Microsatellite Instability,EMAST, and Morphology Associations with T Cell Infiltration in Colorectal Neoplasia

Background and Objectives  

Colorectal tumors are often observed with tumor infiltrating lymphocytes, presumably as a host-immune response, and patterns may segregate by types of genomic instability. Microsatellite unstable (MSI) colorectal cancers contain a pronounced lymphocyte reaction that can pathologically identify these tumors. Colorectal tumors with elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) have not been examined for lymphocyte patterns.     

Validation of the human activity profile in stroke: a comparison of observed, proxy and self-reported scores

PURPOSE: To assess the concurrent validity of the Human Activity Profile (HAP) with stroke and healthy control individuals, when reported by the subject or a proxy and compared to observed performance, used as gold standard; factors related to discrepancies; as well as to determine variables that could best predict physical activity levels. METHODS: A total of 24 stroke and 23 healthy control subjects took part in the study. Functional outcome measures included personal/demographic factors, HAP, the 10-meter walk, and cognition. RESULTS: Strong relationships were found between self-reported and observed scores for both groups (r=0.89-0.99). The relationships between proxy and observed scores were acceptable for stroke (r=0.80-0.87) but lower for control subjects (r=0.65-0.75), with intraclass correlation coefficients (ICCs) ranging from 0.69-0.89. Significant differences were found between proxy and observed scores for stroke, but not for control subjects. Discrepancies between scores showed little predictability from selected variables. For stroke subjects, the strongest variable explaining physical activity levels was walking speed (r2=43%) and the best combination of variables was walking speed plus cognition (r2=55%). CONCLUSIONS: Self-reported HAP was an excellent measure both for stroke and control subjects and related well to observed performance. Proxy reports appear to be valid for stroke subjects. HAP was significantly related to measures of walking speed.     

Founder effects of the homogentisate 1,2-dioxygenase (HGD) gene in a gypsy population and mutation spectrum in the gene among alkaptonuria patients from India

Clinical Rheumatology - Alkaptonuria (AKU) is a rare metabolic disease. The global incidence is 1:100,000 to 1:250,000. However, identification of a founder mutation in a gypsy population from...     

Experimental Investigations on Dry Sliding Wear Behavior of Kevlar and Natural Fiber-Reinforced Hybrid Composites through an RSM–GRA Hybrid Approach

The present work aimed to investigate the dry sliding wear behaviors of hybrid polymer matrix composites made up of Kevlar, bamboo, palm, and Aloe vera as reinforcement materials of varying stacking sequences, along with epoxy as the matrix material. Three combinations of composite laminates with different stacking sequences such as AB, BC, and CA were fabricated by a vacuum-assisted compression molding process. The influence of composite laminates fabricated through various stacking sequences and dry sliding wear test variables such as load, sliding distance, and sliding velocity on the specific wear rate and co-efficient of friction were investigated. Experiments were designed and statistical validation was performed through response surface methodology-based D-optimal design and analysis of variance. The optimization was performed using grey relational analysis (GRA) to identify the optimal parameters to enhance the wear resistance of hybrid polymer composites under dry sliding conditions. The optimal parameters, such as composite combinations of CA, a load of 5 N, a sliding velocity of 3 m/s, and a sliding distance of 1500 m, were obtained. Furthermore, the morphologies of worn-out surfaces were investigated using SEM analysis.     

Programmable self-assembly of M13 bacteriophage for micro-color pattern with a tunable colorization

Over the last decade, the M13 bacteriophage has been used widely in various applications, such as sensors, bio-templating, and solar cells. The M13 colorimetric sensor was developed to detect toxic gases to protect the environment, human health, and national security. Recent developments in phage-based colorimetric sensor technologies have focused on improving the sensing characteristics, such as the sensitivity and selectivity on a large scale. On the other hand, few studies have examined precisely controllable micro-patterning techniques in phage-based self-assembly. This paper developed a color patterning technique through self-assembly of the M13 bacteriophages. The phage was self-assembled into a nanostructure through precise temperature control at the meniscus interface. Furthermore, barcode color patterns could be fabricated using self-assembled M13 bacteriophage on micrometer scale areas by manipulating the grooves on the SiO₂ surface. The color patterns exhibited color tunability based on the phage nano-bundles reactivity. Overall, the proposed color patterning technique is expected to be useful for preparing new color sensors and security patterns.

