Myoclonus-dystonia : distinctive motor and non-motor phenotype from other dystonia syndromes

Background: myoclonus-dystonia (M-D) due to a pathogenic variant of SGCE is an autosomal dominant inherited movement disorder. Apart from motor symptoms, psychiatric disorders are highly prevalent in patients with MD. Previous studies suggest, but never tested directly, that the type of psychiatric disorder differs between dystonia syndromes, probably related to disease specific pathology. Little is known about other non-motor symptoms (NMS) in M.D. Here, we systematically study NMS in M-D in direct comparison to other types of dystonia and healthy controls. Methods: Standardized questionnaires were used to assess type and severity of psychiatric co-morbidity, sleep problems, fatigue and quality of life. Results of M-D patients with a pathogenic variant of SGCE were compared to results of idiopathic cervical dystonia (CD) patients, dopa-responsive dystonia (DRD) patients with a pathogenic variant of GCH1 and controls. Results: We included 164 participants: 41 M-D, 51 CD, 19 DRD patients, 53 controls. Dystonia patients (M-D, CD and DRD) had an increased prevalence of psychiatric disorders compared to controls (56-74% vs. 29%). In M-D we found a significantly increased prevalence of obsessive-compulsive disorder (OCD) and psychosis compared to CD and DRD. All dystonia patients had more sleep problems (49-68% vs. 36%) and fatigue (42-73% vs. 15%) than controls. Compared to other dystonia subtypes, M-D patients reported less excessive daytime sleepiness and fatigue. Conclusion: Psychiatric comorbidity is frequent in all dystonia types, but OCD and psychosis are more common in M-D patients. Further research is necessary to elucidate underlying pathways

Mutational analysis of BTAF1-TBP interaction: BTAF1 can rescue DNA-binding defective TBP mutants

The BTAF1 transcription factor interacts with TATA-binding protein (TBP) to form the B-TFIID complex, which is involved in RNA polymerase II transcription. Here, we present an extensive mapping study of TBP residues involved in BTAF1 interaction. This shows that residues in the concave, DNA-binding surface of TBP are important for BTAF1 binding. In addition, BTAF1 interacts with residues in helix 2 on the convex side of TBP as assayed in protein-protein and in DNA-binding assays. BTAF1 drastically changes the TATA-box binding specificity of TBP, as it is able to recruit DNA-binding defective TBP mutants to both TATA-containing and TATA-less DNA. Interestingly, other helix 2 interacting factors, such as TFIIA and NC2, can also stabilize mutant TBP binding to DNA. In contrast, TFIIB which interacts with a distinct surface of TBP does not display this activity. Since many proteins contact helix 2 of TBP, this provides a molecular basis for mutually exclusive TBP interactions and stresses the importance of this structural element for eukaryotic transcription

Versatile silicon-waveguide supercontinuum for coherent mid-infrared spectroscopy

Infrared spectroscopy is a powerful tool for basic and applied science. The molecular spectral fingerprints in the 3 um to 20 um region provide a means to uniquely identify molecular structure for fundamental spectroscopy, atmospheric chemistry, trace and hazardous gas detection, and biological microscopy. Driven by such applications, the development of low-noise, coherent laser sources with broad, tunable coverage is a topic of great interest. Laser frequency combs possess a unique combination of precisely defined spectral lines and broad bandwidth that can enable the above-mentioned applications. Here, we leverage robust fabrication and geometrical dispersion engineering of silicon nanophotonic waveguides for coherent frequency comb generation spanning 70 THz in the mid-infrared (2.5 um to 6.2 um). Precise waveguide fabrication provides significant spectral broadening and engineered spectra targeted at specific mid-infrared bands. We use this coherent light source for dual-comb spectroscopy at 5 um.Comment: 26 pages, 5 figure

