Daily GDF15 treatment has sex-specific effects on body weight and food intake and does not enhance the effects of voluntary physical activity in mice.

Growth differentiation factor 15 (GDF15) is a stress-induced cytokine that suppresses food intake and causes weight loss. GDF15 also reduces voluntary physical activity and, thus, it is not clear whether combining GDF15 with exercise will be beneficial or if reductions in food intake would be offset by decreases in physical activity. We investigated how GDF15 treatment combined with voluntary wheel running (VWR) would impact weight gain, food intake, adiposity and indices of metabolic health in mice.

Skeletal muscle mitochondrial morphology negatively affected in mice lacking Xin.

Altered mitochondrial structure and function are implicated in the functional decline of skeletal muscle. Numerous cytoskeletal proteins are known to affect mitochondrial homeostasis, but this complex network is still being unraveled. Here, we investigated mitochondrial alterations in mice lacking the cytoskeletal adapter protein, XIN (XIN-/-).

Exploring genetic variants in congenital monosaccharide-disaccharide metabolism: Carrier ratios and phenotypic insights.

Objectives: Adverse food reactions, often underestimated, encompass congenital monosaccharide-disaccharide metabolism disorders, yielding diverse outcomes such as abdominal pain, diarrhea, bleeding disorders, and even death. This study retrospectively scrutinized genetic variants linked to these disorders in a cohort subjected to whole-exome sequence analysis (WES), determining carrier frequencies and genotype-phenotype correlations.

Methods: Data from 484 patients, were retrospectively analyzed using a gene panel (ALDOB, FBP1, GALE, GALK1, GALM, GALT, LCT, SLC2A2, SLC5A1, SI) for congenital monosaccharide-disaccharide metabolism disorders.

A case report of a patient with neurodevelopmental disorder with impaired speech and hyperkinetic movements: A biallelic variant in the ZNF142 gene.

Biallelic pathogenic variations in the zinc finger protein 142 (ZNF142) gene are associated with neurodevelopmental disorder with impaired speech and hyperkinetic movements (NEDISHM). This disorder is characterized by developmental delay, intellectual disability, speech delay, and movement disorders such as dystonia, tremor, ataxia, and chorea. Here, we report a patient who exhibited common neurological features and rarely reported brain MRI findings.

Primary immune regulatory disorders (PIRD): expanding the mutation spectrum in Turkey and identification of sixteen novel variants.

Human Inborn Errors of Immunity (IEIs) encompass a clinically and genetically heterogeneous group of disorders, ranging from mild cases to severe, life-threatening types. Among these, Primary Immune Regulatory Disorders (PIRDs) constitute a subset of IEIs characterized by diverse clinical phenotypes, prominently featuring severe atopy, autoimmunity, lymphoproliferation, hyperinflammation, autoinflammation, and susceptibility to malignancies. According to the latest report from the International Union of Immunological Societies (IUIS), PIRDs arise from mutations in various genes including LYST, RAB27A, AP3B1, AP3D1, PRF1, UNC13D, STX11, STXBP2, FAAP24, SLC7A7, RASGRP1, CD70, CTPS1, RLTPR, ITK, MAGT1, PRKCD, TNFRSF9, SH2DIA, XIAP, CD27 (TNFRSF7), FAS (TNFRSF6), FASLG (TNFSF6), CASP10, CASP8, FADD, LRBA, STAT3, AIRE, ITCH, ZAP70, TPP2, JAK1, PEPD, FOXP3, IL2RA, CTLA4, BACH2, IL2RB, DEF6, FERMT1, IL10, IL10RA, IL10RB, NFAT5, TGFB1, and RIPK1 genes.

Cyclotide-rich fractions containing nanofibers by electrospinning: preparation, characterization and examination of antimicrobial activity.

In this study, antimicrobial nanofibers were produced with the mixtures of polyvinyl alcohol (PVA) and cyclotide-rich fractions by electrospinning method. After extraction, the first separation was carried out with C18 flash chromatography and then fractioned into five separate parts by reversed-phase high-pressure liquid chromatography (RP-HPLC). The molecular weights of cyclotides in each fraction were determined by quadrupole time-of-flight liquid chromatography-mass spectrometry (Q-TOF LC-MS).

Anemia and thrombocytopenia due to a novel BRPF1 variant in a family from Çanakkale with intellectual disability and dysmorphic facies: Case report and review of the literature.

Intellectual developmental disorder with dysmorphic facies and ptosis (IDDDFP) (MIM#617333) is an autosomal dominant disorder characterized by delayed psychomotor development, intellectual disability (ID), and dysmorphic facial features due to pathogenic variations in the Bromodomain- and PHD Finger-Containing Protein (BRPF1) (MIM#602410) gene. Herein, we report the first Turkish patients with IDDDFP. Additionally, the patients had hematopoietic disorders such as anemia and thrombocytopenia, which have not been previously described in IDDDFP patients.

Hematopoietic stem cell transplantation with reduced toxicity conditioning regimen in mitochondrial neurogastrointestinal encephalopathy syndrome.

Background: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disorder due to mutations in the TYMP gene. Clinical findings are characterized by neurologic manifestations and severe gastrointestinal dysfunction. The syndrome is usually fatal, the most effective treatment appears to be hematopoietic stem cell transplantation (HSCT).

Design and modification of frog skin peptide brevinin-1GHa with enhanced antimicrobial activity on Gram-positive bacterial strains.

Naturally occurring frog skin peptides are one of largest sources of antimicrobial peptides that have many advantages including high potency, broad spectrum of targets and low susceptibility to multiple drug-resistance bacteria. However, they also have disadvantages such as hemolytic activity, low stability and high production costs. For these reasons, various strategies have been applied to overcome these drawbacks restricting their use in clinical trials.

