Symbiont diversity is not involved in depth acclimation in the Mediterranean sea whip Eunicella singularis

In symbiotic cnidarians, acclimation to depth and lower irradiance can involve physiological changes in the photosynthetic dinoflagellate endosymbiont, such as increased chlorophyll content, or qualitative modifications in the symbiont population in favour of better adapted strains. It has been argued that a lack of capacity to acquire new symbionts could limit the bathymetric distribution of the host species, or compromise its long-term survival in a changing environment. But is that always true? To address this question, we investigated the symbiont genetic diversity in Eunicella singularis, a Mediterranean sea whip species with a wide bathymetric distribution (10 to 50 m depth), which has recently suffered from mass mortalities after periods of abnormally high sea temperatures. We measured symbiont population densities and chlorophyll content in natural populations, and followed the response of the holobionts after reciprocal transplantations to deep and shallow depths. A total of 161 colonies were sampled at 2 depths (10 and 30 m) at 5 sites in the northwestern Mediterranean. All colonies harboured a single ribosomal Symbiodinium clade (A'), but a relatively high within-clade genetic diversity was found among and within colonies. This diversity was not structured by depth, even though the deeper colonies contained significantly lower population densities of symbionts and less chlorophyll. We did, however, reveal host-symbiont specificity among E. singularis and other Mediterranean cnidarian species. Transplantation experiments revealed a limit of plasticity for symbiont population density and chlorophyll content, which in turn questions the importance of the trophic role of Symbiodinium in E. singularis

MicroRNAs and cancer metabolism reprogramming : the paradigm of metformin

Increasing evidence witnesses that cancer metabolism alterations represent a critical hallmark for many types of human tumors. There is a strong need to understand and dissect the molecular mechanisms underlying cancer metabolism to envisage specific biomarkers and underpin critical molecular components that might represent novel therapeutic targets. One challenge, that is the focus of this review, is the reprogramming of the altered metabolism of a cancer cell toward that of un-transformed cell. The anti-hyperglicemic agent, metformin has proven to be effective in reprogramming the metabolism of cancer cells even from those subpopulations endowed with cancer stem like features and very high chemoresistenace to conventional anticancer treatments. A functional interplay involving selective modulation of microRNAs (miRNAs) takes place along the anticancer metabolic effects exerted by metformin. The implications of this interplay will be also discussed in this review

The Adult Autism Subthreshold Spectrum (AdAS) model: A neurodevelopmental approach to mental disorders

A growing interest has been devoted to adult presentations of Autism Spectrum Disorders. This led to focus on comorbidity between ASD and other mental disorders, mainly (but notlimited to) Borderline Personality Disorders, Post Traumatic Stress Disorders, Mood Disorders and Eating Disorders. The presence of any psychiatric comorbidity can mask ASD, in particular in subjects with no intellectual impairment. To address this psychopathological issue, studies adopting the AdAS questionnaire, an instrument with strong convergent validity with alternative dimensional measures of ASD and excellent internal consistency and test-retest reliability, able to detect subthreshold forms of ASD in adulthood, have been reviewed. Based on these evidences, the Subthreshold Autism Spectrum Model has been developed,which includes threshold-level manifestations but also mild/atypical symptoms of the disorder, gender-specific features, behavioral manifestations and personality traits associated with ASD. This model encompasses, although not coinciding with, the Broad Autism Phenotype. This is a subthreshold form of autism described in the context of the neurodevelopmental trajectory that – starting from autistic traits – might lead to the broad range of mental disorders. Therefore, the Adult Autism Spectrum can be considered a transnosographic dimension. This approach should help to detect individual features for certain autistic cognitive and behavioural patterns that may predispose to other mental disorders

Urinary estrogen metabolites and prostate cancer : a case-control study and meta-analysis

Objective: To investigate prostate cancer (Pca) risk in relation to estrogen metabolism, expressed as urinary 2-hydroxyestrone (2-OHE1), 16α-hydroxyestrone (16α-OHE1) and 2-OHE1 to 16α-OHE1 ratio. Methods: We conducted a case-control study within the Western New York Health Cohort Study (WNYHCS) from 1996 to 2001. From January 2003 through September 2004, we completed the re-call and follow-up of 1092 cohort participants. Cases (n = 26) and controls (n = 110) were matched on age, race and recruitment period according to a 1:4 ratio. We used the unconditional logistic regression to compute crude and adjusted odds ratios (OR) and 95% confident interval (CI) of Pca in relation to 2-OHE1, 16αOHE1 and 2-OHE1 to 16α-OHE1 by tertiles of urine concentrations (stored in a biorepository for an average of 4 years). We identified age, race, education and body mass index as covariates. We also conducted a systematic review of the literature which revealed no additional studies, but we pooled the results from this study with those from a previously conducted case-control study using the DerSimonian-Laird random effects method. Results: We observed a non-significant risk reduction in the highest tertile of 2-OHE1 (OR 0.72, 95% CI 0.25-2.10). Conversely, the odds in the highest tertile of 16α-OHE1 showed a non-significant risk increase (OR 1.76 95% CI 0.62-4.98). There was a suggestion of reduced Pca risk for men in the highest tertile of 2-OHE1 to 16α-OHE1 ratio (OR 0.56, 95% CI 0.19-1.68). The pooled estimates confirmed the association between an increased Pca risk and higher urinary levels of 16α-OHE1 (third vs. first tertile: OR 1.82, 95% CI 1.09-3.05) and the protective effect of a higher 2-OHE 1 to 16α-OHE1 ratio (third vs. first tertile: OR 0.53, 95% CI 0.31-0.90). Conclusion: Our study and the pooled results provide evidence for a differential role of the estrogen hydroxylation pathway in Pca development and encourage further study

