Coastal dune management affects above and belowground biotic characteristics.

Dune vegetation mediates dune-building through trapping wind-blown sand and reduces dune erosion by attenuating wave energy via above- and belowground biomass. Despite the role of vegetation in dune functions, the amount and distribution of biomass within a dune remains poorly quantified due to a lack of ample data. Our objectives were to determine the effects of management history and elevation on (1) dune belowground biotic structure and aboveground community composition and (2) to determine best predictors of belowground biomass.

Shoreface erosion counters blue carbon accumulation in transgressive barrier-island systems.

Landward migration of coastal ecosystems in response to sea-level rise is altering coastal carbon dynamics. Although such landscapes rapidly accumulate soil carbon, barrier-island migration jeopardizes long-term storage through burial and exposure of organic-rich backbarrier deposits along the lower beach and shoreface. Here, we quantify the carbon flux associated with the seaside erosion of backbarrier lagoon and peat deposits along the Virginia Atlantic Coast.

Marine Transgression in Modern Times.

Marine transgression associated with rising sea levels causes coastal erosion, landscape transitions, and displacement of human populations globally. This process takes two general forms. Along open-ocean coasts, active transgression occurs when sediment-delivery rates are unable to keep pace with accommodation creation, leading to wave-driven erosion and/or landward translation of coastal landforms.

Enhanced Vaccine Effectiveness during the Delta Phase of the COVID-19 Pandemic in the Medicare Population Supports a Multilayered Prevention Approach.

Throughout the pandemic, individuals 65 years and older have contributed most COVID-19 related deaths. To best formulate effective vaccination and other prevention policies to protect older adults, large scale observational studies of these higher risk individuals are needed. We conducted a Vaccine Effectiveness (VE) study during the B.

A Predictive Model for Severe COVID-19 in the Medicare Population: A Tool for Prioritizing Primary and Booster COVID-19 Vaccination.

Recommendations for prioritizing COVID-19 vaccination have focused on the elderly at higher risk for severe disease. Existing models for identifying higher-risk individuals lack the needed integration of socio-demographic and clinical risk factors. Using multivariate logistic regression and random forest modeling, we developed a predictive model of severe COVID-19 using clinical data from Medicare claims for 16 million Medicare beneficiaries and socio-economic data from the CDC Social Vulnerability Index.

Electrophysiology on Channel-Forming Proteins in Artificial Lipid Bilayers: Next-Generation Instrumentation for Multiple Recordings in Parallel.

Artificial lipid bilayers have been used for several decades to study channel-forming pores and ion channels in membranes. Until recently, the classical two-chamber setups have been primarily used for studying the biophysical properties of pore forming proteins. Within the last 10 years, instruments for automated lipid bilayer measurements have been developed and are now commercially available.

Millennial-scale hydroclimate control of tropical soil carbon storage.

The storage of organic carbon in the terrestrial biosphere directly affects atmospheric concentrations of carbon dioxide over a wide range of timescales. Within the terrestrial biosphere, the magnitude of carbon storage can vary in response to environmental perturbations such as changing temperature or hydroclimate, potentially generating feedback on the atmospheric inventory of carbon dioxide. Although temperature controls the storage of soil organic carbon at mid and high latitudes, hydroclimate may be the dominant driver of soil carbon persistence in the tropics; however, the sensitivity of tropical soil carbon turnover to large-scale hydroclimate variability remains poorly understood.

Towards complete polypeptide backbone NH assignment via combinatorial labeling.

Combinatorial selective isotope labeling is a valuable tool to facilitate polypeptide backbone resonance assignment in cases of low sensitivity or extensive chemical shift degeneracy. It involves recording of N-HSQC and 2D HN-projections of triple-resonance spectra on a limited set of samples containing different combinations of labeled and unlabeled amino acid types. Using labeling schemes in which the three backbone heteronuclei (amide nitrogen, α-carbon and carbonyl carbon) are enriched in N or C isotopes - individually as well as simultaneously - usually yields abundant amino-acid type information of consecutive residues i and i - 1.

Millennial soil retention of terrestrial organic matter deposited in the Bengal Fan.

The abundance of organic carbon (OC) in vegetation and soils (~2,600 PgC) compared to carbon in the atmosphere (~830 PgC) highlights the importance of terrestrial OC in global carbon budgets. The residence time of OC in continental reservoirs, which sets the rates of carbon exchange between land and atmosphere, represents a key uncertainty in global carbon cycle dynamics. Retention of terrestrial OC can also distort bulk OC- and biomarker-based paleorecords, yet continental storage timescales remain poorly quantified.

Insights into Cotranslational Membrane Protein Insertion by Combined LILBID-Mass Spectrometry and NMR Spectroscopy.

Cotranslational insertion of membrane proteins into defined nanoparticle membranes has been developed as an efficient process to produce highly soluble samples in native-like environments and to study lipid-dependent effects on protein structure and function. Numerous examples of the structural and functional characterization of transporters, ion channels, or G-protein-coupled receptors in cotranslationally formed nanodisc complexes demonstrate the versatility of this approach, although the basic underlying mechanisms of membrane insertion are mainly unknown. We have revealed the first aspects of the insertion of proteins into nanodiscs by combining cell-free expression, noncovalent mass spectrometry, and NMR spectroscopy.

Analyzing native membrane protein assembly in nanodiscs by combined non-covalent mass spectrometry and synthetic biology.

Membrane proteins frequently assemble into higher order homo- or hetero-oligomers within their natural lipid environment. This complex formation can modulate their folding, activity as well as substrate selectivity. Non-disruptive methods avoiding critical steps, such as membrane disintegration, transfer into artificial environments or chemical modifications are therefore essential to analyze molecular mechanisms of native membrane protein assemblies.

