Publications by authors named "Eichler J"

Unlabelled: Despite providing the first example of archaeal N-glycosylation almost 50 years ago, detailed insight into the pathway used by to assemble and attach an N-linked tetrasaccharide decorating glycoproteins in this haloarchaea has only recently appeared. Still, numerous components of this pathway remain to be identified, including sulfotransferase(s), which modify the third and fourth tetrasaccharide sugars. In the present report, a series of bioinformatics, genetic, biochemical, and structural approaches served to reveal how membrane-associated VNG1056C and soluble VNG1057C respectively sulfate the iduronic acid at tetrasaccharide position three and the terminal glucuronic acid, seemingly independent of each other.

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A design of experiments (DoE) approach is applied to the study of nitrogen (N)-doped carbons prepared via a molten salt templating method using the eutectic salt lithium chloride/potassium chloride (LiCl/KCl) and the precursors sucrose and melamine (N precursor). This approach is used to deconvolute effects from surface composition and porosity on the electrocatalytic performance of N-doped carbons as oxygen reduction reaction (ORR) electrocatalysts. Additionally, DoE is implemented to reveal the synthesis-structure-function relationship for the prepared materials over an entire design space.

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Antibody mimetic peptides have evolved as versatile tools for biomedical applications, based on their ability to interfere with protein-protein interactions. We had previously designed a functional mimic of the broadly neutralizing HIV-1 antibody b12 that recognizes the CD4 binding site of the HIV-1 envelope glycoprotein gp120. The molecular details of the interaction of a linear variant of this peptide (H1H3s) with gp120 have now been characterized through cross-linking mass spectrometry, confirming the proposed involvement of the CD4 binding site of gp120 in the interaction.

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Non-invasive physical plasma (NIPP) has been used effectively for wound healing in human medicine for over two decades. The advantages are that NIPP has few side effects, is painless and gentle on the tissue. The therapeutic effect is mediated by reactive oxygen species (ROS).

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Cholesterol is a key component of biological membranes and, like many cellular lipids, is unevenly distributed among organelles. Disruptions in cholesterol trafficking are associated with various pathologies, including lysosomal lipid storage disorders, often characterized by intracellular cholesterol accumulation. A significant challenge in studying cholesterol trafficking is the lack of easy methods to trace this molecule in situ.

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Aims: Transthyretin cardiomyopathy (ATTR-CM) is characterized by episodes of worsening heart failure (WHF) which can include heart failure (HF) hospitalizations or urgent unplanned visits for administration of intravenous diuretics. WHF characterized by outpatient intensification of oral loop diuretics is common yet its prognostic implications for ATTR-CM patients relative to other WHF events remains unclear. We assessed how WHF characterized by outpatient diuretic intensification (ODI) relates to mortality in this population.

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While performed by all three domains of life, N-glycosylation in Archaea is less well described than are the parallel eukaryal and bacterial processes. Still, what is known of the archaeal version of this universal post-translational modification reveals numerous seemingly domain-specific traits. Specifically, the biosynthesis of archaeal N-linked glycans relies on distinct pathway steps and components, rare sugars and sugar modifications, as well as unique lipid carriers upon which N-linked glycans are assembled.

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The swimming device of archaea-the archaellum-presents asparagine (N)-linked glycans. While N-glycosylation serves numerous roles in archaea, including enabling their survival in extreme environments, how this post-translational modification contributes to cell motility remains under-explored. Here, we report the cryo-EM structure of archaellum filaments from the haloarchaeon Halobacterium salinarum, where archaellins, the building blocks of the archaellum, are N-glycosylated, and the N-glycosylation pathway is well-resolved.

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The SLC20A2 transporter supplies phosphate ions (P) for diverse biological functions in vertebrates, yet has not been studied in crustaceans. Unlike vertebrates, whose skeletons are mineralized mainly by calcium phosphate, only minute amounts of P are found in the CaCO-mineralized exoskeletons of invertebrates. In this study, a crustacean SLC20A2 transporter was discovered and P transport to exoskeletal elements was studied with respect to the role of P in invertebrate exoskeleton biomineralization, revealing an evolutionarily conserved mechanism for P transport in both vertebrates and invertebrates.

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Introduction: Conformationally stabilized Env trimers have been developed as antigens for the induction of neutralizing antibodies against HIV-1. However, the non-glycosylated immunodominant base of these soluble antigens may compete with the neutralizing antibody response. This has prompted attempts to couple Env trimers to organic or inorganic nanoparticles with the base facing towards the carrier.

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Many bacterial pathogens employ the type III secretion system (T3SS), a specialized complex that transports effector proteins that manipulate various cellular processes. The T3SS forms a translocon pore within the host-cell membrane consisting of two secreted proteins that transition from a soluble state into a transmembrane complex. Still, the exact sequence of events leading to the formation of a membranous functional pore remains uncertain.

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In an ongoing effort to incorporate active learning and promote higher order learning outcomes in undergraduate organic chemistry, a hybrid ("flipped") classroom structure has been used to facilitate a series of collaborative activities in the first two courses of the lower division organic chemistry sequence. An observational study of seven classes over a five-year period reveals there is a strong correlation between performance on the in-class activities and performance on the final exam across all classes; however, a significant number of students in these courses continue to struggle on both the in-class activities and final exam. The Activity Engagement Survey (AcES) was administered in the most recent course offering included in this study, and these preliminary data suggest that students who achieved lower scores on the in-class activities had lower levels of emotional and behavioral/cognitive engagement and were less likely to work in collaborative groups.

