Publications by authors named "Christoph Schneider"

165 Publications

PPARγ is essential for the development of bone marrow erythroblastic island macrophages and splenic red pulp macrophages.

J Exp Med 2021 May;218(5)

Institute of Molecular Health Sciences, Swiss Federal Institute of Technology, Zurich, Switzerland.

Tissue-resident macrophages play a crucial role in maintaining homeostasis. Macrophage progenitors migrate to tissues perinatally, where environmental cues shape their identity and unique functions. Here, we show that the absence of PPARγ affects neonatal development and VCAM-1 expression of splenic iron-recycling red pulp macrophages (RPMs) and bone marrow erythroblastic island macrophages (EIMs). Transcriptome analysis of the few remaining Pparg-deficient RPM-like and EIM-like cells suggests that PPARγ is required for RPM and EIM identity, cell cycling, migration, and localization, but not function in mature RPMs. Notably, Spi-C, another transcription factor implicated in RPM development, was not essential for neonatal expansion of RPMs, even though the transcriptome of Spic-deficient RPMs was strongly affected and indicated a loss of identity. Similarities shared by Pparg- and Spic-deficient RPM-like cells allowed us to identify pathways that rely on both factors. PPARγ and Spi-C collaborate in inducing transcriptional changes, including VCAM-1 and integrin αD expression, which could be required for progenitor retention in the tissue, allowing access to niche-related signals that finalize differentiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1084/jem.20191314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006858PMC
May 2021

Interrogating the Small Intestine Tuft Cell-ILC2 Circuit Using In Vivo Manipulations.

Curr Protoc 2021 Mar;1(3):e77

Institute of Physiology, University of Zurich, Zurich, Switzerland.

Recent findings position tuft cells as key mediators of intestinal immunity through their production of the cytokine interleukin (IL)-25 and activation of group 2 innate lymphoid cells (ILC2s). Though tuft cells are found in numerous epithelial tissues, their phenotype and function have been best characterized in the small intestine, where robust in vivo techniques have enabled the dissection of their cellular function, ontogeny, and key signaling pathways. We describe methods for the identification, quantification, and manipulation of tuft cells, focusing on analysis of ILC2s as a readout of tuft cell function. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Ex vivo analysis of small intestinal tuft cells and ILC2 by flow cytometry Alternate Protocol: Ex vivo analysis of small intestinal tuft cells and ILC2 by flow cytometry in the context of type 2 inflammation Basic Protocol 2: Ex vivo analysis of small intestinal tuft cells by imaging of intestinal Swiss roll Basic Protocol 3: Tuft-ILC2 circuit activation by oral gavage of adult Nippostrongylus brasiliensis worms Basic Protocol 4: Circuit activation by colonization with Tritrichomonas spp. Basic Protocol 5: Circuit activation by treatment with succinate in drinking water Basic Protocol 6: Circuit activation by treatment with recombinant IL-25.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cpz1.77DOI Listing
March 2021

Cooperative Photoinduced/Brønsted Acid Catalyzed Cycloaddition of Transient Thioaldehydes and -Quinone Methides toward a Synthesis of Benzo[][1,3]oxathiines.

Org Lett 2021 Apr 18;23(7):2682-2686. Epub 2021 Mar 18.

Institut für Organische Chemie, Universität Leipzig, Johannisallee 29, 04103 Leipzig, Germany.

A cooperative, one-pot approach for the in situ generation and ensuing cycloaddition of thioaldehydes and -quinone methides transiently formed under irradiation with UV-A light and Brønsted acid catalysis, respectively, has been developed giving direct access to benzo[][1,3]oxathiines in good to excellent yields and diastereoselectivity. Both electron-rich and electron-poor thioaldehydes easily react with a broad range of -quinone methides at ambient temperature in a short reaction time to furnish a wide variety of ,-heterocycles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.1c00588DOI Listing
April 2021

Cooperative Rh/Chiral Phosphoric Acid Catalysis toward the Highly Stereoselective (3 + 3)-Cycloannulation of Carbonyl Ylides and Indolyl-2-methides.

Org Lett 2021 Apr 15;23(7):2578-2583. Epub 2021 Mar 15.

Institut für Organische Chemie, Universität Leipzig, Johannisallee 29, 04103 Leipzig, Germany.

A stereoselective (3 + 3)-cycloannulation of in situ generated carbonyl ylides with indolyl-2-methides has been developed furnishing oxa-bridged azepino[1,2-]indoles within one synthetic step. This process is enabled by cooperative rhodium and chiral phosphoric acid catalysis to produce both transient intermediates in separate catalytic cycles. The products comprising three stereogenic centers were obtained with good stereoselectivity and yields and display valuable heterocyclic complexity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.1c00489DOI Listing
April 2021

Repeatability of the Individual Response to the Use of Active Recovery the Day After High-Intensity Interval Training: A Double-Crossover Trial.

Int J Sports Physiol Perform 2021 Feb 19:1-9. Epub 2021 Feb 19.

Purpose: To identify whether the use of active recovery (ACT) the day after high-intensity interval training (HIIT) benefits recovery and to assess whether individual responses to ACT are repeatable.

Methods: Eleven well-trained, male intermittent-sport athletes (age: 25.5 ± 1.8 y) completed 4 HIIT sessions, each separated by a 2-week washout period. Of the 4 sessions, 2 were followed by passive recovery (PAS) and 2 by 60 minutes of moderate biking (ACT) 24 hours postexercise in the following sequences: ACT→PAS→ACT→PAS or PAS→ACT→PAS→ACT. Before and after HIIT and after 24 and 48 hours of recovery, maximal voluntary isometric strength (MVIC), countermovement jump height (CMJ), tensiomyographic markers of muscle fatigue (TMG), serum concentration of creatine kinase (CK), muscle soreness (MS), and perceived stress state (PS) were determined.

