Nanomaterial interactions with biomembranes: Bridging the gap between soft matter models and biological context

Synthetic polymers, nanoparticles, and carbon-based materials have great potential in applications including drug delivery, gene transfection, in vitro and in vivo imaging, and the alteration of biological function. Nature and humans use different design strategies to create nanomaterials: biological objects have emerged from billions of years of evolution and from adaptation to their environment resulting in high levels of structural complexity; in contrast, synthetic nanomaterials result from minimalistic but controlled design options limited by the authors' current understanding of the biological world. This conceptual mismatch makes it challenging to create synthetic nanomaterials that possess desired functions in biological media. In many biologically relevant applications, nanomaterials must enter the cell interior to perform their functions. An essential transport barrier is the cell-protecting plasma membrane and hence the understanding of its interaction with nanomaterials is a fundamental task in biotechnology. The authors present open questions in the field of nanomaterial interactions with biological membranes, including: how physical mechanisms and molecular forces acting at the nanoscale restrict or inspire design options; which levels of complexity to include next in computational and experimental models to describe how nanomaterials cross barriers via passive or active processes; and how the biological media and protein corona interfere with nanomaterial functionality. In this Perspective, the authors address these questions with the aim of offering guidelines for the development of next-generation nanomaterials that function in biological media

Vectorial Control of Magnetization by Light

Coherent light-matter interactions have recently extended their applications to the ultrafast control of magnetization in solids. An important but unrealized technique is the manipulation of magnetization vector motion to make it follow an arbitrarily designed multi-dimensional trajectory. Furthermore, for its realization, the phase and amplitude of degenerate modes need to be steered independently. A promising method is to employ Raman-type nonlinear optical processes induced by femtosecond laser pulses, where magnetic oscillations are induced impulsively with a controlled initial phase and an azimuthal angle that follows well defined selection rules determined by the materials' symmetries. Here, we emphasize the fact that temporal variation of the polarization angle of the laser pulses enables us to distinguish between the two degenerate modes. A full manipulation of two-dimensional magnetic oscillations is demonstrated in antiferromagnetic NiO by employing a pair of polarization-twisted optical pulses. These results have lead to a new concept of vectorial control of magnetization by light

Fermionic response from fractionalization in an insulating two-dimensional magnet

Conventionally ordered magnets possess bosonic elementary excitations, called magnons. By contrast, no magnetic insulators in more than one dimension are known whose excitations are not bosons but fermions. Theoretically, some quantum spin liquids (QSLs) -- new topological phases which can occur when quantum fluctuations preclude an ordered state -- are known to exhibit Majorana fermions as quasiparticles arising from fractionalization of spins. Alas, despite much searching, their experimental observation remains elusive. Here, we show that fermionic excitations are remarkably directly evident in experimental Raman scattering data across a broad energy and temperature range in the two-dimensional material $\alpha$-RuCl$_3$. This shows the importance of magnetic materials as hosts of Majorana fermions. In turn, this first systematic evaluation of the dynamics of a QSL at finite temperature emphasizes the role of excited states for detecting such exotic properties associated with otherwise hard-to-identify topological QSLs.Comment: 5 pages, 3 figure

Multimorbidity in bipolar disorder and under-treatment of cardiovascular disease: a cross sectional study

Background: Individuals with serious mental disorders experience poor physical health, especially increased rates of cardiometabolic morbidity and premature morbidity. Recent evidence suggests that individuals with schizophrenia have numerous comorbid physical conditions which may be under-recorded and under-treated but to date very few studies have explored this issue for bipolar disorder. Methods:We conducted a cross-sectional analysis of a dataset of 1,751,841 registered patients within 314 primary-care practices in Scotland, U.K. Bipolar disorder was identified using Read Codes recorded within electronic medical records. Data on 32 common chronic physical conditions were also assessed. Potential prescribing inequalities were evaluated by analyzing prescribing data for coronary heart disease (CHD) and hypertension. Results: Compared to controls, individuals with bipolar disorder were significantly less likely to have no recorded physical conditions (OR 0.59, 95% CI 0.54-0.63) and significantly more likely to have one physical condition (OR 1.27, 95% CI 1.16-1.39), two physical conditions (OR 1.45, 95% CI 1.30-1.62) and three or more physical conditions (OR 1.44, 95% CI 1.30-1.64). People with bipolar disorder also had higher rates of thyroid disorders, chronic kidney disease, chronic pain, chronic obstructive airways disease and diabetes but, surprisingly, lower recorded rates of hypertension and atrial fibrillation. People with bipolar disorder and comorbid CHD or hypertension were significantly more likely to be prescribed no antihypertensive or cholesterol-lowering medications compared to controls, and bipolar individuals with CHD or hypertension were significantly less likely to be on 2 or more antihypertensive agents. Conclusions: Individuals with bipolar disorder are similar to individuals with schizophrenia in having a wide range of comorbid and multiple physical health conditions. They are also less likely than controls to have a primary-care record of cardiovascular conditions such as hypertension and atrial fibrillation. Those with a recorded diagnosis of CHD or hypertension were less likely to be treated with cardiovascular medications and were treated less intensively. This study highlights the high physical healthcare needs of people with bipolar disorder, and provides evidence for a systematic under-recognition and under-treatment of cardiovascular disease in this group

