Resonant elastic X-ray scattering of antiferromagnetic superstructures in EuPtSi3_{3}

We report resonant elastic X-ray scattering (REXS) of long-range magnetic order in EuPtSi$_{\text{3}}$, combining different scattering geometries with full linear polarization analysis to unambiguously identify magnetic scattering contributions. At low temperatures, EuPtSi$_{\text{3}}$ stabilizes type A antiferromagnetism featuring various long-wavelength modulations. For magnetic fields applied in the hard magnetic basal plane, well-defined regimes of cycloidal, conical, and fan-like superstructures may be distinguished that encompass a pocket of commensurate type A order without superstructure. For magnetic field applied along the easy axis, the phase diagram comprises the cycloidal and conical superstructures only. Highlighting the power of polarized REXS, our results reveal a combination of magnetic phases that suggest a highly unusual competition between antiferromagnetic exchange interactions with Dzyaloshinsky--Moriya spin--orbit coupling of similar strength

Electron Tunneling in Ferritin and Associated Biosystems

Ferritin is a 12 nanometer (nm) diameter iron storage protein complex that is found in most plants and animals. A substantial body of evidence has established that electrons can tunnel through and between ferritin protein nanoparticles and that it exhibits Coulomb blockade behavior, which is also seen in quantum dots and nanoparticles. This evidence can be used to understand the behavior of these particles for use in nanoelectronic devices, for biomedical applications and for investigation of quantum biological phenomena. Ferritin also has magnetic properties that make it useful for applications such as memristors and as a contrast agent for magnetic resonance imaging. This article provides a short overview of this evidence, as well as evidence of ferritin structures in vivo and of tunneling in those structures, with an emphasis on ferritin structures in substantia nigra pars compacta (SNc) neurons. Potential biomedical applications that could utilize these ferritin protein nanoparticles are also discussed.</p

Cyclotides Isolated from an Ipecac Root Extract Antagonize the Corticotropin Releasing Factor Type 1 Receptor

Cyclotides are plant derived, cystine-knot stabilized peptides characterized by their natural abundance, sequence variability and structural plasticity. They are abundantly expressed in Rubiaceae, Psychotrieae in particular. Previously the cyclotide kalata B7 was identified to modulate the human oxytocin and vasopressin G protein-coupled receptors (GPCRs), providing molecular validation of the plants’ uterotonic properties and further establishing cyclotides as valuable source for GPCR ligand design. In this study we screened a cyclotide extract derived from the root powder of the South American medicinal plant ipecac (Carapichea ipecacuanha) for its GPCR modulating activity of the corticotropin-releasing factor type 1 receptor (CRF1R). We identified and characterized seven novel cyclotides. One cyclotide, caripe 8, isolated from the most active fraction, was further analyzed and found to antagonize the CRF1R. A nanomolar concentration of this cyclotide (260 nM) reduced CRF potency by ∼4.5-fold. In contrast, caripe 8 did not inhibit forskolin-, or vasopressin-stimulated cAMP responses at the vasopressin V2 receptor, suggesting a CRF1R-specific mode-of-action. These results in conjunction with our previous findings establish cyclotides as modulators of both classes A and B GPCRs. Given the diversity of cyclotides, our data point to other cyclotide-GPCR interactions as potentially important sources of drug-like molecules

