Safety, tolerability, and immunogenicity of the chimpanzee adenovirus type 3-vectored Marburg virus (cAd3-Marburg) vaccine in healthy adults in the USA: a first-in-human, phase 1, open-label, dose-escalation trial.

BACKGROUND: WHO has identified Marburg virus as an emerging virus requiring urgent vaccine research and development, particularly due to its recent emergence in Ghana. We report results from a first-in-human clinical trial evaluating a replication-deficient recombinant chimpanzee adenovirus type 3 (cAd3)-vectored vaccine encoding a wild-type Marburg virus Angola glycoprotein (cAd3-Marburg) in healthy adults. METHODS: We did a first-in-human, phase 1, open-label, dose-escalation trial of the cAd3-Marburg vaccine at the Walter Reed Army Institute of Research Clinical Trials Center in the USA. Healthy adults aged 18-50 years were assigned to receive a single intramuscular dose of cAd3-Marburg vaccine at either 1 × 1010 or 1 × 1011 particle units (pu). Primary safety endpoints included reactogenicity assessed for the first 7 days and all adverse events assessed for 28 days after vaccination. Secondary immunogenicity endpoints were assessment of binding antibody responses and T-cell responses against the Marburg virus glycoprotein insert, and assessment of neutralising antibody responses against the cAd3 vector 4 weeks after vaccination. This study is registered with ClinicalTrials.gov, NCT03475056. FINDINGS: Between Oct 9, 2018, and Jan 31, 2019, 40 healthy adults were enrolled and assigned to receive a single intramuscular dose of cAd3-Marburg vaccine at either 1 × 1010 pu (n=20) or 1 × 1011 pu (n=20). The cAd3-Marburg vaccine was safe, well tolerated, and immunogenic. All enrolled participants received cAd3-Marburg vaccine, with 37 (93%) participants completing follow-up visits; two (5%) participants moved from the area and one (3%) was lost to follow-up. No serious adverse events related to vaccination occurred. Mild to moderate reactogenicity was observed after vaccination, with symptoms of injection site pain and tenderness (27 [68%] of 40 participants), malaise (18 [45%] of 40 participants), headache (17 [43%] of 40 participants), and myalgia (14 [35%] of 40 participants) most commonly reported. Glycoprotein-specific antibodies were induced in 38 (95%) of 40 participants 4 weeks after vaccination, with geometric mean titres of 421 [95% CI 209-846] in the 1 × 1010 pu group and 545 [276-1078] in the 1 × 1011 pu group, and remained significantly elevated at 48 weeks compared with baseline titres (39 [95% CI 13-119] in the 1 ×1010 pu group and 27 [95-156] in the 1 ×1011 pu group; both p<0·0001). T-cell responses to the glycoprotein insert and neutralising responses against the cAd3 vector were also increased at 4 weeks after vaccination. INTERPRETATION: This first-in-human trial of this cAd3-Marburg vaccine showed the agent is safe and immunogenic, with a safety profile similar to previously tested cAd3-vectored filovirus vaccines. 95% of participants produced a glycoprotein-specific antibody response at 4 weeks after a single vaccination, which remained in 70% of participants at 48 weeks. These findings represent a crucial step in the development of a vaccine for emergency deployment against a re-emerging pathogen that has recently expanded its reach to new regions. FUNDING: National Institutes of Health.

Perioperative pain control represents the primary concern for patients considering outpatient shoulder arthroplasty: a survey-based study.

