From Photography to Radiology: How Physicians Leveraged Early Hospital X-ray Machines to Supplant Photographers.

At the end of the nineteenth century, the advent of x-ray machines fueled American medicine's reliance on technology, transforming hospitals and the medical profession. X-ray manufacturers pursued the nascent hospital market as competition and patent feuds accelerated x-ray machine modifications. Hospitals incorporated clunky new machines and employed x-ray photographers, but as the unruly apparatus stabilized, physicians joining the new specialty of radiology discounted the toils of machine troubleshooting and promoted their medically qualified x-ray interpretations.

Advantage of precision metagenomics for urinary tract infection diagnostics.

Background: Urinary tract infections (UTIs) remain a diagnostic challenge and often promote antibiotic overuse. Despite urine culture being the gold standard for UTI diagnosis, some uropathogens may lead to false-negative or inconclusive results. Although PCR testing is fast and highly sensitive, its diagnostic yield is limited to targeted microorganisms.

Nonlinear ultrasonic technique for the characterization of microstructure in additive materials.

This study employs nonlinear ultrasonic techniques to track microstructural changes in additively manufactured metals. The second harmonic generation technique based on the transmission of Rayleigh surface waves is used to measure the acoustic nonlinearity parameter, β. Stainless steel specimens are made through three procedures: traditional wrought manufacturing, laser-powder bed fusion, and laser engineered net shaping.

Monitoring Algal Blooms in drinking water reservoirs using the Landsat 8 Operational Land Imager.

In this study, we demonstrated that the Landsat-8 Operational Land Imager (OLI) sensor is a powerful tool that can provide periodic and system-wide information on the condition of drinking water reservoirs. The OLI is a multispectral radiometer (30 m spatial resolution) that allows ecosystem observations at spatial and temporal scales that allow the environmental community and water managers another means to monitor changes in water quality not feasible with field-based monitoring. Using the provisional Land Surface Reflectance (LSR) product and field-collected chlorophyll- (chl-) concentrations from drinking water monitoring programs in North Carolina and Rhode Island, we compared five established approaches for estimating chl- concentrations using spectral data.

Functional Importance of a Proteoglycan Coreceptor in Pathologic Lymphangiogenesis.

Rationale: Lymphatic vessel growth is mediated by major prolymphangiogenic factors, such as vascular endothelial growth factor (VEGF-C) and VEGF-D, among other endothelial effectors. Heparan sulfate is a linear polysaccharide expressed on proteoglycan core proteins on cell membranes and matrix, playing roles in angiogenesis, although little is known about any function(s) in lymphatic remodeling in vivo.

Objective: To explore the genetic basis and mechanisms, whereby heparan sulfate proteoglycans mediate pathological lymphatic remodeling.

What's a stream without water? Disproportionality in headwater regions impacting water quality.

Headwater streams are critical components of the stream network, yet landowner perceptions, attitudes, and property management behaviors surrounding these intermittent and ephemeral streams are not well understood. Our research uses the concept of watershed disproportionality, where coupled social-biophysical conditions bear a disproportionate responsibility for harmful water quality outcomes, to analyze the potential influence of riparian landowner perceptions and attitudes on water quality in headwater regions. We combine social science survey data, aerial imagery, and an analysis of spatial point processes to assess the relationship between riparian landowner perceptions and attitudes in relation to stream flow regularity.

Functional overlap between chondroitin and heparan sulfate proteoglycans during VEGF-induced sprouting angiogenesis.

Objective: Heparan sulfate proteoglycans regulate key steps of blood vessel formation. The present study was undertaken to investigate if there is a functional overlap between heparan sulfate proteoglycans and chondroitin sulfate proteoglycans during sprouting angiogenesis.

Methods And Results: Using cultures of genetically engineered mouse embryonic stem cells, we show that angiogenic sprouting occurs also in the absence of heparan sulfate biosynthesis.

Lymphatic endothelial heparan sulfate deficiency results in altered growth responses to vascular endothelial growth factor-C (VEGF-C).

Growth and remodeling of lymphatic vasculature occur during development and during various pathologic states. A major stimulus for this process is the unique lymphatic vascular endothelial growth factor-C (VEGF-C). Other endothelial growth factors, such as fibroblast growth factor-2 (FGF-2) or VEGF-A, may also contribute.

