The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological ...conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.
MicroRNAs in plants Reinhart, Brenda J; Weinstein, Earl G; Rhoades, Matthew W ...
Genes & development,
2002-Jul-01, 2002-07-01, 20020701, Volume:
16, Issue:
13
Journal Article
Peer reviewed
Open access
MicroRNAs (miRNAs) are an extensive class of ~22-nucleotide noncoding RNAs thought to regulate gene expression in metazoans. We find that miRNAs are also present in plants, indicating that this class ...of noncoding RNA arose early in eukaryotic evolution. In this paper 16 Arabidopsis miRNAs are described, many of which have differential expression patterns in development. Eight are absolutely conserved in the rice genome. The plant miRNA loci potentially encode stem-loop precursors similar to those processed by Dicer (a ribonuclease III) in animals. Mutation of an Arabidopsis Dicer homolog, CARPEL FACTORY, prevents the accumulation of miRNAs, showing that similar mechanisms direct miRNA processing in plants and animals. The previously described roles of CARPEL FACTORY in the development of Arabidopsis embryos, leaves, and floral meristems suggest that the miRNAs could play regulatory roles in the development of plants as well as animals.
Nearshore estuarine and marine ecosystems-e.g., seagrass meadows, marshes, and mangrove forests-serve many important functions in coastal waters. A better understanding of these habitats, that serve ...as nurseries for marine species, and the factors that create site-specific variability in nursery quality will improve conservation and management of these areas.
A comprehensive photophysical investigation has been carried out on a series of eight complexes of the type (diimine)Pt(−C⋮C−Ar)2, where diimine is a series of 2,2‘-bipyridine (bpy) ligands and ...−C⋮C−Ar is a series of substituted aryl acetylide ligands. In one series of complexes, the energy of the Pt → bpy metal-to-ligand charge transfer (MLCT) excited state is varied by changing the substituents on the 4,4‘- and/or the 5,5‘-positions of the bpy ligand. In a second series of complexes the electronic demand of the aryl acetylide ligand is varied by changing the para substituent (X) on the aryl ring (X = −CF3, −CH3, −OCH3, and −N(CH3)2). The effect of variation of the substituents on the excited states of the complexes has been assessed by examining their UV−visible absorption, variable-temperature photoluminescence, transient absorption, and time-resolved infrared spectroscopy. In addition, the nonradiative decay rates of the series of complexes are subjected to a quantitative energy gap law analysis. The results of this study reveal that in most cases the photophysics of the complexes is dominated by the energetically low lying Pt → bpy 3MLCT state. Some of the complexes also feature a low-lying intraligand (IL) 3π,π* excited state that is derived from transitions between π- and π*-type orbitals localized largely on the aryl acetylide ligands. The involvement of the IL 3π,π* state in the photophysics of some of the complexes is signaled by unusual features in the transient absorption, time-resolved infrared, and photoluminescence spectra and in the excited-state decay kinetics. The time-resolved infrared difference spectroscopy indicates that Pt → bpy MLCT excitation induces a +25 to + 35 cm-1 shift in the frequency of the C⋮C stretching band. This is the first study to report the effect of MLCT excitation on the vibrational frequency of an acetylide ligand.
The microRNAs of Caenorhabditis elegans Lim, Lee P; Lau, Nelson C; Weinstein, Earl G ...
Genes & development,
2003-Apr-15, 2003-04-15, 20030415, Volume:
17, Issue:
8
Journal Article
Peer reviewed
Open access
MicroRNAs (miRNAs) are an abundant class of tiny RNAs thought to regulate the expression of protein-coding genes in plants and animals. In the present study, we describe a computational procedure to ...identify miRNA genes conserved in more than one genome. Applying this program, known as MiRscan, together with molecular identification and validation methods, we have identified most of the miRNA genes in the nematode Caenorhabditis elegans. The total number of validated miRNA genes stands at 88, with no more than 35 genes remaining to be detected or validated. These 88 miRNA genes represent 48 gene families; 46 of these families (comprising 86 of the 88 genes) are conserved in Caenorhabditis briggsae, and 22 families are conserved in humans. More than a third of the worm miRNAs, including newly identified members of the lin-4 and let-7 gene families, are differentially expressed during larval development, suggesting a role for these miRNAs in mediating larval developmental transitions. Most are present at very high steady-state levels-more than 1000 molecules per cell, with some exceeding 50,000 molecules per cell. Our census of the worm miRNAs and their expression patterns helps define this class of noncoding RNAs, lays the groundwork for functional studies, and provides the tools for more comprehensive analyses of miRNA genes in other species.
