KCNK3 Mutation Causes Altered Immune Function in Pulmonary Arterial Hypertension Patients and Mouse Models

Loss of function KCNK3 mutation is one of the gene variants driving hereditary pulmonary arterial hypertension (PAH). KCNK3 is expressed in several cell and tissue types on both membrane and endoplasmic reticulum and potentially plays a role in multiple pathological process associated with PAH. However, the role of various stressors driving the susceptibility of KCNK3 mutation to PAH is unknown. Hence, we exposed kcnk3^fl/fl animals to hypoxia, metabolic diet and low dose lipopolysaccharide (LPS) and performed molecular characterization of their tissue. We also used tissue samples from KCNK3 patients (skin fibroblast derived inducible pluripotent stem cells, blood, lungs, peripheral blood mononuclear cells) and performed microarray, immunohistochemistry (IHC) and mass cytometry time of flight (CyTOF) experiments. Although a hypoxic insult did not alter vascular tone in kcnk3^fl/fl mice, RNASeq study of these lungs implied that inflammatory and metabolic factors were altered, and the follow-up diet study demonstrated a dysregulation of bone marrow cells in kcnk3^fl/fl mice. Finally, a low dose LPS study clearly showed that inflammation could be a possible second hit driving PAH in kcnk3^fl/fl mice. Multiplex, IHC and CyTOF immunophenotyping studies on human samples confirmed the mouse data and strongly indicated that cell mediated, and innate immune responses may drive PAH susceptibility in these patients. In conclusion, loss of function KCNK3 mutation alters various physiological processes from vascular tone to metabolic diet through inflammation. Our data suggests that altered circulating immune cells may drive PAH susceptibility in patients with KCNK3 mutation.     

Copresence of High-Risk Human Papillomaviruses and Epstein–Barr Virus in Colorectal Cancer: A Tissue Microarray and Molecular Study from Lebanon

Colorectal cancer (CRC) is the third most common cause of cancer-related deaths worldwide. Human papillomaviruses (HPVs) and Epstein–Barr virus (EBV) have been reported to be present in different types of human cancers, including CRCs, where they can play a key role in the onset and/or progression of these cancers. Thus, we herein explored the prevalence of high-risk HPVs and EBV in a cohort of 94 CRC tissue samples and 13 colorectal normal tissues from the Lebanese population using polymerase chain reaction, immunohistochemistry, and tissue microarray methodologies. We found that high-risk HPVs are present in 64%, while EBV is present in 29% of our CRC samples. Additionally, our data showed that high-risk HPV types (16, 18, 35, 58, 51, 45, 52, 31, and 33) are the most frequent in CRC in the Lebanese cohort, respectively. Our data point out that HPVs and EBV are copresent in 28% of the samples. Thus, this study clearly suggests that high-risk HPVs and EBV are present/copresent in CRCs, where they could play an important role in colorectal carcinogenesis. Nevertheless, further investigations using a larger cohort are needed to elucidate the possible cooperation between these oncoviruses in the development of CRC.     

A review of fatty acid profiles and antioxidant content in grass-fed and grain-fed beef

Growing consumer interest in grass-fed beef products has raised a number of questions with regard to the perceived differences in nutritional quality between grass-fed and grain-fed cattle. Research spanning three decades suggests that grass-based diets can significantly improve the fatty acid (FA) composition and antioxidant content of beef, albeit with variable impacts on overall palatability. Grass-based diets have been shown to enhance total conjugated linoleic acid (CLA) (C18:2) isomers, trans vaccenic acid (TVA) (C18:1 t11), a precursor to CLA, and omega-3 (n-3) FAs on a g/g fat basis. While the overall concentration of total SFAs is not different between feeding regimens, grass-finished beef tends toward a higher proportion of cholesterol neutral stearic FA (C18:0), and less cholesterol-elevating SFAs such as myristic (C14:0) and palmitic (C16:0) FAs. Several studies suggest that grass-based diets elevate precursors for Vitamin A and E, as well as cancer fighting antioxidants such as glutathione (GT) and superoxide dismutase (SOD) activity as compared to grain-fed contemporaries. Fat conscious consumers will also prefer the overall lower fat content of a grass-fed beef product. However, consumers should be aware that the differences in FA content will also give grass-fed beef a distinct grass flavor and unique cooking qualities that should be considered when making the transition from grain-fed beef. In addition, the fat from grass-finished beef may have a yellowish appearance from the elevated carotenoid content (precursor to Vitamin A). It is also noted that grain-fed beef consumers may achieve similar intakes of both n-3 and CLA through the consumption of higher fat grain-fed portions.     

