A de novo Variant in CROCC identified in a Chinese family implies the potential association with Atlanto-occipital Fusion (AOF)

Poster presentation for the Physoc 2021 annual conference. Atlanto-occipital fusion (AOF) is a rare skeletal malformation causing nerve compression with high risk of fatal. Its genetic information is currently lacking. Through whole-exome sequencing (WES) on a Chinese family having a sporadic proband son of AOF but other healthy family members, we identified a novel variant (chr1: c.4702C>T: p.R1568C) in ciliary rootlet coiled-coil (CROCC). The variant had different genotypes between the proband and healthy family members but with high conservations of “damage” to protein structure based on MutationTaster and SIFT forecast. CROCC gene can be obtained in both healthy (n=220) and non-mutated AOF patient samples (n=68) but absented in five sporadic patients with the novel variant. Furthermore, abnormal of cilia was observed after editing the target sequence on CROCC using CRISPR-Cas9. These results suggested that AOF might be caused by the mutation of the variant c.4702C>T:p.R1568C in CROCC. With strong amino acid conservation and interaction regulation, the variant mutation could cause the signal disorder of skeletal development which may lead to the defective bone formation and finally cause the development of AOF

Implication of a de novo Variant in ciliary rootlet coiledcoil (CROCC) with assimilation of atlas (AOA)

Assimilation of atlas is a rare skeletal malformation causing nerve compression with high risk of fatal. However, the genetic etiology of assimilation of atlas AOA is currently lacking. In this paper, the whole-exome sequencing (WES) analysis was employed to study a Chinese family having a sporadic proband son of assimilation of atlas AOA but other healthy family members. We identified a novel variant in ciliary rootlet coiled-coil gene (NM_014675.5 (CROCC): c.4702C>T (r.4702c>u, p.(Arg1568Cys)). The variant had different genotypes between the proband and healthy family members but with high conservations of “damage” to protein structure based on MutationTaster and SIFT prediction. CROCC gene can be obtained in both healthy (n=220) and non-mutated assimilation of atlas AOA patient samples (n=68) but absented in five sporadic patients with the novel variant. Furthermore, abnormal of cilia was observed after editing the target sequence on CROCC using CRISPR-Cas9. These results suggested that assimilation of atlas AOA might be caused by the mutation of CROCC: c.4702C>T (r.4702c>u, p.(Arg1568Cys)). With strong amino acid conservation and interaction regulation, the variant mutation could cause the signal disorder of skeletal development which may lead to the defective bone formation and finally cause the development of assimilation of atlas AOA

The Genomes of Oryza sativa: A History of Duplications

We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000–40,000. Only 2%–3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family

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

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

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Modified Blair ankle fusion for ankle arthritis

Objective:To investigate the clinical outcome of modified Blair ankle fusion for ankle arthritis. Methods:Between November 2009 and June 2012, 28 patients with ankle arthritis were treated, among whom 11 had obvious foot varus deformity, and 17 were almost normal in appearance. There were 13 males and 15 females with an average age of 49.4 years (range, 23-67 years). The main symptoms included swelling, pain, and a limited range of motion of the ankles. The ankle joints functions were assessed by American Orthopedic Foot and Ankle Society (AOFAS) ankle and hindfoot score and visual analog scale (VAS) preoperatively and at 1 year follow-up. Results:Twenty-eight patients were followed up for 19.8 months on average (range, 1-2 years). Superficial wound infection occurred in 3 cases, and was cured after debridement; the other incisions healed by first intention without complications. All ankles were fused at 1 year follow-up after operation. The symptom was relieved completely in all patients at last follow-up without complication of implant failure, or nonunion. The postoperative AOFAS ankle and hindfoot score was 83.13±3.76, showing significant difference when compared with the preoperative score (45.38±3.21, P&lt;0.01). VAS was significantly decreased from 8.01±0.63 to 2.31±1.05 at 1 year follow-up (P&lt;0.05). Conclusion:Modified Blair ankle fusion has the advantages of high feasiblity, less cost and rigid fixation. It shows high reliability in pain relief and may obtain a good clinical effectiveness. Key words: Ankle; Arthritis; Arthrodesis; Fracture fixation, intramedullar

Associations between Conventional and Emerging Indicators of Dietary Carbohydrate Quality and New-Onset Type 2 Diabetes Mellitus in Chinese Adults

Dietary glycemic index (GI), carbohydrate to fiber ratio (CF) and carbohydrate quality index (CQI) are conventional and emerging indicators for carbohydrate quality. We aimed to investigate the associations between these indicators and new-onset type 2 diabetes mellitus (T2DM) risk among Chinese adults. This prospective cohort study included 14,590 adults from the China Health and Nutrition Survey without cardiometabolic diseases at baseline. The associations between dietary GI, CF and CQI and T2DM risk were assessed using Cox proportional hazard regression analysis and dose&ndash;response relationships were explored using restricted cubic spline and threshold analysis. After a mean follow-up duration of 10 years, a total of 1053 new-onset T2DM cases occurred. There were U-shaped associations between dietary GI and CF and T2DM risk (both P-nonlinear &lt; 0.0001), and T2DM risk was lowest when dietary GI was 72.85 (71.40, 74.05) and CF was 20.55 (17.92, 21.91), respectively (both P-log likelihood ratio &lt; 0.0001). Inverse associations between CQI and T2DM risk specifically existed in participants &lt; 60 y or attended middle school or above (both P-trend &lt; 0.05). These findings indicated that moderate dietary GI and CF range and a higher dietary CQI score may be suggested for T2DM prevention in Chinese adults

A single nucleotide polymorphism of the porcine CXCL8 gene is associated with serum CXCL8 level

C-X-C motif chemokine ligand 8 (CXCL8) gene, a crucial cytokine with roles in the immune system, functions in the inflammatory response by promoting the activation and migration of neutrophils. Previous studies have reported that the CXCL8 gene resides within the quantitative trait locus (QTL). In this report, the porcine CXCL8 gene was selected to investigate its effect on serum immune traits. CXCL8 mRNA expression was also detected by quantitative real-time polymerase chain reaction (PCR). A SNP (NC_010450.4:g.69934997T > C, rs81218904) of the CXCL8 gene was identified by direct nucleotide sequencing and the SNP was genotyped by MALDI-TOF MS in the three pig populations, which consisted of 300 piglets distributed in three pig breeds, Landrace (68 piglets), Large White (158 piglets) and Songliao Black (74 piglets). An in-depth analysis indicated that there was a significant correlation between the SNP and the serum CXCL8 level (20 days) (14 days after vaccination) (p < .05). Our results suggest that the CXCL8 gene may be served as a genetic marker with effects on serum CXCL8 level in the pig disease resistance breeding.Highlights Genomic variant identification and tissues expression analysis of porcine CXCL8 gene. The SNP in porcine CXCL8 gene was significantly associated with serum CXCL8 level in three pig populations. SNP genotyping and association analysis results provided significant evidence for association on serum cytokine trait of porcine CXCL8 gene