Úvod: Prevalence Martin-Gruberovy anastomózy (MGA), spojky n. medianus a ulnaris na předloktí se uvádí v rozmezí 15–39 %. Existují tři různé typy MGA, kdy motorická vlákna jsou v oblasti paže a lokte vedena skrze n. medianus a zásobují svaly ruky inervované n. ulnaris (m. abductor digiti minimi, m. interosseus dorsalis primus či m. adductor pollicis). Soubor a metodika: V pěti EMG laboratořích bylo unifikovanou technikou vyšetřeno 292 zdravých osob ve věku 20–67 let, průměr 39,4 let: 166 žen (256 rukou) a 126 mužů (201 rukou), celkem 457 rukou. Byla provedena motorická a senzitivní neurografie n. ulnaris a n. medianus. Pro detekci MGA mělo zásadní význam hodnocení amplitudy CMAP pro n. ulnaris a n. medianus při stimulaci z oblasti lokte a zápěstí. Výsledky: V našem souboru 457 vyšetřených rukou jsme na 90 rukou našli 109 výskytů MGA. U 30 rukou se jednalo o MGA-I, u 57 rukou o MGA-II a u 22 rukou o MGA-III. Izolované typy MGA se vyskytly v 73 případech, Na 17 rukou se vyskytla kombinace dvou, ojediněle dokonce všech tří typů MGA současně. Závěr: V souboru 292 osob zdravých osob jsme na 457 hodnocených rukou našli MGA v 19,7 %. Nejčastěji se vyskytoval typ MGA-II (12,5 %).

Objective: Martin-Gruber anastomosis (MGA) is a median-to-ulnar nerve communication in the forearm; three types of MGA occur. Typically, motor fibres course through the median nerve in the upper arm and elbow, however, they supply the ulnar-innervated muscles of the hand: abductor digiti minimi (ADM) – MGA-I; first dorsal interosseous (FDI) – MGA-II; or adductor pollicis – MGA-III. The objective was to determine the prevalence of MGA in a study group of healthy volunteers. Methods: Two hundred and ninety-two healthy participants (457 arms) were enrolled. Motor and sensory nerve conduction studies of the ulnar and median nerves were performed. Ulnar and median nerve compound muscle action potential amplitudes were obtained on stimulation at the elbow and wrist. Results: We found 109 cases of MGA in 90 arms (MGA-I in 30 arms; MGA-II in 57 arms; MGA-III in 22 arms). We found isolated MGA types in 73 arms, a combination of two types in 15 arms, and occasionally (2 arms) a simultaneous combination of all three types. Conclusion: The prevalence of MGA was 19.7%. Most frequently, we found MGA-II (prevalence = 12.5%). Significance: MGA does not produce any clinical signs. However, it can change EMG results. The neurophysiologist must be able to logically interpret such findings.

• Keywords
• Martin-Gruberova anastomóza,
• MeSH
• Adult MeSH
• Electromyography methods   utilization   MeSH
• Clinical Studies as Topic MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Median Nerve * physiopathology   MeSH
• Ulnar Nerve * physiopathology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH

• MeSH
• Medical Missions organization & administration   manpower   MeSH
• Publication type
• Newspaper Article MeSH
• Interview MeSH

• Publication type
• Meeting Abstract MeSH

Energy relaxation in light-harvesting complexes has been extensively studied by various ultrafast spectroscopic techniques, the fastest processes being in the sub-100-fs range. At the same time, much slower dynamics have been observed in individual complexes by single-molecule fluorescence spectroscopy (SMS). In this work, we use a pump-probe-type SMS technique to observe the ultrafast energy relaxation in single light-harvesting complexes LH2 of purple bacteria. After excitation at 800 nm, the measured relaxation time distribution of multiple complexes has a peak at 95 fs and is asymmetric, with a tail at slower relaxation times. When tuning the excitation wavelength, the distribution changes in both its shape and position. The observed behavior agrees with what is to be expected from the LH2 excited states structure. As we show by a Redfield theory calculation of the relaxation times, the distribution shape corresponds to the expected effect of Gaussian disorder of the pigment transition energies. By repeatedly measuring few individual complexes for minutes, we find that complexes sample the relaxation time distribution on a timescale of seconds. Furthermore, by comparing the distribution from a single long-lived complex with the whole ensemble, we demonstrate that, regarding the relaxation times, the ensemble can be considered ergodic. Our findings thus agree with the commonly used notion of an ensemble of identical LH2 complexes experiencing slow random fluctuations.