Analysis of Trends in Construction Research: 1985–2002

This paper provides a historical perspective on construction research trends as reflected in the American Society of Civil Engineer’s Journal of Construction Engineering and Management (JCEM). The paper reports the results of an 18-year analysis of JCEM between 1985 and 2002. The analysis focused on such data as author information (affiliations and home countries), as well as the research topics of the technical papers. The paper summarizes the data extracted from the journal and use it to analyze construction research trends. Construction trends reveal that U.S. writers contributed the most papers by that there has been an increasing number of international submissions to the journal. The top research topical areas relate to scheduling, productivity, constructability, simulation, cost control, planning, safety, and computer systems as described in this paper show that research is increasing throughout the world and topics are changing as current needs change. However, there is a need to increase research collaboration between industry and academia, government and academia, and industry and government to advance the construction industry.     

A sensor network for high frequency estimation of water quality constituent fluxes using surrogates

Characterizing spatial and temporal variability in the fluxes and stores of water and water borne constituents is important in understanding the mechanisms and flow paths that carry constituents to a stream and through a watershed. High frequency data collected at multiple sites can be used to more effectively quantify spatial and temporal variability in water quality constituent fluxes than through the use of low frequency water quality grab sampling. However, for many constituents (e.g., sediment and phosphorus) in-situ sensor technology does not currently exist for making high frequency measurements of constituent concentrations. In this paper we describe how water quality measures such as turbidity or specific conductance, which can be measured in-situ with high frequency, can be used as surrogates for other water quality constituents that cannot economically be measured with high frequency to provide continuous time series of water quality constituent concentrations and fluxes. We describe the observing infrastructure required to make high frequency estimates of water quality constituent fluxes based on surrogate data at multiple sites within a sensor network supporting an environmental observatory. This includes the supporting sensor, communication, data management, and data storage and processing infrastructure. We then provide a case study implementation in the Little Bear River watershed of northern Utah, USA, where a wireless sensor network has been developed for estimating total phosphorus and total suspended solids fluxes using turbidity as a surrogate.     

Differential protein expression in exosomal samples taken from trauma patients

Traumatic brain injuries (TBI) are among the most misdiagnosed and underreported types of head trauma. The potential long‐term impact of undiagnosed or incorrectly identified concussions and other head injuries are potentially devastating, as evidenced by the increasing societal burden exhibited by soldiers returning from combat and athletes in contact sports. Concussions and TBI are notoriously difficult to correctly diagnose and prognosis for these injuries is poorly understood. In order to increase the likelihood of successful diagnosis, treatment, and prediction of outcomes, a definitive differential diagnosis will need to be established. The establishment of a “trauma–specific profile” or a panel of known trauma markers will significantly aid in this goal. Small membrane vesicles called exosomes have been shown to contain proteins and injury‐specific biomarkers. In the future it is possible that they could become an important tool, utilized for their diagnostic and therapeutic potential.     

Automated Construction of an Open Reading Frame Library from Sinorhizobium meliloti

An automated, high-throughput, open reading frame (ORF) library construction process has been developed. ORFs from genomic DNA of the microbe Sinorhizobium meliloti were amplified by PCR and cloned into the library vector by homologous recombination instead of traditional ligation. From 960 targets, we successfully generated 723 (75.3%) ORFs from the initial PCR. After cloning the successful samples into the library vector, transforming into E. coli and PCR colony screening, 371 (38.6% overall) ORFs were placed into the new library and sequenced. Our prototype library contained 314 (32.7% overall) clones with sequence identity to the Sinorhizobium meliloti genome.     

Mechanical Properties of the Modified Denture Base Materials and Polymerization Methods: A Systematic Review

Amidst growing technological advancements, newer denture base materials and polymerization methods have been introduced. During fabrication, certain mechanical properties are vital for the clinical longevity of the denture base. This systematic review aimed to explore the effect of newer denture base materials and/or polymerization methods on the mechanical properties of the denture base. An electronic database search of English peer-reviewed published papers was conducted using related keywords from 1 January 2011, up until 31 December 2021. This systematic review was based on guidelines proposed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The search identified 579 papers. However, the inclusion criteria recognized 22 papers for eligibility. The risk of bias was moderate in all studies except in two where it was observed as low. Heat cure polymethyl methacrylate (PMMA) and compression moulding using a water bath is still a widely used base material and polymerization technique, respectively. However, chemically modified PMMA using monomers, oligomers, copolymers and cross-linking agents may have a promising result. Although chemically modified PMMA resin might enhance the mechanical properties of denture base material, no clear inferences can be drawn about the superiority of any polymerization method other than the conventional compression moulding technique.