Cosolvent Exclusion Drives Protein Stability in Trimethylamine N-Oxide and Betaine Solutions.

Using a combination of molecular dynamics simulation, dialysis experiments, and electronic circular dichroism measurements, we studied the solvation thermodynamics of proteins in two osmolyte solutions, trimethylamine N-oxide (TMAO) and betaine. We showed that existing force fields are unable to capture the solvation properties of the proteins lysozyme and ribonuclease T1 and that the inaccurate parametrization of protein-osmolyte interactions in these force fields promoted an unphysical strong thermal denaturation of the trpcage protein. We developed a novel force field for betaine (the KBB force field) which reproduces the experimental solution Kirkwood-Buff integrals and density. We further introduced appropriate scaling to protein-osmolyte interactions in both the betaine and TMAO force fields which led to successful reproduction of experimental protein-osmolyte preferential binding coefficients for lysozyme and ribonuclease T1 and prevention of the unphysical denaturation of trpcage in osmolyte solutions. Correct parametrization of protein-TMAO interactions also led to the stabilization of the collapsed conformations of a disordered elastin-like peptide, while the uncorrected parameters destabilized the collapsed structures. Our results establish that the thermodynamic stability of proteins in both betaine and TMAO solutions is governed by osmolyte exclusion from proteins.

Venomous snakes elicit stronger fear than nonvenomous ones: Psychophysiological response to snake images.

Snakes have been important ambush predators of both primates and human hunter-gatherers throughout their co-evolutionary history. Viperid snakes in particular are responsible for most fatal venomous snakebites worldwide and thus represent a strong selective pressure. They elicit intense fear in humans and are easily recognizable thanks to their distinctive morphotype. In this study, we measured skin resistance (SR) and heart rate (HR) in human subjects exposed to snake pictures eliciting either high fear (10 venomous viperid species) or disgust (10 nonvenomous fossorial species). Venomous snakes subjectively evaluated as frightening trigger a stronger physiological response (higher SR amplitude) than repulsive non-venomous snakes. However, stimuli presented in a block (more intense stimulation) do not trigger a stronger emotional response compared to sequentially presented stimuli (less intense stimulation). There are significant interindividual differences as subjects with high fear of snakes confronted with images of viperid snakes show stronger, longer-lasting, and more frequent changes in SR and higher HR compared to low-fear subjects. Thus, we show that humans demonstrate a remarkable ability to discriminate between dangerous viperids and harmless fossorial snakes, which is also reflected in distinct autonomous body responses.

Pressure, Peptides, and a Piezolyte: Structural Analysis of the Effects of Pressure and Trimethylamine-N-oxide on the Peptide Solvation Shell.

The osmolyte trimethylamine-N-oxide (TMAO) is able to increase the thermodynamic stability of folded proteins, counteracting pressure denaturation. Herein, we report experimental solubility data on penta-alanine (pAla) in aqueous TMAO solutions (at pH = 7 and pH = 13) together with molecular simulation data for pAla, penta-serine (pSer), and an elastin-like peptide (ELP) sequence (VPGVG) under varying pH and pressure conditions. The effect of the peptide end groups on TMAO-peptide interactions is investigated by comparing the solvation of zwitterionic and negatively charged pentamers with the solvation of pentamers with charge-neutral C- and N-termini and linear, virtually infinite, peptide chains stretched across the periodic boundaries of the simulation cell. The experiments and simulations consistently show that TMAO is net-depleted from the pAla-water interface, but local accumulation of TMAO is observed just outside the first hydration shell of the peptide. While the same observations are also made in the simulations of the zwitterionic pentamers (Ala, Ser, and ELP) and virtually infinite peptide chains (Ala and ELP), weak preferential binding of TMAO is instead observed for pAla with neutral end groups at a 1 M TMAO concentration and for an ELP pentamer with capped neutral end groups at a 0.55 M TMAO concentration studied in previous work (Y.-T. Liao et al. Proc. Natl. Acad. Sci. USA, 2017, 114, 2479-2484). The above observations made at 1 bar ambient pressure remain qualitatively unchanged at 500 bar and 2 kbar. Local accumulation of TMAO correlates with a reduction in the total number of peptide-solvent hydrogen bonds, independent of the peptide's primary sequence and the applied pressure. By weakening water hydrogen bonds with the protein backbone, TMAO indirectly contributes to stabilizing internal hydrogen bonds in proteins, thus providing a protein stabilization mechanism beyond net depletion.

The semi-automated algorithm for the detection of bone marrow oedema lesions in patients with axial spondyloarthritis.

