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Background: Economical conversion of lignocellulosic biomass into biofuels and bioproducts is central to the establishment of a robust bioeconomy. This requires a conversion host that is able to both efficiently assimilate the major lignocellulose-derived carbon sources and divert their metabolites toward specific bioproducts. Results: In this study, the carotenogenic yeast Rhodosporidium toruloides was examined for its ability to convert lignocellulose into two non-native sesquiterpenes with biofuel (bisabolene) and pharmaceutical (amorphadiene) applications. We found that R. toruloides can efficiently convert a mixture of glucose and xylose from hydrolyzed lignocellulose into these bioproducts, and unlike many conventional production hosts, its growth and productivity were enhanced in lignocellulosic hydrolysates relative to purified substrates. This organism was demonstrated to have superior growth in corn stover hydrolysates prepared by two different pretreatment methods, one using a novel biocompatible ionic liquid (IL) choline α-ketoglutarate, which produced 261 mg/L of bisabolene at bench scale, and the other using an alkaline pretreatment, which produced 680 mg/L of bisabolene in a high-gravity fed-batch bioreactor. Interestingly, R. toruloides was also observed to assimilate p-coumaric acid liberated from acylated grass lignin in the IL hydrolysate, a finding we verified with purified substrates. R. toruloides was also able to consume several additional compounds with aromatic motifs similar to lignin monomers, suggesting that this organism may have the metabolic potential to convert depolymerized lignin streams alongside lignocellulosic sugars. Conclusions: This study highlights the natural compatibility of R. toruloides with bioprocess conditions relevant to lignocellulosic biorefineries and demonstrates its ability to produce non-native terpenes. [ABSTRACT FROM AUTHOR]

Background: Diabetic patients are at increased risk for future cardiovascular events after ST-segment elevation myocardial infarction (STEMI). Administration of an intracoronary abciximab bolus during primary percutaneous coronary intervention (PCI) may be beneficial in this high-risk subgroup.Objectives: This study sought to report the 1-year clinical outcomes and cardiac magnetic resonance (CMR) findings in STEMI patients with and without diabetes randomized to intracoronary or intravenous abciximab bolus at the time of primary PCI.Methods: Patient-level data from 3 randomized trials were pooled. The primary endpoint was the composite of death or reinfarction. Comprehensive CMR imaging was performed in 1 study.Results: Of 2,470 patients, 473 (19%) had diabetes and 1,997 (81%) did not. At 1 year, the primary endpoint was significantly reduced in diabetic patients randomized to intracoronary abciximab compared with those randomized to intravenous bolus (9.2% vs. 17.6%; hazard ratio [HR]: 0.49; 95% confidence interval [CI]: 0.28 to 0.83; p = 0.009). The intracoronary abciximab bolus did not reduce the primary endpoint in patients without diabetes (7.4% vs. 7.5%; HR: 0.95; 95% CI: 0.68 to 1.33; p = 0.77), resulting in a significant interaction (p = 0.034). Among diabetic patients, intracoronary versus intravenous abciximab bolus was associated with a significantly reduced risk of death (5.8% vs. 11.2%; HR: 0.51; 95% CI: 0.26 to 0.98; p = 0.043) and definite/probable stent thrombosis (1.3% vs. 4.8%; HR: 0.27; 95% CI: 0.08 to 0.98; p = 0.046). At CMR (n = 792), the myocardial salvage index was significantly increased only in diabetic patients randomized to intracoronary compared with intravenous abciximab (54.4; interquartile range: 35.1 to 78.2 vs. 39.0, interquartile range: 24.7 to 61.7; p = 0.011; p for interaction vs. no diabetes = 0.016).Conclusions: In diabetic patients with STEMI, the administration of intracoronary abciximab improved the effectiveness of primary PCI compared with the intravenous bolus. [ABSTRACT FROM AUTHOR]

An allelic variant of protein tyrosine phosphatase nonreceptor type 22 (PTPN22), PTPN22(R620W), is strongly associated with type 1 diabetes (T1D) in humans and increases the risk of T1D by two- to fourfold. The NOD mouse is a spontaneous T1D model that shares with humans many genetic pathways contributing to T1D. We hypothesized that the introduction of the murine orthologous Ptpn22(R619W) mutation to the NOD genome would enhance the spontaneous development of T1D. We microinjected CRISPR-Cas9 and a homology-directed repair template into NOD single-cell zygotes to introduce the Ptpn22(R619W) mutation to its endogenous locus. The resulting Ptpn22(R619W) mice showed increased insulin autoantibodies and earlier onset and higher penetrance of T1D. This is the first report demonstrating enhanced T1D in a mouse modeling human PTPN22(R620W) and the utility of CRISPR-Cas9 for direct genetic alternation of NOD mice. [ABSTRACT FROM AUTHOR]

