Legionella pneumophila macrophage infectivity potentiator protein appendage domains modulate protein dynamics and inhibitor binding.

Macrophage infectivity potentiator (MIP) proteins are widespread in human pathogens including Legionella pneumophila, the causative agent of Legionnaires' disease and protozoans such as Trypanosoma cruzi. All MIP proteins contain a FKBP (FK506 binding protein)-like prolyl-cis/trans-isomerase domain that hence presents an attractive drug target. Some MIPs such as the Legionella pneumophila protein (LpMIP) have additional appendage domains of mostly unknown function. In full-length, homodimeric LpMIP, the N-terminal dimerization domain is linked to the FKBP-like domain via a long, free-standing stalk helix. Combining X-ray crystallography, NMR and EPR spectroscopy and SAXS, we elucidated the importance of the stalk helix for protein dynamics and inhibitor binding to the FKBP-like domain and bidirectional crosstalk between the different protein regions. The first comparison of a microbial MIP and a human FKBP in complex with the same synthetic inhibitor was made possible by high-resolution structures of LpMIP with a [4.3.1]-aza-bicyclic sulfonamide and provides a basis for designing pathogen-selective inhibitors. Through stereospecific methylation, the affinity of inhibitors to L. pneumophila and T. cruzi MIP was greatly improved. The resulting X-ray inhibitor-complex structures of LpMIP and TcMIP at 1.49 and 1.34 Å, respectively, provide a starting point for developing potent inhibitors against MIPs from multiple pathogenic microorganisms.

ARF6 is a host factor for SARS-CoV-2 infection in vitro.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged beta-coronavirus that enter cells via two routes, direct fusion at the plasma membrane or endocytosis followed by fusion with the late endosome/lysosome. While the viral receptor, ACE2, multiple entry factors and the mechanism of fusion of the virus at the plasma membrane have been investigated extensively, viral entry via the endocytic pathway is less understood. By using a human hepatocarcinoma cell line, Huh-7, which is resistant to the antiviral action of the TMPRSS2 inhibitor camostat, we discovered that SARS-CoV-2 entry is not dependent on dynamin but on cholesterol. ADP-ribosylation factor 6 (ARF6) has been described as a host factor for SARS-CoV-2 replication and is involved in the entry and infection of several pathogenic viruses. Using CRISPR/Cas9 genetic deletion, a modest reduction in SARS-CoV-2 uptake and infection in Huh-7 was observed. In addition, pharmacological inhibition of ARF6 with the small molecule NAV-2729 showed a dose-dependent reduction of viral infection. Importantly, NAV-2729 also reduced SARS-CoV-2 viral loads in more physiological models of infection: Calu-3 cells and kidney organoids. This highlighted a role for ARF6 in multiple cell contexts. Together, these experiments point to ARF6 as a putative target to develop antiviral strategies against SARS-CoV-2.

Double inversion recovery MRI versus contrast-enhanced MRI for evaluation of knee synovitis in juvenile idiopathic arthritis.

BACKGROUND: Double inversion recovery (DIR) MRI has the potential to accentuate the synovium without using contrast agents, as it allows simultaneous signal suppression of fluid and fat. The purpose of this study was (1) to compare DIR MRI to conventional contrast-enhanced (CE) MRI for delineation of the synovium in the knee in children with juvenile idiopathic arthritis (JIA) and (2) to assess the agreement between DIR MRI and CE-MRI regarding maximal synovial thickness measurements. RESULTS: In this prospective study, 26 children with JIA who consecutively underwent 3.0-T knee MRI between January 2018 and January 2021 were included (presence of knee arthritis: 13 [50%]; median age: 14 years [interquartile range [IQR]: 11-17]; 14 girls). Median confidence to depict the synovium (0-100 mm visual analogue scale; scored by 2 readers [consensus based]) was 88 (IQR: 79-97) for DIR MRI versus 100 (IQR: 100-100) for CE-MRI (p value = < .001). Maximal synovial thickness per child (millimeters; scored by 4 individual readers) on DIR MRI was greater (p value = < .001) in the children with knee arthritis (2.4 mm [IQR: 2.1-3.1]) than in those without knee arthritis (1.4 mm [IQR: 1.0-1.6]). Good inter-technique agreement for maximal synovial thickness per child was observed (rs = 0.93 [p value = < .001]; inter-reader reliability: ICC DIR MRI = 0.87 [p value = < .001], ICC CE-MRI = 0.90 [p value = < .001]). CONCLUSION: DIR MRI adequately delineated the synovium in the knee of children with JIA and enabled synovial thickness measurement similar to that of CE-MRI. Our results demonstrate that DIR MRI should be considered as a child-friendly alternative to CE-MRI for evaluation of synovitis in children with (suspected) JIA.

