Biomedical subjects
Publications and source records attributed to Jyoti Shah.
Since 2002, plant biologists have begun to apply mass spectrometry to the comprehensive analysis of complex lipids. Such lipidomic analyses have been used to uncover roles for lipids in plant response to stresses and to identify in vivo functions of genes involved in lipid metabolism.
Resistance to an yellow strain of Cucumber mosaic virus [CMV(Y)] in Arabidopsis thaliana ecotype C24 is conferred by the CC-NBS-LRR type R gene, RCY1. RCY1-conferred resistance is accompanied by a hypersensitive response (HR), which is characterized by the development of necrotic local lesion (NLL) at the site of infection that restricts viral spread. To further characterize the role of RCY1 in NLL formation we have identified six recessive CMV(Y)-susceptible rcy1 mutants, four of which contain single amino acid substitutions in RCY1: rcy1-2 contains a D to N substitution in the CC domain, rcy1-3 and rcy1-4 contain R to K and E to K substitutions, respectively, in the LRR domain, and rcy1-6 contains a W to C substitution in the NBS domain. The rcy1-5 and rcy1-7 contain nonsense mutations in the LRR and NBS domains, respectively. Although the virus systemically spread in all six rcy1 mutants, HR-associated cell death was differentially induced in these mutants. In comparison to the wild type C24 plant, HR was not observed in the CMV(Y)-inoculated leaves of the rcy1-3, rcy1-5, rcy1-6 and rcy1-7 mutants. In contrast, delayed NLL development was observed in the virus inoculated leaves of the rcy1-2 and rcy1-4 mutants. In addition, necrosis accompanied by elevated accumulation of PR gene transcript also appeared in the non-inoculated leaves of the rcy1-2 and rcy1-4 mutants. Trans-complementation was observed between the rcy1-2 and rcy1-4 alleles; in F1 plants derived from a cross between rcy1-2 and rcy1-4, HR associated cell death was accelerated and systemic spread of the virus was partially suppressed than in the homozygous rcy1-2 and rcy1-4 plants. Our results suggest that the CC, NBS and LRR domains of RCY1 are required for restriction of virus spread but differentially impact the induction of HR-like cell death. Furthermore, these results also predict inter-molecular interaction involving RCY1 in Arabidopsis resistance to CMV(Y).
Although oxylipins can be synthesized from free fatty acids, recent evidence suggests that oxylipins are components of plastid-localized polar complex lipids in Arabidopsis (Arabidopsis thaliana). Using a combination of electrospray ionization (ESI) collisionally induced dissociation time-of-flight mass spectrometry (MS) to identify acyl chains, ESI triple-quadrupole (Q) MS in the precursor mode to identify the nominal masses of complex polar lipids containing each acyl chain, and ESI Q-time-of-flight MS to confirm the identifications of the complex polar lipid species, 17 species of oxylipin-containing phosphatidylglycerols, monogalactosyldiacylglycerols (MGDG), and digalactosyldiacylglycerols (DGDG) were identified. The oxylipins of these polar complex lipid species include oxophytodienoic acid (OPDA), dinor-OPDA (dnOPDA), 18-carbon ketol acids, and 16-carbon ketol acids. Using ESI triple-Q MS in the precursor mode, the accumulation of five OPDA- and/or dnOPDA-containing MGDG and two OPDA-containing DGDG species were monitored as a function of time in mechanically wounded leaves. In unwounded leaves, the levels of these oxylipin-containing complex lipid species were low, between 0.001 and 0.023 nmol/mg dry weight. However, within the first 15 min after wounding, the levels of OPDA-dnOPDA MGDG, OPDA-OPDA MGDG, and OPDA-OPDA DGDG, each containing two oxylipin chains, increased 200- to 1,000-fold. In contrast, levels of OPDA-hexadecatrienoic acid MGDG, linolenic acid (18:3)-dnOPDA MGDG, OPDA-18:3 MGDG, and OPDA-18:3 DGDG, each containing a single oxylipin chain, rose 2- to 9-fold. The rapid accumulation of high levels of galactolipid species containing OPDA-OPDA and OPDA-dnOPDA in wounded leaves is consistent with these lipids being the primary products of plastidic oxylipin biosynthesis.
