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Abstract Introduction: A recent multiregional whole-exome sequencing of 48 tumour samples from 9 gastric adenocarcinomas discovered PCLO mutations in 23 (47.9%) tumour samples. Based on that unexpected high prevalence of PCLO mutations, we hypothesized a tumour biological significance of PCLO in gastric cancer (GC). Methods: Tumour samples (whole tissue sections) obtained from 466 patients resected for therapy-naive GC were stained with an anti-PCLO antibody. The histoscore for tumour cells and the presence of immunostaining of stromal cells and tumour vessels was documented for each case. An algorithm for PCLO immunopositivity was formed and correlated with clinicopathological patient characteristics. Results: 175 GCs were classified as PCLO positive within tumour cells, and 291 as negative. Stromal cells were positive for PCLO in 106 cases and tumour vessels in 84. PCLO-positive GCs more often showed an intestinal phenotype, a lower T category and were more commonly associated with Helicobacter pylori infection. A separate analysis of PCLO expression in intestinal and diffuse type GCs, respectively, showed no significant correlations. Patients with PCLO negative/low tumour cells showed a shortened overall (14.0 ± 1.4 vs. 16.0 ± 1.8 months) and tumour-specific survival (15.0 ± 1.6 months vs. 17.9 ± 3.6). Comparison of PCLOs genotype with its phenotype in 48 tumour samples obtained from nine cases showed no direct correlations with missense mutations. Conclusion: Our data provide evidence that PCLO is differentially expressed in GC and might delay tumour progression.

Most interpretations of BWV 8/1 submit that Bach’s instrumentation imitates a death knell. The alternative explanation suggested here is that it could be guided by locus amoenus, which in Christian reinterpretation of the ancient concept is connected to paradise. In addition to trees, meadows, and streams, the singing of birds is an audible part of locus amoenus, and Bach’s initial intention to employ the flauto piccolo could be seen as an attempt to imitate it, especially since this instrument and its specific application in BWV 8/1–i. e. for the repetition of notes-is similarly used by Bach’s contemporaries.

James Joyce visited Galway and the Aran Islands in 1912 and took advantage of the occasion to write two articles in Italian that he published in Il Piccolo della Sera in 1912. I analyse the vision that Joyce conveyed of the Spanish Armada both in these articles and later in Ulysses (1922) and in Finnegans Wake (1939). Joyce’s knowledge of the 1588-Armada episode and of the shipwrecks of several Spanish vessels in the vicinity of Galway are the result of both the propagandistic narration usually provided by pro-British historiography and by his presumed readings on the history of the city and the nearby Aran Islands. In such writings, Joyce may have intended, on the one hand, to reflect his tacit acceptance of the imperialism exercised by post-Victorian Britain over Ireland, fully convinced that the decline of the Spanish Empire had begun with the Armada’s defeat against Elizabethan England in 1588. He believed this event gave rise to the birth of the British Empire. On the other hand, Joyce reflects in them his only moderate Irish pride for the supposed humanitarian actions of the population of Galway (the birthplace of Nora), a city he described both as “Spanish” and as sympathetic towards the Armada castaways in Ireland. Joyce’s employment of the Irish chapter of the Gran Armada’s historical episode contributes with a relevant insight about his perception of British imperialism in Ireland.

The presynaptic active zone (AZ) is a specialized microdomain designed for the efficient and repetitive release of neurotransmitter. Bassoon and Piccolo are two high molecular weight components of the AZ, with hypothesized roles in its assembly and structural maintenance. However, glutamatergic synapses lacking either protein exhibit relatively minor defects, presumably due to their significant functional redundancy. In the present study, we have used interference RNAs to eliminate both proteins from glutamatergic synapses, and find that they are essential for maintaining synaptic integrity. Loss of Bassoon and Piccolo leads to the aberrant degradation of multiple presynaptic proteins, culminating in synapse degeneration. This phenotype is mediated in part by the E3 ubiquitin ligase Siah1, an interacting partner of Bassoon and Piccolo whose activity is negatively regulated by their conserved zinc finger domains. Our findings demonstrate a novel role for Bassoon and Piccolo as critical regulators of presynaptic ubiquitination and proteostasis. The presynaptic proteins Bassoon and Piccolo interact with and inhibit the activity of the E3 ubiquitin ligase Siah1 to regulate protein homeostasis and synaptic integrity.

Pre-visual detection of crop disease is critical for food security. Field-based spectroscopic remote sensing offers a method to enable timely detection, but still requires appropriate instrumentation and testing. Soybean plants were spectrally measured throughout a growing season to assess the capacity of leaf and canopy level spectral measurements to detect non-visual foliage symptoms induced by Fusarium virguliforme (Fv, which causes sudden death syndrome). Canopy reflectance measurements were made using the Piccolo Doppio dual field-of-view, two-spectrometer (400 to 1630 nm) system on a tractor. Leaf level measurements were obtained, in different plots, using a handheld spectrometer (400 to 2500 nm). Partial least squares discriminant analysis (PLSDA) was applied to the spectroscopic data to discriminate between Fv-inoculated and control plants. Canopy and leaf spectral data allowed identification of Fv infection, prior to visual symptoms, with classification accuracy of 88% and 91% for calibration, 79% and 87% for cross-validation, and 82% and 92% for validation, respectively. Differences in wavelengths important to prediction by canopy vs. leaf data confirm that there are different bases for accurate predictions among methods. Partial least square regression (PLSR) was used on a late-stage canopy level data to predict soybean seed yield, with calibration, cross-validation and validation R2 values 0.71, 0.59 and 0.62 (p < 0.01), respectively, and validation root mean square error of 0.31 t·ha−1. Spectral data from the tractor mounted system are thus sensitive to the expression of Fv root infection at canopy scale prior to canopy symptoms, suggesting such systems may be effective for precision agricultural research and management.

