Different Amyloid-β Self-Assemblies Have Distinct Effects on Intracellular Tau Aggregation.

Alzheimer's disease (AD) pathology is characterized by the aggregation of beta-amyloid (Aβ) and tau in the form of amyloid plaques and neurofibrillary tangles in the brain. It has been found that a synergistic relationship between these two proteins may contribute to their roles in disease progression. However, how Aβ and tau interact has not been fully characterized. Here, we analyze how tau seeding or aggregation is influenced by different Aβ self-assemblies (fibrils and oligomers). Our cellular assays utilizing tau biosensor cells show that transduction of Aβ oligomers into the cells greatly enhances seeded tau aggregation in a concentration-dependent manner. In contrast, transduced Aβ fibrils slightly reduce tau seeding while untransduced Aβ fibrils promote it. We also observe that the transduction of α-synuclein fibrils, another amyloid protein, has no effect on tau seeding. The enhancement of tau seeding by Aβ oligomers was confirmed using tau fibril seeds derived from both recombinant tau and PS19 mouse brain extracts containing human tau. Our findings highlight the importance of considering the specific form and cellular location of Aβ self-assembly when studying the relationship between Aβ and tau in future AD therapeutic development

The twisted forms of a semisimple group over an fq-curve

Let C be a smooth, projective and geometrically connected curve defined over a finite field Fq . Given a semisimple C −S-group scheme G where S is a finite set of closed points of C, we describe the set of (OS-classes of) twisted forms of G in terms of geometric invariants of its fundamental group F (G)

On the genera of semisimple groups defined over an integral domain of a global function field

Let $K=\mathbb{F}_q(C)$ be the global function field of rational functions over a smooth and projective curve $C$ defined over a finite field $\mathbb{F}_q$. The ring of regular functions on $C-S$ where $S \neq \emptyset$ is any finite set of closed points on $C$ is a Dedekind domain $\mathcal{O}_S$ of $K$. For a semisimple $\mathcal{O}_S$-group $\underline{G}$ with a smooth fundamental group $\underline{F}$, we aim to describe both the set of genera of $\underline{G}$ and its principal genus (the latter if $\underline{G} \otimes_{\mathcal{O}_S} K$ is isotropic at $S$) in terms of abelian groups depending on $\mathcal{O}_S$ and $\underline{F}$ only. This leads to a necessary and sufficient condition for the Hasse local-global principle to hold for certain $\underline{G}$. We also use it to express the Tamagawa number $\tau(G)$ of a semisimple $K$-group $G$ by the Euler Poincar\'e invariant. This facilitates the computation of $\tau(G)$ for twisted $K$-groups.Comment: 18 page

Human leukocyte antigen supertype matching after myeloablative hematopoietic cell transplantation with 7/8 matched unrelated donor allografts: a report from the Center for International Blood and Marrow Transplant Research

The diversity of the human leukocyte antigen (HLA) class I and II alleles can be simplified by consolidating them into fewer supertypes based on functional or predicted structural similarities in epitope-binding grooves of HLA molecules. We studied the impact of matched and mismatched HLA-A (265 versus 429), -B (230 versus 92), -C (365 versus 349), and -DRB1 (153 versus 51) supertypes on clinical outcomes of 1934 patients with acute leukemias or myelodysplasia/myeloproliferative disorders. All patients were reported to the Center for International Blood and Marrow Transplant Research following single-allele mismatched unrelated donor myeloablative conditioning hematopoietic cell transplantation. Single mismatched alleles were categorized into six HLA-A (A01, A01A03, A01A24, A02, A03, A24), six HLA-B (B07, B08, B27, B44, B58, B62), two HLA-C (C1, C2), and five HLA-DRB1 (DR1, DR3, DR4, DR5, DR9) supertypes. Supertype B mismatch was associated with increased risk of grade II-IV acute graft-versus-host disease (hazard ratio =1.78, P=0.0025) compared to supertype B match. Supertype B07-B44 mismatch was associated with a higher incidence of both grade II-IV (hazard ratio=3.11, P=0.002) and III-IV (hazard ratio=3.15, P=0.01) acute graft-versus-host disease. No significant associations were detected between supertype-matched versus -mismatched groups at other HLA loci. These data suggest that avoiding HLA-B supertype mismatches can mitigate the risk of grade II-IV acute graft-versus-host disease in 7/8-mismatched unrelated donor hematopoietic cell transplantation when multiple HLA-B supertype-matched donors are available. Future studies are needed to define the mechanisms by which supertype mismatching affects outcomes after alternative donor hematopoietic cell transplantation