Deletion of the basement membrane heparan sulfate proteoglycan type XVIII collagen causes hypertriglyceridemia in mice and humans.

Background: Lipoprotein lipase (Lpl) acts on triglyceride-rich lipoproteins in the peripheral circulation, liberating free fatty acids for energy metabolism or storage. This essential enzyme is synthesized in parenchymal cells of adipose tissue, heart, and skeletal muscle and migrates to the luminal side of the vascular endothelium where it acts upon circulating lipoproteins. Prior studies suggested that Lpl is immobilized by way of heparan sulfate proteoglycans on the endothelium, but genetically altering endothelial cell heparan sulfate had no effect on Lpl localization or lipolysis.

Loss of the heparan sulfate sulfotransferase, Ndst1, in mammary epithelial cells selectively blocks lobuloalveolar development in mice.

Background: Considerable evidence indicates that heparan sulfate is essential for the development of tissues consisting of branching ducts and tubules. However, there are few examples where specific sulfate residues regulate a specific stage in the formation of such tissues.

Methodology/principal Findings: We examined the role of heparan sulfation in mammary gland branching morphogenesis, lactation and lobuloalveolar development by inactivation of heparan sulfate GlcNAc N-deacetylase/N-sulfotransferase genes (Ndst) in mammary epithelial cells using the Cre-loxP system.

Detection of atypical texture features in early malignant melanoma.

Background: The presence of an atypical (irregular) pigment network (APN) can indicate a diagnosis of melanoma. This study sought to analyze the APN with texture measures.

Methods: For 106 dermoscopy images including 28 melanomas and 78 benign dysplastic nevi, the areas of APN were selected manually.

Insulin-dependent diabetes mellitus in mice does not alter liver heparan sulfate.

Diabetes -associated hyperlipidemia is generally attributed to reduced clearance of plasma lipoproteins, especially remnant lipoproteins enriched in cholesterol and triglycerides. Hepatic clearance of remnants occurs via low density lipoprotein receptors and the heparan sulfate proteoglycan, syndecan-1. Previous studies have suggested alterations in heparan sulfate proteoglycan metabolism in rat and mouse diabetic models, consistent with the idea that diabetic dyslipidemia might be caused by alterations in proteoglycan expression in the liver.

Heparan sulfate 2-O-sulfotransferase is required for triglyceride-rich lipoprotein clearance.

Hepatic clearance of triglyceride-rich lipoproteins depends on heparan sulfate and low density lipoprotein receptors expressed on the basal membrane of hepatocytes. Binding and uptake of the lipoproteins by way of heparan sulfate depends on the degree of sulfation of the chains based on accumulation of plasma triglycerides and delayed clearance of triglyceride-rich lipoproteins in mice bearing a hepatocyte-specific alteration of N-acetylglucosamine (GlcNAc) N-deacetylase-N-sulfotransferase 1 (Ndst1) (MacArthur, J. M.

Syndecan-1 is the primary heparan sulfate proteoglycan mediating hepatic clearance of triglyceride-rich lipoproteins in mice.

Elevated plasma triglyceride levels represent a risk factor for premature atherosclerosis. In mice, accumulation of triglyceride-rich lipoproteins can occur if sulfation of heparan sulfate in hepatocytes is diminished, as this alters hepatic lipoprotein clearance via heparan sulfate proteoglycans (HSPGs). However, the relevant HSPG has not been determined.

Abnormal patterns of lipoprotein lipase release into the plasma in GPIHBP1-deficient mice.

GPIHBP1-deficient mice (Gpihbp1(-/-)) exhibit severe chylomicronemia. GPIHBP1 is located within capillaries of muscle and adipose tissue, and expression of GPIHBP1 in Chinese hamster ovary cells confers upon those cells the ability to bind lipoprotein lipase (LPL). However, there has been absolutely no evidence that GPIHBP1 actually interacts with LPL in vivo.

Heparan sulfate proteoglycans and triglyceride-rich lipoprotein metabolism.

Purpose Of Review: Clearance of triglyceride-rich lipoprotein remnants by the liver is a key step in preventing hypertriglyceridemia, an independent risk factor for cardiovascular disease. We review recent genetic evidence that heparan sulfate proteoglycans work in concert with the LDL receptor in the liver to facilitate binding and clearance of both triglyceride and cholesterol-rich lipoproteins from the circulation.