Results: A 3-way repeated-measure analysis of variance with a triple-nested random effects model revealed a significant (P < .05) fatigue-related time effect of HIIT on markers of fatigue (MVIC↓; CMJ↓; TMG↑; CK↑; MS↑; PS↑). No significant (P > .05) main effect of recovery strategy was detected. In 9 subjects, the individual results revealed inconsistent and nonrepeatable responses to ACT, while a consistent and repeatable positive or negative response to ACT was found in 2 individuals.

Conclusions: The repeated failure of ACT to limit the severity of fatigue was found both at the group level and with most individuals. However, a small percentage of athletes may be more likely to benefit repeatedly from either ACT or PAS. Therefore, the use of ACT should be individualized.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1123/ijspp.2020-0671DOI Listing
February 2021

Monitoring training and recovery responses with heart rate measures during standardized warm-up in elite badminton players.

PLoS One 2020 21;15(12):e0244412. Epub 2020 Dec 21.

Department of Training & Exercise Science, Faculty of Sport Science, Ruhr University Bochum, Bochum, Germany.

Purpose: To investigate short-term training and recovery-related effects on heart rate during a standardized submaximal running test.

Methods: Ten elite badminton players (7 females and 3 males) were monitored during a 12-week training period in preparation for the World Championships. Exercise heart rate (HRex) and perceived exertion were measured in response to a 5-min submaximal shuttle-run test during the morning session warm-up. This test was repeatedly performed on Mondays after 1-2 days of pronounced recovery ('recovered' state; reference condition) and on Fridays following 4 consecutive days of training ('strained' state). In addition, the serum concentration of creatine kinase and urea, perceived recovery-stress states, and jump performance were assessed before warm-up.

Results: Creatine kinase increased in the strained compared to the recovered state and the perceived recovery-stress ratings decreased and increased, respectively (range of average effects sizes: |d| = 0.93-2.90). The overall HRex was 173 bpm and the observed within-player variability (i.e., standard deviation as a coefficient of variation [CV]) was 1.3% (90% confidence interval: 1.2% to 1.5%). A linear reduction of -1.4% (-3.0% to 0.3%) was observed in HRex over the 12-week observational period. HRex was -1.5% lower (-2.2% to -0.9%) in the strained compared to the recovered state, and the standard deviation (as a CV) representing interindividual variability in this response was 0.7% (-0.6% to 1.2%).

Conclusions: Our findings suggest that HRex measured during a standardized warm-up can be sensitive to short-term accumulation of training load, with HRex decreasing on average in response to consecutive days of training within repeated preparatory weekly microcycles. From a practical perspective, it seems advisable to determine intra-individual recovery-strain responses by repeated testing, as HRex responses may vary substantially between and within players.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244412PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751974PMC
March 2021

Brønsted-Acid-Catalyzed (3+2)-Cycloannulation of In-Situ-Generated 3-Methide-3-pyrroles: Asymmetric Synthesis of Cyclopenta[]pyrroles.

Org Lett 2020 Nov 11;22(22):9065-9070. Epub 2020 Nov 11.

Institut für Organische Chemie, Universität Leipzig, Johannisallee 29, 04103 Leipzig, Germany.

An organocatalytic, highly enantioselective addition of cyclic enamides to in-situ-generated 3-methide-3-pyrroles with subsequent cyclization and elimination has been developed. This protocol represents a novel and straightforward route toward polycyclic cyclopenta[]pyrroles with high yields and excellent enantioselectivity. Central to the success is the formation of a chiral, hydrogen-bonded 3-methide-3-pyrrole upon phosphoric-acid-catalyzed dehydration of the starting 1-pyrrol-3-yl carbinol that reacts with the enamide in a stepwise cycloannulation process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.0c03452DOI Listing
November 2020

Plasma citrulline correlates with basolateral amino acid transporter LAT4 expression in human small intestine.

Clin Nutr 2020 Oct 9. Epub 2020 Oct 9.

Institute of Physiology, University of Zurich, Switzerland; Department of Pediatric Surgery, University Children's Hospital of Basel, Switzerland. Electronic address:

Background & Aims: Plasma citrulline, a non-protein amino acid, is a biochemical marker of small intestine enterocyte mass in humans. Indeed, citrulline is highly correlated with residual bowel length in patients with short bowel syndrome. It is known to be synthesised in epithelial cells of the small intestine from other amino acids (precursors). Citrulline is then released into systemic circulation and interconverted into arginine in kidneys. If plasma citrulline concentration depends on abundance of intestinal amino acid transporters is not known. The aim of the present study was to explore whether plasma citrulline concentration correlates with the expression of intestinal amino acid transporters. Furthermore, we assessed if arginine in urine correlates with plasma citrulline.

Methods: Duodenal samples, blood plasma and urine were collected from 43 subjects undergoing routine gastroduodenoscopy. mRNA expression of seven basolateral membrane amino acid transporters/transporter subunits were assessed by real-time PCR. Plasma and urine amino acid concentrations of citrulline, its precursors and other amino acids were analysed using High Performance Liquid Chromatography measurements. Amino acid transporter mRNA expression was correlated with blood plasma and urine levels of citrulline and its precursors using Spearman's rank correlation. Likewise, urine arginine was correlated with plasma citrulline.

Results: Plasma citrulline correlated with the mRNA expression of basolateral amino acid transporter LAT4 (Spearman's r = 0.467, p = 0.028) in small intestine. None of the other basolateral membrane transporters/transporter subunits assessed correlated with plasma citrulline. Plasma citrulline correlated with urinary arginine, (Spearman's r = 0.419, p = 0.017), but not with urinary citrulline or other proteinogenic amino acids in the urine.

