Here we report on the identification and applications of an aqueous 29-atom silver cluster stabilized with 12 lipoate ligands, i.e. Ag29(R-α–LA)12 or (29,12), wherein R-α–LA = R-α-lipoic acid, a ...natural dithiolate. Its uniformity is checked by HPLC-ESI-MS and analytical ultracentrifugation, which confirms its small dimension (∼3 nm hydrodynamic diameter). For the first time, this cluster has been detected intact via electrospray ionization mass spectrometry, allowing one to confirm its composition, its 3- charge-state, and the 8-electron shell configuration of its metallic silver core. Its electronic structure and bonding, including T-symmetry and profound chirality in the outer shell, have been analyzed by DFT quantum-chemical calculations, starting from the known structure of a nonaqueous homologue. The cluster is effective against Methicillin-Resistant Staphylococcus aureus bacteria (MRSA) at a minimum inhibitory concentration (MIC) of 0.6 mg-Ag/mL. A preformed Candida albicans fungal biofilm, impermeable to other antifungal agents, was also inhibited by aqueous solutions of this cluster, in a dose–response manner, with a half-maximal inhibitory concentration (IC50) of 0.94 mg-Ag/mL. Scanning electron micrographs showed the post-treatment ultrastructural changes on both MRSA and C. albicans that are characteristic of those displayed after treatment by larger silver nanoparticles.
We investigated the impact of native freshwater mussel assemblages (order Unionoida) on the abundance and composition of nitrogen‐cycling genes in sediment of an upper Mississippi river habitat. We ...hypothesized that the genomic potential for ammonia and nitrite oxidation would be greater in the sediment with mussel assemblages, presumably due to mussel biodeposition products, namely ammonia and organic carbon. Regardless of the presence of mussels, upper Mississippi river sediment microbial communities had the largest genomic potential for nitrogen fixation followed by urea catabolism, nitrate metabolism, and nitrate assimilation, as evidenced by analysis of nitrogen cycling pathway abundances. However, genes encoding nitrate and nitrite redox reactions, narGHI and nxrAB, were the most abundant functional genes of the nitrogen cycling gene families. Using linear discriminant analysis (LDA), we found nitrification genes were the most important biomarkers for nitrogen cycling genomic potential when mussels were present, and this presented an opposing effect on the abundance of genes encoding nitric oxide reduction. The genes involved in nitrification that increased the most were amoA associated with comammox Nitrospira and nxr homologs associated with Nitrospira. On the other hand, the most distinctive biomarkers of microbial communities without mussels were norB and nrfA, as part of denitrification and dissimilatory nitrate reduction to ammonium pathways, respectively. Ultimately, this research demonstrates the impact of native mollusks on microbial nitrogen cycling in an aquatic agroecosystem.
Metagenomic sequencing of Upper Mississippi River sediments revealed a large genomic potential for nitrate metabolism and minor abundance of genes for anaerobic ammonia oxidation and DNRA pathways. The presence of a well‐established freshwater mussel assemblage in these sediments had significantly increased nitrification potential at the expense of DNRA and nitric oxide reduction. In support of these findings, amoA and nxr genes were the most predominant biomarkers of mussel bed, and these genes were associated with comammox Nitrospira and NOB Nitrospira, respectively.
