Biocatalysis has revolutionized chemical synthesis, providing sustainable methods for preparing various organic molecules. In enzyme-mediated organic synthesis, most reactions involve molecules ...operating from their ground states. Over the past 25 years, there has been an increased interest in enzymatic processes that utilize electronically excited states accessed through photoexcitation. These photobiocatalytic processes involve a diverse array of reaction mechanisms that are complementary to one another. This comprehensive review will describe the state-of-the-art strategies in photobiocatalysis for organic synthesis until December 2022. Apart from reviewing the relevant literature, a central goal of this review is to delineate the mechanistic differences between the general strategies employed in the field. We will organize this review based on the relationship between the photochemical step and the enzymatic transformations. The review will include mechanistic studies, substrate scopes, and protein optimization strategies. By clearly defining mechanistically-distinct strategies in photobiocatalytic chemistry, we hope to illuminate future synthetic opportunities in the area.
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IJS, KILJ, NUK, PNG, UL, UM
Genome-wide association studies have identified multiple genomic loci associated with coronary artery disease, but most are common variants in non-coding regions that provide limited information on ...causal genes and etiology of the disease. To overcome the limited scope that common variants provide, we focused our investigation on low-frequency and rare sequence variations primarily residing in coding regions of the genome.
Using samples of individuals of European ancestry from ten cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, both cross-sectional and prospective analyses were conducted to examine associations between genetic variants and myocardial infarction (MI), coronary heart disease (CHD), and all-cause mortality following these events. For prevalent events, a total of 27,349 participants of European ancestry, including 1831 prevalent MI cases and 2518 prevalent CHD cases were used. For incident cases, a total of 55,736 participants of European ancestry were included (3,031 incident MI cases and 5,425 incident CHD cases). There were 1,860 all-cause deaths among the 3,751 MI and CHD cases from six cohorts that contributed to the analysis of all-cause mortality. Single variant and gene-based analyses were performed separately in each cohort and then meta-analyzed for each outcome. A low-frequency intronic variant (rs988583) in PLCL1 was significantly associated with prevalent MI (OR = 1.80, 95% confidence interval: 1.43, 2.27; P = 7.12 × 10-7). We conducted gene-based burden tests for genes with a cumulative minor allele count (cMAC) ≥ 5 and variants with minor allele frequency (MAF) < 5%. TMPRSS5 and LDLRAD1 were significantly associated with prevalent MI and CHD, respectively, and RC3H2 and ANGPTL4 were significantly associated with incident MI and CHD, respectively. No loci were significantly associated with all-cause mortality following a MI or CHD event.
This study identified one known locus (ANGPTL4) and four new loci (PLCL1, RC3H2, TMPRSS5, and LDLRAD1) associated with cardiovascular disease risk that warrant further investigation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We present a search for new members of the 300 km s−1 stream (300S) near the dwarf galaxy Segue 1 using wide-field survey data. We identify 11 previously unknown bright stream members in the APOGEE-2 ...and SEGUE-1 and 2 spectroscopic surveys. Based on the spatial distribution of the high-velocity stars, we confirm for the first time that this kinematic structure is associated with a 24°-long stream seen in SDSS and Pan-STARRS imaging data. The 300S stars display a metallicity range of −2.17 < Fe/H < −1.24, with an intrinsic dispersion of 0.21 − 0.09 + 0.12 dex. They also have chemical abundance patterns similar to those of Local Group dwarf galaxies, as well as that of the Milky Way halo. Using the open-source code galpy to model the orbit of the stream, we find that the progenitor of the stream passed perigalacticon about 70 Myr ago, with a closest approach to the Galactic center of about 4.1 kpc. Using Pan-STARRS DR1 data, we obtain an integrated stream luminosity of 4 × 103 L . We conclude that the progenitor of the stream was a dwarf galaxy that is probably similar to the satellites that were accreted to build the present-day Milky Way halo.
Many modern imaging sensors must obtain multiple looks or "views" of a target at different orientations to automatically classify it with high confidence. Therefore, when tasked with classifying many ...targets, a mobile sensor may need to travel a long distance to change its position and orientation relative to every target, resulting in costly and time-consuming operations. This article presents a novel and general approach, referred to as informative multiview planning (IMVP) that simultaneously determines the most informative sequence of views and the shortest path between them. The approach is demonstrated on an underwater multitarget classification problem in which a sidescan sonar installed on an unmanned underwater vehicle must classify all targets in minimum time. Simulation and experimental results show that IMVP can achieve the same, or better, classification performance in half the time of existing multiview path planning methods. Also, by determining the most informative views and the shortest path between them, IMVP significantly improves classification efficiency, classification confidence level, as well as performance robustness.
