Soluble Fms-like tyrosine kinase-1 polymorphisms associated with severe-spectrum hypertensive disorders of pregnancy.

Background: sFLT-1 has been implicated in the pathogenesis of HDP. We aimed to examine the role of maternal and fetal polymorphisms in risk of HDP and severe-spectrum disease.

Methods: Cases of HDP (143) and controls (169) from mother-baby dyads were recruited at the Los Angeles County Women's and Children's Hospital (WCH).

The impact of grazing on biodiversity and forest succession in the Brazilian dry forest region is constrained by non-equilibrium dynamics.

The impacts of grazing on rangelands have historically been studied within the framework of the equilibrium model, which predicts significant impacts of grazing on ecosystems. However, in recent decades, studies have observed a non-equilibrium pattern, suggesting that abiotic factors play a primary role compared to grazing. These studies are primarily focused on rangelands, despite animal husbandry occurring in other biomes, such as seasonally dry tropical forests.

Neutrophil-specific expression of JAK2-V617F or CALRmut induces distinct inflammatory profiles in myeloproliferative neoplasia.

Background: Neutrophils play a crucial role in inflammation and in the increased thrombotic risk in myeloproliferative neoplasms (MPNs). We have investigated how neutrophil-specific expression of JAK2-V617F or CALRdel re-programs the functions of neutrophils.

Methods: Ly6G-Cre JAK2-V617F and Ly6G-Cre CALRdel mice were generated.

Crystal Structure and NMR of an α,δ-Peptide Foldamer Helix Shows Side-Chains are Well Placed for Bifunctional Catalysis: Application as a Minimalist Aldolase Mimic.

We report the first NMR and X-ray diffraction (XRD) structures of an unusual 13/11-helix (alternating i, i+1 {NH-O=C} and i, i+3 {C=O-H-N} H-bonds) formed by a heteromeric 1 : 1 sequence of α- and δ-amino acids, and demonstrate the application of this framework towards catalysis. Whilst intramolecular hydrogen bonds (IMHBs) are the clear driver of helix formation in this system, we also observe an apolar interaction between the ethyl residue of one δ-amino acid and the cyclohexyl group of the next δ-residue in the sequence that seems to stabilize one type of helix over another. To the best of our knowledge this type of additional stabilization leading to a specific helical preference has not been observed before.

Activating mutations in JAK2 and CALR differentially affect intracellular calcium flux in store operated calcium entry.

Background: Calcium (Ca) signaling regulates various vital cellular functions, including integrin activation and cell migration. Store-operated calcium entry (SOCE) via calcium release-activated calcium (CRAC) channels represents a major pathway for Ca influx from the extracellular space in multiple cell types. The impact of JAK2-V617F and CALR mutations which are disease initiating in myeloproliferative neoplasms (MPN) on SOCE, calcium flux from the endoplasmic reticulum (ER) to the cytosol, and related key signaling pathways in the presence or absence of erythropoietin (EPO) or thrombopoietin (TPO) is poorly understood.

System-Specific Parameter Optimization for Nonpolarizable and Polarizable Force Fields.

The accuracy of classical force fields (FFs) has been shown to be limited for the simulation of cation-protein systems despite their importance in understanding the processes of life. Improvements can result from optimizing the parameters of classical FFs or by extending the FF formulation by terms describing charge transfer (CT) and polarization (POL) effects. In this work, we introduce our implementation of the CTPOL model in OpenMM, which extends the classical additive FF formula by adding CT and POL.

Shared metadata for data-centric materials science.

The expansive production of data in materials science, their widespread sharing and repurposing requires educated support and stewardship. In order to ensure that this need helps rather than hinders scientific work, the implementation of the FAIR-data principles () must not be too narrow. Besides, the wider materials-science community ought to agree on the strategies to tackle the challenges that are specific to its data, both from computations and experiments.

Crystal Structure and NMR of an α,δ-Peptide Foldamer Helix Shows Side-Chains are Well Placed for Bifunctional Catalysis: Application as a Minimalist Aldolase Mimic.

We report the first NMR and X-ray diffraction (XRD) structures of an unusual 13/11-helix (alternating i, i+1 {NH-O=C} and i, i+3 {C=O-H-N} H-bonds) formed by a heteromeric 1 : 1 sequence of α- and δ-amino acids, and demonstrate the application of this framework towards catalysis. Whilst intramolecular hydrogen bonds (IMHBs) are the clear driver of helix formation in this system, we also observe an apolar interaction between the ethyl residue of one δ-amino acid and the cyclohexyl group of the next δ-residue in the sequence that seems to stabilize one type of helix over another. To the best of our knowledge this type of additional stabilization leading to a specific helical preference has not been observed before.

induces tolerance in human monocytes accompanied with expression changes of cell surface markers.

