Longitudinal trajectories of psychosocial functioning in patients with pre-existing mental disorders after one year of COVID-19 pandemic.

Aims of the present study were to prospectively assess psychosocial functioning trajectories during the COVID pandemic and the possible impact of sociodemographic variables, as well as of COVID-19 pandemic-related factors, on these trajectories, in a sample of patients with pre-existing severe mental disorders. Moreover, we aimed at identifying predictors of impairment in psychosocial functioning over a period of 9 months of COVID-19 pandemic. Patients were recruited during the 3rd wave of the COVID-19 pandemic (T0, March-April 2021) while strict containment measures were applied in Italy, and reassessed after 3 months (T1, June-July 2021), and after 6 months from T1 (T2- November-December 2021), during the 4th wave of COVID pandemic. A sample of 300 subject (out of the 527 subjects recruited at baseline) completed the T2 evaluation. Patients were assessed by: Work and Social Adjustment Scale (WSAS) for psychosocial functioning, Generalized Anxiety Disorder 7-Item (GAD-7) for anxiety symptoms, Patient Health Questionnaire-9 (PHQ-9) for depressive symptoms and the Impact of Events Scale-Revised, for post-traumatic symptoms. Cluster analyses identified 4 trajectories of functioning: the High, Stable Functioning group (N = 77), the Improvement Functioning group (N = 62), the Progressive Impairment group (N = 83) and the Persistent Severe Impairment group (N = 78) respectively. We found that predictors of higher WSAS score at T2 were higher WSAS score at T0 (B = 0.43, p < .001), PHQ scores at baseline >10 (B = 2.89, p < .05), while not living alone was found to be a protective factor (B = -2.5, p < .05). Results of the present study provides insights into the vulnerability of individuals with psychiatric disorders during times of crisis. Study findings can contribute to a better understanding of the specific needs of this population and inform interventions and support strategies.

Structural dynamics of the mitochondrial ADP/ATP carrier revealed by molecular dynamics simulation studies.

The mitochondrial adenosine diphosphate/adenosine triphosphate (ADP/ATP) carrier has been recently crystallized in complex with its specific inhibitor carboxyatractyloside (CATR). In the crystal structure, the six-transmembrane helix bundle that defines the nucleotide translocation pathway is closed on the matrix side due to sharp kinks in the odd-numbered helices. The closed conformation is further sealed by the loops protruding into the matrix that interact through an intricate network of charge-pairs. To gain insight into its structural dynamics we performed molecular dynamics (MD) simulation studies of the ADP/ATP carrier with and without its cocrystallized inhibitor. The two trajectories sampled a conformational space around two different configurations characterized by distinct salt-bridge networks with a significant shift from inter- to intrarepeat bonding on the matrix side in the absence of CATR. Analysis of the geometrical parameters defining the transmembrane helices showed that even-numbered helices can undergo a face rotation, whereas odd-numbered helices can undergo a change in the wobble angle with a conserved proline acting as molecular hinge. Our results provide new information on the dynamical properties of the ADP/ATP carrier and for the first time yield a detailed picture of a stable carrier conformation in absence of the inhibitor.

Active-site copper and zinc ions modulate the quaternary structure of prokaryotic Cu,Zn superoxide dismutase.

The influence of the constitutive metal ions on the equilibrium properties of dimeric Photobacterium leiognathi Cu,Zn superoxide dismutase has been studied for the wild-type and for two mutant protein forms bearing a negative charge in the amino acid clusters at the dimer association interface. Depletion of copper and zinc dissociates the two mutant proteins into monomers, which reassemble toward the dimeric state upon addition of stoichiometric amounts of zinc. Pressure-dependent dissociation is observed for the copper-depleted wild-type and mutated enzymes, as monitored by the fluorescence shift of a unique tryptophan residue located at the subunit association interface. The spectral shift occurs slowly, reaching a plateau after 15-20 minutes, and is fully reversible. The recovery of the original fluorescence properties, after decompression, is fast (less than four minutes), suggesting that the isolated subunit has a relatively stable structure, and excluding the presence of stable intermediates during the dimer-monomer transition. The dimer dissociation process is still incomplete at 6.5 kbar for the copper-depleted wild-type and mutated enzymes, at variance with what is generally observed for oligomeric proteins that dissociate below 3 kbar. Measurement of the degree of dissociation, at two different protein concentrations, allows us to calculate the standard volume variation upon association, Delta V, and the dissociation constant K(d0), at atmospheric pressure, (25 ml/mol and 3 x 10(-7)M, respectively). The holoprotein is fully dimeric even at 6.5 kbar, which allows us to evaluate a lower Delta G degrees limit of 11.5 kcal/mol, corresponding to a dissociation constant K(d0)<10(-9)M.