DNA Rchitect: an R based visualizer for network analysis of chromatin interaction data.

MOTIVATION: Visualization of multiple genomic data generally requires the use of public or commercially hosted browsers. Flexible visualization of chromatin interaction data as genomic features and network components offer informative insights to gene expression. An open source application for visualizing HiC and chromatin conformation-based data as 2D-arcs accompanied by interactive network analyses is valuable. RESULTS: DNA Rchitect is a new tool created to visualize HiC and chromatin conformation-based contacts at high (Kb) and low (Mb) genomic resolutions. The user can upload their pre-filtered HiC experiment in bedpe format to the DNA Rchitect web app that we have hosted or to a version they themselves have deployed. Using DNA Rchitect, the uploaded data allows the user to visualize different interactions of their sample, perform simple network analyses, while also offering visualization of other genomic data types. The user can then download their results for additional network functionality offered in network based programs such as Cytoscape. AVAILABILITY AND IMPLEMENTATION: DNA Rchitect is freely available both as a web application written primarily in R available at http://shiny.immgen.org/DNARchitect/ and as an open source released under an MIT license at: https://github.com/alosdiallo/DNA_Rchitect.

Integrating Spectroscopy with Potato Disease Management.

Spectral phenotyping is an efficient method for the nondestructive characterization of plant biochemical and physiological status. We examined the ability of a full range (350 to 2,500 nm) of foliar spectral data to (i) detect Potato virus Y (PVY) and physiological effects of the disease in visually asymptomatic leaves, (ii) classify different strains of PVY, and (iii) identify specific potato cultivars. Across cultivars, foliar spectral profiles of PVY-infected leaves were statistically different (F = 96.1, P ≤ 0.001) from noninfected leaves. Partial least-squares discriminate analysis (PLS-DA) accurately classified leaves as PVY infected (validation κ = 0.73) and the shortwave infrared spectral regions displayed the strongest correlations with infection status. Although spectral profiles of different PVY strains were statistically different (F = 6.4, P ≤ 0.001), PLS-DA did not classify different strains well (validation κ = 0.12). Spectroscopic retrievals revealed that PVY infection decreased photosynthetic capacity and increased leaf lignin content. Spectral profiles of potato cultivars also differed (F = 9.2, P ≤ 0.001); whereas average spectral classification was high (validation κ = 0.76), the accuracy of classification varied among cultivars. Our study expands the current knowledge base by (i) identifying disease presence before the onset of visual symptoms, (ii) providing specific biochemical and physiological responses to disease infection, and (iii) discriminating between multiple cultivars within a single plant species.

Preferential acquisition and inoculation of PVYNTN over PVYO in potato by the green peach aphid Myzus persicae (Sulzer).

In the past decade, the incidence and distribution of the recombinant, tuber necrotic strain of Potato virus Y (PVYNTN) has been increasing in the US seed potato crop while the ordinary strain (PVYO) has been decreasing. The transmission efficiency of both strains was determined from two potato cultivars when acquired sequentially by the same aphid or when acquired by separate aphids and inoculated to the same plant. PVYNTN was transmitted more efficiently than PVYO and the order of acquisition or inoculation did not affect the preferential transmission of PVYNTN. When a recipient plant became infected with both strains, PVYNTN maintained higher titre than PVYO and would facilitate the acquisition of PVYNTN. Furthermore, the acquisition and transmission of PVYNTN over PVYO was enhanced in the potato cultivar that expressed a strain-specific Ny-like resistance gene that confers partial resistance to PVYO.

Heat treatment of colostrum increases immunoglobulin G absorption efficiency in high-, medium-, and low-quality colostrum.

