Abstract
Background
Worldwide, the cultivated potato, Solanum tuberosum L., is the No. 1 vegetable crop and a critical food security crop. The genome sequence of DM1–3 516 R44, a doubled monoploid ...clone of S. tuberosum Group Phureja, was published in 2011 using a whole-genome shotgun sequencing approach with short-read sequence data. Current advanced sequencing technologies now permit generation of near-complete, high-quality chromosome-scale genome assemblies at minimal cost.
Findings
Here, we present an updated version of the DM1–3 516 R44 genome sequence (v6.1) using Oxford Nanopore Technologies long reads coupled with proximity-by-ligation scaffolding (Hi-C), yielding a chromosome-scale assembly. The new (v6.1) assembly represents 741.6 Mb of sequence (87.8%) of the estimated 844 Mb genome, of which 741.5 Mb is non-gapped with 731.2 Mb anchored to the 12 chromosomes. Use of Oxford Nanopore Technologies full-length complementary DNA sequencing enabled annotation of 32,917 high-confidence protein-coding genes encoding 44,851 gene models that had a significantly improved representation of conserved orthologs compared with the previous annotation. The new assembly has improved contiguity with a 595-fold increase in N50 contig size, 99% reduction in the number of contigs, a 44-fold increase in N50 scaffold size, and an LTR Assembly Index score of 13.56, placing it in the category of reference genome quality. The improved assembly also permitted annotation of the centromeres via alignment to sequencing reads derived from CENH3 nucleosomes.
Conclusions
Access to advanced sequencing technologies and improved software permitted generation of a high-quality, long-read, chromosome-scale assembly and improved annotation dataset for the reference genotype of potato that will facilitate research aimed at improving agronomic traits and understanding genome evolution.
A fundamental requirement for life is the replication of an organism's DNA. Studies in Escherichia coli and Bacillus subtilis have set the paradigm for DNA replication in bacteria. During replication ...initiation in E. coli and B. subtilis, the replicative helicase is loaded onto the DNA at the origin of replication by an ATPase helicase loader. However, most bacteria do not encode homologs to the helicase loaders in E. coli and B. subtilis. Recent work has identified the DciA protein as a predicted helicase operator that may perform a function analogous to the helicase loaders in E. coli and B. subtilis. DciA proteins, which are defined by the presence of a DUF721 domain (termed the DciA domain herein), are conserved in most bacteria but have only been studied in mycobacteria and gammaproteobacteria (Pseudomonas aeruginosa and Vibrio cholerae). Sequences outside the DciA domain in Mycobacterium tuberculosis DciA are essential for protein function but are not conserved in the P. aeruginosa and V. cholerae homologs, raising questions regarding the conservation and evolution of DciA proteins across bacterial phyla. To comprehensively define the DciA protein family, we took a computational evolutionary approach and analyzed the domain architectures and sequence properties of DciA domain-containing proteins across the tree of life. These analyses identified lineage-specific domain architectures among DciA homologs, as well as broadly conserved sequence-structural motifs. The diversity of DciA proteins represents the evolution of helicase operation in bacterial DNA replication and highlights the need for phylum-specific analyses of this fundamental biological process.
Despite the fundamental importance of DNA replication for life, this process remains understudied in bacteria outside Escherichia coli and Bacillus subtilis. In particular, most bacteria do not encode the helicase-loading proteins that are essential in E. coli and B. subtilis for DNA replication. Instead, most bacteria encode a DciA homolog that likely constitutes the predominant mechanism of helicase operation in bacteria. However, it is still unknown how DciA structure and function compare across diverse phyla that encode DciA proteins. In this study, we performed computational evolutionary analyses to uncover tremendous diversity among DciA homologs. These studies provide a significant advance in our understanding of an essential component of the bacterial DNA replication machinery.
Venous congestion is an under-recognized contributor to mortality in critically ill patients. Unfortunately, venous congestion is difficult to measure, and right heart catheterization (RHC) has been ...considered the most readily available means for measuring venous filling pressure. Recently, a novel "Venous Excess Ultrasound (VExUS)" score was developed to noninvasively quantify venous congestion using inferior vena cava (IVC) diameter and Doppler flow through the hepatic, portal, and renal veins. A preliminary retrospective study of post-cardiac surgery patients showed promising results, including a high positive-likelihood ratio of high VExUS grade for acute kidney injury. However, studies have not been reported in broader patient populations, and the relationship between VExUS and conventional measures of venous congestion is unknown. To address these gaps, we prospectively assessed the correlation of VExUS with right atrial pressure (RAP), with comparison to inferior vena cava (IVC) diameter. Patients undergoing RHC at Denver Health Medical Center underwent VExUS examination before their procedure. VExUS grades were assigned before RHC, blinding ultrasonographers to RHC outcomes. After controlling for age, sex, and common comorbidities, we observed a significant positive association between RAP and VExUS grade (P < 0.001, R
= .68). VExUS had a favorable AUC for prediction of a RAP ≥ 12 mmHg (0.99, 95% CI 0.96-1) compared to IVC diameter (0.79, 95% CI 0.65-0.92). These results suggest a strong correlation between VExUS and RAP in a diverse patient population, and support future studies of VExUS as a tool to assess venous congestion and guide management in a spectrum of critical illnesses.
ABSTRACT
Distinguishing high-performing employees imposes choices on managers: Is recognition most effectively delivered publicly or privately? If delivered publicly, what setting is best? This paper ...broadens the accounting literature on the implications of these decisions. Via experiment, I examine how the social bond between recognized employees and those observing the recognition influences the effect of recognition visibility on employee behavior. I find that with weak social bonds, public recognition (versus private) does not result in more beneficial employee behavior. However, when social bonds are strong, employees provide greater pre-recognition effort and respond more positively to public recognition than to private recognition. Overall, my study supports the extensive use of public recognition in practice and helps clarify the collective results from prior accounting studies. My findings also have implications for implementing recognition programs—suggesting managers should consider employee relationships when deciding how and where to recognize their employees.
Many patients with oncogene-driven non–small-cell lung cancer (NSCLC) treated with tyrosine kinase inhibitors experience limited sites of disease progression. This study investigated retrospectively ...the benefits of local ablative therapy (LAT) to central nervous system (CNS) and/or limited systemic disease progression and continuation of crizotinib or erlotinib in patients with metastatic ALK gene rearrangement (ALK+) or EGFR-mutant (EGFR-MT) NSCLC, respectively.
Patients with metastatic ALK+ NSCLC treated with crizotinib (n = 38) and EGFR-MT NSCLC treated with erlotinib (n = 27) were identified at a single institution. Initial response to the respective kinase inhibitors, median progression-free survival (PFS1), and site of first progression were recorded. A subset of patients with either nonleptomeningeal CNS and/or four sites or fewer of extra-CNS progression (oligoprogressive disease) suitable for LAT received either radiation or surgery to these sites and continued on the same tyrosine kinase inhibitors. The subsequent median progression-free survival from the time of first progression (PFS2) and pattern of progression were recorded.
Median progression-free survival in ALK+ patients on crizotinib was 9.0 months, and 13.8 months for EGFR-MT patients on erlotinib. Twenty-five of 51 patients (49%) who progressed were deemed suitable for local therapy (15 ALK+, 10 EGFR-MT; 24 with radiotherapy, one with surgery) and continuation of the same targeted therapy. Post-LAT, 19 of 25 patients progressed again, with median PFS2 of 6.2 months.
Oncogene-addicted NSCLC with CNS and/or limited systemic disease progression (oligoprogressive disease) on relevant targeted therapies is often suitable for LAT and continuation of the targeted agent, and is associated with more than 6 months of additional disease control.
Femoral neck stress fractures (FNSFs) are a unique injury pattern not commonly treated in the civilian trauma population; however, it is particularly high with military trainees engaged in basic ...combat training. To date, no study has surveyed a population of military orthopedic surgeons on treatment preferences for military service members (SMs) with FNSF.
We aim to evaluate the extent of clinical equipoise that exists in the management of these injuries, hypothesizing that there would be consensus in the factors dictating surgical and non-surgical intervention for FNSF.
A 27-question survey was created and sent to U.S. military orthopedic surgeon members of the Society of Military Orthopaedic Surgeons. The survey was designed in order to gather the experience among surgeons in treating FNSF and identifying variables that play a role in the treatment algorithm for these patients. In addition, seven detailed, clinical vignettes were presented to further inquire on surgeon treatment preferences. Binomial distribution analysis was used to evaluate for common trends within the surgeon's treatment preferences.
Seventy orthopedic surgeons completed the survey, the majority of whom were on active duty status in the U.S. Military (82.86%) and having under 5 years of experience (61.43%). Majority of surgeons elected for a multiple screw construct (92.86%), however the orientation of the multiple screws was dependent on whether the fracture was open or closed. Management for compression-sided FNSF involving ≥50% of the femoral neck width, tension-sided FNSF, and stress fractures demonstrating fracture line progression had consensus for operative management. Respondents agreed upon prophylactic fixation of the contralateral hip if the following factors were involved: Complete fracture (98.57%), compression-sided fracture line >75% (88.57%), compression-sided fracture line >50-75% with hip effusion (88.57%), contralateral tension-sided fracture (87.14%), and compression-sided fracture line >50-75% (84.29%). An FNSF < 50% on the contralateral femoral neck or a hip effusion was indeterminate in surgeons indicating need for prophylactic fixation. Majority of surgeons (77.1%) utilized restricted toe-touch weight-bearing for postoperative mobility restrictions.