Conclusions: In this study, we showed for the first time that small intestinal basolateral LAT4 expression correlates with plasma citrulline concentration. This finding indicates that LAT4 has an important function in mediating citrulline efflux from enterocytes. Furthermore, urine arginine correlated with plasma citrulline, indicating arginine in the urine as possible additional marker for small intestine enterocyte mass. Finally, basolateral LAT4 expression along the human small intestine was shown for the first time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clnu.2020.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546687PMC
October 2020

IgA Triggers Cell Death of Neutrophils When Primed by Inflammatory Mediators.

J Immunol 2020 11 2;205(10):2640-2648. Epub 2020 Oct 2.

Institute of Pharmacology, University of Bern, 3010 Bern, Switzerland;

IVIG preparations consisting of pooled IgG are increasingly used for the treatment of autoimmune diseases. IVIG is known to regulate the viability of immune cells, including neutrophils. We report that plasma-derived IgA efficiently triggers death of neutrophils primed by cytokines or TLR agonists. IgA-mediated programmed neutrophil death was PI3K-, p38 MAPK-, and JNK-dependent and evoked anti-inflammatory cytokines in macrophage cocultures. Neutrophils from patients with acute Crohn's disease, rheumatoid arthritis, or sepsis were susceptible to both IgA- and IVIG-mediated death. In contrast to IVIG, IgA did not promote cell death of quiescent neutrophils. Our findings suggest that plasma-derived IgA might provide a therapeutic option for the treatment of neutrophil-associated inflammatory disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.1900883DOI Listing
November 2020

Short Synthesis of Alkaloid (-)-205B.

J Org Chem 2020 10 17;85(19):12724-12730. Epub 2020 Sep 17.

Institut für Organische Chemie, Universität Leipzig, Johannisallee 29, D-04103 Leipzig, Germany.

The alkaloid (-)-205B has in the past served as a testing ground for novel approaches in nitrogen heterocycle synthesis. We herein report a highly straightforward synthesis of (-)-205B in just six synthetic steps, making it the shortest route currently known. The central steps of our approach are a vinylogous Mukaiyama-Mannich reaction to establish the first two stereogenic centers with excellent diastereo- and enantiocontrol followed by zinc-mediated Barbier allylation to set the third chiral center with high substrate control. Upon cyclization of the Barbier product to lactam and enolate methylation, the third ring is annulated by a one-pot sequence of lactam reduction and aza-Prins cyclization to directly set the final stereogenic center with complete -stereoselectivity. As the iminium ion undergoing the aza-Prins cyclization rapidly isomerized to a planar enamine intermediate, the alkaloid was eventually obtained as a 1:1 mixture of C6 diastereomers, which were readily separated by chromatography. Yet, the target natural product was obtained isomerically pure in an overall yield of 12%, which compares favorably with all previous syntheses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.joc.0c01885DOI Listing
October 2020

Phosphoric Acid Catalyzed Formation of Hydrogen-Bonded -Quinone Methides. Enantioselective Cycloaddition with β-Dicarbonyl Compounds toward Benzannulated Oxygen Heterocycles.

J Org Chem 2020 09 26;85(18):11699-11720. Epub 2020 Aug 26.

Institut für Organische Chemie, Universität Leipzig, Johannisallee 29, 04103 Leipzig, Germany.

A full account of the Brønsted acid catalyzed, enantioselective synthesis of 4-chromenes and 1-xanthen-1-ones from -hydroxybenzyl alcohols and β-dicarbonyl compounds is provided. The central step of our strategy is the BINOL-phosphoric acid catalyzed, enantioselective cycloaddition of β-diketones, β-keto nitriles, and β-keto esters to in situ generated, hydrogen-bonded -quinone methides. Upon acid-promoted dehydration, the desired products were obtained with generally excellent yields and enantioselectivity. Detailed mechanistic studies including online-NMR and ESI-MS measurements were conducted to identify relevant synthetic intermediates. A reversible formation of a dimer from the starting alcohol and the reactive -quinone methide in an off-cycle equilibrium was observed, providing a reservoir from which the -quinone methide can be regenerated and introduced into the catalytic cycle again. Reaction progress kinetic analysis was utilized to determine kinetic profiles and rate constants of the reaction uncovering -quinone methide formation as the rate-limiting step. In combination with Hammett plots, these studies document the relationship between -quinone methide stabilization by electronic effects provided by the substituents and the reaction rate of the described process. In addition, DFT calculations reveal a concerted yet highly asynchronous [4 + 2]-cycloaddition pathway and an attractive CH-π interaction between the catalyst's Bu group and the -quinone methide as an important stereochemical control element.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.joc.0c01375DOI Listing
September 2020

Palladium-Catalyzed, Enantioselective (3 + 2)-Cycloannulation of β-Keto Esters with Alkylidene 2-Indoles toward Complex Indole-Based Heterocycles.

Org Lett 2020 Aug 17;22(15):6101-6106. Epub 2020 Jul 17.

Institut für Organische Chemie, Universität Leipzig, Johannisallee 29, D-04103 Leipzig, Germany.

A cooperative approach toward biologically important -fused polycyclic indoles with synthetically challenging tetracyclic [6-5-5-6] and [6-5-5-5] core structures has been developed. The concept is based on a highly stereoselective (3 + 2)-cycloannulation of chiral metal enolates with a reactive vinylogous iminium ion, both generated in situ via dual activation with a single chiral Pd catalyst (5 mol %). Densely functionalized pyrrolo[1,2-]indoles with three contiguous chiral centers were constructed with high stereoselectivities (>95:5 d.r. and up to >99% ee) and excellent yields (up to 99%). ESI-MS studies and additional control experiments provided a clear mechanistic picture of the cycloannulation event. The products were readily transformed into an array of valuable, indole-based, highly complex heterocycles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.0c02166DOI Listing
August 2020

Impact of Air Conditioning Systems on the Outdoor Thermal Environment during Summer in Berlin, Germany.

