Discovery of a Unique Set of Dog-Seroreactive Coccidioides Proteins Using Nucleic Acid Programmable Protein Array.

Valley Fever (VF), caused by fungi in the genus Coccidioides, is a prevalent disease in southwestern and western parts of the United States that affects both humans and animals, such as dogs. Although the immune responses to infection with Coccidioides spp. are not fully characterized, antibody-detection assays are used in conjunction with clinical presentation and radiologic findings to aid in the diagnosis of VF. These assays often use Complement Fixation (CF) and Tube Precipitin (TP) antigens as the main targets of IgG and IgM reactivity, respectively. Our group previously reported evidence of over 800 genes expressed at the protein level in C. posadasii. However, antibody reactivity to the majority of these proteins has never been explored. Using a new, high-throughput screening technology, the Nucleic Acid Programmable Protein Array (NAPPA), we screened serum specimens from dogs against 708 of these previously identified proteins for IgG reactivity. Serum from three separate groups of dogs was analyzed and revealed a small panel of proteins to be further characterized for immuno-reactivity. In addition to CF/CTS1 antigen, sera from most infected dogs showed antibody reactivity to endo-1,3-betaglucanase, peroxisomal matrix protein, and another novel reactive protein, CPSG_05795. These antigens may provide additional targets to aid in antibody-based diagnostics.

Methanogens and Methanotrophs Show Nutrient-Dependent Community Assemblage Patterns Across Tropical Peatlands of the Pastaza-Marañón Basin, Peruvian Amazonia.

Tropical peatlands are globally important carbon reservoirs that play a crucial role in fluxes of atmospheric greenhouse gases. Amazon peatlands are expected to be large source of atmospheric methane (CH4) emissions, however little is understood about the rates of CH4 flux or the microorganisms that mediate it in these environments. Here we studied a mineral nutrient gradient across peatlands in the Pastaza-Marañón Basin, the largest tropical peatland in South America, to describe CH4 fluxes and environmental factors that regulate species assemblages of methanogenic and methanotrophic microorganisms. Peatlands were grouped as minerotrophic, mixed and ombrotrophic categories by their general water source leading to different mineral nutrient content (rich, mixed and poor) quantified by trace elements abundance. Microbial communities clustered dependent on nutrient content (ANOSIM p < 0.001). Higher CH4 flux was associated with minerotrophic communities compared to the other categories. The most dominant methanogens and methanotrophs were represented by Methanobacteriaceae, and Methylocystaceae, respectively. Weighted network analysis demonstrated tight clustering of most methanogen families with minerotrophic-associated microbial families. Populations of Methylocystaceae were present across all peatlands. Null model testing for species assemblage patterns and species rank distributions confirmed non-random aggregations of Methylococcacae methanotroph and methanogen families (p < 0.05). We conclude that in studied amazon peatlands increasing mineral nutrient content provides favorable habitats for Methanobacteriaceae, while Methylocystaceae populations seem to broadly distribute independent of nutrient content.

Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage.

Intermittent fasting (IF), a periodic energy restriction, has been shown to provide health benefits equivalent to prolonged fasting or caloric restriction. However, our understanding of the underlying mechanisms of IF-mediated metabolic benefits is limited. Here we show that isocaloric IF improves metabolic homeostasis against diet-induced obesity and metabolic dysfunction primarily through adipose thermogenesis in mice. IF-induced metabolic benefits require fasting-mediated increases of vascular endothelial growth factor (VEGF) expression in white adipose tissue (WAT). Furthermore, periodic adipose-VEGF overexpression could recapitulate the metabolic improvement of IF in non-fasted animals. Importantly, fasting and adipose-VEGF induce alternative activation of adipose macrophage, which is critical for thermogenesis. Human adipose gene analysis further revealed a positive correlation of adipose VEGF-M2 macrophage-WAT browning axis. The present study uncovers the molecular mechanism of IF-mediated metabolic benefit and suggests that isocaloric IF can be a preventive and therapeutic approach against obesity and metabolic disorders.

Giant Cell Tumor with Secondary Aneurysmal Bone Cyst Shows Heterogeneous Metabolic Pattern on 18F-FDG PET/CT: A Case Report.