The response to therapy with hypolipidemic agents shows considerable individual variation. These differences may be due to the interaction of environmental and genetic factors that affect drug ...bioavailability, receptor function or ligand structure. Our objective was to assess the effect of apolipoprotein (apo) E genotype and gender on lipid-lowering response to the HMG CoA reductase inhibitor, atorvastatin. Genotyping was carried out on DNA from 328 male and female subjects who participated in a multicentric, double-blind clinical trial, and received 10 mg/day of atorvastatin. Our data demonstrate no significant gender differences for LDL cholesterol levels at baseline. Moreover, mean LDL-C lowering was similar in men (−36.2%, range −2.7 to −57.8%) and in women (−38.1%, range −9.5 to −58.5%) as compared to baseline. However, men carrying the
ε2 allele had a significantly higher mean LDL-C response (−44%) than
ε3 homozygotes (−37%) and
ε4 carriers (−34%);
P=0.01 for
apoE group by treatment interaction. No such gene/treatment interactions were noted in women, with those carrying the
ε2 allele showing a similar mean response (−34%) as
ε3 homozygotes (−39%) and
ε4 carriers (−34%). Mean plasma triglyceride lowering with atorvastatin was 17%. A significant
apoE group by treatment interaction (
P=0.010) was also observed in men, with
ε2 carriers being more responsive (−27%) than
ε3/3 (−13%) and
ε4 (−22%). This interaction was not observed in women. In summary, atorvastatin treatment had similar effects on plasma lipid levels in both men and women; however, the
apoE gene locus was a significant predictor of LDL-C and TG responses to atorvastatin therapy in men, but not in women.
Neonatal brain hypoxia–ischemia (HI) results in neuronal cell death. Previous studies indicate that reactive oxygen species, such as superoxide, play a key role in this process. However, the cellular ...sources have not been established. In this study we examine the role of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex in neonatal HI brain injury and elucidate its mechanism of activation. Rat hippocampal slices were exposed to oxygen glucose deprivation (OGD) to mimic the conditions seen in HI. Initial studies confirmed an important role for NADPH oxidase-derived superoxide in the oxidative stress associated with OGD. Further, the OGD-mediated increase in apoptotic cell death was inhibited by the NADPH oxidase inhibitor apocynin. The activation of NADPH oxidase was found to be dependent on the p38 mitogen-activated protein kinase-mediated phosphorylation and activation of the p47phox subunit. Using an adeno-associated virus antisense construct to selectively decrease p47phox expression in neurons showed that this led to inhibition of both the increase in superoxide and the neuronal cell death associated with OGD. We also found that NADPH oxidase inhibition in a neonatal rat model of HI or scavenging hydrogen peroxide reduced brain injury. Thus, we conclude that activation of the NADPH oxidase complex contributes to the oxidative stress during HI and that therapies targeted against this complex could provide neuroprotection against the brain injury associated with neonatal HI.
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▸ Hypoxia–ischemia (HI) stimulates superoxide generation via NADPH oxidase. ▸ NADPH oxidase activation occurs via the phosphorylation of p47phox by p38MAPK. ▸ The toxic metabolite inducing neuronal injury appears to be hydrogen peroxide. ▸ Reducing reactive oxygen species attenuates the neuronal injury associated with HI.
The bulk of plant biomass is comprised of plant cell walls, which are complex polymeric networks, composed of diverse polysaccharides, proteins, polyphenolics, and hydroxyproline-rich glycoproteins ...(HRGPs). Glycosyltransferases (GTs) work together to synthesize the saccharide components of the plant cell wall. The
Arabidopsis thaliana
fucosyltransferases (FUTs),
At
FUT4, and
At
FUT6, are members of the plant-specific GT family 37 (GT37).
At
FUT4 and
At
FUT6 transfer fucose (Fuc) onto arabinose (Ara) residues of arabinogalactan (AG) proteins (AGPs) and have been postulated to be non-redundant AGP-specific FUTs.
At
FUT4 and
At
FUT6 were recombinantly expressed in mammalian HEK293 cells and purified for biochemical analysis. We report an updated understanding on the specificities of
At
FUT4 and
At
FUT6 that are involved in the synthesis of wall localized AGPs. Our findings suggest that they are selective enzymes that can utilize various arabinogalactan (AG)-like and non-AG-like oligosaccharide acceptors, and only require a free, terminal arabinofuranose. We also report with GUS promoter-reporter gene studies that
AtFUT4
and
AtFUT6
gene expression is sub-localized in different parts of developing
A. thaliana
roots.
