Heteropolymers in a Solvent at an Interface

Exact bounds are obtained for the quenched free energy of a polymer with random hydrophobicities in the presence of an interface separating a polar from a non polar solvent. The polymer may be ideal or have steric self-interactions. The bounds allow to prove that a ``neutral'' random polymer is localized near the interface at any temperature, whereas a ``non-neutral'' chain is shown to undergo a delocalization transition at a finite temperature. These results are valid for a quite general a priori probability distribution for both independent and correlated hydrophobic charges. As a particular case we consider random AB-copolymers and confirm recent numerical studies.Comment: 4 pages, no figure

Key interaction patterns in proteins revealed by cluster expansion of the partition function

The native conformation of structured proteins is stabilized by a complex network of interactions. We analyzed the elementary patterns that constitute such network and ranked them according to their importance in shaping protein sequence design. To achieve this goal, we employed a cluster expansion of the partition function in the space of sequences and evaluated numerically the statistical importance of each cluster. An important feature of this procedure is that it is applied to a dense, finite system. We found that patterns that contribute most to the partition function are cycles with even numbers of nodes, while cliques are typically detrimental. Each cluster also gives a contribute to the sequence entropy, which is a measure of the evolutionary designability of a fold. We compared the entropies associated with different interaction patterns to their abundances in the native structures of real proteins

Sequence and structural patterns detected in entangled proteins reveal the importance of co-translational folding

Proteins must fold quickly to acquire their biologically functional three-dimensional native structures. Hence, these are mainly stabilized by local contacts, while intricate topologies such as knots are rare. Here, we reveal the existence of specific patterns adopted by protein sequences and structures to deal with backbone self-entanglement. A large scale analysis of the Protein Data Bank shows that loops significantly intertwined with another chain portion are typically closed by weakly bound amino acids. Why is this energetic frustration maintained? A possible picture is that entangled loops are formed only toward the end of the folding process to avoid kinetic traps. Consistently, these loops are more frequently found to be wrapped around a portion of the chain on their N-terminal side, the one translated earlier at the ribosome. Finally, these motifs are less abundant in natural native states than in simulated protein-like structures, yet they appear in 32% of proteins, which in some cases display an amazingly complex intertwining

Folding Rate Optimization Promotes Frustrated Interactions in Entangled Protein Structures

Many native structures of proteins accomodate complex topological motifs such as knots, lassos, and other geometrical entanglements. How proteins can fold quickly even in the presence of such topological obstacles is a debated question in structural biology. Recently, the hypothesis that energetic frustration might be a mechanism to avoid topological frustration has been put forward based on the empirical observation that loops involved in entanglements are stabilized by weak interactions between amino-acids at their extrema. To verify this idea, we use a toy lattice model for the folding of proteins into two almost identical structures, one entangled and one not. As expected, the folding time is longer when random sequences folds into the entangled structure. This holds also under an evolutionary pressure simulated by optimizing the folding time. It turns out that optmized protein sequences in the entangled structure are in fact characterized by frustrated interactions at the closures of entangled loops. This phenomenon is much less enhanced in the control case where the entanglement is not present. Our findings, which are in agreement with experimental observations, corroborate the idea that an evolutionary pressure shapes the folding funnel to avoid topological and kinetic traps

Neural network time-series classifiers for gravitational-wave searches in single-detector periods

The search for gravitational-wave signals is limited by non-Gaussian transient noises that mimic astrophysical signals. Temporal coincidence between two or more detectors is used to mitigate contamination by these instrumental glitches. However, when a single detector is in operation, coincidence is impossible, and other strategies have to be used. We explore the possibility of using neural network classifiers and present the results obtained with three types of architectures: convolutional neural network, temporal convolutional network, and inception time. The last two architectures are specifically designed to process time-series data. The classifiers are trained on a month of data from the LIGO Livingston detector during the first observing run (O1) to identify data segments that include the signature of a binary black hole merger. Their performances are assessed and compared. We then apply trained classifiers to the remaining three months of O1 data, focusing specifically on single-detector times. The most promising candidate from our search is 2016-01-04 12:24:17 UTC. Although we are not able to constrain the significance of this event to the level conventionally followed in gravitational-wave searches, we show that the signal is compatible with the merger of two black holes with masses $m_1 = 50.7^{+10.4}_{-8.9}\,M_{\odot}$ and $m_2 = 24.4^{+20.2}_{-9.3}\,M_{\odot}$ at the luminosity distance of $d_L = 564^{+812}_{-338}\,\mathrm{Mpc}$.Comment: 29 pages, 11 figures, submitted to CQ