Int J Environ Res Public Health 2020 06 28;17(13). Epub 2020 Jun 28.

Geography Department, Humboldt-Universität zu Berlin, 10117 Berlin, Germany.

This study investigates the effect of anthropogenic heat emissions from air conditioning systems (AC) on air temperature and AC energy consumption in Berlin, Germany. We conduct simulations applying the model system CCLM/DCEP-BEM, a coupled system of the mesoscale climate model COSMO-CLM (CCLM) and the urban Double Canyon Effect Parameterization scheme with a building energy model (DCEP-BEM), for a summer period of 2018. The DCEP-BEM model is designed to explicitly compute the anthropogenic heat emissions from urban buildings and the heat flux transfer between buildings and the atmosphere. We investigate two locations where the AC outdoor units are installed: either on the wall of a building (VerAC) or on the rooftop of a building (HorAC). AC waste heat emissions considerably increase the near-surface air temperature. Compared to a reference scenario without AC systems, the VerAC scenario with a target indoor temperature of 22 ∘ C results in a temperature increase of up to 0 . 6 K . The increase is more pronounced during the night and for urban areas. The effect of HorAC on air temperature is overall smaller than in VerAC. With the target indoor temperature of 22 ∘ C , an urban site's daily average AC energy consumption per floor area of a room is 9 . 1 W / m 2 , which is 35% more than that of a suburban site. This energy-saving results from the urban heat island effect and different building parameters between both sits. The maximum AC energy consumption occurs in the afternoon. When the target indoor temperature rises, the AC energy consumption decreases at a rate of about 16% per 2 K change in indoor temperature. The nighttime near-surface temperature in VerAC scenarios shows a declining trend ( 0 . 06 K per 2 K change) with increasing target indoor temperature. This feature is not obvious in HorAC scenarios which further confirms that HorAC has a smaller impact on near-surface air temperature.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph17134645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369797PMC
June 2020

Enhanced Pro-apoptotic Effects of Fe(II)-Modified IVIG on Human Neutrophils.

Front Immunol 2020 19;11:973. Epub 2020 May 19.

Institute of Pharmacology, University of Bern, Bern, Switzerland.

Mild modification of intravenous immunoglobulin (IVIG) has been reported to result in enhanced polyspecificity and leveraged therapeutic effects in animal models of inflammation. Here, we observed that IVIG modification by ferrous ions, heme or low pH exposure, shifted the repertoires of specificities in different directions. Ferrous ions exposed Fe(II)-IVIG, but not heme or low pH exposed IVIG, showed increased pro-apoptotic effects on neutrophil granulocytes that relied on a FAS-dependent mechanism. These effects were also observed in human neutrophils primed by inflammatory mediators or rheumatoid arthritis joint fluid , or patient neutrophils from acute Crohn's disease. These observations indicate that IVIG-mediated effects on cells can be enhanced by IVIG modification, yet specific modification conditions may be required to target specific molecular pathways and eventually to enhance the therapeutic potential.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2020.00973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248553PMC
March 2021

Reduced tract length of the medial forebrain bundle and the anterior thalamic radiation in bipolar disorder with melancholic depression.

J Affect Disord 2020 09 21;274:8-14. Epub 2020 May 21.

University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland; Translational Research Center, University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland. Electronic address:

Background: The supero-lateral medial forebrain bundle (slMFB) and the anterior thalamic radiation (ATR) play a core role in reward anticipation and motivational processes. In this study, the slMFB and the ATR were investigated in a group of depressed bipolar disorder (BD) and in healthy controls (HC) using tract length as a measure of fibre geometry and fractional anisotropy (FA) as a measure of white matter microstructure. We hypothesized reduced tract length and FA of the slMFB and the ATR in BD. We expect alterations to be driven by the melancholic subtype.

Methods: Nineteen depressed patients with BD and 19 HC matched for age and gender underwent diffusion-weighted magnetic resonance imaging (MRI) scans. Diffusion tensor imaging (DTI) based tractography was used to reconstruct bilateral slMFB and ATR. Mean tract length and FA were computed for the slMFB and the ATR. Mixed-model ANCOVAs and post-hoc ANCOVAs, controlling for age and intracranial volume, were used to compare tract length and FA of bilateral slMFB and ATR between HC and BD and between HC and subgroups with melancholic and non-melancholic symptoms.

Results: In BD we found a significantly shortened tract length of the right slMFB and ATR in BD compared to HC. Subgroup analyses showed that these findings were driven by the melancholic subgroup. Mean-FA did not differ between HC and BD.

Limitations: Sample size CONCLUSIONS: Tract length of the right slMFB and the right ATR is reduced in BD. Those changes of fibre geometry are driven by the melancholic subtype.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jad.2020.05.008DOI Listing
September 2020

Internet-based digital video atlas of sonographic findings for clinical and educational purposes.

J Ultrason 2020 31;20(80):e24-e28. Epub 2020 Mar 31.

Bundeswehrkrankenhaus Berlin , Germany.

A professional and valid ultrasound examination is dependent upon an extensively experienced examiner. Recognition and classification of rare or minimally distinctive findings are a particular source of uncertainty on the part of the examiner. By creating an online-based video database of sonographic findings, we tried to share our own experience for clinical and educational purposes. More than a thousand video clips of documented ultrasound findings were anonymized and cut to a practicable length of between 10 and 25 sec. The findings were critically evaluated and labeled with a primary diagnosis. They were also classified by organ systems and various keywords. An online portal that currently contains more than 1,000 video sequences of typical, non-typical, especially vivid or rare ultrasound findings has been created. The portal is free of charge and accessible for any Internet-capable PC. It is also optimized for use on mobile devices (smartphones, iPads, etc.). Search and location of relevant findings is performed using keywords or a diagnosis-based search function. The Internet address is www.sono.gallery. The video portal is a fast and universally accessible non-commercial platform. Its moving images can be used as an aid in resolving problematic differential diagnoses of typical, non-typical or especially rare ultrasound findings or in verifying one's own findings.

