Lack of correlation of stem cell markers in breast cancer stem cells

BACKGROUND: Various markers are used to identify the unique sub-population of breast cancer cells with stem cell properties. Whether these markers are expressed in all breast cancers, identify the same population of cells, or equate to therapeutic response is controversial. METHODS: We investigated the expression of multiple cancer stem cell markers in human breast cancer samples and cell lines in vitro and in vivo, comparing across and within samples and relating expression with growth and therapeutic response to doxorubicin, docetaxol and radiotherapy. RESULTS: CD24, CD44, ALDH and SOX2 expression, the ability to form mammospheres and side-population cells are variably present in human cancers and cell lines. Each marker identifies a unique rather than common population of cancer cells. In vivo, cells expressing these markers are not specifically localized to the presumptive stem cell niche at the tumour/stroma interface. Repeated therapy does not consistently enrich cells expressing these markers, although ER-negative cells accumulate. CONCLUSIONS: Commonly employed methods identify different cancer cell sub-populations with no consistent therapeutic implications, rather than a single population of cells. The relationships of breast cancer stem cells to clinical parameters will require identification of specific markers or panels for the individual cancer

Retraction: Inactivation of MAP kinase signalling in Myc Transformed Cells and Rescue by LiCl inhibition of GSK3

The corresponding author submitted this article [1] to Molecular Cancer on the assumption that the co-author had agreed to the submission. Since this is not the case, the authors are retracting the article. The corresponding author is deeply sorry for any inconvenience this may have caused to the editorial and publishing staff. An apology is also extended to the readers

Evidence and Ideology in Macroeconomics: The Case of Investment Cycles

The paper reports the principal findings of a long term research project on the description and explanation of business cycles. The research strongly confirmed the older view that business cycles have large systematic components that take the form of investment cycles. These quasi-periodic movements can be represented as low order, stochastic, dynamic processes with complex eigenvalues. Specifically, there is a fixed investment cycle of about 8 years and an inventory cycle of about 4 years. Maximum entropy spectral analysis was employed for the description of the cycles and continuous time econometrics for the explanatory models. The central explanatory mechanism is the second order accelerator, which incorporates adjustment costs both in relation to the capital stock and the rate of investment. By means of parametric resonance it was possible to show, both theoretically and empirically how cycles aggregate from the micro to the macro level. The same mathematical tool was also used to explain the international convergence of cycles. I argue that the theory of investment cycles was abandoned for ideological, not for evidential reasons. Methodological issues are also discussed

Effect of relining, cement type, and thermocycling on push-out bond strength of fiber reinforced posts.

Statement of the problem: Improving the adaptation of fiber reinforced posts through relining may affect the retention of the posts. Purpose: To investigate the effect of post relining, cement type, and thermocycling on the push-out bond strength of fiber reinforced posts. Materials and methods: (48) endodontically treated human teeth were excessively flared using diamond stones. The teeth were divided into two groups; group (1) (n ¼ 24) received glassix glass fiber posts adapted to the flared canals by relining with composite resin and group (2) (n ¼ 24) received non-relined glassix glass fiber post. Samples of each group were divided into three subgroups (n ¼ 8) according to the type of cement used; subgroup (a): luted using Metacem Refill, a total etch resin cement, subgroup (b): luted using Rely X Unicem, a self-adhesive resin cement and subgroup (c): luted using RelyX Luting, a resin modified glass ionomer cement. Half the samples of each subgroup (n ¼ 4) were subjected to thermocycling. The samples were sectioned horizontally into 2 mm thick slices yielding 3 sections for each sample. Retention was evaluated using push out bond strength test using universal testing machine. The maximum failure load was recorded and used to calculate the push-out bond strength. Data was statistically analyzed and mode of failure was assessed using magnifying glass. Results: Relined posts showed statistically significantly higher mean push-out bond strength than non-relined posts. Rely X Unicem showed the statistically significantly highest mean push-out bond strength among tested cements. Metacem showed significantly lower mean push-out bond strength than Rely X Unicem. Rely X Luting showed the statistically significantly lowest mean push-out bond strengths. There was no statistically significant difference between mean push-out bond strength with and without thermocycling. Most failures occurred at the cementedentin interface in the relined group, while adhesive failure occurred at the cement-post interface in non-relined group

Low dose cranial irradiation-induced cerebrovascular damage is reversible in mice