Previous studies with heat-treated colostrum fed to neonatal calves have consistently used average-quality colostrum. Studies have not compared colostrum across a range of immunoglobulin levels. This study was conducted to investigate IgG absorption in neonatal dairy calves using colostrum of various qualities. Colostrum from the Pennsylvania State University dairy was collected over 2 yr and sorted into high, medium, and low quality based on colostrometer measurement. Colostrum within each category was pooled to create 3 unique, uniform batches. Half of each batch was frozen to be fed without heat treatment. The second half of each batch was heat treated at 60°C for 30min. This process was conducted in September 2011, and repeated in June 2012. Colostrum treatments were analyzed for standard plate count, coliforms, noncoliform gram-negative bacteria, and total IgG concentration. Plasma samples were collected from 145 calves 48h after birth and analyzed for IgG1, IgG2, total protein, and hematocrit. Colostrum quality (high, medium, or low), treatment (unheated or heat treated), and their interactions were analyzed as fixed effects, with year included as a random effect. Heat treatment significantly reduced all types of bacteria and IgG concentration. Plasma IgG concentration at 48h increased linearly with the concentration of IgG in the colostrum that was consumed. Heat treatment of colostrum increased plasma IgG concentration by 18.4% and apparent efficiency of absorption by 21.0%. Results of this study suggest that heat treatment of colostrum containing approximately 50 to 100mg IgG/mL increases absorption of IgG from colostrum.

Identifying efficient dairy heifer producers using production costs and data envelopment analysis.

During November and December 2011, data were collected from 44 dairy operations in 13 Pennsylvania counties. Researchers visited each farm to collect information regarding management practices and feeding, and costs for labor, health, bedding, and reproduction for replacement heifers from birth until first calving. Costs per heifer were broken up into 4 time periods: birth until weaning, weaning until 6 mo of age, 6 mo of age until breeding age, and heifers from breeding to calving. Milk production records for each herd were obtained from Dairy Herd Improvement. The average number of milking cows on farms in this study was 197.8 ± 280.1, with a range from 38 to 1,708. Total cost averaged $1,808.23 ± $338.62 from birth until freshening. Raising calves from birth to weaning cost $217.49 ± 86.21; raising heifers from weaning age through 6 mo of age cost $247.38 ± 78.89; raising heifers from 6 mo of age until breeding cost $607.02 ± 192.28; and total cost for bred heifers was $736.33 ± 162.86. Feed costs were the largest component of the cost to raise heifers from birth to calving, accounting for nearly 73% of the total. Data envelopment analysis determined that 9 of the 44 farms had no inefficiencies in inputs or outputs. These farms best combined feed and labor investments, spending, on average, $1,137.40 and $140.62/heifer for feed and labor. These heifers calved at 23.7 mo of age and produced 88.42% of the milk produced by older cows. In contrast, the 35 inefficient farms spent $227 more on feed and $78 more on labor per heifer for animals that calved 1.6 mo later and produced only 82% of the milk made by their mature herdmates. Efficiency was attained by herds with the lowest input costs, but herds with higher input costs were also able to be efficient if age at calving was low and milk production was high for heifers compared with the rest of the herd.

Transmission Efficiency of Potato virus Y strains PVYO and PVYN-Wi by Five Aphid Species.

Potato virus Y (PVY) is a reemerging problem in potato production in North America. Although the "ordinary" strain, PVYO, is still the dominant isolate in U.S. seed potatoes, the recombinant strain of the virus PVYN-Wi (= PVYN:O) has become widespread. An increase in the prevalence of a PVY strain could be due to differences in the efficiency of transmission by aphid vectors. The transmission efficiency by a clone of Myzus persicae was determined for five isolates each of PVYO and PVYN-Wi. An aphid transmission assay was developed based on the use of potato seedlings from true potato seed, allowing for greater control of plant age and growth stage. No apparent differences in transmission by M. persicae were observed. Single isolates of PVYO and PVYN-Wi were tested for their ability to be transmitted from potato to potato by five aphid species: Aphis glycines, A. gossypii, A. nasturtii, M. persicae, and Rhopalosiphum padi. Both PVY isolates showed a similar transmission phenotype in being transmitted efficiently by M. persicae but very poorly or not at all by A. glycines, A. gossypii, and R. padi. The aphid A. nasturtii transmitted both isolates with an intermediate level of efficiency. The data do not support a model for a differential aphid transmissibility being responsible for the increase in the prevalence of PVYN-Wi.

GIP mediates the incretin effect and glucose tolerance by dual actions on α cells and ß cells.

