The majority of biomolecules are intrinsically atomically precise, an important characteristic that enables rational engineering of their recognition and binding properties. However, imparting a ...similar precision to hybrid nanoparticles has been challenging because of the inherent limitations of existing chemical methods and building blocks. Here we report a new approach to form atomically precise and highly tunable hybrid nanomolecules with well-defined three-dimensionality. Perfunctionalization of atomically precise clusters with pentafluoroaryl-terminated linkers produces size-tunable rigid cluster nanomolecules. These species are amenable to facile modification with a variety of thiol-containing molecules and macromolecules. Assembly proceeds at room temperature within hours under mild conditions, and the resulting nanomolecules exhibit high stabilities because of their full covalency. We further demonstrate how these nanomolecules grafted with saccharides can exhibit dramatically improved binding affinity towards a protein. Ultimately, the developed strategy allows the rapid generation of precise molecular assemblies to investigate multivalent interactions.
Hydroxylated PCBs (OH-PCBs) are a class of organic contaminants that have been found recently in the plasma of Great Lakes fish, the source of which is either bioformation from PCBs or accumulation ...from the environment. To address the potential for fish to biotransform PCBs and bioform OH-PCBs juvenile rainbow trout (
Oncorhynchus mykiss; ∼80
g) were exposed to dietary concentrations of an environmentally relevant mixture of PCBs. Eight OH-PCBs were found in the plasma of rainbow trout after 30 days of exposure to the PCBs, the relative pattern of which was similar to those observed in wild lake trout (
Salvelinus namaycush) from Lake Ontario. Hydroxylated-PCBs were not found (detection limit 0.02
pg/g) in the food or control (not PCB-exposed) fish. A curvilinear log
t
1/2–log
K
ow relationship for recalcitrant PCBs was found, similar to previously reported relationships, although
t
1/2 values were longer and shorter than studies using smaller fish or cooler temperatures, respectively. A number of PCB congeners fell below the log
t
1/2–log
K
ow relationship providing the first estimates of non-chiral PCB biotransformation rates in fish. Enantioselective degradation of the chiral congeners PCBs 91 and 136, also indicated biotransformation. Biotransformation of PCBs was structure-dependent with greater biotransformation of PCBs with vicinal hydrogen atoms in the
meta/
para positions, suggesting CYP 2B-like biotransformation. Other chiral congeners with a
meta/
para substitution pattern showed no enantioselective degradation but were biotransformed based on the log
t
1/2–log
K
ow relationship. The results of this study demonstrate that laboratory held rainbow trout can biotransform a number of PCB congeners and that bioformation is likely an important source of OH-PCBs in wild salmonids of the Great Lakes.
► Chiral polychlorinated biphenyls measured at an estuarine site. ► Sediment microbial reductive dechlorination of heavily chlorinated PCBs exists. ► Trophic transfer of biochemically weathered PCBs ...in estuarine food web. ► Fish and dolphins appear to have biotransformed some chiral PCBs.
To investigate the potential for enantioselective transformation and accumulation, the enantiomer distributions of seven polychlorinated biphenyl (PCB) atropisomers were measured in the sediment and biota from a sub-tropical estuary heavily contaminated with Aroclor 1268, a technical mixture of highly chlorinated PCB congeners. Enantiomer fractions (EFs) of PCBs 91, 95, 136, 149, 174, 176, and 183 in marsh sediment, invertebrate, forage and predatory fish species, and bottlenose dolphins were determined. Non-racemic EFs greater than 0.75 were found in sediments for PCBs 136 and 174, likely the result of microbial dechlorination. Although enantiomer fractions in grass shrimp (Palaemonetes spp.) mirrored those of sediment, fish species had EFs that differed significantly from sediment or grass shrimp. Similarly, bottlenose dolphins were also found to contain non-racemic quantities of PCBs 91, 136, 174, 176, and 183. Non-racemic EFs in these biota were likely a result of both uptake of non-racemic proportions of PCBs from the diet and enantioselective biotransformation.
The majority of biomolecules are intrinsically atomically precise, an important characteristic that enables rational engineering of their recognition and binding properties. However, imparting a ...similar precision to hybrid nanoparticles has been challenging because of the inherent limitations of existing chemical methods and building blocks. Here we report a new approach to form atomically precise and highly tunable hybrid nanomolecules with well-defined three-dimensionality. Perfunctionalization of atomically precise clusters with pentafluoroaryl-terminated linkers produces size-tunable rigid cluster nanomolecules. These species are amenable to facile modification with a variety of thiol-containing molecules and macromolecules. Assembly proceeds at room temperature within hours under mild conditions, and the resulting nanomolecules exhibit high stabilities because of their full covalency. We further demonstrate how these nanomolecules grafted with saccharides can exhibit dramatically improved binding affinity towards a protein. Ultimately, the developed strategy allows the rapid generation of precise molecular assemblies to investigate multivalent interactions.
The majority of biomolecules are intrinsically atomically precise, an important characteristic that enables rational engineering of their recognition and binding properties. However, imparting a ...similar precision to hybrid nanoparticles has been challenging because of the inherent limitations of existing chemical methods and building blocks. Here we report a new approach to form atomically precise and highly tunable hybrid nanomolecules with well-defined three-dimensionality. Perfunctionalization of atomically precise clusters with pentafluoroaryl-terminated linkers produces size-tunable rigid cluster nanomolecules. These species are amenable to facile modification with a variety of thiol-containing molecules and macromolecules. Assembly proceeds at room temperature within hours under mild conditions, and the resulting nanomolecules exhibit high stabilities because of their full covalency. We further demonstrate how these nanomolecules grafted with saccharides can exhibit dramatically improved binding affinity towards a protein. Ultimately, the developed strategy allows the rapid generation of precise molecular assemblies to investigate multivalent interactions.
