The Association of Non–Drug-Related Pavlovian-to-Instrumental Transfer Effect in Nucleus Accumbens With Relapse in Alcohol Dependence: A Replication

BACKGROUND: The Pavlovian-to-instrumental transfer (PIT) paradigm measures the effects of Pavlovian conditioned cues on instrumental behavior in the laboratory. A previous study conducted by our research group observed activity in the left nucleus accumbens (NAcc) elicited by a non–drug-related PIT task across patients with alcohol dependence (AD) and healthy control subjects, and the left NAcc PIT effect differentiated patients who subsequently relapsed from those who remained abstinent. In this study, we aimed to examine whether such effects were present in a larger sample collected at a later date. METHODS: A total of 129 recently detoxified patients with AD (21 females) and 74 healthy, age- and gender-matched control subjects (12 females) performing a PIT task during functional magnetic resonance imaging were examined. After task assessments, patients were followed for 6 months. Forty-seven patients relapsed and 37 remained abstinent. RESULTS: We found a significant behavioral non–drug-related PIT effect and PIT-related activity in the NAcc across all participants. Moreover, subsequent relapsers showed stronger behavioral and left NAcc PIT effects than abstainers. These findings are consistent with our previous findings. CONCLUSIONS: Behavioral non–drug-related PIT and neural PIT correlates are associated with prospective relapse risk in AD. This study replicated previous findings and provides evidence for the clinical relevance of PIT mechanisms to treatment outcome in AD. The observed difference between prospective relapsers and abstainers in the NAcc PIT effect in our study is small overall. Future studies are needed to further elucidate the mechanisms and the possible modulators of neural PIT in relapse in AD

Tumor Suppressor Spred2 Interaction with LC3 Promotes Autophagosome Maturation and Induces Autophagy-Dependent Cell Death

The tumor suppressor Spred2 (Sprouty-related EVH1 domain-2) induces cell death in a variety of cancers. However, the underlying mechanism remains to be elucidated. Here we show that Spred2 induces caspase-independent but autophagy-dependent cell death in human cervical carcinoma HeLa and lung cancer A549 cells. We demonstrate that ectopic Spred2 increased both the conversion of microtubule-associated protein 1 light chain 3 (LC3), GFP-LC3 puncta formation and p62/SQSTM1 degradation in A549 and HeLa cells. Conversely, knockdown of Spred2 in tumor cells inhibited upregulation of autophagosome maturation induced by the autophagy inducer Rapamycin, which could be reversed by the rescue Spred2. These data suggest that Spred2 promotes autophagy in tumor cells. Mechanistically, Spred2 co-localized and interacted with LC3 via the LC3-interacting region (LIR) motifs in its SPR domain. Mutations in the LIR motifs or deletion of the SPR domain impaired Spred2-mediated autophagosome maturation and tumor cell death, indicating that functional LIR is required for Spred2 to trigger tumor cell death. Additionally, Spred2 interacted and co-localized with p62/SQSTM1 through its SPR domain. Furthermore, the co-localization of Spred2, p62 and LAMP2 in HeLa cells indicates that p62 may be involved in Spred2-mediated autophagosome maturation. Inhibition of autophagy using the lysosomal inhibitor chloroquine, reduced Spred2-mediated HeLa cell death. Silencing the expression of autophagy-related genes ATG5, LC3 or p62 in HeLa and A549 cells gave similar results, suggesting that autophagy is required for Spred2-induced tumor cell death. Collectively, these data indicate that Spred2 induces tumor cell death in an autophagy-dependent manner

Earlier surgery improves outcomes from painful chronic pancreatitis

The timing of surgery for painful chronic pancreatitis (CP) may affect outcomes. Clinical course, Izbicki pain scores, and pancreatic function were retrospectively compared and analyzed between patients undergoing either early or late surgery (< 3 or ≥ 3 years from diagnosis) for painful CP in a single center from 2007 to 2012. The early surgery group (n = 98) more frequently than the late group (n = 199) had abdominal pain with jaundice (22.4% vs 9.5%, P = .002) and pancreatic mass +/− ductal dilatation (47% vs 27%, P < .001), but less frequently abdominal pain alone (73.5% vs 85.9%, P = .009), ductal dilatation alone (31% vs 71%, P < .001), parenchymal calcification (91.8% vs 100%, P < .001) or exocrine insufficiency (60% vs 72%, P = .034); there were no other significant differences. The early group had longer hospital stay (14.4 vs 12.2 days, P = .009), but no difference in complications. Significantly greater pain relief followed early surgery (complete 69% vs 47%, partial 22% vs 37%, none 8% vs 16%, P = .01) with lower rates of exocrine (60% vs 80%, P = .005) and endocrine insufficiency (36% vs 53%, P = .033). Our data indicate that early surgery results in higher rates of pain relief and pancreatic sufficiency than late surgery for chronic pancreatitis patients. Frey and Berne procedures showed better results than other surgical procedures

