bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying unique exposure-specific transgenerational differentially DNA methylated region epimutations in the genome using hybrid deep learning prediction models
Authors: Mavaie Pegah , Holder Lawrence , Skinner Michael
Published: December 2023

Exposure to environmental toxicants can lead to epimutations in the genome and an increase in differential DNA methylated regions (DMRs) that have been linked to increased susceptibility to various diseases. However, the unique effect of particular toxicants on the genome in terms of leading to unique DMRs for the toxicants has been less studied. One hurdle to such studies is the low number of observed DMRs per toxicants. To address this hurdle, a previously validated hybrid deep-learning cross-exposure prediction model is trained per exposure and used to predict exposure-specific DMRs in the genome. Given these predicted exposure-specific DMRs, a set of unique DMRs per exposure can be identified. Analysis of these unique DMRs through visualization, DNA sequence motif matching, and gene association reveals known and unknown links between individual exposures and their unique effects on the genome. The results indicate the potential ability to define exposure-specific epigenetic markers in the genome and the potential relative impact of different exposures. Therefore, a computational approach to predict exposure-specific transgenerational epimutations was developed, which supported the exposure specificity of ancestral toxicant actions and provided epigenome information on the DMR sites predicted.
Transcatheter edge-to-edge repair for tricuspid valve regurgitation in apolipoprotein A-I–associated cardiac amyloidosis: case report
Authors: Alomari Mohammad , Reddy Prajwal , El Sabbagh Abdallah , Pollak Peter , Lyle Melissa
Published: December 2023

Background

Amyloidosis is defined by abnormal protein folding and subsequent deposition in tissues. Cardiac involvement is usually related to misfolded monoclonal immunoglobulin light chains or misfolded transthyretin; however, apolipoprotein A-1–associated amyloidosis is a hereditary form of amyloidosis resulting from mutations in the AAPOA1 gene that can also result in cardiac amyloidosis. Although there have been advancements in noninvasive algorithms for the diagnosis of cardiac amyloidosis, endomyocardial biopsy (EMB) may still be warranted. All individuals undergoing EMB are susceptible to complications, including tricuspid valve injury resulting in severe tricuspid valve regurgitation.

Case summary

Our patient is a 70-year-old white man presented with symptoms of dyspnoea on exertion and decreased functional capacity, diagnosed previously with apolipoprotein A-I cardiac amyloidosis, confirmed by EMB. He developed progressive right-sided heart failure secondary to iatrogenic flail tricuspid leaflet related to the diagnostic EMB. He underwent a successful transcatheter tricuspid valve edge-to-edge repair with 4D intracardiac echocardiographic guidance. At the recent follow-up, the patient showed improved symptoms, with increased stamina, and transoesophageal echocardiography revealed a 65% ejection fraction and mild tricuspid regurgitation (TR).

Discussion

Tricuspid valve injury is one of the complications associated with EMB, which can result in severe TR. Transcatheter tricuspid valve edge-to-edge repair can be a useful option for patients considered too high risk for surgical intervention, such as those with advanced cardiac amyloidosis.
WATCHMEN: a case report highlighting the closure of a bilobed left atrial appendage using two WATCHMAN-FLX devices
Authors: Sood Abhinav , Kalavakunta Jagadeesh K , Gourineni Venu , Gupta Vishal
Published: December 2023

Background

Left atrial appendage occlusion (LAAO) performed percutaneously has emerged as a widely accepted method for stroke prevention, offering a viable alternative to anticoagulation. Numerous studies have demonstrated the effectiveness and safety of this procedure. However, in certain cases, the use of a single LAAO device may not adequately achieve optimal closure due to variations in the anatomy of the left atrial appendage (LAA).

Case summary

In this manuscript, we highlight the successful closure of a bilobed LAA with a large ostium utilizing two WATCHMAN™ FLX devices and using the double sheath technique. The aim was to achieve optimal closure and address the unique anatomical characteristics of the patient’s LAA.

Discussion

The utilization of two LAAO devices in bilobed appendage anatomy, where a single device may not be sufficient, is possible, although it poses a challenge because of the lack of technical expertise and limited published evidence. Transoesophageal imaging can serve as a valuable tool for assessing the precise anatomy of the LAA and guide the selection and placement of the occlusion devices.
Altered Bile Acid and Pouch Microbiota Composition in Patients With Chronic Pouchitis
Authors: Santiago Priscila , Quinn Kevin P , Chen Jun , Friton Jessica J , Rypstra Chad R , Kashyap Purna C , Raffals Laura E
Published: December 2023

Background

Patients with ulcerative colitis and total abdominal proctocolectomy with ileal pouch-anal anastomosis have a 50% risk of pouchitis and a 5% to 10% risk of chronic pouchitis.

Aims

The goal of the study was to compare pouch microbiota and stool bile acid composition in patients with chronic pouchitis, chronic pouchitis and primary sclerosing cholangitis, and normal pouch.

Methods

Patients with ulcerative colitis and ileal pouch-anal anastomosis were recruited from March 20, 2014, to August 6, 2019, and categorized into normal pouch, chronic pouchitis, and chronic pouchitis/primary sclerosing cholangitis groups. Stool samples were subjected to bile acid quantification and 16S rRNA gene sequencing. Statistical comparisons of absolute bile acid abundance and pouch microbiota α-diversity, β-diversity, and taxa abundance were performed among the patient groups.

