Structure, Physicochemical Properties and Biological Activity of Lipopolysaccharide from the Rhizospheric Bacterium Ochrobactrum quorumnocens T1Kr02, Containing d-Fucose Residues.

Lipopolysaccharides (LPSs) are major components of the outer membranes of Gram-negative bacteria. In this work, the structure of the O-polysaccharide of Ochrobactrum quorumnocens T1Kr02 was identified by nuclear magnetic resonance (NMR), and the physical-chemical properties and biological activity of LPS were also investigated. The NMR analysis showed that the O-polysaccharide has the following structure: →2)-ß-d-Fucf-(1→3)-ß-d-Fucp-(1→. The structure of the periplasmic glucan coextracted with LPS was established by NMR spectroscopy and chemical methods: →2)-ß-d-Glcp-(1→. Non-stoichiometric modifications were identified in both polysaccharides: 50% of d-fucofuranose residues at position 3 were O-acetylated, and 15% of d-Glcp residues at position 6 were linked with succinate. This is the first report of a polysaccharide containing both d-fucopyranose and d-fucofuranose residues. The fatty acid analysis of the LPS showed the prevalence of 3-hydroxytetradecanoic, hexadecenoic, octadecenoic, lactobacillic, and 27-hydroxyoctacosanoic acids. The dynamic light scattering demonstrated that LPS (in an aqueous solution) formed supramolecular particles with a size of 72.2 nm and a zeta-potential of -21.5 mV. The LPS solution (10 mkg/mL) promoted the growth of potato microplants under in vitro conditions. Thus, LPS of O. quorumnocens T1Kr02 can be recommended as a promoter for plants and as a source of biotechnological production of d-fucose.

Surgical Innovations in Tracheal Reconstruction: A Review on Synthetic Material Fabrication.

Background and Objectives: The aim of this review is to explore the recent surgical innovations in tracheal reconstruction by evaluating the uses of synthetic material fabrication when dealing with tracheomalacia or stenotic pathologies, then discussing the challenges holding back these innovations. Materials and Methods: A targeted non-systematic review of published literature relating to tracheal reconstruction was performed within the PubMed database to help identify how synthetic materials are utilised to innovate tracheal reconstruction. Results: The advancements in 3D printing to aid synthetic material fabrication have unveiled promising alternatives to conventional approaches. Achieving successful tracheal reconstruction through this technology demands that the 3D models exhibit biocompatibility with neighbouring tracheal elements by encompassing vasculature, chondral foundation, and immunocompatibility. Tracheal reconstruction has employed grafts and scaffolds, showing a promising beginning in vivo. Concurrently, the integration of resorbable models and stem cell therapy serves to underscore their viability and application in the context of tracheal pathologies. Despite this, certain barriers hinder its advancement in surgery. The intricate tracheal structure has posed a challenge for researchers seeking novel approaches to support its growth and regeneration. Conclusions: The potential of synthetic material fabrication has shown promising outcomes in initial studies involving smaller animals. Yet, to fully realise the applicability of these innovative developments, research must progress toward clinical trials. These trials would ascertain the anatomical and physiological effects on the human body, enabling a thorough evaluation of post-operative outcomes and any potential complications linked to the materials or cells implanted in the trachea.

Continuous-Flow Divergent Lithiation of 2,3-Dihalopyridines: Deprotolithiation versus Halogen Dance.

We describe herein the first halogen dance (HD) in continuous flow on 2-chloro-3-bromopyridine by selectively trapping a (pyridin-4-yl)lithium species that is known to undergo the halogen-dance process. In addition, this lithiated intermediate was trapped at lower temperature before the HD occurs. The HD process was extended to fluoro-iodopyridines by using various electrophiles to afford 28 examples with yields ranging from 42 to 97 % with very short residence times. Finally, scale up of the reaction was demonstrated, affording a promising space-time yield (STY) of 4.2 kg.h-1 .L-1 .

Ultrasound-assisted co-precipitation synthesis of GdFeO3 nanoparticles: structure, magnetic and MRI contrast properties.

