Polysaccharide functionalization reduces lipid vesicle stiffness.

The biophysical properties of lipid vesicles are important for their stability and integrity, key parameters that control the performance when these vesicles are used for drug delivery. The vesicle properties are determined by the composition of lipids used to form the vesicle. However, for a given lipid composition, they can also be tailored by tethering polymers to the membrane. Typically, synthetic polymers like polyethyleneglycol are used to increase vesicle stability, but the use of polysaccharides in this context is much less explored. Here, we report a general method for functionalizing lipid vesicles with polysaccharides by binding them to cholesterol. We incorporate the polysaccharides on the outer membrane leaflet of giant unilamellar vesicles (GUVs) and investigate their effect on membrane mechanics using micropipette aspiration. We find that the presence of the glycolipid functionalization produces an unexpected softening of GUVs with fluid-like membranes. By contrast, the functionalization of GUVs with polyethylene glycol does not reduce their stretching modulus. This work provides the potential means to study membrane-bound meshworks of polysaccharides similar to the cellular glycocalyx; moreover, it can be used for tuning the mechanical properties of drug delivery vehicles.

Electrolyte-induced aggregation of zein protein nanoparticles in aqueous dispersions.

Ion specific effects on the charging and aggregation features of zein nanoparticles (ZNP) were studied in aqueous suspensions by electrophoretic and time-resolved dynamic light scattering techniques. The influence of mono- and multivalent counterions on the colloidal stability was investigated for positively and negatively charged particles at pH values below and above the isoelectric point, respectively. The sequence of the destabilization power of monovalent salts followed the prediction of the indirect Hofmeister series for positively charged particles, while the direct Hofmeister series for negatively charged ones assumed a hydrophobic character for their surface. The multivalent ions destabilized the oppositely charged ZNPs more effectively and the aggregation process followed the Schulze-Hardy rule. For some multivalent ions, strong adsorption led to charge reversal resulting in restabilization of the suspensions. The experimental critical coagulation concentrations (CCCs) could be well-predicted with the theory developed by Derjaguin, Landau, Verwey and Overbeek indicating that the aggregation processes were mainly driven by electrical double layer repulsion and van der Waals attraction. The ion specific dependence of the CCCs is owing to the modification of the surface charge through ion adsorption at different extents. These results are crucial for drug delivery applications, where inorganic electrolytes are present in ZNP samples.

Multicompartment calcium alginate microreactors to reduce substrate inhibition in enzyme cascade reactions.

The formation of macromolecularly enriched condensates through associative or segregative liquid-liquid phase separation phenomena is known to play a central role in controlling various cellular functions in nature. The potential to spatially and temporally modulate multistep chemical reactions and pathways has inspired the use of phase-separated systems for the development of various synthetic colloidal micro- and nanoreactor systems. Here, we report a rational and synthetically minimal design strategy to emulate intended spatiotemporal functions in morphologically intricate and structurally defined calcium alginate hydrogel microreactors possessing multicompartmentalized internal architectures. Specifically, we implement a thermal phase separation protocol to achieve fine-control over liquid-liquid phase separation inside complex aqueous emulsion droplet templates that are loaded with hydrophilic polymer mixtures. Subsequent gelation of alginate-containing droplet templates using a novel freeze-thaw approach that can be applied to both scalable batch production or more precise microfluidic methods yields particle replicas, in which subcompartmentalized architectures can be retained. Larger active components can be enriched in the internal compartments due to their preferential solubility, and we show that selective sequestration of enzymes serves to create desired microenvironments to control and tune the reaction kinetics of a multistep enzyme cascade by reducing their mutual interference. This demonstration of mitigating substrate inhibition that is based primarily on optimizing the multicompartmentalized hydrogel particle morphology offers new opportunities for the simple and synthetically-minimal batch generation of hydrogel-based synthesis microreactors.

Association of Tumor Necrosis Factor-Alpha with Psychopathology in Patients with Schizophrenia.

