Publications by authors named "Thomas Volz"

46 Publications

Hidradenitis Suppurativa: Where We Are and Where We Are Going.

Cells 2021 08 15;10(8). Epub 2021 Aug 15.

Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease primarily affecting apocrine gland-rich areas of the body. It is a multifactorial disease in which genetic and environmental factors play a key role. The primary defect in HS pathophysiology involves follicular occlusion of the folliculopilosebaceous unit, followed by follicular rupture and immune responses. Innate pro-inflammatory cytokines (e.g., IL-1β, and TNF-α); mediators of activated T helper (Th)1 and Th17 cells (e.g., IFN-γ, and IL-17); and effector mechanisms of neutrophilic granulocytes, macrophages, and plasma cells are involved. On the other hand, HS lesions contain anti-inflammatory mediators (e.g., IL-10) and show limited activity of Th22 cells. The inflammatory vicious circle finally results in pain, purulence, tissue destruction, and scarring. HS pathogenesis is still enigmatic, and a valid animal model for HS is currently not available. All these aspects represent a challenge for the development of therapeutic approaches, which are urgently needed for this debilitating disease. Available treatments are limited, mostly off-label, and surgical interventions are often required to achieve remission. In this paper, we provide an overview of the current knowledge surrounding HS, including the diagnosis, pathogenesis, treatments, and existing translational studies.
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http://dx.doi.org/10.3390/cells10082094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392140PMC
August 2021

Exciton-Exciton Interaction beyond the Hydrogenic Picture in a MoSe_{2} Monolayer in the Strong Light-Matter Coupling Regime.

Phys Rev Lett 2021 Apr;126(16):167401

Univ. Grenoble Alpes, CNRS, Grenoble INP, Institut Néel, 38000 Grenoble, France.

In transition metal dichalcogenides' layers of atomic-scale thickness, the electron-hole Coulomb interaction potential is strongly influenced by the sharp discontinuity of the dielectric function across the layer plane. This feature results in peculiar nonhydrogenic excitonic states in which exciton-mediated optical nonlinearities are predicted to be enhanced compared to their hydrogenic counterparts. To demonstrate this enhancement, we perform optical transmission spectroscopy of a MoSe_{2} monolayer placed in the strong coupling regime with the mode of an optical microcavity and analyze the results quantitatively with a nonlinear input-output theory. We find an enhancement of both the exciton-exciton interaction and of the excitonic fermionic saturation with respect to realistic values expected in the hydrogenic picture. Such results demonstrate that unconventional excitons in MoSe_{2} are highly favorable for the implementation of large exciton-mediated optical nonlinearities, potentially working up to room temperature.
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http://dx.doi.org/10.1103/PhysRevLett.126.167401DOI Listing
April 2021

Rescue of STAT3 Function in Hyper-IgE Syndrome Using Adenine Base Editing.

CRISPR J 2021 04;4(2):178-190

Translational Immunology in Environmental Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany; Technical University of Munich, Munich, Germany.

STAT3-hyper IgE syndrome (STAT3-HIES) is a primary immunodeficiency presenting with destructive lung disease along with other symptoms. CRISPR-Cas9-mediated adenine base editors (ABEs) have the potential to correct one of the most common STAT3-HIES causing heterozygous mutations (c.1144C>T/p.R382W). As a proof-of-concept, we successfully applied ABEs to correct p.R382W in patient fibroblasts and induced pluripotent stem cells (iPSCs). Treated primary STAT3-HIES patient fibroblasts showed a correction efficiency of 29% ± 7% without detectable off-target effects evaluated through whole-genome and high-throughput sequencing. Compared with untreated patient fibroblasts, corrected single-cell clones showed functional rescue of STAT3 signaling with significantly increased STAT3 DNA-binding activity and target gene expression of and . Patient-derived iPSCs were corrected with an efficiency of 30% ± 6% and differentiated to alveolar organoids showing preserved plasticity in treated cells. In conclusion, our results are supportive for ABE-based gene correction as a potential causative treatment of STAT3-HIES.
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http://dx.doi.org/10.1089/crispr.2020.0111DOI Listing
April 2021

Rekonstruktion der Augenbraue unter Erhalt ihrer Länge mittels modifizierter O-T-Plastik mit horizontaler Teilung der Braue.