Superparamagnetic nanocrystals of gadolinium orthoferrite (GdFeO3) with close to isometric morphology were successfully synthesized by heat treatment of gadolinium and iron(III) hydroxides obtained by direct co-precipitation with and without ultrasonic irradiation. The obtained samples were investigated by PXRD, low-temperature nitrogen adsorption-desorption isotherm measurements, HRTEM and VSM. It was established that ultrasonication during co-precipitation led to a decrease in the average size of GdFeO3 crystallites obtained after heat treatment by approximately 19%, an increase in their BET specific surface area by more than two times, a decrease in the degree of their aggregation by about five times and an improvement in their magnetic properties due to the increase in phase homogeneity. The colloidal solutions of the GdFeO3 nanoparticles synthesized using ultrasound were investigated by 1H NMR to measure the T1 and T2 relaxation times of water protons at 0.47 T. The resulting relaxivities r1 and r2 were approximately recalculated at 1.5, 3 and 4.7 T on the basis of a semi-statistical ad hoc method by analyzing the literature data for a number of structurally similar compounds with reported relaxivity values at different NMR frequencies. According to the experimental and predicted values of the r2/r1 ratio, the investigated GdFeO3 sample may be classified as a T1-contrast agent for MRI at 0.47 and 1.5 T, as a T1-T2 dual-modal contrast agent at 3 T and as a T2-contrast agent at 4.7 T.

Anti-Proliferative and Cytoprotective Activity of Aryl Carbamate and Aryl Urea Derivatives with Alkyl Groups and Chlorine as Substituents.

Natural cytokinines are a promising group of cytoprotective and anti-tumor agents. In this research, we synthesized a set of aryl carbamate, pyridyl urea, and aryl urea cytokinine analogs with alkyl and chlorine substitutions and tested their antiproliferative activity in MDA-MB-231, A-375, and U-87 MG cell lines, and cytoprotective properties in H2O2 and CoCl2 models. Aryl carbamates with the oxamate moiety were selectively anti-proliferative for the cancer cell lines tested, while the aryl ureas were inactive. In the cytoprotection studies, the same aryl carbamates were able to counteract the CoCl2 cytotoxicity by 3-8%. The possible molecular targets of the aryl carbamates during the anti-proliferative action were the adenosine A2 receptor and CDK2. The obtained results are promising for the development of novel anti-cancer therapeutics.

An empirical comparison of univariate versus multivariate methods for the analysis of brain-behavior mapping.

Lesion symptom mapping (LSM) tools are used on brain injury data to identify the neural structures critical for a given behavior or symptom. Univariate lesion symptom mapping (ULSM) methods provide statistical comparisons of behavioral test scores in patients with and without a lesion on a voxel by voxel basis. More recently, multivariate lesion symptom mapping (MLSM) methods have been developed that consider the effects of all lesioned voxels in one model simultaneously. In the current study, we provide a much-needed systematic comparison of several ULSM and MLSM methods, using both synthetic and real data to identify the potential strengths and weaknesses of both approaches. We tested the spatial precision of each LSM method for both single and dual (network type) anatomical target simulations across anatomical target location, sample size, noise level, and lesion smoothing. Additionally, we performed false positive simulations to identify the characteristics associated with each method's spurious findings. Simulations showed no clear superiority of either ULSM or MLSM methods overall, but rather highlighted specific advantages of different methods. No single method produced a thresholded LSM map that exclusively delineated brain regions associated with the target behavior. Thus, different LSM methods are indicated, depending on the particular study design, specific hypotheses, and sample size. Overall, we recommend the use of both ULSM and MLSM methods in tandem to enhance confidence in the results: Brain foci identified as significant across both types of methods are unlikely to be spurious and can be confidently reported as robust results.

Changes in the fatty acid composition of pine needle lipids under the aluminum smelter emissions.

Changes in the fatty acid (FA) composition of total lipids of Pinus sylvestris needles at different pollution levels caused by emissions from a large aluminum smelter (BrAS) have been studied. In the needles of trees from unpolluted (background) territories, the FA spectrum is represented by 24 acids with prevalence of unsaturated FAs (71.6%). The main unsaturated FA are represented by oleic (C18: 1ω9), linoleic (C18: 2ω6), and α-linolenic (C18: 3ω3) acids. Under the influence of BrAS emissions, the total amount of identified FAs in the needles and the proportion of unsaturated FAs decrease, while the fraction of saturated FAs, on the contrary, increases from 25.4% in unpolluted needles to 33.2% in polluted ones. The content of palmitic FA (C16:0) in the needles exceeds background values by 1.5 times, behenic acid (C22:0) - by 1.6-2.5 times, arachidic acid (C20:0) - by 1.5 times, palmitic margaric acid (C17:0) - by 1.5-2.3 times. These FAs play the important role in the protection of plant membranes from the effects of abiotic stress factors, making them less permeable. The sum of short-chain saturated FAs (C12:0, C14:0, C15:0) increase by 4.8 times in needles of trees that are highly polluted. Pentadecanoic (C15:0) acid is found in the needles only in the background areas and at the low pollution level. With a more severe pollution, C15:0 is not identified, but lauric acid with the cis-configuration of double bonds in the structure (izo-C12:0) appears. The presence of "relict" ∆5-polymethylene FAs in the composition of pine needle membrane lipids is determined. In the background areas, they account for 12.9% of the total FAs. With the industrial pollution intensification, their total content increases and reaches 14.1%. ∆5-polymethylene FAs are also able to protect membranes against negative influences. Thus, changes in the quantitative and qualitative FA composition of pine needle total lipids indicate the activation of the stabilization mechanisms of membrane lipids due to their tight packing in a bilayer. It is one of the adaptive reactions of Pinus sylvestris in response to the impact of the aluminum industry emissions.