ARF6 is a host factor for SARS-CoV-2 infection in vitro.

SARS-CoV-2 is a newly emerged beta-coronavirus that enter cells via two routes, direct fusion at the plasma membrane or endocytosis followed by fusion with the late endosome/lysosome. While the viral receptor, ACE2, multiple entry factors, and the mechanism of fusion of the virus at the plasma membrane have been extensively investigated, viral entry via the endocytic pathway is less understood. By using a human hepatocarcinoma cell line, Huh-7, which is resistant to the antiviral action of the TMPRSS2 inhibitor camostat, we discovered that SARS-CoV-2 entry is not dependent on dynamin but dependent on cholesterol. ADP-ribosylation factor 6 (ARF6) has been described as a host factor for SARS-CoV-2 replication and it is involved in the entry and infection of several pathogenic viruses. Using CRISPR-Cas9 genetic deletion, we observed that ARF6 is important for SARS-CoV-2 uptake and infection in Huh-7. This finding was corroborated using a pharmacologic inhibitor, whereby the ARF6 inhibitor NAV-2729 showed a dose-dependent inhibition of viral infection. Importantly, NAV-2729 reduced SARS-CoV-2 viral loads also in more physiologic models of infection: Calu-3 and kidney organoids. This highlighted the importance of ARF6 in multiple cell contexts. Together, these experiments points to ARF6 as a putative target to develop antiviral strategies against SARS-CoV-2.

Immune and stem cell compartments of acetabular and femoral bone marrow in hip osteoarthritis patients.

OBJECTIVE: Hip osteoarthritis (OA) affects all components of the osteochondral unit, leading to bone marrow (BM) lesions, and unknown consequences on BM cell functionality. We analyzed the cellular composition in OA-affected acetabula compared to proximal femur shafts obtained of hip OA patients to reveal yet not explored immune and stem cell compartments. DESIGN: Combining flow cytometry, cellular assays and transcription analyses, we performed extensive ex vivo phenotyping of acetabular BM cells from 18 hip OA patients, comparing them with their counterparts from patient-matched femoral shaft BM samples. Findings were related to differences in skeletal sites and age. RESULTS: Acetabular BM had a greater frequency of T-lymphocytes, non-hematopoietic cells and colony-forming units fibroblastic potential than femoral BM. The incidence of acetabular CD45+CD3+ T-lymphocytes increased (95% CI: 0.1770 to 0.0.8416), while clonogenic hematopoietic progenitors declined (95% CI: -0.9023 to -0.2399) with age of patients. On the other side, in femoral BM, we observed higher B-lymphocyte, myeloid and erythroid cell frequencies. Acetabular mesenchymal stromal cells (MSCs) showed a senescent profile associated with the expression of survival and inflammation-related genes. Efficient osteogenic and chondrogenic differentiation was detected in acetabular MSCs, while adipogenesis was more pronounced in their femoral counterparts. CONCLUSION: Our results suggest that distinctions in BM cellular compartments and MSCs may be due to the influence of the OA-stressed microenvironment, but also acetabular vs femoral shaft-specific peculiarities cannot be excluded. These results bring new knowledge on acetabular BM cell populations and may be addressed as novel pathogenic mechanisms and therapeutic targets in OA.

