Recent identification of the Arabidopsis thaliana tyrosylprotein sulfotransferase (TPST) and a group of Tyr-sulfated peptides known as root meristem growth factors (RGFs) highlights the importance of protein Tyr sulfation in plant growth and development. Here, we report the action mechanism of TPST in maintenance of the root stem cell niche, which in the Arabidopsis root meristem is an area of four mitotically inactive quiescent cells plus the surrounding mitotically active stem cells. Mutation of TPST leads to defective maintenance of the root stem cell niche, decreased meristematic activity, and stunted root growth. We show that TPST expression is positively regulated by auxin and that mutation of this gene affects auxin distribution by reducing local expression levels of several PIN genes and auxin biosynthetic genes in the stem cell niche region. We also show that mutation of TPST impairs basal-and auxin-induced expression of the PLETHORA (PLT) stem cell transcription factor genes and that overexpression of PLT2 rescues the root meristem defects of the loss-offunction mutant of TPST. Together, these results support that TPST acts to maintain root stem cell niche by regulating basal-and auxin-induced expression of PLT1 and PLT2. TPST-dependent sulfation of RGFs provides a link between auxin and PLTs in regulating root stem cell niche maintenance.

Based on the tight-binding model, we investigate band structures of graphene nanohole ͑GNH͒ superlattices as a function of NH size and density. One common origin of band gaps for GNH superlattices with NHs of either armchair or zigzag edges is the quantum-confinement effect due to the periodic potential introduced by the NHs, which turns the semimetallic sheet into a direct-gap semiconductor. Additional band gaps also open for GNH superlattices with NHs of zigzag edges in a ferromagnetic ground state, arising from the staggered sublattice potential on the zigzag edges due to edge magnetization. Our calculations reveal a generic scaling relation that both types of band gaps increase linearly with the product of NH size and density.The electronic structure of nanoscale carbon materials such as fullerenes and carbon nanotubes has been intensively studied during the past two decades. 1 Among the carbon materials, graphene is a rapidly rising star showing a wealth of interesting unconventional electronic properties and a broad range of potential applications. 2 In addition to twodimensional ͑2D͒ graphene sheet, much attention has also been drawn to graphene-based low-dimensional nanostructures such as zero-dimensional nanodots 3-5 and nanoholes ͑antidots͒, 6-9 one-dimensional nanoribbons, 10-16 as well as 2D graphene nanohole superlattices. 6-8 These structures exhibit unique electronic structures different from the graphene sheet itself and hence offering other application potentials.There are two key effects in determining the electronic properties of these low-dimensional graphene nanostructures: the size effect and edge effect, the former induces quantum confinement converting the semimetal graphene into semiconductors and the latter induces edge magnetism as well as opening a small band gap. Both these effects have been extensively studied in graphene nanoribbons and show strong size and shape dependences. [10][11][12][13][14][15][16] For example, it has been shown that the band gap of nanoribbons scales inversely with their width 10-12 and nanoribbons with zigzag edges may have either a ferromagnetic ͑FM͒ or antiferromagnetic ͑AFM͒ ground state depending on their edge orientations. 8,10,16 On the other hand, less studies have been done for 2D GNH superlattices. Pedersen et al. 7 showed a linear scaling of the band gaps for circular GNH superlattice. However, it has been recently observed that graphene edges are generally straight stabilized with either armchair or zigzag edges. 17,18 Motivated by these new experiments, we have carried out tight-binding ͑TB͒ calculations and theoretical analyses to investigate the relationship between the band gap and the nanohole size/density for GNH superlattices with armchair and zigzag edges.Our numerical calculations show that both the armchairand zigzag-edged triangular GNH ͑TGNH͒ and rhombus GNH ͑RGNH͒ superlattices have nonzero and direct band gaps. The band gaps of armchair GNH superlattice originate solely from the quantum-confinement effect of 2D periodic potential cre...