Metabolic syndrome and postmenopausal breast cancer in the ORDET cohort : a nested case-control study

Background and aims: The increase in breast cancer incidence over recent decades has been accompanied by an increase in the frequency of metabolic syndrome. Several studies suggest that breast cancer risk is associated with the components of metabolic syndrome (high serum glucose and triglycerides, low HDL-cholesterol, high blood pressure, and abdominal obesity), but no prospective study has investigated risk in relation to the presence of explicitly defined metabolic syndrome. We investigated associations between metabolic syndrome, its components, and breast cancer risk in a nested case-control study on postmenopausal women of the ORDET cohort. Methods and results: After a median follow-up of 13.5 years, 163 women developed breast cancer; metabolic syndrome was present in 29.8%. Four matched controls per case were selected by incidence density sampling, and rate ratios were estimated by conditional logistic regression. Metabolic syndrome (i.e. presence of three or more metabolic syndrome components) was significantly associated with breast cancer risk (rate ratio 1.58 [95% confidence interval 1.07-2.33]), with a significant risk increase for increasing number of components (P for trend 0.004). Among individual metabolic syndrome components, only low serum HDL-cholesterol and high triglycerides were significantly associated with increased risk. Conclusions: This prospective study indicates that metabolic syndrome is an important risk factor for breast cancer in postmenopausal women. Although serum HDL-cholesterol and triglycerides had the strongest association with breast cancer, all components may contribute to increased risk by multiple interacting mechanisms. Prevention or reversal of metabolic syndrome by life-style changes may be effective in preventing breast cancer in postmenopausal women

A novel approach to breast cancer prevention: reducing excessive ovarian androgen production in elderly women

Minimizing endogenous estrogen production and activity in women at high risk for breast cancer is a prominent approach to prevention of the disease. A number of clinical trials have shown that the administration of selective-estrogen receptor modulators or aromatase inhibitors significantly reduces the incidence of breast cancer in healthy women. Unfortunately, these drugs often produce adverse effects on the quality of life and are, therefore, poorly accepted by many women, even those who are at high risk for breast cancer. We propose a novel alternative approach to decreasing estrogen production: suppression of ovarian synthesis of the androgen precursors of estrogens by administration of long-acting gonadotropin-releasing hormone analogs to women with ovarian stromal hyperplasia. The specific target population would be elderly postmenopausal women, at increased risk of breast cancer, and with high blood levels of testosterone, marker of ovarian hyperandrogenemia, and recognized factor of risk for breast cancer. Testosterone levels are measured at baseline to identify women at risk and during the follow-up to evaluate the effectiveness of therapy. The postmenopausal ovary is an important source of excessive androgen production which originates from the ovarian interstitial cell hyperplasia frequently present in breast cancer patients. We propose to counter the source of androgen excess in women with ovarian stromal hyperplasia, thus reducing the substrate for estrogen formation without completely inhibiting estrogen synthesis. Available evidence indicates that gonadotropin-releasing hormone analogs can be safely used for breast cancer prevention in postmenopausal women

In vivo and in vitro evidence that intrinsic upper- and lower-limb skeletal muscle function is unaffected by ageing and disuse in oldest-old humans

Aim: To parse out the impact of advanced ageing and disuse on skeletal muscle function, we utilized both in vivo and in vitro techniques to comprehensively assess upper- and lower-limb muscle contractile properties in 8 young (YG; 25 6 years) and 8 oldest-old mobile (OM; 87 5 years) and 8 immobile (OI; 88 4 years) women. Methods: In vivo, maximal voluntary contraction (MVC), electrically evoked resting twitch force (RT), and physiological cross-sectional area (PCSA) of the quadriceps and elbow flexors were assessed. Muscle biopsies of the vastus lateralis and biceps brachii facilitated the in vitro assessment of single fibre-specific tension (Po). Results: In vivo, compared to the young, both the OM and OI exhibited a more pronounced loss of MVC in the lower limb [OM (60%) and OI (75%)] than the upper limb (OM = 51%; OI = 47%). Taking into account the reduction in muscle PCSA (OM = 10%; OI = 18%), only evident in the lower limb, by calculating voluntary muscle-specific force, the lower limb of the OI (40%) was more compromised than the OM (13%). However, in vivo, RT in both upper and lower limbs (approx. 9.8 N m cm 2) and Po (approx. 123 mN mm 2), assessed in vitro, implies preserved intrinsic contractile function in all muscles of the oldest-old and were well correlated (r = 0.81). Conclusion: These findings suggest that in the oldest-old, neither advanced ageing nor disuse, per se, impacts intrinsic skeletal muscle function, as assessed in vitro. However, in vivo, muscle function is attenuated by age and exacerbated by disuse, implicating factors other than skeletal muscle, such as neuromuscular control, in this diminution of function. Keywords in vitro, in vivo, oldest-old, sarcopeni