The boreal summer intraseasonal oscillation (BSISO) is a dominant tropical mode with a period of 30–60 days, which offers an opportunity for intraseasonal forecasting of the Asian summer monsoon. The ...present study provides a preliminary, yet up-to-date, assessment of the prediction skill of the BSISO in four state-of-the-art models: the ECMWF model, the University of Hawaii (UH) model, the NCEP Climate Forecast System, version 2 (CFSv2), and version 1 for the 2008 summer (CFSv1), which is a common year of two international programs: the Year of Tropical Convection (YOTC) and Asian Monsoon Years (AMY). The mean prediction skill over the global tropics and Southeast Asia for first three models reaches about 1–2 (3) weeks for BSISO-related rainfall (850-hPa zonal wind), measured as the lead time when the spatial anomaly correlation coefficient drops to 0.5. The skill of CFSv1 is consistently lower than the other three. The strengths and weaknesses of the CFSv2, UH, and ECMWF models in forecasting the BSISO for this specific year are further revealed. The ECMWF and UH have relatively better performance for northward-propagating BSISO when the initial convection is near the equator, although they suffer from an early false BSISO onset when initial convection is in the off-equatorial monsoon trough. However, CFSv2 does not have a false onset problem when the initial convection is in monsoon trough, but it does have a problem with very slow northward propagation. After combining the forecasts of CFSv2 and UH into an equal-weighted multimodel ensemble, the resultant skill is slightly better than that of individual models. An empirical model shows a comparable skill with the dynamical models. A combined dynamical–empirical ensemble advances the intraseasonal forecast skill of BSISO-related rainfall to three weeks.
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BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The reviews in social media are produced continuously by a large and uncontrolled number of users. To capture the mixture of sentiment and topics simultaneously in reviews is still a challenging ...task. In this paper, we present a novel probabilistic model framework based on the non-parametric hierarchical Dirichlet process (HDP) topic model, called non-parametric joint sentiment topic mixture model (NJST), which adds a sentiment level to the HDP topic model and detects sentiment and topics simultaneously from reviews. Then considered the dynamic nature of social media data, we propose dynamic NJST (dNJST) which adds time decay dependencies of historical epochs to the current epochs. Compared with the existing sentiment topic mixture models which are based on latent Dirichlet allocation (LDA), the biggest difference of NJST and dNJST is that they can determine topic number automatically. We implement NJST and dNJST with online variational inference algorithms, and incorporate the sentiment priors of words into NJST and dNJST with HowNet lexicon. The experiment results in some Chinese social media dataset show that dNJST can effectively detect and track dynamic sentiment and topics.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract
Although schizophrenia is a brain disorder, increasing evidence suggests that there may be body-wide involvement in this illness. However, direct evidence of brain structures involved in the ...presumed peripheral-central interaction in schizophrenia is still unclear. Seventy-nine previously treatment-naïve first-episode schizophrenia patients who were within 2-week antipsychotics initial stabilization, and 41 age- and sex-matched healthy controls were enrolled in the study. Group differences in subcortical brain regional structures measured by MRI and the subclinical cardiovascular, metabolic, immune, and neuroendocrine biomarkers as indexed by allostatic load, and their associations were explored. Compared with controls, patients with schizophrenia had significantly higher allostatic load (P = .001). Lateral ventricle (P < .001), choroid plexus (P < .001), and thalamus volumes (P < .001) were significantly larger, whereas amygdala volume (P = .001) was significantly smaller in patients. The choroid plexus alone was significantly correlated with higher allostatic load after age, sex, education level, and the total intracranial volume were taken into account (t = 3.60, P < .001). Allostatic load was also significantly correlated with PANSS positive (r = 0.28, P = .016) and negative (r = −0.31, P = .008) symptoms, but in opposite directions. The peripheral multisystemic and central nervous system abnormalities in schizophrenia may interact through the choroid plexus during the early stage of the illness. The choroid plexus might provide a sensitive structural biomarker to study the treatment and prevention of brain-periphery interaction abnormalities in schizophrenia.
Cysticercosis caused by the metacestode larval stage of Taenia hydatigena is a disease of veterinary and economic importance. A considerable level of genetic variation among isolates of different ...intermediate hosts and locations has been documented. Generally, data on the genetic population structure of T. hydatigena is scanty and lacking in Nigeria. Meanwhile, similar findings in other cestodes like Echinococcus spp. have been found to be of epidemiological importance. Our aim, therefore, was to characterize and compare the genetic diversity of T. hydatigena population in Nigeria based on three mitochondrial DNA markers as well as to assess the phylogenetic relationship with populations from other geographical regions.