• MeSH
• Bacteriochlorophylls chemistry   radiation effects   MeSH
• Time MeSH
• Spectrometry, Fluorescence methods   MeSH
• Microscopy, Confocal MeSH
• Lasers MeSH
• Statistics, Nonparametric MeSH
• Normal Distribution MeSH
• Energy Transfer * MeSH
• Rhodopseudomonas chemistry   MeSH
• Light MeSH
• Light-Harvesting Protein Complexes chemistry   radiation effects   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Comparative Study MeSH

Hungarosoma bokori Verhoeff, 1928 is a millipede species which was originally classified solely on the basis of a female specimen. Subsequently, a long history of field searching for and surmising about the systematic position of this small, enigmatic species followed. In April 2013, 85 years after its first description, a series of nine specimens were sampled in the type locality, the Abaliget Cave, in southern Hungary. An adult male was collected for the first time, along with females and juveniles. Descriptions of the gonopods and the female vulvae, both important for considerations of the systematic position of the species, are presented for the first time. Revision and re-designation of the type material was made.The cryptic life of the species is connected with its activity in winter, and its known fragmented distribution corresponds with its presence in undisturbed microhabitats having a specific microclimate, often in the soil at cave entrances.Molecular methods showed a positive detection of the intracellular prokaryotic parasite Wolbachia in H. bokori, reflecting its highly probable parthenogenetic character in the main part of its known area of occurrence. This is the first demonstration of Wolbachia in a millipede.The legitimacy of the family Hungarosomatidae Ceuca, 1974, as a separate taxon was analysed using morphological and molecular approaches. Results of both methods confirmed the existence of a distinct phyletic line. DNA barcoding has shown its closest position to Attemsiidae Verhoeff, 1899, or Neoatractosomatidae Verhoeff, 1901. Based on records from Austria, the Czech Republic, Hungary and Slovakia, the residual circum-pannonic distribution that the whole genus (family) probably represents is proposed.

• MeSH
• Arthropods anatomy & histology   classification   genetics   microbiology   MeSH
• Species Specificity MeSH
• Ecosystem MeSH
• Caves MeSH
• Parthenogenesis MeSH
• DNA Barcoding, Taxonomic MeSH
• Wolbachia genetics   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Hungary MeSH

In the major peripheral plant light-harvesting complex LHCII, excitation energy is transferred between chlorophylls along an energetic cascade before it is transmitted further into the photosynthetic assembly to be converted into chemical energy. The efficiency of these energy transfer processes involves a complicated interplay of pigment-protein structural reorganization and protein dynamic disorder, and the system must stay robust within the fluctuating protein environment. The final, lowest energy site has been proposed to exist within a trimeric excitonically coupled chlorophyll (Chl) cluster, comprising Chls a610-a611-a612. We studied an LHCII monomer with a site-specific mutation resulting in the loss of Chls a611and a612, and find that this mutant exhibits two predominant overlapping fluorescence bands. From a combination of bulk measurements, single-molecule fluorescence characterization, and modeling, we propose the two fluorescence bands originate from differing conditions of exciton delocalization and localization realized in the mutant. Disruption of the excitonically coupled terminal emitter Chl trimer results in an increased sensitivity of the excited state energy landscape to the disorder induced by the protein conformations. Consequently, the mutant demonstrates a loss of energy transfer efficiency. On the contrary, in the wild-type complex, the strong resonance coupling and correspondingly high degree of excitation delocalization within the Chls a610-a611-a612 cluster dampens the influence of the environment and ensures optimal communication with neighboring pigments. These results indicate that the terminal emitter trimer is thus an essential design principle for maintaining the efficient light-harvesting function of LHCII in the presence of protein disorder.