Giant cell tumor (GCT) is a generally benign bone tumor accounting for approximately 5 % of all primary bone neoplasms. Cystic components in GCTs that indicate secondary aneurysmal bone cysts (ABCs) are reported in 14 % of GCTs. Although both of them have been described separately in previous reports that may show considerable fluorodeoxyglucose (FDG) uptake despite their benign nature, the findings of GCT with secondary ABC on 18F-FDG positron emission tomography/computed tomography (PET/CT) have not been well-known. We report a case of GCT with secondary ABC in a 26-year-old woman. 18F-FDG PET/CT revealed a heterogeneous hypermetabolic lesion in the left proximal femur with the maximum standardized uptake value of 4.7. The solid components of the tumor showed higher FDG uptake than the cystic components. These observations suggest that the ABC components in GCTs show heterogeneous metabolic patterns on 18F-FDG PET/CT.

Inferior vena cava filter insertion through the popliteal vein: enabling the percutaneous endovenous intervention of deep vein thrombosis with a single venous access approach in a single session.

PURPOSE: We aimed to evaluate the efficiency of placing an inferior vena cava (IVC) filter through the same popliteal vein access site used for percutaneous endovenous intervention in patients with extensive lower extremity deep vein thrombosis. METHODS: This retrospective study included 21 patients who underwent IVC filter insertion through the popliteal vein over a three-year period. Patient medical records were reviewed for the location of the deep vein thrombosis, result of filter removal, and total number of endovascular procedures needed for filter insertion and recanalization of the lower extremity venous system. Follow-up lower extremity computed tomography (CT) venography was also reviewed in each patient to assess the degree of filter tilt in the IVC. RESULTS: All patients had extensive lower extremity deep vein thrombosis involving the iliac vein and/or femoral vein. Seventeen patients showed deep vein thrombosis of the calf veins. In all patients, IVC filter insertion and the recanalization procedure were performed during a single procedure through the single popliteal vein access site. In the 17 patients undergoing follow-up CT, the mean tilt angle of the filter was 7.14°±4.48° in the coronal plane and 8.77°±5.49° in the sagittal plane. Filter retrieval was successful in 16 of 17 patients (94.1%) in whom filter retrieval was attempted. CONCLUSION: Transpopliteal IVC filter insertion is an efficient technique that results in low rates of significant filter tilt and enables a single session procedure using a single venous access site for filter insertion and percutaneous endovenous intervention.

Noninvasive biomarkers for acute hepatotoxicity induced by 1,3-dichloro-2-propanol: hyperpolarized 13C dynamic MR spectroscopy.

The purpose of this study was to investigate the cellular metabolite change for acute hepatotoxicity induced by 1,3-dichloro-2-propanol (1,3-DCP) in rats and its correlations with the enzyme levels. In order to induce acute hepatotoxicity, a single subcutaneous injection of 1,3-DCP (80 mg/kg) was given to six male Sprague-Dawley rats. Hyperpolarized (13)C dynamic magnetic resonance spectroscopy (MRS) was performed on rat liver following injection of hyperpolarized [1-(13)C] pyruvate. The levels of serum aspartate am inotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) in the 1,3-DCP treated rats were significantly increased as compared with those in normal rats. In the dynamic (13)C MR spectra, the ratios of [1-(13)C] lactate to the total carbon and [1-(13)C] alanine to the total carbon in the 1,3-DCP treated rats were significantly increased, and there were positive correlations between cellular metabolic changes and enzyme levels. The levels of [1-(13)C] lactate and [1-(13)C] alanine are potentially considered as important biomarkers for the 1,3-DCP-induced acute hepatotoxicity.

Fused 99mTc-HDP SPECT/MR imaging of reverse Hill-Sachs deformity.

Reverse Hill-Sachs deformity is a term for a linear impression fracture of the anteromedial humeral head caused by a posterior shoulder dislocation, which is an extremely rare subtype of shoulder dislocations and caused by an epileptic seizure, an electric shock or trauma. Herein, we illustrate the findings of bone pinhole study, MRI and fused SPECT/MR imaging of reverse Hill-Sachs deformity caused by posterior shoulder dislocation after motor cycle accident in a 41-year-old man.