Glucose-dependent insulinotropic polypeptide (GIP) communicates nutrient intake from the gut to islets, enabling optimal levels of insulin secretion via the GIP receptor (GIPR) on ß cells. The GIPR is also expressed in α cells, and GIP stimulates glucagon secretion; however, the role of this action in the postprandial state is unknown. Here, we demonstrate that GIP potentiates amino acid-stimulated glucagon secretion, documenting a similar nutrient-dependent action to that described in ß cells. Moreover, we demonstrate that GIP activity in α cells contributes to insulin secretion by invoking paracrine α to ß cell communication. Last, specific loss of GIPR activity in α cells prevents glucagon secretion in response to a meal stimulus, limiting insulin secretion and driving glucose intolerance. Together, these data uncover an important axis by which GIPR activity in α cells is necessary to coordinate the optimal level of both glucagon and insulin secretion to maintain postprandial homeostasis.

Mechanisms of arthropod transmission of plant and animal viruses.

A majority of the plant-infecting viruses and many of the animal-infecting viruses are dependent upon arthropod vectors for transmission between hosts and/or as alternative hosts. The viruses have evolved specific associations with their vectors, and we are beginning to understand the underlying mechanisms that regulate the virus transmission process. A majority of plant viruses are carried on the cuticle lining of a vector's mouthparts or foregut. This initially appeared to be simple mechanical contamination, but it is now known to be a biologically complex interaction between specific virus proteins and as yet unidentified vector cuticle-associated compounds. Numerous other plant viruses and the majority of animal viruses are carried within the body of the vector. These viruses have evolved specific mechanisms to enable them to be transported through multiple tissues and to evade vector defenses. In response, vector species have evolved so that not all individuals within a species are susceptible to virus infection or can serve as a competent vector. Not only are the virus components of the transmission process being identified, but also the genetic and physiological components of the vectors which determine their ability to be used successfully by the virus are being elucidated. The mechanisms of arthropod-virus associations are many and complex, but common themes are beginning to emerge which may allow the development of novel strategies to ultimately control epidemics caused by arthropod-borne viruses.

Identification of Potato virus Y Strains Associated with Tuber Damage During a Recent Virus Outbreak in Potato in Idaho.

Potato virus Y (PVY) causes substantial losses in potato production by decreasing yields and affecting the quality of potato tubers. Management of PVY in potato is dependent primarily on potato seed certification programs to prevent or limit initial levels of virus inoculum. Prior to 1990, the ordinary strain of PVY (PVYO) was the predominant virus in North America. PVYO induces clear foliar symptoms in many potato cultivars, allowing successful management in seed potato through a combination of visual inspections and limited laboratory testing. In recent years, necrotic strains of PVY (PVYN, PVYNTN, and PVYN:O) have begun to spread in the United States, many of which induce mild symptoms in potato, making them more difficult to manage through visual inspections. In addition to reducing yield, necrotic isolates may also cause external and internal damage in tubers of susceptible cultivars, which is known as potato tuber necrotic ringspot disease (PTNRD). Tuber necrotic strains of PVY have been reported across the northern United States (1,2,4), although limited information is available on their incidence and spread in commercial potato production. During June and July of 2007, 38 random samples were collected from three different commercial fields displaying disease problems (cvs. Russet Ranger, Alturas, and Russet Burbank) in the vicinity of Idaho Falls, ID. Plants collected showed various degrees of mosaic and leaf yellowing. By using double-antibody sandwich (DAS)-ELISA and reverse transcription (RT)-PCR, 25 of these plants were identified as PVY positive. The mutiplex RT-PCR assay (3) confirmed that nine plants were infected with PVYNTN and 11 with PVYN:O. No RT-PCR products were amplified from five samples. During September and October of 2007, 25 tuber samples (cv. Russet Burbank) showing various degrees of unusual internal symptoms (e.g., brown spots) were collected near Idaho Falls, ID. Twenty-two tubers were found PVY positive by DAS-ELISA, and multiplex RT-PCR determined 13 of those were PVYNTN, three were PVYO, one was a PVYNTN/N:O mixture, and one was a PVYO/N:O mixture. No RT-PCR products were amplified from four samples. In October 2007, six tubers showing distinct external tuber damage characteristic of PTNRD (cv. Highland Russet) were collected near Twin Falls, ID. All six tubers were determined to be PVY positive by DAS-ELISA, and RT-PCR identified five as infected with PVYNTN and one with PVYN:O. All the mixtures were easily separated by inoculating tobacco plants followed by subsequent testing of individual plants. Asymptomatic tubers from the same lot not showing PTNRD damage were found PVY negative by DAS-ELISA and RT-PCR. All PVYNTN isolates collected during 2007 were inoculated into tobacco plants (Nicotiana tabacum L. cv. Xanthi) and confirmed to induce systemic vein necrosis. Limited sequencing of four of the PVYNTN isolates determined that they contained recombinant junctions 2 and 3, identifying them as being related to the European strain of PVYNTN (3). The data suggest an increase in distribution and incidence of necrotic strains of PVY in commercial, potato-production areas in Idaho during an outbreak in 2007 and the potential for an increase in PTNRD. References: (1) P. M. Baldauf et al. Plant Dis. 90:559, 2006. (2) J. M. Crosslin et al. Plant Dis. 90:1102, 2006. (3) J. H. Lorenzen et al. Plant Dis. 90:935, 2006. (4) L. M. Piche et al. Phytopathology 94:1368, 2004.