• MeSH
• Arabidopsis metabolism   MeSH
• Fluorescence MeSH
• Protein Multimerization MeSH
• Mutation MeSH
• Arabidopsis Proteins chemistry   genetics   metabolism   MeSH
• Light-Harvesting Protein Complexes chemistry   genetics   metabolism   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Alternative polyadenylation (APA) modulates mRNA processing in the 3'-untranslated regions (3' UTR), affecting mRNA stability and translation efficiency. Research into genetically regulated APA has the potential to provide insights into cancer risk. In this study, we conducted large APA-wide association studies to investigate associations between APA levels and cancer risk. Genetic models were built to predict APA levels in multiple tissues using genotype and RNA sequencing data from 1,337 samples from the Genotype-Tissue Expression project. Associations of genetically predicted APA levels with cancer risk were assessed by applying the prediction models to data from large genome-wide association studies of six common cancers among European ancestry populations: breast, ovarian, prostate, colorectal, lung, and pancreatic cancers. A total of 58 risk genes (corresponding to 76 APA sites) were associated with at least one type of cancer, including 25 genes previously not linked to cancer susceptibility. Of the identified risk APAs, 97.4% and 26.3% were supported by 3'-UTR APA quantitative trait loci and colocalization analyses, respectively. Luciferase reporter assays for four selected putative regulatory 3'-UTR variants demonstrated that the risk alleles of 3'-UTR variants, rs324015 (STAT6), rs2280503 (DIP2B), rs1128450 (FBXO38), and rs145220637 (LDHA), significantly increased the posttranscriptional activities of their target genes compared with reference alleles. Furthermore, knockdown of the target genes confirmed their ability to promote proliferation and migration. Overall, this study provides insights into the role of APA in the genetic susceptibility to common cancers. Significance: Systematic evaluation of associations of alternative polyadenylation with cancer risk reveals 58 putative susceptibility genes, highlighting the contribution of genetically regulated alternative polyadenylation of 3'UTRs to genetic susceptibility to cancer.

• MeSH
• 3' Untranslated Regions * genetics   MeSH
• Genome-Wide Association Study * MeSH
• Genetic Predisposition to Disease * MeSH
• Polymorphism, Single Nucleotide MeSH
• Humans MeSH
• Quantitative Trait Loci MeSH
• RNA, Messenger genetics   metabolism   MeSH
• Cell Line, Tumor MeSH
• Neoplasms * genetics   MeSH
• Polyadenylation * MeSH
• Gene Expression Regulation, Neoplastic MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Tuberous sclerosis complex (TSC) is a monogenetic disease that arises due to mutations in either the TSC1 or TSC2 gene and affects multiple organ systems. One of the hallmark manifestations of TSC are cortical malformations referred to as cortical tubers. These tubers are frequently associated with treatment-resistant epilepsy. Some of these patients are candidates for epilepsy surgery. White matter abnormalities, such as loss of myelin and oligodendroglia, have been described in a small subset of resected tubers but mechanisms underlying this phenomenon are unclear. Herein, we analyzed a variety of neuropathologic and immunohistochemical features in gray and white matter areas of resected cortical tubers from 46 TSC patients using semi-automated quantitative image analysis. We observed divergent amounts of myelin basic protein as well as numbers of oligodendroglia in both gray and white matter when compared with matched controls. Analyses of clinical data indicated that reduced numbers of oligodendroglia were associated with lower numbers on the intelligence quotient scale and that lower amounts of myelin-associated oligodendrocyte basic protein were associated with the presence of autism-spectrum disorder. In conclusion, myelin pathology in cortical tubers extends beyond the white matter and may be linked to cognitive dysfunction in TSC patients.

• MeSH
• White Matter pathology   MeSH
• Humans MeSH
• Cerebral Cortex pathology   MeSH
• Myelin Sheath pathology   MeSH
• Oligodendroglia pathology   MeSH
• Gray Matter pathology   MeSH
• Tuberous Sclerosis pathology   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: Glycemic traits-such as hyperinsulinemia, hyperglycemia, and type 2 diabetes-have been associated with higher colorectal cancer risk in observational studies; however, causality of these associations is uncertain. We used Mendelian randomization (MR) to estimate the causal effects of fasting insulin, 2-hour glucose, fasting glucose, glycated hemoglobin (HbA1c), and type 2 diabetes with colorectal cancer. METHODS: Genome-wide association study summary data were used to identify genetic variants associated with circulating levels of fasting insulin (n = 34), 2-hour glucose (n = 13), fasting glucose (n = 70), HbA1c (n = 221), and type 2 diabetes (n = 268). Using 2-sample MR, we examined these variants in relation to colorectal cancer risk (48 214 case patient and 64 159 control patients). RESULTS: In inverse-variance models, higher fasting insulin levels increased colorectal cancer risk (odds ratio [OR] per 1-SD = 1.65, 95% confidence interval [CI] = 1.15 to 2.36). We found no evidence of any effect of 2-hour glucose (OR per 1-SD = 1.02, 95% CI = 0.86 to 1.21) or fasting glucose (OR per 1-SD = 1.04, 95% CI = 0.88 to 1.23) concentrations on colorectal cancer risk. Genetic liability to type 2 diabetes (OR per 1-unit increase in log odds = 1.04, 95% CI = 1.01 to 1.07) and higher HbA1c levels (OR per 1-SD = 1.09, 95% CI = 1.00 to 1.19) increased colorectal cancer risk, although these findings may have been biased by pleiotropy. Higher HbA1c concentrations increased rectal cancer risk in men (OR per 1-SD = 1.21, 95% CI = 1.05 to 1.40), but not in women. CONCLUSIONS: Our results support a causal effect of higher fasting insulin, but not glucose traits or type 2 diabetes, on increased colorectal cancer risk. This suggests that pharmacological or lifestyle interventions that lower circulating insulin levels may be beneficial in preventing colorectal tumorigenesis.