Reduced incidence of Prevotella and other fermenters in intestinal microflora of autistic children.

High proportions of autistic children suffer from gastrointestinal (GI) disorders, implying a link between autism and abnormalities in gut microbial functions. Increasing evidence from recent high-throughput sequencing analyses indicates that disturbances in composition and diversity of gut microbiome are associated with various disease conditions. However, microbiome-level studies on autism are limited and mostly focused on pathogenic bacteria. Therefore, here we aimed to define systemic changes in gut microbiome associated with autism and autism-related GI problems. We recruited 20 neurotypical and 20 autistic children accompanied by a survey of both autistic severity and GI symptoms. By pyrosequencing the V2/V3 regions in bacterial 16S rDNA from fecal DNA samples, we compared gut microbiomes of GI symptom-free neurotypical children with those of autistic children mostly presenting GI symptoms. Unexpectedly, the presence of autistic symptoms, rather than the severity of GI symptoms, was associated with less diverse gut microbiomes. Further, rigorous statistical tests with multiple testing corrections showed significantly lower abundances of the genera Prevotella, Coprococcus, and unclassified Veillonellaceae in autistic samples. These are intriguingly versatile carbohydrate-degrading and/or fermenting bacteria, suggesting a potential influence of unusual diet patterns observed in autistic children. However, multivariate analyses showed that autism-related changes in both overall diversity and individual genus abundances were correlated with the presence of autistic symptoms but not with their diet patterns. Taken together, autism and accompanying GI symptoms were characterized by distinct and less diverse gut microbial compositions with lower levels of Prevotella, Coprococcus, and unclassified Veillonellaceae.

Cavernous hemangioma of the ilium mimicking aggressive malignant bone tumor with increased activity on (18)F-FDG PET/CT.

Osseous hemangioma is a benign vascular tumor, and it usually occurs in the vertebrae and the skull. However, hemangiomas of flat bones are rare, and there are very few reports that describe the radiologic findings of osseous hemangioma of the ilium. We report a unique case of large cavernous hemangioma mimicking a chondrogenic malignant bone tumor originated from the ilium in a 22-year-old female. The mass showed stippled calcifications, heterogeneous enhancement with thick septa and enhanced soft tissue components on CT and MR, and also this mass demonstrated heterogeneous 2-fluoro [fluorine-18]-2-deoxy-D-glucose ((18)F-FDG) uptake on (18)F-FDG PET/CT.

Adipose vascular endothelial growth factor regulates metabolic homeostasis through angiogenesis.

Vascular endothelial growth factor A (VEGF) is highly expressed in adipose tissue. Its role, however, has not been fully elucidated. Here, we reveal the metabolic role of adipose-VEGF by studying mice with deletion (VEGF(AdΔ)) or doxycycline-inducible overexpression of a VEGF transgene (VEGF(AdTg)) in the adipose tissue. VEGF(AdΔ) mice have reduced adipose vascular density and show adipose hypoxia, apoptosis, inflammation, and metabolic defects on a high-fat diet. In contrast, induction of VEGF expression in VEGF(AdTg) mice leads to increased adipose vasculature and reduced hypoxia. The latter changes are sufficient to counteract an established compromising effect of high-fat diet on the metabolism, indicating that metabolic misbalance is reversible by adipose vessel density increase. Our data clearly show the essential role of VEGF signaling for adequate adipose function. Besides revealing insights into the molecular mechanisms of obesity-related metabolic diseases, this study points to the therapeutic potential of increased adipose angiogenesis.

Medullary carcinoma of the breast: MRI findings.

