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JOURNAL ARTICLE
D Garrett Brown, Michaela Murphy, Roberto Cadeddu, Rickesha Bell, Allison Weis, Tyson Chiaro, Kendra Klag, Jubel Morgan, Hilary Coon, W Zac Stephens, Marco Bortolato, June L Round
Multiple neurological disorders are associated with gastrointestinal (GI) symptoms, including autism spectrum disorder (ASD). However, it is unclear whether GI distress itself can modify aspects of behavior. Here, we show that mice that experience repeated colitis have impaired active social engagement, as measured by interactions with a foreign mouse, even though signs of colitis were no longer present. We then tested the hypothesis that individuals with ASD harbor a microbiota that might differentially influence GI health by performing microbiota transplantation studies into male germfree animals, followed by induction of colitis...
March 30, 2024: Nature Communications
#2
REVIEW
Caterina Branca, Marco Bortolato
Tics are sudden, repetitive movements or vocalizations. Tic disorders, such as Tourette syndrome (TS), are contributed by the interplay of genetic risk factors and environmental variables, leading to abnormalities in the functioning of the cortico-striatal-thalamo-cortical (CSTC) circuitry. Various neurotransmitter systems, such as gamma-aminobutyric acid (GABA) and dopamine, are implicated in the pathophysiology of these disorders. Building on the evidence that tic disorders are predominant in males and exacerbated by stress, emerging research is focusing on the involvement of neuroactive steroids, including dehydroepiandrosterone sulfate (DHEAS) and allopregnanolone, in the ontogeny of tics and other phenotypes associated with TS...
March 20, 2024: Neuroscience and Biobehavioral Reviews
#3
JOURNAL ARTICLE
Derek P Metcalf, Zachary L Glick, Andrea Bortolato, Andy Jiang, Daniel L Cheney, C David Sherrill
The protein-ligand binding free energy is a central quantity in structure-based computational drug discovery efforts. Although popular alchemical methods provide sound statistical means of computing the binding free energy of a large breadth of systems, they are generally too costly to be applied at the same frequency as end point or ligand-based methods. By contrast, these data-driven approaches are typically fast enough to address thousands of systems but with reduced transferability to unseen systems. We introduce DrΔ G -Net (or simply Dragnet), an equivariant graph neural network that can blend ligand-based and protein-ligand data-driven approaches...
March 12, 2024: Journal of Chemical Information and Modeling
#4
JOURNAL ARTICLE
Gabriele Floris, Sean C Godar, Giulia Braccagni, Ignazio S Piras, Alicia Ravens, Mary T Zanda, Matthew J Huentelman, Marco Bortolato
Persistence is the propensity to maintain goal-directed actions despite adversities. While this temperamental trait is crucial to mitigate depression risk, its neurobiological foundations remain elusive. Developing behavioral tasks to capture persistence in animal models is crucial for understanding its molecular underpinnings. Here, we introduce the Sinking Platform Test (SPT), a novel high-throughput paradigm to measure persistence. Mice were trained to exit a water-filled tank by ascending onto a platform above water level...
February 23, 2024: Neuropsychopharmacology
#5
JOURNAL ARTICLE
Saionara Nunes de Oliveira, Jussara Gue Martini, Jaime Alonso Caravaca-Morera, Marta Lenise do Prado, Bruna Pedroso Canever, Carina Bortolato-Major, Neide da Silva Knihs
OBJECTIVE: To understand the pedagogical elements necessary for the debriefing to favor the development of reflective thinking. METHOD: A single case study developed at the Centro de Simulación en Salud of the Escuela de Enfermería of the Universidad de Costa Rica in October 2018. Data were collected through interviews, observation and document analysis. For data analysis, the strategy of theoretical propositions and the construction of explanation technique were used...