BACKGROUND: Outpatient (OP) total shoulder arthroplasty (TSA) with same-day discharge can now be performed safely in appropriately selected patients. Patient knowledge and perspectives regarding OP TSA are yet unknown and such information may inform surgeon decision-making and provide a framework for addressing patient concerns. The goal of this study was to understand and quantify patient knowledge of and concerns for OP TSA, with a working hypothesis that majority of patients are unaware of OP TSA as a realistic option and that their primary concern would be postoperative pain control. METHODS: This was a retrospective cohort study at a tertiary care academic medical center including patients who underwent anatomic or reverse shoulder arthroplasty and completed an OP TSA expectations questionnaire/survey. This survey was provided preoperatively and included demographic factors, self-rated health evaluation, and perioperative expectations. Surveys evaluated whether patients undergoing TSA had any prior awareness of OP TSA and evaluated their primary concern with same-day discharge. Secondary questions included an assessment of patient expectations of outcomes of outpatient vs. inpatient surgery as well as their expected length of inpatient stay. RESULTS: A total of 122 patients who underwent anatomic and reverse shoulder arthroplasty completed the questionnaire and comprised the study cohort. Fifty-two (42.6%) of the patients were unaware that OP TSA was an option, and 26 (50%) of these were comfortable with the idea of OP TSA. Comfort with OP TSA was significantly associated with higher subjective patient-reported health status. Fifty-eight patients (47.5%) expected that following TSA they would require <24 hours of in-hospital postoperative care. The primary concern for patients considering OP TSA was postoperative pain control, endorsed by 44.3% of patients, compared with 13.1% of patients stating this would be their primary concern if admitted as an inpatient postoperatively. Pain control being a primary concern was significantly different between those considering outpatient vs. inpatient TSA. Most patients anticipated that OP shoulder arthroplasty would lead to a better (36%) or comparable (53%) outcome, whereas only 11% had concerns that it would lead to a worse outcome. CONCLUSION: Expanding OP TSA crucially depends on awareness and education. Perceived ability to control pain is an important concern. Patients may benefit from preoperative counseling, including emphasizing a comprehensive postoperative pain management strategy.

The Potential of Dietary Bioactive Compounds against SARS-CoV-2 and COVID-19-Induced Endothelial Dysfunction.

COVID-19 is an endothelial disease. All the major comorbidities that increase the risk for severe SARS-CoV-2 infection and severe COVID-19 including old age, obesity, diabetes, hypertension, respiratory disease, compromised immune system, coronary artery disease or heart failure are associated with dysfunctional endothelium. Genetics and environmental factors (epigenetics) are major risk factors for endothelial dysfunction. Individuals with metabolic syndrome are at increased risk for severe SARS-CoV-2 infection and poor COVID-19 outcomes and higher risk of mortality. Old age is a non-modifiable risk factor. All other risk factors are modifiable. This review also identifies dietary risk factors for endothelial dysfunction. Potential dietary preventions that address endothelial dysfunction and its sequelae may have an important role in preventing SARS-CoV-2 infection severity and are key factors for future research to address. This review presents some dietary bioactives with demonstrated efficacy against dysfunctional endothelial cells. This review also covers dietary bioactives with efficacy against SARS-CoV-2 infection. Dietary bioactive compounds that prevent endothelial dysfunction and its sequelae, especially in the gastrointestinal tract, will result in more effective prevention of SARS-CoV-2 variant infection severity and are key factors for future food research to address.

Emergent Optoelectronic Properties of Mixed-Dimensional Heterojunctions.

ConspectusThe electronic dimensionality of a material is defined by the number of spatial degrees of confinement of its electronic wave function. Low-dimensional semiconductor nanomaterials with at least one degree of spatial confinement have optoelectronic properties that are tunable with size and environment (dielectric and chemical) and are of particular interest for optoelectronic applications such as light detection, light harvesting, and photocatalysis. By combining nanomaterials of differing dimensionalities, mixed-dimensional heterojunctions (MDHJs) exploit the desirable characteristics of their components. For example, the strong optical absorption of zero-dimensional (0D) materials combined with the high charge carrier mobilities of two-dimensional (2D) materials widens the spectral response and enhances the responsivity of mixed-dimensional photodetectors, which has implications for ultrathin, flexible optoelectronic devices. MDHJs are highly sensitive to (i) interfacial chemistry because of large surface area-to-volume ratios and (ii) electric fields, which are incompletely screened because of the ultrathin nature of MDHJs. This sensitivity presents opportunities for control of physical phenomena in MDHJs through chemical modification, optical excitation, externally applied electric fields, and other environmental parameters. Since this fast-moving research area is beginning to pose and answer fundamental questions that underlie the fundamental optoelectronic behavior of MDHJs, it is an opportune time to assess progress and suggest future directions in this field.In this Account, we first outline the characteristic properties, advantages, and challenges for low-dimensional materials, many of which arise as a result of quantum confinement effects. The optoelectronic properties and performance of MDHJs are primarily determined by dynamics of excitons and charge carriers at their interfaces, where these particles tunnel, trap, scatter, and/or recombine on the time scales of tens of femtoseconds to hundreds of nanoseconds. We discuss several photophysical phenomena that deviate from those observed in bulk heterojunctions, as well as factors that can be used to vary, probe, and ultimately control the behavior of excitons and charge carriers in MDHJ systems. We then discuss optoelectronic applications of MDHJs, namely, photodetectors, photovoltaics, and photocatalysts, and identify current performance limits compared to state-of-the-art benchmarks. Finally, we suggest strategies to extend the current understanding of dynamics in MDHJs toward the realization of stimuli-driven responses, particularly with respect to exciton delocalization, quantum emission, interfacial morphology, responsivity to external stimuli, spin selectivity, and usage of chemically reactive materials.