Phase I trial on the safety of topical rhVEGF on chronic neuropathic diabetic foot ulcers.

OBJECTIVE: To assess the safety/tolerability and perform a preliminary efficacy evaluation of a multiple-dosing regimen of recombinant human vascular endothelial growth factor (VEGF165 or rhVEGF; telbermin) applied topically to chronic diabetic neuropathic foot ulcers. METHOD: Subjects with type 1 or 2 diabetes mellitus were randomised to receive either topical applied telbermin (72 microg/cm2) (n=29) or placebo (n=26) treatment to the foot ulcer surface in conjunction with standard ulcer care. Subjects received treatment every 48 hours (maximum three doses per week) for up to six weeks. Weekly 35mm photography, quantitative planimetry and physical examinations documented the ulcer appearance, surface area and stage. Safety endpoints included incidence of clinically significant hypotension, adverse events and ulcer infection. Exploratory efficacy endpoints included percentage reduction in total ulcer surface area, incidence of complete ulcer healing and time to complete ulcer healing. RESULTS: Incidence of adverse events was comparable in the two treatment groups. None of the adverse events were attributed to study drug, and no hypotension was observed as a result of telbermin treatment. Occurrence of infected study ulcers appeared to be balanced between the treatment groups. Positive trends suggestive of potential signals of biological activity were observed for incidence of complete ulcer healing (41.4% telbermin versus 26.9% placebo at day 43 [P=0.39]) and time to complete ulcer healing (25th percentile of 32.5 days telbermin versus 43.0 days placebo [log-rank P=0.13]). CONCLUSION: The topical application of telbermin 72 microg/cm2 three times a week for up to six weeks appeared to be well tolerated. Further studies are required to characterise the safety/efficacy of telbermin more completely.

Role of food type in yohimbine- and pellet-priming-induced reinstatement of food seeking.

We have recently adapted a reinstatement model, commonly used to study relapse to drugs of abuse, to study the role of stress and anxiety in relapse to palatable food seeking [Ghitza UE, Gray SM, Epstein DH, Rice KC, Shaham Y. The anxiogenic drug yohimbine reinstates palatable food seeking in a rat relapse model: a role of CRF(1) receptors. Neuropsychopharmacology [in press]]. We found that the anxiogenic drug yohimbine, as well as pellet-priming, reinstate food seeking in food restricted rats previously trained to lever press for palatable food pellets (25% fat, 48% carbohydrate). Here, we studied the generality of the effect of yohimbine and pellet priming on reinstatement of food seeking by using three distinct pellet types: non-sucrose carbohydrate (NSC) (5.5% fat, 60% carbohydrate, 4.5% fiber), fiber (0% fat, 0% carbohydrate, 91% fiber) and sucrose (0% fat, 91% carbohydrate, 4% fiber). Rats were placed on a restricted diet (75-80% of daily standard food) and for 9-12 intermittent training days (9 h/day, every other day) lever-pressed for the food pellets under a fixed ratio-1 (20-s timeout) reinforcement schedule. Subsequently, the rats were given 9-10 daily extinction sessions during which lever-presses were not reinforced, and were then injected with yohimbine (0, 0.5, 1.0, 2.0 mg/kg, i.p.) or given a single food pellet to induce reinstatement of food seeking. Yohimbine reinstated food seeking previously reinforced by NSC and sucrose pellets, but had a minimal effect on food seeking in rats previously trained to lever press for fiber pellets. Pellet priming produced a greater degree of reinstatement of lever pressing in rats previously trained on NSC pellets than in rats trained on fiber or sucrose pellets. Results suggest that the magnitude of the effect of yohimbine and pellet priming on reinstatement of food seeking depends in part on the composition of the food pellets used during training.

