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Most of the described species in kingdom Fungi are contained in two phyla, the Ascomycota and the Basidiomycota (subkingdom Dikarya). As a result, our understanding of the biology of the kingdom is heavily influenced by traits observed in Dikarya, such as aerial spore dispersal and life cycles dominated by mitosis of haploid nuclei. We now appreciate that Fungi comprises numerous phylum-level lineages in addition to those of Dikarya, but the phylogeny and genetic characteristics of most of these lineages are poorly understood due to limited genome sampling. Here, we addressed major evolutionary trends in the non-Dikarya fungi by phylogenomic analysis of 69 newly generated draft genome sequences of the zoosporic (flagellated) lineages of true fungi. Our phylogeny indicated five lineages of zoosporic fungi and placed Blastocladiomycota, which has an alternation of haploid and diploid generations, as branching closer to the Dikarya than to the Chytridiomyceta. Our estimates of heterozygosity based on genome sequence data indicate that the zoosporic lineages plus the Zoopagomycota are frequently characterized by diploid-dominant life cycles. We mapped additional traits, such as ancestral cell-cycle regulators, cell-membrane- and cell-wall-associated genes, and the use of the amino acid selenocysteine on the phylogeny and found that these ancestral traits that are shared with Metazoa have been subject to extensive parallel loss across zoosporic lineages. Together, our results indicate a gradual transition in the genetics and cell biology of fungi from their ancestor and caution against assuming that traits measured in Dikarya are typical of other fungal lineages.

KCTD10, a member of the potassium channel tetramerization domain (KCTD) family, is implicated in neuropsychiatric disorders and functions as a substrate recognition component within the RING-type ubiquitin ligase complex. A rare de novo variant of KCTD10, p.C124W, was identified in schizophrenia cases, yet its underlying pathogenesis remains unexplored. Here, we demonstrate that heterozygous KCTD10 C124W mice display pronounced synaptic abnormalities and exhibit schizophrenia-like behaviors. Mechanistically, we reveal that KCTD10 undergoes liquid-liquid phase separation (LLPS), a process orchestrated by its intrinsically disordered region (IDR). p.C124W mutation disrupts this LLPS capability, leading to diminished degradation of RHOB and subsequent excessive accumulation in the postsynaptic density fractions. Notably, neither IDR deletion nor p.C124W mutation in KCTD10 mitigates the synaptic abnormalities caused by Kctd10 deficiency. Thus, our findings implicate that LLPS may be associated with the pathogenesis of KCTD10-associated brain disorders and highlight the potential of targeting RHOB as a therapeutic strategy for diseases linked to mutations in KCTD10 or RHOB., Competing Interests: Competing interests statement:The authors declare no competing interest.

Silicon micromachined calorimeters ("calorimeter on a chip") are used to measure heat capacities and phase transition enthalpies for thin film, single crystal, and powder samples (5-500 mug). The technology is thus compatible with the small samples produced in multianvil and large diamond anvil cells. Techniques for handling small samples and attaching them to the calorimetric devices have been developed. Initial data illustrate application to CoO and to Fe(2)SiO(4) olivine and spinel, a quenched high pressure phase metastable at ambient conditions. The calorimetric entropy of the olivine-spinel transition in Fe(2)SiO(4) (-16 +/- 5 J/mol.K) is in good agreement with that calculated from phase equilibrium data (-14 +/- 3 J/mol.K). A magnetic transition in iron silicate spinel, detected previously by Mossbauer spectroscopy, is seen in the calorimetric signal.

The pharmacological properties of voltage-dependent calcium channel (VDCC) subtypes appear mainly to be determined by the alpha1 pore-forming subunit but, whether P-and Q-type VDCCs are encoded by the same alpha1 gene presently is unresolved. To investigate this, we used IgG antibodies to presynaptic VDCCs at motor nerve terminals that underlie muscle weakness in the autoimmune Lambert-Eaton myasthenic syndrome (LEMS). We first studied their action on changes in intracellular free Ca2+ concentration [Ca2+]i in human embryonic kidney (HEK293) cell lines expressing different combinations of human recombinant VDCC subunits. Incubation for 18 h with LEMS IgG (2 mg/ml) caused a significant dose-dependent reduction in the K+-stimulated [Ca2+]i increase in the alpha1A cell line but not in the alpha1B, alpha1C, alpha1D, and alpha1E cell lines, establishing the alpha1A subunit as the target for these autoantibodies. Exploiting this specificity, we incubated cultured rat cerebellar neurones with LEMS IgG and observed a reduction in P-type current in Purkinje cells and both P- and Q-type currents in granule cells. These data are consistent with the hypothesis that the alpha1A gene encodes for the pore-forming subunit of both P-type and Q-type VDCCs.