A professional and valid ultrasound examination is dependent upon an extensively experienced examiner. Recognition and classification of rare or minimally distinctive findings are a particular source of uncertainty on the part of the examiner. By creating an online-based video database of sonographic findings, we tried to share our own experience for clinical and educational purposes. More than a thousand video clips of documented ultrasound findings were anonymized and cut to a practicable length of between 10 and 25 sec. The findings were critically evaluated and labeled with a primary diagnosis. They were also classified by organ systems and various keywords. An online portal that currently contains more than 1,000 video sequences of typical, non-typical, especially vivid or rare ultrasound findings has been created. The portal is free of charge and accessible for any Internet-capable PC. It is also optimized for use on mobile devices (smartphones, iPads, etc.). Search and location of relevant findings is performed using keywords or a diagnosis-based search function. The Internet address is www.sono.gallery. The video portal is a fast and universally accessible non-commercial platform. Its moving images can be used as an aid in resolving problematic differential diagnoses of typical, non-typical or especially rare ultrasound findings or in verifying one’s own findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15557/JoU.2020.0005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266063PMC
March 2020

Unravelling the configuration of transient ortho-quinone methides by combining microfluidics with gas phase vibrational spectroscopy.

Phys Chem Chem Phys 2020 Feb;22(8):4610-4616

Institut für Analytische Chemie, Universität Leipzig, Linnéstraße 3, D-04103 Leipzig, Germany.

The alkylidene double bond configuration of transient ortho-quinone methides (o-QMs) is studied by cryogenic ion trap vibrational spectroscopy. To this end, o-QMs are formed from ortho-hydroxy benzhydryl alcohols in a Brønsted acid mediated dehydration reaction on a microfluidic chip reactor and the E/Z isomer ratio is determined by comparing the measured gas phase mid-infrared fingerprints with the predicted harmonic spectra from density functional theory calculations. Control over the stereochemistry is achieved by exploiting steric repulsion interactions between the substituents adjacent to the formal double bond of the o-QMs. Attempts to manipulate the ratio of the E- and Z-isomers by varying the reaction conditions were unsuccessful. This observation suggests a low isomerization barrier and hence shorter equilibration times with respect to the on-chip residence time. The fluxional character of the formal double bond is confirmed in 13C-labelling experiments, which reveal a substantially red-shifted CC stretching frequency characteristic for extended, conjugated π-systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9cp06435dDOI Listing
February 2020

Tissue-specific pathways extrude activated ILC2s to disseminate type 2 immunity.

J Exp Med 2020 04;217(4)

Department of Medicine, University of California, San Francisco, San Francisco, CA.

Group 2 innate lymphoid cells (ILC2s) are tissue-resident cells prominent at barrier sites. Although precursors are found in blood, mature ILC2s can enter the circulation after small intestinal perturbation by migratory helminths and move to distant tissues to influence the local reparative response. Using fate-mapping and methods to bypass the lung or intestinal phases of Nippostrongylus brasiliensis infection, we show that blood ILC2s comprise heterogeneous populations derived from distinct tissues that are dependent on alarmins matched to the receptor profile of the specific tissue ILC2s. Activation of local ILC2s by tissue-specific alarmins induced their proliferation, lymph node migration, and blood dissemination, thus systemically distributing type 2 cytokines. These studies uncover a possible mechanism by which local innate responses transition to systemic type 2 responses by extrusion of activated sentinel ILC2s from tissue into the circulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1084/jem.20191172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144525PMC
April 2020

Cooperative Catalysis for the Highly Diastereo- and Enantioselective [4+3]-Cycloannulation of ortho-Quinone Methides and Carbonyl Ylides.

Angew Chem Int Ed Engl 2020 03 23;59(14):5536-5540. Epub 2020 Jan 23.

Institut für Organische Chemie, Universität Leipzig, Johannisallee 29, 04103, Leipzig, Germany.

We describe herein a highly diastereo- and enantioselective [4+3]-cycloannulation of ortho-quinone methides and carbonyl ylides to furnish functionalized oxa-bridged dibenzooxacines with excellent yields and stereoselectivity in a single synthetic step. The combination of rhodium and chiral phosphoric acid catalysis working in concert to generate both transient intermediates in situ provides direct access to complex bicyclic products with two quaternary and one tertiary stereogenic centers. The products may be further functionalized into valuable and enantiomerically highly enriched building blocks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.201913603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155103PMC
March 2020

Fetal monocytes possess increased metabolic capacity and replace primitive macrophages in tissue macrophage development.

EMBO J 2020 02 2;39(3):e103205. Epub 2020 Jan 2.

Department of Biology, Institute of Molecular Health Sciences, ETH Zürich, Zürich, Switzerland.

Tissue-resident macrophages (MΦ ) originate from at least two distinct waves of erythro-myeloid progenitors (EMP) arising in the yolk sac (YS) at E7.5 and E8.5 with the latter going through a liver monocyte intermediate. The relative potential of these precursors in determining development and functional capacity of MΦ remains unclear. Here, we studied development of alveolar macrophages (AM) after single and competitive transplantation of different precursors from YS, fetal liver, and fetal lung into neonatal Csf2ra mice, which lack endogenous AM. Fetal monocytes, promoted by Myb, outcompeted primitive MΦ (pMΦ) in empty AM niches and preferentially developed to mature AM, which is associated with enhanced mitochondrial respiratory and glycolytic capacity and repression of the transcription factors c-Maf and MafB. Interestingly, AM derived from pMΦ failed to efficiently clear alveolar proteinosis and protect from fatal lung failure following influenza virus infection. Thus, our data demonstrate superior developmental and functional capacity of fetal monocytes over pMΦ in AM development and underlying mechanisms explaining replacement of pMΦ in fetal tissues.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15252/embj.2019103205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996567PMC
February 2020

Real-time EEG Feedback on Alpha Power Lateralization Leads to Behavioral Improvements in a Covert Attention Task.