Genetic Regulation of Polerovirus and Luteovirus Transmission in the Aphid Schizaphis graminum.

ABSTRACT Sexual forms of two genotypes of the aphid Schizaphis graminum, one a vector, the other a nonvector of two viruses that cause barley yellow dwarf disease (Barley yellow dwarf virus [BYDV]-SGV, luteovirus and Cereal yellow dwarf virus-RPV, polerovirus), were mated to generate F1 and F2 populations. Segregation of the transmission phenotype for both viruses in the F1 and F2 populations indicated that the transmission phenotype is under genetic control and that the parents are heterozygous for genes involved in transmission. The ability to transmit both viruses was correlated within the F1 and F2 populations, suggesting that a major gene or linked genes regulate the transmission. However, individual hybrid genotypes differed significantly in their ability to transmit each virus, indicating that in addition to a major gene, minor genes can affect the transmission of each virus independently. Gut and salivary gland associated transmission barriers were identified in the nonvector parent and some progeny, while other progeny possessed only a gut barrier or a salivary gland barrier. Hemolymph factors do not appear to be involved in determining the transmission phenotype. These results provide direct evidence that aphid transmission of luteoviruses is genetically regulated in the insect and that the tissue-specific barriers to virus transmission are not genetically linked.

Biological and Serological Properties of Potato virus Y Isolates in Northeastern United States Potato.

A survey of six potato viruses, Potato virus A (PVA), Potato virus M (PVM), Potato virus S(PVS), Potato virus X (PVX), Potato virus Y (PVY), and Potato leafroll virus (PLRV), was conducted in New York and Maine during 2002 and 2003. Leaf samples were tested by enzyme-linked immunosorbent assay and PVY-positive samples were further tested to determine whether a necrotic strain of PVY (PVYN) or a strain able to induce necrosis in tobacco and in potato tubers (PVYNTN) were present. In both years, PVY and PVS were identified in a majority of the samples, and mixed infections predominated in 83% of the symptomatic leaves in 2002. Of the total 394 PVY-positive samples, 3 reacted with monoclonal antibody (MAb) 1F5 and caused veinal necrosis (VN) in tobacco. Two of these isolates caused tuber necrosis in the potato cv. Yukon Gold. Three PVY isolates reacted with MAb 1F5 but did not cause VN in tobacco, and two caused VN but did not react with MAb 1F5. None of these eight isolates were able to overcome the Ry resistance gene in the potato cultivar Eva, but several were able to overcome the Ny resistance gene found in Allegany. PVYN isolates were not widespread in the northeastern United States; however, several PVY isolates differed from both PVYN and the ordinary strain of PVY and may represent strain recombinants.

Identification of Small Grains Genotypes Resistant to Soilborne wheat mosaic virus.

Soilborne wheat mosaic virus (SBWMV) was detected in New York in 1998 for the first time and has been associated with yield loss where identified. We assessed 115 regionally adapted small grains genotypes for resistance to SBWMV over four growing seasons. Resistance to SBWMV reduces the percentage of plants that develop detectable viral titer and symptoms. Logistic regression was used to analyze disease incidence data and was compared with a general linear model for categorizing relative resistance to SBWMV. Logistic regression facilitated assessment of the effects of small sample size, low disease incidence, and nonuniform disease distribution. By increasing sample size from 20 to 30 stems per replicate, the number of resistance categories was increased through improved resolution of intermediate resistance classes. In environments with low disease incidence, the number of genotypes categorized as susceptible decreased while intermediate genotypes appeared to be resistant in the analysis. Inclusion of disease distribution data as covariates in a spatially balanced experiment did not increase the power of the logistic analysis. No genotype assessed in multiple years was immune to infection. However, 41 of the regionally adapted genotypes tested repeatedly expressed strong resistance to SBWMV, providing growers a choice of cultivars resistant to SBWMV.

