Molecular Insight into the Effect of HIV-TAT Protein on Amyloid-β Peptides.

Increased deposition of amyloid-β (Aβ) plaques in the brain is a frequent pathological feature observed in human immunodeficiency virus (HIV)-positive patients. Emerging evidence indicates that HIV regulatory proteins, particularly the transactivator of transcription (TAT) protein, could interact with Aβ peptide, accelerating the formation of Aβ plaques in the brain and potentially contributing to the onset of Alzheimer's disease in individuals with HIV infection. Nevertheless, the molecular mechanisms underlying these processes remain unclear.

The stability and dynamics of the Aβ40/Aβ42 interlaced mixed fibrils.

The accumulation of fibrillar amyloid-β (Aβ) aggregates in the brain, predominantly comprising 40- and 42-residue amyloid-β (Aβ40 and Aβ42), is a major pathological hallmark of Alzheimer's disease (AD). Aβ40 and Aβ42 naturally coexist in the brain under normal physiological conditions, and their interplay is generally considered to be a critical factor in the progression of AD. In addition to forming homogeneous oligomers and fibrils, Aβ40 and Aβ42 are also reported to co-assemble into hetero-oligomers and interlaced mixed fibrils, as evidenced by solid-state nuclear magnetic resonance spectroscopy (NMR), high molecular weight mass spectrometry and cross-seeding experiments.

Catalytic Reaction Mechanism of Bacterial GH92 α-1,2-Mannosidase: A QM/MM Metadynamics Study.

The catalytic mechanism of a -dependent family 92 -mannosidase, which is abundantly present in human gut flora and malfunctions leading to the lysosomal storage disease α-mannosidosis, has been investigated using quantum mechanics/molecular mechanics and metadynamics methods. Computational efforts show that the enzyme follows a conformational itinerary of and the ion serves a dual purpose, as it not only distorts the sugar ring but also plays a crucial role in orchestrating the arrangement of catalytic residues. This orchestration, in turn, contributes to the facilitation of conformers for the ensuing reaction.

Evaluation of the thickness and internal structure of the masseter muscle with ultrasonography in female bruxism patients.

Objectives: The aim of this study was to evaluate the differences in the thickness and internal structure of the masseter muscle in individuals with and without bruxism by ultrasonography.

Materials And Methods: A total of 60 female patients with and without bruxism whose ages were ranging between 20 and 35 were included in the study. The masseter muscle thickness was measured during rest and maximum bite position.

Resolution exchange with tunneling for enhanced sampling of protein landscapes.

Simulations of protein folding and protein association happen on timescales that are orders of magnitude larger than what can typically be covered in all-atom molecular dynamics simulations. Use of low-resolution models alleviates this problem but may reduce the accuracy of the simulations. We introduce a replica-exchange-based multiscale sampling technique that combines the faster sampling in coarse-grained simulations with the potentially higher accuracy of all-atom simulations.

Interconversion between Serum Amyloid A Native and Fibril Conformations.

Overexpression of serum amyloid A (SAA) can lead to a form of amyloidosis where the fibrils are made of SAA fragments, most often SAA. Using Replica Exchange with Tunneling, we study the conversion of a SAA chain between the folded conformation and a fibril conformation. We find that the basins in the free energy landscape corresponding to the two motifs are separated by barriers of only about 2-3 .

Role of Notch, IL-1 and leptin expression in colorectal cancer.

An increasing number of studies have shown that angiogenesis has an important role in the progression of cancer. The growth of a new network of blood vessels is crucial for tumor growth and metastasis, which is promoted by several proangiogenic factors. Leptin, an essential adipokine that is secreted from fat tissue, is one of these pro-angiogenic factors.

Investigation of thyroid blood tests and thyroid ultrasound findings of patients with rosacea.

We aimed to investigate the relationship between rosacea and thyroid diseases by analyzing thyroid blood tests and ultrasound findings of our patients recently diagnosed with rosacea. This study was designed as a prospective, single-center study. Dermatological examination findings, lesion locations were recorded, and rosacea clinical scores were calculated for all study group patients.

Enhanced B7-H4 expression in gliomas with low PD-L1 expression identifies super-cold tumors.

Background: Characterizing expression profiles of different immune checkpoint molecules are promising for personalized checkpoint inhibitory immunotherapy. Gliomas have been shown as potential targets for immune checkpoint inhibitors recently. Our study was performed to determine coexpression levels of two major B7 immune regulatory molecules programmed death ligand 1 (PD-L1) and B7-H4, both of which have been demonstrated to inhibit antitumor host immunity in gliomas.

Diagnostic accuracy of panoramic radiography and ultrasonography in detecting periapical lesions using periapical radiography as a gold standard.

Objectives: The purpose of this study was to compare the accuracy of imaging techniques in diagnosing periapical lesions.

Methods: Imaging records of 80 patients (51 females, 29 males, aged between 14 and 75 years) including periapical and panoramic radiographs and ultrasonographic images were selected from databases of Selcuk University Dentistry Faculty. Periapical radiographs were accepted as gold-standard and 160 anterior maxillary and mandibular teeth with or without periapical lesion were included to the study.

Metabolic disturbances and cardiovascular risk factors in obese children with vitamin D deficiency.

Objectives: The prevalence of obesity among children and adolescents has been rapidly increasing in recent years. Obese individuals are at risk of vitamin D deficiency. The aim of this study was to investigate the relationship between vitamin D deficiency and anthropometric measurements, cardiovascular risk factors, and glucose homeostasis in obese children.

Accuracy of the demirjian, willems and cameriere methods of estimating dental age on turkish children.