INTRODUCTION: The object of this study was to compare the technical ability of general surgery and urology trainees to perform a small bowel anastomosis using a life-like bench model. METHODS: Forty subjects were divided into two groups based on the stage of their training. Specialist registrars (SpRs) trained for 1 to 3 years were defined as junior SpRs, and those with 4 to 6 years of training were defined as senior SpRs. They were asked to perform a small bowel anastomosis on a standard latex model using the same equipment, suture material, and standardized instructions. Trainees were assessed by three trained observers based on a global rating scale. RESULTS: Interrater reliability was 0.83 for the general surgical group and 0.88 for the urology group. The median scores obtained by the junior SpRs were lower than those achieved by the senior SpRs, and general surgical trainees consistently performed better than their matched urology group. This difference reached statistical significance for the senior group. CONCLUSIONS: Global rating scores provide a reliable, valid method for assessing technical skills between specialties when performing a small bowel anastomosis. We provide reasons why general surgeons may be more proficient at this task than urologists. These findings have possible application to identifying trainees who need additional training and may also provide a mechanism to ensure competence in this task.
Fusarium head blight (FHB) is a devastating disease of wheat and barley which causes extensive losses worldwide. Monogenic, gene-for-gene resistance to FHB has not been reported. The best source of resistance to FHB is a complex, quantitative trait derived from the wheat cv. Sumai 3. Here, we show that the Arabidopsis thaliana NPR1 gene (AtNPR1), which regulates the activation of systemic acquired resistance, when expressed in the FHB-susceptible wheat cv. Bobwhite, confers a heritable, type II resistance to FHB caused by Fusarium graminearum. The heightened FHB resistance in the transgenic AtNPRI -expressing wheat is associated with the faster activation of defense response when challenged by the fungus. PR1 expression is induced rapidly to a high level in the fungus-challenged spikes of the AtNPR1-expressing wheat. Furthermore, benzothiadiazole, a functional analog of salicylic acid, induced PR1 expression faster and to a higher level in the AtNPR1-expressing wheat than in the nontransgenic plants. We suggest that FHB resistance in the AtNPR1-expressing wheat is a result of these plants being more responsive to an endogenous activator of plant defense. Our results demonstrate that NPR1 is an effective candidate for controlling FHB.
Prostate cancer is the most prevalent nondermatological malignancy affecting men in the Western world. An increase in public awareness has led to earlier detection. Accepted treatments for localized prostate cancer include active surveillance, radical prostatectomy, interstitial brachytherapy, external beam radiotherapy and watchful waiting. The authors discuss the rationale for the different approaches together with outcomes including toxicity. Novel approaches are also explored. The management of locally advanced disease has long been a challenge and the evolving evidence is reviewed.
Despite the increased detection of prostate cancer at an early stage, men are still dying of this disease. Management of advanced disease focuses on controlling the disease process, palliation of symptoms and improving quality of life. In this review, the basis for androgen deprivation in hormone-dependent disease is discussed and the role of maximum and intermittent androgen deprivation, as well as management options for hormone-refractory disease is addressed. Local radiotherapy continues to be of importance in pain control and the maintenance of quality of life. Radiopharmaceuticals and bisphosphonates also have a role to play, the latter particularly in the reduction of skeletal-related events. Chemotherapy in hormone-refractory disease is now well established following pivotal trials demonstrating a survival benefit with docetaxel. The emergence of novel agents targeting growth factors, angiogenesis and immunotherapy present exciting possibilities for future treatment.
Aphids, which are phloem-feeding insects, cause extensive loss of plant productivity and are vectors of plant viruses. Aphid feeding causes changes in resource allocation in the host, resulting in an increase in flow of nutrients to the insect-infested tissue. We hypothesized that leaf senescence, which is involved in the programmed degradation of cellular components and the export of nutrients out of the senescing leaf, could be utilized by plants to limit aphid growth. Using Arabidopsis (Arabidopsis thaliana) and green peach aphid (GPA; Myzus persicae Sulzer), we found that GPA feeding induced premature chlorosis and cell death, and increased the expression of SENESCENCE ASSOCIATED GENES (SAGs), all hallmarks of leaf senescence. Hypersenescence was accompanied by enhanced resistance against GPA in the Arabidopsis constitutive expresser of PR genes5 and suppressor of SA insensitivity2 mutant plants. In contrast, resistance against GPA was compromised in the phytoalexin deficient4 (pad4) mutant plant. The PAD4 gene, which is expressed at elevated level in response to GPA feeding, modulates the GPA feeding-induced leaf senescence. In comparison to the wild-type plant, GPA feeding-induced chlorophyll loss, cell death, and SAG expression were delayed in the pad4 mutant. Although PAD4 is associated with camalexin synthesis and salicylic acid (SA) signaling, camalexin and SA signaling are not important for restricting GPA growth; growth of GPA on the camalexin-biosynthesis mutant, pad3, and the SA deficient2 and NahG plants and the SA-signaling mutant, nonexpresser of PR genes1, were comparable to that on the wild-type plant. Our results suggest that PAD4 modulates the activation of senescence in the aphid-infested leaves, which contributes to basal resistance to GPA.