An 89Zr-HDL PET Tracer Monitors Response to a CSF1R Inhibitor

The immune function within the tumor microenvironment has become a prominent therapeutic target, with tumor-associated macrophages (TAMs) playing a critical role in immune suppression. We propose an 89Zr-labeled high-density lipoprotein (89Zr-HDL) nanotracer as a means of monitoring response to immunotherapy. Methods: Female MMTV-PyMT mice were treated with pexidartinib, a colony-stimulating factor 1 receptor (CSF1R) inhibitor, to reduce TAM density. The accumulation of 89Zr-HDL within the tumor was assessed using PET/CT imaging and autoradiography, whereas TAM burden was determined using immunofluorescence. Results: A significant reduction in 89Zr-HDL accumulation was observed in PET/CT images, with 2.9% ± 0.3% and 3.7% ± 0.2% injected dose/g for the pexidartinib- and vehicle-treated mice, respectively. This reduction was corroborated ex vivo and correlated with decreased TAM density. Conclusion: These results support the potential use of 89Zr-HDL nanoparticles as a PET tracer to quickly monitor the response to CSF1R inhibitors and other therapeutic strategies targeting TAMs.We thank the Small Animal Imaging Core, the Radiochemistry and Molecular Imaging Probes Core, and the Molecular Cytology Core at Memorial Sloan Kettering Cancer Center. This work was supported by National Institutes of Health grants R01 CA204441, P30 CA008748 and R01 CA220234. The authors thank the Tow Foundation and Memorial Sloan Kettering Cancer Center's Center for Molecular Imaging & Nanotechnology (CMINT), the Imaging and Radiation Sciences Program and the MSK Molecularly Targeted Intraoperative Imaging Fund.S

Towards an understanding of the rapid decline of the cosmic star formation rate

We present a first analysis of deep 24 micron observations with the Spitzer Space Telescope of a sample of nearly 1500 galaxies in a thin redshift slice, 0.65<z<0.75. We combine the infrared data with redshifts, rest-frame luminosities, and colors from COMBO-17, and with morphologies from Hubble Space Telescope images collected by the GEMS and GOODS projects. To characterize the decline in star-formation rate (SFR) since z~0.7, we estimate the total thermal infrared (IR) luminosities, SFRs, and stellar masses for the galaxies in this sample. At z~0.7, nearly 40% of intermediate and high-mass galaxies (with stellar masses >2x10^10 solar masses) are undergoing a period of intense star formation above their past-averaged SFR. In contrast, less than 1% of equally-massive galaxies in the local universe have similarly intense star formation activity. Morphologically-undisturbed galaxies dominate the total infrared luminosity density and SFR density: at z~0.7, more than half of the intensely star-forming galaxies have spiral morphologies, whereas less than \~30% are strongly interacting. Thus, a decline in major-merger rate is not the underlying cause of the rapid decline in cosmic SFR since z~0.7. Physical properties that do not strongly affect galaxy morphology - for example, gas consumption and weak interactions with small satellite galaxies - appear to be responsible.Comment: To appear in the Astrophysical Journal 1 June 2005. 14 pages with 8 embedded figure

The Impact of Depression, Anxiety and Personality Disorders on the Outcome of Patients with Functional Limb Weakness – Individual Patient Data Meta-Analysis

Objective: Psychiatric comorbidities such as depression, anxiety, and personality disorders are common in patients with functional limb weakness/paresis (FND-par). The impact of these conditions on the prognosis of FND-par has not been systematically reviewed. The aim of this study was to identify a potential prognostic effect of comorbid depression, anxiety, and/or personality disorder on prognosis in patients with FND-par. Methods: A systematic review was performed to identify studies that reported measures of baseline depression, anxiety, and/or personality disorder, and physical disability. An individual patient data meta-analysis was subsequently performed. Results: Eight studies comprising 348 individuals were included (7 prospective cohorts; 1 case-control study). There was heterogeneity in sample size, follow-up duration, and treatment modality. Depression and anxiety were present in 51.4% and 53.0% of FND-par patients, respectively. In individuals whose FND-par improved, there was no significant difference between those with versus without depression (52.6% vs 47.4%, p = 0.69) or those with versus without anxiety (50.3% vs 49.7%, p = 0.38). Meta-analysis showed no clear impact of baseline depression or anxiety per se [pooled OR for depression 0.85 (95%CI 0.50–1.45; p = 0.40) and anxiety 0.84 (95%CI 0.51–1.38; p = 0.91)]; and of depression or anxiety severity [pooled OR for depression 1.23 (95%CI 0.63–2.39; p = 0.91) and anxiety 1.40 (95%CI 0.70–2.78; p = 0.58)] on FND-par outcome. Insufficient data were available to assess the impact of personality disorders. Conclusion: We found no evidence that depression or anxiety influenced outcome in FND-par. Large-scale, prospective studies in FND-par, and other FND subtypes, are needed to fully contextualize the impact of concurrent mental health concerns on outcomes.</p

Association of hypomagnesemia and liver injury, role of gut-barrier dysfunction and inflammation: Efficacy of abstinence, and 2-week medical management in alcohol use disorder patients.