• MeSH
• Genome-Wide Association Study MeSH
• Diabetes Mellitus, Type 2 * complications   epidemiology   genetics   MeSH
• Glycated Hemoglobin analysis   MeSH
• Hyperinsulinism * complications   genetics   MeSH
• Insulin MeSH
• Polymorphism, Single Nucleotide MeSH
• Colorectal Neoplasms * complications   epidemiology   genetics   MeSH
• Blood Glucose analysis   genetics   MeSH
• Humans MeSH
• Mendelian Randomization Analysis MeSH
• Risk Factors MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited neurocutaneous disorder caused by inactivating mutations in TSC1 or TSC2, key regulators of the mechanistic target of rapamycin complex 1 (mTORC1) pathway. In the CNS, TSC is characterized by cortical tubers, subependymal nodules and subependymal giant cell astrocytomas (SEGAs). SEGAs may lead to impaired circulation of CSF resulting in hydrocephalus and raised intracranial pressure in patients with TSC. Currently, surgical resection and mTORC1 inhibitors are the recommended treatment options for patients with SEGA. In the present study, high-throughput RNA-sequencing (SEGAs n = 19, periventricular control n = 8) was used in combination with computational approaches to unravel the complexity of SEGA development. We identified 9400 mRNAs and 94 microRNAs differentially expressed in SEGAs compared to control tissue. The SEGA transcriptome profile was enriched for the mitogen-activated protein kinase (MAPK) pathway, a major regulator of cell proliferation and survival. Analysis at the protein level confirmed that extracellular signal-regulated kinase (ERK) is activated in SEGAs. Subsequently, the inhibition of ERK independently of mTORC1 blockade decreased efficiently the proliferation of primary patient-derived SEGA cultures. Furthermore, we found that LAMTOR1, LAMTOR2, LAMTOR3, LAMTOR4 and LAMTOR5 were overexpressed at both gene and protein levels in SEGA compared to control tissue. Taken together LAMTOR1-5 can form a complex, known as the 'Ragulator' complex, which is known to activate both mTORC1 and MAPK/ERK pathways. Overall, this study shows that the MAPK/ERK pathway could be used as a target for treatment independent of, or in combination with mTORC1 inhibitors for TSC patients. Moreover, our study provides initial evidence of a possible link between the constitutive activated mTORC1 pathway and a secondary driver pathway of tumour growth.

• MeSH
• Adaptor Proteins, Signal Transducing genetics   metabolism   MeSH
• Astrocytoma etiology   genetics   metabolism   MeSH
• Astrocytes drug effects   metabolism   MeSH
• Butadienes pharmacology   MeSH
• Child MeSH
• Adult MeSH
• Extracellular Signal-Regulated MAP Kinases antagonists & inhibitors   genetics   metabolism   MeSH
• Tuberous Sclerosis Complex 1 Protein genetics   MeSH
• Enzyme Inhibitors pharmacology   MeSH
• Intracellular Signaling Peptides and Proteins genetics   metabolism   MeSH
• Infant MeSH
• Humans MeSH
• MAP Kinase Signaling System genetics   MeSH
• RNA, Messenger metabolism   MeSH
• MicroRNAs metabolism   MeSH
• Adolescent MeSH
• Young Adult MeSH
• Mechanistic Target of Rapamycin Complex 1 MeSH
• Tumor Cells, Cultured MeSH
• Brain Neoplasms complications   genetics   metabolism   MeSH
• Nitriles pharmacology   MeSH
• Child, Preschool MeSH
• Sequence Analysis, RNA MeSH
• RNA-Seq MeSH
• Gene Expression Profiling MeSH
• Tuberous Sclerosis Complex 2 Protein genetics   MeSH
• Tuberous Sclerosis complications   genetics   MeSH
• Guanine Nucleotide Exchange Factors genetics   metabolism   MeSH
• High-Throughput Nucleotide Sequencing MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH