The Pathosystems Resource Integration Center (PATRIC) is the bacterial Bioinformatics Resource Center (https://www.patricbrc.org). Recent changes to PATRIC include a redesign of the web interface and ...some new services that provide users with a platform that takes them from raw reads to an integrated analysis experience. The redesigned interface allows researchers direct access to tools and data, and the emphasis has changed to user-created genome-groups, with detailed summaries and views of the data that researchers have selected. Perhaps the biggest change has been the enhanced capability for researchers to analyze their private data and compare it to the available public data. Researchers can assemble their raw sequence reads and annotate the contigs using RASTtk. PATRIC also provides services for RNA-Seq, variation, model reconstruction and differential expression analysis, all delivered through an updated private workspace. Private data can be compared by 'virtual integration' to any of PATRIC's public data. The number of genomes available for comparison in PATRIC has expanded to over 80 000, with a special emphasis on genomes with antimicrobial resistance data. PATRIC uses this data to improve both subsystem annotation and k-mer classification, and tags new genomes as having signatures that indicate susceptibility or resistance to specific antibiotics.
ABSTRACT
We present the first satellite system of the Large Binocular Telescope Satellites Of Nearby Galaxies Survey (LBT-SONG), a survey to characterize the close satellite populations of Large ...Magellanic Cloud to Milky-Way-mass, star-forming galaxies in the Local Volume. In this paper, we describe our unresolved diffuse satellite finding and completeness measurement methodology and apply this framework to NGC 628, an isolated galaxy with ∼1/4 the stellar mass of the Milky Way. We present two new dwarf satellite galaxy candidates: NGC 628 dwA, and dwB with MV = −12.2 and −7.7, respectively. NGC 628 dwA is a classical dwarf while NGC 628 dwB is a low-luminosity galaxy that appears to have been quenched after reionization. Completeness corrections indicate that the presence of these two satellites is consistent with CDM predictions. The satellite colours indicate that the galaxies are neither actively star forming nor do they have the purely ancient stellar populations characteristic of ultrafaint dwarfs. Instead, and consistent with our previous work on the NGC 4214 system, they show signs of recent quenching, further indicating that environmental quenching can play a role in modifying satellite populations even for hosts smaller than the Milky Way.
Marine microbes exhibit seasonal cycles in community composition, yet the key drivers of these patterns and microbial population fidelity to specific environmental conditions remain to be determined. ...To begin addressing these questions, we characterized microbial dynamics weekly for 3 years at a temperate, coastal site with dramatic environmental seasonality. This high-resolution time series reveals that changes in microbial community composition are not continuous; over the duration of the time series, the community instead resolves into distinct summer and winter profiles with rapid spring and fall transitions between these states. Here, we show that these community shifts involve switching between closely related strains that exhibit either summer or winter preferences. Moreover, taxa repeat this process annually in both this and another temperate coastal time series, suggesting that this phenomenon may be widespread in marine ecosystems. To address potential biogeochemical impacts of these community changes, PICRUSt-based metagenomes predict seasonality in transporters, photosynthetic proteins, peptidases and carbohydrate metabolic pathways in spite of closely related summer- and winter-associated taxa. Thus, even small temperature shifts, such as those predicted by climate change models, could affect both the structure and function of marine ecosystems.
Heating of nanoparticles (NPs) using an AC magnetic field depends on several factors, and optimization of these parameters can improve the efficiency of heat generation for effective cancer therapy ...while administering a low NP treatment dose. This study investigated magnetic field strength and frequency, NP size, NP concentration, and solution viscosity as important parameters that impact the heating efficiency of iron oxide NPs with magnetite (Fe3O4) and maghemite (γ-Fe2O3) crystal structures. Heating efficiencies were determined for each experimental setting, with specific absorption rates (SARs) ranging from 3.7 to 325.9W/g Fe. Magnetic heating was conducted on iron oxide NPs synthesized in our laboratories (with average core sizes of 8, 11, 13, and 18nm), as well as commercially-available iron oxides (with average core sizes of 8, 9, and 16nm). The experimental magnetic coil system made it possible to isolate the effect of magnetic field parameters and independently study the effect on heat generation. The highest SAR values were found for the 18nm synthesized particles and the maghemite nanopowder. Magnetic field strengths were applied in the range of 15.1–47.7kA/m, with field frequencies ranging from 123 to 430kHz. The best heating was observed for the highest field strengths and frequencies tested, with results following trends predicted by the Rosensweig equation. An increase in solution viscosity led to lower heating rates in nanoparticle solutions, which can have significant implications for the application of magnetic fluid hyperthermia in vivo.