BACKGROUND: High-dose radiation-induced blood-brain barrier breakdown contributes to acute radiation toxicity syndrome and delayed brain injury, but there are few data on the effects of low dose cranial irradiation. Our goal was to measure blood-brain barrier changes after low (0.1 Gy), moderate (2 Gy) and high (10 Gy) dose irradiation under in vivo and in vitro conditions. METHODOLOGY: Cranial irradiation was performed on 10-day-old and 10-week-old mice. Blood-brain barrier permeability for Evans blue, body weight and number of peripheral mononuclear and circulating endothelial progenitor cells were evaluated 1, 4 and 26 weeks postirradiation. Barrier properties of primary mouse brain endothelial cells co-cultured with glial cells were determined by measurement of resistance and permeability for marker molecules and staining for interendothelial junctions. Endothelial senescence was determined by senescence associated β-galactosidase staining. PRINCIPLE FINDINGS: Extravasation of Evans blue increased in cerebrum and cerebellum in adult mice 1 week and in infant mice 4 weeks postirradiation at all treatment doses. Head irradiation with 10 Gy decreased body weight. The number of circulating endothelial progenitor cells in blood was decreased 1 day after irradiation with 0.1 and 2 Gy. Increase in the permeability of cultured brain endothelial monolayers for fluorescein and albumin was time- and radiation dose dependent and accompanied by changes in junctional immunostaining for claudin-5, ZO-1 and β-catenin. The number of cultured brain endothelial and glial cells decreased from third day of postirradiation and senescence in endothelial cells increased at 2 and 10 Gy. CONCLUSION: Not only high but low and moderate doses of cranial irradiation increase permeability of cerebral vessels in mice, but this effect is reversible by 6 months. In-vitro experiments suggest that irradiation changes junctional morphology, decreases cell number and causes senescence in brain endothelial cells

Surfaceome interrogation using an RNA-seq approach highlights leukemia initiating cell biomarkers in an LMO2 T cell transgenic model

The surfaceome is critical because surface proteins provide a gateway for internal signals and transfer of molecules into cells, and surfaceome differences can influence therapy response. We have used a surfaceome analysis method, based on comparing RNA-seq data between normal and abnormal cells (Surfaceome DataBase Mining or Surfaceome DBM), to identify sets of upregulated cell surface protein mRNAs in an LMO2-mediated T-ALL mouse model and corroborated by protein detection using antibodies. In this model the leukemia initiating cells (LICs) comprise pre-leukaemic, differentiation inhibited thymocytes allowing us to provide a profile of the LIC surfaceome in which GPR56, CD53 and CD59a are co-expressed with CD25. Implementation of cell surface interaction assays demonstrates fluid interaction of surface proteins and CD25 is only internalized when co-localized with other proteins. The Surfaceome DBM approach to analyse cancer cell surfaceomes is a way to find targetable surface biomarkers for clinical conditions where RNA-seq data from normal and abnormal cell are available

Genetic variation in sorghum germplasm from Sudan, ICRISAT, and USA assessed by simple sequence repeats (SSRs)

Assessment of genetic variability in crops has a strong impact on plant breeding and conservation of genetic resources. It is particularly useful in the characterization of individuals, accessions, and cultivars in determining duplications in germplasm collections and for selecting parents. The objective of this study was to estimate genetic diversity and to obtain information on the genetic relationship among 96 sorghum [Sorghum bicolor (L.) Moench] accessions from Sudan, ICRISAT, and Nebraska, USA, using 16 simple sequence repeats (SSRs). In total, 117 polymorphic bands were detected with a mean of 7.3 alleles per SSR locus. By this approach each accession is uniquely fingerprinted. Genetic similarity estimates ranged from 0 to 0.91, with a mean of 0.30. The polymorphic information content (PIC) for SSRs ranged from 0.46 (SB4-72) to 0.87 (SBAGF06). Diversity index (DI) for all accessions was 0.71. Within subgroups, DI was 0.63 for Sudanese landraces and improved cultivars, 0.49 for PI accessions, 0.42 for Nebraska derivatives, 0.39 for the ICRISAT advanced breeding lines (ABLs), 0.65 for the Feterita group, 0.71 for the Milo group, 0.63 for a Synthetic group (new breeding materials), 0.68 for the Hegiri group, and 0.47 for the Mugud group. Mantel statistics revealed a good fit of the unweighted pair-grouped method with arithmetic average (UPGMA) cluster to the original genetic similarity (GS) data (r = 0.867). UPGMA clustering produced two main clusters comprising mainly nonimproved germplasm (gene bank accessions and Nebraska population derivatives), and improved genotypes (cultivars, Gadarif collections, and ICRISAT advanced lines). Grouping of accessions by UPGMA cluster analysis matched with the geographical origin and/or pedigree information (Sudan, USA, ICRISAT), the adaptation zone (Gadarif area, Sudan), and morphological characters (Feterita, Mugud, and Milo types), indicating the strong differentiation among the sorghum materials

Rapidly progressive dementia with thalamic degeneration and peculiar cortical prion protein immunoreactivity, but absence of proteinase K resistant PrP: a new disease entity?

