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Institute
HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders
(2021)
Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10−3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response.
Evolution of nematic fluctuations in CaK(Fe1−xNix)4As4 with spin-vortex crystal magnetic order
(2020)
The CaK(Fe1−xNix)4As4 superconductors resemble the archetypal 122-type iron-based materials but have a crystal structure with distinctly lower symmetry. This family hosts one of the few examples of the so-called spin-vortex crystal magnetic order, a non-collinear magnetic configuration that preserves tetragonal symmetry, in contrast to the orthorhombic collinear stripe-type magnetic configuration common to the 122-type systems. Thus, nematic order is completely absent from its phase diagram. To investigate the evolution of nematic fluctuations in such a case, we present elastoresistance and elastic modulus measurements in CaK(Fe1−xNix)4As4 (x=0−0.05) combined with phenomenological modeling and density functional theory. We find clear experimental signatures of considerable nematic fluctuations, including softening of the Young's modulus Y[110] and a Curie-Weiss type divergence of the B2g elastoresistance coefficient in CaK(Fe0.951Ni0.049)4As4. Overall, nematic fluctuations within this series bear strong similarities to the hole-doped Ba1−xKxFe2As2 series, including a substitution-induced sign change. Our theoretical analysis addresses the effect of the specific crystal symmetry of the 1144-type structure in determining its magnetic ground state and on the nematic fluctuations.
Layered {\alpha}-RuCl3 is a promising material to potentially realize the long-sought Kitaev quantum spin liquid with fractionalized excitations. While evidence of this exotic state has been reported under a modest in-plane magnetic field, such behavior is largely inconsistent with theoretical expectations of Kitaev phases emerging only in out-of-plane fields. These predicted field-induced states have been mostly out of reach due to the strong easy-plane anisotropy of bulk crystals, however. We use a combination of tunneling spectroscopy, magnetotransport, electron diffraction, and ab initio calculations to study the layer-dependent magnons, anisotropy, structure, and exchange coupling in atomically thin samples. Due to structural distortions, the sign of the average off-diagonal exchange changes in monolayer {\alpha}-RuCl3, leading to a reversal of magnetic anisotropy to easy-axis. Our work provides a new avenue to tune the magnetic interactions in {\alpha}-RuCl3 and allows theoretically predicted quantum spin liquid phases for out-of-plane fields to be more experimentally accessible.
Members of the ATP‐binding cassette (ABC) transporter superfamily translocate a broad spectrum of chemically diverse substrates. While their eponymous ATP‐binding cassette in the nucleotide‐binding domains (NBDs) is highly conserved, their transmembrane domains (TMDs) forming the translocation pathway exhibit distinct folds and topologies, suggesting that during evolution the ancient motor domains were combined with different transmembrane mechanical systems to orchestrate a variety of cellular processes. In recent years, it has become increasingly evident that the distinct TMD folds are best suited to categorize the multitude of ABC transporters. We therefore propose a new ABC transporter classification that is based on structural homology in the TMDs:
Knowledge about the biogeographic affinities of the world’s tropical forests helps to better understand regional differences in forest structure, diversity, composition, and dynamics. Such understanding will enable anticipation of region-specific responses to global environmental change. Modern phylogenies, in combination with broad coverage of species inventory data, now allow for global biogeographic analyses that take species evolutionary distance into account. Here we present a classification of the world’s tropical forests based on their phylogenetic similarity. We identify five principal floristic regions and their floristic relationships: (i) Indo-Pacific, (ii) Subtropical, (iii) African, (iv) American, and (v) Dry forests. Our results do not support the traditional neo- versus paleotropical forest division but instead separate the combined American and African forests from their Indo-Pacific counterparts. We also find indications for the existence of a global dry forest region, with representatives in America, Africa, Madagascar, and India. Additionally, a northern-hemisphere Subtropical forest region was identified with representatives in Asia and America, providing support for a link between Asian and American northern-hemisphere forests.