Regional diversity in subsistence among early farmers in Southeast Europe revealed by archaeological organic residues.

The spread of early farming across Europe from its origins in Southwest Asia was a culturally transformative process which took place over millennia. Within regions, the pace of the transition was probably related to the particular climatic and environmental conditions encountered, as well as the nature of localized hunter-gatherer and farmer interactions. The establishment of farming in the interior of the Balkans represents the first movement of Southwest Asian livestock beyond their natural climatic range, and widespread evidence now exists for early pottery being used extensively for dairying. However, pottery lipid residues from sites in the Iron Gates region of the Danube in the northern Balkans show that here, Neolithic pottery was being used predominantly for processing aquatic resources. This stands out not only within the surrounding region but also contrasts markedly with Neolithic pottery use across wider Europe. These findings provide evidence for the strategic diversity within the wider cultural and economic practices during the Neolithic, with this exceptional environmental and cultural setting offering alternative opportunities despite the dominance of farming in the wider region.

Copper-Catalyzed Enantioselective Formation of C-CF3 Centers from ß-CF3 -Substituted Acrylates and Acrylonitriles.

The catalytic asymmetric synthesis of ß-trifluoromethylated esters or nitriles is reported. The use of an in situ formed chiral Cu-H complex allowed the enantioselective reduction of ß-trifluoromethylated acrylates or acrylonitriles. The reaction proceeds smoothly affording the corresponding enantioenriched products in good to excellent yields and outstanding enantioselectivities (up to 98 % ee). The mechanism of the reaction was studied, and a plausible reaction pathway was suggested accordingly. Finally, the versatility of the products was highlighted through functional group manipulations.

Mild Homologation of Esters through Continuous Flow Chloroacetate Claisen Reactions.

The selective chloromethylenation of functionalized esters using chloroacetic acid (CA) and LiHMDS (HMDS=hexamethyldisilazide) in a continuous-flow setup is reported. This Claisen homologation is for the first time extended to bis-chloromethylenation using dichloroacetic acid (DCA), thus giving access to under-explored α,α'-bis-chloroketones. The use of flow conditions enables efficient generation and reaction of the unstable chloroacetate dianion intermediates, leading to unprecedented mild and scalable reaction conditions at an economical reagent stoichiometry (-10 °C, <1 min, 1.0-2.4 equiv dianion). The clean reaction profiles allow subsequent use of the unpurified crude products, which is demonstrated in the synthesis of various heterocycles of broad interest. Furthermore, we report a novel, catalyst-free substitution of the obtained monochloro ketone products with (hetero)aryl zinc enolates to give valuable 1,4-diketones.

Copper-Mediated Introduction of the CF2 PO(OEt)2 Motif: Scope and Limitations.

Herein, a general procedure to access CF2 PO(OEt)2 -containing molecules is reported. The reagent CuCF2 PO(OEt)2 is accessible by a simple protocol and a broad range of substrates can be functionalised. The procedure allows the conversion of aryl diazonium salts, as well as aryl, heteroaryl, vinyl and alkynyl iodonium salts, into the corresponding fluorinated molecules at room temperature. Mechanistic studies were performed to gain a better understanding of the reaction pathway. Under similar conditions, vinyl and aryl iodides, allyl halides, and benzyl bromides were also functionalised, and the scope and limitations of the reaction were studied. Finally, the procedure was extended to disulfides to offer new access to SCF2 PO(OEt)2 -containing molecules.

What Do Language Disorders Reveal about Brain-Language Relationships? From Classic Models to Network Approaches.

