Clinical and immunological features of an APLAID patient caused by a novel mutation in PLCG2

BackgroundThe APLAID syndrome is a rare primary immunodeficiency caused by gain-of-function mutations in the PLCG2 gene. We present a 7-year-old APLAID patient who has recurrent blistering skin lesions, skin infections in the perineum, a rectal perineal fistula, and inflammatory bowel disease.MethodsTo determine the genetic cause of our patient, WES and bioinformatics analysis were performed. Flow cytometry was used for phenotyping immune cell populations in peripheral blood. Cytokines released into plasma were analyzed using protein chip technology. The PBMCs of patient and a healthy child were subjected to single-cell RNA-sequencing analysis.ResultsThe patient carried a novel de novo missense mutation c.2534T>C in exon 24 of the PLCG2 gene that causes a leucine to serine amino acid substitution (p.Leu845Ser). Bioinformatics analysis revealed that this mutation had a negative impact on the structure of the PLCγ2 protein, which is highly conserved in many other species. Immunophenotyping by flow cytometry revealed that in addition to the typical decrease in circulating memory B cells, the levels of myeloid dendritic cells (mDCs) in the children’s peripheral blood were significantly lower, as were the CD4+ effector T cells induced by their activation. Single-cell sequencing revealed that the proportion of different types of cells in the peripheral blood of the APLAID patient changed.ConclusionsWe present the first case of APLAID with severely reduced myeloid dendritic cells carrying a novel PLCG2 mutation, and conducted a comprehensive analysis of immunological features in the ALPAID patient, which has not been mentioned in previous reports. This study expands the spectrum of APLAID-associated immunophenotype and genotype. The detailed immune analyses in this patient may provide a basis for the development of targeted therapies for this severe autoinflammatory disease

Porous Pyrene Organic Cage with Unusual Absorption Bathochromic-Shift Enables Visible Light Photocatalysis

We have constructed a novel porous pyrene-based organic cage, PyTC1, through the condensation reaction of cyclohexanediamine with 5,5&prime;-(pyrene-1,6-diyl)diisophthalaldehyde. Single-crystal X-ray diffraction analysis reveals the effective intercage C&ndash;H...&pi; interaction between cyclohexanediimine and pyrene segments. Such a soft intercage C&ndash;H...&pi; interaction, rather than a classic J-aggregate with slipped &pi;&ndash;&pi;-stacking configuration, induced an unusual bathochromic shift of pyrene-based chromophore absorption from an ultraviolet region of PyTC1 in solution to the visible light region of PyTC1 in solid-state. This enabled heterogeneous visible light photocatalysis of aerobic hydroxylation of benzeneboronic acid derivatives. To the best of our knowledge, this is the first report that represents an absorption bathochromic shift caused by C&ndash;H...&pi; interaction. Such phenomenon could endow visible-light-driven photocatalysis that originally could only be achieved using UV light with the same chromophore. &nbsp;</p

Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a $Z$ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 $< p_{\textrm{T}} < 100$ GeV and in the pseudorapidity range $2.5 < \eta < 4$. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb$^{-1}$. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb public pages

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

Measurement of the ratios of branching fractions R(D∗)\mathcal{R}(D^{*}) and R(D0)\mathcal{R}(D^{0})

The ratios of branching fractions $\mathcal{R}(D^{*})\equiv\mathcal{B}(\bar{B}\to D^{*}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(\bar{B}\to D^{*}\mu^{-}\bar{\nu}_{\mu})$ and $\mathcal{R}(D^{0})\equiv\mathcal{B}(B^{-}\to D^{0}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(B^{-}\to D^{0}\mu^{-}\bar{\nu}_{\mu})$ are measured, assuming isospin symmetry, using a sample of proton-proton collision data corresponding to 3.0 fb${ }^{-1}$ of integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The tau lepton is identified in the decay mode $\tau^{-}\to\mu^{-}\nu_{\tau}\bar{\nu}_{\mu}$. The measured values are $\mathcal{R}(D^{*})=0.281\pm0.018\pm0.024$ and $\mathcal{R}(D^{0})=0.441\pm0.060\pm0.066$, where the first uncertainty is statistical and the second is systematic. The correlation between these measurements is $\rho=-0.43$. Results are consistent with the current average of these quantities and are at a combined 1.9 standard deviations from the predictions based on lepton flavor universality in the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-039.html (LHCb public pages