Structure-Activity Relationship of the Antimalarial Ozonide Artefenomel (OZ439).

Building on insights gained from the discovery of the antimalarial ozonide arterolane (OZ277), we now describe the structure-activity relationship (SAR) of the antimalarial ozonide artefenomel (OZ439). Primary and secondary amino ozonides had higher metabolic stabilities than tertiary amino ozonides, consistent with their higher pK and lower log D values. For primary amino ozonides, addition of polar functional groups decreased in vivo antimalarial efficacy.

Acceleration of protein backbone NMR assignment by combinatorial labeling: Application to a small molecule binding study.

Selective labeling with stable isotopes has long been recognized as a valuable tool in protein NMR to alleviate signal overlap and sensitivity limitations. In this study, combinatorial N-, C -, and C'-selective labeling has been used during the backbone assignment of human cyclophilin D to explore binding of an inhibitor molecule. Using a cell-free expression system, a scheme that involves N, 1- C, 2- C, fully N/ C, and unlabeled amino acids was optimized to gain a maximum of assignment information from three samples.

Heat Generation During Bone Drilling: A Comparison Between Industrial and Orthopaedic Drill Bits.

Objectives: Cortical bone drilling for preparation of screw placement is common in multiple surgical fields. The heat generated while drilling may reach thresholds high enough to cause osteonecrosis. This can compromise implant stability.

Thumb Reconstruction with Arthrodesis to the Second Metacarpal following Sarcoma Excision.

Primary sarcomas of the thumb metacarpal are rare malignant lesions. Surgical treatment involves amputation versus tumor resection with thumb reconstruction. If complete tumor resection is possible, thumb preservation may be considered, as the thumb is vital to hand function.

Combining in Vitro Folding with Cell Free Protein Synthesis for Membrane Protein Expression.

Cell free protein synthesis (CFPS) has emerged as a promising methodology for protein expression. While polypeptide production is very reliable and efficient using CFPS, the correct cotranslational folding of membrane proteins during CFPS is still a challenge. In this contribution, we describe a two-step protocol in which the integral membrane protein is initially expressed by CFPS as a precipitate followed by an in vitro folding procedure using lipid vesicles for converting the protein precipitate to the correctly folded protein.

Membrane protein production in Escherichia coli cell-free lysates.

Cell-free protein production has become a core technology in the rapidly spreading field of synthetic biology. In particular the synthesis of membrane proteins, highly problematic proteins in conventional cellular production systems, is an ideal application for cell-free expression. A large variety of artificial as well as natural environments for the optimal co-translational folding and stabilization of membrane proteins can rationally be designed.

Disubstituted 1-aryl-4-aminopiperidine library synthesis using computational drug design and high-throughput batch and flow technologies.

A platform that incorporates computational library design, parallel solution-phase synthesis, continuous flow hydrogenation, and automated high throughput purification and reformatting technologies was applied to the production of a 120-member library of 1-aryl-4-aminopiperidine analogues for drug discovery screening. The application described herein demonstrates the advantages of computational library design coupled with a flexible, modular approach to library synthesis. The enabling technologies described can be readily adopted by the traditional medicinal chemist without extensive training and lengthy process development times.

How to switch a master switch.

The crystal structure of a nucleotide exchange factor in white blood cells reveals an autoinhibitory mechanism that reinforces the switch-like behaviour of the signalling protein Ras.

Picoliter cell lysate assays in microfluidic droplet compartments for directed enzyme evolution.

We demonstrate the utility of a microfluidic platform in which water-in-oil droplet compartments serve to miniaturize cell lysate assays by a million-fold for directed enzyme evolution. Screening hydrolytic activities of a promiscuous sulfatase demonstrates that this extreme miniaturization to the single-cell level does not come at a high price in signal quality. Moreover, the quantitative readout delivers a level of precision previously limited to screening methodologies with restricted throughput.

Characterization of molecular interactions between ACP and halogenase domains in the Curacin A polyketide synthase.

Polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs) are large multidomain proteins present in microorganisms that produce bioactive compounds. Curacin A is such a bioactive compound with potent anti-proliferative activity. During its biosynthesis the growing substrate is bound covalently to an acyl carrier protein (ACP) that is able to access catalytic sites of neighboring domains for chain elongation and modification.

Evaluation of a commercial packed bed flow hydrogenator for reaction screening, optimization, and synthesis.

The performance of the ThalesNano H-Cube(®), a commercial packed bed flow hydrogenator, was evaluated in the context of small scale reaction screening and optimization. A model reaction, the reduction of styrene to ethylbenzene through a 10% Pd/C catalyst bed, was used to examine performance at various pressure settings, over sequential runs, and with commercial catalyst cartridges. In addition, the consistency of the hydrogen flow was indirectly measured by in-line UV spectroscopy.

The synthesis of a multiblock osteotropic polyrotaxane by copper(I)-catalyzed huisgen 1,3-dipolar cycloaddition.

The design and synthesis of a novel bone-targeting polyrotaxane delivery system that utilizes alendronate (ALN) as targeting moiety is presented in this manuscript. For the introduction of ALN, it is first conjugated to α-cyclodextrin (α-CD) and subsequently threaded onto a short poly(ethylene glycol) (PEG) chain, forming a pseudopolyrotaxane. Using click chemistry, this assembly is copolymerized with bulky monomers that bear imaging and/or therapeutic agent(s) to prevent ALN-functionalized α-CD from dethreading.