J Dtsch Dermatol Ges 2021 Apr;19(4):631-634

Dermatologische Klinik, Universitätsspital Basel, Basel, Schweiz.

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http://dx.doi.org/10.1111/ddg.14421_gDOI Listing
April 2021

Connexin43 gap junction drives fascia mobilization and repair of deep skin wounds.

Matrix Biol 2021 03 27;97:58-71. Epub 2021 Jan 27.

Helmholtz Zentrum München, Institute of Lung Biology and Disease, Comprehensive Pneumology Center, Munich, Germany; Helmholtz Zentrum München, Institute of Regenerative Biology and Medicine, Munich, Germany. Electronic address:

Deep and voluminous skin wounds are repaired with scars, by mobilization of fibroblasts and extracellular matrix from fascia, deep below the skin. The molecular trigger of this novel repair mechanism is incompletely understood. Here we reveal that the gap junction alpha-1 protein (Connexin43, Cx43) is the key to patch repair of deep wounds. By combining full-thickness wound models with fibroblast lineage specific transgenic lines, we show Cx43 expression is substantially upregulated in specialized fibroblasts of the fascia deep beneath the skin that are responsible for scar formation. Using live imaging of fascia fibroblasts and fate tracing of the fascia extracellular matrix we show that Cx43 inhibition disrupts calcium oscillations in cultured fibroblasts and that this inhibits collective migration of fascia EPFs necessary to mobilize fascia matrix into open wounds. Cell-cell communication through Cx43 thus mediates matrix movement and scar formation, and is necessary for patch repair of voluminous wounds. These mechanistic findings have broad clinical implications toward treating fibrosis, aggravated scarring and impaired wound healing.
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http://dx.doi.org/10.1016/j.matbio.2021.01.005DOI Listing
March 2021

Reconstruction of the eyebrow, preserving its length with a modified O-to-T plasty and horizontal division of the eyebrow.

J Dtsch Dermatol Ges 2021 04 19;19(4):633-636. Epub 2021 Jan 19.

Dermatologische Klinik, Universitätsspital Basel, Basel, Schweiz.

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http://dx.doi.org/10.1111/ddg.14421DOI Listing
April 2021

Geometric Pathway to Scalable Quantum Sensing.

Phys Rev Lett 2020 Nov;125(19):190403

Center for Engineered Quantum Systems, Department of Physics and Astronomy, Macquarie University, North Ryde, 2109 New South Wales, Australia.

Entangled resources enable quantum sensing that achieves Heisenberg scaling, a quadratic improvement on the standard quantum limit, but preparing large N spin entangled states is challenging in the presence of decoherence. We present a quantum control strategy using highly nonlinear geometric phase gates which can be used for generic state or unitary synthesis on the Dicke subspace with O(N) or O(N^{2}) gates, respectively. The method uses a dispersive coupling of the spins to a common bosonic mode and does not require addressability, special detunings, or interactions between the spins. By using amplitude amplification our control sequence for preparing states ideal for metrology can be significantly simplified to O(N^{5/4}) geometric phase gates with action angles O(1/N) that are more robust to mode decay. The geometrically closed path of the control operations ensures the gates are insensitive to the initial state of the mode and the sequence has built-in dynamical decoupling providing resilience to dephasing errors.
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http://dx.doi.org/10.1103/PhysRevLett.125.190403DOI Listing
November 2020

Injury triggers fascia fibroblast collective cell migration to drive scar formation through N-cadherin.

Nat Commun 2020 11 6;11(1):5653. Epub 2020 Nov 6.

Helmholtz Zentrum München, Institute of Lung Biology and Disease, Group Regenerative Biology and Medicine, Munich, Germany.

