Sedimentation and time-of-transition techniques for measuring grain-size distributions in lagoonal flats: comparability of results

A comparative study was performed of three instruments used to measure the grain-size distribution of thirty sediment samples from shallow lagoonal flats: the hydrometer, the Sedigraph 5100 and the CIS-1. The hydrometer and Sedigraph are based on sedimentation whereas the CIS-1 uses the time of transition. The percentage of the samples accounted for by the <8 lm fraction was not affected by the technique used, but this was not the case with the clay fraction (<2 lm). Due to its relative independence from the analytical method applied, the <8 lm fraction can be used in ternary diagram classifications. This fraction also has an environmental significance in coastal lagoons in terms of hydrodynamics, organic enrichment and macrozoobenthos assemblages. The linear relationships obtained in this study may provide useful operational indications for similar studies

Notch signaling sustains the expression of Mcl-1 and the activity of eIF4E to promote cell survival in CLL

In chronic lymphocytic leukemia (CLL), Notch1 and Notch2 signaling is constitutively activated and contributes to apoptosis resistance. We show that genetic inhibition of either Notch1 or Notch2, through small-interfering RNA, increases apoptosis of CLL cells and is associated with decreased levels of the anti-apoptotic protein Mcl-1. Thus, Notch signaling promotes CLL cell survival at least in part by sustaining Mcl-1 expression. In CLL cells, an enhanced Notch activation also contributes to the increase in Mcl-1 expression and cell survival induced by IL-4.Mcl-1 downregulation by Notch targeting is not due to reduced transcription or degradation by caspases, but in part, to increased degradation by the proteasome. Mcl-1 downregulation by Notch targeting is also accompanied by reduced phosphorylation of eukaryotic translation initiation factor 4E (eIF4E), suggesting that this protein is another target of Notch signaling in CLL cells.Overall, we show that Notch signaling sustains CLL cell survival by promoting Mcl-1 expression and eIF4E activity, and given the oncogenic role of these factors, we underscore the therapeutic potential of Notch inhibition in CLL

The Rat Medial Prefrontal Cortex Exhibits Flexible Neural Activity States during the Performance of an Odor Span Task

Medial prefrontal cortex (mPFC) activity is fundamental for working memory (WM), attention, and behavioral inhibition; however, a comprehensive understanding of the neural computations underlying these processes is still forthcoming. Toward this goal, neural recordings were obtained from the mPFC of awake, behaving rats performing an odor span task of WM capacity. Neural populations were observed to encode distinct task epochs and the transitions between epochs were accompanied by abrupt shifts in neural activity patterns. Putative pyramidal neuron activity increased earlier in the delay for sessions where rats achieved higher spans. Furthermore, increased putative interneuron activity was only observed at the termination of the delay thus indicating that local processing in inhibitory networks was a unique feature to initiate foraging. During foraging, changes in neural activity patterns associated with the approach to a novel odor, but not familiar odors, were robust. Collectively, these data suggest that distinct mPFC activity states underlie the delay, foraging, and reward epochs of the odor span task. Transitions between these states likely enables adaptive behavior in dynamic environments that place strong demands on the substrates of working memory

Biogenic sediments from coastal ecosystems to beach-dune systems: implications for the adaptation of mixed and carbonate beaches to future sea level rise

