Intra-protein interacting collective modes in the terahertz frequency region.

Understanding how proteins work requires a thorough understanding of their internal dynamics. Proteins support a wide range of motions, from the femtoseconds to seconds time scale, relevant to crucial biological functions. In this context, the term "protein collective dynamics" refers to the complex patterns of coordinated motions of numerous atoms throughout the protein in the sub-picosecond time scale (terahertz frequency region). It is hypothesized that these dynamics have a substantial impact on the regulation of functional dynamical mechanisms, including ligand binding and allosteric signalling, charge transport direction, and the regulation of thermodynamic and thermal transport properties. Using the theoretical framework of hydrodynamics, the collective dynamics of proteins had previously been described in a manner akin to that of simple liquids, i.e. in terms of a single acoustic-like excitation, related to intra-protein vibrational motions. Here, we employ an interacting-mode model to analyse the results from molecular dynamics simulations and we unveil that the vibrational landscape of proteins is populated by multiple acoustic-like and low-frequency optic-like modes, with mixed symmetry and interfering with each other. We propose an interpretation at the molecular level of the observed scenario that we relate to the side-chains and the hydrogen-bonded networks dynamics. The present insights provide a perspective for understanding the molecular mechanisms underlying the energy redistribution processes in the interior of proteins.

Monitoring of anthropogenic microplastic pollution in antarctic fish (emerald rockcod) from the Terranova Bay after a quarter of century.

Monitoring the occurrence of microplastic contamination in the Antarctic area is the key to implement policy measures for waste regulations in the research stations. Antarctic fish Trematomus bernachii is a suitable species for establishing microplastic contamination and for investigating changes over time in the concentration and type of microplastics in the Antarctic region. In this paper a total of 78 fish, caught during the 37th Italian Antarctic expedition (2021-2022) in the Ross Sea (Antarctica) were analysed. Different microfibers and dyes were identified by Raman spectroscopy and the results were compared with those obtained for fish sampled in 1998. Differences in polymer type emerged with a predominance of synthetic fibers with respect to natural ones. These changes appear to be related to the increased human activities in the Antarctica over the last twenty years and highlights the need to improve the environmental sustainability of the numerous research stations operating throughout that area.

Electric-field induced entropic effects in liquid water.

Externally applied electric fields in liquid water can induce a plethora of effects with wide implications in electrochemistry and hydrogen-based technologies. Although some effort has been made to elucidate the thermodynamics associated with the application of electric fields in aqueous systems, to the best of our knowledge, field-induced effects on the total and local entropy of bulk water have never been presented so far. Here, we report on classical TIP4P/2005 and ab initio molecular dynamics simulations measuring entropic contributions carried by diverse field intensities in liquid water at room temperature. We find that strong fields are capable of aligning large fractions of molecular dipoles. Nevertheless, the order-maker action of the field leads to quite modest entropy reductions in classical simulations. Albeit more significant variations are recorded during first-principles simulations, the associated entropy modifications are small compared to the entropy change involved in the freezing phenomenon, even at intense fields slightly beneath the molecular dissociation threshold. This finding further corroborates the idea that electrofreezing (i.e., the electric-field-induced crystallization) cannot take place in bulk water at room temperature. In addition, here, we propose a molecular-dynamics-based analysis (3D-2PT) that spatially resolves the local entropy and the number density of bulk water under an electric field, which enables us to map their field-induced changes in the environment of reference H2O molecules. By returning detailed spatial maps of the local order, the proposed approach is capable of establishing a link between entropic and structural modifications with atomistic resolution.

Spectroscopic Fingerprints of Cavity Formation and Solute Insertion as a Measure of Hydration Entropic Loss and Enthalpic Gain.

Hydration free energies are dictated by a subtle balance of hydrophobic and hydrophilic interactions. We present here a spectroscopic approach, which gives direct access to the two main contributions: Using THz-spectroscopy to probe the frequency range of the intermolecular stretch (150-200 cm-1 ) and the hindered rotations (450-600 cm-1 ), the local contributions due to cavity formation and hydrophilic interactions can be traced back. We show that via THz calorimetry these fingerprints can be correlated 1 : 1 with the group specific solvation entropy and enthalpy. This allows to deduce separately the hydrophobic (i.e. cavity formation) and hydrophilic contributions to thermodynamics, as shown for hydrated alcohols as a case study. Accompanying molecular dynamics simulations quantitatively support our experimental results. In the future our approach will allow to dissect hydration contributions in inhomogeneous mixtures and under non-equilibrium conditions.