Scars are more severe when the subcutaneous fascia beneath the dermis is injured upon surgical or traumatic wounding. Here, we present a detailed analysis of fascia cell mobilisation by using deep tissue intravital live imaging of acute surgical wounds, fibroblast lineage-specific transgenic mice, and skin-fascia explants (scar-like tissue in a dish - SCAD). We observe that injury triggers a swarming-like collective cell migration of fascia fibroblasts that progressively contracts the skin and form scars. Swarming is exclusive to fascia fibroblasts, and requires the upregulation of N-cadherin. Both swarming and N-cadherin expression are absent from fibroblasts in the upper skin layers and the oral mucosa, tissues that repair wounds with minimal scar. Impeding N-cadherin binding inhibits swarming and skin contraction, and leads to reduced scarring in SCADs and in animals. Fibroblast swarming and N-cadherin thus provide therapeutic avenues to curtail fascia mobilisation and pathological fibrotic responses across a range of medical settings.
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http://dx.doi.org/10.1038/s41467-020-19425-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648088PMC
November 2020

Temporär gestielte nasolabiale Schwenklappenplastik mit Flügeln zur Rekonstruktion kombinierter Nasenspitzen-Columella-Defekte.

J Dtsch Dermatol Ges 2020 Jun;18(6):644-647

Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein, Fakultät für Medizin, Technische Universität München, Deutschland.

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http://dx.doi.org/10.1111/ddg.14111_gDOI Listing
June 2020

Two-stage pedicled interpolation flap with wings for reconstruction of combined nasal tip/columella defects.

J Dtsch Dermatol Ges 2020 Jun 24;18(6):644-647. Epub 2020 May 24.

Department of Dermatology and Allergology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.

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http://dx.doi.org/10.1111/ddg.14111DOI Listing
June 2020

Characterization of optofluidic devices for the sorting of sub-micrometer particles.

Appl Opt 2020 Jan;59(2):271-276

In this work, we investigate methods of fabricating a device for the optical actuation of nanoparticles. To create the microfluidic channel, we pursued three fabrication methods: SU-8 to molded polydimethylsiloxane soft lithography, laser etching of glass, and deep reactive ion etching of fused silica. We measured the surface roughness of the etched sidewalls, and the laser power transmission through each device. We then measured the radiation pressure on 0.5-µm particles in the best-performing fabricated device (etched fused silica) and in a square glass capillary.
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http://dx.doi.org/10.1364/AO.59.000271DOI Listing
January 2020

Patch repair of deep wounds by mobilized fascia.

Nature 2019 12 27;576(7786):287-292. Epub 2019 Nov 27.

Group Regenerative Biology and Medicine, Institute of Lung Biology and Disease, Helmholtz Zentrum München, Munich, Germany.

Mammals form scars to quickly seal wounds and ensure survival by an incompletely understood mechanism. Here we show that skin scars originate from prefabricated matrix in the subcutaneous fascia. Fate mapping and live imaging revealed that fascia fibroblasts rise to the skin surface after wounding, dragging their surrounding extracellular jelly-like matrix, including embedded blood vessels, macrophages and peripheral nerves, to form the provisional matrix. Genetic ablation of fascia fibroblasts prevented matrix from homing into wounds and resulted in defective scars, whereas placing an impermeable film beneath the skin-preventing fascia fibroblasts from migrating upwards-led to chronic open wounds. Thus, fascia contains a specialized prefabricated kit of sentry fibroblasts, embedded within a movable sealant, that preassemble together diverse cell types and matrix components needed to heal wounds. Our findings suggest that chronic and excessive skin wounds may be attributed to the mobility of the fascia matrix.
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http://dx.doi.org/10.1038/s41586-019-1794-yDOI Listing
December 2019

Targeting tumor-resident mast cells for effective anti-melanoma immune responses.

JCI Insight 2019 10 3;4(19). Epub 2019 Oct 3.

Department of Dermatology and Allergy, School of Medicine, Technical University of Munich, Munich, Germany.

Immune checkpoint blockade has revolutionized cancer treatment. Patients developing immune mediated adverse events, such as colitis, appear to particularly benefit from immune checkpoint inhibition. Yet, the contributing mechanisms are largely unknown. We identified a systemic LPS signature in melanoma patients with colitis following anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) checkpoint inhibitor treatment and hypothesized that intestinal microbiota-derived LPS contributes to therapeutic efficacy. Because activation of immune cells within the tumor microenvironment is considered most promising to effectively control cancer, we analyzed human and murine melanoma for known sentinels of LPS. We identified mast cells (MCs) accumulating in and around melanomas and showed that effective melanoma immune control was dependent on LPS-activated MCs recruiting tumor-infiltrating effector T cells by secretion of CXCL10. Importantly, CXCL10 was also upregulated in human melanomas with immune regression and in patients with colitis induced by anti-CTLA-4 antibody. Furthermore, we demonstrate that CXCL10 upregulation and an MC signature at the site of melanomas are biomarkers for better patient survival. These findings provide conclusive evidence for a "Trojan horse treatment strategy" in which the plasticity of cancer-resident immune cells, such as MCs, is used as a target to boost tumor immune defense.
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http://dx.doi.org/10.1172/jci.insight.125057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6795496PMC
October 2019

[Chronic wounds].