Coastal ecosystems produce and store carbonate particles, which play a significant role in the carbonate dynamics of coastal areas and may contribute to the sediment budget of adjacent beaches. In the nearshore seabed of temperate zones (e.g. Mediterranean Sea and South Australia), marine biogenic carbonates are mainly produced inside sea-grass meadows. This study quantifies the contribution of biogenic sediments, mainly produced in Posidonia oceanica seagrass meadows and secondarily in photophilic algal communities, to the sediment budget of a Mediterranean beach-dune system (San Giovanni beach, western Sardinia, western Mediterranean Sea). A set of geophysical, petrographic and sedimentological data was used to estimate the sediment volume and composition of the beach-dune system as a whole. The San Giovanni beach-dune system contains 3797000 +/- 404000 t of sediment, 83% (3137000 +/- 404000 t) of which is located in the coastal wedge, 16% (619000 +/- 88000 t) in the dune fields and 1% (41000 +/- 15000 t) in the sub-aerial beach. The sediments are composed of mixed modern bioclastic and relict bioclastic and non-bioclastic grains from various sources. The system receives a large input of modern bioclastic grains, mainly composed of rhodophytes, molluscs and bryozoans, which derive from sediment production of present-day carbonate factories, particularly P. oceanica seagrass meadows. Radiocarbon dating of modern bioclastic grains indicated that they were produced during the last 4.37 kyr. This value was used to estimate the longterm deposition rates of modern bioclastic sediments in the various beach compartments. The total deposition rate of modern bioclastic grains is 46000 +/- 5000 t century 1, mainly deposited in the coastal wedge (39000 +/- 4000 t century(-1)) and dunes (7000 +/- 1000 t century(-1)), and 46 000 t represents similar to 1.2% of the total beach-dune sediment mass. Carbonate production from coastal ecosystems was estimated to be 132000/307000 t century(-1), 28% (15%/34 %) of which is transported to the beach-dune system, thus significantly contributing to the beach sediment budget.The contribution to the beach sediment budget represents a further ecosystem service, which our data can help quantify, provided by P. oceanica. The value of this sediment-supply service is in addition to the other important ecological services provided by seagrass meadows. The dependence of the beach sediment budget on carbonate production associated with coastal ecosystems has several implications for the adaptation of mixed and carbonate beaches to the loss of seagrass meadows due to local impacts and the changes expected to occur over the next few decades in coastal ecosystems following sea level rise

An Historical Overview: The Discovery of How NK Cells Can Kill Enemies, Recruit Defense Troops, and More

Natural killer (NK) cells were originally defined as effector lymphocytes of innate immunity characterized by the unique ability of killing tumor and virally infected cells without any prior priming and expansion of specific clones. The \u201cmissing-self\u201d theory, proposed by Klas Karre, the seminal discovery of the first prototypic HLA class I-specific inhibitory receptors, and, later, of the Natural Cytotoxicity Receptors (NCRs) by Alessandro Moretta, provided the bases to understand the puzzling behavior of NK cells. Actually, those discoveries proved crucial also for many of the achievements that, along the years, have contributed to the modern view of these cells. Indeed, NK cells, besides killing susceptible targets, are now known to functionally interact with different immune cells, sense pathogens using TLR, adapt their responses to the local environment, and, even, mount a sort of immunological memory. In this review, we will specifically focus on the main activating NK receptors and on their crucial role in the ever-increasing number of functions assigned to NK cells and other innate lymphoid cells (ILCs)

NOTCH1 Aberrations in Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is an incurable B-cell neoplasm characterized by highly variable clinical outcomes. In recent years, genomic and molecular studies revealed a remarkable heterogeneity in CLL, which mirrored the clinical diversity of this disease. These studies profoundly enhanced our understanding of leukemia cell biology and led to the identification of new biomarkers with potential prognostic and therapeutic significance. Accumulating evidence indicates a key role of deregulated NOTCH1 signaling and NOTCH1 mutations in CLL. This review highlights recent discoveries that improve our understanding of the pathophysiological NOTCH1 signaling in CLL and the clinical impact of NOTCH1 mutations in retrospective and prospective trials. In addition, we discuss the rationale for a therapeutic strategy aiming at inhibiting NOTCH1 signaling in CLL, along with an overview on the currently available NOTCH1-directed approaches

Impact of contra-lateral breast reshaping on mammographic surveillance in women undergoing breast reconstruction following mastectomy for breast cancer

Background: The ultimate goal of breast reconstruction is to achieve symmetry with the contra-lateral breast. Contra-lateral procedures with wide parenchymal rearrangements are suspected to impair mammographic surveillance. This study aims to evaluate the impact on mammographic detection of mastopexies and breast reductions for contralateral adjustment in breast reconstruction. Patients and methods: We retrospectively evaluated 105 women affected by uni-lateral breast cancer who underwent mastectomy and immediate two-stage reconstruction between 2002 and 2007. We considered three groups according to the contra-lateral reshaping technique: mastopexy or breast reduction with inferior dermoglandular flap (group 1); mastopexy or breast reduction without inferior dermoglandular flap (group 2); no contra-lateral reshaping (group 3). We assessed qualitative mammographic variations and breast density in the three groups. Results: Statistically significant differences have been found when comparing reshaped groups with non reshaped groups regarding parenchymal distortions, skin thickening and stromal edema, but these differences did not affect cancer surveillance. The surveillance mammography diagnostic accuracy in contra-lateral cancer detection was not significantly different between the three groups (p ¼ 0.56), such as the need for MRI for equivocal findings at mammographic contra-lateral breast (p ¼ 0.77) and the need for core-biopsies to confirm mammographic suspect of contra-lateral breast cancer (p ¼ 0.90). Conclusions: This study confirms previous reports regarding the safety of mastopexies and breast reductions when performed in the setting of contra-lateral breast reshaping after breast reconstruction. Mammographic accuracy, sensitivity and specificity are not affected by the glandular re-arrangement. These results provide a further validation of the safety of current reconstructive paradigms