BACKGROUND: Human prion diseases are a group of rare fatal neurodegenerative conditions with well-developed clinical and neuropathological diagnostic criteria. Recent observations have expanded the spectrum of prion diseases beyond the classically recognized forms. RESULTS: In the present study we report six patients with a novel, apparently sporadic disease characterised by thalamic degeneration and rapidly progressive dementia (duration of illness 2-12 months; age at death: 55-81 years). Light and electron microscopic immunostaining for the prion protein (PrP) revealed a peculiar intraneuritic distribution in neocortical regions. Proteinase K resistant PrP (PrPres) was undetectable by Western blotting in frontal cortex from the three cases with frozen tissue, even after enrichment for PrPres by centrifugation or by phosphotungstic acid precipitation. Conformation-dependent immunoassay analysis using a range of PK digestion conditions (and no PK digestion) produced only very limited evidence of meaningful D-N (denatured/native) values, indicative of the presence of disease-associated PrP (PrPSc) in these cases, when the results were compared with appropriate negative control groups. CONCLUSIONS: Our observation expands the spectrum of conditions associated with rapidly progressive dementia and may have implications for the understanding of the pathogenesis of prion diseases

The prevalence of depression and anxiety symptoms and their associated factors among patients with cancer in Qatar: A cross-sectional study

Background: Cancer is a significant global health challenge. One of the biggest health issues that cancer patients face is depression and anxiety. This has a significant impact on their quality of life and treatment outcomes. Aim: The aim of this study was to investigate the frequency of depression and anxiety among cancer patients in Qatar. Materials and methods: This study was a cross-sectional design using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) scales. A total of 500 cancer patients were surveyed from the National Center for Cancer Care and Research in Doha. Results: The study found that a significant proportion of cancer patients suffered from depression, with an average PHQ-9 score indicating mild levels of severity. Depression was commonly categorized as mild, with a smaller percentage experiencing moderate, moderate-to-severe, or severe depression. Additionally, patients were predominantly anxious, as reflected by an average GAD-7 score, with most patients experiencing mild to moderate symptoms, while a few experienced moderate or severe anxiety. These findings highlight the significant prevalence of both depression and anxiety among cancer patients, pointing to the importance of comprehensive mental health support. Moreover, patients with advanced-stage cancer, those in their 40s and 60s, those undergoing radiotherapy or hormone therapy, and female patients were found to be more susceptible to depression and anxiety. Conclusion: Treatment of mental health issues is essential to enhancing the effectiveness of cancer treatment. Cancer patients can have a higher quality of life and better adherence to cancer treatments when mental illnesses such as depression and anxiety are identified and treated early. Furthermore, most patients reported having depression and anxiety, according to the study, which showed that these conditions were more common in Qatar than in other countries. Several demographic groups have been linked to higher rates of depression and anxiety, including women, middle-aged adults, people with stage IV cancer, and patients receiving therapies such as radiotherapy and chemotherapy.Scopu

Exploring the multimodal role of yucca schidigera extract in protection against chronic ammonia exposure targeting: Growth, metabolic, stress and inflammatory responses in nile tilapia (oreochromis niloticus l.)

Ammonia is a critical hazardous nitrogen metabolic product in aquaculture. Despite trials for its control, ammonia intoxication remains one of the most critical issues to overcome. In this study, we explored the modulatory effect and potential mechanism by which Yucca schidigera extract (YSE) can ameliorate ammonia intoxication-induced adverse effects on tilapia health and metabolism. A total number of 120 Nile tilapia were evenly assigned into four groups with three replicates each. The first group served as normal control group; the second group was exposed to ammonia alone from the beginning of the experiment and for four weeks. The third group was supplied with YSE in water at a dose of 8 mg/L and exposed to ammonia. The fourth group was supplied with YSE only in water at a dose of 8 mg/L. YSE supplementation succeeded in improving water quality by reducing pH and ammonia levels. Moreover, YSE supplementation markedly alleviated chronic ammonia-induced adverse impacts on fish growth by increasing the final body weight (FBW), specific growth rate (SGR), feed intake and protein efficiency ratio (PER) while reducing the feed conversion ratio (FCR) via improvements in food intake, elevation of hepatic insulin-like growth factor (ILGF-1) and suppression of myostatin (MSTN) expression levels with the restoration of lipid reserves and the activation of lipogenic potential in adipose tissue as demonstrated by changes in the circulating metabolite levels. In addition, the levels of hepato-renal injury biomarkers were restored, hepatic lipid peroxidation was inhibited and the levels of hepatic antioxidant biomarkers were enhanced. Therefore, the current study suggests that YSE supplementation exerted an ameliorative role against chronic ammonia-induced oxidative stress and toxic effects due to its free radical-scavenging potential, potent antioxidant activities and anti-inflammatory effects