Experimental Evidence for Sex Differences in Sexual Variety Preferences: Support for the Coolidge Effect in Humans.

We examined sex differences in preferences for sexual variety and novelty to determine whether the Coolidge effect plays a role in human sexuality. In two experimental studies that employed different manipulations, we found converging evidence that men showed a greater preference for variety in potential short-term mates than did women. In the first study, men (n = 281) were more likely than women (n = 353) to select a variety of mates when given the opportunity to distribute chances to have sex with different individuals in hypothetical situations. This sex difference was evident regardless of the targets' attractiveness and age. Further, men found it more appealing if their committed romantic/sexual partners frequently changed their physical appearance, while women reported that they modified their physical appearance more frequently than did men, potentially appealing to male desires for novelty. In the second study, when participants were given a hypothetical dating task using photographs of potential short-term mates, men (n = 40) were more likely than women (n = 56) to select a novel person to date. Collectively, these findings lend support to the idea that sex differences in preferences for sexual variety and novelty are a salient sex-specific evolved component of the repertoire of human mating strategies.

The Young Age and Plant-Based Diet Hypothesis for Low SARS-CoV-2 Infection and COVID-19 Pandemic in Sub-Saharan Africa.

Since the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that caused the coronavirus disease-19 (COVID-19), in December 2019, the infection has spread around the globe. Some of the risk factors include social distancing, mask wearing, hand washing with soap, obesity, diabetes, hypertension, asthma, cardiovascular disease, and dysbiosis. Evidence has shown the incidence of total infection and death rates to be lower in sub-Saharan Africa when compared with North Africa, Europe and North America and many other parts of the world. The higher the metabolic syndrome rate, the higher the risk of SARS-CoV-2 infection. Africa has a lower rate of metabolic syndrome risk than many other continents. This paradox has puzzled several in the biomedical and scientific communities. Published results of research have demonstrated the exciting correlation that the combination of young age of the population coupled with their native plant-based diet has lowered their risk factors. The plant-based diet include whole grains (millet, sorghum), legumes (black-eye peas, dry beans, soybean), vegetables, potato, sweet potato, yams, squash, banana, pumpkin seeds, and moringa leaves, and lower consumption of meat. The plant-based diet results in a different gut microbiota than of most of the rest of the world. This has a significant impact on the survival rate of other populations. The "plant-based diet" results in lower rates of obesity, diabetes and dysbiosis, which could contribute to lower and less severe infections. However, these hypotheses need to be supported by more clinical and biostatistics data.

Antiferromagnetic Semiconductor BaFMn0.5Te with Unique Mn Ordering and Red Photoluminescence.

Semiconductors possessing both magnetic and optoelectronic properties are rare and promise applications in opto-spintronics. Here we report the mixed-anion semiconductor BaFMn0.5Te with a band gap of 1.76 eV and a work function of 5.08 eV, harboring both antiferromagnetism (AFM) and strong red photoluminescence (PL). The synthesis of BaFMn0.5Te in quantitative yield was accomplished using the "panoramic synthesis" technique and synchrotron radiation to obtain the full reaction map, from which we determined that the compound forms upon heating at 850 °C via an intermediate unknown phase. The structure refinement required the use of a (3+1)-dimensional superspace group Cmme(α01/2)0ss. The material crystallizes into a ZrCuSiAs-like structure with alternating [BaF]+ and [Mn0.5Te]- layers and has a commensurately modulated structure with the q-vector of 1/6a* + 1/6b* + 1/2c* at room temperature arising from the unique ordering pattern of Mn2+ cations. Long-range AFM order emerges below 90 K, with two-dimensional short-range AFM correlations above the transition temperature. First-principles calculations indicate that BaFMn0.5Te is an indirect band gap semiconductor with the gap opening between Te 5p and Mn 3d orbitals, and the magnetic interactions between nearest-neighbor Mn2+ atoms are antiferromagnetic. Steady-state PL spectra show a broad strong emission centered at ∼700 nm, which we believe originates from the energy manifolds of the modulated Mn2+ sublattice and its defects. Time-resolved PL measurements reveal an increase in excited-state lifetimes with longer probe wavelengths, from 93 ns (at 650 nm) to 345 ns (at 800 nm), and a delayed growth (6.5 ± 0.3 ns) in the kinetics at 800 nm with a concomitant decay (4.1 ± 0.1 ns) at 675 nm. Together, these observations suggest that there are multiple emissive states, with higher energy states populating lower energy states by energy transfer.