We investigated the relationship between serum tumor necrosis factor-alpha (TNF-α) levels and psychopathological symptoms, clinical and socio-demographic characteristics and antipsychotic therapy in individuals with schizophrenia. TNF-α levels were measured in 90 patients with schizophrenia and 90 healthy controls matched by age, gender, smoking status, and body mass index. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of psychopathology in patients. No significant differences in TNF-α levels were detected between the patients and controls (p=0.736). TNF-α levels were not correlated with total, positive, negative, general, or composite PANSS scores (all p>0.05). A significant negative correlation was observed between TNF-α levels and the PANSS cognitive factor (ρ=-0.222, p=0.035). A hierarchical regression analysis identified the cognitive factor as a significant predictor of the TNF-α level (beta=-0.258, t=-2.257, p=0.027). There were no significant differences in TNF-α levels among patients treated with different types of antipsychotics (p=0.596). TNF-α levels correlated positively with the age of onset (ρ=0.233, p=0.027) and negatively with illness duration (ρ=-0.247, p=0.019) and antipsychotic treatment duration (ρ=-0.256, p=0.015). These results indicate that TNF-α may be involved in cognitive impairment in schizophrenia, and would be a potential clinical-state marker in schizophrenia.

Dynamic In Situ Monitoring of the Salt Counter-ion Effect on Surfactant Effectiveness Using Reconfigurable Janus Emulsions.

A straightforward method for visualization and quantification of surfactant effectiveness within different electrolyte environments based on using reconfigurable Janus emulsions as novel optical probes is reported. More specifically, we investigated the effect of different types and concentrations of salt counter-ions on the surfactant surface excess of commercial ionic and non-ionic surfactants, namely sodium dodecyl sulfate (SDS) and Tween 80 via in situ monitoring the morphological reconfigurations of biphasic Janus emulsions comprising hydrocarbon and fluorocarbon oils. We find that significant variations in interfacial tensions of SDS-stabilized interfaces (up to 15 mN·m-1) can be evoked by titrating mono-, di-, and trivalent cationic counter-ions, which is coherent with the lyotropic (Hofmeister) series. In contrast, the salt counter-ion effect on the surfactant effectiveness was less pronounced for the non-ionic surfactant Tween 80 (∼3 mN·m-1). Our results reveal a facile in situ method for monitoring the central role of electrolyte type and concentration on surfactant effectiveness and, more broadly, illustrate that Janus emulsions serve as powerful optical probes to dynamically study the properties of surfactants at liquid interfaces. We demonstrate the utility of our findings for an electro-induced morphological reconfiguration of Janus droplet morphologies by dynamically tuning Cu2+ concentration in solution using an electrode setup. The latter provides a unique platform for liquid-phase, real-time, and continuous tuning of Janus droplet morphologies, e.g., for their application in sensing and dynamic optical device platforms.

Surface modification of two-dimensional layered double hydroxide nanoparticles with biopolymers for biomedical applications.

Layered double hydroxides (LDHs) are appealing nanomaterials for (bio)medical applications and their potential is threefold. One can gain advantage of the structure of LDH frame (i.e., layered morphology), anion exchanging property towards drugs with acidic character and tendency for facile surface modification with biopolymers. This review focuses on the third aspect, as it is necessary to evaluate the advantages of polymer adsorption on LDH surfaces. Beside the short discussion on fundamental and structural features of LDHs, LDH-biopolymer interactions will be classified in terms of the effect on the colloidal stability of the dispersions. Thereafter, an overview on the biocompatibility and biomedical applications of LDH-biopolymer composite materials will be given. Finally, the advances made in the field will be summarized and future research directions will be suggested.

Stimuli-Responsive Aggregation of High Molar Mass Poly(N,N-Diethylacrylamide)-b-Poly(4-Acryloylmorpholine) in Tetrahydrofuran.

