Random Matrix approach to collective behavior and bulk universality in protein dynamics

Covariance matrices of amino acid displacements, commonly used to characterize the large-scale movements of proteins, are investigated through the prism of Random Matrix Theory. Bulk universality is detected in the local spacing statistics of noise-dressed eigenmodes, which is well described by a Brody distribution with parameter $\beta\simeq 0.8$. This finding, supported by other consistent indicators, implies a novel quantitative criterion to single out the collective degrees of freedom of the protein from the majority of high-energy, localized vibrations.Comment: 4 pages, 7 figure

Fluctuations, Finite-Size Effects and the Thermodynamic Limit in Computer Simulations: Revisiting the Spatial Block Analysis Method

The spatial block analysis (SBA) method has been introduced to efficiently extrapolate thermodynamic quantities from finite-size computer simulations of a large variety of physical systems. In the particular case of simple liquids and liquid mixtures, by subdividing the simulation box into blocks of increasing size and calculating volume-dependent fluctuations of the number of particles, it is possible to extrapolate the bulk isothermal compressibility and Kirkwood–Buff integrals in the thermodynamic limit. Only by explicitly including finite-size effects, ubiquitous in computer simulations, into the SBA method, the extrapolation to the thermodynamic limit can be achieved. In this review, we discuss two of these finite-size effects in the context of the SBA method due to (i) the statistical ensemble and (ii) the finite integration domains used in computer simulations. To illustrate the method, we consider prototypical liquids and liquid mixtures described by truncated and shifted Lennard–Jones (TSLJ) potentials. Furthermore, we show some of the most recent developments of the SBA method, in particular its use to calculate chemical potentials of liquids in a wide range of density/concentration conditions

Hidradenitis Suppurativa Cancer Risk: A Review of the Literature

Fabrizio Martora,* Nello Tommasino,* Teresa Battista,* Luca Potestio, Matteo Megna Section of Dermatology - Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy*These authors contributed equally to this workCorrespondence: Fabrizio Martora, Section of Dermatology - Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, Napoli, 80131, Italy, Tel +39-081-7462457, Fax +39-081-7462442, Email [email protected]: This systematic review explores the increased cancer risk in patients with hidradenitis suppurativa (HS), particularly cutaneous squamous cell carcinoma (SCC) and lymphoma. Chronic inflammation and immune dysregulation in HS are identified as key factors contributing to malignant transformation, often observed in areas of prolonged tissue damage.Objectives and Results: The NOTCH signaling pathway, disrupted by smoking, plays a dual role in cancer, acting as both a tumor suppressor and a proto-oncogene depending on the context. Mutations in NOTCH and TP53 are common in SCC linked to HS, with a prevalence of 0.5% to 4.6%, predominantly in men and localized to the buttock and anogenital regions. Histological analyses suggest that malignant transformation occurs within keratinized epithelium, supported by altered cytokeratin expression. Immune dysregulation in HS-affected areas, compounded by scarring and lymphatic disruption, further exacerbates tumorigenic potential. While anti-TNF-alpha therapies have been implicated in cancer risk, conflicting evidence and meta-analyses suggest no consistent increase in non-melanoma skin cancers (NMSC). Similarly, IL-17 inhibitors show potential risks but lack robust evidence in HS-specific populations.Conclusion: In conclusion, HS-associated malignancies, particularly SCC, underscore the need for further research to elucidate the mechanisms linking chronic inflammation to cancer development. Insights from such studies could guide preventative and therapeutic strategies, improving outcomes for HS patients.Keywords: hidradenitis suppurativa, treatment, skin cance

Hypergammaglobulinemia in Hidradenitis Suppurativa Patients: A New Emerging Association

Fabrizio Martora,* Teresa Battista,* Antonella Giordano, Luca Potestio, Matteo Megna Dermatology Unit, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy*These authors contributed equally to this workCorrespondence: Fabrizio Martora, Section of Dermatology - Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, Napoli, 80131, Italy, Tel +39 - 081 – 7462457, Fax +39 - 081 – 7462442, Email [email protected]: Hypergammaglobulinemia is a sign of B cell and plasma cell hyperactivity marked by elevated levels of gamma globulins, proteins within the gamma fraction of serum electrophoresis, linked to diseases like acute hepatitis, Hodgkin’s lymphoma, autoimmune conditions, and neoplasms. Monoclonal gammopathy of undetermined significance (MGUS) is found in 3.2% of individuals over 50 and 5.3% over 70 due to immunosenescence, the gradual immune decline influenced by chronic infections, malnutrition, hormonal dysregulation, and smoking. This retrospective, single-center observational study explored the association between hypergammaglobulinemia and Hidradenitis Suppurativa (HS) based on sex, age, disease severity (IHS4 score), and Adalimumab treatment. Sixty patients (54% women, 46% men, average age 47) were observed over 12 months. Hypergammaglobulinemia was found in 68% of patients, with the highest prevalence in the 15– 29 age group (80%). It was also associated with increased disease severity, particularly in younger patients, who showed a reduced clinical response to Adalimumab (average HiSCR difference of 25%). While common inflammation markers like CRP and ESR remain essential for HS management, this study highlighted that hypergammaglobulinemia is more prevalent in younger patients with severe forms of HS. Unlike older patients, where immunosenescence can lead to more normal gamma globulin levels, younger patients demonstrated a strong link between chronic inflammation and disease. The findings suggest further investigation is needed to determine whether hypergammaglobulinemia is merely a marker or contributes to HS pathogenesis. If validated, hypergammaglobulinemia could be used to monitor disease progression and customize treatments. In conclusion, integrating immunological assessments into HS management could improve patient outcomes, particularly in younger demographics. With larger studies, hypergammaglobulinemia might be considered a predictive factor for HS, especially for severe or treatment-resistant cases.Keywords: hidradenitis suppurativa, hypergammaglobulinemia, immunosenescenc

