FEL-based wave-mixing spectroscopy at FERMI

I hereby report on the forthcoming development of non-linear coherent spectroscopy in the extreme ultraviolet (EUV) and soft x-ray range at the FERMI free-electron laser (FEL) facility. This class of experiments is routinely used in the optical domain, where fully coherent photon sources (i.e., lasers) are available. These methods have not yet developed in the EUV/x-ray range, since photon sources having characteristics comparable with those of table-top lasers were not available so far. Such a void is being filled by seeded FELs sources, such as FERMI, which are in many respects similar to conventional lasers. EUV/soft x-ray non-linear coherent spectroscopy will be initially focused on the study of collective atomic dynamics in disordered systems. However, recent advances achieved at FERMI, such as the capability to radiate multiple and multi-color seeded FEL pulses, opens up the possibility to largely extend the possible applications of such experimental techniques

Assessing the effective connectivity of premotor areas during real vs imagined grasping: a DCM-PEB approach

The parieto-frontal circuit underlying grasping, which requires the serial involvement of the anterior intraparietal area (aIPs) and the ventral premotor cortex (PMv), has been recently extended enlightening the role of the dorsal premotor cortex (PMd). The supplementary motor area (SMA) has been also suggested to encode grip force for grasping actions; furthermore, both PMd and SMA are known to play a crucial role in motor imagery. Here, we aimed at assessing the dynamic couplings between left aIPs, PMv, PMd, SMA and primary motor cortex (M1) by comparing executed and imagined right-hand grasping, using Dynamic Causal Modelling (DCM) and Parametrical Empirical Bayes (PEB) analyses. 24 subjects underwent an fMRI exam (3T) during which they were asked to perform or imagine a grasping movement visually cued by photographs of commonly used objects. We tested whether the two conditions a) exert a modulatory effect on both forward and feedback couplings among our areas of interest, and b) differ in terms of strength and sign of these parameters. Results of the real condition confirmed the serial involvement of aIPs, PMv and M1. PMv also exerted a positive influence on PMd and SMA, but received an inhibitory feedback only from PMd. Our results suggest that a general motor program for grasping is planned by the aIPs-PMv circuit; then, PMd and SMA encode high-level features of the movement. During imagery, the connection strength from aIPs to PMv was weaker and the information flow stopped in PMv; thus, a less complex motor program was planned. Moreover, results suggest that SMA and PMd cooperate to prevent motor execution. In conclusion, the comparison between execution and imagery reveals that during grasping premotor areas dynamically interplay in different ways, depending on task demands

High-frequency subsurface and bulk dynamics of liquid indium

We have performed bulk and surface-sensitive inelastic x-ray scattering experiments on liquid indium with 3 meV energy resolution. The experimental data are well reproduced within a generalized hydrodynamic model including structural and microscopic relaxation processes. We find a longitudinal viscosity of 22 mPa s in the near-surface region compared to 7.4 mPa s in the bulk. The origin of the increase is associated with a slowing down of the collective dynamics in a subsurface region of 4.6 nm. © 2007 The American Physical Society

Neural representations underlying mental imagery as unveiled by representation similarity analysis

It is commonly acknowledged that visual imagery and perception rely on the same content-dependent brain areas in the high-level visual cortex (HVC). However, the way in which our brain processes and organizes previous acquired knowledge to allow the generation of mental images is still a matter of debate. Here, we performed a representation similarity analysis of three previous fMRI experiments conducted in our laboratory to characterize the neural representation underlying imagery and perception of objects, buildings and faces and to disclose possible dissimilarities in the neural structure of such representations. To this aim, we built representational dissimilarity matrices (RDMs) by computing multivariate distances between the activity patterns associated with each pair of stimuli in the content-dependent areas of the HVC and HC. We found that spatial information is widely coded in the HVC during perception (i.e. RSC, PPA and OPA) and imagery (OPA and PPA). Also, visual information seems to be coded in both preferred and non-preferred regions of the HVC, supporting a distributed view of encoding. Overall, the present results shed light upon the spatial coding of imagined and perceived exemplars in the HVC

A Beckwith–Wiedemann-associated CDKN1C mutation allows the identification of a novel nuclear localization signal in human p57Kip2

p57Kip2 protein is a member of the CIP/Kip family, mainly localized in the nucleus where it exerts its Cyclin/CDKs inhibitory function. In addition, the protein plays key roles in embryogenesis, differentiation, and carcinogenesis depending on its cellular localization and interactors. Mutations of CDKN1C, the gene encoding human p57Kip2, result in the development of different genetic diseases, including Beckwith–Wiedemann, IMAGe and Silver–Russell syndromes. We investigated a specific Beckwith–Wiedemann associated CDKN1C change (c.946 C>T) that results in the substitution of the C-terminal amino acid (arginine 316) with a tryptophan (R316W-p57Kip2). We found a clear redistribution of R316W-p57Kip2, in that while the wild-type p57Kip2 mostly occurs in the nucleus, the mutant form is also distributed in the cytoplasm. Transfection of two expression constructs encoding the p57Kip2 N-and C-terminal domain, respectively, allows the mapping of the nuclear localization signal(s) (NLSs) between residues 220–316. Moreover, by removing the basic RKRLR sequence at the protein C-terminus (from 312 to 316 residue), p57Kip2 was confined in the cytosol, implying that this sequence is absolutely required for nuclear entry. In conclusion, we identified an unreported p57Kip2 NLS and suggest that its absence or mutation might be of relevance in CDKN1C-associated human diseases determining significant changes of p57Kip2 localization/regulatory roles