Studies of language disorders have shaped our understanding of brain-language relationships over the last two centuries. This article provides a review of this research and how our thinking has changed over the years regarding how the brain processes language. In the 19th century, a series of famous case studies linked distinct speech and language functions to specific portions of the left hemisphere of the brain, regions that later came to be known as Broca's and Wernicke's areas. One hundred years later, the emergence of new brain imaging tools allowed for the visualization of brain injuries in vivo that ushered in a new era of brain-behavior research and greatly expanded our understanding of the neural processes of language. Toward the end of the 20th century, sophisticated neuroimaging approaches allowed for the visualization of both structural and functional brain activity associated with language processing in both healthy individuals and in those with language disturbance. More recently, language is thought to be mediated by a much broader expanse of neural networks that covers a large number of cortical and subcortical regions and their interconnecting fiber pathways. Injury to both grey and white matter has been seen to affect the complexities of language in unique ways that have altered how we think about brain-language relationships. The findings that support this paradigm shift are described here along with the methodologies that helped to discover them, with some final thoughts on future directions, techniques, and treatment interventions for those with communication impairments. (JINS, 2017, 23, 741-754).

The Distribution of Activation Markers and Selectins on Peripheral T Lymphocytes in Preeclampsia.

INTRODUCTION: Impaired maternal immune tolerance resulting in systemic inflammation plays a pivotal role in the pathogenesis of preeclampsia. Phenotypical changes of monocytes and neutrophil granulocytes have already been studied in preeclampsia, and some studies also included T lymphocyte activation markers; however, the results are controversial and a comprehensive analysis of activation markers is lacking. The characteristics of cellular adhesion molecules in preeclampsia are yet to be described. MATERIAL AND METHODS: Peripheral blood samples of 18 preeclamptic patients and 20 healthy pregnant women in the third trimester were evaluated using flow cytometry to characterize the cell surface expression of T lymphocyte activation markers and selectins. RESULTS: We found an elevated ratio of HLA-DR and CD122-, CD62E-, and CD62L-expressing cells among the CD4+ T lymphocytes in PE in comparison to healthy pregnancy. No alterations were found in the prevalence of CD69-, CD25-, and CD62P-expressing lymphocytes and CD11c-expressing monocytes. CONCLUSIONS: Our findings support the role of activated T lymphocytes and specific cell adhesion molecules in the pathogenesis of preeclampsia.

Partial Attenuation of Respiratory Syncytial Virus with a Deletion of a Small Hydrophobic Gene Is Associated with Elevated Interleukin-1ß Responses.

UNLABELLED: The small hydrophobic (SH) gene of respiratory syncytial virus (RSV), a major cause of infant hospitalization, encodes a viroporin of unknown function. SH gene knockout virus (RSV ΔSH) is partially attenuated in vivo, but not in vitro, suggesting that the SH protein may have an immunomodulatory role. RSV ΔSH has been tested as a live attenuated vaccine in humans and cattle, and here we demonstrate that it protected against viral rechallenge in mice. We compared the immune response to infection with RSV wild type and RSV ΔSH in vivo using BALB/c mice and in vitro using epithelial cells, neutrophils, and macrophages. Strikingly, the interleukin-1ß (IL-1ß) response to RSV ΔSH infection was greater than to wild-type RSV, in spite of a decreased viral load, and when IL-1ß was blocked in vivo, the viral load returned to wild-type levels. A significantly greater IL-1ß response to RSV ΔSH was also detected in vitro, with higher-magnitude responses in neutrophils and macrophages than in epithelial cells. Depleting macrophages (with clodronate liposome) and neutrophils (with anti-Ly6G/1A8) demonstrated the contribution of these cells to the IL-1ß response in vivo, the first demonstration of neutrophilic IL-1ß production in response to viral lung infection. In this study, we describe an increased IL-1ß response to RSV ΔSH, which may explain the attenuation in vivo and supports targeting the SH gene in live attenuated vaccines. IMPORTANCE: There is a pressing need for a vaccine for respiratory syncytial virus (RSV). A number of live attenuated RSV vaccine strains have been developed in which the small hydrophobic (SH) gene has been deleted, even though the function of the SH protein is unknown. The structure of the SH protein has recently been solved, showing it is a pore-forming protein (viroporin). Here, we demonstrate that the IL-1ß response to RSV ΔSH is greater in spite of a lower viral load, which contributes to the attenuation in vivo. This potentially suggests a novel method by which viruses can evade the host response. As all Pneumovirinae and some Paramyxovirinae carry similar SH genes, this new understanding may also enable the development of live attenuated vaccines for both RSV and other members of the Paramyxoviridae.