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Introduction: The Weight Bias Internalization Scale and the Modified Weight Bias Internalization Scale are well-established self-report questionnaires for assessing weight bias internalization, which is widespread among bariatric patients. However, among this group, psychometric properties of the Weight Bias Internalization Scale have only been examined in small samples showing unsatisfactory model fit and have not been explored for the modified questionnaire.

Methods: This study psychometrically evaluated and compared the Weight Bias Internalization Scale and Modified Weight Bias Internalization Scale in a large sample of prebariatric patients (N = 825, mean age = 46.

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Only a few localised ice streams drain most of the ice from the Greenland Ice Sheet. Thus, understanding ice stream behaviour and its temporal variability is crucially important to predict future sea-level change. The interior trunk of the 700 km-long North-East Greenland Ice Stream (NEGIS) is remarkable due to the lack of any clear bedrock channel to explain its presence.

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Protein degradation, which occurs in all cells, is essential for proper cellular function by regulating many cellular processes, destroying misfolded proteins, and providing protein building blocks under starvation conditions. As proteolysis is a destructive process, it is carried out by tightly regulated enzymes that evolved to interact with their protein substrates in a highly controlled and selective manner. The agents of protein degradation include proteasomes, AAA+ proteolytic machines found in all kingdoms of life.

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Archaea are microorganisms that comprise a distinct branch of the universal tree of life and which are best known as extremophiles, residing in a variety of environments characterized by harsh physical conditions. One seemingly universal trait of Archaea is the ability to perform N-glycosylation. At the same time, archaeal N-linked glycans present variety in terms of both composition and architecture not seen in the parallel eukaryal or bacterial processes.

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Ensuring site-selectivity in covalent chemical modification of proteins is one of the major challenges in chemical biology and related biomedical disciplines. Most current strategies either utilize the selectivity of proteases, or are based on reactions involving the thiol groups of cysteine residues. We have modified a pair of heterodimeric coiled-coil peptides to enable the selective covalent stabilization of the dimer without using enzymes or cysteine moieties.

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In recent years, it has become clear that intrinsically disordered protein segments play diverse functional roles in many cellular processes, thus leading to a reassessment of the classical structure-function paradigm. One class of intrinsically disordered protein segments is entropic clocks, corresponding to unstructured random protein chains involved in timing cellular processes. Such clocks were shown to modulate ion channel processes underlying action potential generation, propagation, and transmission.

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Applying a design of experiments methodology to the molten salt synthesis of nanoporous carbons enables inverse design and optimization of nitrogen (N)-rich carbon adsorbents with excellent CO /N selectivity and appreciable CO capacity for carbon capture via swing adsorption from dilute gas mixtures such as natural gas combined cycle flue gas. This data-driven study reveals fundamental structure-function relationships between the synthesis conditions, physicochemical properties, and achievable selective adsorption performance of N-rich nanoporous carbons derived from molten salt synthesis for CO capture. Taking advantage of size-sieving separation of CO (3.

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N-glycosylation is a post-translational modification of proteins that occurs across all three domains of life. In Archaea, N-glycosylation is crucial for cell stability and motility, but importantly also has significant implications for virus-host interactions. While some archaeal viruses present glycosylated proteins or interact with glycosylated host proteins, the direct influence of N-glycosylation on archaeal virus-host interactions remains to be elucidated.

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PG16 is a broadly neutralizing antibody that binds to the gp120 subunit of the HIV-1 Env protein. The major interaction site is formed by the unusually long complementarity determining region (CDR) H3. The CDRH3 residue Tyr100H is known to represent a tyrosine sulfation site; however, this modification is not present in the experimental complex structure of PG16 with full-length HIV-1 Env.

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The use of bioresorbable magnesium (Mg)-based elastic stable intramedullary nails (ESIN) is highly promising for the treatment of pediatric long-bone fractures. Being fully resorbable, a removal surgery is not required, preventing repeated physical and psychological stress for the child. Further, the osteoconductive properties of the material support fracture healing.

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: Life with more than a grain of salt.

Microbiology (Reading)

April 2023

is a halophilic (salt-loving) archaeon that grows in salt concentrations near or at saturation. Although isolated from salted fish a century ago, it was the 1971 discovery of bacteriorhodopsin, the light-driven proton pump, that raised interest in across a range of disciplines, including biophysics, chemistry, molecular evolution and biotechnology. have since contributed to numerous discoveries, such as advances in membrane protein structure determination and the first example of a non-eukaryal glycoprotein.

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Flavin-dependent L-lactate dehydrogenase (LDH) from baker's yeast (Saccharomyces cerevisiae) reversibly catalyzes the oxidation of L-lactate to L-pyruvate. In this study, four different enzymatic constructs were generated, and their catalytic and electrochemical properties were compared. Specifically, a truncated form of the native enzyme that includes only the catalytic domain, the native enzyme that includes an intrinsic electron-transferring cytochrome b2, a novel artificial enzyme containing a minimal cytochrome c and a version of the enzyme containing a fusion between two cytochromes were designed.

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Introduction: Although the association between gout and cardiovascular disease (CVD) has been extensively studied, scarce data are available for the Black population. We aimed to assess the association between gout and CVD in a predominantly Black urban population with gout.

Methods: A cross-sectional analysis was performed between a gout cohort and an age-/sex-matched control group.

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