MMW Fortschr Med 2019 03;161(5):48-56

Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein, Technische Universität München, Biedersteiner Str. 29, D-80802, München, Deutschland.

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http://dx.doi.org/10.1007/s15006-019-0006-xDOI Listing
March 2019

[Acute wounds].

MMW Fortschr Med 2019 03;161(4):46-53

Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein, Technische Universität München, Biedersteiner Str. 29, D-80802, München, Deutschland.

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http://dx.doi.org/10.1007/s15006-019-0005-yDOI Listing
March 2019

Drug-induced Linear IgA Bullous Dermatosis: A Case Report and Review of the Literature.

Acta Derm Venereol 2019 May;99(6):508-515

Department of Dermatology and Allergology, Technical University Munich, DE-80802 Munich, Germany.

Linear IgA bullous dermatosis (LABD) is a rare subepidermal autoimmune blistering disease characterized by linear deposition of IgA along the basement membrane zone. Although most reported cases are idiopathic, there is a subset of patients with drug-induced LABD. Various drugs have been associated with the drug-induced form of the disease. This paper reviews the literature on drugs reported to elicit linear IgA dermatosis and its specific clinical presentation. In addition, a case report of a 77-year-old male patient with linear IgA dermatosis induced by vancomycin is described. The aim of this paper is to emphasize the need to include this differential diagnosis in cases of suspected adverse drug reactions, as well as to highlight the role of drugs in LABD.
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http://dx.doi.org/10.2340/00015555-3154DOI Listing
May 2019

Emergence of quantum correlations from interacting fibre-cavity polaritons.

Nat Mater 2019 03 18;18(3):213-218. Epub 2019 Feb 18.

Department of Physics and Astronomy, Macquarie University, Sydney, New South Wales, Australia.

Over the past decade, exciton-polaritons in semiconductor microcavities have revealed themselves as one of the richest realizations of a light-based quantum fluid, subject to fascinating new physics and potential applications. For instance, in the regime of large two-body interactions, polaritons can be used to manipulate the quantum properties of a light field. In this work, we report on the emergence of quantum correlations in laser light transmitted through a fibre-cavity polariton system. We observe a dispersive shape of the autocorrelation function around the polariton resonance that indicates the onset of this regime. The weak amplitude of these correlations indicates a state that still remains far from a low-photon-number state. Nonetheless, given the underlying physical mechanism, our work opens up the prospect of eventually using polaritons to turn laser light into single photons.
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http://dx.doi.org/10.1038/s41563-019-0281-zDOI Listing
March 2019

Combination of Surgery and Nd:YAG Laser Therapy for Recalcitrant Viral Warts: A Successful Therapeutic Approach for Immunosuppressed Patients.

Acta Derm Venereol 2019 Mar;99(3):349-350

Department of Dermatology and Allergology, Klinikum rechts der Isar, Technical University of Munich, 80802 Munich, Germany.

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http://dx.doi.org/10.2340/00015555-3092DOI Listing
March 2019

Basistherapie bei atopischer Dermatitis - Neues und Bewährtes.

J Dtsch Dermatol Ges 2018 Aug;16(8):976-980

Klinik und Poliklinik für Dermatologie und Allergologie des Klinikums rechts der Isar der Technischen Universität München.

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http://dx.doi.org/10.1111/ddg.13594_gDOI Listing
August 2018

Basic skin care in atopic dermatitis - new and established treatment options.

J Dtsch Dermatol Ges 2018 Aug 11;16(8):976-979. Epub 2018 Jul 11.

Department of Dermatology and Allergology, University Medical Center, Technical University of Munich, Munich, Germany.