Cinnamyl alcohol dehydrogenase (CAD) catalyzes the last step in monolignol biosynthesis and genetic evidence indicates CAD deficiency in grasses both decreases overall lignin, alters lignin structure ...and increases enzymatic recovery of sugars. To ascertain the effect of CAD downregulation in switchgrass, RNA mediated silencing of CAD was induced through Agrobacterium mediated transformation of cv. “Alamo” with an inverted repeat construct containing a fragment derived from the coding sequence of PviCAD2 . The resulting primary transformants accumulated less CAD RNA transcript and protein than control transformants and were demonstrated to be stably transformed with between 1 and 5 copies of the T-DNA. CAD activity against coniferaldehyde, and sinapaldehyde in stems of silenced lines was significantly reduced as was overall lignin and cutin. Glucose release from ground samples pretreated with ammonium hydroxide and digested with cellulases was greater than in control transformants. When stained with the lignin and cutin specific stain phloroglucinol-HCl the staining intensity of one line indicated greater incorporation of hydroxycinnamyl aldehydes in the lignin.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We developed a metagenomic next-generation sequencing (mNGS) test using cell-free DNA from body fluids to identify pathogens. The performance of mNGS testing of 182 body fluids from 160 patients with ...acute illness was evaluated using two sequencing platforms in comparison to microbiological testing using culture, 16S bacterial PCR and/or 28S-internal transcribed ribosomal gene spacer (28S-ITS) fungal PCR. Test sensitivity and specificity of detection were 79 and 91% for bacteria and 91 and 89% for fungi, respectively, by Illumina sequencing; and 75 and 81% for bacteria and 91 and 100% for fungi, respectively, by nanopore sequencing. In a case series of 12 patients with culture/PCR-negative body fluids but for whom an infectious diagnosis was ultimately established, seven (58%) were mNGS positive. Real-time computational analysis enabled pathogen identification by nanopore sequencing in a median 50-min sequencing and 6-h sample-to-answer time. Rapid mNGS testing is a promising tool for diagnosis of unknown infections from body fluids.
Type 2 diabetes (T2D) is a progressive disease whereby there is often deterioration in glucose control despite escalation in treatment. There is significant heterogeneity to this progression of ...glycemia after onset of diabetes, yet the factors that influence glycemic progression are not well understood. Given the tremendous burden of diabetes in the Chinese population, and limited knowledge on factors that influence glycemia, we aim to identify the clinical and genetic predictors for glycemic progression in Chinese patients with T2D. In 1995-2007, 7,091 insulin-naïve Chinese patients (mean age 56.8 ± 13.3 SD years; mean age of T2D onset 51.1 ± 12.7 years; 47% men; 28.4% current or ex-smokers; median duration of diabetes 4 IQR: 1-9 years; mean HbA1c 7.4% ± 1.7%; mean body mass index BMI 25.3 ± 4.0 kg/m.sup.2) were followed prospectively in the Hong Kong Diabetes Register. We examined associations of BMI and other clinical and genetic factors with glycemic progression defined as requirement of continuous insulin treatment, or 2 consecutive HbA1c greater than or equal to8.5% while on greater than or equal to2 oral glucose-lowering drugs (OGLDs), with validation in another multicenter cohort of Hong Kong Diabetes Biobank. During a median follow-up period of 8.8 (IQR: 4.8-13.3) years, incidence of glycemic progression was 48.0 (95% confidence interval CI 46.3-49.8) per 1,000 person-years with 2,519 patients started on insulin. Among the latter, 33.2% had a lag period of 1.3 years before insulin was initiated. Risk of progression was associated with extremes of BMI and high HbA1c. On multivariate Cox analysis, early age at diagnosis, microvascular complications, high triglyceride levels, and tobacco use were additional independent predictors for glycemic progression. A polygenic risk score (PRS) including 123 known risk variants for T2D also predicted rapid progression to insulin therapy (hazard ratio HR: 1.07 95% CI 1.03-1.12 per SD; P = 0.001), with validation in the replication cohort (HR: 1.24 95% CI 1.06-1.46 per SD; P = 0.008). A PRS using 63 BMI-related variants predicted BMI (beta SE = 0.312 0.057 per SD; P = 5.84 x 10.sup.-8) but not glycemic progression (HR: 1.01 95% CI 0.96-1.05 per SD; P = 0.747). Limitations of this study include potential misdiagnosis of T2D and lack of detailed data of drug use during follow-up in the replication cohort. Our results show that approximately 5% of patients with T2D failed OGLDs annually in this clinic-based cohort. The independent associations of modifiable and genetic risk factors allow more precise identification of high-risk patients for early intensive control of multiple risk factors to prevent glycemic progression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In a trial involving 304 veterans with stable PTSD, prazosin did not alleviate distressing dreams and did not improve sleep quality or overall clinical symptoms over 10 or 26 weeks. This result is in ...contrast to findings in several previous smaller or briefer trials.
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