Estrogen metabolism and mammographic density in postmenopausal women : a cross-sectional study

Background: Prospective studies have consistently found that postmenopausal breast cancer risk increases with circulating estrogens; however, findings from studies of estrogens and mammographic density (MD), an intermediate marker of breast cancer risk, have been inconsistent. We investigated the cross-sectional associations of urinary estrogens, and their 2-, 4-, and 16-hydroxylated metabolites with MD. Methods: Postmenopausal women without breast cancer (n = 194), ages 48 to 82 years, and reporting no current menopausal hormone therapy use were enrolled at a clinic in Western NY in 2005. Urinary estrogens and estrogen metabolites were measured using mass spectrometry. Percent MD and dense area (cm2) were measured using computer-assisted analyses of digitized films. Linear regression models were used to estimate associations of log-transformed estrogen measures with MD while adjusting for age, body mass index (BMI), parity, and past hormone therapy use. Results: Urinary concentrations of most individual estrogens and metabolites were not associated with MD; however, across the interdecile range of the ratio of parent estrogens (estrone and estradiol) to their metabolites, MD increased by 6.8 percentage points (P = 0.02) and dense area increased by 10.3 cm2 (P = 0.03). Across the interdecile ranges of the ratios of 2-, 4-, and 16-hydroxylation pathways to the parent estrogens, MD declined by 6.2 (P = 0.03), 6.4 (P = 0.04), and 5.7 (P = 0.05) percentage points, respectively. All associations remained apparent in models without adjustment for BMI. Conclusion: In this study of postmenopausal women, less extensive hydroxylation of parent estrogens was associated with higher MD. Impact: Hydroxylation of estrogens may modulate postmenopausal breast cancer risk through a pathway involving MD

Performance of three model-based iterative reconstruction algorithms using a CT task-based image quality metric

In this study we evaluated the task-based image quality of a low contrast clinical task for the abdomen protocol (e.g., pancreatic tumour) of three different CT vendors, exploiting three model-based iterative reconstruction (MBIR) levels. We used three CT systems equipped with a full, partial, advanced MBIR algorithms. Acquisitions were performed on a phantom at three dose levels. Acquisitions were reconstructed with a standard kernel, using filtered back projection algorithm (FBP) and three levels of the MBIR. The noise power spectrum (NPS), the normalized one (nNPS) and the task-based transfer function (TTF) were computed following the method proposed by the American Association of Physicists in Medicine task group report-233 (AAPM TG-233). Detectability index (d') of a small lesion (small feature; 100 HU and 5-mm diameter) was calculated using non-prewhitening with eye-filter model observer (NPWE).The nNPS, NPS and TTF changed differently depending on CT system. Higher values of d' were obtained with advanced-MBIR, followed by full-MBIR and partial-MBIR.Task-based image quality was assessed for three CT scanners of different vendors, considering a clinical question. Detectability can be a tool for protocol optimisation and dose reduction since the same dose levels on different scanners correspond to different d' values.Comment: 7 pages, 5 figures, 3 table

Agave negatively regulates YAP and TAZ transcriptionally and post-translationally in osteosarcoma cell lines

Osteosarcoma (OS) is the most aggressive type of primary solid tumor that develops in bone. Whilst conventional chemotherapy can improve survival rates, the outcome for patients with metastatic or recurrent OS remains poor, so novel treatment agents and strategies are required. Research into new anticancer therapies has paved the way for the utilisation of natural compounds as they are typically less expensive and less toxic compared to conventional chemotherapeutics. Previously published works indicate that Agave exhibits anticancer properties, however potential molecular mechanisms remain poorly understood. In the present study, we investigate the anticancer effects of Agave leaf extract in OS cells suggesting that Agave inhibits cell viability, colony formation, and cell migration, and can induce apoptosis in OS cell lines. Moreover, Agave sensitizes OS cells to cisplatin (CDDP) and radiation, to overcome chemo- and radio-resistance. We demonstrate that Agave extract induces a marked decrease of Yes Associated Protein (YAP) and Tafazzin (TAZ) mRNA and protein expression upon treatment. We propose an initial mechanism of action in which Agave induces YAP/TAZ protein degradation, followed by a secondary event whereby Agave inhibits YAP/TAZ transcription, effectively deregulating the Nuclear Factor kappa B (NF-\u3baB) p65:p50 heterodimers responsible for transcriptional induction of YAP and TAZ