Ultrasound and MR muscle imaging in new onset idiopathic inflammatory myopathies at diagnosis and after treatment: a comparative pilot study.

OBJECTIVES: To prospectively compare ultrasound (US) and whole-body MRI for detection of muscle abnormalities compatible with idiopathic inflammatory myopathies (IIM). METHODS: Newly diagnosed IIM patients underwent US (14 muscles) and MRI (36 muscles) at diagnosis and after nine weeks monotherapy with intravenous immunoglobulin. Muscles were compatible with IIM when quantitative US echo-intensity (EI) z scores was ≥1.5, semi-quantitative US Heckmatt score was ≥2, qualitative US was abnormal, or when MRI showed oedema on T2-weighted images. At patient level, findings were classified as abnormal when quantitative US EI z scores was >1.5 (n = 3 muscles), >2.5 (n = 2 muscles) or >3.5 (n = 1 muscle), or if ≥3 muscles showed abnormalities as described above for the other diagnostic methods. RESULTS: At diagnosis, in 18 patients US of 252 muscles revealed abnormalities in 36 muscles (14%) with quantitative, in 153 (61%) with semi-quantitative and in 168 (67%) with qualitative analysis. MRI showed oedema in 476 out of 623 muscles (76%). Five patients (28%) reached abnormal classification with quantitative US, 16 (89%) with semi-quantitative and qualitative US, and all patients (100%) with MRI. Nine-week follow-up of 12 patients showed no change over time with quantitative US or MRI, and a decrease in abnormalities with semi-quantitative US (P <0.01), and qualitative US (P <0.01). CONCLUSION: At diagnosis, MRI was more sensitive than US to detect muscle abnormalities compatible with IIM. Semi-quantitative US and qualitative US detected abnormalities in the majority of the patients while evaluating fewer muscles than MRI and showed change over time after nine weeks of treatment.

The value of MRI STIR signal intensity on return to play prognosis and reinjury risk estimation in athletes with acute hamstring injuries.

OBJECTIVES: Previous studies have shown low to moderate evidence for a variety of magnetic resonance imaging (MRI) features as prognostic factors in athletes with hamstring injuries. Short-tau inversion recovery (STIR) signal intensity has not yet been investigated for assessing the prognosis of acute muscle injuries. Our aim was to explore the relationship between MRI STIR signal intensity and time to return to play (RTP) and to investigate the association between MRI STIR and reinjury risk in athletes with acute hamstring injuries. STUDY DESIGN: Case-control study. METHODS: We used MRI STIR to measure intramuscular signal intensity in patients with clinically diagnosed hamstring injuries at two time points: at injury and RTP. At injury, we calculated the association of MRI STIR signal intensity with the time to RTP and reinjury risk. At RTP, the association of MRI STIR signal intensity and reinjury risk and the change in MRI STIR signal intensity over time on reinjury risk was evaluated. RESULTS: 51 patients were included. We found increased MRI STIR signal intensity: (1) at time of injury not to be associated with time to RTP, (2) at time of injury to be associated with a slightly lower risk for reinjury: odds 0.986 (0.975-0.998, p=0.02) and (3) at RTP not to be associated with reinjury risk. (4) We found no association between the change in MRI STIR signal intensity over time and reinjury risk. CONCLUSION: Increased MRI STIR signal intensity at injury has no value in time to RTP prognosis, but is associated with a reduced reinjury risk.

The road to optimal acceleration of Dixon imaging and quantitative T2-mapping in the ankle using compressed sensing and parallel imaging.