Basic skin care (basic therapy) is a mainstay in the treatment of atopic dermatitis, irrespective of disease severity and current disease activity. Consistent application of basic skin care plays a key role in restoring skin barrier function and reducing xerosis as well as pruritus. Moreover, it has been shown that concurrent basic therapy has steroid-sparing effects in acute disease flares. In long-term atopic dermatitis management, the use of basic skin care is associated with prolonged recurrence-free intervals. Recent studies have also demonstrated that early initiation of basic skin therapy has protective effects in infants at risk of developing atopic dermatitis. The present review addresses these topics with a focus on established treatments and new developments.
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http://dx.doi.org/10.1111/ddg.13594DOI Listing
August 2018

Induction of IL-10-balanced immune profiles following exposure to LTA from Staphylococcus epidermidis.

Exp Dermatol 2018 04;27(4):318-326

Department of Dermatology and Allergology, Technical University Munich, Munich, Germany.

Staphylococcus epidermidis colonises human skin without apparent inflammation, but a dominance of S. epidermidis and S. aureus is characteristic of cutaneous microbial dysbiosis in atopic dermatitis (AD). While S. aureus can trigger AD, the role of S. epidermidis is less understood. We characterised consequences of innate immune sensing of lipoteichoic acid (LTA) preparations derived from S. epidermidis (epi-LTA) or S. aureus (aureus-LTA). Therefore, dendritic cell (DC) activation and consecutive priming of antigen-specific T cells following exposure of DC to epi-LTA or aureus-LTA were investigated. Mimicking acute AD, exposure of DC to IL-4 and LTAs was analysed. Exposure to epi-LTA or aureus-LTA activated human immune cells and murine dendritic cells (DCs) via TLR2/MyD88, however, resulting in divergent immune profiles. Differences between LTAs were significant for IL-6, IL-12p40 and IL-12p70 but not for IL-10, which was best reflected by the IL-12p70-to-IL-10 ratio being IL-10-balanced for epi-LTA but pro-inflammatory for aureus-LTA. LTA-exposed DCs activated CD4+ T cells; however, while T-cell-derived IL-10 was equivalent between LTAs, IFN-γ and IL-17 were significantly higher for aureus-LTA. Mimicking acute AD by exposing DCs to IL-4 and LTAs revealed that IL-4 significantly and uniformly suppressed epi-LTA-induced cytokine production, keeping the IL-12p70-to-IL-10 ratio balanced. In contrast, exposure of DCs to aureus-LTA and IL-4 enhanced IL-12p70 but suppressed IL-10 levels, further unbalancing the IL-12p70-to-IL-10 ratio. These data demonstrate opposing immune consequences following exposure to staphylococcal LTAs. Epi-LTA induced IL-10-balanced, aureus-LTA pro-inflammatory immune profiles.
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http://dx.doi.org/10.1111/exd.13540DOI Listing
April 2018

Room-temperature spontaneous superradiance from single diamond nanocrystals.

Nat Commun 2017 10 31;8(1):1205. Epub 2017 Oct 31.

Department of Physics & Astronomy, Macquarie University, NSW, 2109, Australia.

Superradiance (SR) is a cooperative phenomenon which occurs when an ensemble of quantum emitters couples collectively to a mode of the electromagnetic field as a single, massive dipole that radiates photons at an enhanced rate. Previous studies on solid-state systems either reported SR from sizeable crystals with at least one spatial dimension much larger than the wavelength of the light and/or only close to liquid-helium temperatures. Here, we report the observation of room-temperature superradiance from single, highly luminescent diamond nanocrystals with spatial dimensions much smaller than the wavelength of light, and each containing a large number (~ 10) of embedded nitrogen-vacancy (NV) centres. The results pave the way towards a systematic study of SR in a well-controlled, solid-state quantum system at room temperature.
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http://dx.doi.org/10.1038/s41467-017-01397-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663960PMC
October 2017

Successful Treatment of Severe Recalcitrant Hidradenitis Suppurativa with the Interleukin-17A Antibody Secukinumab.

Acta Derm Venereol 2018 01;98(1):151-152

Department of Dermatology and Allergology, Technical University Munich, Munich, Germany.

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http://dx.doi.org/10.2340/00015555-2794DOI Listing
January 2018

Imaging of fatty tumors: appearance of subcutaneous lipomas in optoacoustic images.

J Biophotonics 2017 Aug 9;10(8):983-989. Epub 2017 May 9.