Experiment designs have been developed for tunable colorization film by temperature control during self-assembly processing based on the M13 bacteriophage. The micro-color pattern was fabricated and demonstrated for humidity detection.     

In-cell SHAPE reveals that free 30S ribosome subunits are in the inactive state

It was shown decades ago that purified 30S ribosome subunits readily interconvert between “active” and “inactive” conformations in a switch that involves changes in the functionally important neck and decoding regions. However, the physiological significance of this conformational change had remained unknown. In exponentially growing Escherichia coli cells, RNA SHAPE probing revealed that 16S rRNA largely adopts the inactive conformation in stably assembled, mature 30S subunits and the active conformation in translating (70S) ribosomes. Inactive 30S subunits bind mRNA as efficiently as active subunits but initiate translation more slowly. Mutations that inhibited interconversion between states compromised translation in vivo. Binding by the small antibiotic paromomycin induced the inactive-to-active conversion, consistent with a low-energy barrier between the two states. Despite the small energetic barrier between states, but consistent with slow translation initiation and a functional role in vivo, interconversion involved large-scale changes in structure in the neck region that likely propagate across the 30S body via helix 44. These findings suggest the inactive state is a biologically relevant alternate conformation that regulates ribosome function as a conformational switch.Forty-five years ago, Zamir, Elson, and their colleagues reported that purified 30S subunits of the ribosome undergo a readily reversible conformational change between “active” and “inactive” states and proposed that this conformational rearrangement might mimic a natural process (1). Noller and coworkers used chemical probing to show that this conformational change occurs in the neck and decoding center regions of the 16S ribosomal RNA (rRNA) and has “the appearance of a reciprocal interconversion between two differently structured states” (2). Recent structural analyses indicate that the protein-free 16S rRNA adopts alternative base-paired conformations in the neck region that are conserved among diverse eubacterial and archeal organisms (3). The ability to sample multiple conformations in this region is also conserved in eukaryotes (4). The original studies on the inactive and active states noted that probing ribosomes in cells might allow the biological roles of these states to be established (1, 2). Here we make use of recent innovations in in-cell RNA SHAPE (selective 2′-hydroxyl acylation analyzed by primer extension) probing (5) to interrogate the structure of 16S rRNA in free 30S subunits, in actively translating ribosomes, and in mutant ribosomes in exponentially growing Escherichia coli.     

Protective effect of grape seed proanthocyanidins against cholesterol cholic acid diet-induced hypercholesterolemia in rats

BackgroundDietary cholesterol plays an important role in the development of atherogenesis and cardiovascular diseases. We explored the prospective effect of grape seed proanthocyanidins in controlling hypercholesterolemia induced oxidative injury and apoptosis in atherogenic animals.MethodsFour groups of male Wistar rats (250–300 g) were used for the study. Group I served as control and received vehicle (saline) alone, Group II served as the induction group fed with a high-cholesterol diet (rat chow supplemented with 4% cholesterol and 1% cholic acid—CC diet) for 30 days, Group III served as drug control and was treated with grape seed proanthocyanidins (100 mg/kg body weight) orally for 30 days, and Group IV animals were fed with CC diet for 30 days along with grape seed proanthocyanidins (100 mg/kg body weight) orally.ResultsCC diet induced an abnormal increase in lipid peroxidation, tissue cholesterol, triglyceride, serum low-density lipoprotein, and very low density lipoprotein, and decreased the high-density lipoprotein concentration. Altered activity of cardiac and serum creatine kinase, accompanied by a decreased cardiac enzymatic and nonenzymatic antioxidant defense system and an increase in the expression of cytochrome c and caspases-3, was observed in CC diet-fed rats. These changes were partially restored in the grape seed proanthocyanidin-treated group.ConclusionGrape seed proanthocyanidins have cardioprotective effects against CC diet-induced hypercholesterolemia via their ability to reduce, directly or indirectly, free radicals in the myocardium.