TiO2 Nanoparticles Dispersion in Block-Copolymer Aqueous Solutions: Nanoarchitectonics for Self-Assembly and Aggregation.

Achieving homogenous dispersion of nanoparticles inside a polymeric matrix is a great challenge for numerous applications. In the present study, we aim at understanding the role of different factors on the dispersion properties of TiO2 in pluronic F-127 mixtures. The mixtures were prepared with different pH and guest/host ratios and investigated by UV-Vis spectroscopy, dynamic light scattering, infrared spectroscopy and electrical conductivity. Depending on the preparation conditions, different amounts of TiO2 were loaded within the copolymer as quantitatively determined by UV-Vis spectroscopy. The different content of nanoparticles has direct implications on the gelation and micellization of pluronic analyzed by dynamic light scattering. The information derived on the self-assembly behavior was interpreted in relation to the infrared and conductivity measurements results. Together, these results shed light on the most favorable conditions for improving the nanoparticle dispersion inside the copolymer matrix and suggest a possible strategy to design functional nanoparticle-polymer systems.

Neurogenic Dysphagia and Nutrition in Disorder of Consciousness: An Overview with Practical Advices on an "Old" but Still Actual Clinical Problem.

Neurogenic dysphagia is a difficulty in swallowing food caused by disease or impairment of the nervous system, including stroke and traumatic brain injury. The most clinically apparent complication of neurogenic dysphagia is pulmonary aspiration, which may manifest itself acutely as choking or coughing, respiratory distress, wheezing, gasping or gurgling, and tachycardia. However, chronic symptoms, including weight loss, production of excessive oral secretions and aspiration pneumonia, may be also present, especially in patients with a disorder of consciousness (DOC). Usually, patients with dysphagia after the acute phase need to be treated with enteral nutrition using a feeding tube. This avoids patient malnutrition and supports the rehabilitation program. This narrative review aims to investigate dysphagia and its complications and management in patients with DOC. Clinical indications and practical advice on how to assess and treat this complex problem are also provided.

Acute onset of bulbar amyotrophic lateral sclerosis after flu - look at the differential diagnosis: A case report.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting upper and lower motor neurones. It can be either familial (fALS) or sporadic (sALS). ALS is characterized by muscle weakness and atrophy that can involve the limbs and trunk (i.e. the spinal form of the disease) or speech and swallowing (i.e. the bulbar form). The aetiology of sALS remains unclear although a gene-environment interaction has been proposed as a concomitant trigger for the neurodegenerative process together with viral infections, smoking, heavy metals and pesticide exposure. Herein, we report the case of a 67-year-old woman who experienced an acute onset of bulbar ALS with an atypical clinical course that was probably triggered by a bout of influenza.

Telemedicine for Facio-Scapulo-Humeral Muscular Dystrophy: A multidisciplinary approach to improve quality of life and reduce hospitalization rate?

BACKGROUND: Facio-Scapulo-Humeral Muscular Dystrophy (FSHD) is an autosomal dominant inherited disorder characterized by a variable and asymmetric involvement of facial, trunk, upper and lower extremity muscles. Although respiratory weakness is a relatively unknown feature of FSHD, it is not rare. Telemedicine has been used in a variety of health care fields, but only recently, with the advent of sophisticated technology, its interest among health professionals became evident, even in such diseases. OBJECTIVE: To demonstrate the telemedicine efficacy in FSHD. METHODS: Four siblings affected by a severe form of FSHD, living in a rural area far away from the referral center for neuromuscular diseases, who used a wheelchair, suffered from chronic respiratory failure and were provided with long-term non-invasive mechanical ventilation, received a 6-month period of telemedicine support. This consisted of video conferencing (respiratory physiotherapy, psychological support, neurological and pneumological assessment, nurse-coach supervision) and telemonitoring of cardiorespiratory variables (oxygen saturation, blood pressure, and heart rate). RESULTS: We performed 540 video conference sessions per patient, including three daily contacts with short monitoring oximetry measurements, blood pressure, and heart-rate measurements, psychological support, neurological and pneumological assessment, nurse-coach supervision. CONCLUSIONS: Our findings indicate that our telemedicine system was user-friendly, efficient for the home treatment of FSHD, and allowed reducing hospital admissions.