OBJECTIVE: The objective of our study was to describe the MRI findings of medullary carcinoma of the breast and to correlate those findings with the histopathologic findings. MATERIALS AND METHODS: From January 2005 to June 2010, MR images of 15 patients (age range, 32-73 years; mean age, 50 years) with pathologically confirmed medullary carcinoma of the breast were retrospectively evaluated according to BI-RADS. MR images were reviewed for the following: enhancement type (mass vs nonmass), size, shape, margins, contrast enhancement, signal intensity, and time-intensity curve pattern on a dynamic study. These MR features were correlated with the histopathologic features. RESULTS: All 15 tumors were seen as a mass on MRI. The median size of the masses was 2.7 cm (range, 1.5-6.3 cm) and the most common features were an oval or lobular shape (13/15, 86.7%) and a circumscribed margin (13/15, 86.7%). Rim enhancement with enhancing internal septations was seen in seven masses (46.7%), and rim enhancement was seen in six masses (40%). A hypointense rim on T2-weighted images was seen in nine tumors (9/15, 60%). Last, the kinetics curve showed a rapid initial increase in enhancement and a washout or plateau pattern on delayed phase imaging in all 15 tumors. CONCLUSION: On MRI, medullary carcinomas of the breast appeared as masses with an oval or lobular shape and circumscribed margins. Rim enhancement with or without enhancing internal septations was frequently seen on contrast enhancement.

Paget disease of the breast: mammographic, US, and MR imaging findings with pathologic correlation.

Paget disease is a rare malignancy of the breast characterized by infiltration of the nipple epidermis by adenocarcinoma cells. The clinical features of Paget disease are characteristic and should increase the likelihood of the diagnosis being made. An important point is that more than 90% of cases of Paget disease are associated with an additional underlying breast malignancy. Paget disease is frequently associated with ductal carcinoma in situ (DCIS) in the underlying lactiferous ducts of the nipple-areolar complex; it may even be associated with DCIS or invasive breast cancer elsewhere in the breast, at least 2 cm from the nipple-areolar complex. Nevertheless, mammographic findings may be negative in up to 50% of cases. Magnetic resonance (MR) imaging can be useful in patients with Paget disease for evaluation of the nipple-areolar complex and identification of an additional underlying malignancy in the breast. The appropriate surgical treatment must be carefully selected and individualized on the basis of radiologic findings, especially those obtained with breast MR imaging.

Sonographic findings of invasive cribriform carcinoma of the breast.

The purpose of this series was to evaluate the sonographic features of invasive cribriform carcinoma of the breast. Between 2004 and 2010, 3 patients had confirmed invasive cribriform carcinoma of the breast in our institution, and all of them underwent sonography. Sonograms showed masses with an oval (n = 2) or irregular (n = 1) shape, partially microlobulated (n = 2) or well-circumscribed (n = 1) margins, and a hypoechoic (n = 2) or an isoechoic (n = 1) internal echo texture. Sonographic assessments were classified as Breast Imaging Reporting and Data System category 4 in all 3 cases. Although invasive cribriform carcinoma is a rare breast malignancy, awareness of its sonographic features will be helpful for the diagnosis.

Eukaryotic protein domains as functional units of cellular evolution.

Modular protein domains are functional units that can be modified through the acquisition of new intrinsic activities or by the formation of novel domain combinations, thereby contributing to the evolution of proteins with new biological properties. Here, we assign proteins to groups with related domain compositions and functional properties, termed "domain clubs," which we use to compare multiple eukaryotic proteomes. This analysis shows that different domain types can take distinct evolutionary trajectories, which correlate with the conservation, gain, expansion, or decay of particular biological processes. Evolutionary jumps are associated with a domain that coordinately acquires a new intrinsic function and enters new domain clubs, thereby providing the modified domain with access to a new cellular microenvironment. We also coordinately analyzed the covalent and noncovalent interactions of different domain types to assess the molecular compartment occupied by each domain. This reveals that specific subsets of domains demarcate particular cellular processes, such as growth factor signaling, chromatin remodeling, apoptotic and inflammatory responses, or vesicular trafficking. We suggest that domains, and the proteins in which they reside, are selected during evolution through reciprocal interactions with protein domains in their local microenvironment. Based on this scheme, we propose a mechanism by which Tudor domains may have evolved to support different modes of epigenetic regulation and suggest a role for the germline group of mammalian Tudor domains in Piwi-regulated RNA biology.

Mouse Piwi interactome identifies binding mechanism of Tdrkh Tudor domain to arginine methylated Miwi.