Most interpretations of BWV 8/1 submit that Bach’s instrumentation imitates a death knell. The alternative explanation suggested here is that it could be guided by locus amoenus, which in Christian reinterpretation of the ancient concept is connected to paradise. In addition to trees, meadows, and streams, the singing of birds is an audible part of locus amoenus, and Bach’s initial intention to employ the flauto piccolo could be seen as an attempt to imitate it, especially since this instrument and its specific application in BWV 8/1–i. e. for the repetition of notes-is similarly used by Bach’s contemporaries.

Methamphetamine (METH), the most widely distributed psychostimulant, aberrantly activates the reward system in the brain to induce addictive behaviors. The presynaptic protein “Piccolo”, encoded by Pclo, was identified as a METH-responsive protein with enhanced expression in the nucleus accumbens (NAc) in mice. Although the physiological and pathological significance of Piccolo has been identified in dopaminergic signaling, its role in METH-induced behavioral abnormalities and the underlying mechanisms remain unclear. To clarify such functions, mice with Piccolo knockdown in the NAc (NAc-miPiccolo mice) by local injection of an adeno-associated virus vector carrying miRNA targeting Pclo were generated and investigated. NAc-miPiccolo mice exhibited suppressed hyperlocomotion, sensitization, and conditioned place preference behavior induced by systemic administration of METH. The excessive release of dopamine in the NAc was reduced in NAc-miPiccolo mice at baseline and in response to METH. These results suggest that Piccolo in the NAc is involved in METH-induced behavioral alterations and is a candidate therapeutic target for the treatment of drug addiction.

In this multi-centre study, the mid- to long-term efficacy and safety of the Amplatzer Piccolo Occluder in patent ductus arteriosus closure in premature and term infants as well as children were discussed. Methods. Between 2016 and 2021, 645 patients, 152 of whom were less than 1 month old, underwent ductus closure with the Piccolo device from five different centres in Turkey. The median age of the patients was 2.2 years, and the mean narrowest point of duct diameter was 1.8 mm. Sixty-two patients weighed ≤ 1.5 kg, 90 patients 1.5–3 kg, and the mean follow-up was 20.4 months. In 396, the duct was closed by the retrograde route. Ductal anatomy was Type A in 285, C in 72, E in 171, and F in 64 patients. Fluoroscopy duration was 6.2 min. The procedure success rate was 99.1%. Device embolisation occurred in 13 patients (2%), and 11 were retrieved with a snare. Cardiac perforation and death developed in one premature baby. The left pulmonary artery and the descending aorta stenosis were observed in 3 (0.4%) and in 5 patients (0.5%). Results. Piccolo device is safe and effective in closing ductus in all age groups. It has low profile for use in premature and newborn babies, a small embolisation risk, and a low residual shunt rate after closure. Conclusion. The Piccolo device can be considered as close an ideal occluder. The lower profile, smaller delivery catheter size, and symmetry of this device allow for a venous or arterial approach.

We present the case of a 4-month-old, former 23-week premature baby who underwent patent ductus arteriosus device closure in the cardiac catheterisation lab with an Amplatzer Piccolo™ device at 12 weeks of life. This was complicated by late migration of the device into the aorta resulting in severe obstruction and requiring surgical intervention.

Background and Aims Transcatheter closure of patent ductus arteriosus (PDA), particularly with the Amplatzer Piccolo Occluder, offers advantages over surgical closure, including better recovery and lower risk of complications. Although its smaller profile is preferred for neonatal endovascular closure, it may be used in patients of varying ages. This study aims to evaluate the effectiveness of the Piccolo device in PDA treatment beyond premature newborns. Methods A retrospective study was conducted on patients who underwent PDA closure with the Piccolo device at our institution between January 2021 and December 2023. Results Twenty‐nine patients underwent transcatheter closure with the Piccolo device, with a mean age of 24 months (IQR: 5–23) and a mean weight of 10.4 kg (IQR: 5.6–13.8). The average ductus arteriosus diameter was 1.65 mm (IQR: 1.0–1.9), and the most commonly used device size was 4/4 mm (n = 14), followed by 5/4 mm (n = 5) and 3/4 mm (n = 4). Successful closure was achieved in 28 patients (96.5%) without evidence of persistent shunt after closure. No device embolization or local complications were observed after the procedure. One patient died during hospitalization due to unrelated complications of intestinal perforation. During follow‐up of at least 6 months, no stenosis of the left pulmonary artery or aorta was identified in any patient. Conclusion These findings suggest a potential extension of the utility of the Piccolo device beyond the neonatal phase, demonstrating its safety and efficacy in older pediatric patients weighing over 2 kg, without a significant increase in complications or mortality rates.