An acetylcholinesterase biosensor for determination of low concentrations of Paraoxon and Dichlorvos

The characterization of an economic and ease-to-use carbon paste acetylcholinesterase (AChE) based biosensor to determine the concentration of pesticides Paraoxon and Dichlorvos is discussed. AChE hydrolyses acetylthiocholine (ATCh) in thiocoline (TC) and acetic acid (AA). When AChE is immobilized into a paste carbon working electrode kept at +410mV vs. Ag/AgCl electrode, the enzyme reaction rate using acetylthiocholine chloride (ATCl) as substrate is monitored as a current intensity. Because Paraoxon and Dichlorvos inhibit the AChE reaction, the decrease of the current intensity, at fixed ATCl concentration, is a measure of their concentration. Linear calibration curves for Paraoxon and Dichlorvos determination have been obtained. The detection limits resulted to be 0.86ppb and 4.2ppb for Paraoxon and Dichlorvos, respectively, while the extension of the linear range was up 23ppb for the former pesticide and up to 33ppb for the latter. Because the inhibited enzyme can be reactivated when immediately treated with an oxime, the biosensor reactivation has been studied when 1,1'-trimethylene bis 4-formylpyridinium bromide dioxime (TMB-4) and pyridine 2-aldoxime methiodide (2-PAM) were used. TMB-4 resulted more effective. The comparison with the behavior of similar AChE based biosensors is also presented

The mixed longitudinal–transverse nature of collective modes in water

We report high-resolution, high-statistics inelastic x-ray scattering measurements of the dynamic structure factor of water as a function of momentum and energy transfer in various thermodynamic conditions, including high-pressure liquid near the melting point, supercooled liquid and polycrystalline ice. For momentum transfer values below 8 nm−1, two collective excitations associated with longitudinal and transverse acoustic modes were observed. Above 8 nm−1, another excitation was detected in the liquid. Comparison with polycrystalline data and molecular dynamics simulations suggests that this mode is related to longitudinal–transverse mixing of mode symmetry

Adiponectin and Sarcopenia: A Systematic Review With Meta-Analysis

Background: Sarcopenia is a progressive loss of skeletal muscle mass whose pathophysiology has been proposed to possibly involve mechanisms of altered inflammatory status and endocrine function. Adiponectin has been shown to modulate inflammatory status and muscle metabolism. However, the possible association between adiponectin levels and sarcopenia is poorly understood. In order to fill this gap, in the present manuscript we aimed to summarize the current evidence with a systematic review and a meta-analysis of studies reporting serum adiponectin levels in patients with sarcopenia compared to non-sarcopenic controls. Methods: An electronic search through Medline/PubMed, Cochrane Library, and Science Direct was performed till March 1, 2020. From the included papers, meta-analysis of cross-sectional studies comparing serum levels of adiponectin between patients with sarcopenia and controls was performed. Results: Out of 1,370 initial studies, seven studies were meta-analyzed. Sarcopenic participants had significantly higher levels of adiponectin Hedges’ g with 95% confidence interval (CI): 1.20 (0.19–2.22), p = 0.02 than controls. Subgroup analysis, performed in Asian population and focused on identification of the condition based on AWGS criteria, reported higher adiponectin levels in sarcopenic population (2.1 (0.17–4.03), p = 0.03 and I2 = 98.98%. Meta-regression analysis revealed female gender to significantly influence the results as demonstrated by beta = 0.14 (95% CI (0.010–0.280), p = 0.040). Conclusions: Our meta-analysis found evidence that sarcopenia is associated with higher adiponectin levels. However, caution is warranted on the interpretation of these findings, and future longitudinal research is required to disentangle and better understand the topic

Short-wavelength four wave mixing experiments using single and two-color schemes at FERMI

The development of ultra-bright extreme ultraviolet (EUV) and X-ray free electron laser (FEL) sources has enabled the extension of wave-mixing approaches into the short wavelength regime. Such a class of experiments relies upon nonlinear interactions among multiple light pulses offering a unique tool for exploring the dynamics of ultrafast processes and correlations between selected excitations at relevant length and time scales adding elemental and site selectivity as well. Besides the availability of a suitable photon source, the implementation of wave mixing methodology requires efforts in developing the instrumental set-up. We have realized at the FERMI FEL two dedicated set-ups to handle multiple FEL beams with preselected parameters in a non-collinear fashion and control their interaction sequence at the target. These unique apparatuses, combined with the exceptional characteristics of the seeded FERMI FEL, have allowed us to make the first steps into this field and further advances are foreseen in the near future

Primary Tumor Resection for Metastatic Colorectal, Gastric and Pancreatic Cancer Patients: In Search of Scientific Evidence to Inform Clinical Practice

The management of the primary tumor in metastatic colorectal, gastric and pancreatic cancer patients may be challenging. Indeed, primary tumor progression could be associated with severe symptoms, compromising the quality of life and the feasibility of effective systemic therapy, and might result in life-threatening complications. While retrospective series have suggested that surgery on the primary tumor may confer a survival advantage even in asymptomatic patients, randomized trials seem not to definitively support this hypothesis. We discuss the evidence for and against primary tumor resection for patients with metastatic gastrointestinal (colorectal, gastric and pancreatic) cancers treated with systemic therapies and put in context the pros and cons of the onco-surgical approach in the time of precision oncology. We also evaluate current ongoing trials on this topic, anticipating how these will influence both research and everyday practice