Functionalizing Cellulose Nanocrystals with Click Modifiable Carbohydrate-Binding Modules.

Functionalized cellulose nanocrystals (CNC) have unique properties that make them attractive in various applications such as drug delivery, hydrogels, and emulsions. However, the predominant chemical methods currently used to functionalize cellulose nanocrystals have a large environmental footprint. Although greener methods are desirable, the relatively inert nature of cellulose crystals presents a major challenge to their potential modification in aqueous media. In the work reported here, carbohydrate binding modules (CBMs) were used to introduce new functionality to cellulose surfaces. CBM2a, which has a strong affinity for crystalline cellulose, was functionalized with an alkyne at the terminal amine position. The alkyne group, which was introduced onto the cellulose surface with CBM2a, underwent a Click reaction with polyethylene glycol (PEG) to modify CNC surfaces. This provided a strong, non-covalent modification of cellulose surfaces that was carried out in a one-pot reaction in aqueous media. The CBM-PEG modification of cellulose surfaces increased CNC redispersion after drying and improved suspension stability based on steric interactions. It was apparent that hybrid polysaccharide-protein, self-assembled nanoparticles could be effectively produced, with potential for nanomedicine, immunoassay, and drug delivery applications.

Synthesis, Structure, and Compositional Tuning of the Layered Oxide Tellurides Sr2MnO2Cu2- xTe2 and Sr2CoO2Cu2Te2.

The synthesis and structure of two new transition metal oxide tellurides, Sr2MnO2Cu1.82(2)Te2 and Sr2CoO2Cu2Te2, are reported. Sr2CoO2Cu2Te2 with the purely divalent Co2+ ion in the oxide layers has magnetic ordering based on antiferromagnetic interactions between nearest neighbors and appears to be inert to attempted topotactic oxidation by partial removal of the Cu ions. In contrast, the Mn analogue with the more oxidizable transition metal ion has a 9(1)% Cu deficiency in the telluride layer when synthesized at high temperatures, corresponding to a Mn oxidation state of +2.18(2), and neutron powder diffraction revealed the presence of a sole highly asymmetric Warren-type magnetic peak, characteristic of magnetic ordering that is highly two-dimensional and not fully developed over a long range. Topotactic oxidation by the chemical deintercalation of further copper using a solution of I2 in acetonitrile offers control over the Mn oxidation state and, hence, the magnetic ordering: oxidation yielded Sr2MnO2Cu1.58(2)Te2 (Mn oxidation state of +2.42(2)) in which ferromagnetic interactions between Mn ions result from Mn2+/3+ mixed valence, resulting in a long-range-ordered A-type antiferromagnet with ferromagnetic MnO2 layers coupled antiferromagnetically.

Assessing patient preferences for switching from warfarin to direct oral anticoagulants.

Warfarin remains the most commonly prescribed oral anticoagulant in the United States, but it has disadvantages such as dietary interactions and frequent laboratory monitoring. Direct oral anticoagulants (DOACs) have been introduced as safer and equally effective alternatives to warfarin. This study assessed patient preference for warfarin or DOAC based on a willingness to pay more for potential DOAC benefits. Current warfarin patients with atrial fibrillation or venous thromboembolism enrolled in the University of Utah Health Thrombosis Service were given a one-time electronic survey that assessed preferences between warfarin and DOACs using scenarios comparing effectiveness, safety, and convenience. When DOACs were preferred, patients were asked how much more they would be willing to pay monthly for the perceived advantages associated with DOACs. With 123 completed surveys, 68% of patients preferred to stay on warfarin. No particular factor influenced patient preference (lack of routine laboratory monitoring, lower risks of major bleeding, and fewer dietary interactions). Reduced stroke risk was associated with the highest value (willing to pay an additional $21). Considering all factors, patients preferring DOACs would pay a median $18 extra per month for the additional benefits. Prior exposure to DOACs was associated with preference for DOACs. Many patients currently taking warfarin preferred to stay on warfarin when given the choice, despite DOAC benefits. Willingness to pay extra for DOAC advantages did not exceed $20 in the majority of survey respondents. Previous DOAC exposure influences patient preference and perceived value for DOACs.