Brain Topogr 2020 01 17;33(1):48-59. Epub 2019 Jul 17.

Chair for Brain-Machine Interface (CNBI), École Polytechnique Fédérale de Lausanne (EPFL), 1202, Geneva, Switzerland.

Visual attention can be spatially oriented, even in the absence of saccadic eye-movements, to facilitate the processing of incoming visual information. One behavioral proxy for this so-called covert visuospatial attention (CVSA) is the validity effect (VE): the reduction in reaction time (RT) to visual stimuli at attended locations and the increase in RT to stimuli at unattended locations. At the electrophysiological level, one correlate of CVSA is the lateralization in the occipital [Formula: see text]-band oscillations, resulting from [Formula: see text]-power increases ipsilateral and decreases contralateral to the attended hemifield. While this [Formula: see text]-band lateralization has been considerably studied using electroencephalography (EEG) or magnetoencephalography (MEG), little is known about whether it can be trained to improve CVSA behaviorally. In this cross-over sham-controlled study we used continuous real-time feedback of the occipital [Formula: see text]-lateralization to modulate behavioral and electrophysiological markers of covert attention. Fourteen subjects performed a cued CVSA task, involving fast responses to covertly attended stimuli. During real-time feedback runs, trials extended in time if subjects reached states of high [Formula: see text]-lateralization. Crucially, the ongoing [Formula: see text]-lateralization was fed back to the subject by changing the color of the attended stimulus. We hypothesized that this ability to self-monitor lapses in CVSA and thus being able to refocus attention accordingly would lead to improved CVSA performance during subsequent testing. We probed the effect of the intervention by evaluating the pre-post changes in the VE and the [Formula: see text]-lateralization. Behaviorally, results showed a significant interaction between feedback (experimental-sham) and time (pre-post) for the validity effect, with an increase in performance only for the experimental condition. We did not find corresponding pre-post changes in the [Formula: see text]-lateralization. Our findings suggest that EEG-based real-time feedback is a promising tool to enhance the level of covert visuospatial attention, especially with respect to behavioral changes. This opens up the exploration of applications of the proposed training method for the cognitive rehabilitation of attentional disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10548-019-00725-9DOI Listing
January 2020

Copeptin - a biomarker of short-term mortality risk (7 days) in patients with end-stage liver disease.

Clin Chem Lab Med 2019 Nov;57(12):1897-1905

Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany.

Background For many patients with end-stage liver disease, liver transplantation represents the only curative therapy. Transplant recipients are scored and ranked using the model for end-stage liver disease (MELD/MELD-Na). Circulatory impairment is known to deteriorate outcomes; however, it is not incorporated into the current allocation system's score. The aim of our study is to analyze the predictive value of copeptin as a biomarker of circulatory impairment and increased short-term mortality risk in patients with end-stage liver disease. Methods We conducted a retrospective observational study of 615 patients with end-stage liver disease. Patients were recruited using assessments performed during the evaluation process for liver transplantation. Copeptin values were analyzed in comparison to MELD-Na, interleukin 6 (IL-6), and C-reactive protein (CRP). Results Elevated levels of copeptin, IL-6 and CRP, as well as high MELD-Na scores, were significantly correlated with mortality. In a comparison of copeptin-tertiles, patients in group T3 (16.3 pmol/L or more) showed a significantly higher mortality risk (hazard ratio 11.2, p < 0.001). After adjusting for MELD-Na, copeptin remains an independent predictor of mortality. It shows its greatest prognostic strength in short-term mortality, where it performs comparable to MELD-Na (AUROC for 7 day-mortality, 0.941/0.939; p = 0.981) and shows an additional predictive value to MELD-Na for short-term mortality (7 days, p: 0.046; 30 days, p: 0.006). Conclusions Copeptin presents a valuable individual biomarker in detecting patients at risk for short-term mortality. Further studies should be performed to confirm our findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/cclm-2019-0023DOI Listing
November 2019

Heart Rate Variability Monitoring During Strength and High-Intensity Interval Training Overload Microcycles.

Front Physiol 2019 22;10:582. Epub 2019 May 22.

Department of Training and Exercise Science, Faculty of Sport Science, Ruhr University Bochum, Bochum, Germany.

In two independent study arms, we determine the effects of strength training (ST) and high-intensity interval training (HIIT) overload on cardiac autonomic modulation by measuring heart rate (HR) and vagal heart rate variability (HRV). In the study, 37 well-trained athletes (ST: 7 female, 12 male; HIIT: 9 female, 9 male) were subjected to orthostatic tests (HR and HRV recordings) each day during a 4-day baseline period, a 6-day overload microcycle, and a 4-day recovery period. Discipline-specific performance was assessed before and 1 and 4 days after training. Following ST overload, supine HR, and vagal HRV (Ln RMSSD) were clearly increased and decreased (small effects), respectively, and the standing recordings remained unchanged. In contrast, HIIT overload resulted in decreased HR and increased Ln RMSSD in the standing position (small effects), whereas supine recordings remained unaltered. During the recovery period, these responses were reversed (ST: small effects, HIIT: trivial to small effects). The correlations between changes in HR, vagal HRV measures, and performance were weak or inconsistent. At the group and individual levels, moderate to strong negative correlations were found between HR and Ln RMSSD when analyzing changes between testing days (ST: supine and standing position, HIIT: standing position) and individual time series, respectively. Use of rolling 2-4-day averages enabled more precise estimation of mean changes with smaller confidence intervals compared to single-day values of HR or Ln RMSSD. However, the use of averaged values displayed unclear effects for evaluating associations between HR, vagal HRV measures, and performance changes, and have the potential to be detrimental for classification of individual short-term responses. Measures of HR and Ln RMSSD during an orthostatic test could reveal different autonomic responses following ST or HIIT which may not be discovered by supine or standing measures alone. However, these autonomic changes were not consistently related to short-term changes in performance and the use of rolling averages may alter these relationships differently on group and individual level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2019.00582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538885PMC
May 2019

Tissue-Resident Group 2 Innate Lymphoid Cells Differentiate by Layered Ontogeny and In Situ Perinatal Priming.

