Immunocytokines are a promising immunotherapeutic approach against glioblastoma.

Glioblastoma is a poorly immunogenic cancer, and the successes with recent immunotherapies in extracranial malignancies have, so far, not been translated to this devastating disease. Therefore, there is an urgent need for new strategies to convert the immunologically cold glioma microenvironment into a hot one to enable effective antitumor immunity. Using the L19 antibody, which is specific to a tumor-associated epitope of extracellular fibronectin, we developed antibody-cytokine fusions-immunocytokines-with interleukin-2 (IL2), IL12, or tumor necrosis factor (TNF).

Ubiquitin Phosphorylation at Thr12 Modulates the DNA Damage Response.

The ubiquitin system regulates the DNA damage response (DDR) by modifying histone H2A at Lys15 (H2AK15ub) and triggering downstream signaling events. Here, we find that phosphorylation of ubiquitin at Thr12 (pUbT12) controls the DDR by inhibiting the function of 53BP1, a key factor for DNA double-strand break repair by non-homologous end joining (NHEJ). Detectable as a chromatin modification on H2AK15ub, pUbT12 accumulates in nuclear foci and is increased upon DNA damage.

Nearshore Zone Dynamics Determine Pathway of Organic Carbon From Eroding Permafrost Coasts.

Collapse of permafrost coasts delivers large quantities of particulate organic carbon (POC) to Arctic coastal areas. With rapidly changing environmental conditions, sediment and organic carbon (OC) mobilization and transport pathways are also changing. Here, we assess the sources and sinks of POC in the highly dynamic nearshore zone of Herschel Island-Qikiqtaruk (Yukon, Canada).

An Antibody-Tumor Necrosis Factor Fusion Protein that Synergizes with Oxaliplatin for Treatment of Colorectal Cancer.

We have cloned and characterized a novel fusion protein (Sm3E-TNF), consisting of the mAb, S 6m3E, in single-chain Fv fragment format, fused to murine TNF. The protein, which was expressed in mammalian cells and purified as a noncovalent stable homotrimer, bound to the cognate carcinoembryonic antigen (CEA) and retained TNF activity. A quantitative biodistribution experiment, performed in immunocompetent mice with CT26 colon carcinomas transfected with human CEA, revealed that Sm3E-TNF was able to preferentially accumulate in the tumors with excellent selectivity (tumor:blood ratio = 56:1, 24 hours after intravenous administration).

The targeted delivery of interleukin-12 to the carcinoembryonic antigen increases the intratumoral density of NK and CD8 T cell in an immunocompetent mouse model of colorectal cancer.

The recent success achieved by immune checkpoint inhibitors in the field of immuno-oncology has been less evident for the treatment of metastatic colorectal cancer (mCRC) patients. To date, cancer immunotherapy has been efficacious only in few patients bearing high mutational burden (less than 25%) mCRCs. In this Communication, we report the generation of a novel antibody cytokine fusion protein (termed Sm3E-mIL12) targeting the CRC-associated carcinoembryonic antigen (CEA).

Unconventional Yeasts Are Tolerant to Common Antifungals, and Has Low Baseline Sensitivity to Captan, Cyprodinil, and Difenoconazole.

Many yeasts have demonstrated intrinsic insensitivity to certain antifungal agents. Unlike the fungicide resistance of medically relevant yeasts, which is highly undesirable, intrinsic insensitivity to fungicides in antagonistic yeasts intended for use as biocontrol agents may be of great value. Understanding how frequently tolerance exists in naturally occurring yeasts and their underlying molecular mechanisms is important for exploring the potential of biocontrol yeasts and fungicide combinations for plant protection.

MCDA Index Tool: an interactive software to develop indices and rankings.

A web-based software, called (https://www.mcdaindex.net/), is presented in this paper.

The neonicotinoid thiacloprid causes transcriptional alteration of genes associated with mitochondria at environmental concentrations in honey bees.

Thiacloprid is widely used in agriculture and may affect pollinators. However, its molecular effects are poorly known. Here, we report the global gene expression profile in the brain of honey bee foragers assessed by RNA-sequencing.

Rational design of a fluorescent microneedle tattoo for minimally invasive monitoring of lymphatic function.