Role of Terahertz (THz) Fluctuations in the Allosteric Properties of the PDZ Domains.

With the aim of investigating the relationship between the fast fluctuations of proteins and their allosteric behavior, we perform molecular dynamics simulations of two model PDZ domains with differential allosteric responses. We focus on protein dynamics in the THz regime (0.1-3 THz) as opposed to lower frequencies. By characterizing the dynamic modulation of the protein backbone induced by ligand binding in terms of single residue and pairwise distance fluctuations, we identify a response nucleus modulated by the ligand that is visible only at THz frequencies. The residues of this nucleus undergo a significant stiffening and an increase in mutual coordination upon binding. Additionally, we find that the dynamic modulation is significantly more intense for the side chains, where it is also redistributed to distal regions not immediately in contact with the ligand allowing us to better define the response nucleus at THz frequencies. The overlap between the known allosterically responding residues of the investigated PDZ domains and the modulated region highlighted here suggests that fast THz dynamics could play a role in allosteric mechanisms.

Probing Intermolecular Interactions in Phospholipid Bilayers by Far-Infrared Spectroscopy.

Fast thermal fluctuations and low frequency phonon modes are thought to play a part in the dynamic mechanisms of many important biological functions in cell membranes. Here we report a detailed far-infrared study of the molecular subpicosecond motions of phospholipid bilayers at various hydrations. We show that these systems sustain several low frequency collective modes and deduce that they arise from vibrations of different lipids interacting through intermolecular van der Waals forces. Furthermore, we observe that the low frequency vibrations of lipid membrane have strong similarities with the subpicosecond motions of liquid water and suggest that resonance mechanisms are an important element to the dynamics coupling between membranes and their hydration water.

Influence of Alcohols on the Lateral Diffusion in Phospholipid Membranes.

The effects of hexanol and octanol on the lateral mobility of 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) bilayer are investigated by means of pulsed-gradient stimulated-echo NMR spectroscopy. Three distinct diffusions are identified for the DMPC/alcohol systems. They are ascribed to the water, the alcohol, and the lipid. We find that the presence of alcohols promotes the lipid diffusion process both in the liquid and in the interdigitated phases. Furthermore, using the Arrhenius approach, the activation energies are calculated. An explanation in terms of a free volume model, that takes into account also the observed increase of the activation energy in both phases, is proposed. The results obtained here are compared with those presented in our previous work on 1,2-palmitoyl-sn-glycero-3-phosphocholine (DPPC) in order to examine the dependence of the lipid translational diffusion process upon the membrane acyl chain length. A peculiar influence of alcohols on different membranes is found.

Enzymatic turnover of macromolecules generates long-lasting protein-water-coupled motions beyond reaction steady state.

The main focus of enzymology is on the enzyme rates, substrate structures, and reactivity, whereas the role of solvent dynamics in mediating the biological reaction is often left aside owing to its complex molecular behavior. We used integrated X-ray- and terahertz- based time-resolved spectroscopic tools to study protein-water dynamics during proteolysis of collagen-like substrates by a matrix metalloproteinase. We show equilibration of structural kinetic transitions in the millisecond timescale during degradation of the two model substrates collagen and gelatin, which have different supersecondary structure and flexibility. Unexpectedly, the detected changes in collective enzyme-substrate-water-coupled motions persisted well beyond steady state for both substrates while displaying substrate-specific behaviors. Molecular dynamics simulations further showed that a hydration funnel (i.e., a gradient in retardation of hydrogen bond (HB) dynamics toward the active site) is substrate-dependent, exhibiting a steeper gradient for the more complex enzyme-collagen system. The long-lasting changes in protein-water dynamics reflect a collection of local energetic equilibrium states specifically formed during substrate conversion. Thus, the observed long-lasting water dynamics contribute to the net enzyme reactivity, impacting substrate binding, positional catalysis, and product release.

Molecular dynamics simulation of short-wavelength collective dynamics of phospholipid membranes.