Immunity 2019 06 22;50(6):1425-1438.e5. Epub 2019 May 22.

Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA, USA. Electronic address:

The perinatal period is a critical window for distribution of innate tissue-resident immune cells within developing organs. Despite epidemiologic evidence implicating the early-life environment in the risk for allergy, temporally controlled lineage tracing of group 2 innate lymphoid cells (ILC2s) during this period remains unstudied. Using complementary fate-mapping approaches and reporters for ILC2 activation, we show that ILC2s appeared in multiple organs during late gestation like tissue macrophages, but, unlike the latter, a majority of peripheral ILC2 pools were generated de novo during the postnatal window. This period was accompanied by systemic ILC2 priming and acquisition of tissue-specific transcriptomes. Although perinatal ILC2s were variably replaced across tissues with age, the dramatic increases in tissue ILC2s following helminth infection were mediated through local expansion independent of de novo generation by bone marrow hematopoiesis. We provide comprehensive temporally controlled fate mapping of an innate lymphocyte subset with notable nuances as compared to tissue macrophage ontogeny.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.immuni.2019.04.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6645687PMC
June 2019

Brønsted Acid-Catalyzed, Diastereo- and Enantioselective, Intramolecular Oxa-Diels-Alder Reaction of ortho-Quinone Methides and Unactivated Dienophiles.

J Org Chem 2019 06 29;84(11):7175-7188. Epub 2019 May 29.

Institute of Organic Chemistry , University of Leipzig , Johannisallee 29 , 04103 Leipzig , Germany.

A stereoselective, phosphoric acid-catalyzed synthesis of dihydrochromenochromenes has been developed using transient ortho-quinone methides ( o-QMs). Three contiguous stereogenic centers were formed with excellent yields, partially as single diastereomers and with moderate to excellent enantioselectivity. This intramolecular hetero-Diels-Alder reaction features unactivated dienophiles and o-QM precursors tethered by a simple phenoxy linker and furnishes cycloadducts with a prominent structural motif found in many natural products. Through an appropriate choice of dienophile configuration and backbone substitution either exo- or endo-stereoisomers were formed selectively with up to a 96:04 enantiomeric ratio.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.joc.9b00860DOI Listing
June 2019

Regulation of immune responses by tuft cells.

Nat Rev Immunol 2019 09;19(9):584-593

Department of Medicine, University of California-San Francisco, San Francisco, CA, USA.

Tuft cells are rare, secretory epithelial cells that generated scant immunological interest until contemporaneous reports in 2016 linked tuft cells with type 2 immunity in the small intestine. Tuft cells have the capacity to produce an unusual spectrum of biological effector molecules, including IL-25, eicosanoids implicated in allergy (such as cysteinyl leukotrienes and prostaglandin D) and the neurotransmitter acetylcholine. In most cases, the extracellular signals controlling tuft cell effector function are unknown, but signal transduction is thought to proceed via canonical, G protein-coupled receptor-dependent pathways involving components of the signalling pathway used by type II taste bud cells to sense sweet, bitter and umami compounds. Tuft cells are ideally positioned as chemosensory sentinels that can detect and relay information from diverse luminal substances via what appear to be stereotyped outputs to initiate both positive and aversive responses through populations of immune and neuronal cells. Despite recent insights, numerous questions remain regarding tuft cell lineage, diversity and effector mechanisms and how tuft cells interface with the immunological niche in the tissues where they reside.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41577-019-0176-xDOI Listing
September 2019

A spontaneous leptin receptor point mutation causes obesity and differentially affects leptin signaling in hypothalamic nuclei resulting in metabolic dysfunctions distinct from db/db mice.

Mol Metab 2019 07 25;25:131-141. Epub 2019 Apr 25.

Institute of Molecular Biomedicine, Department Biology, ETH Zürich, Switzerland. Electronic address:

Objective: Leptin (Lep) plays a crucial role in controlling food intake and energy expenditure. Defective Lep/LepRb-signaling leads to fat accumulation, massive obesity, and the development of diabetes. We serendipitously noticed spontaneous development of obesity similar to LepR-deficient (db/db) mice in offspring from a C57BL/6J breeding and transmittance of the phenotype in a Mendelian manner. Candidate gene sequencing revealed a spontaneous point mutation in the LepRb gene. We investigated leptin responsiveness, leptin receptor signaling and metabolic phenotype of this novel LepRb mutant mouse variant.

Methods: Overexpression and functional tests of the mutant LepRb in 3T3 cells. Measurement of leptin responsiveness in hypothalamic nuclei, glucose tolerance, food uptake and energy expenditure in the mutant mice.

Results: The mutation results in the exchange of a glycine for serine (G506S) and introduces an alternative splice acceptor which, when used, encodes for a protein with a 40aa deletion that is retained in the cytoplasm. LepRb signaling was abrogated in the hypothalamic ventromedial nucleus (VMN) and dorsomedial nucleus (DMN), but only partially reduced in the hypothalamic arcuate nucleus (ARC) of LepRb mice, most likely due to differential splicing in neurons located in the respective regions of the hypothalamus. Extensive metabolic characterization of these mice revealed interesting differences in the control of food intake, glucose tolerance, energy expenditure, and fat accumulation in LepRb compared with LepRb-deficient db/db mice.