NOTCH1-mutated chronic lymphocytic leukemia displays high endoplasmic reticulum stress response with druggable potential

IntroductionConstitutive activation of NOTCH1-wild-type (NT1-WT) signaling is associated with poor outcomes in chronic lymphocytic leukemia (CLL), and NOTCH1 mutation (c.7541_7542delCT), which potentiates NOTCH1 signaling, worsens the prognosis. However, the specific mechanisms of NOTCH1 deregulation are still poorly understood. Accumulative evidence mentioned endoplasmic reticulum (ER) stress/unfolded protein response (UPR) as a key targetable pathway in CLL. In this study, we investigated the impact of NOTCH1 deregulation on CLL cell response to ER stress induction, with the aim of identifying new therapeutic opportunities for CLL.MethodsWe performed a bioinformatics analysis of NOTCH1-mutated (NT1-M) and NT1-WT CLL to identify differentially expressed genes (DEGs) using the rank product test. Quantitative real-time polymerase chain reaction (qPCR), Western blotting, cytosolic Ca2+, and annexin V/propidium iodide (PI) assay were used to detect curcumin ER stress induction effects. A median-effect equation was used for drug combination tests. The experimental mouse model Eμ-TCL1 was used to evaluate the impact of ER stress exacerbation by curcumin treatment on the progression of leukemic cells and NOTCH1 signaling.Results and discussionBioinformatics analysis revealed gene enrichment of the components of the ER stress/UPR pathway in NT1-M compared to those in NT1-WT CLL. Ectopic expression of NOTCH1 mutation upregulated the levels of ER stress response markers in the PGA1 CLL cell line. Primary NT1-M CLL was more sensitive to curcumin as documented by a significant perturbation in Ca2+ homeostasis and higher expression of ER stress/UPR markers compared to NT1-WT cells. It was also accompanied by a significantly higher apoptotic response mediated by C/EBP homologous protein (CHOP) expression, caspase 4 cleavage, and downregulation of NOTCH1 signaling in NT1-M CLL cells. Curcumin potentiated the apoptotic effect of venetoclax in NT1-M CLL cells. In Eμ-TCL1 leukemic mice, the administration of curcumin activated ER stress in splenic B cells ex vivo and significantly reduced the percentage of CD19+/CD5+ cells infiltrating the spleen, liver, and bone marrow (BM). These cellular effects were associated with reduced NOTCH1 activity in leukemic cells and resulted in prolonged survival of curcumin-treated mice. Overall, our results indicate that ER stress induction in NT1-M CLL might represent a new therapeutic opportunity for these high-risk CLL patients and improve the therapeutic effect of drugs currently used in CLL

Engineering Reconnaissance Following the October 2016 Central Italy Earthquakes - Version 2

