Structural network heterogeneities and network dynamics: a possible dynamical mechanism for hippocampal memory reactivation

The hippocampus has the capacity for reactivating recently acquired memories [1-3] and it is hypothesized that one of the functions of sleep reactivation is the facilitation of consolidation of novel memory traces [4-11]. The dynamic and network processes underlying such a reactivation remain, however, unknown. We show that such a reactivation characterized by local, self-sustained activity of a network region may be an inherent property of the recurrent excitatory-inhibitory network with a heterogeneous structure. The entry into the reactivation phase is mediated through a physiologically feasible regulation of global excitability and external input sources, while the reactivated component of the network is formed through induced network heterogeneities during learning. We show that structural changes needed for robust reactivation of a given network region are well within known physiological parameters [12,13].Comment: 16 pages, 5 figure

THE SAMOTHRACE EARTHQUAKE OF MAY 2014 AND THE DISPLACEMENTS ESTIMATIONS USING PERMANENT GPS STATIONS DATA

Η συμβολή των δικτύων GPS στην παρακολούθηση σεισμικών φαινομένων είναι σημαντική καθώς παρέχει άμεση γεωμετρική πληροφορία στο γήινο φλοιό χρησιμοποιώντας δορυφορικές παρατηρήσεις. Στη παρούσα μελέτη εξετάζονται οι μετακινήσεις στη θέση των μόνιμων σταθμών GPS, που προέρχονται από έντονα σεισμικά φαινόμενα στη περιοχή του Β. Αιγαίου μετά τον έντονο σεισμό στις 24 Μαΐου του 2014. Οι μετακινήσεις στο οριζόντιο επίπεδο μετά το σεισμό για το νησί της Σαμοθράκης εκτιμήθηκαν σε 9.4 cm και για το νησί της Λήμνου σε 5.2 cm αντιστοίχως. Διάστημα μελέτης επτά ημερών ήταν ικανό για να φανεί ότι η παραμόρφωση εξελίχθηκε σταδιακά σε διάστημα δύο ημερών.The contribution of GPS networks in monitoring seismic events is important because they can provide a direct geometrical information on the Earth's crust using satellite observations In this study position displacements of permanent GPS stations are determined due to intense seismic events in the North Aegean area after the strong earthquake on May 24, 2014. The horizontal coseismic displacements for the Samothrace Island were estimated at 9.4 cm and for Lemnos Island at 5.2 cm respectively. A study period of seven days was enough to show that the deformation evolved into two days

High-level secretion of native recombinant human calreticulin in yeast

Additional file 2. Elution profiles of recombinant CRT in anion-exchange chromatography. Separation of CRT from S. cerevisiae (A and B) was performed on a pre-packed 5 ml Q-Sepharose column (GE LifeSciences cat. no. 17-5156-01), equilibrated with 20 mM l-His, pH 5.5, 100 mM NaCl buffer, in 15 column volumes linear gradient from 100 mM to 500 mM NaCl. Separation of CRT from P. pastoris (C and D) was performed on a 15 ml Q-Sepharose sorbent (GE LifeSciences cat. no. 17-0510-10) packed into the XK 16/20 column (GE Lifesciences, cat. no. 28-9889-37), equilibrated with 20 mM l-His, pH 5.5, 100 mM NaCl buffer, in 10 column volumes linear gradient from 100 to 500 mM NaCl. Elution profiles (A and C) and SDS-PAGE gels of corresponding fractions (B and D) are shown. Dashed lines define fractions that were pooled and used for further experiments with purified protein

Transcriptional evidence for the "Reverse Warburg Effect" in human breast cancer tumor stroma and metastasis: Similarities with oxidative stress, inflammation, Alzheimer's disease, and "Neuron-Glia Metabolic Coupling"