The monitoring of lymphatic drainage is of great importance, particularly in the context of the early detection and diagnosis of several diseases. Existing methods of imaging and monitoring lymphatic drainage can be costly and require trained personnel, posing problems for at-home or point-of-care monitoring. Recently, an alternative approach has been proposed, consisting of using microneedles to deliver a near-infrared (NIR) fluorescent tattoo to the skin, which can be monitored with traditional laboratory-based fluorescence detectors.

Signaling phospholipids in plant development: small couriers determining cell fate.

The survival of plants hinges on their ability to perceive various environmental stimuli and translate them into appropriate biochemical responses. Phospholipids, a class of membrane lipid compounds that are asymmetrically distributed within plant cells, stand out among signal transmitters for their diversity of mechanisms by which they modulate stress and developmental processes. By modifying the chemo-physical properties of the plasma membrane (PM) as well as vesicle trafficking, phospholipids contribute to changes in the protein membrane landscape, and hence, signaling responses.

Expression of green fluorescent protein defines a specific population of lamina II excitatory interneurons in the GRP::eGFP mouse.

Dorsal horn excitatory interneurons that express gastrin-releasing peptide (GRP) are part of the circuit for pruritogen-evoked itch. They have been extensively studied in a transgenic line in which enhanced green fluorescent protein (eGFP) is expressed under control of the Grp gene. The GRP-eGFP cells are separate from several other neurochemically-defined excitatory interneuron populations, and correspond to a class previously defined as transient central cells.

Particulate Organic Matter Dynamics in a Permafrost Headwater Stream and the Kolyma River Mainstem.

Ongoing rapid arctic warming leads to extensive permafrost thaw, which in turn increases the hydrologic connectivity of the landscape by opening up subsurface flow paths. Suspended particulate organic matter (POM) has proven useful to trace permafrost thaw signals in arctic rivers, which may experience higher organic matter loads in the future due to expansion and increasing intensity of thaw processes such as thermokarst and river bank erosion. Here we focus on the Kolyma River watershed in Northeast Siberia, the world's largest watershed entirely underlain by continuous permafrost.

Netrin-1 receptor DCC is required for the contralateral topography of lamina I anterolateral system neurons.

Anterolateral system (AS) neurons relay nociceptive information from the spinal cord to the brain, protecting the body from harm by evoking a variety of behaviours and autonomic responses. The developmental programs that guide the connectivity of AS neurons remain poorly understood. Spinofugal axons cross the spinal midline in response to Netrin-1 signalling through its receptor deleted in colorectal carcinoma (DCC); however, the relevance of this canonical pathway to AS neuron development has only been demonstrated recently.

Topological Polymer Chemistry Enters Materials Science: Expanding the Applicability of Cyclic Polymers.

Polymer-topology effects can alter technologically relevant properties when cyclic macromolecules are applied within diverse materials formulations. These include coatings, polymer networks, or nanostructures for delivering therapeutics. While substituting linear building blocks with cyclic analogues in commonly studied materials is itself of fundamental interest, an even more fascinating observation has been that the introduction of physical or chemical boundaries (e.

Selective Fragments for the CREBBP Bromodomain Identified from an Encoded Self-assembly Chemical Library.

DNA-encoded chemical libraries (DECLs) are collections of chemical moieties individually coupled to distinctive DNA barcodes. Compounds can be displayed either at the end of a single DNA strand (i. e.

Reticulate evolution as a management challenge: Patterns of admixture with phylogenetic distance in endemic fishes of western North America.

Admixture in natural populations is a long-standing management challenge, with population genomic approaches offering means for adjudication. We now more clearly understand the permeability of species boundaries and the potential of admixture for promoting adaptive evolution. These issues particularly resonate in western North America, where tectonism and aridity have fragmented and reshuffled rivers over millennia, in turn promoting reticulation among endemic fishes, a situation compounded by anthropogenic habitat modifications and non-native introductions.

Insecticides cause transcriptional alterations of endocrine related genes in the brain of honey bee foragers.

Bees are exposed to endocrine active insecticides. Here we assessed expressional alteration of marker genes indicative of endocrine effects in the brain of honey bees. We exposed foragers to chlorpyrifos, cypermethrin and thiacloprid and assessed the expression of genes after exposure for 24 h, 48 h and 72 h.

Projections from the dorsomedial division of the bed nucleus of the stria terminalis to hypothalamic nuclei in the mouse.