Between August and November 2016, three major earthquake events occurred in Central Italy. The first event, with M6.1, took place on 24 August 2016, the second (M5.9) on 26 October, and the third (M6.5) on 30 October 2016. Each event was followed by numerous aftershocks. As shown in Figure 1.1, this earthquake sequence occurred in a gap between two earlier damaging events, the 1997 M6.1 Umbria-Marche earthquake to the north-west and the 2009 M6.1 L’Aquila earthquake to the south-east. This gap had been previously recognized as a zone of elevated risk (GdL INGV sul terremoto di Amatrice, 2016). These events occurred along the spine of the Apennine Mountain range on normal faults and had rake angles ranging from -80 to -100 deg, which corresponds to normal faulting. Each of these events produced substantial damage to local towns and villages. The 24 August event caused massive damages to the following villages: Arquata del Tronto, Accumoli, Amatrice, and Pescara del Tronto. In total, there were 299 fatalities (www.ilgiornale.it), generally from collapses of unreinforced masonry dwellings. The October events caused significant new damage in the villages of Visso, Ussita, and Norcia, although they did not produce fatalities, since the area had largely been evacuated. The NSF-funded Geotechnical Extreme Events Reconnaissance (GEER) association, with co-funding from the B. John Garrick Institute for the Risk Sciences at UCLA and the NSF I/UCRC Center for Unmanned Aircraft Systems (C-UAS) at BYU, mobilized a US-based team to the area in two main phases: (1) following the 24 August event, from early September to early October 2016, and (2) following the October events, between the end of November and the beginning of December 2016. The US team worked in close collaboration with Italian researchers organized under the auspices of the Italian Geotechnical Society, the Italian Center for Seismic Microzonation and its Applications, the Consortium ReLUIS, Centre of Competence of Department of Civil Protection and the DIsaster RECovery Team of Politecnico di Torino. The objective of the Italy-US GEER team was to collect and document perishable data that is essential to advance knowledge of earthquake effects, which ultimately leads to improved procedures for characterization and mitigation of seismic risk. The Italy-US GEER team was multi-disciplinary, with expertise in geology, seismology, geomatics, geotechnical engineering, and structural engineering. The composition of the team was largely the same for the two mobilizations, particularly on the Italian side. Our approach was to combine traditional reconnaissance activities of on-ground recording and mapping of field conditions, with advanced imaging and damage detection routines enabled by state-of-the-art geomatics technology. GEER coordinated its reconnaissance activities with those of the Earthquake Engineering Research Institute (EERI), although the EERI mobilization to the October events was delayed and remains pending as of this writing (April 2017). For the August event reconnaissance, EERI focused on emergency response and recovery, in combination with documenting the effectiveness of public policies related to seismic retrofit. As such, GEER had responsibility for documenting structural damage patterns in addition to geotechnical effects. This report is focused on the reconnaissance activities performed following the October 2016 events. More information about the GEER reconnaissance activities and main findings following the 24 August 2016 event, can be found in GEER (2016). The objective of this document is to provide a summary of our findings, with an emphasis of documentation of data. In general, we do not seek to interpret data, but rather to present it as thoroughly as practical. Moreover, we minimize the presentation of background information already given in GEER (2016), so that the focus is on the effects of the October events. As such, this report and GEER (2016) are inseparable companion documents. Similar to reconnaissance activities following the 24 August 2016 event, the GEER team investigated earthquake effects on slopes, villages, and major infrastructure. Figure 1.2 shows the most strongly affected region and locations described subsequently pertaining to: 1. Surface fault rupture; 2. Recorded ground motions; 3. Landslides and rockfalls; 4. Mud volcanoes; 5. Investigated bridge structures; 6. Villages and hamlets for which mapping of building performance was performed

Thirty-year changes (1970 to 2000) in bathymetry and sediment texture recorded in the Lagoon of Venice sub-basins, Italy.

A detailed comparison was made of two bathymetric charts of the Lagoon of Venice (LV) from 1970 and 2000, in tandem with a comparison of sediment grain size data. Analysis of the data revealed marked changes in both morphology and sedimentation, with more than 50% of the 400 km2 assessed in this study 15-20 cm shallower in 1970 than in 2000. The four sub-basins into which the LV is subdivided saw different patterns of change. The Northern basin A was identified as “pristine”, i.e. still in quasi-natural condition, with slight clay enrichment and a small degree of deepening (4-5 cm), essentially due to sea level rise (SLR). The bathymetry and sedimentology of the northern-central sub-basin B (identified as “urban”) and the southern-central basin C (identified as “open”) were affected by infill activities and excavation of industrial navigation channels in the 1970s, causing the loss of ~ 60 km2 of mudflats, and creating an “open” lagoon. The southernmost basin D (identified as “exploited-subsiding”) of the LV was found to be relatively unchanged and still in semi-natural condition. Comparison of sediment types showed depletion of fine-grained fractions ( 63 µm) was recorded, except in the southern-central sub-basin C where medium and coarse sand fractions declined. The results suggest that climate-related SLR accounts for a small fraction of bathymetric change, whilst variations in hydrodynamics (currents and wind patterns) and sediment supply are likely causal factors for the different evolution of the four sub-basins. Definition of the attributes of each sub-basin provided data that was essential not only for the LV but also for predicting the fate of transitional environments facing both anthropic (fishing, navigation, land use changes) as well natural (SLR, eustatism) forcing factors