Loss of a stearoyl-ACP desaturase activity in the Arabidopsis thaliana ssi2 mutant confers susceptibility to the necrotroph, Botrytis cinerea. In contrast, the ssi2 mutant exhibits enhanced resistance to Pseudomonas syringae, Peronospora parasitica, and Cucumber mosaic virus. The altered basal resistance to these pathogens in the ssi2 mutant plant is accompanied by the constitutive accumulation of elevated salicylic acid (SA) level and expression of the pathogenesis-related 1 (PR1) gene, the inability of jasmonic acid (JA) to activate expression of the defensin gene, PDF1.2, and the spontaneous death of cells. Here, we show that presence of the eds5 and pad4 mutant alleles compromises the ssi2-conferred resistance to Pseudomonas syringae pv. maculicola. In contrast, resistance to B. cinerea was restored in the ssi2 eds5 and ssi2 pad4 double-mutant plants. However, resistance to B. cinerea was not accompanied by the restoration of JA responsiveness in the ssi2 eds5 and ssi2 pad4 plants. The ssi2 eds5 and ssi2 pad4 plants retain the ssi2-conferred spontaneous cell death phenotype, suggesting that cell death is not a major factor that predisposes the ssi2 mutant to infection by B. cinerea. Furthermore, the high SA content of the ssi2 pad4 plant, combined with our previous observation that the SA-deficient ssi2 nahG plant succumbs to infection by B. cinerea, suggests that elevated SA level does not have a causal role in the ssi2-conferred susceptibility to B. cinerea. Our results suggest that interaction between an SSI2-dependent factor or factors and an EDS5- and PAD4-dependent mechanism or mechanisms modulates defense to B. cinerea.
Lipids and lipid metabolites influence pathogenesis and resistance mechanisms associated with plant-microbe interactions. Some microorganisms sense their presence on a host by perceiving plant surface waxes, whereas others produce toxins that target plant lipid metabolism. In contrast, plants have evolved to recognize microbial lipopolysaccharides (LPSs), sphingolipids, and lipid-binding proteins as elicitors of defense response. Recent studies have demonstrated that the plasma membrane provides a surface on which some plant resistance (R) proteins perceive pathogen-derived effectors and thus confer race-specific resistance. Plant cell membranes also serve as reservoirs from which biologically active lipids and precursors of oxidized lipids are released. Some of these oxylipins, for example jasmonic acid (JA), are important signal molecules in plant defense. Arabidopsis thaliana is an excellent model plant to elucidate the biosynthesis and metabolism of lipids and lipid metabolites, and the characterization of signaling mechanisms involved in the modulation of plant defense responses by phytolipids. This review focuses on recent studies that highlight the involvement of lipids and lipid metabolites, and enzymes involved in lipid metabolism and modification in plant disease resistance.
Systemic acquired resistance (SAR) is a broad-spectrum resistance mechanism in plants that is activated in naive organs after exposure of another organ to a necrotizing pathogen. The organs manifesting SAR exhibit an increase in levels of salicylic acid (SA) and expression of the PATHOGENESIS-RELATED1 (PR1) gene. SA signaling is required for the manifestation of SAR. We demonstrate here that the Arabidopsis thaliana suppressor of fatty acid desaturase deficiency1 (sfd1) mutation compromises the SAR-conferred enhanced resistance to Pseudomonas syringae pv maculicola. In addition, the sfd1 mutation diminished the SAR-associated accumulation of elevated levels of SA and PR1 gene transcript in the distal leaves of plants previously exposed to an avirulent pathogen. However, the basal resistance to virulent and avirulent strains of P. syringae and the accumulation of elevated levels of SA and PR1 gene transcript in the pathogen-inoculated leaves of sfd1 were not compromised. Furthermore, the application of the SA functional analog benzothiadiazole enhanced disease resistance in the sfd1 mutant plants. SFD1 encodes a putative dihydroxyacetone phosphate (DHAP) reductase, which complemented the glycerol-3-phosphate auxotrophy of the DHAP reductase-deficient Escherichia coli gpsA mutant. Plastid glycerolipid composition was altered in the sfd1 mutant plant, suggesting that SFD1 is involved in lipid metabolism and that an SFD1 product lipid(s) is important for the activation of SAR.