2024: Revista Gaúcha de Enfermagem
#6
JOURNAL ARTICLE
Elena Bortolato, Laura Ventura
This paper aims to contribute to refining the e -values for testing precise hypotheses, especially when dealing with nuisance parameters, leveraging the effectiveness of asymptotic expansions of the posterior. The proposed approach offers the advantage of bypassing the need for elicitation of priors and reference functions for the nuisance parameters and the multidimensional integration step. For this purpose, starting from a Laplace approximation, a posterior distribution for the parameter of interest is only considered and then a suitable objective matching prior is introduced, ensuring that the posterior mode aligns with an equivariant frequentist estimator...
January 9, 2024: Entropy
#7
JOURNAL ARTICLE
Maira D Carabajal, Santiago A Bortolato, Franco T Lisandrini, Alejandro C Olivieri
BACKGROUND: the chemometric processing of second-order chromatographic-spectral data is usually carried out with the aid of multivariate curve resolution-alternating least-squares (MCR-ALS). Recently, an alternative procedure was described based on the estimation of image moments for each data matrix and subsequent application of multiple linear regression after suitable variable selection. RESULTS: The analysis of both simulated and experimental data leads to the conclusion that the image moment method, although can cope with chromatographic lack of reproducibility across injections, it only performs well in the absence of uncalibrated interferents...
February 1, 2024: Analytica Chimica Acta
#8
JOURNAL ARTICLE
Daniele Mazzarella, Tommaso Bortolato, Giorgio Pelosi, Luca Dell'Amico
Herein, we document the design and development of a novel (3 + 2) cycloaddition reaction aided by the activity of an organic photocatalyst and visible light. The process is extremely fast, taking place in a few minutes, with virtually complete atom economy. A large variety of structurally diverse aziridines were used as masked ylides in the presence of different types of dipolarophiles (28 examples with up to 94% yield and >95 : 5 dr). Mechanistic insights obtained from photophysical, electrochemical and experimental studies highlight that the chemistry is driven by the in situ generation of the reactive ylide through two consecutive electron-transfer processes...
December 20, 2023: Chemical Science
#9
JOURNAL ARTICLE
Eduard Antonie van Bodegraven, Sanne Lof, Leia Jones, Béatrice Aussilhou, Gao Yong, Wei Jishu, Rosa Klotz, Dario Missael Rocha-Castellanos, Ippei Matsumato, Charles de Ponthaud, Kimitaka Tanaka, Esther Biesel, Emmanuele Kauffmann, Traian Dumitrascu, Yuichi Nagakawa, Pablo Martí-Cruchaga, Geert Roeyen, Alessandro Zerbi, Mara Goetz, Vincent de Meijer, Patrick Pessaux, Povilas Ignatavicius, Ihsan Demir, Mario Giuffrida, Bobby Tingstedt, Marco Vito Marino, Sotiris Mastoridis, Maximilian Brunner, Isabel Mora-Oliver, Cecilia Bortolato, Aisté Gulla, Thomas Apers, Hélène Hermand, Yusuke Mitsuka, Irinel Popescu, Ugo Boggi, Uwe Wittel, Satoshi Hirano, Sébastien Gaujoux, Keiko Kamei, Carlos Fernández-Del Castillo, Thilo Hackert, Jiang Kuirong, Miao Yi, Alain Sauvanet, Marc Besselink, Mohammad Abu Hilal, Safi Dokmak
OBJECTIVE: To develop a prediction model for major morbidity and endocrine dysfunction after CP which could help in tailoring the use of this procedure. SUMMARY BACKGROUND DATA: Central pancreatectomy (CP) is a parenchyma-sparing alternative to distal pancreatectomy for symptomatic benign and pre-malignant tumors in body and neck of the pancreas CP lowers the risk of new-onset diabetes and exocrine pancreatic insufficiency compared to distal pancreatectomy but it is thought to increase the risk of short-term complications including postoperative pancreatic fistula (POPF)...
