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C5-substituted 2,4-diaminoquinazoline inhibitors of the decapping scavenger enzyme DcpS (DAQ-DcpSi) have been developed for the treatment of spinal muscular atrophy (SMA), which is caused by genetic deficiency in the Survival Motor Neuron (SMN) protein. These compounds are claimed to act as SMN2 transcriptional activators but data underlying that claim are equivocal. In addition it is unclear whether the claimed effects on SMN2 are a direct consequence of DcpS inhibitor or might be a consequence of lysosomotropism, which is known to be neuroprotective. DAQ-DcpSi effects were characterized in cells in vitro utilizing DcpS knockdown and 7-methyl analogues as probes for DcpS vs non-DcpS-mediated effects. We also performed analysis of Smn transcript levels, RNA-Seq analysis of the transcriptome and SMN protein in order to identify affected pathways underlying the therapeutic effect, and studied lysosomotropic and non-lysosomotropic DAQ-DCpSi effects in 2B/- SMA mice. Treatment of cells caused modest and transient SMN2 mRNA increases with either no change or a decrease in SMNΔ7 and no change in SMN1 transcripts or SMN protein. RNA-Seq analysis of DAQ-DcpSi-treated N2a cells revealed significant changes in expression (both up and down) of approximately 2,000 genes across a broad range of pathways. Treatment of 2B/- SMA mice with both lysomotropic and non-lysosomotropic DAQ-DcpSi compounds had similar effects on disease phenotype indicating that the therapeutic mechanism of action is not a consequence of lysosomotropism. In striking contrast to the findings in vitro, Smn transcripts were robustly changed in tissues but there was no increase in SMN protein levels in spinal cord. We conclude that DAQ-DcpSi have reproducible benefit in SMA mice and a broad spectrum of biological effects in vitro and in vivo, but these are complex, context specific, and not the result of simple SMN2 transcriptional activation.

The sperm whale (Physeter macrocephalus) emits a typical short acoustic signal, defined as a "click", almost continuously while diving. It is produced in different time patterns to acoustically explore the environment and communicate with conspecifics. Each emitted click has a multi-pulse structure, resulting from the production of the sound within the sperm whale's head. A Stable Inter Pulse Interval (Stable IPI) can be identified among the pulses that compose a single click. Applying specific algorithms, the measurement of this interval provides useful information to assess the total length of the animal recorded. In January 2005, a cabled hydrophone array was deployed at a depth of 2,100 m in the Central Mediterranean Sea, 25 km offshore Catania (Ionian Sea). The acoustic antenna, named OνDE (Ocean noise Detection Experiment), was in operation until November 2006. OνDE provided real time acoustic data used to perform Passive Acoustic Monitoring (PAM) of cetacean sound emissions. In this work, an innovative approach was applied to automatically measure the Stable IPI of the clicks, performing a cepstrum analysis to the energy (square amplitude) of the signals. About 2,100 five-minute recordings were processed to study the size distribution of the sperm whales detected during the OνDE long term deep-sea acoustic monitoring. Stable IPIs were measured in the range between 2.1 ms and 6.4 ms. The equations of Gordon (1991) and of Growcott (2011) were used to convert the IPIs into measures of size. The results revealed that the sperm whales recorded were distributed in length from about 7.5 m to 14 m. The size category most represented was from 9 m to 12 m (adult females or juvenile males) and specimens longer than 14 m (old males) seemed to be absent.

In recent years, an increasing number of surveys have definitively confirmed the seasonal presence of fin whales (Balaenoptera physalus) in highly productive regions of the Mediterranean Sea. Despite this, very little is yet known about the routes that the species seasonally follows within the Mediterranean basin and, particularly, in the Ionian area. The present study assesses for the first time fin whale acoustic presence offshore Eastern Sicily (Ionian Sea), throughout the processing of about 10 months of continuous acoustic monitoring. The recording of fin whale vocalizations was made possible by the cabled deep-sea multidisciplinary observatory, "NEMO-SN1", deployed 25 km off the Catania harbor at a depth of about 2,100 meters. NEMO-SN1 is an operational node of the European Multidisciplinary Seafloor and water-column Observatory (EMSO) Research Infrastructure. The observatory was equipped with a low-frequency hydrophone (bandwidth: 0.05 Hz-1 kHz, sampling rate: 2 kHz) which continuously acquired data from July 2012 to May 2013. About 7,200 hours of acoustic data were analyzed by means of spectrogram display. Calls with the typical structure and patterns associated to the Mediterranean fin whale population were identified and monitored in the area for the first time. Furthermore, a background noise analysis within the fin whale communication frequency band (17.9-22.5 Hz) was conducted to investigate possible detection-masking effects. The study confirms the hypothesis that fin whales are present in the Ionian Sea throughout all seasons, with peaks in call detection rate during spring and summer months. The analysis also demonstrates that calls were more frequently detected in low background noise conditions. Further analysis will be performed to understand whether observed levels of noise limit the acoustic detection of the fin whales vocalizations, or whether the animals vocalize less in the presence of high background noise.

The deep ocean is the largest and least known ecosystem on Earth. It hosts numerous pelagic organisms, most of which are able to emit light. Here we present a unique data set consisting of a 2.5-year long record of light emission by deep-sea pelagic organisms, measured from December 2007 to June 2010 at the ANTARES underwater neutrino telescope in the deep NW Mediterranean Sea, jointly with synchronous hydrological records. This is the longest continuous time-series of deep-sea bioluminescence ever recorded. Our record reveals several weeks long, seasonal bioluminescence blooms with light intensity up to two orders of magnitude higher than background values, which correlate to changes in the properties of deep waters. Such changes are triggered by the winter cooling and evaporation experienced by the upper ocean layer in the Gulf of Lion that leads to the formation and subsequent sinking of dense water through a process known as "open-sea convection". It episodically renews the deep water of the study area and conveys fresh organic matter that fuels the deep ecosystems. Luminous bacteria most likely are the main contributors to the observed deep-sea bioluminescence blooms. Our observations demonstrate a consistent and rapid connection between deep open-sea convection and bathypelagic biological activity, as expressed by bioluminescence. In a setting where dense water formation events are likely to decline under global warming scenarios enhancing ocean stratification, in situ observatories become essential as environmental sentinels for the monitoring and understanding of deep-sea ecosystem shifts.