Activation-induced deaminase (AID) mediates the somatic hypermutation (SHM) of Ig variable (V) regions that is required for the affinity maturation of the antibody response. An intensive analysis of a published database of somatic hypermutations that arose in the IGHV3-23*01 human V region expressed in vivo by human memory B cells revealed that the focus of mutations in complementary determining region (CDR)1 and CDR2 coincided with a combination of overlapping AGCT hotspots, the absence of AID cold spots, and an abundance of polymerase eta hotspots. If the overlapping hotspots in the CDR1 or CDR2 did not undergo mutation, the frequency of mutations throughout the V region was reduced. To model this result, we examined the mutation of the human IGHV3-23*01 biochemically and in the endogenous heavy chain locus of Ramos B cells. Deep sequencing revealed that IGHV3-23*01 in Ramos cells accumulates AID-induced mutations primarily in the AGCT in CDR2, which was also the most frequent site of mutation in vivo. Replacing the overlapping hotspots in CDR1 and CDR2 with neutral or cold motifs resulted in a reduction in mutations within the modified motifs and, to some degree, throughout the V region. In addition, some of the overlapping hotspots in the CDRs were at sites in which replacement mutations could change the structure of the CDR loops. Our analysis suggests that the local sequence environment of the V region, and especially of the CDR1 and CDR2, is highly evolved to recruit mutations to key residues in the CDRs of the IgV region.A fter an encounter with antigen and subsequent migration into the germinal centers of the secondary lymphoid organs, B cells undergo a regulated cascade of mutational events that occur at a very high frequency and are largely restricted to the variable (V) and switch (S) regions of the Ig heavy chain locus and the V region of the light chain locus. These mutagenic events are responsible for the somatic hypermutation (SHM) of the V regions and the class switch recombination of the constant (C) regions that are required for protective antibodies (1, 2). Both SHM and class switch recombination are initiated by activationinduced deaminase (AID) that preferentially deaminates the dC residues in WRC (W = A/T, R = A/G) hotspot motifs at frequencies 2-10-fold higher than SYC (S = G/C; Y = C/T) cold spots (3-7). During V region SHM, the resulting dU:G mismatch can then be replicated during S-phase to produce transition mutations, be processed by uracil-DNA glycosylase 2 and apurinic/ apyrimidinic endonucleases through the base excision repair pathway to produce both transitions and transversions (8-10), or be recognized by MutS homolog (MSH)2/MSH6 of the mismatch repair (MMR) complex that recruits the low-fidelity polymerase eta (Polη) to generate additional mutations at neighboring A:T residues (11).The specificity of AID targeting to the Ig gene has been under intense investigation. Studies have shown that AID deamination and mutagenesis targets single-stranded DNA substrates generated during ...

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During somatic hypermutation (SHM), activation-induced deaminase (AID) mutates deoxycytidine on single-stranded DNA (ssDNA) generated by the transcription machinery, but the detailed mechanism remains unclear. Here we report a higher abundance of RNA polymerase II (Pol II) at the immunoglobulin heavy chain variable (Igh-V) region compared to the constant region and partially transcribed Igh RNAs, suggesting a slower Pol II progression at Igh-V that could result in some early/premature transcription termination after prolonged pausing/stalling of Pol II. Knocking down RNA exosome complexes, which could decrease premature transcription termination, leads to decreased SHM. Knocking down Spt5, which can augment premature transcription termination, leads to increases in both SHM and the abundance of ssDNA substrates. Collectively, our data support the model that, following the reduction of Pol II progression (pausing or stalling) at the Igh-V, additional steps such as premature transcription termination are involved in providing ssDNA substrates for AID during SHM.

The dwarfing gene D-53 is one of a few dominant genes for dwarfing in rice (Oryza sativa L.). In the present study, our genetic analysis confirmed that mutant characteristics including dwarfing, profuse tillering, thin stems and small panicles are all controlled by the dominant D-53 gene. We measured the length of each internode of KL908, a D-53-carrying line, and classified the dwarfism of KL908 into the dn-type. In addition, we measured elongation of the second sheath and α α α α α-amylase activity in the endosperm, and we characterized KL908 as a dwarf mutant that was neither gibberellic acid-deficient nor gibberellic acid-insensitive. Using a large F 2 population obtained by crossing KL908 with a wild-type variety, NJ6, the D-53 gene was mapped to the terminal region of the short arm of chromosome 11, with one simple sequence repeat marker, Ds3, co-segregating, and the other, K81114, located 0.6 cM away.

BackgroundThe global outbreak of coronavirus disease 2019 (COVID-19) has turned into a worldwide public health crisis and caused more than 100,000,000 severe cases. Progressive lymphopenia, especially in T cells, was a prominent clinical feature of severe COVID-19. Activated HLA-DR+CD38+ CD8+ T cells were enriched over a prolonged period from the lymphopenia patients who died from Ebola and influenza infection and in severe patients infected with SARS-CoV-2. However, the CD38+HLA-DR+ CD8+ T population was reported to play contradictory roles in SARS-CoV-2 infection.MethodsA total of 42 COVID-19 patients, including 32 mild or moderate and 10 severe or critical cases, who received care at Beijing Ditan Hospital were recruited into this retrospective study. Blood samples were first collected within 3 days of the hospital admission and once every 3–7 days during hospitalization. The longitudinal flow cytometric data were examined during hospitalization. Moreover, we evaluated serum levels of 45 cytokines/chemokines/growth factors and 14 soluble checkpoints using Luminex multiplex assay longitudinally.ResultsWe revealed that the HLA-DR+CD38+ CD8+ T population was heterogeneous, and could be divided into two subsets with distinct characteristics: HLA-DR+CD38dim and HLA-DR+CD38hi. We observed a persistent accumulation of HLA-DR+CD38hi CD8+ T cells in severe COVID-19 patients. These HLA-DR+CD38hi CD8+ T cells were in a state of overactivation and consequent dysregulation manifested by expression of multiple inhibitory and stimulatory checkpoints, higher apoptotic sensitivity, impaired killing potential, and more exhausted transcriptional regulation compared to HLA-DR+CD38dim CD8+ T cells. Moreover, the clinical and laboratory data supported that only HLA-DR+CD38hi CD8+ T cells were associated with systemic inflammation, tissue injury, and immune disorders of severe COVID-19 patients.ConclusionsOur findings indicated that HLA-DR+CD38hi CD8+ T cells were correlated with disease severity of COVID-19 rather than HLA-DR+CD38dim population.

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