ß-Cell secretory defects are present in pancreatic insufficient cystic fibrosis with 1-hour oral glucose tolerance test glucose ≥155 mg/dL.

BACKGROUND: Patients with pancreatic insufficient cystic fibrosis (PI-CF) meeting standard criteria for normal glucose tolerance display impaired ß-cell secretory capacity and early-phase insulin secretion defects. We sought evidence of impaired ß-cell secretory capacity, a measure of functional ß-cell mass, among those with early glucose intolerance (EGI), defined as 1-hour oral glucose tolerance test (OGTT) glucose ≥155 mg/dL (8.6 mmol/L). METHODS: A cross-sectional study was conducted in the Penn and CHOP Clinical & Translational Research Centers. PI-CF categorized by OGTT as normal (PI-NGT: 1-hour glucose <155 mg/dL and 2-hour <140 mg/dL [7.8 mmol/L]; n = 13), PI-EGI (1-hour ≥155 mg/dL and 2-hour <140 mg/dL; n = 13), impaired (PI-IGT: 2-hour ≥140 and <200 mg/dL [11.1 mmol/L]; n = 8), and diabetic (cystic fibrosis-related diabetes, CFRD: 2-hour ≥200 mg/dL; n = 8) participated. Post-prandial glucose tolerance and insulin secretion, and ß-cell secretory capacity and demand were derived from mixed-meal tolerance tests (MMTTs), and glucose-potentiated arginine (GPA) tests, respectively. RESULTS: PI-EGI had elevated post-prandial glucose with reduced early-phase insulin secretion during MMTT compared to PI-NGT (P < .05). PI-EGI also exhibited impaired acute insulin and C-peptide responses to GPA (P < .01 vs PI-NGT), measures of ß-cell secretory capacity. Proinsulin secretory ratios were higher under hyperglycemic clamp conditions in PI-IGT and CFRD (P < .05 vs PI-NGT), and correlated with 1-hour glucose in PI-CF (P < .01). CONCLUSIONS: PI-CF patients with 1-hour OGTT glucose ≥155 mg/dL already manifest impaired ß-cell secretory capacity with associated early-phase insulin secretion defects. Avoiding hyperglycemia in patients with EGI may be important for preventing excessive insulin demand indicated by disproportionately increased proinsulin secretion.

Synthesis, Structure, and Properties of the Layered Oxide Chalcogenides Sr2CuO2Cu2S2 and Sr2CuO2Cu2Se2.

The structures of two new oxide chalcogenide phases, Sr2CuO2Cu2S2 and Sr2CuO2Cu2Se2, are reported, both of which contain infinite CuO2 planes containing Cu2+ and which have Cu+ ions in the sulfide or selenide layers. Powder neutron diffraction measurements show that Sr2CuO2Cu2Se2 exhibits long-range magnetic ordering with a magnetic structure based on antiferromagnetic interactions between nearest-neighbor Cu2+ ions, leading to a √2 a × âˆš2 a × 2 c expansion of the nuclear cell. The ordered moment of 0.39(6) µB on the Cu2+ ions at 1.7 K is consistent with the value predicted by density functional theory calculations. The compounds are structurally related to the cuprate superconductors and may also be considered as analogues of the parent phases of this class of superconductor such as Sr2CuO2Cl2 or La2CuO4. In the present case, however, the top of the chalcogenide-based valence band is very close to the vacant Cu2+ 3d states of the conduction band, leading to relatively high measured conductivity.

Pilot Study of the Tart Cherry Juice for the Treatment of Insomnia and Investigation of Mechanisms.

