Glaucomatous Patterns in Frequency Doubling Technology (FDT) Perimetry Data Identified by Unsupervised Machine Learning Classifiers

Purpose

The variational Bayesian independent component analysis-mixture model (VIM), an unsupervised machine-learning classifier, was used to automatically separate Matrix Frequency Doubling Technology (FDT) perimetry data into clusters of healthy and glaucomatous eyes, and to identify axes representing statistically independent patterns of defect in the glaucoma clusters.

Methods

FDT measurements were obtained from 1,190 eyes with normal FDT results and 786 eyes with abnormal FDT results from the UCSD-based Diagnostic Innovations in Glaucoma Study (DIGS) and African Descent and Glaucoma Evaluation Study (ADAGES). For all eyes, VIM input was 52 threshold test points from the 24-2 test pattern, plus age.

Results

FDT mean deviation was −1.00 dB (S.D. = 2.80 dB) and −5.57 dB (S.D. = 5.09 dB) in FDT-normal eyes and FDT-abnormal eyes, respectively (p<0.001). VIM identified meaningful clusters of FDT data and positioned a set of statistically independent axes through the mean of each cluster. The optimal VIM model separated the FDT fields into 3 clusters. Cluster N contained primarily normal fields (1109/1190, specificity 93.1%) and clusters G₁ and G₂ combined, contained primarily abnormal fields (651/786, sensitivity 82.8%). For clusters G₁ and G₂ the optimal number of axes were 2 and 5, respectively. Patterns automatically generated along axes within the glaucoma clusters were similar to those known to be indicative of glaucoma. Fields located farther from the normal mean on each glaucoma axis showed increasing field defect severity.

Conclusions

VIM successfully separated FDT fields from healthy and glaucoma eyes without a priori information about class membership, and identified familiar glaucomatous patterns of loss.     

Altered tubulin assembly dynamics with N-homocysteinylated human 4R/1N tau in vitro

Tau isoforms promote neuronal integrity through binding and stabilization of microtubule proteins (MTP). It has been shown that hyperphosphorylation of tau contributes to Alzheimer’s disease (AD) pathology and related tauopathies. However, other pathogenic modifications of tau have not been well characterized. It is well accepted that elevated level of homocysteine (Hcy) is associated with neurodegenerative diseases such as AD. As a result of N-homocysteinylation of lysine residues, Hcy becomes a component of proteins, as a protein–homocystamide adduct, which affects protein structure and function. Here we demonstrate that N-homocysteinylation of human tau (4R/1N isoform) inhibits its function via impaired tau–tubulin specific binding and MTP assembly dynamics in vitro.     

Carcinogenic and Non-carcinogenic Risk Assessment of Heavy Metals in Groundwater Wells in Neyshabur Plain,Iran

The present work reports the As, Cr, Cu, Pb, Zn, and Fe concentrations of drinking water samples in Neyshabur Plain, Iran. This study aimed also to ascertain the potential consumers’ health risk of heavy metal intake. Heavy metal concentrations were analyzed by inductively coupled plasma optical emission spectrometry. The highest and lowest average values in the analyzed water samples were observed for Fe (9.78 ± 5.61 μg/L) and As (1.30 ± 2.99 μg/L), respectively. These values were well below the limits recommended by the World Health Organization and the Iranian national standard. Heavy metal pollution index and heavy metal evaluation index were used to evaluate drinking water quality. The risk index was calculated by chronic daily intake and hazard quotient according to the United States Environmental Protection Agency approach. Heavy metal pollution index in all the samples was less than 100, indicating that it is a low-level heavy metal. The total risk of all heavy metals in the urban environment varied from 40.164 × 10⁻⁷ to 174.8 × 10⁻⁷. In this research, the maximum average of risk belonged to lead and copper with the respective values of 60.10 × 10⁻⁷and 33.99 × 10⁻⁷ from the selected wells. However, considering the toxic effect of some elements, including Pb and As, in the chronic exposure of consumers, we suggest a continuous evaluation and monitoring of drinking water resources.

     

TWIST1 correlates with Notch signaling pathway to develop esophageal squamous cell carcinoma

Molecular and Cellular Biochemistry - Notch signaling pathway mediates different biological processes including stem cell self-renewal, progenitor cell fate decision, and terminal differentiation....     

Melatonin: An important anticancer agent in colorectal cancer

Colorectal cancer is one of the most common cancers among the elderly, which is also seen in the forms of hereditary syndromes occurring in younger individuals. Numerous studies have been conducted to understand the molecular and cellular pathobiology underlying colorectal cancer. These studies have found that cellular signaling pathways are at the core of colorectal cancer pathology. Because of this, new agents have been proposed as possible candidates to accompany routine therapy regimens. One of these agents is melatonin, a neuro-hormone known best for its essential role in upholding the circadian rhythm and orchestrating the many physiologic changes it accompanies. Melatonin is shown to be able to modulate many signaling pathways involved in many essential cell functions, which if deregulated cause an accelerated pace towards cancer. More so, melatonin is involved in the regulation of immune function, tumor microenvironment, and acts as an antioxidant agent. Many studies have focused on the beneficial effects of melatonin in colorectal cancers, such as induction of apoptosis, increased sensitivity to chemotherapy agents and radiotherapy, limiting cellular proliferation, migration, and invasion. The present review aims to illustrate the known significance of melatonin in colorectal cancer and to address possible clinical use.     