OBJECTIVE: This study aimed to find the optimal acceleration factor achievable with CS-SENSE for a clinical ankle protocol while maintaining comparable image quality. METHODS: We explored the optimal acceleration achievable with factor CS-SENSE, for an ankle protocol with T2-weighted, PD-weighted TSE-Dixon (coronal, axial and sagittal) and T2-mapping (sagittal) sequences, on a 3 T MRI-scanner. This study contained three steps: (1) phantom test, (2) pilot test on healthy volunteers, (3) anatomical assessment on a cohort of healthy volunteers and a quantitative analysis. CS-SENSE images (acceleration factors between 2.0× and 12.0×) were compared to reference SENSE images (acceleration factor 2.0×). Three blinded radiologists evaluated the image quality and provided an anatomical assessment using a five-point Likert scale of 25 anatomical regions. RESULTS: The total acquisition time of the TSE-Dixon sequence was reduced by 45 % from 13'38″ to 7'37″ (acceleration factor between 3.6× and 4.0×), the T2-mapping scan time was reduced by 31 % from 5'28″ to 3'47″ (acceleration factor of 3.0×), while maintaining comparable image quality. The results from the anatomical assessment of SENSE 2.0× versus CS-SENSE 3.6× were comparable in 88.7 % as shown by the 5-point Likert scale measurements. The T2-relaxation measurements had a good correlation of ρ = 0.7 between SENSE and CS-SENSE. CONCLUSION: We found an optimum acceleration factor with CS-SENSE between 3.6× and 4.0× for TSE-Dixon and 3.0× for T2-mapping sequences in a clinical MR imaging protocol of the ankle. The total scan time was reduced by 41 % while maintaining adequate image quality.

TNF-α and its soluble receptors mediate the relationship between prior severe mood episodes and cognitive dysfunction in euthymic bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is one of the most disabling mental health conditions in the world. Symptoms of cognitive impairment in BD contribute directly to occupational and social deficiencies and are very difficult to treat. Converging evidence suggests that BD patients have increased peripheral markers of inflammation. The hypothesis of neuroprogression in BD postulates that cognitive deficits develop over the course of the illness and are influenced by prior severe mood episodes, leading to wear-and-tear on the brain- however, there exists a paucity of data statistically testing a mediating role of immune molecules in cognitive dysfunction in BD. METHODS: This is a cross-sectional study. We measured serum levels of tumor necrosis factor alpha (TNF-α), and soluble (s) TNF receptors one and two (sTNF-R1 and sTNF-R2) in 219 euthymic BD patients and 52 Healthy Controls (HCs). Structural equation modeling (SEM) was used for the primary purpose of assessing whether TNF markers (measured by the multiple indicators TNF-α, sTNF-R1 and sTNF-R2) mediate the effect or number of prior severe mood episodes (number of prior psychiatric hospitalizations) on cognitive performance. RESULTS: BD and HC groups did not differ on circulating levels of TNF molecules in the present study. However, we found higher sTNF-R1 concentration in 'late-stage' BD illness (>1 prior psychiatric hospitalization) compared to those in early stage illness. In the subsequent SEM, we found that the model fits the data acceptably (Chi-square = 49.2, p = 0.3), and had a 'close fit' (RMSEA = 0.02, PCLOSE = 0.9). Holding covariates constant (age, sex, premorbid IQ, education, and race), we found that the standardized indirect effect was significant, p = 0.015, 90%CI [-0.07, -0.01], indicating that the estimated model was consistent with peripheral TNF markers partially mediating a causal effect of severe mood episodes on executive function. CONCLUSIONS: Our results indicate that circulating levels of TNF molecules partially mediate the relationship between prior severe mood episodes and executive function in BD. These results may implicate TNF variables in the neuroprogressive course of BD and could point to novel interventions for cognition.

Modulation of tactile perception by Virtual Reality distraction: The role of individual and VR-related factors.