In early-stage Parkinson′s disease (PD), cognitive impairment is common, and a variety of cognitive domains including memory, attention, and executive functioning may be affected. Cerebrospinal fluid ...(CSF) biomarkers are potential markers of cognitive functioning. We aimed to explore whether CSF α-synuclein species, neurofilament light chain, amyloid-β42, and tau are associated with cognitive performance in early-stage PD patients. CSF levels of total-α-synuclein and phosphorylated-α-synuclein, neurofilament light chain, amyloid-β42, and total-tau and phosphorylated-tau were measured in 26 PD patients (disease duration ≤5 years and Hoehn and Yahr stage 1–2.5). Multivariable linear regression models, adjusted for age, gender, and educational level, were used to assess the relationship between CSF biomarker levels and memory, attention, executive and visuospatial function, and language performance scores. In 26 early-stage PD patients, attention and memory were the most commonly affected domains. A higher CSF phosphorylated-α-synuclein/total-α-synuclein ratio was associated with better executive functioning (sβ = 0.40). Higher CSF neurofilament light was associated with worse memory (sβ = −0.59), attentional (sβ = −0.32), and executive functioning (sβ = −0.35). Reduced CSF amyloid-β42 levels were associated with poorer attentional functioning (sβ = 0.35). Higher CSF phosphorylated-tau was associated with worse language functioning (sβ = −0.33). Thus, CSF biomarker levels, in particular neurofilament light, were related to the most commonly affected cognitive domains in early-stage PD. This indicates that CSF biomarker levels may identify early-stage PD patients who are at an increased risk of developing cognitive impairment.
Treatment of Psoriasis Greaves, Malcolm W; Weinstein, Gerald D
The New England journal of medicine,
03/1995, Volume:
332, Issue:
9
Journal Article
Peer reviewed
Psoriasis is a chronic, genetically influenced, remitting and relapsing scaly and inflammatory skin disorder that affects 1 to 3 percent of the world's population. The diagnosis is made on clinical ...grounds, although histologic examination of a skin-biopsy specimen may be helpful. Psoriasis is a disabling, though rarely life-threatening, disease with a social and economic impact that is underestimated by physicians and other health care providers. Recently, progress has been made in understanding the pathogenesis of psoriasis, and therapeutic advances are improving the care of even severely affected patients.
There are several types of psoriasis, including pustular, guttate, and arthritic variants. . . .
To examine practice patterns and compare survival outcomes between total laryngectomy (TL) and larynx preservation chemoradiation (LP-CRT) in the setting of T4a larynx cancer, using a large national ...cancer registry.
Using the National Cancer Database, we identified 969 patients from 2003 to 2006 with T4a squamous cell larynx cancer receiving definitive treatment with either initial TL plus adjuvant therapy or LP-CRT. Univariate and multivariable logistic regression were used to assess predictors of undergoing surgery. Survival outcomes were compared using Kaplan-Meier and propensity score-adjusted and inverse probability of treatment-weighted Cox proportional hazards methods. Sensitivity analyses were performed to account for unmeasured confounders.
A total of 616 patients (64%) received LP-CRT, and 353 (36%) received TL. On multivariable logistic regression, patients with advanced nodal disease were less likely to receive TL (N2 vs N0, 26.6% vs 43.4%, odds ratio OR 0.52, 95% confidence interval CI 0.37-0.73; N3 vs N0, 19.1% vs 43.4%, OR 0.23, 95% CI 0.07-0.77), whereas patients treated in high case-volume facilities were more likely to receive TL (46.1% vs 31.5%, OR 1.78, 95% CI 1.27-2.48). Median survival for TL versus LP was 61 versus 39 months (P<.001). After controlling for potential confounders, LP-CRT had inferior overall survival compared with TL (hazard ratio 1.31, 95% CI 1.10-1.57), and with the inverse probability of treatment-weighted model (hazard ratio 1.25, 95% CI 1.05-1.49). This survival difference was shown to be robust on additional sensitivity analyses.
Most patients with T4a larynx cancer receive LP-CRT, despite guidelines suggesting TL as the preferred initial approach. Patients receiving LP-CRT had more advanced nodal disease and worse overall survival. Previous studies of (non-T4a) locally advanced larynx cancer showing no difference in survival between LP-CRT and TL may not apply to T4a disease, and patients should be counseled accordingly.
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