Angew Chem Int Ed Engl
November 2024
Peripheral modification is often the main approach to optimize natural products for improved biological activity or desired physicochemical properties. This procedure inevitably increases molecular weight, often accompanied by undesired increased lipophilicity. Removing structural elements from natural products is not always tolerated.
View Article and Find Full Text PDFBackground: More responsive, reliable, and clinically valid endpoints of disability are essential to reduce size, duration, and burden of clinical trials in adult persons with spinal muscular atrophy (aPwSMA).
Objective: The aim is to investigate the feasibility of smartphone-based assessments in aPwSMA and provide evidence on the reliability and construct validity of sensor-derived measures (SDMs) of mobility and manual dexterity collected remotely in aPwSMA.
Methods: Data were collected from 59 aPwSMA (23 walkers, 20 sitters and 16 non-sitters) and 30 age-matched healthy controls (HC).
Tumor microtubes (TMs) connect glioma cells to a network with considerable relevance for tumor progression and therapy resistance. However, the determination of TM-interconnectivity in individual tumors is challenging and the impact on patient survival unresolved. Here, we establish a connectivity signature from single-cell RNA-sequenced (scRNA-Seq) xenografted primary glioblastoma (GB) cells using a dye uptake methodology, and validate it with recording of cellular calcium epochs and clinical correlations.
View Article and Find Full Text PDFThis review discusses small molecule antibiotics approved for clinical use in the time frame 2010-2022. This time span saw the approval of four synthetic antibiotics (bedaquiline, pretomanid, delafloxacin, tedizolid), nine natural product derivatives (ceftaroline fosamil, cefiderocol, plazomicin, omadacycline, eravacycline, sarecycline, lefamulin, dalbavancin, oritavancin), and one natural product (fidaxomicin).
View Article and Find Full Text PDFFidaxomicin (Fdx) is a natural product antibiotic with potent activity against Clostridioides difficile and other Gram-positive bacteria such as Mycobacterium tuberculosis. Only a few Fdx derivatives have been synthesized and examined for their biological activity in the 50 years since its discovery. Fdx has a well-studied mechanism of action, namely inhibition of the bacterial RNA polymerase.
View Article and Find Full Text PDFInternet Things (Amst)
November 2022
The Internet of Things (IoT) provides a simple framework to control online devices easily. IoT is now a commonplace tool used by technology companies but is rarely used in biology experiments. IoT can benefit cloud biology research through alarm notifications, automation, and the real-time monitoring of experiments.
View Article and Find Full Text PDFWe experimentally demonstrate, based on a generic concept for creating 1-to-M couplers, single-mode 3D optical splitters leveraging adiabatic power transfer towards up to 4 output ports. We use the CMOS compatible additive (3+1)D flash-two-photon polymerization (TPP) printing for fast and scalable fabrication. Optical coupling losses of our splitters are reduced below our measurement sensitivity of 0.
View Article and Find Full Text PDFBackground: Glioblastomas are characterized by aggressive and infiltrative growth, and by striking heterogeneity. The aim of this study was to investigate whether tumor cell proliferation and invasion are interrelated, or rather distinct features of different cell populations.
Methods: Tumor cell invasion and proliferation were longitudinally determined in real-time using 3D in vivo 2-photon laser scanning microscopy over weeks.
Allylic cyclitols were investigated as covalent inhibitors of glycoside hydrolases by chemical, enzymatic, proteomic, and computational methods. This approach was inspired by the C cyclitol natural product streptol glucoside, which features a potential carbohydrate leaving group in the 4-position (carbohydrate numbering). To test this hypothesis, carbocyclic inhibitors with leaving groups in the 4- and 6- positions were prepared.
View Article and Find Full Text PDFDiffuse gliomas, particularly glioblastomas, are incurable brain tumours. They are characterized by networks of interconnected brain tumour cells that communicate via Ca transients. However, the networks' architecture and communication strategy and how these influence tumour biology remain unknown.
View Article and Find Full Text PDFThe overall benefit of surgical treatments for patients with glioma is undisputed. We have shown preclinically that brain tumor cells form a network that is capable of detecting damage to the tumor, and repair itself. The aim of this study was to determine whether a similar mechanism might contribute to local recurrence in the clinical setting.
View Article and Find Full Text PDFSimultaneous longitudinal imaging across multiple conditions and replicates has been crucial for scientific studies aiming to understand biological processes and disease. Yet, imaging systems capable of accomplishing these tasks are economically unattainable for most academic and teaching laboratories around the world. Here, we propose the Picroscope, which is the first low-cost system for simultaneous longitudinal biological imaging made primarily using off-the-shelf and 3D-printed materials.
View Article and Find Full Text PDFBoth the perivascular niche (PVN) and the integration into multicellular networks by tumor microtubes (TMs) have been associated with progression and resistance to therapies in glioblastoma, but their specific contribution remained unknown. By long-term tracking of tumor cell fate and dynamics in the live mouse brain, differential therapeutic responses in both niches are determined. Both the PVN, a preferential location of long-term quiescent glioma cells, and network integration facilitate resistance against cytotoxic effects of radiotherapy and chemotherapy-independently of each other, but with additive effects.