BACKGROUND: Virtual reality (VR) has shown to be an effective distraction method in health care. However, questions remain regarding individual and VR-related factors that may modulate the effect of VR. PURPOSE: To explore the effect of VR distraction on tactile perception thresholds in healthy volunteers, in relation to personal characteristics and interactivity of VR applications. METHODS: A randomized three way cross-over study was conducted to investigate the effects of active and passive VR applications in 50 healthy participants. Main outcome measures were monofilament detection thresholds (MDT) and electrical detection thresholds (EDT). Personal characteristics (e.g. age, gender, susceptibility for immersion) and immersion in the VR conditions were analyzed for their effect on VR induced threshold differences. RESULTS: The use of VR caused a significant increase in both MDT and EDT compared to the control condition (MDT: F (2, 76) = 20.174, p < 0.001; EDT F (2, 76) = 6.907, p = 0.002). Furthermore, a significant difference in favour of active VR compared to passive VR was found in MDT (p = 0.012), but not in EDT. No significant gender effect was found. There was a significant positive correlation between age and active VR distraction (r = 0.333, p = 0.018). Immersion in the VR world was positively correlated with the effect of VR, whereas visualization and daydreaming were negatively correlated with VR effects. CONCLUSION: VR increased tactile perception thresholds, with active VR having the largest effect. Results indicate that the efficacy of VR may increase with increasing age. Gender did not affect VR susceptibility.

Hierarchical collective motion of a mixture of active dipolar Janus particles and passive charged colloids in two dimensions.

We use computer simulations to study the behavior of a mixture of large passive charged colloids in a suspension of smaller active dipolar Janus particles. We find that when a single charged colloid is present in solution, it acquires a rotational or translational motion depending on how the active dipoles self-assemble on its surface to form active complexes. The collective behavior of these complexes is quite remarkable, and includes swarming behavior and coherent macroscopic motion. We detail how the variety of different phenomenologies emerging in this system can ultimately be controlled by the strength of the active forces and the relative concentration of the two species.

RNase 7 downregulates TH2 cytokine production by activated human T cells.

BACKGROUND: The antimicrobial peptide (AMP) RNase 7 is constitutively expressed in the epidermis of healthy human skin and has been found to be upregulated in chronic inflammatory skin diseases such as atopic dermatitis and psoriasis. Activated T cells in lesional skin of patients with atopic dermatitis (AD) and psoriasis (PSO) might be directly exposed to RNase 7. In addition to their antimicrobial activity, immunoregulatory functions have been published for several AMPs. In this study, we investigated immunoregulatory effects of the antimicrobial peptide RNase 7 on activated T cells. METHODS: Isolated human CD3+T cells were stimulated with RNase 7 and screened for possible effects by mRNA microarray analysis. The results of the mRNA microarray were confirmed in isolated CD4+T cells and in polarized TH2 cells using skin-derived native RNase 7 and a recombinant ribonuclease-inactive RNase 7 mutant. Activation of GATA3 was analysed by electrophoretic mobility shift assay. RESULTS: Treatment of activated human CD4+T cells and TH2 cells with RNase 7 selectively reduced the expression of TH2 cytokines (IL-13, IL-4 and IL-5). Experiments with a ribonuclease-inactive recombinant RNase 7 mutant showed that RNase 7 ribonuclease activity is dispensable for the observed regulatory effect. We further demonstrate that CD4+T cells from AD patients revealed a significantly less pronounced downregulation of IL-13 in response to RNase 7 compared to healthy control. Finally, we show that GATA3 activation was diminished upon cultivation of T cells with RNase 7. CONCLUSION: Our data indicate that RNase 7 has immunomodulatory functions on TH2 cells and decreases the production of TH2 cytokines in the skin.

Phantom Study Investigating the Accuracy of Manual and Automatic Image Fusion with the GE Logiq E9: Implications for use in Percutaneous Liver Interventions.