Exposure of human monocytes to lipopolysaccharide (LPS) or other pathogen-associated molecular pattern (PAMPs) induces a temporary insensitivity to subsequent LPS challenges, a cellular state called endotoxin tolerance (ET), associated with the pathogenesis of sepsis. In this study, we aimed to characterize the cellular state of human monocytes from healthy donors stimulated with in comparison to TLR2-specific ligands. We analyzed induced gene expression changes after 2 and 24 hours by amplicon sequencing (RNA-AmpliSeq) and compared the pro-inflammatory response after 2 hours with the response in re-stimulation experiments.

Impact of anion polarizability on ion pairing in microhydrated salt clusters.

Despite longstanding interest in the mechanism of salt dissolution in aqueous media, a molecular level understanding remains incomplete. Here, cryogenic ion trap vibrational action spectroscopy is combined with electronic structure calculations to track salt hydration in a gas phase model system one water molecule at a time. The infrared photodissociation spectra of microhydrated lithium dihalide anions [LiXX'(HO) ] (XX' = I, ClI and Cl; = 1-3) in the OH stretching region (3800-2800 cm) provide a detailed picture of how anion polarizability influences the competition among ion-ion, ion-water and water-water interactions.

Better force fields start with better data: A data set of cation dipeptide interactions.

We present a data set from a first-principles study of amino-methylated and acetylated (capped) dipeptides of the 20 proteinogenic amino acids - including alternative possible side chain protonation states and their interactions with selected divalent cations (Ca, Mg and Ba). The data covers 21,909 stationary points on the respective potential-energy surfaces in a wide relative energy range of up to 4 eV (390 kJ/mol). Relevant properties of interest, like partial charges, were derived for the conformers.

Thromboinflammation in Myeloproliferative Neoplasms (MPN)-A Puzzle Still to Be Solved.

Myeloproliferative neoplasms (MPNs), a group of malignant hematological disorders, occur as a consequence of somatic mutations in the hematopoietic stem cell compartment and show excessive accumulation of mature myeloid cells in the blood. A major cause of morbidity and mortality in these patients is the marked prothrombotic state leading to venous and arterial thrombosis, including myocardial infarction (MI), deep vein thrombosis (DVT), and strokes. Additionally, many MPN patients suffer from inflammation-mediated constitutional symptoms, such as fever, night sweats, fatigue, and cachexia.

Di-butyl phthalate (DBP) induces defects during embryonic eye development in zebrafish.

Di-butyl phthalate (DBP) is a phthalate ester (PAEs) added during the manufacturing of plastics to make them stronger, yet more pliable. DBP is noncovalently bound to plastics resulting in leaching into the environment. Concerning concentrations of DBP have been noted in surface and groundwater, aquatic ecosystems, soil and atmospheric environments globally.

Anti-inflammatory treatment in MPN: targeting TNFR1 and TNFR2 in JAK2-V617F-induced disease.

Chronic nonresolving inflammatory syndrome is a major disease feature in myeloproliferative neoplasms (MPNs). Systemic inflammation promotes the growth of the JAK2-V617F+ hematopoietic stem cell clone and is associated with constitutive symptoms (eg, fever, cachexia, and fatigue). Therefore, it is being discussed whether anti-inflammatory therapy, in addition to the well-established JAK inhibitor therapy, may be beneficial in the control of constitutive symptoms.

Anti-IL-6 cytokine treatment has no impact on elevated hematocrit or splenomegaly in a polycythemia vera mouse model.

Somatic mutations in JAK2, MPL and Calreticulin and inflammation play a key role in pathophysiology of chronic myeloproliferative neoplasia (CMN). One of the most prominent cytokines elevated in serum of Polycythemia vera patients is interleukin-6 (IL-6). Currently, it is being discussed whether suppression of inflammation by anti-cytokine approaches as anti-IL-6 treatment may be therapeutically useful in CMN.

Developing Brain Glucose Transporters, Serotonin, Serotonin Transporter, and Oxytocin Receptor Expression in Response to Early-Life Hypocaloric and Hypercaloric Dietary, and Air Pollutant Exposures.