The self-assembly of block copolymers constitutes a timely research area in polymer science with implications for applications like sensing or drug-delivery. Here, the unprecedented aggregation behavior of high molar mass block copolymer poly(N,N-diethylacrylamide)-b-poly(4-acryloylmorpholine) (PDEA-b-PAM) (Mn >400 kg mol-1 ) in organic solvent tetrahydrofuran (THF) is investigated. To elucidate the aggregation, dynamic light scattering, cryo-transmission electron microscopy, and turbidimetry are employed. The aggregate formation is assigned to the unprecedented upper critical solution temperature behavior of PAM in THF at elevated concentrations (> 6 wt.%) and high molar masses. Various future directions for this new thermo-responsive block copolymer are envisioned, for example, in the areas of photonics or templating of inorganic structures.

Association of polygenic risk scores, traumatic life events and coping strategies with war-related PTSD diagnosis and symptom severity in the South Eastern Europe (SEE)-PTSD cohort.

OBJECTIVES: Posttraumatic stress disorder (PTSD) is triggered by extremely stressful environmental events and characterized by high emotional distress, re-experiencing of trauma, avoidance and hypervigilance. The present study uses polygenic risk scores (PRS) derived from the UK Biobank (UKBB) mega-cohort analysis as part of the PGC PTSD GWAS effort to determine the heritable basis of PTSD in the South Eastern Europe (SEE)-PTSD cohort. We further analyzed the relation between PRS and additional disease-related variables, such as number and intensity of life events, coping, sex and age at war on PTSD and CAPS as outcome variables. METHODS: Association of PRS, number and intensity of life events, coping, sex and age on PTSD were calculated using logistic regression in a total of 321 subjects with current and remitted PTSD and 337 controls previously subjected to traumatic events but not having PTSD. In addition, PRS and other disease-related variables were tested for association with PTSD symptom severity, measured by the Clinician Administrated PTSD Scale (CAPS) by liner regression. To assess the relationship between the main outcomes PTSD diagnosis and symptom severity, each of the examined variables was adjusted for all other PTSD related variables. RESULTS: The categorical analysis showed significant polygenic risk in patients with remitted PTSD and the total sample, whereas no effects were found on symptom severity. Intensity of life events as well as the individual coping style were significantly associated with PTSD diagnosis in both current and remitted cases. The dimensional analyses showed as association of war-related frequency of trauma with symptom severity, whereas the intensity of trauma yielded significant results independently of trauma timing in current PTSD. CONCLUSIONS: The present PRS application in the SEE-PTSD cohort confirms modest but significant polygenic risk for PTSD diagnosis. Environmental factors, mainly the intensity of traumatic life events and negative coping strategies, yielded associations with PTSD both categorically and dimensionally with more significant p-values. This suggests that, at least in the present cohort of war-related trauma, the association of environmental factors and current individual coping strategies with PTSD psychopathology was stronger than the polygenic risk.

Spiky pygmy devils: revision of the genus Discotettix (Orthoptera: Tetrigidae) and synonymy of Discotettiginae with Scelimeninae.

