Cytomegalovirus (CMV) is the most prevalent infectious agent causing neurological dysfunction in the developing brain. This study analysed the different patterns of tissue damage, particularly in the ...brain, of fetuses with documented CMV infection. We studied 45 fetuses at 20-21 weeks of gestation with congenital CMV infection documented by invasive positive prenatal diagnosis. At the time of amniocentesis, abnormal ultrasound findings had been recorded for 13 of the 45 fetuses (29%). Histological and immunohistochemical characterization was performed on the placenta, brain, heart, lung, liver, kidney, and pancreas. The different degrees of brain damage were correlated with tissue viral load, inflammatory response, placental functionality, and extramedullary haematopoiesis. Even though a high CMV load was detected in all amniotic fluids, brain infection occurred in only 62% of the fetuses and with different degrees of severity. Tissues with a low viral load showed a globally weak inflammatory response, and fetuses had only mild brain damage, whereas tissues with a high CMV load showed prominent infiltration of the activated cytotoxic CD8+ T-lymphocytes responsible for immune-mediated damage. Furthermore, severe placental infection was associated with diffuse villitis and necrosis, consistent with functional impairment and possible consequent hypoxic cerebral damage. Brain injury induced by CMV congenital infection may be the result of uncontrolled viral replication, immune-mediated damage by cytotoxic CD8+ T-lymphocytes, and, in the presence of placental insufficiency, fetal hypoxia.
Loss of phosphatase and tensin homologue deleted in chromosome 10 (PTEN) function in advanced colorectal cancer (CRC) may represent one of the resistance mechanisms to cetuximab by interfering with ...the epidermal growth factor receptor signal transduction pathway.
PTEN expression tested by indirect immunofluorescence was evaluated both on primary (n=43) and on metastatic (n=24) sites in CRC patients treated with cetuximab.
The loss of PTEN expression tested on metastatic sites was negatively associated with response (100% progressive disease (PD) in PTEN-negative cases vs 30% PD in PTEN-positive cases; P<0.05), PFS (0.8 vs 8.2 months; P<0.001) and OS (2.9 vs 14.2 months; P<0.001).
A potential role of PTEN in the anti-tumour activity of cetuximab could be hypothesised.
Along with neuronal mechanisms devoted to memory consolidation –including long term potentiation of synaptic strength as prominent electrophysiological correlate, and inherent dendritic spines ...stabilization as structural counterpart– negative control of memory formation and synaptic plasticity has been described at the molecular and behavioral level. Within this work, we report a role for the epigenetic corepressor Lysine Specific Demethylase 1 (LSD1) as a negative neuroplastic factor whose stress-enhanced activity may participate in coping with adverse experiences. Constitutively increasing LSD1 activity via knocking out its dominant negative splicing isoform neuroLSD1 (neuroLSD1KO mice), we observed extensive structural, functional and behavioral signs of excitatory decay, including disrupted memory consolidation. A similar LSD1 increase, obtained with acute antisense oligonucleotide-mediated neuroLSD1 splicing knock down in primary neuronal cultures, dampens spontaneous glutamatergic transmission, reducing mEPSCs. Remarkably, LSD1 physiological increase occurs in response to psychosocial stress-induced glutamatergic signaling. Since this mechanism entails neuroLSD1 splicing downregulation, we conclude that LSD1/neuroLSD1 ratio modulation in the hippocampus is instrumental to a negative homeostatic feedback, restraining glutamatergic neuroplasticity in response to glutamate. The active process of forgetting provides memories with salience. With our work, we propose that softening memory traces of adversities could further represent a stress-coping process in which LSD1/neuroLSD1 ratio modulation may help preserving healthy emotional references.