PURPOSE: To determine the accuracy of automatic and manual co-registration methods for image fusion of three-dimensional computed tomography (CT) with real-time ultrasonography (US) for image-guided liver interventions. MATERIALS AND METHODS: CT images of a skills phantom with liver lesions were acquired and co-registered to US using GE Logiq E9 navigation software. Manual co-registration was compared to automatic and semiautomatic co-registration using an active tracker. Also, manual point registration was compared to plane registration with and without an additional translation point. Finally, comparison was made between manual and automatic selection of reference points. In each experiment, accuracy of the co-registration method was determined by measurement of the residual displacement in phantom lesions by two independent observers. RESULTS: Mean displacements for a superficial and deep liver lesion were comparable after manual and semiautomatic co-registration: 2.4 and 2.0 mm versus 2.0 and 2.5 mm, respectively. Both methods were significantly better than automatic co-registration: 5.9 and 5.2 mm residual displacement (p < 0.001; p < 0.01). The accuracy of manual point registration was higher than that of plane registration, the latter being heavily dependent on accurate matching of axial CT and US images by the operator. Automatic reference point selection resulted in significantly lower registration accuracy compared to manual point selection despite lower root-mean-square deviation (RMSD) values. CONCLUSION: The accuracy of manual and semiautomatic co-registration is better than that of automatic co-registration. For manual co-registration using a plane, choosing the correct plane orientation is an essential first step in the registration process. Automatic reference point selection based on RMSD values is error-prone.

Differential expression of antimicrobial peptides in psoriasis and psoriatic arthritis as a novel contributory mechanism for skin and joint disease heterogeneity.

OBJECTIVES: This study tested the hypothesis that a differential innate immune antimicrobial peptide (AMP) profile was evident between the skin and joints in psoriasis and psoriatic arthritis (PsA) and that PsA synovitis may have a distinct AMP pattern compared to other arthropathies. METHOD: Twenty-two cases had knee biopsies [10 PsA, eight rheumatoid arthritis (RA), and four osteoarthritis (OA)]. Lesional and non-lesional skin biopsies in psoriasis and control tissue were also obtained (n = 4 each). Immunohistochemistry with semi-quantitative scoring of both synovium and skin was performed using the following panel of AMPs: S100 A8, S100 A9, human neutrophil peptides 1-3 (HNP1-3), human ß-defensins 2 and 3 (hBD-2 and hBD-3), cathelicidin LL-37, psoriasin (S100 A7), and ribonuclease 7 (RNase 7). RESULTS: Similar expression of S100 A8, S100 A9, and HNP1-3 was detectable in PsA and RA synovium but only in the synovium sublining layer (SSL). No expression of psoriasin, RNase 7, hBD-2, and hBD-3 could be detected in the synovial tissue of PsA, RA, or OA. All psoriasis skin samples exhibited broad expression of all investigated AMPs, with strong keratinocyte expression. CONCLUSIONS: Given that some AMPs, especially hBD-2, are genetically linked to psoriasis and are only expressed in the skin, these findings show how differential AMP expression in innate immune responses may contribute to disease heterogeneity between PsA and psoriasis and provides a genetic basis for the non-progression of psoriasis subgroups to PsA.

Off-resonance suppression for multispectral MR imaging near metallic implants.

PURPOSE: Metal artifact reduction in MRI within clinically feasible scan-times without through-plane aliasing. THEORY AND METHODS: Existing metal artifact reduction techniques include view angle tilting (VAT), which resolves in-plane distortions, and multispectral imaging (MSI) techniques, such as slice encoding for metal artifact correction (SEMAC) and multi-acquisition with variable resonances image combination (MAVRIC), that further reduce image distortions, but significantly increase scan-time. Scan-time depends on anatomy size and anticipated total spectral content of the signal. Signals outside the anticipated spatial region may cause through-plane back-folding. Off-resonance suppression (ORS), using different gradient amplitudes for excitation and refocusing, is proposed to provide well-defined spatial-spectral selectivity in MSI to allow scan-time reduction and flexibility of scan-orientation. Comparisons of MSI techniques with and without ORS were made in phantom and volunteer experiments. RESULTS: Off-resonance suppressed SEMAC (ORS-SEMAC) and outer-region suppressed MAVRIC (ORS-MAVRIC) required limited through-plane phase encoding steps compared with original MSI. Whereas SEMAC (scan time: 5'46") and MAVRIC (4'12") suffered from through-plane aliasing, ORS-SEMAC and ORS-MAVRIC allowed alias-free imaging in the same scan-times. CONCLUSION: ORS can be used in MSI to limit the selected spatial-spectral region and contribute to metal artifact reduction in clinically feasible scan-times while avoiding slice aliasing.