Tudor domains are protein modules that mediate protein-protein interactions, potentially by binding to methylated ligands. A group of germline specific single and multiTudor domain containing proteins (TDRDs) represented by drosophila Tudor and its mammalian orthologs Tdrd1, Tdrd4/RNF17, and Tdrd6 play evolutionarily conserved roles in germinal granule/nuage formation and germ cell specification and differentiation. However, their physiological ligands, and the biochemical and structural basis for ligand recognition, are largely unclear. Here, by immunoprecipitation of endogenous murine Piwi proteins (Miwi and Mili) and proteomic analysis of complexes related to the piRNA pathway, we show that the TDRD group of Tudor proteins are physiological binding partners of Piwi family proteins. In addition, mass spectrometry indicates that arginine residues in RG repeats at the N-termini of Miwi and Mili are methylated in vivo. Notably, we found that Tdrkh/Tdrd2, a novel single Tudor domain containing protein identified in the Miwi complex, is expressed in the cytoplasm of male germ cells and directly associates with Miwi. Mutagenesis studies mapped the Miwi-Tdrkh interaction to the very N-terminal RG/RA repeats of Miwi and showed that the Tdrkh Tudor domain is critical for binding. Furthermore, we have solved the crystal structure of the Tdrkh Tudor domain, which revealed an aromatic binding pocket and negatively charged binding surface appropriate for accommodating methylated arginine. Our findings identify a methylation-directed protein interaction mechanism in germ cells mediated by germline Tudor domains and methylated Piwi family proteins, and suggest a complex mode of regulating the organization and function of Piwi proteins in piRNA silencing pathways.

Molecular MR imaging for visualizing ICAM-1 expression in the inflamed synovium of collagen-induced arthritic mice.

OBJECTIVE: To determine the utility of intercellular adhesion molecule (ICAM)-1 antibody-conjugated gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA-anti-ICAM-1) as a targeted contrast agent for the molecular magnetic resonance imaging (MRI) in collagen-induced arthritis (CIA). MATERIALS AND METHODS: THREE GROUPS OF MICE WERE USED: non-arthritic normal, CIA mice in both the early inflammatory and chronic destructive phases. The MR images of knee joints were obtained before and after injection of Gd-DTPA-anti-ICAM-1, Gd-DTPA, and Gd-DTPA-Immunoglobulin G (Ig G) and were analyzed quantitatively. The patterns of enhancement on the MR images were compared with the histological and immunohistochemical ICAM-1 staining. RESULTS: The images obtained after injection of Gd-DTPA-anti-ICAM-1 displayed gradually increasing signal enhancement from the moment following injection (mean +/- standard deviation [SD]: 424.3 +/- 35.2, n = 3) to 24 hours (532 +/- 11.3), rather than on pre-enhanced images (293 +/- 37.6) in the early inflammatory phase of CIA mice. However, signal enhancement by Gd-DTPA and Gd-DTPA-IgG disappeared after 80 minutes and 24 hours, respectively. In addition, no significant enhancement was seen in the chronic destructive phase of CIA mice, even though they also showed inflammatory changes on T2-weighted MR images. ICAM-1 expression was demonstrated in the endothelium and proliferating synovium of the early inflammatory phase of CIA mice, but not in the chronic destructive phase. CONCLUSION: Molecular MRI with Gd-DTPA-anti-ICAM-1 displays specific images targeted to ICAM-1 that is expressed in the inflamed synovium of CIA. This novel tool may be useful for the early diagnosis and differentiation of the various stages of rheumatoid arthritis.

Inhaled corticosteroid-related tooth problems in asthmatics.

