Fatty acid desaturase-2 (ahFAD2) mutant alleles in peanut (Arachis hypogaea L.) pre-breeding lines: an insight into the source, features, discourse, and selection of novel pre-breeding lines

High oleic peanuts and derived food products offer longer shelf life benefits to the food processing industry in addition to multiple health benefits to the consumers. The two mutant alleles, ahFAD2A and ahFAD2B control composition of oleic, linoleic and palmitic acid content in peanut. A total of 563 peanut pre-breeding lines were tested for the presence ahFAD2A and ahFAD2B mutant alleles using allele specific markers. The ahFAD2A mutant allele was present in 82 lines, while none of these lines had ahFAD2B mutant allele. Among botanical types, ahFAD2A mutant allele was more frequent in lines with Virginia growth habit than Spanish bunch although no correlation of ahFAD2A mutant allele with high oleic acid content and growth habit could be established. Oleic and linoleic acid content in 82 prebreeding lines ranged from 39.70 to 62.70% and 17.76 to 31.95%, respectively, with maximum oleic to linoleic acid ratio of 4. Oleic acid was found to be negatively correlated with linoleic and palmitic acid. Further, pre-breeding lines with ahFAD2A mutant allele, high oleic content and high oleic to linoleic ratio were investigated and novel lines were identified for resistance to late leaf spot, short duration, higher pod yield and other yield related traits. These novel pre-breeding lines can be used as a potential donor in peanut improvement programme and to diversify the primary gene pool including initiating further research on induction of fresh ahFAD2B mutant allele

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years

Rupture of the ilio-psoas tendon after a total hip arthroplasty: an unusual cause of radio-lucency of the lesser trochanter simulating a malignancy

Avulsion fracture or progressive radiolucency of lesser trochanter is considered a pathognomic finding in patients with malignancies. Although surgical release of the iliopsoas tendon may be required during a total hip arthroplasty (THA), there is no literature on spontaneous rupture of the ilio-psoas tendon after a THA causing significant functional impairment. We report here such a case, which developed progressive radiolucency of the lesser trochanter over six years after a THA, simulating a malignancy. The diagnosis was confirmed by MRI. Because of the chronic nature of the lesion, gross retraction of the tendon into the pelvis, and low demand of our patient, he was treated by physiotherapy and gait training. Injury to the ilio-psoas tendon can occur in various steps of the THA and extreme care should be taken to avoid this injury. Prevention during surgery is better, although there are no reports of repair in the THA setting. This condition should be considered in patients who present with progressive radioluceny of the lesser trochanter, especially in the setting of a hip/pelvic surgery. Awareness and earlier recognition of the signs and symptoms of this condition will aid in diagnosis and will direct appropriate management

Metallothionein in human oesophagus, Barrett's epithelium and adenocarcinoma

The potential of the metal-binding protein, metallothionein, in assessing the progression of normal oesophagus through Barrett's to adenocarcinoma was investigated. Metallothionein was quantitatively determined in resected tissues from patients undergoing oesophagectomy for high grade dysplasia/adenocarcinoma and in biopsies from patients with Barrett's syndrome. In 10 cancer patients, metallothionein concentrations in adenocarcinoma were not significantly different from normal oesophagus, although six had elevated metallothionein concentrations in the metaplastic tissue bordering the adenocarcinoma. In 17 out of 20 non-cancer patients with Barrett's epithelium, metallothionein was significantly increased by 108% (P<0.004). There was no association between the metallothionein levels in Barrett's epithelium and the presence of inflammatory cells, metaplasia or dysplasia. Metallothionein is a marker of progression from normal to Barrett's epithelium but is not increased in oesophageal adenocarcinoma

Metallothionein – overexpression as a highly significant prognostic factor in melanoma: a prospective study on 1270 patients

Metallothioneins (MT) are ubiquitous, intracellular small proteins with high affinity for heavy metal ions. In the last decades, it was shown that MT overexpression in a variety of cancers is associated with resistance to anticancer drugs and is combined with a poor prognosis. In this prospective study, we examined the role of MT overexpression in melanoma patients as a prognostic factor for progression and survival. Between 1993 and 2004, 3386 patients with primary cutaneous melanoma were investigated by using a monoclonal antibody against MT on routinely fixed, paraffin-embedded tissues. In all, 1270 patients could be followed up for further statistical analysis (Fisher's exact test, Mantel–Haenszel χ2 test, Kaplan–Meier curves). The MT data of disease-free interval and overall survival were compared univariately and multivariately in Cox regression analysis. Immunohistochemical overexpression of MT in tumour cells of patients with primary melanoma (310 of 1270; 24.4%) was associated with a higher risk for progression (117 of 167; 70.1%) and reduced survival (80 of 110; 72.7%) of the disease (P<0.0001). Similarly, Kaplan–Meier curves gave highly significant disadvantages for the MT-positive group. Univariate analysis (relative risk 7.4; 95% confidence interval (CI) 5.2–10.2; P<0.0001 for progression; relative risk 7.1; 95% CI 4.7–10.9; P<0.0001 for survival), as well as multivariate analysis with other prognostic markers resulted in MT overexpression as a highly significant and independent factor for prognosis in primary melanoma

Quantitative metric profiles capture three-dimensional temporospatial architecture to discriminate cellular functional states

<p>Abstract</p> <p>Background</p> <p>Computational analysis of tissue structure reveals sub-visual differences in tissue functional states by extracting quantitative signature features that establish a diagnostic profile. Incomplete and/or inaccurate profiles contribute to misdiagnosis.</p> <p>Methods</p> <p>In order to create more complete tissue structure profiles, we adapted our cell-graph method for extracting quantitative features from histopathology images to now capture temporospatial traits of three-dimensional collagen hydrogel cell cultures. Cell-graphs were proposed to characterize the spatial organization between the cells in tissues by exploiting graph theory wherein the nuclei of the cells constitute the <it>nodes </it>and the approximate adjacency of cells are represented with <it>edges</it>. We chose 11 different cell types representing non-tumorigenic, pre-cancerous, and malignant states from multiple tissue origins.</p> <p>Results</p> <p>We built cell-graphs from the cellular hydrogel images and computed a large set of features describing the structural characteristics captured by the graphs over time. Using three-mode tensor analysis, we identified the five most significant features (metrics) that capture the compactness, clustering, and spatial uniformity of the 3D architectural changes for each cell type throughout the time course. Importantly, four of these metrics are also the discriminative features for our histopathology data from our previous studies.</p> <p>Conclusions</p> <p>Together, these descriptive metrics provide rigorous quantitative representations of image information that other image analysis methods do not. Examining the changes in these five metrics allowed us to easily discriminate between all 11 cell types, whereas differences from visual examination of the images are not as apparent. These results demonstrate that application of the cell-graph technique to 3D image data yields discriminative metrics that have the potential to improve the accuracy of image-based tissue profiles, and thus improve the detection and diagnosis of disease.</p