The preparation and characterization of highly fluorinated poly(arylene alkylene ether)s

Peer reviewed: YesNRC publication: Ye

Ring-opening polymerization of polyarylates

146-150A series of new macrocyclic arylates have been efficiently synthesized and unambiguously characterized by a combination of GPC, MS (FAB) and 1<span style="font-size:11.0pt;font-family: " calibri","sans-serif";mso-ascii-theme-font:minor-latin;mso-fareast-font-family:="" "times="" new="" roman";mso-fareast-theme-font:minor-fareast;mso-hansi-theme-font:="" minor-latin;mso-bidi-font-family:arial;mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="">H <span style="font-size:11.0pt; font-family:" calibri","sans-serif";mso-ascii-theme-font:minor-latin;mso-fareast-font-family:="" "times="" new="" roman";mso-fareast-theme-font:minor-fareast;mso-hansi-theme-font:="" minor-latin;mso-bidi-font-family:"times="" roman";mso-ansi-language:en-us;="" mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">NMR. These macrocycles undergo facile ring opening polymerization in the presence of anionic initiators to give high molecular weight polyarylates.</span

Synthesis and characterizations of highly fluorinated poly(arylene ether)s for quadratic nonlinear optics

New highly fluorinated poly(arylene ether sulfone)s (FPAES), poly(arylene ether ketone)s (FPAEK), and poly(arylene ether)s with several types of NLO chromophores as pendant groups were obtained by a polycondensation reaction using very mild conditions. The different polymer structures were designed with the objective to investigate the influence of both the polarity of the chromophore and the nature of the tether between the NLO chromophore and the chain. The resulting copolymers have glass transition temperatures (Tg\u2019s) varying between 160 and 215\ub0C, and they are stable up to 280\ub0C under nitrogen. Although these copolymers are soluble in common organic solvents, cyclohexanone gave the best film quality and was used for the film preparation. After optimization of the poling conditions, the in situ second harmonic generation (SHG) measurements gave nonresonant values of the second-order susceptibilities d33 ranging from 2 to 8 pm/V, and the SHG signals of the poled polymer films were found to be thermally stable below 130\ub0C. Although being comparable with the values obtained for similar polymers and chromophores in the literature, d\u2083\u2083 are smaller than those obtained for more conventional NLO polymers like PMMA-Disperse Red One (PMMA-DR1), which was taken as a reference. An unusual drop of the SHG signal during cooling was found in the thermally assisted orientation process. This drop occurred at a characteristic temperature below Tg. In this relaxation process which has never been observed, intra- and interchain dipolar interactions are shown to play an important role, which is amplified in the case of chromophores which have their donor group embedded in the main chain, connected by two rigid tethers.Peer reviewed: YesNRC publication: Ye

Poly(ethyleneoxide-block-methylmethacrylate) derived recessed nanodisc electrode array as an ultrasensitive electrochemical sensing platform for immunosensor

In this work, we present the synthesis of amphiphilic diblock copolymer poly(ethylene oxide-block-methylmethacrylate) (PEO-b-PMMA) using atom transfer radical polymerization and demonstrate its application for the fabrication of recessed nanodisk-array electrode (RNE) as a platform for protein detection. For the fabrication of thin-film, PEO-b-PMMA was spin-coated on the silicon wafer and the phase separation was achieved by a unique direct immersion annealing technique followed by washing with the water/methanol solution to remove the PEO phase. The microphase separation and comprehensive porosity characterizations were done using AFM and electron microscopy. Later, the thin film was loaded on the surface of the glassy carbon electrode by wedge transfer technique and the RNE property of the mesoporous thin film was confirmed using cyclic voltammetry (CV). For the protein sensing application, the thin film-coated electrode was biotinylated using EDC-NHS chemistry, followed by the blocking of the non-specific sites using bovine serum albumin (BSA). The reduction in the CV current and the increase in the channel resistance in EIS at each stage of fabrication confirmed the successful immobilization. For the streptavidin detection, the RNE displayed an ultra-low detection limit of 0.15 fg/ml with enhanced selectivity which confirms the potential of PEO-b-PMMA based RNE as an ultrasensitive immunosensor platform for any biomarker detection. © 2021 Elsevier B.V