22 research outputs found
Network-driven plasma proteomics expose molecular changes in the Alzheimer’s brain
Background Biological pathways that significantly contribute to sporadic
Alzheimer’s disease are largely unknown and cannot be observed directly.
Cognitive symptoms appear only decades after the molecular disease onset,
further complicating analyses. As a consequence, molecular research is often
restricted to late-stage post-mortem studies of brain tissue. However, the
disease process is expected to trigger numerous cellular signaling pathways
and modulate the local and systemic environment, and resulting changes in
secreted signaling molecules carry information about otherwise inaccessible
pathological processes. Results To access this information we probed relative
levels of close to 600 secreted signaling proteins from patients’ blood
samples using antibody microarrays and mapped disease-specific molecular
networks. Using these networks as seeds we then employed independent genome
and transcriptome data sets to corroborate potential pathogenic pathways.
Conclusions We identified Growth-Differentiation Factor (GDF) signaling as a
novel Alzheimer’s disease-relevant pathway supported by in vivo and in vitro
follow-up experiments, demonstrating the existence of a highly informative
link between cellular pathology and changes in circulatory signaling proteins
Network-Driven Plasma Proteomics Expose Molecular Changes in the Alzheimer\u27s Brain
Background: Biological pathways that significantly contribute to sporadic Alzheimer’s disease are largely unknown and cannot be observed directly. Cognitive symptoms appear only decades after the molecular disease onset, further complicating analyses. As a consequence, molecular research is often restricted to late-stage post-mortem studies of brain tissue. However, the disease process is expected to trigger numerous cellular signaling pathways and modulate the local and systemic environment, and resulting changes in secreted signaling molecules carry information about otherwise inaccessible pathological processes. Results: To access this information we probed relative levels of close to 600 secreted signaling proteins from patients’ blood samples using antibody microarrays and mapped disease-specific molecular networks. Using these networks as seeds we then employed independent genome and transcriptome data sets to corroborate potential pathogenic pathways. Conclusions: We identified Growth-Differentiation Factor (GDF) signaling as a novel Alzheimer’s disease-relevant pathway supported by in vivo and in vitro follow-up experiments, demonstrating the existence of a highly informative link between cellular pathology and changes in circulatory signaling proteins
Degradation of DEET and Caffeine under UV/Chlorine and Simulated Sunlight/Chlorine Conditions
Photoactivation
of aqueous chlorine could promote degradation of
chlorine-resistant and photochemically stable chemicals accumulated
in swimming pools. This study investigated the degradation of two
such chemicals, <i>N</i>,<i>N</i>-diethyl-3-methylbenzamide
(DEET) and caffeine, by low pressure ultraviolet (UV) light and simulated
sunlight (SS) activated free chlorine (FC) in different water matrices.
Both DEET and caffeine were rapidly degraded by UV/FC and SS/FC but
exhibited different kinetic behaviors. The degradation of DEET followed
pseudo-first-order kinetics, whereas the degradation of caffeine accelerated
with reaction. Mechanistic study revealed that, under UV/FC, ·OH
and Cl· were responsible for degradation of DEET, whereas ClO·
related reactive species (ClOrrs), generated by the reaction between
FC and ·OH/Cl·, played a major role in addition to ·OH
and Cl· in degrading caffeine. Reaction rate constants of DEET
and caffeine with the respective radical species were estimated. The
imidazole moiety of caffeine was critical for the special reactivity
with ClOrrs. Water matrix such as pH had a stronger impact on the
UV/FC process than the SS/FC process. In saltwater matrix under UV/FC
and SS/FC, the degradation of DEET was significantly inhibited, but
the degradation of caffeine was much faster than that in nonsalty
solutions. The interaction between Br<sup>–</sup> and Cl<sup>–</sup> may play an important role in the degradation of caffeine
by UV/FC in saltwater. Reaction product analysis showed similar product
patterns by UV/FC and SS/FC and minimal formation of chlorinated intermediates
and disinfection byproducts
Identification of five serum protein markers for detection of ovarian cancer by antibody arrays.
BACKGROUND:Protein and antibody arrays have emerged as a promising technology to study protein expression and protein function in a high-throughput manner. These arrays also represent a new opportunity to profile protein expression levels in cancer patients' samples and to identify useful biosignatures for clinical diagnosis, disease classification, prediction, drug development and patient care. We applied antibody arrays to discover a panel of proteins which may serve as biomarkers to distinguish between patients with ovarian cancer and normal controls. METHODOLOGY/PRINCIPAL FINDINGS:Using a case-control study design of 34 ovarian cancer patients and 53 age-matched healthy controls, we profiled the expression levels of 174 proteins using antibody array technology and determined the CA125 level using ELISA. The expression levels of those proteins were analyzed using 3 discriminant methods, including artificial neural network, classification tree and split-point score analysis. A panel of 5 serum protein markers (MSP-alpha, TIMP-4, PDGF-R alpha, and OPG and CA125) was identified, which could effectively detect ovarian cancer with high specificity (95%) and high sensitivity (100%), with AUC =0.98, while CA125 alone had an AUC of 0.87. CONCLUSIONS/SIGNIFICANCE:Our pilot study has shown the promising set of 5 serum markers for ovarian cancer detection
Degradation of Pharmaceuticals and Metabolite in Synthetic Human Urine by UV, UV/H<sub>2</sub>O<sub>2</sub>, and UV/PDS
To
minimize environmental pharmaceutical micropollutants, treatment
of human urine could be an efficient approach due to the high pharmaceutical
concentration and toxic potential excreted in urine. This study investigated
the degradation kinetics and mechanisms of sulfamethoxazole (SMX),
trimethoprim (TMP) and N<sub>4</sub>-acetyl-sulfamethoxazole (acetyl-SMX)
in synthetic fresh and hydrolyzed human urines by low-pressure UV,
and UV combined with H<sub>2</sub>O<sub>2</sub> and peroxydisulfate
(PDS). The objective was to compare the two advanced oxidation processes
(AOPs) and assess the impact of urine matrices. All three compounds
reacted quickly in the AOPs, exhibiting rate constants of (6.09–8.53)
× 10<sup>9</sup> M<sup>–1</sup>·s<sup>–1</sup> with hydroxyl radical, and (2.35–16.1) × 10<sup>9</sup> M<sup>–1</sup>·s<sup>–1</sup> with sulfate radical.