Background And Aim: Age estimation plays a significant role in forensic science, archeology, pediatric endocrinology and clinical dentistry. Tooth development is a reliable pathway for age estimation, especially in children. The aim of this study was to evaluate the accuracy of the Demirjian method (DM), Willems method (WM) and Cameriere method (CM).

Pyridyl-Acyl Hydrazone Rotaxanes and Molecular Shuttles.

We report on rotaxanes featuring a pyridyl-acyl hydrazone moiety on the axle as a photo/thermal-switchable macrocycle binding site. The pyridyl-acyl E-hydrazone acts as a hydrogen bonding template that directs the assembly of a benzylic amide macrocycle around the axle to form [2]rotaxanes in up to 85% yield; the corresponding Z-hydrazone thread affords no rotaxane under similar conditions. However, the E-rotaxane can be smoothly converted into the Z-rotaxane in 98% yield under UV irradiation.

Freestyle Perforator-Based Fasciocutaneous Flap Reconstruction in Nicolau Syndrome-Related Tissue Necrosis.

The actual pathology of the Nicolau syndrome (NS) is still unknown. It is thought to involve direct vascular damage and vasospasm. Many NS cases were reported in the literature but a treatment protocol is still not established.

Replica-exchange-with-tunneling for fast exploration of protein landscapes.

While the use of replica-exchange molecular dynamics in protein simulations has become ubiquitous, its utility is limited in many practical applications. We propose to overcome some shortcomings that hold back its use in settings such as multi-scale or explicit solvent simulations by integrating ideas of hybrid MC/MD into the replica-exchange protocol. This Replica-Exchange-with-Tunneling method is tested by simulating the Trp-cage protein, a system often used in molecular biophysics for testing sampling techniques.

Multicanonical Molecular Dynamics Simulations of the N-terminal Domain of Protein L9.

We describe multicanonical molecular dynamic simulations of the N-terminal domain of the protein L9. Analyzing free energy landscapes and thermal ordering, we propose a possible folding mechanism for the protein. By comparing our results with that of molecular dynamics runs of the protein at constant temperature, we find that multicanonical molecular dynamics leads to orders of magnitude higher sampling of folding transitions.

Folding and self-assembly of a small heterotetramer.

Designed miniproteins offer a possibility to study folding and association of protein complexes, both experimentally and in silico. Using replica exchange molecular dynamics and the coarse-grain UNRES force field, we have simulated the folding and self-assembly of the heterotetramer BBAThet1, comparing it with that of the homotetramer BBAT1 which has the same size and ββα-fold. For both proteins, association of the tetramer precedes and facilitates folding of the individual chains.

Sampling of Protein Folding Transitions: Multicanonical Versus Replica Exchange Molecular Dynamics.

We compare the efficiency of multicanonical and replica exchange molecular dynamics for the sampling of folding/unfolding events in simulations of proteins with end-to-end -sheet. In Go-model simulations of the 75-residue MNK6, we observe improvement factors of 30 in the number of folding/unfolding events of multicanonical molecular dynamics over replica exchange molecular dynamics. As an application, we use this enhanced sampling to study the folding landscape of the 36-residue DS119 with an all-atom physical force field and implicit solvent.

In silico cross seeding of Aβ and amylin fibril-like oligomers.

Recent epidemiological data have shown that patients suffering from Type 2 Diabetes Mellitus have an increased risk to develop Alzheimer's disease and vice versa. A possible explanation is the cross-sequence interaction between Aβ and amylin. Because the resulting amyloid oligomers are difficult to probe in experiments, we investigate stability and conformational changes of Aβ-amylin heteroassemblies through molecular dynamics simulations.

Leptin receptor (Ob-R) mRNA expression and serum leptin concentration in patients with colorectal and metastatic colorectal cancer.

The objective of the present study was to investigate the effect of leptin on the progression of colorectal carcinoma to metastatic disease by analyzing the serum leptin concentration and Ob-R gene expression in colon cancer tissues. Tissue samples were obtained from 31 patients who underwent surgical resection for colon (18 cases) and metastatic colon (13 cases) cancer. Serum leptin concentration was determined by an enzyme-linked immunosorbent assay (ELISA) and Ob-R mRNA expression by real-time polymerase chain reaction (RT-PCR) for both groups.

Autonomous shuttling driven by an oscillating reaction: proof of principle in a cucurbit[7]uril-Bodipy pseudorotaxane.

A bipyridinium dication-substituted Bodipy fluorophore, with a terminal carboxylic acid function, provides two alternative stations for cucurbit[7]uril. Changing pH from basic to acidic results in shuttling of the cucurbit[7]uril from one station to another. In addition, this shuttling is accompanied by a change in the emissive properties of the Bodipy dye, which is only observed in the presence of cucurbit[7]uril.

The effects of image compression on quantitative measurements of digital panoramic radiographs.

Objectives: The aims of this study were to explore how image compression affects density, fractal dimension, linear and angular measurements on digital panoramic images and assess inter and intra-observer repeatability of these measurements.

Study Design: Sixty-one digital panoramic images in TIFF format (Tagged Image File Format) were compressed to JPEG (Joint Photographic Experts Group) images. Two observers measured gonial angle, antegonial angle, mandibular cortical width, coronal pulp width of maxillary and mandibular first molar, tooth length of maxillary and mandibular first molar on the left side of these images twice.

Enhancing the affinity of SEB-binding peptides by repeating their sequence.

The utilization of peptide ligands in biosensors and bioassays is dependent on achieving high affinity of these peptides toward their targets. In a previous report, we identified 12-mer peptides that could selectively bind to Staphylococcal enterotoxin B (SEB) using a phage-display library. In this study, we explore for new modification approaches to enhance the affinity of two different SEB-binding peptides.