A quantitative trait locus for the number of days from sowing to seedling emergence in maize

Quantitative trait locus (QTL) mapping provides useful information for breeding programs since it allows the estimation of genomic locations and genetic effects of chromosomal regions related to the expression of quantitative traits. The number of days from sowing to seedling emergence (NDSSE) is an important agronomic trait in a maize (Zea mays L.) breeding project which is related to yield. To determine its genetic basis, a recombinant inbred line (RIL) population and two nitrogen (N) regimes were used to detect the QTLs associated with NDSSE; as a result, one QTL was identified under high N regime, on chromosome 9, which could explain 6.20% of phenotypic variance and a decrease of 0.18 of NDSSE due to an additive effect. These results are beneficial for understanding the genetic basis of NDSSE in maize breeding project.Key words: Maize (Zea mays L.), quantitative trait locus, recombinant inbred line, nitrogen

Rapid generation of endogenously driven transcriptional reporters in cells through CRISPR/Cas9

CRISPR/Cas9 technologies have been employed for genome editing to achieve gene knockouts and knock-ins in somatic cells. Similarly, certain endogenous genes have been tagged with fluorescent proteins. Often, the detection of tagged proteins requires high expression and sophisticated tools such as confocal microscopy and flow cytometry. Therefore, a simple, sensitive and robust transcriptional reporter system driven by endogenous promoter for studies into transcriptional regulation is desirable. We report a CRISPR/Cas9-based methodology for rapidly integrating a firefly luciferase gene in somatic cells under the control of endogenous promoter, using the TGFβ-responsive gene PAI-1. Our strategy employed a polycistronic cassette containing a non-fused GFP protein to ensure the detection of transgene delivery and rapid isolation of positive clones. We demonstrate that firefly luciferase cDNA can be efficiently delivered downstream of the promoter of the TGFβ-responsive gene PAI-1. Using chemical and genetic regulators of TGFβ signalling, we show that it mimics the transcriptional regulation of endogenous PAI-1 expression. Our unique approach has the potential to expedite studies on transcription of any gene in the context of its native chromatin landscape in somatic cells, allowing for robust high-throughput chemical and genetic screens

An Evidence-Based Medical Review on Promoting Gastrointestinal Function Recovery After Colorectal Cancer Surgery

Chun-Yu Zhao,1 Wan-Hong Shi,2 Zheng-Qi Wen,3 Yong-Mei Jin,4 Yun-Bo Shang,5 Lei Zheng,3 Juan Li,2 Xin-Min Chen2 1School of Nursing, Dali University, Dali, 671000, People’s Republic of China; 2Department of General Surgery, Third People’s Hospital of Yunnan Province, Kun Ming, 650000, People’s Republic of China; 3Department of Surgical Oncology, the First Affiliated Hospital of Kunming Medical University, Kun Ming, 650000, People’s Republic of China; 4Department of Nursing, Shanghai Seventh People’s Hospital, Shanghai, 200137, People’s Republic of China; 5Department of Emergency, Third People’s Hospital of Yunnan Province, Kun Ming, 650000, People’s Republic of ChinaCorrespondence: Yun-Bo Shang, Department of Emergency, Third People’s Hospital of Yunnan Province, No. 292 of Beijing Road, Guandu District, Kun Ming, 650000, People’s Republic of China, Tel +86-13708876606, Fax +8663196549, Email [email protected] Zheng-Qi Wen, Department of Surgical oncology, The First Affiliated Hospital of Kunming Medical University, Kun Ming, 650000, People’s Republic of China, Tel +86-13888079932, Email [email protected]: The objective of this study was to search for, evaluate, and summarize data related to a faster postoperative recovery in patients with colorectal cancer (CRC) based on literature from China as well as internationally. This will serve as an evidence-based foundation for the clinical implementation of enhanced postoperative recovery of gastrointestinal function in patients with CRC.Methods: Based on the hierarchical “ 6S” evidence model, we conducted a systematic search of computerized decision-support systems, guideline websites, as well as domestic and international databases for evidence, guidelines, expert consensus statements, clinical decision-making, best practices, evidence summaries, and systematic reviews of interventions focusing on accelerating gastrointestinal function rehabilitation after CRC surgery. The time limit for the search was from the date of creation of the database to January 2023. Two researchers evaluated the quality of the literature that was included, and we extracted data and summarized the evidence from those publications that fulfilled the quality criteria.Results: The review included a total of 21 publications, comprising 6 guidelines, 6 systematic reviews, 3 expert consensus statements, 4 randomized controlled trials, and 2 evidence summaries. We summarized 51 best evidence findings across five areas: organizational management, preoperative risk assessment, education, intraoperative monitoring, and postoperative management.Conclusion: There is a wide variety and wealth of information available on interventions to promote enhanced postoperative recovery of gastrointestinal function in patients with CRC. The use of evidence is discussed, keeping in mind the practical situation in China.Keywords: colorectal cancer, evidence-based nursing, evidence summary, gastrointestinal function recovery, postoperativ

Scanning and filling : ultra-dense SNP genotyping combining genotyping-by-sequencing, SNP array and whole-genome resequencing data

Genotyping-by-sequencing (GBS) represents a highly cost-effective high-throughput genotyping approach. By nature, however, GBS is subject to generating sizeable amounts of missing data and these will need to be imputed for many downstream analyses. The extent to which such missing data can be tolerated in calling SNPs has not been explored widely. In this work, we first explore the use of imputation to fill in missing genotypes in GBS datasets. Importantly, we use whole genome resequencing data to assess the accuracy of the imputed data. Using a panel of 301 soybean accessions, we show that over 62,000 SNPs could be called when tolerating up to 80% missing data, a five-fold increase over the number called when tolerating up to 20% missing data. At all levels of missing data examined (between 20% and 80%), the resulting SNP datasets were of uniformly high accuracy (96– 98%). We then used imputation to combine complementary SNP datasets derived from GBS and a SNP array (SoySNP50K). We thus produced an enhanced dataset of >100,000 SNPs and the genotypes at the previously untyped loci were again imputed with a high level of accuracy (95%). Of the >4,000,000 SNPs identified through resequencing 23 accessions (among the 301 used in the GBS analysis), 1.4 million tag SNPs were used as a reference to impute this large set of SNPs on the entire panel of 301 accessions. These previously untyped loci could be imputed with around 90% accuracy. Finally, we used the 100K SNP dataset (GBS + SoySNP50K) to perform a GWAS on seed oil content within this collection of soybean accessions. Both the number of significant marker-trait associations and the peak significance levels were improved considerably using this enhanced catalog of SNPs relative to a smaller catalog resulting from GBS alone at 20% missing data. Our results demonstrate that imputation can be used to fill in both missing genotypes and untyped loci with very high accuracy and that this leads to more powerful genetic analyses

Solving Nonlinear Parabolic Equations by a Strongly Implicit Finite-Difference Scheme

We discuss the numerical solution of nonlinear parabolic partial differential equations, exhibiting finite speed of propagation, via a strongly implicit finite-difference scheme with formal truncation error $\mathcal{O}\left[(\Delta x)^2 + (\Delta t)^2 \right]$. Our application of interest is the spreading of viscous gravity currents in the study of which these type of differential equations arise. Viscous gravity currents are low Reynolds number (viscous forces dominate inertial forces) flow phenomena in which a dense, viscous fluid displaces a lighter (usually immiscible) fluid. The fluids may be confined by the sidewalls of a channel or propagate in an unconfined two-dimensional (or axisymmetric three-dimensional) geometry. Under the lubrication approximation, the mathematical description of the spreading of these fluids reduces to solving the so-called thin-film equation for the current's shape $h(x,t)$. To solve such nonlinear parabolic equations we propose a finite-difference scheme based on the Crank--Nicolson idea. We implement the scheme for problems involving a single spatial coordinate (i.e., two-dimensional, axisymmetric or spherically-symmetric three-dimensional currents) on an equispaced but staggered grid. We benchmark the scheme against analytical solutions and highlight its strong numerical stability by specifically considering the spreading of non-Newtonian power-law fluids in a variable-width confined channel-like geometry (a "Hele-Shaw cell") subject to a given mass conservation/balance constraint. We show that this constraint can be implemented by re-expressing it as nonlinear flux boundary conditions on the domain's endpoints. Then, we show numerically that the scheme achieves its full second-order accuracy in space and time. We also highlight through numerical simulations how the proposed scheme accurately respects the mass conservation/balance constraint.Comment: 36 pages, 9 figures, Springer book class; v2 includes improvements and corrections; to appear as a contribution in "Applied Wave Mathematics II

Toll-like receptor 4 is a therapeutic target for prevention and treatment of liver failure