View Article and Find Full Text PDFBackground: Glioma is sensitive to microtubule-targeting agents (MTAs), but most MTAs do not cross the blood brain barrier (BBB). To address this limitation, we developed the new chemical entity, ST-401, a brain-penetrant MTA.
Methods: Synthesis of ST-401.
Despite advances in the treatment of solid tumors, the prognosis of patients with many cancers remains poor, particularly of those with primary and metastatic brain tumors. In the last years, "Cancer Neuroscience" emerged as novel field of research at the crossroads of oncology and classical neuroscience. In primary brain tumors, including glioblastoma (GB), communicating networks that render tumor cells resistant against cytotoxic therapies were identified.
View Article and Find Full Text PDFThe natural product antibiotic fidaxomicin is a marketed drug for the treatment of bacterial infections in the gut. Due to its promising activities against , the development of next generation fidaxomicin analogs is of great interest. This article reviews the most recent advances, including the elucidation of a unique mode of action by cryo-EM structures, and the efforts towards the clarification of the biosynthetic pathway.
View Article and Find Full Text PDFThe establishment of neuronal and glial networks in the brain depends on the activities of neural progenitors, which are influenced by cell-intrinsic mechanisms, interactions with the local microenvironment and long-range signaling. Progress in neuroscience has helped identify key factors in CNS development. In parallel, studies in recent years have increased our understanding of molecular and cellular factors in the development and growth of primary brain tumors.
View Article and Find Full Text PDFOptical activity requires chirality and is a paradigm for chirality. Here, we present experiments on its mechanical counterpart, acoustical activity. The notion "activity" refers the rotation of the linear polarization axis of a transversely polarized (optical or mechanical) wave.
View Article and Find Full Text PDFEarly and progressive colonization of the healthy brain is one hallmark of diffuse gliomas, including glioblastomas. We recently discovered ultralong (>10 to hundreds of microns) membrane protrusions [tumor microtubes (TMs)] extended by glioma cells. TMs have been associated with the capacity of glioma cells to effectively invade the brain and proliferate.
View Article and Find Full Text PDFBackground: Primary and adaptive resistance against chemo- and radiotherapy and local recurrence after surgery limit the benefits from these standard treatments in glioma patients. Recently we found that glioma cells can extend ultra-long membrane protrusions, "tumor microtubes" (TMs), for brain invasion, proliferation, and interconnection of single cells to a syncytium that is resistant to radiotherapy. We wondered whether TMs also convey resistance to the other 2 standard treatment modalities.
View Article and Find Full Text PDFAstrocytic brain tumours, including glioblastomas, are incurable neoplasms characterized by diffusely infiltrative growth. Here we show that many tumour cells in astrocytomas extend ultra-long membrane protrusions, and use these distinct tumour microtubes as routes for brain invasion, proliferation, and to interconnect over long distances. The resulting network allows multicellular communication through microtube-associated gap junctions.
View Article and Find Full Text PDFWe evaluate the encapsulation and packaging reliability of a fully integrated wireless neural interface based on a Utah Slant Electrode Array/integrated neural interface-recording version 5 (USEA/INI-R5) system by monitoring the long term in vitro functional stability and recording longevity. The INI encapsulated with 6 µm Parylene-C was immersed in phosphate buffered saline (PBS) for a period of over 276 days (with the monitoring of the functional device still ongoing). The full functionality (wireless radio-frequency power, command and signal transmission) and the ability of the electrodes to record artificial neural signals even after 276 days of PBS soaking with little change (within 14%) in signal/noise amplitude constitute a major milestone in long term stability and allow us to study and evaluate the encapsulation reliability, functional stability and its potential usefulness for a wireless neural interface for future chronic implants.
View Article and Find Full Text PDFThe rapid increase of the applications for Lab-on-a-chip devices has attracted the interest of researchers and engineers on standard process of the electronics industry for low production costs and large scale development, necessary for disposable applications. The printed circuit board technology could be used for this purpose, in particular for the wide range of materials available. In this paper, assays on biocompatibility of materials used for Lab-on-a-chip fabrication has been carried out using two tumor cell lines growing in suspension, the human chronic myelogenous leukemia K562 cell line, able to undergo erythroid differentiation when cultured with chemical inducers, and the lymphoblastoid cell line (LCL), extensively used for screening of cytotoxic T-lymphocytes (CTLs).
View Article and Find Full Text PDFPrinted circuit board (PCB) technology can be used for producing lab-on-a-chip (LOAC) devices. PCBs are characterized by low production costs and large-scale development, both essential elements in the frame of disposable applications. LOAC platforms have been employed not only for diagnostic and/or analytical purposes, but also for identification and isolation of eukaryotic cells, including cancer and stem cells.
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