Association of the OPRM1 A118G polymorphism and Pavlovian-to-instrumental transfer: Clinical relevance for alcohol dependence

Background: Pavlovian-to-instrumental transfer (PIT) quantifies the extent to which a stimulus that has been associated with reward or punishment alters operant behaviour. In alcohol dependence (AD), the PIT effect serves as a paradigmatic model of cue-induced relapse. Preclinical studies have suggested a critical role of the opioid system in modulating Pavlovian–instrumental interactions. The A118G polymorphism of the OPRM1 gene affects opioid receptor availability and function. Furthermore, this polymorphism interacts with cue-induced approach behaviour and is a potential biomarker for pharmacological treatment response in AD. In this study, we tested whether the OPRM1 polymorphism is associated with the PIT effect and relapse in AD. Methods: Using a PIT task, we examined three independent samples: young healthy subjects ( N = 161), detoxified alcohol-dependent patients ( N = 186) and age-matched healthy controls ( N = 105). We used data from a larger study designed to assess the role of learning mechanisms in the development and maintenance of AD. Subjects were genotyped for the A118G (rs1799971) polymorphism of the OPRM1 gene. Relapse was assessed after three months. Results: In all three samples, participants with the minor OPRM1 G-Allele (G+ carriers) showed increased expression of the PIT effect in the absence of learning differences. Relapse was not associated with the OPRM1 polymorphism. Instead, G+ carriers displaying increased PIT effects were particularly prone to relapse. Conclusion: These results support a role for the opioid system in incentive salience motivation. Furthermore, they inform a mechanistic model of aberrant salience processing and are in line with the pharmacological potential of opioid receptor targets in the treatment of AD

The trail of water and the delivery of volatiles to habitable planets

Water is fundamental to our understanding of the evolution of planetary systems and the delivery of volatiles to the surfaces of potentially habitable planets. Yet, we currently have essentially no facilities capable of observing this key species comprehensively. With this white paper, we argue that we need a relatively large, cold space-based observatory equipped with a high-resolution spectrometer, in the mid- through far-infrared wavelength range (25-600~$\mu$m) in order to answer basic questions about planet formation, such as where the Earth got its water, how giant planets and planetesimals grow, and whether water is generally available to planets forming in the habitable zone of their host stars.Comment: Science white paper submitted to the Astro2020 Decadal Surve

Joint Attention for Automated Video Editing

International audienceJoint attention refers to the shared focal points of attention for occupants in a space. In this work, we introduce a computational definition of joint attention for the automated editing of meetings in multi-camera environments from the AMI corpus. Using extracted head pose and individual headset amplitude as features, we developed three editing methods: (1) a naive audio-based method that selects the camera using only the headset input, (2) a rule-based edit that selects cameras at a fixed pacing using pose data, and (3) an editing algorithm using LSTM (Long-short term memory) learned joint-attention from both pose and audio data, trained on expert edits. The methods are evaluated qualitatively against the human edit, and quantitatively in a user study with 22 participants. Results indicate that LSTM-trained joint attention produces edits that are comparable to the expert edit, offering a wider range of camera views than audio, while being more generalizable as compared to rule-based methods

Genomotyping of Coxiella burnetii Using Microarrays Reveals a Conserved Genomotype for Hard Tick Isolates

C. burnetii is a Gram-negative intracellular Y-proteobacteria that causes the zoonotic disease Q fever. Q fever can manifest as an acute or chronic illness. Different typing methods have been previously developed to classify C. burnetii isolates to explore its pathogenicity. Here, we report a comprehensive genomotyping method based on the presence or absence of genes using microarrays. The genomotyping method was then tested in 52 isolates obtained from different geographic areas, different hosts and patients with different clinical manifestations. The analysis revealed the presence of 10 genomotypes organized into 3 groups, with a topology congruent with that obtained through multi-spacer typing. We also found that only 4 genomotypes were specifically associated with acute Q fever, whereas all of the genomotypes could be associated to chronic human infection. Serendipitously, the genomotyping results revealed that all hard tick isolates, including the Nine Mile strain, belong to the same genomotype

Basic Atomic Physics

Contains reports on seven research projects.National Science Foundation (Grant PHY 87-06560)Joint Services Electronics Program (Contract DAAL03-86-K-0001)Joint Services Electronics Program (Contract DAAL03-89-C-0002)National Science Foundation (Grant PHY 86-05893)U.S. Navy - Office of Naval Research (Contract N00014-83-K-0695)U.S. Navy - Office of Naval Research (Contract N00014-89-J-1207

Basic Atomic Physics

Contains reports on five research projects.Joint Services Electronics Program Contract DAAL03-89-C-0001National Science Foundation Grant PHY 87-06560National Science Foundation Contract PHY 86-05893U.S. Army Research Office Contract DAAL03-89-K-0082U.S. Navy - Office of Naval Research Contract N00014-89-J-1207U.S. Navy - Office of Naval Research Contract N00014-83-K-069