The aim of the study was to create the efficient tool for semi-automated detection of bone marrow oedema lesions in patients with axial spondyloarthritis (axSpA). MRI examinations of 22 sacroiliac joints of patients with confirmed axSpA-related sacroiliitis (median SPARCC score: 14 points) were included into the study. Design of our algorithm is based on Maksymowych et al. evaluation method and consists of the following steps: manual segmentation of bones (T1W sequence), automated detection of reference signal region, sacroiliac joint central lines and ROIs, a division of ROIs into quadrants, automated detection of inflammatory changes (STIR sequence). As a gold standard, two sets of manual lesion delineations were created. Two approaches to the performance assessment of lesion detection were considered: pixel-wise (detections compared pixel by pixel) and quadrant-wise (quadrant to quadrant). Statistical analysis was performed using Spearman's correlation coefficient. Correlation coefficient obtained for pixel-wise comparison of semi-automated and manual detections was 0.87 (p = 0.001), while for quadrant-wise analysis was 0.83 (p = 0.001). The correlation between two sets of manual detections was 0.91 for pixel-wise comparison (p = 0.001) and 0.88 (p = 0.001) for quadrant-wise approach. Spearman's correlation between two manual assessments was not statistically different from the correlation between semi-automated and manual evaluations, both for pixel- (p = 0.14) and quadrant-wise (p = 0.17) analysis. Average single slice processing time: 0.64 ± 0.30 s. Our method allows for objective detection of bone marrow oedema lesions in patients with axSpA. The quantification of affected pixels and quadrants has comparable reliability to manual assessment.

The superficial temporal artery: A meta-analysis of its prevalence and morphology.

INTRODUCTION: The superficial temporal artery (STA) is a terminal branch of the external carotid artery. It supplies the regions of scalp and face. The morphometrical data concerning STAs are not consistent; therefore, in this systemic review and meta-analysis, we aimed in this to provide an up-to-date data on its anatomic features. MATERIAL AND METHODS: In order to do this, PubMed, Embase, ScienceDirect, and Web of Science were searched. We followed the Preferred Reporting Items and Review and Meta-Analyses guidelines for the meta-analysis. Studies that reported the prevalence and anatomical data regarding STA were included in further analyses. RESULTS: Out of 1,446 studies initially evaluated, 21 were included in the meta-analysis (874 patients/donors). The STA diameter was 1.5 mm (95% confidence interval [CI]: 1.47-1.53 mm). The frontal and parietal branches of the STA were present in 97.6% (95% CIs: 94.6-99.5%) and 96.4% (95% CIs: 93.5-98.5%) of the cases, respectively. The STA bifurcation point was located above the zygomatic arch in 79.1% (95% CI: 68.0-84.3), below the zygomatic arch in 6.7% (95% CI: 2.4-12.1), and on the zygomatic arch in 11.1% of the cases (95% CI: 5.4-17.5). There was no bifurcation of the STA in 3.1% of the cases (95% CI: 0.4-7.3). CONCLUSION: The most comprehensive analysis of STA morphological features is presented. The results from this evidence-based anatomical study will improve understanding of the clinical STA anatomy, which in turn has major implications for understanding the STA in clinical practice.

Scary and nasty beasts: Self-reported fear and disgust of common phobic animals.

Animal phobias are one of the most prevalent mental disorders. We analysed how fear and disgust, two emotions involved in their onset and maintenance, are elicited by common phobic animals. In an online survey, the subjects rated 25 animal images according to elicited fear and disgust. Additionally, they completed four psychometrics, the Fear Survey Schedule II (FSS), Disgust Scale - Revised (DS-R), Snake Questionnaire (SNAQ), and Spider Questionnaire (SPQ). Based on a redundancy analysis, fear and disgust image ratings could be described by two axes, one reflecting a general negative perception of animals associated with higher FSS and DS-R scores and the second one describing a specific aversion to snakes and spiders associated with higher SNAQ and SPQ scores. The animals can be separated into five distinct clusters: (1) non-slimy invertebrates; (2) snakes; (3) mice, rats, and bats; (4) human endo- and exoparasites (intestinal helminths and louse); and (5) farm/pet animals. However, only snakes, spiders, and parasites evoke intense fear and disgust in the non-clinical population. In conclusion, rating animal images according to fear and disgust can be an alternative and reliable method to standard scales. Moreover, tendencies to overgeneralize irrational fears onto other harmless species from the same category can be used for quick animal phobia detection.

The Arteries of the Central Forehead: Implications for Facial Plastic Surgery.

BACKGROUND: The forehead has substantial importance as an aesthetic unit. The central and supraorbital parts of this area are supplied by the supratrochlear (ST) and supraorbital (SO) arteries as well as the recently defined paracentral (PA) and central arteries. OBJECTIVES: The authors aimed to assess the morphometry of the vessels of the forehead in the context of plastic surgery and minimally invasive cosmetic procedures. METHODS: This research included 40 cadavers directed for forensic autopsy and subjected to postmortem computed tomography angiography. In total, 75 hemifaces were examined for the course and location of arteries relative to the bones and surrounding structures. RESULTS: The arteries were observed as follows: ST in 97.3%, SO in 89.3%, and PA in 44.0%. The PA can be expected in the 13-mm-wide zone starting 2 mm laterally from the midline. The ST should be expected in the 10-mm-wide area extended laterally from the tenth millimeter from the midline, and the SO should be expected in the slightly wider (11 mm) area extending laterally from the 20th millimeter from the midline. For the proximal main trunks of the ST and SO arteries, we observed no overlap between the zones of occurrence, whereas the zones for the PA and ST main proximal trunks did overlap. No distinctive central artery was observed in the midline region of the forehead, but instead a network of small vessels in the midline region was visible. CONCLUSIONS: The ST is the main and most conservative artery of this region and the PA is the most variable. A unique and detailed anatomical map was created to better understand the vasculature of the forehead area.

Anatomical Map of the Facial Artery for Facial Reconstruction and Aesthetic Procedures.

BACKGROUND: The facial artery (FA) is the main blood vessel supplying the anterior face and an understanding of its anatomy is crucial in facial reconstruction and aesthetic procedures. OBJECTIVES: The aim of this study was to assess the many anatomical features of the FA utilizing a multidimensional approach. METHODS: Head and neck computed tomographic angiographies of 131 patients (255 FAs) with good image quality were evaluated. The FA was classified according to its termination pattern, course, and location with reference to soft tissue/bone surrounding structures. RESULTS: In total, each branch was present as follows: the submental artery (44.8%), the inferior labial artery (60%), the superior labial artery (82.2%), the lateral nasal artery (25.1%), and the angular artery (42.5%). The most common FA course was the classic course, situated medially to the nasolabial fold (27.1%). In total 65.5% of the arteries were located medially to the nasolabial fold, and only 12.3% of them were totally situated lateral to the nasolabial fold. The median distance (with quartiles) from the inferior orbital rim reached the FA after the superior labial artery branched off in 50.2% of cases and was 36.6 mm (33.4; 43.3). The angle between the FA and the inferior border of the mandible was 49.8o (31.9; 72.4). The horizontal distances between the oral commissure and naris to the FA were 8.5 ± 4.0 mm and 12.1 ± 6.7 mm, respectively. CONCLUSIONS: An anatomical map summarizing the major measurements and geometry of the FA was generated. The detailed anatomy and relative positioning of the FA should be considered to avoid any unexpected complications in plastic surgery.

The transverse facial artery anatomy: Implications for plastic surgery procedures.

BACKGROUND: The transverse facial artery (TFA) perfuses the lateral face. Knowledge of topographical anatomy of the lateral face is crucial for safe procedural performance in aesthetic and plastic surgery, especially the face lift flap and face transplant. The aim of the present study was to assess detailed TFA morphometrical features. PATIENTS AND METHODS: One-hundred computed tomography head angiographies were analyzed. TFA numbers and origins were recorded bilaterally (200 cases). TFA diameters and lengths in addition to their positions in relation to neighboring vessels and the zygomatic arches were measured. RESULTS: TFA was present in 96% of cases (192/200, left = 97, right = 95). A single TFA was present in 95.3% and double TFAs were present in 4.7% of cases. In 91.7%, the TFA originated from the superficial temporal artery, and in 3.1%, it originated from the external carotid artery. One left TFA originated from the maxillary artery. The TFA was significantly longer on the right than on the left side (56.6±26.0 versus 47.3±22.2 mm; p = 0.03). The TFA mean diameter was 1.0±0.4 mm (range: 0.4-2.2 mm) with no difference between face sides. TFA length correlated with its diameter (r = 0.46, p <0.05). The TFA always originated below the zygomatic arch, and it should be found in the 8.8 mm wide area beginning 17.0mm below the lower border of the zygomatic arch. CONCLUSIONS: The TFA has a significant role in lateral face vascularization, and absence of this vessel is very uncommon.

The Superficial Temporal Artery: Anatomical Map for Facial Reconstruction and Aesthetic Procedures.

BACKGROUND: The superficial temporal artery (STA), a terminal branch of the external carotid artery, supplies multiple regions of the scalp and face. Knowledge of the STA is important for reconstructive and aesthetic procedures of the head and face. OBJECTIVES: The aim of this study was to map the STA in relation to anatomical landmarks. METHODS: Computed tomographic head angiographies of 215 patients were included in this study; the final analysis comprised 419 STAs. The STA's main branches and variants were identified. The diameters of the STA and its frontal and occipital branches were measured, and the distance between the STA tree and anatomical landmarks was delineated. RESULTS: Frontal and parietal branches were recorded in 98.1% and 90.7% of patients, respectively. The mean diameters, measured 1 and 7 cm from the STA bifurcation for the frontal branch, were 0.97 ± 0.32 and 0.81 ± 0.26 mm, respectively, and for the parietal branch, the diameters were 0.96 ± 0.28 and 0.76 ± 0.23 mm, respectively. The STA bifurcation point was located above the zygomatic arch (ZA) in 75.6%, below in 14.7%, and on the ZA in 9.7% of patients. The mean distance from the ZA center to the STA bifurcation was 16.8 ± 16.0 mm. CONCLUSIONS: The STA artery and its main branches follow a conservative course, and serious anatomical variations are relatively rare. The STA and its main branches may be localized using simple anatomical landmarks. An anatomical map showing artery-free zones in the lateral forehead region was presented, which may prove useful for plastic, reconstructive, and aesthetic surgeons.Level of Evidence: 4.