Spiky pygmy devils (Tetrigidae: Discotettiginae) are, because of the spiky pronotal projections and widened subapical antennal segments, among the most unique pygmy grasshoppers in Southeast (SE) Asia. The taxonomy of the group was unclear in the past, so this study brings a taxonomic and biographical review of the genus Discotettix Costa, 1864. New terminology of the pronotal projections is proposed for Scelimeninae. All valid species hitherto included in the genus are redescribed; a new genus is established for Discotettix shelfordi Hancock, 1907, Disconius Skejo, Pushkar et Tumbrinck gen. n., so a new combination is established for the species (Disconius shelfordi comb. n.). New synonymy is established: Discotettix selysi Bolívar, 1887 = Discotettix selangori Mahmood, Idris et Salmah, 2007 syn. n. Three new species are described and a key to Discotettix species is provided. The genus now includes seven species (1) Discotettix aruanus Skejo, Pushkar et Tumbrinck sp. n. from Aru; (2) D. belzebuth (Serville, 1838) from Borneo; (3) D. doriae Bolívar, 1898 stat. resurr. from the Mentawai islands; (4) D. kirscheyi Skejo, Pushkar, Tumbrinck et Tan sp. n. from Northeast (NE) Borneo; (5) D. scabridus (Stål, 1877) endemic to Mindanao and Samar; (6) D. selysi Bolívar, 1887 from Sumatra and peninsular Malaysia; (7) D. sumatrensis Skejo, Pushkar et Tumbrinck sp. n. endemic to southern Sumatra. Moreover, Discotettix is again subdivided into two subgenera: Mnesarchus Stål, 1877 stat. resurr. (D. scabridus) and nominotypical one (other species). Widened antennal segments are the only character common to all Discotettiginae genera, but this trait does not have great taxonomic importance, as it is homoplastic, meaning that it appeared in distant Tetrigidae groups independently. Discotettix is herewith transferred to the subfamily Scelimeninae and accordingly, the subfamily Discotettiginae Hancock, 1907 syn. n. becomes a junior synonym of the subfamily Scelimeninae Bolívar, 1887. The tribe Discotettigini stat. resurr., on the other hand, gathers corticolous genera of the Scelimeninae (Austrohancockia Günther, 1938, Bidentatettix Zheng, 1992, Disconius gen. n. Discotettix, Eufalconius Günther, 1938, Gibbotettix Zheng, 1992, Paragavialidium Zheng, 1994, Gavialidium Saussure, 1862, and Tegotettix Hancock, 1913), while the tribe Scelimenini becomes restricted to amphibious taxa. All taxa are described and amply depicted with both museum specimens and in situ photographs. An identification key is provided. The morphology and function of widened antennae in Discotettigini are discussed.

Facile Monitoring of Water Hardness Levels Using Responsive Complex Emulsions.

The cationic content of water represents a major quality control parameter that needs to be followed by a rapid, on-site, and low-cost method. Herein, we report a novel method for a facile monitoring of the mineral content of drinking water by making use of responsive complex emulsions. The morphology of biphasic oil-in-water droplets solely depends on the balance of interfacial tensions, and we demonstrate that changes in the surfactant effectiveness, caused by variations in the mineral content inside the continuous phase, can be visualized by monitoring internal droplet shapes. An addition of metal cations can significantly influence the surfactant critical micelle concentrations and the surface excess values and therefore induce changes in the effectiveness of ionic surfactants, such as sodium dodecyl sulfate. The morphological response of Janus emulsions droplets was tracked via a simple microscopic setup. We observed that the extent of the droplet response was dependent on the salt concentration and valency, with divalent cations (responsive for water hardness), resulting in a more pronounced response. In this way, Ca2+ and Mg2+ levels could be quantitatively measured, which we showcased by determination of the mineral content of commercial water samples. The herein demonstrated device concept may provide a new alternative rapid monitoring of water hardness levels in a simple and cost-effective setup.

The true colours of the Formidable Pygmy Grasshopper (Notocerus formidabilis Günther, 1974) from the Sava region (Madagascar).

The Formidable Pygmy Grasshopper, Notocerus formidabilis Günther, 1974 (Tetrigidae: 'Malagasy Metrodorinae'), is certainly a stunning, extraordinary insect. Despite the fact that the species was described almost 50 years ago, its beauty had remained completely hidden until recently. The bright yellow colouration of the minute warts on its dorsal hump and even brighter purple-yellowish colouration of its abdomen have been, tragically, completely lost in museum specimens. Luckily, photographs of three live females taken in 2007, 2009 and 2015 were recently uploaded to the iNaturalist platform by the first author of this paper, where they were identified as N. formidabilis by the middle and last authors. Along with a male and a female discovered in the MNHN collections (Paris) and the holotype female, these are the only records of the species. All six records are presented and depicted in the present study, and the variation of the species is discussed for the first time. This rare species seems to be endemic to NE Madagascar, a region of truly wonderful diversity.

Nanocomposite-based dual enzyme system for broad-spectrum scavenging of reactive oxygen species.

