs and HPV-related dysplasia (HPV-dy). All suspected FGS cases were treated with praziquantel on the day of colposcopy, and all images of suspected CC or HPV-dy were re-assessed by a gynecologist and, if needed, patients were then provided with additional colposcopy for histologic diagnosis and treatment. We describe three cases of FGS and HPV-related precancerous lesions detected during the project, discussing the state of art of the relationship between CC, FGS and HPV and the real-life challenges encountered in terms of both patient compliance and the diagnostic and treatment cascade. Despite the current diagnostic limitations, a screening for FGS via colposcopy may contribute to the early identification of CC or precancerous lesions. The addition of visual inspection with acetic acid (VIA) during colposcopy for FGS screening could improve its impact on CC screening. In addition, although there is limited evidence of the effectiveness of praziquantel in FGS, treatment should in any case be proposed for suspicious lesions, given its safety and ease of administration. The benefit of combined screening could be maximised by increasing the availability of good quality services and improve awareness of both diseases among wome

Intracerebral Administration of Heat-Inactivated Staphylococcus Epidermidis Enhances Oncolysis and Prolongs Survival in a 9L Orthotopic Gliosarcoma Model

Background/Aims: The association between postoperative infection and prolonged survival in high-grade glioma is still a matter of debate. Previously we demonstrated that the intracerebral (i.c.) injection of heat-inactivated staphylococcal epitopes (HISE) resulted in a well-defined infux of immunocompetent cells across the blood-brain barrier. The present study investigated the potential antitumoral effect of HISE-immunostimulation in an experimental glioma model. Methods: Wistar rats were intracerebrally implanted with 9L gliosarcoma cells (n=6), 9L cells mixed with HISE (n=12), or phosphate buffered saline (n=4). Tumor growth was measured by serial magnetic resonance imaging (MRI). After death due to the tumor burden, the brains were histopathologically assessed for inflammation and oncolysis. A toxicity assay was performed to quantify potential impairment of HISE on tumor cell growth in vitro. Results: Animals treated by HISE showed a significant increase in average survival and even complete regression of an already established mass in one case. Naïve 9L gliosarcomas failed to recruit significant numbers of systemic immune cells. In contrast, concomitant intracerebral HISE inoculation lead to a oncolysis and a distinct peri- and intratumoral infiltration of macrophages, CD8 and CD4 co-expressing T-lymphocytes in two thirds of the tumor-bearing animals. The toxicity screening showed HISE-mediated oncolysis to be ineffective ex vivo. Conclusion: This study describes a novel approach for combatting malignant glioma using inactivated staphylococci as potent immunomodulators. Our results provide an outline for investigating the strategic potential of bacteria as emerging future therapeutics

Development of a bleeding scale and hemostasis algorithm in cranial neurosurgery

Effective hemostasis is crucial in neurosurgery as anatomical and functional considerations reduce tolerance for any bleeding. The classification of bleeding severities is a necessary step to enable neurosurgeons to counteract bleeding during surgery.Even though bleeding scales are used for a variety of surgical specialties, they cannot be transferred to cranial neurosurgery without adaption, and no consensus on the nature of such a classification exists to date. Moreover, there is plethora of topical hemostasis products with diverse mechanisms of action and application available. Clinical studies investigating those products used in neurosurgery did not define standardized procedures. This article demonstrates the systematic establishment of both a bleeding scale and a hemostasis algorithm to close this gap in the assessment of intracranial bleeding.The expert panel consisting of 7 members from different neurosurgical centers developed a qualitative bleeding scale with the peculiarities of neurosurgical procedures, based on the experience of each member in daily practice. The hemostasis algorithm is a recommendation for neurosurgeons to aid in the decision-making process to control any sort of bleeding, taking into account the rational use of available hemostatics, depending on type and location of bleeding, as well as the mechanism of action of such agents. Effectiveness of hemostasis, surgery times and economic costs can be optimized by applying the algorithm in daily practice

Pattern of Functional TTX-Resistant Sodium Channels Reveals a Developmental Stage of Human iPSC- and ESC-Derived Nociceptors

Human pluripotent stem cells (hPSCs) offer the opportunity to generate neuronal cells, including nociceptors. Using a chemical-based approach, we generated nociceptive sensory neurons from HUES6 embryonic stem cells and retrovirally reprogrammed induced hPSCs derived from fibroblasts. The nociceptive neurons expressed respective markers and showed tetrodotoxin-sensitive (TTXs) and -resistant (TTXr) voltage-gated sodium currents in patch-clamp experiments. In contrast to their counterparts from rodent dorsal root ganglia, TTXr currents of hPSC-derived nociceptors unexpectedly displayed a significantly more hyperpolarized voltage dependence of activation and fast inactivation. This apparent discrepancy is most likely due to a substantial expression of the developmentally important sodium channel NAV1.5. In view of the obstacles to recapitulate neuropathic pain in animal models, our data advance hPSC-derived nociceptors as a better model to study developmental and pathogenetic processes in human nociceptive neurons and to develop more specific small molecules to attenuate pain

GSK3ß-dependent dysregulation of neurodevelopment in SPG11-patient induced pluripotent stem cell model

Objective: Mutations in the spastic paraplegia gene 11 (SPG11), encoding spatacsin, cause the most frequent form of autosomal-recessive complex hereditary spastic paraplegia (HSP) and juvenile-onset amyotrophic lateral sclerosis (ALS5). When SPG11 is mutated, patients frequently present with spastic paraparesis, a thin corpus callosum, and cognitive impairment. We previously delineated a neurodegenerative phenotype in neurons of these patients. In the current study, we recapitulated early developmental phenotypes of SPG11 and outlined their cellular and molecular mechanisms in patient-specific induced pluripotent stem cell (iPSC)-derived cortical neural progenitor cells (NPCs). Methods: We generated and characterized iPSC-derived NPCs and neurons from 3 SPG11 patients and 2 age-matched controls. Results: Gene expression profiling of SPG11-NPCs revealed widespread transcriptional alterations in neurodevelopmental pathways. These include changes in cell-cycle, neurogenesis, cortical development pathways, in addition to autophagic deficits. More important, the GSK3ss-signaling pathway was found to be dysregulated in SPG11-NPCs. Impaired proliferation of SPG11-NPCs resulted in a significant diminution in the number of neural cells. The decrease in mitotically active SPG11-NPCs was rescued by GSK3 modulation. Interpretation: This iPSC-derived NPC model provides the first evidence for an early neurodevelopmental phenotype in SPG11, with GSK3ss as a potential novel target to reverse the disease phenotype