In fresh urine matrix, the pharmaceuticals’ indirect photolysis
was significantly suppressed by the scavenging effect of urine citrate
and urea. In hydrolyzed urine matrix, the indirect photolysis was
strongly affected by inorganic urine constituents. Chloride had no
apparent impact on UV/H<sub>2</sub>O<sub>2</sub>, but significantly
raised the hydroxyl radical concentration in UV/PDS. Carbonate species
reacted with hydroxyl or sulfate radical to generate carbonate radical,
which degraded SMX and TMP, primarily due to the presence of aromatic
amino group(s) (<i>k</i> = 2.68 Ă— 10<sup>8</sup> and
3.45 × 10<sup>7</sup> M<sup>–1</sup>·s<sup>–1</sup>) but reacted slowly with acetyl-SMX. Ammonia reacted with hydroxyl
or sulfate radical to generate reactive nitrogen species that could
react appreciably only with SMX. Kinetic simulation of radical concentrations,
along with products analysis, helped elucidate the major reactive
species in the pharmaceuticals’ degradation. Overall, the AOPs’
performance was higher in the hydrolyzed urine than fresh urine matrix
with UV/PDS better than UV/H<sub>2</sub>O<sub>2</sub>, and varied
significantly depending on pharmaceutical’s structure
Rapid Disinfection by Peracetic Acid Combined with UV Irradiation
This study proposes a novel disinfection
process by sequential
application of peracetic acid (PAA) and ultraviolet light (UV), on
the basis of elucidation of disinfection mechanisms under UV/PAA.
Results show that hydroxyl radicals, generated by UV-activated PAA,
contribute to the enhanced inactivation of Escherichia
coli under UV/PAA compared to PAA alone or UV alone.
Furthermore, the location of hydroxyl radical generation is a critical
factor. Unlike UV/H<sub>2</sub>O<sub>2</sub>, which generates hydroxyl
radicals mainly in the bulk solution, the hydroxyl radicals under
UV/PAA are produced close to or inside E. coli cells, due to PAA diffusion. Therefore, hydroxyl radicals exert
significantly stronger disinfection power under UV/PAA than under
UV/H<sub>2</sub>O<sub>2</sub> conditions. Pre-exposing E. coli to PAA in the dark followed by application
of UV (i.e., a PAA-UV/PAA process) promotes diffusion of PAA to the
cells and achieves excellent disinfection efficiency while saving
more than half of the energy cost associated with UV compared to simultaneous
application of UV and PAA. The effectiveness of this new disinfection
strategy has been demonstrated not only in lab water but also in wastewater
matrices
PPCP Degradation by Chlorine–UV Processes in Ammoniacal Water: New Reaction Insights, Kinetic Modeling, and DBP Formation
The combination of chlorine and UV
(i.e., chlorine–UV process)
has been attracting more attention in recent years due to its ready
incorporation into existing water treatment facilities to remove PPCPs.
However, limited information is available on the impact of total ammonia
nitrogen (TAN). This study investigated two model PPCPs, <i>N,N</i>-diethyl-3-toluamide (DEET) and caffeine (CAF), in the two stages
of the chlorine–UV process (i.e., chlorination and UV/chlorÂ(am)Âine)
to elucidate the impact of TAN. During chlorination, the degradation
of DEET and CAF was positively correlated with the overall consumption
of total chlorine by TAN. Reactive nitrogen intermediates, including
HNO/NO<sup>–</sup> and ONOOH/ONOO<sup>–</sup>, along
with <sup>•</sup>OH were identified as major contributors to
the removal of DEET and CAF. During UV irradiation, DEET and CAF were
degraded under UV/chlorine or UV/NH<sub>2</sub>Cl conditions. <sup>•</sup>OH and <sup>•</sup>Cl were the major reactive
species to degrade DEET and CAF under UV/NH<sub>2</sub>Cl conditions,
whereas <sup>•</sup>OCl played a major role for degrading CAF
under UV/chlorine conditions. Numerical models were developed to predict
the removal of DEET and CAF under chlorination–UV process.
Chlorinated disinfection byproducts were detected. Overall, this study
presented kinetic features and mechanistic insights on the degradation
of PPCPs under the chlorine–UV process in ammoniacal water