Caveolin-1 (-/-) null stromal cells are a novel genetic model for cancer-associated fibroblasts and myofibroblasts. Here, we used an unbiased informatics analysis of transcriptional gene profiling to show that Cav-1 (-/-) bone-marrow derived stromal cells bear a striking resemblance to the activated tumor stroma of human breast cancers. More specifically, the transcriptional profiles of Cav-1 (-/-) stromal cells were most closely related to the primary tumor stroma of breast cancer patients that had undergone lymph-node (LN) metastasis. This is consistent with previous morphological data demonstrating that a loss of stromal Cav-1 protein (by immuno-histochemical staining in the fibroblast compartment) is significantly associated with increased LN-metastasis. We also provide evidence that the tumor stroma of human breast cancers shows a transcriptional shift towards oxidative stress, DNA damage/repair, inflammation, hypoxia, and aerobic glycolysis, consistent with the "Reverse Warburg Effect". Finally, the tumor stroma of "metastasis-prone" breast cancer patients was most closely related to the transcriptional profiles derived from the brains of patients with Alzheimer's disease. This suggests that certain fundamental biological processes are common to both an activated tumor stroma and neuro-degenerative stress. These processes may include oxidative stress, NO over-production (peroxynitrite formation), inflammation, hypoxia, and mitochondrial dysfunction, which are thought to occur in Alzheimer's disease pathology. Thus, a loss of Cav-1 expression in cancer-associated myofibroblasts may be a protein biomarker for oxidative stress, aerobic glycolysis, and inflammation, driving the "Reverse Warburg Effect" in the tumor micro-environment and cancer cell metastasis

Disparities in care and outcomes for primary liver cancer in England during 2008–2018: a cohort study of 8.52 million primary care population using the QResearch database

Background: Liver cancer has one of the fastest rising incidence and mortality rates among all cancers in the UK, but it receives little attention. This study aims to understand the disparities in epidemiology and clinical pathways of primary liver cancer and identify the gaps for early detection and diagnosis of liver cancer in England. Methods: This study used a dynamic English primary care cohort of 8.52 million individuals aged ≥25 years in the QResearch database during 2008–2018, followed up to June 2021. The crude and age-standardised incidence rates, and the observed survival duration were calculated by sex and three liver cancer subtypes, including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (CCA), and other specified/unspecified primary liver cancer. Regression models were used to investigate factors associated with an incident diagnosis of liver cancer, emergency presentation, late stage at diagnosis, receiving treatments, and survival duration after diagnosis by subtype. Findings: 7331 patients were diagnosed with primary liver cancer during follow-up. The age-standardised incidence rates increased over the study period, particularly for HCC in men (increased by 60%). Age, sex, socioeconomic deprivation, ethnicity, and geographical regions were all significantly associated with liver cancer incidence in the English primary care population. People aged ≥80 years were more likely to be diagnosed through emergency presentation and in late stages, less likely to receive treatments and had poorer survival than those aged <60 years. Men had a higher risk of being diagnosed with liver cancer than women, with a hazard ratio (HR) of 3.9 (95% confidence interval 3.6–4.2) for HCC, 1.2 (1.1–1.3) for CCA, and 1.7 (1.5–2.0) for other specified/unspecified liver cancer. Compared with white British, Asians and Black Africans were more likely to be diagnosed with HCC. Patients with higher socioeconomic deprivation were more likely to be diagnosed through the emergency route. Survival rates were poor overall. Patients diagnosed with HCC had better survival rates (14.5% at 10-year survival, 13.1%–16.0%) compared to CCA (4.4%, 3.4%–5.6%) and other specified/unspecified liver cancer (12.5%, 10.1%–15.2%). For 62.7% of patients with missing/unknown stage in liver cancer, their survival outcomes were between those diagnosed in Stages III and IV. Interpretation: This study provides an overview of the current epidemiology and the disparities in clinical pathways of primary liver cancer in England between 2008 and 2018. A complex public health approach is needed to tackle the rapid increase in incidence and the poor survival of liver cancer. Further studies are urgently needed to address the gaps in early detection and diagnosis of liver cancer in England. Funding: The Early Detection of Hepatocellular Liver Cancer (DeLIVER) project is funded by Cancer Research UK (Early Detection Programme Award, grant reference: C30358/A29725)