December 11, 2023: Annals of Surgery
#10
JOURNAL ARTICLE
Collin J Anderson, Roberto Cadeddu, Daria Nesterovich Anderson, Job A Huxford, Easton R VanLuik, Karen Odeh, Christopher Pittenger, Stefan M Pulst, Marco Bortolato
BACKGROUND: Self-grooming behavior in rodents serves as a valuable behavioral index for investigating stereotyped and perseverative responses. Most current grooming analyses rely on video observation, which lacks standardization, efficiency, and quantitative information about force. To address these limitations, we developed an automated paradigm to analyze grooming using a force-plate actometer. NEW METHOD: Grooming behavior is quantified by calculating ratios of relevant movement power spectral bands...
November 28, 2023: Journal of Neuroscience Methods
#11
JOURNAL ARTICLE
Tatiana Bortolato, Angela D Friederici, Cédric Girard-Buttoz, Roman M Wittig, Catherine Crockford
One universal feature of human language is its versatility in communicating about juxtapositions of everyday events. Versatile combinatorial systems of communication can be selected for if (a) several vocal units are flexibly combined into numerous and long vocal sequences and (b) vocal sequences relate to numerous daily life events. We propose (b) is more likely during simultaneous or serial (concomitant) events than single events. We analyzed 9,391 vocal utterances across the repertoire of wild chimpanzees and their events of production...
November 17, 2023: IScience
#12
JOURNAL ARTICLE
Sven Grawunder, Natalie Uomini, Liran Samuni, Tatiana Bortolato, Cédric Girard-Buttoz, Roman M Wittig, Catherine Crockford
No abstract text is available yet for this article.
November 20, 2023: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
#13
Collin J Anderson, Roberto Cadeddu, Daria Nesterovich Anderson, Job A Huxford, Easton R VanLuik, Karen Odeh, Christopher Pittenger, Stefan M Pulst, Marco Bortolato
BACKGROUND: Self-grooming behavior in rodents serves as a valuable model for investigating stereotyped and perseverative responses. Most current grooming analyses primarily rely on video observation, which lacks standardization, efficiency, and quantitative information about force. To address these limitations, we developed an automated paradigm to analyze grooming using a force-plate actometer. NEW METHOD: Grooming behavior is quantified by calculating ratios of relevant movement power spectral bands...
July 12, 2023: bioRxiv
#14
JOURNAL ARTICLE
Ignazio S Piras, Giulia Braccagni, Matthew J Huentelman, Marco Bortolato
AIMS: Antisocial personality disorder (ASPD) and conduct disorder (CD) are characterized by a persistent pattern of violations of societal norms and others' rights. Ample evidence shows that the pathophysiology of these disorders is contributed by orbitofrontal cortex (OFC) alterations, yet the underlying molecular mechanisms remain elusive. To address this knowledge gap, we performed the first-ever RNA sequencing study of postmortem OFC samples from subjects with a lifetime diagnosis of ASPD and/or CD...
June 2, 2023: CNS Neuroscience & Therapeutics
#15
JOURNAL ARTICLE
Sara Cuadros, Giulio Goti, Giorgia Barison, Alfredo Raulli, Tommaso Bortolato, Giorgio Pelosi, Paolo Costa, Luca Dell'Amico
Here, we report a general approach to the synthesis of the difluoroalkyl bicycloalcanes (CF2-BCAs), as structural surrogates of aryl ketones and ethers. The chemistry is driven by a dihydrobenzoacridine photocatalyst, that engages in a catalytic electron-donor acceptor (EDA) complex, or directly single-electron reduce the fluorinated substrate. These two convergent manifolds lead to the generation of the R-CF2 radical, that reacts with the [1.1.1]- or [3.1.1.]-propellane. The method is extremely general, and extendable to complex bioactive molecules (30 examples, up to 87% yield)...