Institute for Biological and Medical Imaging, Technische Universität München and Helmholtz Zentrum München, Ingoldstädter Landstraße 1, D-, 85764, Neuherberg, Germany.

A wide variety of subcutaneous soft-tissue masses may be seen in clinical practice. Clinical examination based on palpation alone is often insufficient to identify the nature and exact origin of the mass, in which case imaging is necessary. We used handheld multispectral optoacoustic imaging technology (MSOT) in a proof-of-principle study to image superficial fatty tumors and compare the images with diagnostic ultrasound. Fatty tumors were clearly visualized by MSOT and exhibited a spectral signature which differed from normal fatty tissue or muscle tissue. Our findings further indicated that MSOT offers highly complementary contrast to sonography. Based on the performance achieved, we foresee a promising role for MSOT in the diagnosis and evaluation of subcutaneous soft-tissue masses. Picture: Pseudo-color representation of a cross-sectional multi-spectral optoacoustic slice through a subcutaneous lipoma. Multi-spectral information is encoded in color. The lipoma can clearly be distinguished from the surrounding tissue based on its color. Scalebar 1 cm.
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http://dx.doi.org/10.1002/jbio.201600274DOI Listing
August 2017

Stimulated emission from nitrogen-vacancy centres in diamond.

Nat Commun 2017 01 27;8:14000. Epub 2017 Jan 27.

Chemical and Quantum Physics, School of Science, RMIT University, Melbourne, Victoria 3001, Australia.

Stimulated emission is the process fundamental to laser operation, thereby producing coherent photon output. Despite negatively charged nitrogen-vacancy (NV) centres being discussed as a potential laser medium since the 1980s, there have been no definitive observations of stimulated emission from ensembles of NV to date. Here we show both theoretical and experimental evidence for stimulated emission from NV using light in the phonon sidebands around 700 nm. Furthermore, we show the transition from stimulated emission to photoionization as the stimulating laser wavelength is reduced from 700 to 620 nm. While lasing at the zero-phonon line is suppressed by ionization, our results open the possibility of diamond lasers based on NV centres, tuneable over the phonon sideband. This broadens the applications of NV magnetometers from single centre nanoscale sensors to a new generation of ultra-precise ensemble laser sensors, which exploit the contrast and signal amplification of a lasing system.
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http://dx.doi.org/10.1038/ncomms14000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5290152PMC
January 2017

Staphylococcus aureus-derived lipoteichoic acid induces temporary T-cell paralysis independent of Toll-like receptor 2.

J Allergy Clin Immunol 2016 09 3;138(3):780-790.e6. Epub 2016 Mar 3.

Department of Dermatology, Eberhard Karls University, Liebermeisterstr, Tubingen, Germany; Department of Dermatology and Allergology, Technische Universität München, Munich, Germany. Electronic address:

Background: The interplay between microbes and surface organs, such as the skin, shapes a complex immune system with several checks and balances. The first-line defense is mediated by innate immune pathways leading to inflammation. In the second phase specific T cells invade the infected organ, amplifying inflammation and defense. Consecutively, termination of inflammation is crucial to avoid chronic inflammation triggered by microbes, such as in patients with atopic dermatitis.

Objective: We aimed to elucidate how the Staphylococcus aureus-derived cell-wall component lipoteichoic acid (LTA) governs the second phase of immune responses when high concentrations of LTA access T cells directly through disrupted skin.

Methods: We analyzed the direct exposure of T cells to LTA in vitro. For in vivo analyses, we used fluorescein isothiocyanate contact hypersensitivity and ovalbumin-induced dermatitis as models for TH2-mediated cutaneous inflammation.

Results: We observed that LTA potently suppressed T-lymphocyte activation in a Toll-like receptor 2-independent manner. LTA-exposed T cells did not proliferate and did not produce cytokines. Importantly, these T cells remained completely viable and were responsive to consecutive activation signals on subsequent removal of LTA. Thus LTA exposure resulted in temporary functional T-cell paralysis. In vivo experiments revealed that T-cell cytokine production and cutaneous recall responses were significantly suppressed by LTA.

Conclusion: We identified a new mechanism through which bacterial compounds directly but temporarily modulate adaptive immune responses.
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http://dx.doi.org/10.1016/j.jaci.2015.11.043DOI Listing
September 2016

How the innate immune system trains immunity: lessons from studying atopic dermatitis and cutaneous bacteria.