Perturbed maternal diet and prenatal exposure to air pollution (AP) affect the fetal brain, predisposing to postnatal neurobehavioral disorders. Glucose transporters (GLUTs) are key in fueling neurotransmission; deficiency of the neuronal isoform GLUT3 culminates in autism spectrum disorders. Along with the different neurotransmitters, serotonin (5-HT) and oxytocin (OXT) are critical for the development of neural connectivity.

Benchmarking polarizable and non-polarizable force fields for Ca-peptides against a comprehensive QM dataset.

Explicit description of atomic polarizability is critical for the accurate treatment of inter-molecular interactions by force fields (FFs) in molecular dynamics (MD) simulations aiming to investigate complex electrostatic environments such as metal-binding sites of metalloproteins. Several models exist to describe key monovalent and divalent cations interacting with proteins. Many of these models have been developed from ion-amino-acid interactions and/or aqueous-phase data on cation solvation.

Murine maternal dietary restriction affects neural Humanin expression and cellular profile.

To understand the cellular basis for the neurodevelopmental effects of intrauterine growth restriction (IUGR), we examined the global and regional expression of various cell types within murine (Mus musculus) fetal brain. Our model employed maternal calorie restriction to 50% daily food intake from gestation day 10-19, producing IUGR offspring. Offspring had smaller head sizes with larger head:body ratios indicating a head sparing IUGR effect.

Socioeconomic differences among resident, users and neighbour populations of a protected area in the Brazilian dry forest.

Protected areas are an important strategy to safeguard biodiversity. However, if social development is not considered, biological conservation targets may not be achieved. In this empirical study, we assess the relationship between poverty and conservation goals in dry forests within a 62,000-ha Brazilian National Park (Caatinga biome).

Probing chirality recognition of protonated glutamic acid dimers by gas-phase vibrational spectroscopy and first-principles simulations.

The homochirality of the amino acid metabolism still puzzles biochemists. Vibrational spectroscopy of mass-selected gas-phase amino acids and their clusters can precisely reveal their conformation and might ultimately help to decode the interactions responsible for chirality recognition. Infrared photodissociation (IRPD) and conformer-selective IR-IR hole burning spectra of protonated glutamic acid dimers (LL-/LD-Glu2H+) recorded in the fingerprint and XH stretch ranges (1100-1900 and 2600-3600 cm-1) provide direct insight into their stereospecific interactions.

Structure and Reactivity of Al-O(H)-Al Moieties in Siloxide Frameworks: Solution and Gas-Phase Model Studies.

Even though aluminas and aluminosilicates have found widespread application, a consistent molecular understanding of their surface heterogeneity and the behavior of defects resulting from hydroxylation/dehydroxylation remains unclear. Here, we study the well-defined molecular model compound, [Al (μ -OH) (THF) (PhSi(OSiPh O) ) ], 1, to gain insight into the acid-base reactivity of cyclic trinuclear Al (μ -OH) moieties at the atomic level. We find that, like zeolites, they are sufficiently acidic to catalyze the isomerization of olefins.

The Lysosomal Protein Arylsulfatase B Is a Key Enzyme Involved in Skeletal Turnover.

Skeletal pathologies are frequently observed in lysosomal storage disorders, yet the relevance of specific lysosomal enzymes in bone remodeling cell types is poorly defined. Two lysosomal enzymes, ie, cathepsin K (Ctsk) and Acp5 (also known as tartrate-resistant acid phosphatase), have long been known as molecular marker proteins of differentiated osteoclasts. However, whereas the cysteine protease Ctsk is directly involved in the degradation of bone matrix proteins, the molecular function of Acp5 in osteoclasts is still unknown.

Lévy foraging patterns of rural humans.

Movement patterns resembling Lévy walks, often attributed to the execution of an advantageous probabilistic searching strategy, are found in a wide variety of organisms, from cells to human hunter-gatherers. It has been suggested that such movement patterns may be fundamental to how humans interact and experience the world and that they may have arisen early in our genus with the evolution of a hunting and gathering lifestyle. Here we show that Lévy walks are evident in the Me'Phaa of Mexico, in Brazilian Cariri farmers and in Amazonian farmers when gathering firewood, wild fruit and nuts.

The Structure of the Protonated Serine Octamer.

The amino acid serine has long been known to form a protonated "magic-number" cluster containing eight monomer units that shows an unusually high abundance in mass spectra and has a remarkable homochiral preference. Despite many experimental and theoretical studies, there is no consensus on a SerH structure that is in agreement with all experimental observations. Here, we present the structure of SerH determined by a combination of infrared spectroscopy and ab initio molecular dynamics simulations.