•Heating was tested in seven iron oxide nanoparticles for different magnetic fields.•Confirms an optimal nanoparticle size for heating that agrees with the literature.•Verifies Rosenweig's equation to predict the effect of field frequency on heating.•Reports reduced heating in high viscosity environments.
Recent progress in engineering the genomes of large animals has spurred increased interest in developing better animal models for diseases where current options are inadequate. Here, we report the ...creation of Yucatan miniature pigs with targeted disruptions of the low-density lipoprotein receptor (LDLR) gene in an effort to provide an improved large animal model of familial hypercholesterolemia and atherosclerosis. Yucatan miniature pigs are well established as translational research models because of similarities to humans in physiology, anatomy, genetics, and size. Using recombinant adeno-associated virus-mediated gene targeting and somatic cell nuclear transfer, male and female LDLR+/- pigs were generated. Subsequent breeding of heterozygotes produced LDLR-/- pigs. When fed a standard swine diet (low fat, no cholesterol), LDLR+/- pigs exhibited a moderate, but consistent increase in total and LDL cholesterol, while LDLR-/- pigs had considerably elevated levels. This severe hypercholesterolemia in homozygote animals resulted in atherosclerotic lesions in the coronary arteries and abdominal aorta that resemble human atherosclerosis. These phenotypes were more severe and developed over a shorter time when fed a diet containing natural sources of fat and cholesterol. LDLR-targeted Yucatan miniature pigs offer several advantages over existing large animal models including size, consistency, availability, and versatility. This new model of cardiovascular disease could be an important resource for developing and testing novel detection and treatment strategies for coronary and aortic atherosclerosis and its complications.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Endogenous circadian clocks orchestrate several metabolic and signaling pathways that are known to modulate lifespan, suggesting clocks as potential targets for manipulation of metabolism and ...lifespan. We report here that the core circadian clock genes, timeless (tim) and period (per), are required for the metabolic and lifespan responses to DR in Drosophila. Consistent with the involvement of a circadian mechanism, DR enhances the amplitude of cycling of most circadian clock genes, including tim, in peripheral tissues. Mass-spectrometry-based lipidomic analysis suggests a role of tim in cycling of specific medium chain triglycerides under DR. Furthermore, overexpression of tim in peripheral tissues improves its oscillatory amplitude and extends lifespan under ad libitum conditions. Importantly, effects of tim on lifespan appear to be mediated through enhanced fat turnover. These findings identify a critical role for specific clock genes in modulating the effects of nutrient manipulation on fat metabolism and aging.
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•DR enhances the magnitude of cyclic expression of circadian clock genes•timeless (tim) and period are required for the optimal DR response in Drosophila•tim regulates fat metabolism and cycling of medium chain triglycerides upon DR•Overexpression of tim increases amplitude and extends lifespan under AL conditions
Dietary restriction (DR) is known to boost fat metabolism and lifespan. Katewa et al. reveal that peripheral circadian clocks play a key role in this response and that DR increases clock gene expression. Overexpression of timeless mimics the effects of DR and extends fly lifespan under ad libitum conditions.
Terrestrial organic matter is believed to play an important role in promoting resilient estuarine food webs, but the inherent interconnectivity of estuarine systems often obscures the origins and ...importance of these terrestrial inputs. To determine the relative contributions of terrestrial (allochthonous) and aquatic (autochthonous) organic matter to the estuarine food web, we analyzed carbon, nitrogen, and sulfur stable isotopes from multiple trophic levels, environmental strata, and habitats throughout the estuarine habitat mosaic. We used a Bayesian stable isotope mixing model (SIMM) to parse out relationships among primary producers, invertebrates, and a pelagic and demersal fish species (juvenile Chinook salmon and sculpin, respectively). The study was carried out in the Nisqually River Delta (NRD), Washington, USA, a recently-restored, macrotidal estuary with a diverse habitat mosaic. Plant groupings of macroalgae, eelgrass, and tidal marsh plants served as the primary base components of the NRD food web. About 90% of demersal sculpin diets were comprised of benthic and pelagic crustaceans that were fed by autochthonous organic matter contributions from aquatic vegetation. Juvenile salmon, on the other hand, derived their energy from a mix of terrestrial, pelagic, and benthic prey, including insects, dipterans, and crustaceans. Consequently, allochthonous terrestrial contributions of organic matter were much greater for salmon, ranging between 26 and 43%. These findings demonstrate how connectivity among estuarine habitat types and environmental strata facilitates organic matter subsidies. This suggests that management actions that improve or restore lateral habitat connectivity as well as terrestrial-aquatic linkages may enhance allochthonous subsidies, promoting increased prey resources and ecosystem benefits in estuaries.