BACKGROUND: Insomnia is common in the elderly and is associated with chronic disease, but use of hypnotics increases the incidence of falls. Montmorency tart cherry juice has improved insomnia by self-report questionnaire. STUDY QUESTION: Is insomnia confirmed by polysomnography and is tryptophan availability a potential mechanism for treating insomnia? STUDY DESIGN: A placebo-controlled balanced crossover study with subjects older than 50 years and insomnia were randomized to placebo (2 weeks) or cherry juice (2 weeks) (240 mL 2 times/d) separated by a 2-week washout. MEASURES AND OUTCOMES: Sleep was evaluated by polysomnography and 5 validated questionnaires. Serum indoleamine 2,3-dioxygenase (IDO), the kynurenine-to-tryptophan ratio, and prostaglandin E2 were measured. In vitro, Caco-2 cells were stimulated with interferon-gamma, and the ability of cherry juice procyanidin to inhibit IDO which degrades tryptophan and stimulates inflammation was measured. The content of procyanidin B-2 and other major anthocyanins in cherry juice were determined. RESULTS: Eleven subjects were randomized; 3 with sleep apnea were excluded and referred. The 8 completers with insomnia increased sleep time by 84 minutes on polysomnography (P = 0.0182) and sleep efficiency increased on the Pittsburgh Sleep Quality Index (P = 0.03). Other questionnaires showed no significant differences. The serum kynurenine-to-tryptophan ratio decreased, as did the level of prostaglandin E2 (both P < 0.05). In vitro, cherry juice procyanidin B-2 dose-dependently inhibited IDO. CONCLUSIONS: Cherry juice increased sleep time and sleep efficiency. Cherry juice procyanidin B-2 inhibited IDO, increased tryptophan availability, reduced inflammation, and may be partially responsible for improvement in insomnia.

The increase of the global donor inventory is of limited benefit to patients of non-Northwestern European descent.

Between 2001 and 2012, the number of unrelated donors registered worldwide increased from 7 to 21 million, and the number of public cord blood units increased to over 500,000. We addressed the question of whether this expansion resulted in higher percentages of patients reaching transplantation. Unrelated donor searches were evaluated for 3,124 eligible patients in the Netherlands in two cohorts (2001-2006, n=995; 2007-2012, n=2129), comparing results for patients of Northwestern European and non-Northwestern European origin. Endpoints were 'donor found' and 'transplantation reached'. The substantial growth of the donor inventory over the period studied did not increase the median number of potential unrelated donors (n=7) for non-Northwestern European patients, but almost doubled the number for Northwestern European patients from 42 to 71. Before and after 2007, an unrelated donor or cord blood was identified for 91% and 95%, respectively, of Northwestern European patients and for 65% and 82% of non-Northwestern European patients (P<0.0001). Non-Northwestern European patients more often needed a cord blood transplant. The degree of HLA matching was significantly lower for non-Northwestern European patients (P<0.0006). The time needed to identify a donor decreased for both populations. The percentage of Northwestern European patients reaching transplantation increased from 77% to 83% and for non-Northwestern European patients from 57% to 72% (P=0.0003). The increase of the global inventory resulted in more transplants for patients lacking a family donor, although the quality and quantity of (potential) haematopoietic cell grafts for patients of a non-Northwestern European descent remained inferior, indicating the need for adaptation of recruitment.

Mechanistic insights into the liquefaction stage of enzyme-mediated biomass deconstruction.

Effective enzyme-mediated viscosity reduction, disaggregation, or "liquefaction," is required to overcome the rheological challenges resulting from the fibrous, hygroscopic nature of lignocellulosic biomass, particularly at the high solids loadings that will be required for an economically viable process. However, the actual mechanisms involved in enzyme-mediated liquefaction, as determined by viscosity or yield stress reduction, have yet to be fully resolved. Particle fragmentation, interparticle interaction, material dilution, and water-retention capacity were compared for their ability to quantify enzyme-mediated liquefaction of model and more realistic pretreated biomass substrates. It was apparent that material dilution and particle fragmentation occurred simultaneously and that both mechanisms contributed to viscosity/yield stress reduction. However, their relative importance was dependent on the nature of the biomass substrate. Interparticle interaction and enzyme-mediated changes to these interactions was shown to have a significant effect on slurry rheology. Liquefaction was shown to result from the combined action of material dilution, particle fragmentation, and alteration of interactions at particle surfaces. However, the observed changes in water retention capacity did not correlate with yield stress reduction. The relative importance of each mechanism was significantly influenced by the nature of the biomass substrate and its physicochemical properties. An ongoing challenge is that mechanisms, such as refining, which enhance enzyme accessibility to the cellulosic component of the substrate, are detrimental to slurry rheology and will likely impede enzyme-mediated liquefaction when high substrate concentrations are used.