Electronic Sensors for Assessing Interactions between Healthcare Workers and Patients under Airborne Precautions

International audienceBackground: Direct observation has been widely used to assess interactions between healthcare workers (HCWs) and patients but is time-consuming and feasible only over short periods. We used a Radio Frequency Identification Device (RFID) system to automatically measure HCW-patient interactions. Methods: We equipped 50 patient rooms with fixed sensors and 111 HCW volunteers with mobile sensors in two clinical wards of two hospitals. For 3 months, we recorded all interactions between HCWs and 54 patients under airborne precautions for suspected (n=40) or confirmed (n=14) tuberculosis. Number and duration of HCW entries into patient rooms were collected daily. Concomitantly, we directly observed room entries and interviewed HCWs to evaluate their self- perception of the number and duration of contacts with tuberculosis patients. Results: After signal reconstruction, 5490 interactions were recorded between 82 HCWs and 54 tuberculosis patients during 404 days of airborne isolation. Median (interquartile range) interaction duration was 2.1 (0.8-4.4) min overall, 2.3 (0.8-5.0) in the mornings, 1.8 (0.8-3.7) in the afternoons, and 2.0 (0.7-4.3) at night (P,1024). Number of interactions/day/HCW was 3.0 (1.0-6.0) and total daily duration was 7.6 (2.4-22.5) min. Durations estimated from 28 direct observations and 26 interviews were not significantly different from those recorded by the network. Conclusions: The RFID was well accepted by HCWs. This original technique holds promise for accurately and continuously measuring interactions between HCWs and patients, as a less resource-consuming substitute for direct observation. The results could be used to model the transmission of significant pathogens. HCW perceptions of interactions with patients accurately reflected reality

The EpsE Flagellar Clutch Is Bifunctional and Synergizes with EPS Biosynthesis to Promote Bacillus subtilis Biofilm Formation

Many bacteria inhibit motility concomitant with the synthesis of an extracellular polysaccharide matrix and the formation of biofilm aggregates. In Bacillus subtilis biofilms, motility is inhibited by EpsE, which acts as a clutch on the flagella rotor to inhibit motility, and which is encoded within the 15 gene eps operon required for EPS production. EpsE shows sequence similarity to the glycosyltransferase family of enzymes, and we demonstrate that the conserved active site motif is required for EPS biosynthesis. We also screen for residues specifically required for either clutch or enzymatic activity and demonstrate that the two functions are genetically separable. Finally, we show that, whereas EPS synthesis activity is dominant for biofilm formation, both functions of EpsE synergize to stabilize cell aggregates and relieve selective pressure to abolish motility by genetic mutation. Thus, the transition from motility to biofilm formation may be governed by a single bifunctional enzyme

Profiles of Human Serum Antibody Responses Elicited by Three Leading HIV Vaccines Focusing on the Induction of Env-Specific Antibodies

In the current report, we compared the specificities of antibody responses in sera from volunteers enrolled in three US NIH-supported HIV vaccine trials using different immunization regimens. HIV-1 Env-specific binding antibody, neutralizing antibody, antibody-dependent cell-mediated cytotoxicity (ADCC), and profiles of antibody specificity were analyzed for human immune sera collected from vaccinees enrolled in the NIH HIV Vaccine Trial Network (HVTN) Study #041 (recombinant protein alone), HVTN Study #203 (poxviral vector prime-protein boost), and the DP6-001 study (DNA prime-protein boost). Vaccinees from HVTN Study #041 had the highest neutralizing antibody activities against the sensitive virus along with the highest binding antibody responses, particularly those directed toward the V3 loop. DP6-001 sera showed a higher frequency of positive neutralizing antibody activities against more resistant viral isolate with a significantly higher CD4 binding site (CD4bs) antibody response compared to both HVTN studies #041 and #203. No differences were found in CD4-induced (CD4i) antibody responses, ADCC activity, or complement activation by Env-specific antibody among these sera. Given recent renewed interest in realizing the importance of antibody responses for next generation HIV vaccine development, different antibody profiles shown in the current report, based on the analysis of a wide range of antibody parameters, provide critical biomarker information for the selection of HIV vaccines for more advanced human studies and, in particular, those that can elicit antibodies targeting conformational-sensitive and functionally conserved epitopes

Long-Lasting Inhibitory Effects of Fetal Liver Mesenchymal Stem Cells on T-Lymphocyte Proliferation

Human bone marrow mesenchymal stem cells (BM-MSC) are multipotent progenitor cells that have transient immunomodulatory properties on Natural Killer (NK) cells, Dendritic Cells (DC), and T cells. This study compared the use of MSC isolated from bone marrow and fetal liver (FL-MSC) to determine which displayed the most efficient immunosuppressive effects on T cell activation. Although both types of MSC exhibit similar phenotype profile, FL-MSC displays a much more extended in vitro life-span and immunomodulatory properties. When co-cultured with CD3/CD28-stimulated T cells, both BM-MSC and FL-MSC affected T cell proliferation by inhibiting their entry into the cell cycle, by inducing the down-regulation of phospho-retinoblastoma (pRb), cyclins A and D1, as well as up-regulating p27kip1expression. The T cell inhibition by MSC was not due to the soluble HLA-G5 isoform, but to the surface expression of HLA-G1, as shown by the need of cell-cell contact and by the use of neutralizing anti-HLA-G antibodies. To note, in a HLA-G-mediated fashion, MSC facilitated the expansion of a CD4low/CD8low T subset that had decreased secretion of IFN-γ, and an induced secretion of the immunomodulatory cytokine IL-10. Because of their longer lasting in vitro immunosuppressive properties, mainly mediated by HLA-G, and their more efficient induction of IL-10 production and T cell apoptosis, fetal liver MSC could be considered a new tool for MSC therapy to prevent allograft rejection

Regulation of Apoptotic Pathways by Stylophora pistillata (Anthozoa, Pocilloporidae) to Survive Thermal Stress and Bleaching

Elevated seawater temperatures are associated with coral bleaching events and related mortality. Nevertheless, some coral species are able to survive bleaching and recover. The apoptotic responses associated to this ability were studied over 3 years in the coral Stylophora pistillata from the Gulf of Eilat subjected to long term thermal stress. These include caspase activity and the expression profiles of the S. pistillata caspase and Bcl-2 genes (StyCasp and StyBcl-2-like) cloned in this study. In corals exposed to thermal stress (32 or 34°C), caspase activity and the expression levels of the StyBcl-2-like gene increased over time (6–48 h) and declined to basal levels within 72 h of thermal stress. Distinct transcript levels were obtained for the StyCasp gene, with stimulated expression from 6 to 48 h of 34°C thermal stress, coinciding with the onset of bleaching. Increased cell death was detected in situ only between 6 to 48 h of stress and was limited to the gastroderm. The bleached corals survived up to one month at 32°C, and recovered back symbionts when placed at 24°C. These results point to a two-stage response in corals that withstand thermal stress: (i) the onset of apoptosis, accompanied by rapid activation of anti-oxidant/anti-apoptotic mediators that block the progression of apoptosis to other cells and (ii) acclimatization of the coral to the chronic thermal stress alongside the completion of symbiosis breakdown. Accordingly, the coral's ability to rapidly curb apoptosis appears to be the most important trait affecting the coral's thermotolerance and survival

PESSTO: survey description and products from the first data release by the Public ESO Spectroscopic Survey of Transient Objects

Context. The Public European Southern Observatory Spectroscopic Survey of Transient Objects (PESSTO) began as a public spectroscopic survey in April 2012. PESSTO classifies transients from publicly available sources and wide-field surveys, and selects science targets for detailed spectroscopic and photometric follow-up. PESSTO runs for nine months of the year, January – April and August – December inclusive, and typically has allocations of 10 nights per month. Aims. We describe the data reduction strategy and data products that are publicly available through the ESO archive as the Spectroscopic Survey data release 1 (SSDR1). Methods. PESSTO uses the New Technology Telescope with the instruments EFOSC2 and SOFI to provide optical and NIR spectroscopy and imaging. We target supernovae and optical transients brighter than 20.5m for classification. Science targets are selected for follow-up based on the PESSTO science goal of extending knowledge of the extremes of the supernova population. We use standard EFOSC2 set-ups providing spectra with resolutions of 13–18 Å between 3345−9995 Å. A subset of the brighter science targets are selected for SOFI spectroscopy with the blue and red grisms (0.935−2.53 μm and resolutions 23−33 Å) and imaging with broadband JHKs filters. Results. This first data release (SSDR1) contains flux calibrated spectra from the first year (April 2012–2013). A total of 221 confirmed supernovae were classified, and we released calibrated optical spectra and classifications publicly within 24 h of the data being taken (via WISeREP). The data in SSDR1 replace those released spectra. They have more reliable and quantifiable flux calibrations, correction for telluric absorption, and are made available in standard ESO Phase 3 formats. We estimate the absolute accuracy of the flux calibrations for EFOSC2 across the whole survey in SSDR1 to be typically ~15%, although a number of spectra will have less reliable absolute flux calibration because of weather and slit losses. Acquisition images for each spectrum are available which, in principle, can allow the user to refine the absolute flux calibration. The standard NIR reduction process does not produce high accuracy absolute spectrophotometry but synthetic photometry with accompanying JHKs imaging can improve this. Whenever possible, reduced SOFI images are provided to allow this. Conclusions. Future data releases will focus on improving the automated flux calibration of the data products. The rapid turnaround between discovery and classification and access to reliable pipeline processed data products has allowed early science papers in the first few months of the survey