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Systemic deletion of senescent cells leads to robust improvements in cognitive, cardiovascular, and whole‐body metabolism, but their role in tissue reparative processes is incompletely understood. We ...hypothesized that senolytic drugs would enhance regeneration in aged skeletal muscle. Young (3 months) and old (20 months) male C57Bl/6J mice were administered the senolytics dasatinib (5 mg/kg) and quercetin (50 mg/kg) or vehicle bi‐weekly for 4 months. Tibialis anterior (TA) was then injected with 1.2% BaCl2 or PBS 7‐ or 28 days prior to euthanization. Senescence‐associated β‐Galactosidase positive (SA β‐Gal+) cell abundance was low in muscle from both young and old mice and increased similarly 7 days following injury in both age groups, with no effect of D+Q. Most SA β‐Gal+ cells were also CD11b+ in young and old mice 7‐ and 14 days following injury, suggesting they are infiltrating immune cells. By 14 days, SA β‐Gal+/CD11b+ cells from old mice expressed senescence genes, whereas those from young mice expressed higher levels of genes characteristic of anti‐inflammatory macrophages. SA β‐Gal+ cells remained elevated in old compared to young mice 28 days following injury, which were reduced by D+Q only in the old mice. In D+Q‐treated old mice, muscle regenerated following injury to a greater extent compared to vehicle‐treated old mice, having larger fiber cross‐sectional area after 28 days. Conversely, D+Q blunted regeneration in young mice. In vitro experiments suggested D+Q directly improve myogenic progenitor cell proliferation. Enhanced physical function and improved muscle regeneration demonstrate that senolytics have beneficial effects only in old mice.
Senolytics improve muscle regeneration in old mice, while providing no benefit in young mice. Old mice display more satellite cells, reduced inflammation, a lower senescent cell burden, and increased gene expression of bioenergetic pathways relative to untreated old mice.
AID/APOBEC family enzymes are best known for deaminating cytosine bases to uracil in single-stranded DNA, with characteristic sequence preferences that can produce mutational signatures in targets ...such as retroviral and cancer cell genomes. These deaminases have also been proposed to function in DNA demethylation via deamination of either 5-methylcytosine (mC) or TET-oxidized mC bases (ox-mCs), which include 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine. One specific family member, APOBEC3A (A3A), has been shown to readily deaminate mC, raising the prospect of broader activity on ox-mCs. To investigate this claim, we developed a novel assay that allows for parallel profiling of activity on all modified cytosines. Our steady-state kinetic analysis reveals that A3A discriminates against all ox-mCs by >3700-fold, arguing that ox-mC deamination does not contribute substantially to demethylation. A3A is, by contrast, highly proficient at C/mC deamination. Under conditions of excess enzyme, C/mC bases can be deaminated to completion in long DNA segments, regardless of sequence context. Interestingly, under limiting A3A, the sequence preferences observed with targeting unmodified cytosine are further exaggerated when deaminating mC. Our study informs how methylation, oxidation, and deamination can interplay in the genome and suggests A3A's potential utility as a biotechnological tool to discriminate between cytosine modification states.
This study quantitatively synthesized literature to identify gender differences in the prevalence of frailty in heart failure (HF).
The intersection of frailty and HF continues to garner interest. ...Almost half of patients with HF are frail; however, gender differences in frailty in HF are poorly understood.
We performed a literature search to identify studies that reported prevalence of frailty by gender in HF. Random-effects meta-analysis was used to quantify the relative and absolute risk of frailty in women compared with men with HF, overall, and by Physical and Multidimensional Frailty measures. Meta-regression was performed to examine the influence of study age and functional class on relative risk in HF.
Twenty-nine studies involving 8854 adults with HF were included. Overall in HF, women had a 26% higher relative risk of being frail compared with men (95% CI = 1.14–1.38, z = 4.69, p < 0.001, I2 = 76.5%). The overall absolute risk for women compared to men with HF being frail was 10% (95% CI = 0.06–0.15, z = 4.41, p < 0.001). The relative risk of frailty was slightly higher among studies that used Physical measures (relative risk = 1.27, p < 0.001) compared with studies that used Multidimensional measures (relative risk = 1.24, p = 0.024). There were no significant relationships between relative risk and either study age or functional class.
In HF, frailty affects women significantly more than men. Future work should focus on elucidating potential causes of gender differences in frailty in HF.
•Frailty is highly prevalent in heart failure.•Women have a 26% higher relative risk than men to be frail in heart failure.•More gender-balanced studies of frailty in heart failure should be pursued.
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