PALAEOSEISMOLOGICAL INVESTIGATION OF THE GYRTONI FAULT (THESSALY, CENTRAL GREECE)

Two paleoseismological trenches were excavated across the Gyrtoni Fault in NE Thessaly and studied in order to understand the recent seismotectonic behavior of this structure. Twenty five fluvial-colluvial sediment and pottery samples from both the upthrown and the downthrown fault blocks were investigated. Optically Stimulated Luminescence (OSL) dating has been applied to date both sedimentary depositspalaeosoils and pottery fragments. Paleoseismological analysis of the two trenches indicates evidence of three surface faulting events in the time span between 1.42 ±0.06 ka and 5.59 ± 0.13 ka. The observed vertical displacement per event of ~0.50 m corresponds to an Mw 6.5 ± 0.1 earthquake. An average fault slip rate of 0.41 ± 0.01 mm/yr and an average recurrence of 1.39 ± 0.14 ka for earthquakes were estimated. The results documented the activity of the fault and since the return period from the most recent event (minimum age 1.42 ± 0.06 ka) has expired, the possibility for reactivation of this active structure in the near future should be included in Seismic Hazard Assessment

Reference range of liver corrected T1 values in a population at low risk for fatty liver disease-a UK Biobank sub-study, with an appendix of interesting cases

Purpose: Corrected T1 (cT1) value is a novel MRI-based quantitative metric for assessing a composite of liver inflammation and fibrosis. It has been shown to distinguish between non-alcoholic fatty liver disease (NAFL) and non-alcoholic steatohepatitis. However, these studies were conducted in patients at high risk for liver disease. This study establishes the normal reference range of cT1 values for a large UK population, and assesses interactions of age and gender. Methods: MR data were acquired on a 1.5T system as part of the UK Biobank Imaging Enhancement study. Measures for Proton Density Fat Fraction and cT1 were calculated from the MRI data using a multi-parametric MRI software application. Data that did not meet quality criteria were excluded from further analysis. Inter and intra-reader variability was estimated in a set of data. A cohort at low risk for NAFL was identified by excluding individuals with BMI ≥ 25kg/m2 and PDFF ≥ 5%. Of the 2816 participants with data of suitable quality, 1037 (37%) were classified as at low risk. Results: The cT1 values in the low risk population ranged from 573 to 852 ms with a median of 666 ms and interquartile range from 643-694 ms. Iron correction of T1 was necessary in 36.5% of this reference population. Age and gender had minimal effect on cT1 values. Conclusion: The majority of cT1 values are tightly clustered in a population at low risk for NAFL; suggesting it has the potential to serve as a new quantitative imaging biomarker for studies of liver health and disease

Differential impact of chronic stress along the hippocampal dorsal–ventral axis

First published online 06 February 2014Stress impacts differently in distinct brain regions. However, so far few studies have focused on the differential responses triggered by stressful stimuli on the intrinsic functional heterogeneity of the hippocampal axis. In this study, we assessed the functional and structural alterations caused by exposure to a chronic unpredictable stress (CUS) paradigm on the dorsal-ventral axis of the hippocampus. The morphological analysis demonstrated that CUS had opposite outcomes in the structure of the dorsal (DH) and ventral hippocampus (VH): whereas in the DH, stress triggered a volumetric reduction as a result of atrophy of CA3 and CA1 apical dendrites, in the VH there was an increase in hippocampal volume concurrent with the increase of CA3 apical dendrites. In parallel, electrophysiological data revealed that stress led to a decrease in VH LTD. In summary, the present work showed that stress impacts differently on the structure and function of the DH and VH which contributes to better understand the overall spectrum of the central effects of stress.Pinto V and Mota C were supported by Fundacao para a Ciencia e Tecnologia (FCT) grants (SFRH/BPD/69132/2010; SFRH/BD/81881/2011, respectively). This work was supported by an FCT grant (PTDC/SAU-NSC/120590/2010). The authors declare no competing financial interests