Conclusions: This study provides further insight into differences of the leptin responsiveness in VMN, DMN, and ARC and its metabolic consequences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.molmet.2019.04.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601129PMC
July 2019

A Meta-Analysis of the Effects of Foam Rolling on Performance and Recovery.

Front Physiol 2019 9;10:376. Epub 2019 Apr 9.

Faculty of Sport Science, Ruhr University, Bochum, Germany.

Foam rolling is thought to improve muscular performance and flexibility as well as to alleviate muscle fatigue and soreness. For this reason, foam rolling has become a popular intervention in all kinds of sport settings used to increase the efficiency of training or competition preparation as well as to speed post-exercise recovery. The objective of this meta-analysis was to compare the effects of foam rolling applied (pre-rolling as a warm-up activity) and (post-rolling as a recovery strategy) exercise on sprint, jump, and strength performance as well as on flexibility and muscle pain outcomes and to identify whether self-massage with a foam roller or a roller massager is more effective. A comprehensive and structured literature search was performed using the PubMed, Google Scholar, PEDro, and Cochrane Library search engines. Twenty-one studies were located that met the inclusion criteria. Fourteen studies used pre-rolling, while seven studies used post-rolling. Pre-rolling resulted in a small improvement in sprint performance (+0.7%, = 0.28) and flexibility (+4.0%, = 0.34), whereas the effect on jump (-1.9%, = 0.09) and strength performance (+1.8%, = 0.12) was negligible. Post-rolling slightly attenuated exercise-induced decreases in sprint (+3.1%, = 0.34) and strength performance (+3.9 %, = 0.21). It also reduced muscle pain perception (+6.0%, = 0.47), whereas its effect on jump performance (-0.2%, = 0.06) was trivial. Of the twenty-one studies, fourteen used foam rollers, while the other seven used roller massage bars/sticks. A tendency was found for foam rollers to offer larger effects on the recovery of strength performance (+5.6%, = 0.27 vs. -0.1%, = -0.01) than roller massagers. The differences in the effects between foam rolling devices in terms of pre-rolling did not seem to be of practical relevance (overall performance: +2.7 %, = 0.11 vs. +0.4%, = 0.21; flexibility: +5.0%, = 0.32 vs. +1.6%, = 0.39). Overall, it was determined that the effects of foam rolling on performance and recovery are rather minor and partly negligible, but can be relevant in some cases (e.g., to increase sprint performance and flexibility or to reduce muscle pain sensation). Evidence seems to justify the widespread use of foam rolling as a warm-up activity rather than a recovery tool.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2019.00376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465761PMC
April 2019

Differential Recognition of Diet-Derived Neu5Gc-Neoantigens on Glycan Microarrays by Carbohydrate-Specific Pooled Human IgG and IgA Antibodies.

Bioconjug Chem 2019 05 24;30(5):1565-1574. Epub 2019 Apr 24.

The George S. Wise Faculty of Life Sciences, Department of Cell Research and Immunology , Tel Aviv University , Tel Aviv 69978 , Israel.

Sialic acids (Sias) cover vertebrate cell surface glycans. N-Acetylneuraminic acid (Neu5Ac) and its hydroxylated form N-glycolylneuraminic acid (Neu5Gc) are common Sia in mammals. Humans cannot synthesize Neu5Gc but accumulate it on cells through red-meat rich diets, generating numerous immunogenic Neu5Gc-neoantigens. Consequently, humans have diverse anti-Neu5Gc antibodies affecting xenotransplantation, cancer, atherosclerosis, and infertility. Anti-Neu5Gc antibodies circulate as IgG, IgM, and IgA isotypes; however, repertoires of the different isotypes in a large population have not been studied yet. Here, we used glycan microarrays to investigate anti-Neu5Gc IgGs and IgAs in intravenous immunoglobulin (IVIG) or pooled human IgA, respectively. Binding patterns on microarrays fabricated with Neu5Gc- and Neu5Ac-glycans, together with inhibition assays, revealed that different IVIG preparations have highly specific anti-Neu5Gc IgG reactivity with closely related repertoires, while IgAs show cross-reactivity against several Neu5Ac-glycans. Such different anti-Neu5Gc IgG/IgA repertoires in individuals could possibly mediate distinctive effects on human diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.bioconjchem.9b00273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756923PMC
May 2019

Siglec-9 Regulates an Effector Memory CD8 T-cell Subset That Congregates in the Melanoma Tumor Microenvironment.

Cancer Immunol Res 2019 05 15;7(5):707-718. Epub 2019 Apr 15.

Institute of Pharmacology, University of Bern, Bern, Switzerland.

Emerging evidence suggests an immunosuppressive role of altered tumor glycosylation due to downregulation of innate immune responses via immunoregulatory Siglecs. In contrast, human T cells, a major anticancer effector cell, only rarely express Siglecs. However, here, we report that the majority of intratumoral, but not peripheral blood, cytotoxic CD8 T cells expressed Siglec-9 in melanoma. We identified Siglec-9 CD8 T cells as a subset of effector memory cells with high functional capacity and signatures of clonal expansion. This cytotoxic T-cell subset was functionally inhibited in the presence of Siglec-9 ligands or by Siglec-9 engagement by specific antibodies. TCR signaling pathways and key effector functions (cytotoxicity, cytokine production) of CD8 T cells were suppressed by Siglec-9 engagement, which was associated with the phosphorylation of the inhibitory protein tyrosine phosphatase SHP-1, but not SHP-2. Expression of cognate Siglec-9 ligands was observed on the majority of tumor cells in primary and metastatic melanoma specimens. Targeting the tumor-restricted, glycosylation-dependent Siglec-9 axis may unleash this intratumoral T-cell subset, while confining T-cell activation to the tumor microenvironment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/2326-6066.CIR-18-0505DOI Listing
May 2019