This paper describes a modular architecture based on the dual-active bridge (DAB) converter in input-series–output-parallel (ISOP) connection. This work is focused on the input voltage sharing to ensure a proper operation of each module by means of an active control of input and output voltages. A small-signal model of the modular architecture is proposed and a decoupled control loops’ scheme is used to implement the control strategy. An experimental setup has been built in order to validate the model of the DAB converter in ISOP connection and the proposed control strategy, taking different operating conditions and constructive parameter values into account. [ABSTRACT FROM AUTHOR]

Background: Placental growth factor (PlGF) induces angiogenesis and promotes tissue repair, and plasma PlGF levels change markedly during acute myocardial infarction (AMI). Currently, the impact of obstructive sleep apnea (OSA) in patients with AMI is a subject of debate. Our objective was to evaluate the relationships between PlGF levels and both the severity of acute coronary syndrome (ACS) and short-term outcomes after ACS in patients with and without OSA. Methods: A total of 538 consecutive patients (312 OSA patients and 226 controls) admitted for ACS were included in this study. All patients underwent polygraphy in the first 72 hours after hospital admission. The severity of disease and short-term prognoses were evaluated during the hospitalization period. Plasma PlGF levels were measured using an electrochemiluminescence immunoassay. Results: Patients with OSA were significantly older and more frequently hypertensive and had higher BMIs than those without OSA. After adjusting for age, smoking status, BMI and hypertension, PlGF levels were significantly elevated in patients with OSA compared with patients without OSA (19.9 pg/mL, interquartile range: 16.6–24.5 pg/mL; 18.5 pg/mL, interquartile range: 14.7–22.7 pg/mL; p<0.001), and a higher apnea-hypopnea index (AHI) was associated with higher PlGF concentrations (p<0.003). Patients with higher levels of PlGF had also an increased odds ratio for the presence of 3 or more diseased vessels and for a Killip score>1, even after adjustment. Conclusions: The results of this study show that in patients with ACS, elevated plasma levels of PlGF are associated with the presence of OSA and with adverse outcomes during short-term follow-up. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Dopamine ( DA) is a potent neuromodulator known to influence glutamatergic transmission in striatal medium spiny neurons ( MSNs). It acts on D1- and D2-like DA receptors that are expressed on two distinct subpopulations. MSNs projecting to the substantia nigra express D1 receptors (D1Rs), while those projecting to the lateral globus pallidus express D2 receptors (D2Rs). D1R signalling in particular can increase excitatory transmission through varied protein kinase A-dependent, cell-autonomous pathways. Mechanisms by which D1R signalling could increase excitatory transmission in D2R-bearing MSNs have been relatively less explored. Herein, the possibility is considered that D1R agonists increase levels of soluble factors that subsequently influence N-methyl- d-aspartate ( NMDA)-stimulated calcium flux in D2R neurons. This study focuses on matrix metalloproteinases ( MMPs) and MMP-generated integrin binding ligands, important soluble effectors of glutamatergic transmission that may be elevated in the setting of excess DA. It was observed that DA and a D1R agonist, SKF81297, increase MMP activity in extracts from striatal slices, as determined by cleavage of the substrate β-dystroglycan. Using mice engineered to express the calcium indicator GCa MP3 in striatopallidal D2R-bearing neurons, it was also observed that SKF81297 pretreatment of slices (60 min) potentiates NMDA-stimulated calcium increases in this subpopulation. Effects are diminished by pretreatment with an antagonist of MMP activity or an inhibitor of integrin-dependent signalling. Together, results suggest that DA signalling can increase excitatory transmission in D2R neurons through an MMP-dependent mechanism. Future studies may be warranted to determine whether D1R-stimulated MMP-dependent processes contribute to behaviours in which increased activity in striatopallidal MSNs plays a role. [ABSTRACT FROM AUTHOR]

Background Although intracoronary abciximab failed to improve prognosis compared with intravenous route in unselected ST-segment elevation myocardial infarction (STEMI) patients, little is known about the role of intracoronary abciximab in diabetic patients. Objectives To evaluate the efficacy of intracoronary abciximab administration in diabetic patients with STEMI undergoing primary percutaneous coronary intervention (PCI). Methods Reperfusional and clinical outcomes of intracoronary abciximab compared with intravenous bolus abciximab according to diabetic status were evaluated in a pooled analysis of five randomized trials including 3158 STEMI patients. The primary clinical endpoint of the study was the composite of death or reinfarction at 30-day follow-up. Results Among 584 diabetic patients (18.5%), the composite of death or reinfarction was significantly reduced with intracoronary abciximab compared to intravenous abciximab (4.7% vs. 8.8%; rate ratio [RR], 0.50; 95% confidence intervals [CI], 0.26–0.99; p = 0.04), driven by numerically lower deaths (3.7% vs. 6.4%; RR, 0.56; 95% CI, 0.26–1.20; p = 0.13). Moreover, a significant reduction in definite or probable stent thrombosis was observed in patients receiving intracoronary abciximab (1% vs. 3.5%; RR, 0.27; 95% CI, 0.07–0.99; p = 0.04). Although formal tests for interaction were not significant, no clinical benefit was apparent in the cohort of STEMI patients without diabetes (n = 2574). Conclusions In diabetic patients with STEMI undergoing primary PCI, intracoronary abciximab may improve clinical outcomes as compared with standard intravenous use. These findings require confirmation in a dedicated randomized trial. [ABSTRACT FROM AUTHOR]

How to manage smoke evacuation and filter pneumoperitoneum during laparoscopy to minimize potential viral spread: different methods from SoMe - a video vignette I Dear Editor i , Even though previous studies on hepatitis B virus showed that it could be found in the intra-abdominal gas, there is no evidence so far of the presence of SARS-CoV2 particles in the gas used during laparoscopy, but it is prudent to perform laparoscopy with safety strategies to avoid diffusion of potentially infected intra-abdominal aerosol into the operating room [[1], 1-6, [2], [4], [6]]. How to manage smoke evacuation and filter pneumoperitoneum during laparoscopy. [Extracted from the article]

Background: In an effort to ensure future energy security, reduce greenhouse gas emissions and create domestic jobs, the US has invested in technologies to develop sustainable biofuels and bioproducts from renewable carbon sources such as lignocellulosic biomass. Bio-derived jet fuel is of particular interest as aviation is less amenable to electrification compared to other modes of transportation and synthetic biology provides the ability to tailor fuel properties to enhance performance. Specific energy and energy density are important properties in determining the attractiveness of potential bio-derived jet fuels. For example, increased energy content can give the industry options such as longer range, higher load or reduced takeoff weight. Energy-dense sesquiterpenes have been identified as potential next-generation jet fuels that can be renewably produced from lignocellulosic biomass. Results: We developed a biomass deconstruction and conversion process that enabled the production of two tricyclic sesquiterpenes, epi-isozizaene and prespatane, from the woody biomass poplar using the versatile basidiomycete Rhodosporidium toruloides. We demonstrated terpene production at both bench and bioreactor scales, with prespatane titers reaching 1173.6 mg/L when grown in poplar hydrolysate in a 2 L bioreactor. Additionally, we examined the theoretical fuel properties of prespatane and epi-isozizaene in their hydrogenated states as blending options for jet fuel, and compared them to aviation fuel, Jet A. Conclusion: Our findings indicate that prespatane and epi-isozizaene in their hydrogenated states would be attractive blending options in Jet A or other lower density renewable jet fuels as they would improve viscosity and increase their energy density. Saturated epi-isozizaene and saturated prespatane have energy densities that are 16.6 and 18.8% higher than Jet A, respectively. These results highlight the potential of R. toruloides as a production host for the sustainable and scalable production of bio-derived jet fuel blends, and this is the first report of prespatane as an alternative jet fuel. [ABSTRACT FROM AUTHOR]

Background: Many microbes used for the rapid discovery and development of metabolic pathways have sensitivities to final products and process reagents. Isopentenol (3-methyl-3-buten-1-ol), a biogasoline candidate, has an established heterologous gene pathway but is toxic to several microbial hosts. Reagents used in the pretreatment of plant biomass, such as ionic liquids, also inhibit growth of many host strains. We explored the use of Corynebacterium glutamicum as an alternative host to address these constraints. Results: We found C. glutamicum ATCC 13032 to be tolerant to both the final product, isopentenol, as well to three classes of ionic liquids. A heterologous mevalonate-based isopentenol pathway was engineered in C. glutamicum. Targeted proteomics for the heterologous pathway proteins indicated that the 3-hydroxy-3-methylglutaryl-coenzyme A reductase protein, HmgR, is a potential rate-limiting enzyme in this synthetic pathway. Isopentenol titers were improved from undetectable to 1.25 g/L by combining three approaches: media optimization; substitution of an NADH-dependent HmgR homolog from Silicibacter pomeroyi; and development of a C. glutamicum ∆poxB ∆ldhA host chassis. Conclusions: We describe the successful expression of a heterologous mevalonate-based pathway in the Gram-positive industrial microorganism, C. glutamicum, for the production of the biogasoline candidate, isopentenol. We identified critical genetic factors to harness the isopentenol pathway in C. glutamicum. Further media and cultivation optimization enabled isopentenol production from sorghum biomass hydrolysates. [ABSTRACT FROM AUTHOR]

Summary Understanding how complex brain wiring is produced during development is a daunting challenge. In Drosophila , information from 800 retinal ommatidia is processed in distinct brain neuropiles, each subdivided into 800 matching retinotopic columns. The lobula plate comprises four T4 and four T5 neuronal subtypes. T4 neurons respond to bright edge motion, whereas T5 neurons respond to dark edge motion. Each is tuned to motion in one of the four cardinal directions, effectively establishing eight concurrent retinotopic maps to support wide-field motion. We discovered a mode of neurogenesis where two sequential Notch-dependent divisions of either a horizontal or a vertical progenitor produce matching sets of two T4 and two T5 neurons retinotopically coincident with pairwise opposite direction selectivity. We show that retinotopy is an emergent characteristic of this neurogenic program and derives directly from neuronal birth order. Our work illustrates how simple developmental rules can implement complex neural organization. [ABSTRACT FROM AUTHOR]