The Role of Interleukin 23/17 Axis in Psoriasis Management: A Comprehensive Review of Clinical Trials

Luca Potestio,* Fabrizio Martora,* Giuseppe Lauletta, Ylenia Vallone, Teresa Battista, Matteo Megna Section of Dermatology - Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy*These authors contributed equally to this workCorrespondence: Luca Potestio, Section of Dermatology - Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, Napoli, 80131, Italy, Tel +39 - 081 – 7462457, Fax +39 - 081 - 7462442, Email [email protected]: Psoriasis pathogenesis is influenced by genetic factors and characterized by a complex interplay between genetic predisposition and various environmental triggers. These triggers set off metabolic processes involving inflammation, cell signaling, immune response dysregulation, and antigen presentation. Several types of innate and adaptive immune cells are involved in psoriasis. Among the cytokine cascade which leads to psoriasis development, the interleukin (IL)-23/Th17 axis, especially IL-17 production, emerges as crucial. Recognizing the pivotal role of this axis has facilitated the development of selective and effective biological drugs, such as anti-IL17 and anti-IL23 monoclonal antibodies. These drugs aim to achieve the complete or near-complete disappearance of psoriatic lesions, as indicated by PASI100 and PASI90 responses, respectively. In this context, the aim of our review was to delve into the functioning of the IL-23/Th17 axis, its dysregulation in psoriasis pathogenesis, and the therapeutic potential of its inhibition. Currently, 4 anti-IL17 (secukinumab, ixekizumab, bimekizumab and brodalumab) and 3 anti-IL23 (guselkumab, risankizumab and tildrakizumab) have been approved. All these drugs showed high levels of effectiveness in both clinical trials and real-life experiences, with an excellent profile in terms of safety. Certainly, furthers studies will allow for better characterization of biologics’ profile, in order to administer the right drug for the right patients at the right moment.Keywords: psoriasis, management, clinical trial, IL-17/23 axi

Corresponding Functional Dynamics across the Hsp90 Chaperone Family: Insights from a Multiscale Analysis of MD Simulations

Understanding how local protein modifications, such as binding small-molecule ligands, can trigger and regulate large-scale motions of large protein domains is a major open issue in molecular biology. We address various aspects of this problem by analyzing and comparing atomistic simulations of Hsp90 family representatives for which crystal structures of the full length protein are available: mammalian Grp94, yeast Hsp90 and E.coli HtpG. These chaperones are studied in complex with the natural ligands ATP, ADP and in the Apo state. Common key aspects of their functional dynamics are elucidated with a novel multi-scale comparison of their internal dynamics. Starting from the atomic resolution investigation of internal fluctuations and geometric strain patterns, a novel analysis of domain dynamics is developed. The results reveal that the ligand-dependent structural modulations mostly consist of relative rigid-like movements of a limited number of quasi-rigid domains, shared by the three proteins. Two common primary hinges for such movements are identified. The first hinge, whose functional role has been demonstrated by several experimental approaches, is located at the boundary between the N-terminal and Middle-domains. The second hinge is located at the end of a three-helix bundle in the Middle-domain and unfolds/unpacks going from the ATP- to the ADP-state. This latter site could represent a promising novel druggable allosteric site common to all chaperones

Owning the problem: Media portrayals of overweight dogs and the shared determinants of the health of human and companion animal populations

Weight-related health problems have become a common topic in Western mass media. News-coverage has also extended to overweight pets, particularly since 2003 when the U.S. National Academy of Sciences announced that obesity was also afflicting co-habiting companion animals in record numbers. To characterize and track views in popular circulation on causes, consequences and responsibilities vis-à-vis weight gain and obesity, in pets as well as in people, this study examines portrayals of overweight dogs that appeared from 2000 through 2009 in British, American and Australian mass media. The ethnographic content analysis drew inspiration from the literature in population health, animal-human relationships, communication framing and the active nature of texts in cosmopolitan societies. Three main types of media articles about overweight dogs appeared during this period: 1) reports emphasizing facts and figures; 2) stories emphasizing personal prescriptions for dog owners, and 3) societal critiques. To help ordinary people make sense of canine obesity, media articles often highlight that dogs share the lifestyle of their human companion or owner, yet the implications of shared social and physical environments is rarely considered when it comes to solutions. Instead, media coverage exhorts people who share their lives with overweight dogs to ‘own the problem’ and, with resolve, to normalize their dog’s physical condition by imposing dietary, exercise and relationship changes, thereby individualizing culpability rather than linking it to broader systemic issues. Keywords: Companion animals; Media; Narrative analysis; Obesity; Public understandin