Association between elevated TGA-IgA titers and older age at diagnosis with absence of HBV seroconversion in celiac children

Patients with celiac disease can have a low rate of protective hepatitis B (HBV) antibody titers after vaccination. We aimed to evaluate the HBV seroconversion in celiac disease (CD) children at the time of diagnosis as well as to identify the presence of possible predictive factors. Celiac disease children were prospectively enrolled and tested for antibodies against the S protein of HBV (HBsAg) at time of diagnosis between January 2009 and February 2020. Based on the serologic response to the vaccine, "responders" and "non-responders" were identified. Statistical analysis has been performed through R statistical software (3.5.1 version, R core Team) Of 96 CD children evaluated, 41.7% (n = 40) showed non-protective or absent antibody titers against HBV. Elevated IgA-antibodies against transglutaminase 2 (TGA-IgA) values and older age at diagnosis were associated with an absent seroconversion to HBV vaccine, while presenting symptoms were not significant. An elevated prevalence of absent seroconversion to HBV vaccine exists in this cohort of CD patients at the time of disease diagnosis. Elevated TGA-IgA titers and older age at diagnosis seem to negatively predict seroconversion. Further studies are needed to identify the real profile of "non-responders", aiming to organize surveillance and eventual revaccination strategy

Type 1 diabetes, thyroid, gastric and adrenal humoral autoantibodies are present altogether in almost one third of adult celiac patients at diagnosis, with a higher frequency than children and adolescent celiac patients

Background: No data are available on the frequency of organ-specific humoral autoimmunity at diagnosis of adult celiac disease (CD). Aim: To evaluate the humoral immunoreactivities specific of type 1 diabetes (T1D), thyroid (THD), atrophic-gastritis (AG) and Addison’s (AD) diseases in 92 adult CD patients at diagnosis and 237 adult healthy subjects (CTRL). Methods: T1D, THD and AD specific autoantibodies were analyzed by radioimmunoprecipitation assays. AG autoantibodies were detected by enzyme-linked immunosorbent assay. Results: Of 92 CD patients, 31.5% were positive for at least one of the organ-specific autoantibodies investigated (p <.0001 vs CTRL). Thyroid, diabetes, gastric and adrenal-autoantibodies, that increase with age at diagnosis, were detected in 12.0%, 10.9%, 10.9%, 2.2% of CD patients, respectively. Gastric- and diabetes- rather than thyroid- and adrenal-autoimmunity seem to be specifically related to presence of CD. Conclusions: One third of adult CD patients at diagnosis is target of at least one organ-specific autoantibody. A systematic organ-specific autoantibody screening in these patients might be of value to promptly identify, prevent or treat the relative diseases

Fasting Neurotensin Levels in Pediatric Celiac Disease Compared with a Control Cohort

Background and Aims. Neurotensin (NT) is a gut hormone secreted by specific endocrine cells scattered throughout the epithelial layer of the small intestine, which has been identified as an important mediator in several gastrointestinal functions and disease conditions. Its potential involvement in celiac disease (CD) has been investigated, but there are conflicting findings. The aim of this study was to evaluate serum NT levels in children with CD at diagnosis, compared to a control group, and to investigate whether NT correlated in CD patients with symptoms, antibody response, and intestinal mucosal damage. Materials and Methods. Children (1-16 years old) undergoing gastrointestinal endoscopy for CD or for other clinical reasons were included in this study. Patients with CD diagnosed according to the 2012 European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines without biopsy were also recruited. Fasting serum samples were analyzed for NT levels using ELISA. Logistic regression, Wilcoxon rank sum, and Spearman's rank tests were used for statistical analysis. Results. Thirty children (18 females, 2.2-15.9 years old) were enrolled. Of 25 patients who underwent endoscopy, 9 were CD patients, 13 were controls, and 3 were excluded due to nonspecific inflammation at duodenal biopsy. CD was diagnosed in 5 patients without biopsy. NT median was higher in CD patients compared to controls (13.25 (IQR 9.4-17.5) pg/ml vs. 7.8 (IQR 7.6-10) pg/ml; p=0.02). No statistically significant association between NT and clinical, serological, or histological data of CD was observed in this CD cohort. Conclusions. To our knowledge, this is the first study that evaluates NT in CD children from Italy. Results show that NT is higher in the serum of CD children at diagnosis compared to controls. However, larger-scale studies are required to validate these findings. Whether serum NT levels can be an adjunctive marker for pediatric CD remains currently elusive