A comparative study of machine learning methods for predicting the evolution of brain connectivity from a baseline timepoint.

Background: Predicting the evolution of the brain network, also called connectome, by foreseeing changes in the connectivity weights linking pairs of anatomical regions makes it possible to spot connectivity-related neurological disorders in earlier stages and detect the development of potential connectomic anomalies. Remarkably, such a challenging prediction problem remains least explored in the predictive connectomics literature. It is a known fact that machine learning (ML) methods have proven their predictive abilities in a wide variety of computer vision problems.

Atomic resolution map of the soluble amyloid beta assembly toxic surfaces.

Soluble amyloid beta assemblies (Aβ ) are neurotoxic and play a central role in the early phases of the pathogenesis cascade leading to Alzheimer's disease. However, the current knowledge about the molecular determinants of Aβ toxicity is at best scant. Here, we comparatively analyze Aβ prepared in the absence or presence of a catechin library that modulates cellular toxicity.

A Systemic-Onset Juvenile Idiopathic Arthritis Patient with Reduced Anakinra Treatment Admitted with an Attack.

Interleukin-1 plays an important role in the pathogenesis of systemic-onset juvenile idiopathic arthritis (SoJIA), and the use of anti-interleukin-1 therapy has been increasing. We report a case of a 14-year-old male patient with SoJIA. He was in remission with anakinra treatment for almost 2 years.

A National Registry of Thalassemia in Turkey: Demographic and Disease Characteristics of Patients, Achievements, and Challenges in Prevention.

Objective: The Turkish Society of Pediatric Hematology set up a National Hemoglobinopathy Registry to demonstrate the demographic and disease characteristics of patients and assess the efficacy of a hemoglobinopathy control program (HCP) over 10 years in Turkey.

Materials And Methods: A total of 2046 patients from 27 thalassemia centers were registered, of which 1988 were eligible for analysis. This cohort mainly comprised patients with β-thalassemia major (n=1658, 83.

Less is More: Design of a Highly Stable Disulfide-Deleted Mutant of Analgesic Cyclic α-Conotoxin Vc1.1.

Cyclic α-conotoxin Vc1.1 (cVc1.1) is an orally active peptide with analgesic activity in rat models of neuropathic pain.

Engineered protease inhibitors based on sunflower trypsin inhibitor-1 (SFTI-1) provide insights into the role of sequence and conformation in Laskowski mechanism inhibition.

Laskowski inhibitors regulate serine proteases by an intriguing mode of action that involves deceiving the protease into synthesizing a peptide bond. Studies exploring naturally occurring Laskowski inhibitors have uncovered several structural features that convey the inhibitor's resistance to hydrolysis and exceptional binding affinity. However, in the context of Laskowski inhibitor engineering, the way that various modifications intended to fine-tune an inhibitor's potency and selectivity impact on its association and dissociation rates remains unclear.

Design and synthesis of truncated EGF-A peptides that restore LDL-R recycling in the presence of PCSK9 in vitro.

Disrupting the binding interaction between proprotein convertase (PCSK9) and the epidermal growth factor-like domain A (EGF-A domain) in the low-density lipoprotein receptor (LDL-R) is a promising strategy to promote LDL-R recycling and thereby lower circulating cholesterol levels. In this study, truncated 26 amino acid EGF-A analogs were designed and synthesized, and their structures were analyzed in solution and in complex with PCSK9. The most potent peptide had an increased binding affinity for PCSK9 (KD = 0.

Factor v deficiency associated with congenital cardiac disorder and intracranial hemorrage.

Factor V deficiency is an inherited disorder, in which the clotting factor V is low. The disorder is very rare, occurring in only one in one million people. It is inherited as an autosomal recessive disorder.

Oxytocic plant cyclotides as templates for peptide G protein-coupled receptor ligand design.

Cyclotides are plant peptides comprising a circular backbone and three conserved disulfide bonds that confer them with exceptional stability. They were originally discovered in Oldenlandia affinis based on their use in traditional African medicine to accelerate labor. Recently, cyclotides have been identified in numerous plant species of the coffee, violet, cucurbit, pea, potato, and grass families.

Characterization of a novel α-conotoxin TxID from Conus textile that potently blocks rat α3β4 nicotinic acetylcholine receptors.

The α3β4 nAChRs are implicated in pain sensation in the PNS and addiction to nicotine in the CNS. We identified an α-4/6-conotoxin (CTx) TxID from Conus textile. The new toxin consists of 15 amino acid residues with two disulfide bonds.

Synthesis of cyclic disulfide-rich peptides.

In this chapter we describe two SPPS approaches for producing cyclic disulfide-rich peptides in our laboratory, including cyclotides from plants, cyclic conotoxins from cone snail venoms, chlorotoxin from scorpion venom, and the sunflower trypsin inhibitor peptide, SFTI-1.

The three-dimensional solution structure of mini-M conotoxin BtIIIA reveals a disconnection between disulfide connectivity and peptide fold.

Conotoxins are bioactive peptides from the venoms of marine snails and have been divided into several superfamilies based on homologies in their precursor sequences. The M-superfamily conotoxins can be further divided into five branches based on the number of residues in the third loop of the peptide sequence. Recently two M-1 branch conotoxins (tx3a and mr3e) with a C1-C5, C2-C4, C3-C6 disulfide connectivity and one M-2 branch conotoxin (mr3a) with a C1-C6, C2-C4, C3-C5 disulfide connectivity were described.