A broad-spectrum reactive oxygen species (ROS)-scavenging hybrid material (CASCADE) was developed by sequential adsorption of heparin (HEP) and poly(L-lysine) (PLL) polyelectrolytes together with superoxide dismutase (SOD) and horseradish peroxidase (HRP) antioxidant enzymes on layered double hydroxide (LDH) nanoclay support. The synthetic conditions were optimized so that CASCADE possessed remarkable structural (no enzyme leakage) and colloidal (excellent resistance against salt-induced aggregation) stability. The obtained composite was active in decomposition of both superoxide radical anions and hydrogen peroxide in biochemical assays revealing that the strong electrostatic interaction with the functionalized support led to high enzyme loadings, nevertheless, it did not interfere with the native enzyme conformation. In vitro tests demonstrated that ROS generated in human cervical adenocarcinoma cells were successfully consumed by the hybrid material. The cellular uptake was not accompanied with any toxicity effects, which makes the developed CASCADE a promising candidate for treatment of oxidative stress-related diseases.

Cascade communication in disordered networks of enzyme-loaded microdroplets.

A network of aqueous emulsion droplets that exhibits programmed and directional chemical inter-droplet communication is described. A non-reciprocal transfer of substrates between enzyme-containing aqueous emulsion droplets is realized by (biochemically) induced osmolarity gradients and concomitant concentration gradients are used to direct a multistep enzymatic cascade reaction across multiple droplets.

Cockscomb-shaped twighopper, Cladonotus bhaskari sp. n., a new and rare pygmy grasshopper species from Sri Lanka (Orthoptera: Tetrigidae: Cladonotinae).

The paper describes a new species of a Sri Lankan twighopper, genus Cladonotus Saussure, 1862 (Orthoptera: Tetrigidae: Cladonotini), C. bhaskari sp. n., based on a single female specimen collected and photographed by T. Kirschey in 2016 in Sinharaja rainforest (SW Sri Lanka). The new species is clearly distinguished from other species of the genus by its long and spine-like frontomedial projection and cockscomb-shaped promedial projection. Species of this genus resemble tiny twigs, hence the name 'twighopper'. Our new specimen is the first known female of the genus, and we also present the first photograph of the member of this genus in the natural habitat. An annotated identification key for the Cladonotus species is provided. Furthermore, we synonymize genus Hypsaeus Bolívar, 1887 syn. nov. with Hymenotes Westwood, 1837, based on the pronotal variability of the leaf-like pygmy grasshoppers in the Philippines and introduce one new combination-Hymenotes westwoodi (Bolívar, 1887) comb. nov..

Mental Health and Self-Esteem of Active Athletes.

INTRODUCTION: Systematic and continuous physical exercise of certain intensity and volume is irreplaceable in the stages of growth and development and in preventing impairments of the biological, functional and health state of the human organism.Many studies show that physical exercise contributes to development and reinforcement of mental health and increases self-esteem. Examine mental health and self-esteem of active athletes. SUBJECTS AND METHODS: The subjects of the study are active athletes from Herzegovina and students of the Faculty of Health Studies in Mostar. Mental health and self-esteem were measured by a sociodemographic questionnaire, The Symptom Checklist-90 and the Satisfaction With Life Scale. RESULTS: There is a statistically significant difference in the frequency of exercise, active athletes have the highest percentage (100%) and state that they exercise often (almost every day) while university students have a significantly lower percentage (20%).Students scored significantly higher on the subscales for somatization, obsessive - compulsive symptoms, interpersonal vulnerability, depression, anxiety, aggression, phobia, and paranoia than active athletes. Active athletes have statistically higher scores for almost all the claims of the subjective assessment of life satisfaction. CONCLUSION: Active athletes showed significantly less psychological symptoms and better mental health, greater life satisfaction and higher self-esteem than students of the Faculty of Health Studies in Mostar.

The story of the Malagasy devils (Orthoptera, Tetrigidae): Holocerus lucifer in the north and H. devriesei sp. nov. in the south?