June 1, 2023: Angewandte Chemie
#16
JOURNAL ARTICLE
Roberto Cadeddu, Meghan Van Zandt, Luca Spiro Santovito, Karen Odeh, Collin J Anderson, Deirdre Flanagan, Peter Nordkild, Graziano Pinna, Christopher Pittenger, Marco Bortolato
Ample evidence suggests that acute stress can worsen symptom severity in Tourette syndrome (TS); however, the neurobiological underpinnings of this phenomenon remain poorly understood. We previously showed that acute stress exacerbates tic-like and other TS-associated responses via the neurosteroid allopregnanolone (AP) in an animal model of repetitive behavioral pathology. To verify the relevance of this mechanism to tic pathophysiology, here we tested the effects of AP in a mouse model recapitulating the partial depletion of dorsolateral cholinergic interneurons (CINs) seen in post-mortem studies of TS...
May 17, 2023: Neuropsychopharmacology
#17
JOURNAL ARTICLE
Roberto Frau, Francesco Traccis, Luca Concas, Roberto Cadeddu, Laura J Mosher, Peter Nordkild, Nilesh W Gaikwad, Marco Bortolato
RATIONALE: The prepulse inhibition (PPI) of the startle reflex is the best-established index of sensorimotor gating. We documented that the neurosteroid allopregnanolone (AP) is necessary to reduce PPI in response to D1 dopamine receptor agonists. Since Sprague-Dawley (SD) rats are poorly sensitive to the PPI-disrupting effects of these drugs, we hypothesized that AP might increase this susceptibility. OBJECTIVES: We tested whether AP is sufficient to increase the vulnerability of SD rats to PPI deficits in response to the D1 receptor full agonist SKF82958...
May 2, 2023: Psychopharmacology
#18
JOURNAL ARTICLE
Sara Pedretti, Maria Carmen De Santis, Vittorio Vavassori, Barbara Bortolato, Riccardo Ray Colciago, Emanuela Cagna, Daniela Patrizia Doino, Alessandra Cocchi, Marianna Alessandra Gerardi, Daniela Alterio, Stefano Maria Magrini, Sandro Tonoli
BACKGROUND: Image-guided radiation therapy (IGRT) has changed clinical practice. We proposed a survey to radiotherapy centers in Lombardy to picture the current clinical practice of its use. RESEARCH DESIGN AND METHODS: The survey consisted of 32 multiple-choice questions, divided into five topics: type of hospital, patients treated in 2019, number of LINACs; presence of protocols and staff involved in IGRT; IGRT in stereotaxis; IGRT in non-stereotactic treatments; availability of medical and technical staff...
May 2, 2023: Expert Review of Anticancer Therapy
#19
JOURNAL ARTICLE
Valeria Serra, Sonia Aroni, Marco Bortolato, Roberto Frau, Miriam Melis
Vulnerability to cocaine use disorder depends upon a combination of genetic and environmental risk factors. While early life adversity is a critical environmental vulnerability factor for drug misuse, allelic variants of the monoamine oxidase A (MAOA) gene have been shown to moderate its influence on the risk of drug-related problems. However, data on the interactions between MAOA variants and early life stress (ES) with respect to predisposition to cocaine abuse are limited. Here, we show that a mouse model capturing the interaction of genetic (low-activity alleles of the Maoa gene; MAOANeo ) and environmental (i...
April 18, 2023: Neuropharmacology
#20
JOURNAL ARTICLE
Dahlia R Weiss, Andrea Bortolato, Yongnian Sun, Xianmei Cai, Chon Lai, Sixuan Guo, Lihong Shi, Veerabahu Shanmugasundaram
Molecular glues are small molecules that simultaneously bind to two proteins, creating a chemically induced protein-protein interface. CELMoDs (cereblon E3 ligase modulators) are a class of molecular glues that promote recruitment of neosubstrate proteins to the E3 ubiquitin ligase cereblon (CRBN) for poly-Lys48-ubiquitination and proteasomal degradation. Ternary complex structures of clinical CELMoDs CC-885 and CC-90009 bound to CRBN and neosubstrate G1 to S phase transition protein 1 (GSPT1) have been experimentally determined...
April 10, 2023: Journal of Chemical Information and Modeling
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