Comparison of fine and coarse fractions in terms of sources and dynamics is scarce in southeast Mediterranean countries; differences are relevant because of the importance of natural sources like sea ...spray and Saharan dust advection, because most of the monitoring networks are limited to PM10. In this work, the main seasonal variabilities of sources and processes involving fine and coarse PM (particulate matter) were studied at the Environmental-Climate Observatory of Lecce (Southern Italy). Simultaneous PM2.5 and PM10 samples were collected between July 2013 and July 2014 and chemically analysed to determine concentrations of several species: OC (organic carbon) and EC (elemental carbon) via thermo-optical analysis, 9 major ions via IC, and 23 metals via ICP-MS. Data was processed through mass closure analysis and Positive Matrix Factorization (PMF) receptor model characterizing seasonal variabilities of nine sources contributions. Organic and inorganic secondary aerosol accounts for 43% of PM2.5 and 12% of PM2.5–10 with small seasonal changes. SIA (secondary inorganic aerosol) seasonal pattern is opposite to that of SOC (secondary organic carbon). SOC is larger during the cold period, sulphate (the major contributor to SIA) is larger during summer. Two forms of nitrate were identified: NaNO3, correlated with chloride depletion and aging of sea-spray, mainly present in PM2.5–10; NH4NO3 more abundant in PM2.5. Biomass burning is a relevant source with larger contribution during autumn and winter because of the influence of domestic heating, however, is not negligible in spring and summer, because of the contributions of fires and agricultural practices. Mass closure analysis and PMF results identify two soil sources: crustal associated to long range transport and carbonates associated to local resuspended dust. Both sources contributes to the coarse fraction and have different dynamics with crustal source contributing mainly in high winds from SE conditions and carbonates during high winds from North direction.
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•Composition and sources of PM2.5 and PM2.5–10 are investigated in South-eastern Italy.•Secondary organic and inorganic components were 43% of PM2.5 with opposite seasonal trends.•Two forms of nitrate were observed: sodium nitrate and ammonium nitrate (only in winter).•PMF and mass-closure identified two soil sources accounting for 29% of PM2.5–10.•Biomass burning is an important source at the urban background site even during warm seasons.
To study the influence of polluted air-mass transport carrying ozone （O3） and black carbon （BC） in the high Himalayas, since March 2006 the Nepal Climate Observatory at Pyramid （NCO-P） GAW-WMO global ...station （Nepal, 5079 m a.s.l.） is operative. During the first 5-year measurements, the O3 and BC concentrations have shown a mean value of 48 ± 12 ppb （± standard deviation） and 208 ± 374 ng/m3, respectively. Both O3 and BC showed well defined seasonal cycles with maxima during pre-monsoon （O3 ： 61.3 ± 7.7 ppbV; BC： 444 ± 433 ng/m3） and minima during the summer monsoon （O3 ： 40.1 ± 12.4 ppbV; BC： 64 ± 101 ng/m3）. The analysis of the days characterised by the presence of a significant BC increase with respect to the typical seasonal cycle identified 156 days affected by ＂acute＂ pollution events, corresponding to 9.1% of the entire data-set. Such events mostly occur in the pre-monsoon period, when the O3 diurnal variability is strongly related to the transport of polluted air-mass rich on BC. On average, these ＂acute＂ pollution events were characterised by dramatic increases of BC （352%） and O3 （29%） levels compared with the remaining days.
A shallow ice core was extracted at the summit of Mera Peak at 6376 m a.s.l. in the southern flank of the Nepalese Himalaya range. From this core, we reconstructed the seasonal deposition fluxes of ...dust and refractory black carbon (rBC) since 1999. This archive presents well preserved seasonal cycles based on a monsoonal precipitation pattern. According to the seasonal precipitation regime in which 80% of annual precipitation falls between June and September, we estimated changes in the concentrations of these aerosols in surface snow. The analyses revealed that mass fluxes are a few orders of magnitude higher for dust (10.4 ± 2.8 g m−2 yr−1 than for rBC (7.9 ± 2.8 mg m−2 yr−1). The relative lack of seasonality in the dust record may reflect a high background level of dust inputs, whether from local or regional sources. Over the 10-year record, no deposition flux trends were detected for any of the species of interest. The data were then used to simulate changes in the surface snow albedo over time and the potential melting caused by these impurities. Mean potential melting caused by dust and rBC combined was 713 kg m−2 yr−1, and for rBC alone, 342 kg m−2 yr−1 for rBC under certain assumptions. Compared to the melting rate measured using the mass and energy balance at 5360 m a.s.l. on Mera Glacier between November 2009 and October 2010, i.e. 3000 kg m−2 yr−1 and 3690 kg m−2 yr−1 respectively, the impact of rBC represents less than 16% of annual potential melting while the contribution of dust and rBC combined to surface melting represents a maximum of 26%. Over the 10-year period, rBC variability in the ice core signal primarily reflected variability of the monsoon signal rather than variations in the intensity of emissions.
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