J Dtsch Dermatol Ges 2016 Feb 20;14(2):153-6. Epub 2016 Jan 20.

Department of Dermatology and Allergology, TUM School of Medicine, Technische Universität München, Germany.

The skin is the largest organ at the interface between environment and host. It plays a major protective role against pathogens as physical barrier, as site of first recognition, and as orchestrator of consecutive immune responses. In this process, immunological crosstalk between skin-resident and immune cells is required, and fixed innate immune responses were previously believed to orchestrate adaptive immunity of B and T lymphocytes. Today, we understand that diverse qualities of immune responses to different microbes need to be regulated by also varying responses at the level of first microbe recognition through receptors of the innate immune system. Only fine-tuning of the innate immune system allows for the orchestration of immune responses to the microbiota in the absence of inflammation as well as to pathogens in the context of protective responses including inflammation. Understanding how innate immunity precisely adapts is also important for diseases such as atopic dermatitis (AD) with chronic inflammation. In this review, we present data on how the innate immune system actually fine-tunes its responses with special focus on the immunological consequences of cutaneous innate immune sensing through TLR2. These new insights are highly relevant for understanding microbiota-associated state of health, immune defense, and the pathogenesis underlying chronic cutaneous inflammation as seen in AD.
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http://dx.doi.org/10.1111/ddg.12843DOI Listing
February 2016

The role of innate immune signaling in the pathogenesis of atopic dermatitis and consequences for treatments.

Semin Immunopathol 2016 Jan 16;38(1):29-43. Epub 2015 Nov 16.

Department of Dermatology and Allergology, TUM School of Medicine, Technische Universität München, Munich, Germany.

The skin is the largest organ at the interface between the environment and the host. Consequently, the skin plays a central role in mounting effective host defense. In addition to pathogens, the microbiota and the host immune system are in permanent contact and communication via the skin. Consequences of this permanent interaction are a unique and partly symbiotic relationship, a tight interdependence between these partners, and also a functional "setting the clock," in which, in the healthy steady state, an induction of protective responses to pathogens is guaranteed. At the same time, commensal microbes contribute to the alertness of the immune system and to the maintenance of immune tolerance. Atopic dermatitis (AD) is a chronic inflammatory skin disease based on a complex genetic trait with defects in cutaneous barrier, in stabilizing skin integrity. Most of AD patients develop deviated innate and adaptive immune responses. As a result, increased susceptibility to cutaneous infection is found in AD patients, and the interactions between these microbes and the skin participate in the development of chronic cutaneous inflammation. The role of the adaptive immune system was characterized in much detail, less though the contribution of innate immunity to AD pathogenesis. It is rather recent evidence that demonstrates a dominant role of components of the innate immune system not only for protecting from microbial invasion but also by orchestrating chronic skin inflammation. In this review we discuss the role of innate immune signaling and consecutive immune networks important for the pathogenesis and management of AD.
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http://dx.doi.org/10.1007/s00281-015-0544-yDOI Listing
January 2016

Nano-assembly of nanodiamonds by conjugation to actin filaments.

J Biophotonics 2016 Mar 22;9(3):296-304. Epub 2015 Aug 22.

Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, NSW, 2109, Australia.

Fluorescent nanodiamonds (NDs) are remarkable objects. They possess unique mechanical and optical properties combined with high surface areas and controllable surface reactivity. They are non-toxic and hence suited for use in biological environments. NDs are also readily available and commercially inexpensive. Here, the exceptional capability of controlling and tailoring their surface chemistry is demonstrated. Small, bright diamond nanocrystals (size ˜30 nm) are conjugated to protein filaments of actin (length ˜3-7 µm). The conjugation to actin filaments is extremely selective and highly target-specific. These unique features, together with the relative simplicity of the conjugation-targeting method, make functionalised nanodiamonds a powerful and versatile platform in biomedicine and quantum nanotechnologies. Applications ranging from using NDs as superior biological markers to, potentially, developing novel bottom-up approaches for the fabrication of hybrid quantum devices that would bridge across the bio/solid-state interface are presented and discussed.
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http://dx.doi.org/10.1002/jbio.201500167DOI Listing
March 2016
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