Ripple artifact reduction using slice overlap in slice encoding for metal artifact correction.

PURPOSE: Multispectral imaging (MSI) significantly reduces metal artifacts. Yet, especially in techniques that use gradient selection, such as slice encoding for metal artifact correction (SEMAC), a residual ripple artifact may be prominent. Here, an analysis is presented of the ripple artifact and of slice overlap as an approach to reduce the artifact. METHODS: The ripple artifact was analyzed theoretically to clarify its cause. Slice overlap, conceptually similar to spectral bin overlap in multi-acquisition with variable resonances image combination (MAVRIC), was achieved by reducing the selection gradient and, thus, increasing the slice profile width. Time domain simulations and phantom experiments were performed to validate the analyses and proposed solution. RESULTS: Discontinuities between slices are aggravated by signal displacement in the frequency encoding direction in areas with deviating B0. Specifically, it was demonstrated that ripple artifacts appear only where B0 varies both in-plane and through-plane. Simulations and phantom studies of metal implants confirmed the efficacy of slice overlap to reduce the artifact. CONCLUSION: The ripple artifact is an important limitation of gradient selection based MSI techniques, and can be understood using the presented simulations. At a scan-time penalty, slice overlap effectively addressed the artifact, thereby improving image quality near metal implants.

The role of particle shape in active depletion.

Using numerical simulations, we study how a solution of small active disks, acting as depletants, induces effective interactions on large passive colloids. Specifically, we analyze how the range, strength, and sign of these interactions are crucially dependent on the shape of the colloids. Our findings indicate that while colloidal rods experience a long-ranged predominantly attractive interaction, colloidal disks feel a repulsive force that is short-ranged in nature and grows in strength with the size ratio between the colloids and active depletants. For colloidal rods, simple scaling arguments are proposed to characterize the strength of these induced interactions.

[The skin's own antibiotics. Important features of antimicrobial peptides for clinical practice]. / Hauteigene Antibiotika. Wichtige Erkenntnisse über antimikrobielle Peptide für Klinik und Praxis.

Despite permanent confrontation with a potentially harmful environment, its own microbiota and the fact that minor injuries occur frequently in everyday life, skin infections are a rare event. A chemical barrier of antimicrobial peptides (AMP), some of them constitutively expressed, others inducible by various stimuli, contributes to the integument's resistance. AMP are evolutionarily old components of the innate immunity which became the focus of interest due to their broad spectrum of activity against microorganisms and the rare occurrence of antimicrobial resistance. These attributes make them promising alternative candidates for future antibiotics. Furthermore various dermatological diseases are associated with an altered expression of these molecules, which might then play a pathogenetic role. In addition to their antimicrobial activity, some AMP have immunomodulatory effects and can promote wound healing, properties which currently are under intensive research.

Activity-induced collapse and reexpansion of rigid polymers.

We study the elastic properties of a rigid filament in a bath of self-propelled particles. We find that while fully flexible filaments swell monotonically upon increasing the strength of the propelling force, rigid filaments soften for moderate activities, collapse into metastable hairpins for intermediate strengths, and eventually reexpand when the strength of the activity of the surrounding fluid is large. This collapse and reexpansion of the filament with the bath activity is reminiscent of the behavior observed in polyelectrolytes in the presence of different concentrations of multivalent salt.