As stressful environment is a potent modulator of feeding, we seek in the present work to decipher the neuroanatomical basis for an interplay between stress and feeding behaviors. For this, we combined anterograde and retrograde tracing with immunohistochemical approaches to investigate the patterns of projections between the dorsomedial division of the bed nucleus of the stria terminalis (BNST), well connected to the amygdala, and hypothalamic structures such as the paraventricular (PVH) and dorsomedial (DMH), the arcuate (ARH) nuclei and the lateral hypothalamic areas (LHA) known to control feeding and motivated behaviors. We particularly focused our study on afferences to proopiomelanocortin (POMC), agouti-related peptide (AgRP), melanin-concentrating-hormone (MCH) and orexin (ORX) neurons characteristics of the ARH and the LHA, respectively.

Comment on Liu et al. "Discrepancies of Measured SAR between Traditional and Fast Measuring Systems." , 2020, , 2111.

An article published in the compares two types of specific absorption rate measurement systems-a fast system using a time-domain array and a traditional system using probe scanning. While the time-domain array system is analyzed in detail under idealized conditions, the probe-scanning system evaluation used a fixed set of scanning and evaluation parameters that are not fully compliant with the requirements of the published standards. This leads to a false comparison and the incorrect conclusion that time-domain array systems can be theoretically more accurate than probe-scanning systems.

Laser thermal therapy for epilepsy surgery: current standing and future perspectives.

More than 130-year ago, Sir Victor Horsley delivered a landmark address to the British Medical Association, in which he described successful localization and resection of an epileptogenic focus resulting in seizure freedom for the patient. Several important steps in epilepsy surgery have been achieved since, including resection techniques such as anterior temporal lobectomy and selective amygdalohippocampectomy, both resulting in 70-80% seizure freedom and distinct differences in neuropsychological outcomes. The most recent addition to techniques for epilepsy surgery is minimally invasive thermal therapy.

Effects of environmental steroid mixtures are regulated by individual steroid receptor signaling.

Fish are exposed to steroids of different classes in contaminated waters, but their effects are not sufficiently understood. Here we employed an anti-sense technique using morpholino oligonucleotides to knockdown the glucocorticoid receptors (GRs, GRα and GRβ) and androgen receptor (AR) to investigate their role in physiological and transcriptional responses. To this end, zebrafish embryos were exposed to clobetasol propionate (CLO), androstenedione (A4) and mixtures containing different classes of steroids.

Exercise promotes satellite cell contribution to myofibers in a load-dependent manner.

Background: Satellite cells (SCs) are required for muscle repair following injury and are involved in muscle remodeling upon muscular contractions. Exercise stimulates SC accumulation and myonuclear accretion. To what extent exercise training at different mechanical loads drive SC contribution to myonuclei however is unknown.

Complexation with a Cognate Antibody Fragment Facilitates Affinity Measurements of Fluorescein-Linked Small Molecule Ligands.

The availability of reliable methods for the characterization of the binding of small molecule ligands to protein targets is crucially important for drug discovery. We have adapted a method, routinely used for the characterization of monoclonal antibodies (enzyme-linked immunosorbent assay, or "ELISA"), to small molecule ligands, using fluorescein conjugates and antifluorescein antibodies as detection reagents. The new small molecule-ELISA methodology was tested using a panel of binders specific to carbonic anhydrase II, with dissociation constants ranging between 6 μM and 14 nM.

Reliability and Influence on Decision Making of fully-automated vs. semi-automated Software Packages for Procedural Planning in TAVI.

Precise procedural planning is crucial to achieve excellent results in patients undergoing Transcatheter aortic valve implantation (TAVI). The aim of this study was to compare the semi-automated 3mensio (3 m) software to the fully-automated HeartNavigator3 (HN) software. We randomly selected 100 patients from our in-house TAVI-registry and compared aortic annulus and perimeter as well as coronary distances between 3m-measurements and post-hoc HN-measurements.

Development of an ELISA for the quantification of mycolactone, the cytotoxic macrolide toxin of Mycobacterium ulcerans.

Mycolactones, macrolide cytotoxins, are key virulence factors of Mycobacterium ulcerans, the etiological agent of the chronic necrotizing skin disease Buruli ulcer. There is urgent need for a simple point-of-care laboratory test for Buruli ulcer and mycolactone represents a promising target for the development of an immunological assay. However, for a long time, all efforts to generate mycolactone-specific antibodies have failed.