(1) We investigated the involvement of serum magnesium level in early alcoholic liver disease (ALD), gut barrier dysfunction, and inflammation in alcohol use disorder (AUD) patients; and lastly, the efficacy of 2-week abstinence and medical management to alleviate hypomagnesemia. (2) Forty-eight heavy drinking AUD patients (34 males (M)/14 females (F)) participated in this study. Patients were grouped by serum alanine aminotransferase (ALT) level (a marker of liver injury) as group 1 (Group 1 (Gr.1); ALT ≤ 40 U/L, 7M/8F, without any indication of early-stage ALD) and group 2 (Group 2 (Gr.2); ALT \u3e 40 U/L, 27M/6F or early-stage ALD). These patients were sub-divided within each group into patients with normal magnesium (0.85 and more mmol/L) and deficient magnesium (less than 0.85 mmol/L) levels. All participants were assessed at baseline (BL) and received standard medical management for 2 weeks with reassessment at the treatment end (2w). (3) Female participants of this study showed a significantly lower baseline level of magnesium than their male counterparts. Gr.2 patients showed a greater propensity in the necrotic type of liver cell death, who reported higher chronic and recent heavy drinking. Magnesium level improved to the normal range in Gr.2 post-treatment, especially in the hypomagnesemia sub-group (0.77 ± 0.06 mmol/L (BL) vs. 0.85 ± 0.05 mmol/L (2w), p = 0.02). In Gr.2, both apoptotic (K18M30) and necrotic (K18M65) responses were significantly and independently associated with inflammasome activity comprising of LBP (Lipopolysaccharide binding-protein) and TNFα (Tumor necrosis factor -α), along with serum magnesium. (4) In AUD patients with liver injury, 2-week medical management seems to improve magnesium to a normal level. This group exhibited inflammatory activity (LBP and TNFα) contributing to clinically significant hypomagnesemia. In this group, the level of magnesium, along with the unique inflammatory activity, seems to significantly predict apoptotic and necrotic types of hepatocyte death

Human and computational models of atopic dermatitis:A review and perspectives by an expert panel of the International Eczema Council

Atopic dermatitis (AD) is a prevalent disease worldwide and is associated with systemic comorbidities representing a significant burden on patients, their families, and society. Therapeutic options for AD remain limited, in part because of a lack of well-characterized animal models. There has been increasing interest in developing experimental approaches to study the pathogenesis of human AD in vivo, in vitro, and in silico to better define pathophysiologic mechanisms and identify novel therapeutic targets and biomarkers that predict therapeutic response. This review critically appraises a range of models, including genetic mutations relevant to AD, experimental challenge of human skin in vivo, tissue culture models, integration of “omics” data sets, and development of predictive computational models. Although no one individual model recapitulates the complex AD pathophysiology, our review highlights insights gained into key elements of cutaneous biology, molecular pathways, and therapeutic target identification through each approach. Recent developments in computational analysis, including application of machine learning and a systems approach to data integration and predictive modeling, highlight the applicability of these methods to AD subclassification (endotyping), therapy development, and precision medicine. Such predictive modeling will highlight knowledge gaps, further inform refinement of biological models, and support new experimental and systems approaches to AD

Extracting Block Copolymer Dynamics from GISAXS

4th. International symposium on DSA.(2018)4th. International symposium on DSA. 11-13. November, 2F Pearl Room, Sapporo Park Hotel. Japan (2018) .-http://dsasymp.org/program.htm