Background and aims: Toll-like receptor 4 (TLR4) plays an essential role in mediating organ injury in acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). Here we assess whether inhibiting TLR4 signaling can ameliorate liver failure and serve as a potential treatment. / Material and Methods: Circulating TLR4 ligands and hepatic TLR4 expression was measured in plasma samples and liver biopsies from patients with cirrhosis. TAK-242 (TLR4 inhibitor) was tested in vivo with 10mg/Kg, i.p. in rodent models of ACLF (bile duct ligation + lipopolysaccharide (LPS); carbontetrachloride + LPS) and ALF (Galactosamine + LPS) and in vitro on immortalized human monocytes (THP-1) and hepatocytes (HHL5).. The in vivo therapeutic effect was assessed by coma free survival, organ injury and cytokine release and in vitro by measuring IL6, IL1b or cell injury (TUNEL), respectively. / Results: In patients with cirrhosis, hepatic TLR4 expression was upregulated and circulating TLR4 ligands were increased (p<0.001). ACLF in rodents was associated with a switch from apoptotic cell death in ALF to non-apoptotic forms of cell death. TAK-242 reduced LPS induced cytokine secretion and cell death (p=0.002) in hepatocytes and monocytes in vitro. In rodent models of ACLF, TAK-242 administration improved coma free survival, reduced the degree of hepatocyte cell death in liver p<0.001) and kidneys (p=0.048) and reduced circulating cytokine levels (IL1b p<0.001). In a rodent model of ALF TAK-242 prevented organ injury (p<0.001) and systemic inflammation (IL1b p<0.001). / Conclusion: This study shows that TLR4 signaling is a key factor in the development of both ACLF and ALF and its inhibition improves severity of organ injury and outcome. TAK-242 may be of therapeutic relevance in patients with liver failure

Gene expression drives the evolution of dominance.

Dominance is a fundamental concept in molecular genetics and has implications for understanding patterns of genetic variation, evolution, and complex traits. However, despite its importance, the degree of dominance in natural populations is poorly quantified. Here, we leverage multiple mating systems in natural populations of Arabidopsis to co-estimate the distribution of fitness effects and dominance coefficients of new amino acid changing mutations. We find that more deleterious mutations are more likely to be recessive than less deleterious mutations. Further, this pattern holds across gene categories, but varies with the connectivity and expression patterns of genes. Our work argues that dominance arises as a consequence of the functional importance of genes and their optimal expression levels

The polygenic nature of telomere length and the anti-ageing properties of lithium

Telomere length is a promising biomarker for age-related disease and a potential anti-ageing drug target. Here, we study the genetic architecture of telomere length and the repositioning potential of lithium as an anti-ageing medication. LD score regression applied to the largest telomere length genome-wide association study to-date, revealed SNP-chip heritability estimates of 7.29%, with polygenic risk scoring capturing 4.4% of the variance in telomere length in an independent cohort (p = 6.17 × 10-5). Gene-enrichment analysis identified 13 genes associated with telomere length, with the most significant being the leucine rich repeat gene, LRRC34 (p = 3.69 × 10-18). In the context of lithium, we confirm that chronic use in a sample of 384 bipolar disorder patients is associated with longer telomeres (p = 0.03). As complementary evidence, we studied three orthologs of telomere length regulators in a Caenorhabditis elegans model of lithium-induced extended longevity and found all transcripts to be affected post-treatment (p  0.05). Consequently, this suggests that lithium may be catalysing the activity of endogenous mechanisms that promote telomere lengthening, whereby its efficacy eventually becomes limited by each individual's inherent telomere maintenance capabilities. Our work indicates a potential use of polygenic risk scoring for the prediction of adult telomere length and consequently lithium's anti-ageing efficacy

Arc Discharge Synthesis and Photoluminescence of 3D Feather-like AlN Nanostructures

A complex three-dimensional (3D) feather-like AlN nanostructure was synthesized by a direct reaction of high-purity Al granules with nitrogen using an arc discharge method. By adjusting the discharge time, a coral-like nanostructure, which evolved from the feather-like nanostructure, has also been observed. The novel 3D feather-like AlN nanostructure has a hierarchical dendritic structure, which means that the angle between the trunk stem and its branch is always about 30° in any part of the structure. The fine branches on the surface of the feather-like nanostructure have shown a uniform fish scale shape, which are about 100 nm long, 10 nm thick and several tens of nanometers in width. An alternate growth model has been proposed to explain the novel nanostructure. The spectrum of the feather-like products shows a strong blue emission band centered at 438 nm (2.84 eV), which indicates their potential application as blue light-emitting diodes