Reverse methanogenesis and respiration in methanotrophic archaea

Anaerobic oxidation of methane (AOM) is catalyzed by anaerobic methane-oxidizing archaea (ANME) via a reverse and modified methanogenesis pathway. Methanogens can also reverse the methanogenesis pathway to oxidize methane, but only during net methane production (i.e., "trace methane oxidation"). In turn, ANME can produce methane, but only during net methane oxidation (i.e., enzymatic back flux). Net AOM is exergonic when coupled to an external electron acceptor such as sulfate (ANME-1, ANME-2abc, and ANME-3), nitrate (ANME-2d), or metal (oxides). In this review, the reversibility of the methanogenesis pathway and essential differences between ANME and methanogens are described by combining published information with domain based (meta)genome comparison of archaeal methanotrophs and selected archaea. These differences include abundances and special structure of methyl coenzyme M reductase and of multiheme cytochromes and the presence of menaquinones or methanophenazines. ANME-2a and ANME-2d can use electron acceptors other than sulfate or nitrate for AOM, respectively. Environmental studies suggest that ANME-2d are also involved in sulfate-dependent AOM. ANME-1 seem to use a different mechanism for disposal of electrons and possibly are less versatile in electron acceptors use than ANME-2. Future research will shed light on the molecular basis of reversal of the methanogenic pathway and electron transfer in different ANME types.The authors thank Stefanie Berger (RU,Nijmegen) for critical reading of the manuscript. This research is supported by the Soehngen Institute of Anaerobic Microbiology (SIAM) Gravitation Grant (024.002.002) of the Netherlands Ministry of Education, Culture and Science and the Netherlands Organisation for Scientific Research (NWO). Mike S. M. Jetten was further supported by ERC AG 339880 Eco-MoM and Alfons J. M. Stams was supported by ERC AG 323009 Novel Anaerobes.info:eu-repo/semantics/publishedVersio

Metabolism and occurrence of methanogenic and sulfate-reducing syntrophic acetate oxidizing communities in haloalkaline environments

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmicb. 2018.03039/full#supplementary-materialAnaerobic syntrophic acetate oxidation (SAO) is a thermodynamically unfavorable process involving a syntrophic acetate oxidizing bacterium (SAOB) that forms interspecies electron carriers (IECs). These IECs are consumed by syntrophic partners, typically hydrogenotrophic methanogenic archaea or sulfate reducing bacteria. In this work, the metabolism and occurrence of SAOB at extremely haloalkaline conditions were investigated, using highly enriched methanogenic (M-SAO) and sulfate-reducing (S-SAO) cultures from south-eastern Siberian hypersaline soda lakes. Activity tests with the M-SAO and S-SAO cultures and thermodynamic calculations indicated that hydrogen and formate are important IECs in both SAO cultures. Metagenomic analysis of the M-SAO cultures showed that the dominant SAOB was Candidatus Syntrophonatronum acetioxidans, and a near-complete draft genome of this SAOB was reconstructed. Ca. S. acetioxidans has all genes necessary for operating the Wood-Ljungdahl pathway, which is likely employed for acetate oxidation. It also encodes several genes essential to thrive at haloalkaline conditions; including a Na+-dependent ATP synthase and marker genes for salt-out strategies for osmotic homeostasis at high soda conditions. Membrane lipid analysis of the M-SAO culture showed the presence of unusual bacterial diether membrane lipids which are presumably beneficial at extreme haloalkaline conditions. To determine the importance of SAO in haloalkaline environments, previously obtained 16S rRNA gene sequencing data and metagenomic data of five different hypersaline soda lake sediment samples were investigated, including the soda lakes where the enrichment cultures originated from. The draft genome of Ca. S. acetioxidans showed highest identity with two metagenome-assembled genomes (MAGs) of putative SAOBs that belonged to the highly abundant and diverse Syntrophomonadaceae family present in the soda lake sediments. The 16S rRNA amplicon datasets of the soda lake sediments showed a high similarity of reads to Ca. S. acetioxidans with abundance as high as 1.3% of all reads, whereas aceticlastic methanogens and acetate oxidizing sulfate-reducers were not abundant (0.1%) or could not be detected. These combined results indicate that SAO is the primary anaerobic acetate oxidizing pathway at extreme haloalkaline conditions performed by haloalkaliphilic syntrophic consortia.This research was supported by the Soehngen Institute of AnaerobicMicrobiology(SIAM) Gravitation grant(024.002.002) of the Netherlands Ministry of Education, Culture and Science and the Netherlands Organisation for Scientific Research (NWO). GM and CV were supported by the ERC Advanced Grant PARASOL (No. 322551). DS also received support from the Russian Foundation for Basic Research (16-04-00035) and the Russian Academy of Sciences and Federal Agency of Scientific Organizations(0104-2018-0033), AS by the ERC Advanced Grant Novel Anaerobes (No. 323009), and JD by the ERC Advanced Grant Microlipids (No.694569).info:eu-repo/semantics/publishedVersio

Mid-infrared frequency comb generation and spectroscopy with few-cycle pulses and chi((2)) nonlinear optics

FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPThe mid-infrared atmospheric window of 3-5.5 mu m holds valuable information regarding molecular composition and function for fundamental and applied spectroscopy. Using a robust, mode-locked fiberlaser source of < U fs pulses in the near infrared, we exp1241316FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2018/26673-5The authors acknowledge support from the National Institute of Standards and Technology, the DARPA SCOUT Program, the National Science Foundation (Grand No. 1708743), and the Air Force Office of Scientific Research (Grants No. FA9550-16-1-0016 and No. FA