Madagascar is home to some of the largest and most colorful pygmy grasshoppers (Tetrigidae) in the world, known as 'Malagasy Metrodorinae'. Among them, Devil's pygmy grasshoppers (genus Holocerus Bolívar, 1887) are unique in having two long spines on the back, which are modified internal lateral pronotal carinae. The genus Holocerus was composed of two species - H. lucifer (Serville, 1838) and H. taurus Rehn, 1929 syn. nov., but here it is evidenced that the latter represents a junior synonym of the former. Simultaneously, H. devriesei sp. nov. is described as a species new to science. Holocerus lucifer is a northern species of paler coloration and longer spines (distributed from Marojejy and Maroantsetra in the north to Zahamena in the south), whereas H. devriesei sp. nov. represents the southern and darker species (distributed from Vohimana and Andasibe-Mantadia in the south to the Antongil Bay in the north). There are potential overlaps in the distribution of the two species, but without more georeferenced localities, it is impossible to discriminate whether they occur only sympatrically or also syntopically.

Temperature sensitive water-in-water emulsions.

A novel approach for a temperature-sensitive stabilization of water-in-water (W/W) emulsions is described. Specifically, we leveraged the thermal induced conformation change of tailored thermoresponsive block copolymers to reversibly stabilize and destabilize water-water interfaces. In addition, we investigated our approach to reversibly tune the reaction kinetics of enzymes compartmentalized within aqueous two-phase systems.

Responsive Janus and Cerberus emulsions via temperature-induced phase separation in aqueous polymer mixtures.

Complex aqueous emulsions represent a promising material platform for the encapsulation of cells, pharmaceuticals, or nutrients, for the fabrication of structured particles, as well as for mimicking the barrier-free compartmentalization of biomolecules found in living cells. Herein, we report a novel, simple, and scalable method of creating multicomponent aqueous droplets with highly uniform internal droplet morphologies that can be controllably altered after emulsification by making use of a thermal phase separation approach. Specifically, temperature-induced phase separation inside as-formed emulsion droplets comprising aqueous mixtures of two or more hydrophilic polymers allows for the generation of Janus and Cerberus emulsion droplets with adjustable internal morphologies that are solely controlled by a balance of interfacial tensions. We demonstrate our approach by applying both, microfluidic and scalable batch production, and present a detailed model study with predictive capabilities that enables fine-tuning and dynamically altering the droplet morphology as a function of types, molecular weights, and hydrophilicities of the polymers as well as the surfactant hydrophilic-lipophilic balance. The ability to rationally design complex aqueous emulsion droplets with previously unattainable dynamic control over their morphologies after emulsification entails the potential to design new responsive soft materials with implications for a variety of applications beyond encapsulation, including the design of complex adaptive and self-regulating materials, e.g. for chemical and biological sensing applications.

Cascade Kinetics in an Enzyme-Loaded Aqueous Two-Phase System.

Macromolecular crowding plays a critical role in the kinetics of enzymatic reactions. Dynamic compartmentalization of biological components in living cells due to liquid-liquid phase separation represents an important cell regulatory mechanism that can increase enzyme concentration locally and influence the diffusion of substrates. In the present study, we probed partitioning of two enzymes (horseradish-peroxidase and urate-oxidase) in a poly(ethylene glycol)-dextran aqueous two-phase system (ATPS) as a function of salt concentration and ion position in the Hofmeister series. Moreover, we investigated enzymatic cascade reactions and their kinetics within the ATPS, which revealed a strong influence of the ion hydration stemming from the background electrolyte on the partitioning coefficients of proteins following the Hofmeister series. As a result, we were able to realize cross-partitioning of two enzymes because of different protein net charges at a chosen pH. Our study reveals a strong dependency of the enzyme activity on the substrate type and crowding agent interaction on the final kinetics of enzymatic reactions in the ATPS and therefore provides substantial implications en route toward dynamic regulation of reactivity in synthetic protocells.