BACKGROUND: Objective evaluation of technical skills is now possible. The aim of this study was to evaluate whether a previously validated assessment tool can discriminate between junior and senior higher surgical trainees (HST) with regard to their technical skills. METHODS: Fifteen junior trainees (years 1 to 3) and 15 senior (years 4 to 6) were asked to perform a series of bench-model tasks, which included knot-tie at depth, vertical mattress suturing, sebaceous cyst excision, small bowel anastomosis, and saphenofemoral junction dissection. Analysis of performance included the Imperial College Surgical Assessment Device, which analyzed positional data such as total number of movements, total distance traveled, and time taken, and video-based qualitative evaluation of performance using global rating scales. In addition, all participants were asked to complete a self-assessment using exactly the same scoring system used by the observers. Statistical analysis included nonparametric tests and Cronbach's alpha was used for interrater reliability (IRR) A P value less than 0.05 was deemed significant. RESULTS: There were no significant differences in performance between junior and senior trainees for most of the tasks (IRR was 0.8 to 0.9). However, significant differences in performance were noted, in favor of the junior group, for knot-tie at depth, for two of the three parameters measured (total number of movements, P = 0.004; time taken, P = 0.01). CONCLUSIONS: In the absence of any significant differences between the groups, we can conclude that there is a ceiling effect (years 3 to 4) in performance beyond which pure technical skills, as measured by this tool, can no longer discriminate between levels of experience. Increasing the sensitivity of future assessment tools is necessary for better evaluation of performance levels. This finding also may imply that for the evaluation of senior trainees, other aspects of surgical competence should be assessed.
Gene-for-gene resistance to a yellow strain of cucumber mosaic virus [CMV(Y)] is conferred by the dominant RESISTANCE to CMV(Y) (RCY1) allele in the Arabidopsis thaliana ecotype C24. RCY1-conferred resistance to CMV(Y) and expression of the Pathogenesis-related 1 (PR-1) and PR-5 genes are partially compromised by the eds5 mutation and the nahG transgene that block accumulation of salicylic acid (SA). In contrast, the RCY1-conferred resistance to CMV(Y) is not affected by the jasmonic acid (JA)-insensitive coi1 and jar1 mutations. Interestingly, we report here that in contrast to the eds5 RCY1 plant, the eds5 coi1 RCY1 double-mutant plant exhibited a higher level of resistance to CMV(Y). Presence of the coi1 mutant allele also restored the CMV(Y)-activated expression of the PR-1 and PR-5 gene in the eds5 coi1 RCY1 plant. In contrast to the PR-1 and PR-5 genes, expression of the JA-dependent PLANT DEFENSIN 1.2 (PDF1.2) and HEVEIN-LIKE PROTEIN (HEL) genes was elevated in the CMV(Y)-inoculated leaves of the eds5 RCY1 plant, but not in the virus-inoculated leaves of the wild-type RCY1 and coi1 RCY1 plants. We propose that antagonistic interactions between the SA and JA signaling mechanisms modulate defense gene expression and the activation of RCY1-conferred gene-for-gene resistance to CMV(Y).
The Arabidopsis thaliana SSI2 gene encodes a plastid-localized stearoyl-ACP desaturase. The recessive ssi2 mutant allele confers constitutive accumulation of the pathogenesis-related-1 (PR-1) gene transcript and salicylic acid (SA), and enhanced resistance to bacterial and oomycete pathogens. In addition, the ssi2 mutant is a dwarf and spontaneously develops lesions containing dead cells. Here, we show that the ssi2 mutant also confers enhanced resistance to Cucumber mosaic virus (CMV). Compared with the wild-type plant, viral multiplication and systemic spread were diminished in the ssi2 mutant plant. However, unlike the ssi2-conferred resistance to bacterial and oomycete pathogens, the ssi2-conferred enhanced resistance to CMV was retained in the SA-deficient ssi2 nahG plant. In addition, SA application was not effective in limiting CMV multiplication and systemic spread in the CMV-susceptible wild-type plant. The acd1, acd2, and cpr5 mutants which, like the ssi2 mutant, accumulate elevated SA levels, constitutively express the PR-1 gene, spontaneously develop lesions containing dead cells, and are dwarfs, are, however, fully susceptible to CMV. Our results suggest that dwarfing, cell death, and constitutive activation of SA signaling are not important for the ssi2-conferred enhanced resistance to CMV. However, the sfd1 and sfd4 mutations, which affect lipid metabolism, suppress the ssi2-conferred enhanced resistance to CMV, thus implicating a lipid or lipids in the ssi2-conferred resistance to CMV. Interestingly, the ssi2-conferred resistance to CMV was compromised in the ssi2 eds5 plant, suggesting the involvement of an SA-independent, EDS5-dependent mechanism in the ssi2-conferred resistance to CMV.