Consensus exists for surgical and non-surgical management of FNSF by U.S. military orthopedic surgeons, despite the preponderance of surgeons reporting a low annual volume of FNSF cases treated. However, there are certain aspects in the operative and non-operative management of FNSF that are unanimously adhered to. Specifically, our results demonstrate that there is no clear indication on the management of FNSF when an associated hip effusion is involved. Additionally, the indications for surgically treating contralateral FNSF are unclear.
IV.
Novel internalin P homologs in Listeria Conner, Kayla N.; Burke, Joseph T.; Ravi, Janani ...
Microbial genomics,
07/2022, Letnik:
8, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Listeria monocytogenes
(
Lm
) is a bacterial pathogen that causes listeriosis in immunocompromised individuals, particularly pregnant women. Several virulence factors support the intracellular ...lifecycle of
Lm
and facilitate cell-to-cell spread, allowing it to occupy multiple niches within the host and cross-protective barriers, including the placenta. One family of virulence factors, internalins, contributes to
Lm
pathogenicity by inducing specific uptake and conferring tissue tropism. Over 25 internalins have been identified thus far, but only a few have been extensively studied. Internalins contain leucine-rich repeat (LRR) domains that enable protein-protein interactions, allowing
Lm
to bind host proteins. Notably, other
Listeria
species express internalins but cannot colonize human hosts, prompting questions regarding the evolution of internalins within the genus
Listeria
. Internalin P (InlP) promotes placental colonization through interaction with the host protein afadin. Although prior studies of InlP have begun to elucidate its role in
Lm
pathogenesis, there remains a lack of information regarding homologs in other
Listeria
species. Here, we have used a computational evolutionary approach to identify InlP homologs in additional
Listeria
species. We found that
Listeria ivanovii londoniensis
(
Liv
) and
Listeria seeligeri
(
Ls
) encode InlP homologs. We also found InlP-like homologs in
Listeria innocua
and the recently identified species
Listeria costaricensis
. All newly identified homologs lack the full-length LRR6 and LRR7 domains found in
Lm
’s InlP. These findings are informative regarding the evolution of one key
Lm
virulence factor, InlP, and serve as a springboard for future evolutionary studies of
Lm
pathogenesis as well as mechanistic studies of
Listeria
internalins.
Sustainable crop production requires nutrient inputs to replace what was removed or lost. Replenishing nutrients using fertilizers and animal wastes is one of the most common input practices. While ...there is considerable research evaluating the efficacy of fertilizer and manure-based inputs for crop performance, nutrient use efficiency, and the subsequent impact to the environment, the influence of these inputs on soil health properties is less understood. The goals of this review are to summarize the state of literature on the influence of chemical fertilizer and manure-based inputs on soil health and to identify research gaps to refine efforts toward improved soil health, sustainability, and soil carbon storage. Conclusions suggest that chemical fertilizer inputs can increase soil organic matter and soil health provided that additions are not beyond what a plant can utilize. Manure-based inputs contribute to soil organic carbon and associated metrics; however, direct comparison of products is difficult as they are generally applied on a nutrient basis rather than carbon basis, which differentially affects their influence on soil health. Overall, nutrient-containing inputs show beneficial influences on soil health metrics; however, more focused research into their influence on soil health is needed.
Background
The effects of edge‐to‐edge percutaneous mitral valve repair on the shape and size of the mitral annulus and its relation to mitral regurgitation (MR) have not been well characterized. We ...evaluated acute changes in mitral annular shape and dimensions, and their effect on MR severity, in patients with functional and degenerative MR following MitraClip®.
Methods
Patients that underwent MitraClip® between January 2013 and May 2016 at our institution were retrospectively reviewed. Exclusions: inadequate images, prior mitral valve repair, and rapid atrial fibrillation. Intra‐procedure TEE 3D images acquired prior to and after implantation of MitraClip® were analyzed using software to model the mitral valve apparatus.
Results
Of seventy‐eight patients that underwent MitraClip® procedure, 60 were eligible. Mean age was 78.3 ± 11 years. Severe MR (4+) was present in 37 patients, moderately/severe MR (3+) in 23. All patients achieved MR reduction to ≤2. 3D annular circumference, bicommissural diameter, and anteroposterior diameter had a significant size reduction after MitraClip®. None of the mitral annular measures had significantly different mean change between the large and small MR change groups at the 0.05 significance level.
Conclusions
In patients with functional or degenerative MR, the MitraClip® significantly affect mitral annular dimensions; however, these changes do not correlate with the immediate MR reduction.
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