Identification of Small Grains Genotypes Resistant to Wheat spindle streak mosaic virus.

Once Wheat spindle streak mosaic virus (WSSMV) becomes established in a field, the only available control strategy is the planting of resistant genotypes. In this study, we assessed 112 genotypes of winter wheat, rye, triticale, and barley for resistance to WSSMV in a 3-year trial in a field that had been used continuously for WSSMV evaluation for over 20 years. Because resistance to WSSMV reduces the percentage of plants that develop detectable virus titer and symptoms, we collected and analyzed disease incidence data. None of the genotypes was immune to infection. Sixty-two of the regionally adapted genotypes repeatedly expressed resistance to WSSMV, thus providing growers with a choice of cultivars resistant to WSSMV. Because of a significant interaction between genotypes and environment (year), genotypes should be assessed for incidence of symptomatic plants in multiple years, particularly when differentiating intermediate responses from highly susceptible and highly resistant responses.

Plant virus proteins involved in natural vector transmission.

Plant viruses transmitted by invertebrate vectors either reversibly bind to vector mouthparts or are internalized by the vector and later secreted. Viral proteins mediate the binding of plant viruses to vector mouthparts and the transport of virus across vector-cell membranes. Both mechanisms probably involve conformational changes of virus proteins during their association with the vector.

Psychosocial approaches to suicide prevention: applications to patients with bipolar disorder.

Hopelessness, dysfunctional attitudes, and poor problem-solving abilities are psychosocial risk factors that have been identified as predictors of suicide. These psychosocial risk factors may help clinicians apply specific therapies and treatments to patients with bipolar disorder at risk for suicide. A search of the literature on suicide prevention revealed 17 randomized, controlled studies, which the authors reviewed to determine the efficacy of strategies aimed at eliminating psychosocial risk factors for suicide. Three strategies emerged as efficacious: (1) applying interventions to elicit emergency care by patients at times of distress; (2) training in problem-solving strategies; and (3) combining comprehensive interventions that include problem solving with intensive rehearsal of cognitive, social, emotional-labeling, and distress-tolerance skills. On the basis of their review of the literature, the authors make recommendations for suicide prevention for patients with bipolar disorder.

Mood disorders and suicide.

The mood disorders unipolar major depression and bipolar disorder increase the risk of suicidal ideation, attempted suicide, and death by completed suicide. This article reviews the epidemiologic data on the relationship between mood disorders and suicide, with an emphasis on the substantial risk of suicide, while reassessing older data that may no longer apply. Widespread underdiagnosis and undertreatment of major depression and bipolar disorder contribute to an unacceptable risk of suicide, a preventable tragedy.

Suicide prevention: increasing education and awareness.

Suicide is a serious and complex public health problem. Health care providers, including both psychiatrists and primary care physicians, are just beginning to understand the intricacies involved in suicide and its prevention. Suicide rates continue to rise, making the education of the public and physicians regarding awareness and prevention, recognition of a wide range of risk factors, and research into suicide prevention strategies very important.

Comparison of separation methods in the 125I-radioimmunoassay of serum cortisol.

Solid-phase first antibody (SP), liquid-phase double-antibody (DA), and pre-precipitated double-antibody (PPT) separation methods have been compared in a radioimmunoassay (RIA) for cortisol in unextracted serum. Both double-antibody methods gave values for pools close to target values assigned by gas chromatography-mass spectrometry (GCMS) whereas the SP assay had a significant negative bias, p less than 0.001 (mean biases: SP -8%, DA -2%, PPT -3%). The SP and DA assays gave average values on patients' samples 12% and 4% lower than values by PPT. These differences could be attributed to different recoveries in the three methods. Between-assay precision of the DA and PPT systems was better than SP (mean CV:SP 11%, DA 7%, PPT 5%). This allowed sensitivity in the PPT assay comparable to that of SP and DA to be achieved, despite the less steep slope of the calibration curve. The DA and PPT assays have several practical advantages over SP. In addition, the PPT assay requires only a 1-hour incubation. It is concluded that the PPT separation system is the method of choice in terms of precision and practical convenience.