PURPOSE: Urology is one of the most common specialties chosen by surgical trainees. This study set out to determine what factors influence the decision in pursuing a career in urology as opposed to other surgical specialties. MATERIALS AND METHODS: A questionnaire was mailed to 844 urologists of various career levels within the UK. Subjects were asked to document the top three factors that influenced their choice of urology as a career. Specifically, they were asked whether their undergraduate teaching was an influence. RESULTS: Completed surveys were received from 362 respondents. Less than one-third of the respondents were influenced by their undergraduate urology exposure. The top five reasons cited for pursing a career in urology were: (i) a positive role model; (ii) postgraduate urology experience; (iii) the wide variety of procedures encompassing open and endoscopic work; (iv) the lifestyle; and (v) the pleasant personalities of urologists when compared with other specialties. CONCLUSIONS: This is the first study if its kind to establish the factors influencing career choices. As urology continues to be eroded from undergraduate curricula, the data support the view that undergraduate urology exposure is not the most influential factor.
The Arabidopsis thaliana (L.) Heyhn. genome contains 45 genes that show substantial sequence similarity to the tobacco ( Nicotiana tabacum L.) HIN1 (harpin-induced) gene and the Arabidopsis NDR1 (non-race-specific disease resistance) gene. Of these, the nine ( NHL1 to NHL3, NHL8 to NHL12 and NHL22) that bear the highest identity to HIN1 were selected and their expression in various situations was examined. We found that NHL10 behaves like the tobacco HIN1 gene in that its transcripts are abundant in senescing leaves and they specifically accumulate during the hypersensitive response (HR) caused by exposure to an avirulent Cucumber mosaic virus (CMV) strain. Spermine, a novel inducer of tobacco PR (pathogenesis-related) genes, was found to up-regulate expression of NHL3, NHL10 and NDR1. Green fluorescent protein-fusion experiments indicated that NHL2 and NHL10, and possibly NDR1 are localized in the chloroplasts. Studies using Arabidopsis mutants defective in salicylic acid (SA), ethylene and jasmonic acid signalling revealed that the senescence-associated expression of NHL10 is mediated by a pathway that involves SA but that NHL10 expression during CMV-induced HR and spermine treatment is totally independent of SA.
A loss-of-function mutation in the Arabidopsis SSI2/FAB2 gene, which encodes a plastidic stearoyl-acyl-carrier protein desaturase, has pleiotropic effects. The ssi2 mutant plant is dwarf, spontaneously develops lesions containing dead cells, accumulates increased salicylic acid (SA) levels, and constitutively expresses SA-mediated, NPR1-dependent and -independent defense responses. In parallel, jasmonic acid-regulated signaling is compromised in the ssi2 mutant. In an effort to discern the involvement of lipids in the ssi2-conferred developmental and defense phenotypes, we identified suppressors of fatty acid (stearoyl) desaturase deficiency (sfd) mutants. The sfd1, sfd2, and sfd4 mutant alleles suppress the ssi2-conferred dwarfing and lesion development, the NPR1-independent expression of the PATHOGENESIS-RELATED1 (PR1) gene, and resistance to Pseudomonas syringae pv maculicola. The sfd1 and sfd4 mutant alleles also depress ssi2-conferred PR1 expression in NPR1-containing sfd1 ssi2 and sfd4 ssi2 plants. By contrast, the sfd2 ssi2 plant retains the ssi2-conferred high-level expression of PR1. In parallel with the loss of ssi2-conferred constitutive SA signaling, the ability of jasmonic acid to activate PDF1.2 expression is reinstated in the sfd1 ssi2 npr1 plant. sfd4 is a mutation in the FAD6 gene that encodes a plastidic omega6-desaturase that is involved in the synthesis of polyunsaturated fatty acid-containing lipids. Because the levels of plastid complex lipid species containing hexadecatrienoic acid are depressed in all of the sfd ssi2 npr1 plants, we propose that these lipids are involved in the manifestation of the ssi2-conferred phenotypes.
Salicylic acid is an important signal molecule in plant defense. In the past two years, significant progress has been made in understanding the mechanism of salicylic-acid biosynthesis and signaling in plants. A pathway similar to that found in some bacteria synthesizes salicylic acid from chorismate via isochorismate. Salicylic-acid signaling is mediated by at least two mechanisms, one requiring the NON-EXPRESSOR OF PR1 (NPR1) gene and a second that is independent of NPR1. Feedback loops involving salicylic acid modulate upstream signals. These feedback loops may provide a point for integrating developmental, environmental and other defense-associated signals, and thus fine-tune the defense responses of plants.