The interaction of beta-lactoglobulin with ciprofloxacin and kanamycin; a spectroscopic and molecular modeling approach

A vast research has been conducted to find suitable and safe carriers for vital and pH-sensitive drugs including antibiotics. This article reports the use of easily accessible and abundant purified beta-lactoglobulin (β-LG) protein as the potential carrier of widely used Kanamycin (Kana) and Ciprofloxacin (Cip) antibiotics. Spectroscopic techniques (Fluorescence, UV–vis, Circular Dichroism) combined with molecular docking were used to determine the binding mechanism of these drugs. Fluorescence studies showed moderate binding affinity with the calculated binding constants K_Cip = 60.1 (±0.2)?×?10³ M^?1 and K_kana = 2.5 (±0.6)?×?10³ M^?1 with the order of Cip > Kana. Results of UV–vis were consistent with fluorescence measurements and demonstrated a stronger complexation for Cip rather than Kana. The secondary structure of β-LG was preserved upon interaction with Kana; however, a reduction in β-sheet content from 39.1 to 31.9% was convoyed with an increase in α-helix from 12.8 to 20.5% due to complexation of Cip. Molecular docking studies demonstrated that preferred binding sites of these drugs are not the same and several amino acids are involved in stabilizing the interaction. Based on the achieved results, Kana and Cip can spontaneously bind to β-LG and this protein may serve as their transport vehicle.     

Differences in proliferation rate between CADASIL and control vascular smooth muscle cells are related to increased TGFβ expression

Cerebral autosomal‐dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a familial fatal progressive degenerative disorder. One of the pathological hallmarks of CADASIL is a dramatic reduction of vascular smooth muscle cells (VSMCs) in cerebral arteries. Using VSMCs from the vasculature of the human umbilical cord, placenta and cerebrum of CADASIL patients, we found that CADASIL VSMCs had a lower proliferation rate compared to control VSMCs. Exposure of control VSMCs and endothelial cells (ECs) to media derived from CADASIL VSMCs lowered the proliferation rate of all cells examined. By quantitative RT‐PCR analysis, we observed increased Transforming growth factor‐β (TGFβ) gene expression in CADASIL VSMCs. Adding TGFβ‐neutralizing antibody restored the proliferation rate of CADASIL VSMCs. We assessed proliferation differences in the presence or absence of TGFβ‐neutralizing antibody in ECs co‐cultured with VSMCs. ECs co‐cultured with CADASIL VSMCs exhibited a lower proliferation rate than those co‐cultured with control VSMCs, and neutralization of TGFβ normalized the proliferation rate of ECs co‐cultured with CADASIL VSMCs. We suggest that increased TGFβ expression in CADASIL VSMCs is involved in the reduced VSMC proliferation in CADASIL and may play a role in situ in altered proliferation of neighbouring cells in the vasculature.     

Combining population genomics and ecological niche modeling to assess taxon limits between Carex jemtlandica and C. lepidocarpa

Carex section Ceratocystis (Cyperaceae) is a group of recently evolved plant species, in which hybridization is frequent, introgression is documented, taxonomy is complex, and morphological boundaries are vague. Within this section, a unified taxonomic treatment of the Carex jemtlandica–Carex lepidocarpa species complex does not exist, and Norway may currently be the sole country accepting species rank for both. Carex jemtlandica is mainly confined to Fennoscandia and is thus a Fennoscandian conservation responsibility. This motivated us to test the principal hypothesis that both C. jemtlandica and C. lepidocarpa represent evolutionary significant units, and that both deserve their current recognition at species level. We investigated their evolutionary distinctiveness in Norway,using restriction site-associated DNA sequencing and ecological niche modeling. Our genomic results reveal two genetic clusters, largely corresponding to C. jemtlandica and C. lepidocarpa that also remain distinct in sympatry, despite clear indications of ongoing hybridization and introgression. The ecological niche modeling suggests that they occupy different environmental niches. Jointly, our results clearly show that C. jemtlandica and C. lepidocarpa represent separately evolving entities that should qualify recognition as evolutionary significant units. Given the high level of introgression compared to other hybridizing species pairs in Carex we recommend treating C. jemtlandica as a subspecies of C. lepidocarpa.     

Cement-Organobentonite Admixtures for Stabilization/Solidification of PAH-Contaminated Soil: A Laboratory Study

The feasibility of using Portland cement and organobentonite to stabilize and solidify Polycyclic Aromatic Hydrocarbons (PAH) contaminated soil was examined. Naphthalene and phenanthrene in solid and dissolved phases were selected as PAHs compounds to represent organic contaminants in the soil. Different tests including Toxicity Characteristics Leaching Procedure (TCLP), Unconfined Compressive Strength (UCS), and permeability tests were conducted on the stabilization/solidification (S/S) contaminated soils. The leaching test results confirmed a significant reduction in the leaching of naphthalene and phenanthrene from the stabilized soil specimen by adding 2%, 5%, and 10% of organoclay during solidification/stabilization. Based on the results for the tested ranges of cement and organoclay for S/S contaminated soil, the optimum mix design includes 5% of cement and 2% of organoclay. The observation in this study confirmed that organoclay particles sorbed the organic contaminates and therefore naphthalene and phenanthrene leachate concentration will be reduced. Moreover, results show that increasing the curing time of S/S products reduces the naphthalene and phenanthrene leachate concentration.