BACKGROUND: The recent Global Initiative for Asthma guideline states that inhaled corticosteroids (ICSs) may induce osteoporosis as a systemic adverse effect. New ICSs, such as fluticasone propionate, have a high topical potency and may therefore induce tooth problems as a result of direct exposure without hepatic metabolism more frequently than older ICSs. OBJECTIVE: We evaluated asthma patients who underwent long-term treatment with a new ICS to determine if they had tooth problems that were related to osteoporosis of the mandible. METHODS: When the conventional bone mineral density (BMD) of asthmatics that received the ICS treatment for at least one year was measured using dual-energy X-ray absorptiometry, the BMD of the mandible was also measured. The T-score of the mandible BMD was then determined based on the mean BMD +/- the standard deviation of normal young adults. RESULT: Asthma patients with tooth loss (n = 36) and with caries or other tooth problems (n = 28) were found to have a significantly higher prevalence of osteoporosis in the mandible than those without tooth problems (n = 17; 22.2%, 7.1%, 0%, respectively; chi(2) = 6.34, p < 0.05). In addition, the presence of mandibular osteoporosis (odds ratio: 6.14, p = 0.02) and a T-score of < -1.0 for the femoral neck (odds ratio: 3.25, p = 0.01) were found to be significant risk factors for tooth loss in the asthma patients. Finally, the T-score of the mandible was found to be correlated with age (r = -0.316, p < 0.01), and with the T-scores of the lumbar spine (r = 0.413, p < 0.001) and femoral neck (r = 0.446, p < 0.001). CONCLUSION: Tooth loss in asthma patients undergoing long-term treatment with a topically potent ICS was found to be related to a decrease in BMD, especially in the mandible. Therefore, patients using these types of ICS should have their mandibular BMD checked regularly, especially if they have any risk factors for osteoporosis. In addition, it would be wise for such patients to reduce their ICS dose.

Multidetector-row computed tomographic evaluation of myocardial perfusion in reperfused chronic myocardial infarction: value of color-coded perfusion map in a porcine model.

We aimed to develop color-coded CT perfusion maps (CPM) of infarcted myocardium and assess the utility of CPM in evaluating ischemic heart disease on a cardiac multi-detector CT (MDCT) in a porcine reperfused-myocardial-infarction model. Myocardial infarctions were induced by 30 min occlusions of the proximal left anterior descending coronary artery (LAD) in 17 healthy adult female pigs. First-pass and 5 min-delayed cardiac MDCTs were performed after 4 weeks of LAD occlusion. Myocardial CPMs were obtained by using the CPM program. Triphenyltetrazolium chloride (TTC)-staining was performed on the cardiac specimens. We analyzed the intermodality agreement on the size and location of the myocardial infarctions. TTC staining revealed myocardial infarction in 16 of 17 pigs, and 15 of these (94%) showed matched infarcts on the CPM and first-pass images. The areas of perfusion deficit noted in early arterial phase images and CPM coincided exactly with the areas of poor TTC staining in 12 of 15 pigs (80%). In the three remaining pigs, the areas of poor TTC staining were larger than those of a perfusion deficit demonstrated by either early arterial phase images or CPM. The agreement between these tests is calculated to be moderate to good (k = 0.736, P < 0.05). Ten myocardial segments in 4 of the 15 pigs (27%) with hypoattenuated myocardium showed a delayed enhancement on the 5 min-delayed images. Contrast-enhanced MDCT was useful and accurate in detecting chronic myocardial infarction; CPM was helpful in visualizing the infarcted myocardium.

Efficacy of MRI versus arthroscopy for evaluation of sinus tarsi syndrome.

BACKGROUND: Magnetic resonance imaging (MRI) has been used to diagnose sinus tarsi syndrome (STS) because of its non-invasiveness and accuracy. The purpose of the present study was to evaluate the diagnostic efficiency of MRI compared with subtalar arthroscopy for STS. MATERIALS AND METHODS: Twenty-eight patients (30 feet) who had undergone both MRI and subtalar arthroscopy for STS were evaluated. MRI results were compared with arthroscopic findings, which were considered the standard. Sensitivity, specificity, and positive and negative predictive values were calculated, and correlations between MRI and arthroscopic findings were investigated. RESULTS: MRI was found to detect interosseous talocalcaneal ligament (ITCL) tears, cervical ligament (CL) tears, sinus tarsi fat alterations, and synovial thickening, with sensitivities, specificities, positive and negative predictive accuracies of: 44%, 60%, 85%, 18% (ITCL tears); 73%, 89%, 80%, 86% (CL tears); 71%, 92%, 93%, 71% (sinus tarsi fat alterations); and 86%, 87%, 67%, 95% (synovial thickening). Correlations between MRI and arthroscopic findings showed full agreement in 10%, partial agreement in 50%, and no agreement in 40%. CONCLUSION: MRI is useful for detecting CL tears, sinus tarsi fat alterations, and synovial thickening, but is inadequate for correctly detecting ITCL tears.