Adult ADHD and suicide

While suicidal behaviour has been implicated in a plethora of psychiatric disorders including depression, psychoses and substance abuse, its association with adult ADHD is largely under-researched. Given that emotional instability and the high prevalence of comorbid conditions such as mood disorders and alcohol/drug dependence are typical for ADHD, the question of suicide risk must not be neglected in this patient group. A review of the current literature focusing on this issue provides strong evidence that ADHD patients are at a significant risk for experiencing suicidal ideations and committing suicide. For daily clinical practice, it is therefore essential to incorporate this aspect into the diagnostic and therapeutic process and to take preventive measures.     

Interaction of the HOPS complex with Syntaxin 17 mediates autophagosome clearance in Drosophila

Homotypic fusion and vacuole protein sorting (HOPS) is a tethering complex required for trafficking to the vacuole/lysosome in yeast. Specific interaction of HOPS with certain SNARE (soluble NSF attachment protein receptor) proteins ensures the fusion of appropriate vesicles. HOPS function is less well characterized in metazoans. We show that all six HOPS subunits (Vps11 [vacuolar protein sorting 11]/CG32350, Vps18/Dor, Vps16A, Vps33A/Car, Vps39/CG7146, and Vps41/Lt) are required for fusion of autophagosomes with lysosomes in Drosophila. Loss of these genes results in large-scale accumulation of autophagosomes and blocks autophagic degradation under basal, starvation-induced, and developmental conditions. We find that HOPS colocalizes and interacts with Syntaxin 17 (Syx17), the recently identified autophagosomal SNARE required for fusion in Drosophila and mammals, suggesting their association is critical during tethering and fusion of autophagosomes with lysosomes. HOPS, but not Syx17, is also required for endocytic down-regulation of Notch and Boss in developing eyes and for proper trafficking to lysosomes and eye pigment granules. We also show that the formation of autophagosomes and their fusion with lysosomes is largely unaffected in null mutants of Vps38/UVRAG (UV radiation resistance associated), a suggested binding partner of HOPS in mammals, while endocytic breakdown and lysosome biogenesis is perturbed. Our results establish the role of HOPS and its likely mechanism of action during autophagy in metazoans.     

The crystal structure of pyrimidine/thiamin biosynthesis precursor-like domain-containing protein CAE31940 from proteobacterium Bordetella bronchiseptica RB50, and evolutionary insight into the NMT1/THI5 family

We report a 2.0 Å structure of the CAE31940 protein, a proteobacterial NMT1/THI5-like domain-containing protein. We also discuss the primary and tertiary structure similarity with its homologs. The highly conserved FGGXMP motif was identified in CAE31940, which corresponds to the GCCCX motif located in the vicinity of the active center characteristic for THi5-like proteins found in yeast. This suggests that the FGGXMP motif may be a unique hallmark of proteobacterial NMT1/THI5-like proteins.     

Widespread desert affiliation of trebouxiophycean algae (Trebouxiophyceae,Chlorophyta) including discovery of three new desert genera

Unlike most other green algae, trebouxiophyceans are predominantly aerophytic and contain many symbiotic representatives. In recent years, a number of new terrestrial trebouxiophycean taxa were described from soils, tree bark, and lichens. The present phylogenetic study reveals three new lineages of free‐living trebouxiophyceans found in North American desert soil crusts and proposes new generic names to accommodate them: Desertella, Eremochloris, and Xerochlorella. This survey of desert isolates also led to discovery of representatives of seven existing genera of trebouxiophyceans. Two of these genera have never been reported to contain desert representatives and one was known previously only from aquatic habitats. Furthermore, we expand the known geographic range of the recently described genus Chloropyrula, heretofore only known from the Ural Mountains. We demonstrate that the diversity of trebouxiophyceans is still underestimated and poorly understood, and that most major trebouxiophycean lineages contain desert‐dwelling taxa.     

Chemical synthesis of the 5-taurinomethyl(-2-thio)uridine modified anticodon arm of the human mitochondrial tRNALeu(UUR) and tRNALys

5-Taurinomethyluridine (τm⁵U) and 5-taurinomethyl-2-thiouridine (τm⁵s²U) are located at the wobble position of human mitochondrial (hmt) tRNA^Leu(UUR) and tRNA^Lys, respectively. Both hypermodified units restrict decoding of the third codon letter to A and G. Pathogenic mutations in the genes encoding hmt-tRNA^Leu(UUR) and hmt-tRNA^Lys are responsible for the loss of the discussed modifications and, as a consequence, for the occurrence of severe mitochondrial dysfunctions (MELAS, MERRF). Synthetic oligoribonucleotides bearing modified nucleosides are a versatile tool for studying mechanisms of genetic message translation and accompanying pathologies at nucleoside resolution. In this paper, we present site-specific chemical incorporation of τm⁵U and τm⁵s²U into 17-mers related to the sequence of the anticodon arms hmt-tRNA^Leu(UUR) and hmt-tRNA^Lys, respectively employing phosphoramidite chemistry on CPG support. Selected protecting groups for the sulfonic acid (4-(tert-butyldiphenylsilanyloxy)-2,2-dimethylbutyl) and the exoamine function (-C(O)CF₃) are compatible with the blockage of the canonical monomeric units. The synthesis of τm⁵s²U-modified RNA fragment was performed under conditions eliminating the formation of side products of 2-thiocarbonyl group oxidation and/or oxidative desulphurization. The structure of the final oligomers was confirmed by mass spectroscopy and enzymatic cleavage data.     

Tracking the contribution of inductive bias to individualised internal models

Internal models capture the regularities of the environment and are central to understanding how humans adapt to environmental statistics. In general, the correct internal model is unknown to observers, instead they rely on an approximate model that is continually adapted throughout learning. However, experimenters assume an ideal observer model, which captures stimulus structure but ignores the diverging hypotheses that humans form during learning. We combine non-parametric Bayesian methods and probabilistic programming to infer rich and dynamic individualised internal models from response times. We demonstrate that the approach is capable of characterizing the discrepancy between the internal model maintained by individuals and the ideal observer model and to track the evolution of the contribution of the ideal observer model to the internal model throughout training. In particular, in an implicit visuomotor sequence learning task the identified discrepancy revealed an inductive bias that was consistent across individuals but varied in strength and persistence.     

Transcriptional profiling identifies critical steps of cell cycle reprogramming necessary for Plasmodiophora brassicae‐driven gall formation in Arabidopsis

Plasmodiophora brassicae is a soil‐borne biotroph whose life cycle involves reprogramming host developmental processes leading to the formation of galls on its underground parts. Formation of such structures involves modification of the host cell cycle leading initially to hyperplasia, increasing the number of cells to be invaded, followed by overgrowth of cells colonised by the pathogen. Here we show that P. brassicae infection stimulates formation of the E2Fa/RBR1 complex and upregulation of MYB3R1, MYB3R4 and A‐ and B‐type cyclin expression. These factors were previously described as important regulators of the G2?M cell cycle checkpoint. As a consequence of this manipulation, a large population of host hypocotyl cells are delayed in cell cycle exit and maintained in the proliferative state. We also report that, during further maturation of galls, enlargement of host cells invaded by the pathogen involves endoreduplication leading to increased ploidy levels. This study characterises two aspects of the cell cycle reprogramming efforts of P. brassicae: systemic, related to the disturbance of host hypocotyl developmental programs by preventing cell cycle exit; and local, related to the stimulation of cell enlargement via increased endocycle activity.     

SorCS2 Controls Functional Expression of Amino Acid Transporter EAAT3 and Protects Neurons from Oxidative Stress and Epilepsy-Induced Pathology

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