In the present study, we described the genetic variation and diversity of T. hydatigena isolates from Nigerian sheep and goats using three full-length mitochondrial genes: the cytochrome c oxidase subunit 1 (cox1), NADH dehydrogenase subunit 1 (nad1), and NADH dehydrogenase subunit 5 (nad5).
The median-joining network of concatenated cox1-nad1-nad5 sequences indicated that T. hydatigena metacestodes of sheep origin were genetically distinct from those obtained in goats and this was supported by high F
values of nad1, cox1, and concatenated cox1-nad1-nad5 sequences. Genetic variation was also found to be higher in isolates from goats than from sheep.
To the best of our knowledge, the present study described the genetic variation of T. hydatigena population for the first time in Nigeria using full-length mitochondrial genes and suggests the existence of host-specific variants. The population indices of the different DNA markers suggest that analysis of long mitochondrial DNA fragments may provide more information on the molecular ecology of T. hydatigena. We recommend that future studies employ long mitochondrial DNA sequence in order to provide reliable data that would explain the extent of genetic variation in different hosts/locations and the biological and epidemiological significance.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Inhibition of G-protein-coupled receptor kinase 2 (GRK2) is an emerging treatment option for heart failure. Because GRK2 is also indispensable for growth and development, we analyzed the impact of ...GRK2 inhibition on cell growth and proliferation. Inhibition of GRK2 by the dominant-negative GRK2-K220R did not affect the proliferation of cultured cells. In contrast, upon xenograft transplantation of cells into immunodeficient mice, the dominant-negative GRK2-K220R or a GRK2-specific peptide inhibitor increased tumor mass. The enhanced tumor growth upon GRK2 inhibition was attributed to the growth-promoting MAPK pathway because dual inhibition of the GRK2 and RAF-MAPK axis by the Raf kinase inhibitor protein (RKIP) did not increase tumor mass. The MAPK cascade contributed to the cardioprotective profile of GRK2 inhibition by preventing cardiomyocyte death, whereas dual inhibition of RAF/MAPK and GRK2 by RKIP induced cardiomyocyte apoptosis, cardiac dysfunction, and signs of heart failure. Thus, cardioprotective signaling induced by GRK2 inhibition is overlapping with tumor growth promotion.
Background: Mechanisms underlying the cardioprotective profile of G-protein-coupled receptor kinase 2 (GRK2) inhibitors are incompletely understood.
Results: GRK2 inhibition activated the growth-promoting MAPK pathway, which contributed to cardioprotection by preventing cardiomyocyte death.
Conclusion: Cardioprotective activity of GRK2 inhibitors overlaps with enhanced tumor growth.
Significance: A promising class of kinase inhibitors for heart failure treatment shows overlapping of cardioprotective signaling with tumor growth promotion.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The inositol hexakisphosphate kinases (IP6Ks) are the principal enzymes that generate inositol pyrophosphates. There are three IP6Ks (IP6K1, 2, and 3). Functions of IP6K1 and IP6K2 have been ...substantially delineated, but little is known of IP6K3's role in normal physiology, especially in the brain. To elucidate functions of IP6K3, we generated mice with targeted deletion of IP6K3. We demonstrate that IP6K3 is highly concentrated in the brain in cerebellar Purkinje cells. IP6K3 physiologically binds to the cytoskeletal proteins adducin and spectrin, whose mutual interactions are perturbed in IP6K3-null mutants. Consequently, IP6K3 knock-out cerebella manifest abnormalities in Purkinje cell structure and synapse number, and the mutant mice display deficits in motor learning and coordination. Thus, IP6K3 is a major determinant of cytoskeletal disposition and function of cerebellar Purkinje cells.
We identified and cloned a family of three inositol hexakisphosphate kinases (IP6Ks) that generate the inositol pyrophosphates, most notably 5-diphosphoinositol pentakisphosphate (IP7). Of these, IP6K3 has been least characterized. In the present study we generated IP6K3 knock-out mice and show that IP6K3 is highly expressed in cerebellar Purkinje cells. IP6K3-deleted mice display defects of motor learning and coordination. IP6K3-null mice manifest aberrations of Purkinje cells with a diminished number of synapses. IP6K3 interacts with the cytoskeletal proteins spectrin and adducin whose altered disposition in IP6K3 knock-out mice may mediate phenotypic features of the mutant mice. These findings afford molecular/cytoskeletal mechanisms by which the inositol polyphosphate system impacts brain function.
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