We investigated the short-wavelength longitudinal and transverse collective dynamics of the fluid and gel phases of phospholipid bilayers by means of molecular dynamics simulation. Similarly to a crystal, the spectrum of collective excitations in a bilayer consists of longitudinal and transverse acoustic modes, though modified by disorder. Beside acoustic modes, a series of broad dispersionless excitations are revealed. The dispersion curves of the observed excitations may be represented in a pseudo-Brillouin zone scheme centered around the spatial correlation peak of the acyl chains. The study provides evidence for a resonant interaction between the lowest frequency optical phonon and the longitudinal acoustic mode.

New insights into the role of water in biological function: studying solvated biomolecules using terahertz absorption spectroscopy in conjunction with molecular dynamics simulations.

In life science, water is the ubiquitous solvent, sometimes even called the "matrix of life". There is increasing experimental and theoretical evidence that solvation water is not a passive spectator in biomolecular processes. New experimental techniques can quantify how water interacts with biomolecules and, in doing so, differs from "bulk" water. Terahertz (THz) absorption spectroscopy has turned out to be a powerful tool to study (bio)molecular hydration. The main concepts that have been developed in the recent years to describe the underlying solute-induced sub-picosecond dynamics of the hydration shell are discussed herein. Moreover, we highlight recent findings that show the significance of hydrogen bond dynamics for the function of antifreeze proteins and for molecular recognition. In all of these examples, a gradient of water motion toward functional sites of proteins is observed, the so-called "hydration funnel". By means of molecular dynamics simulations, we provide new evidence for a specific water-protein coupling as the cause of the observed dynamical heterogeneity. The efficiency of the coupling at THz frequencies is explained in terms of a two-tier (short- and long-range) solute-solvent interaction.

On the Coupling between the Collective Dynamics of Proteins and Their Hydration Water.

Picosecond time scale dynamics of hydrated proteins has been connected with the onset of biological activity as it coincides with solvent-solute hydrogen bond rearrangements and amino acid rotational relaxation time scales. The presence and fluctuations of protein hydration water (PHW) largely influence protein motions that are believed to be slaved to those of the solvent, yet to date, how protein and hydration water dynamics are coupled remains unclear. Here, we provide a significant advance in characterizing this coupling; we present the first full study of both the longitudinal and transverse coherent collective motions in a protein-solvent system. The data show unexpectedly the presence in the water dynamics of collective modes belonging to the protein. The properties of these modes, in particular, their propagation velocities and amplitudes, indicate a strengthening of the interactions and a higher rigidity of the network of solvent molecules close to the protein surface. Accordingly, the present study presents the most compelling and clear evidence of a very strong dynamical coupling between a protein and its hydration water, previously suggested by studies using various experimental techniques.

Sexual dysfunction in male patients with multiple sclerosis: a need for counseling!

Sexuality and sexual health are significant factors in determining the quality of life (QoL). Multiple sclerosis (MS) is one of the most serious causes of neurological disability in young adults, therefore it can considerably reduce sexuality. Physical and cognitive symptoms of MS as well as mental and psycho-social issues can directly affect sexual life and body representation, causing reduced libido and self-esteem. Male patients with MS frequently develop sexual dysfunction (SD) as a result of their neurological impairment: in fact physical, psychological and neuropsychological changes indirectly interfere in the sexual response. Thus, MS physicians' greater concern on SD has led to the enhancement of diagnostic and therapeutic diagnoses on neurogenic SD. Given the increasing number of people coping with MS, a more effective focus on MS-related problems, including SD, is absolutely essential to provide the patients and their partner with the necessary information to achieve a better sexual health and consequently improve their QoL. This review aims to investigate the epidemiology and pathophysiology of SD in male patients, provide an insight into multidisciplinary diagnostic and therapeutic approaches, and focus on the need of proper counseling.

The hypothalamic-neurohypophyseal system: current and future treatment of vasopressin and oxytocyn related disorders.

The hypothalamus and posterior pituitary form a complex neurohumoral system playing a key role in maintaining body fluid homeostasis and reproductive function. We review the pathophysiology mechanisms of posterior pituitary hormones and their implications, beyond water balance and delivery, in social functioning, pair bonding and affiliative behavior. Actual and future treatments for neurohypophysis related disorders are also discussed, particularly focusing on the development of new therapeutic compounds and patents.