Recurrent autoimmune hepatitis (AIH) and de novo AIH are 2 important causes of late graft failure after liver transplantation (LT). Recurrent AIH occurs in patients who undergo LT for AIH. De novo ...AIH occurs in patients who are transplanted for etiologies other than AIH. Although typically treated with standard treatment for AIH, including corticosteroids and azathioprine, both recurrent and de novo AIH may progress to end-stage liver disease requiring retransplantation.
Placing clips in nodes with biopsy-confirmed metastasis before initiating neoadjuvant therapy allows for evaluation of response in breast cancer. Our goal was to determine if pathologic changes in ...clipped nodes reflect the status of the nodal basin and if targeted axillary dissection (TAD), which includes sentinel lymph node dissection (SLND) and selective localization and removal of clipped nodes, improves the false-negative rate (FNR) compared with SLND alone.
A prospective study of patients with biopsy-confirmed nodal metastases with a clip placed in the sampled node was performed. After neoadjuvant therapy, patients underwent axillary surgery and the pathology of the clipped node was compared with other nodes. Patients undergoing TAD had SLND and selective removal of the clipped node using iodine-125 seed localization. The FNR was determined in patients undergoing complete axillary lymphadenectomy (ALND).
Of 208 patients enrolled in this study, 191 underwent ALND, with residual disease identified in 120 (63%). The clipped node revealed metastases in 115 patients, resulting in an FNR of 4.2% (95% CI, 1.4 to 9.5) for the clipped node. In patients undergoing SLND and ALND (n = 118), the FNR was 10.1% (95% CI, 4.2 to 19.8), which included seven false-negative events in 69 patients with residual disease. Adding evaluation of the clipped node reduced the FNR to 1.4% (95% CI, 0.03 to 7.3; P = .03). The clipped node was not retrieved as an SLN in 23% (31 of 134) of patients, including six with negative SLNs but metastasis in the clipped node. TAD followed by ALND was performed in 85 patients, with an FNR of 2.0% (1 of 50; 95% CI, 0.05 to 10.7).
Marking nodes with biopsy-confirmed metastatic disease allows for selective removal and improves pathologic evaluation for residual nodal disease after chemotherapy.
Vertebral fractures are a hallmark of postmenopausal osteoporosis and an important end point in trials of osteoporosis treatment, but the clinical significance of these fractures remains uncertain.
...To determine the association of new vertebral fractures with back pain and back-related functional limitation in older women.
Prospective observational study.
Multicenter Study of Osteoporotic Fractures.
7223 white women aged 65 years and older.
Lateral spine radiographs were obtained at baseline and at a follow-up examination an average of 3.7 years later. Prevalent and incident radiographic vertebral fractures were assessed by quantitative morphometry. Frequency and severity of back pain, disability in doing six activities involving the back, and days of bed rest and days of limited activity due to back pain were assessed annually by questionnaire during follow-up.
Among women without a vertebral fracture at baseline, those with at least one incident vertebral fracture were more likely to have increased back pain (odds ratio OR, 2.4 95% CI, 1.7 to 3.3) and back disability (OR, 2.6 CI, 1.9 to 3.7) and at least 1 day of bed rest due to back pain (OR, 6.7 CI, 4.4 to 10.2) and 7 days of limited activity due to back pain per year (OR, 3.8 CI, 2.7 to 5.0). Among women with a fracture at baseline, those with an incident vertebral fracture also had a greater risk for increased back pain (OR, 2.0 CI, 1.4 to 2.8) and back disability (OR, 2.2 CI, 1.5 to 3.1) and at least 1 day of bed rest (OR, 7.9 CI, 4.9 to 12.9) and 7 days of limited activity per year (OR, 3.5 CI, 2.4 to 5.0). Women with incident fracture had about 10 additional limited-activity days and 1 to 2 days of bed rest per year. New vertebral fractures that did not come to medical attention were associated with increased back pain and functional limitation.
New vertebral fractures, even those not recognized clinically, are associated with substantial increases in back pain and functional limitation due to back pain in older white women. Prevention of new vertebral fractures should reduce the burden of back pain and functional limitation in women with vertebral osteoporosis.
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