New Prospects toward the Synthesis of Difluoromethylated Phosphate Mimics.

The difluoromethyl phosphonate motif plays a crucial role in the development of bioactive molecules as it is considered as a phosphate bioisoster. Since 2010, a renewal of interest to enlarge the panel of reactions to access these difluoromethylated phosphonate-containing molecules has been witnessed. This Concept article charts the recent progress that has been made.

Copper Salt-Controlled Divergent Reactivity of [Cu]CF2 PO(OEt)2 with α-Diazocarbonyl Derivatives.

Herein, we report a copper salt-controlled divergent reactivity toward α-diazocarbonyl compounds. By a simple change of the copper counteranion under identical reaction conditions, the reported method allowed an easy access to either (Z)-α-fluorovinylphosphonate or alkyl-SCF2 PO(OEt)2 derivatives in good yields. Mechanistic studies were performed and suggested two different pathways to explain the formation of these products.

[XeOXeOXe](2+), the Missing Oxide of Xenon(II); Synthesis, Raman Spectrum, and X-ray Crystal Structure of [XeOXeOXe][µ-F(ReO2F3)2]2.

The [XeOXeOXe](2+) cation provides an unprecedented example of a xenon(II) oxide and a noble-gas oxocation as well as a rare example of a noble-gas dication. The [XeOXeOXe](2+) cation was synthesized as its [µ-F(ReO2F3)2](-) salt by reaction of ReO3F with XeF2 in anhydrous HF at -30 °C. Red-orange [XeOXeOXe][µ-F(ReO2F3)2]2 rapidly decomposes to XeF2, ReO2F3, Xe, and O2 when the solid or its HF solutions are warmed above -20 °C. The crystal structure of [XeOXeOXe][µ-F(ReO2F3)2]2 consists of a planar, zigzag-shaped [XeOXeOXe](2+) cation (C2h symmetry) that is fluorine bridged through its terminal xenon atoms to two [µ-F(ReO2F3)2](-) anions. The Raman spectra of the natural abundance and (18)O-enriched [XeOXeOXe](2+) salts are consistent with a centrosymmetric (C2h) cation geometry. A proposed reaction pathway leading to [XeOXeOXe][µ-F(ReO2F3)2]2 consists of a series of oxygen/fluorine metathesis reactions that are presumably mediated by the transient HOXeF molecule. Quantum-chemical calculations were used to aid in the vibrational assignments of [Xe(16/18)OXe(16/18)OXe][µ-F(Re(16/18)O2F3)2]2 and to assess the bonding in [XeOXeOXe](2+) by NBO, QTAIM, ELF, and MEPS analyses. Ion pair interactions occur through Re-Fµ---Xe bridges, which are predominantly electrostatic in nature and result from polarization of the Fµ-atom electron densities by the exposed core charges of the terminal xenon atoms. Each xenon(II) atom is surrounded by a torus of xenon valence electron density comprised of the three valence electron lone pairs. The positive regions of the terminal xenon atoms and associated fluorine bridge bonds correspond to the positive σ-holes and donor interactions that are associated with "halogen bonding".

Seasonal changes in the content of dehydrins in mesophyll cells of common pine needles.

The appearance of dehydrins (DHNs) in cells is required for the development of cold resistance. DHNs are therefore considered specific markers of cold resistance by some authors. DHNs accumulate in plants concomitantly with a reduction of intracellular water content, and presumably protect membranes and proteins from damage caused by moisture loss. DHN content in pine needles increases in spring and autumn when moisture availability and temperatures are most unfavorable. The present work is focused on seasonal changes in DHN content in various mesophyll-cell compartments of pine (Pinus sylvestris L.) needles in association with changes in environmental factors. In spring, the number of thylakoid membranes per granum was lower than in summer and autumn. An increase in needle content of DHNs with approximate masses of 76, 73, 72, 35, and 17 kD in spring and autumn, associated with needle dehydration during this period, is shown here. The largest increase in DHN content was observed in spring, with the highest amount of DHNs presented in chloroplast membrane system including grana thylakoids, stromal thylakoids, and the two chloroplast envelope membranes and in cell walls. In the autumn, most DHNs were localized in chloroplasts and mitochondria.