Recent Findings: Partial reduction of sulfation of liver heparan sulfate using the Cre-loxP system caused accumulation of hepatic and dietary triglyceride-rich lipoprotein particles due to delayed clearance.

Heparan sulfate proteoglycans provide a signal to Plasmodium sporozoites to stop migrating and productively invade host cells.

Malaria infection is initiated when Anopheles mosquitoes inject Plasmodium sporozoites into the skin. Sporozoites subsequently reach the liver, invading and developing within hepatocytes. Sporozoites contact and traverse many cell types as they migrate from skin to liver; however, the mechanism by which they switch from a migratory mode to an invasive mode is unclear.

Genetic alteration of endothelial heparan sulfate selectively inhibits tumor angiogenesis.

To examine the role of endothelial heparan sulfate during angiogenesis, we generated mice bearing an endothelial-targeted deletion in the biosynthetic enzyme N-acetylglucosamine N-deacetylase/N-sulfotransferase 1 (Ndst1). Physiological angiogenesis during cutaneous wound repair was unaffected, as was growth and reproductive capacity of the mice. In contrast, pathological angiogenesis in experimental tumors was altered, resulting in smaller tumors and reduced microvascular density and branching.

Heparan sulphate proteoglycans fine-tune mammalian physiology.

Heparan sulphate proteoglycans reside on the plasma membrane of all animal cells studied so far and are a major component of extracellular matrices. Studies of model organisms and human diseases have demonstrated their importance in development and normal physiology. A recurrent theme is the electrostatic interaction of the heparan sulphate chains with protein ligands, which affects metabolism, transport, information transfer, support and regulation in all organ systems.

Evolution of carbohydrate antigens--microbial forces shaping host glycomes?

Many glycans show remarkably discontinuous distribution across evolutionary lineages. These differences play major roles when organisms belonging to different lineages interact as host-pathogen or host-symbiont. Certain lineage-specific glycans have become important signals for multicellular host organisms, which use them as molecular signatures of their pathogens and symbionts through recognition by a toolkit of innate defense molecules.

Liver heparan sulfate proteoglycans mediate clearance of triglyceride-rich lipoproteins independently of LDL receptor family members.

We examined the role of hepatic heparan sulfate in triglyceride-rich lipoprotein metabolism by inactivating the biosynthetic gene GlcNAc N-deacetylase/N-sulfotransferase 1 (Ndst1) in hepatocytes using the Cre-loxP system, which resulted in an approximately 50% reduction in sulfation of liver heparan sulfate. Mice were viable and healthy, but they accumulated triglyceride-rich lipoprotein particles containing apoB-100, apoB-48, apoE, and apoCI-IV. Compounding the mutation with LDL receptor deficiency caused enhanced accumulation of both cholesterol- and triglyceride-rich particles compared with mice lacking only LDL receptors, suggesting that heparan sulfate participates in the clearance of cholesterol-rich lipoproteins as well.

Hyperopic shift with posterior bowing of a Collamer posterior chamber intraocular lens.

Two patients developed a hyperopic shift following uneventful phacoemulsification with implantation of a Collamer plate-haptic intraocular lens (Staar Surgical) in the capsular bag. Posterior bowing of the IOL was corrected by IOL exchange, achieving near emmetropia.

Identification of novel chondroitin proteoglycans in Caenorhabditis elegans: embryonic cell division depends on CPG-1 and CPG-2.

Vertebrates produce multiple chondroitin sulfate proteoglycans that play important roles in development and tissue mechanics. In the nematode Caenorhabditis elegans, the chondroitin chains lack sulfate but nevertheless play essential roles in embryonic development and vulval morphogenesis. However, assignment of these functions to specific proteoglycans has been limited by the lack of identified core proteins.

Cell surface heparan sulfate promotes replication of Toxoplasma gondii.

Previous work suggests that cell surface heparan sulfate acts as a receptor for the Apicomplexan parasite Toxoplasma gondii. Using Chinese hamster ovary cell mutants defective in heparan sulfate biosynthesis, we show that heparan sulfate is necessary and sufficient for infectivity. Further, we demonstrate that the parasite requires N sulfation of heparan sulfate initiated by N-deacetylase/N-sulfotransferase-1, but 2-O sulfation and 6-O sulfation appear to be dispensable.