The use of carbohydrate binding modules (CBMs) to monitor changes in fragmentation and cellulose fiber surface morphology during cellulase- and Swollenin-induced deconstruction of lignocellulosic substrates.

Although the actions of many of the hydrolytic enzymes involved in cellulose hydrolysis are relatively well understood, the contributions that amorphogenesis-inducing proteins might contribute to cellulose deconstruction are still relatively undefined. Earlier work has shown that disruptive proteins, such as the non-hydrolytic non-oxidative protein Swollenin, can open up and disaggregate the less-ordered regions of lignocellulosic substrates. Within the cellulosic fraction, relatively disordered, amorphous regions known as dislocations are known to occur along the length of the fibers. It was postulated that Swollenin might act synergistically with hydrolytic enzymes to initiate biomass deconstruction within these dislocation regions. Carbohydrate binding modules (CBMs) that preferentially bind to cellulosic substructures were fluorescently labeled. They were imaged, using confocal microscopy, to assess the distribution of crystalline and amorphous cellulose at the fiber surface, as well as to track changes in surface morphology over the course of enzymatic hydrolysis and fiber fragmentation. Swollenin was shown to promote targeted disruption of the cellulosic structure at fiber dislocations.

Adaptive evolution and metabolic engineering of a cellobiose- and xylose- negative Corynebacterium glutamicum that co-utilizes cellobiose and xylose.

BACKGROUND: An efficient microbial cell factory requires a microorganism that can utilize a broad range of substrates to economically produce value-added chemicals and fuels. The industrially important bacterium Corynebacterium glutamicum has been studied to broaden substrate utilizations for lignocellulose-derived sugars. However, C. glutamicum ATCC 13032 is incapable of PTS-dependent utilization of cellobiose because it has missing genes annotated to ß-glucosidases (bG) and cellobiose-specific PTS permease. RESULTS: We have engineered and evolved a cellobiose-negative and xylose-negative C. glutamicum that utilizes cellobiose as sole carbon and co-ferments cellobiose and xylose. NGS-genomic and DNA microarray-transcriptomic analysis revealed the multiple genetic mutations for the evolved cellobiose-utilizing strains. As a result, a consortium of mutated transporters and metabolic and auxiliary proteins was responsible for the efficient cellobiose uptake. Evolved and engineered strains expressing an intracellular bG showed a better rate of growth rate on cellobiose as sole carbon source than did other bG-secreting or bG-displaying C. glutamicum strains under aerobic culture. Our strain was also capable of co-fermenting cellobiose and xylose without a biphasic growth, although additional pentose transporter expression did not enhance the xylose uptake rate. We subsequently assessed the strains for simultaneous saccharification and fermentation of cellulosic substrates derived from Canadian Ponderosa Pine. CONCLUSIONS: The combinatorial strategies of metabolic engineering and adaptive evolution enabled to construct C. glutamicum strains that were able to co-ferment cellobiose and xylose. This work could be useful in development of recombinant C. glutamicum strains for efficient lignocellulosic-biomass conversion to produce value-added chemicals and fuels.

Crystal and Magnetic Structures of the Oxide Sulfides CaCoSO and BaCoSO.

CaCoSO, synthesized from CaO, Co, and S at 900 °C, is isostructural with CaZnSO and CaFeSO. The structure is non-centrosymmetric by virtue of the arrangement of the vertex-sharing CoS3O tetrahedra which are linked by their sulfide vertices to form layers. The crystal structure adopts space group P63mc (No. 186), and the lattice parameters are a = 3.7524(9) Å and c = 11.138(3) Å at room temperature with two formula units in the unit cell. The compound is highly insulating, and powder neutron diffraction measurements reveal long-range antiferromagnetic order with a propagation vector k = (1/3, 1/3, 1/2). The magnetic scattering from a powder sample can be modeled starting from a 120° arrangement of Co(2+) spin vectors in the triangular planes and then applying a canting out of the planes which can be modeled in the magnetic space group C(c)c (space group 9.40 in the Belov, Neronova, and Smirnova (BNS) scheme) with Co(2+) moments of 2.72(5) µ(B). The antiferromagnetic structure of the recently reported compound BaCoSO, which has a very different crystal structure from CaCoSO, is also described, and this magnetic structure and the magnitude of the ordered moment (2.75(2) µ(B)) are found by experiment to be similar to those predicted computationally.