Results

A total of 51 samples were analyzed. Both α-diversity (P = .01, species richness) and β-diversity (P = .001) significantly differed among groups. Lithocholic acid was significantly lower in patients with chronic pouchitis/primary sclerosing cholangitis than in those with chronic pouchitis (P = .01) or normal pouch (P = .03). Decreased α-diversity was associated with an increased primary to secondary bile acid ratio (P = .002), which was also associated with changes in β-diversity (P = .006).

Conclusions

Pouch microbiota α- and β-diversity differed among patients with normal pouch, chronic pouchitis, and chronic pouchitis/primary sclerosing cholangitis. Lithocholic acid level and primary to secondary bile acid ratio were highly associated with pouch microbiota richness, structure, and composition. These findings emphasize the associations between pouch microbiota and bile acid composition in dysbiosis and altered metabolism, suggesting that secondary bile acids are decreased in chronic pouchitis.
Analyzing inexact hypergradients for bilevel learning
Authors: Ehrhardt Matthias J , Roberts Lindon
Published: December 2023

Estimating hyperparameters has been a long-standing problem in machine learning. We consider the case where the task at hand is modeled as the solution to an optimization problem. Here the exact gradient with respect to the hyperparameters cannot be feasibly computed and approximate strategies are required. We introduce a unified framework for computing hypergradients that generalizes existing methods based on the implicit function theorem and automatic differentiation/backpropagation, showing that these two seemingly disparate approaches are actually tightly connected. Our framework is extremely flexible, allowing its subproblems to be solved with any suitable method, to any degree of accuracy. We derive a priori and computable a posteriori error bounds for all our methods and numerically show that our a posteriori bounds are usually more accurate. Our numerical results also show that, surprisingly, for efficient bilevel optimization, the choice of hypergradient algorithm is at least as important as the choice of lower-level solver.
Chloroplast Genome Sequences and Phylogenetic Analysis of Eight Newly Sequenced Caryophyllaceae Species
Authors: Liu Rongpeng , Mu Zejing , Du Xiaolang , Zhong Guoyue , Wang Xiaoyun
Published: December 2023

Background

Caryophyllaceae is a big family composed of many economic and medicinal species. However, the phylogeny of the family is insufficient and genome data are lacking for many species.

Objective

Using next-generation sequencing (NGS) to acquire the chloroplast (cp) genomes of Eremogone acicularis (F.N.Williams) Ikonn., E. brevipetala (Tsui & L.H.Zhou) Sadeghian & Zarre, E. bryophylla (Fernald) Pusalkar & D.K.Singh, E. kansuensis (Maxim.) Dillenb. & Kadereit, Shivparvatia glanduligera (Edgew.) Pusalkar & D.K.Singh, Silene atsaensis (Marq.) Bocquet, S. caespitella Williams, and S. lhassana (Williams) Majumdar.

Methods

Bioinformatic software was used to conduct the comparative genome and phylogeny analysis of these cp genomes.

Results

The eight cp genomes were 132 188–151 919 bp in length, containing 130–132 genes. A/T was dominant in simple sequence repeats (SSRs). Forward repeats and palindromic repeats were the most frequent in long terminal repeats (LTRs). Compared with the four species of Eremogone Fenzl, the inverted repeat (IR) boundaries of S. caespitella, S. atsaensis, S. lhassana, and Sh. glanduligera were significantly expanded. Four and one mutational hotspots were identified in the large single copy (LSC) region and small single copy (SSC) region, respectively. The ratio of nonsynonymous substitution to synonymous substitution (Ka/Ks ratio) showed these cp genomes may have undergone strong purifying selection. In the phylogenetic trees, both Silene L. and Eremogone were monophyletic groups. However, Sh. glanduligera was closely related to Amaranthus hypochondriacus.

Conclusion

These results have provided new evidence and useful information for species identification, evolution, and genetic research on the Caryophyllaceae.

Highlights

In this study, eight newly sequenced cp genomes of Caryophyllaceae species were reported for the first time.
Accuracy of enteric methane emission models for cattle in sub-Saharan Africa: status quo and the way forward
Authors: Bateki Christian A , Wilkes Andreas , Schlecht Eva
Published: December 2023

Cattle emit over 65% of enteric methane (CH4) in sub-Saharan Africa (SSA), making them the focus of many mitigation strategies targeting livestock emissions. Since measured feed intake data are sparse, emission factors for enteric CH4 (EFCH4) are mainly estimated indirectly from gross energy intake (GEI) using the net energy (NE) requirements for different metabolic processes in cattle. However, all NE requirement systems commonly used for cattle in SSA were developed for cattle in temperate regions. Therefore, we assessed the suitability of different enteric CH4 models for estimating the GEI of cattle in SSA. The Intergovernmental Panel on Climate Change (IPCC) and South African models were identified as the main tier 2-based methods used to estimate enteric CH4 emissions from cattle in SSA. In the IPCC model, EFCH4 was estimated as (GEI * [Ym/100])/55.65, where Ym is the conversion factor (%) of gross energy in feed to CH4 and 55.65 the energy content of CH4 (MJ/kg). The GEI was estimated based on NE requirements for different metabolic processes in cattle as per the American National Research Council. In the South African model, EFCH4 was estimated as (Y/100 * GEI/55.22), where Y is the CH4 yield and 55.22 is the energy content of CH4; Y was calculated from the dry matter (DM) digestibility while GEI was calculated by predicting DM intake and multiplying it by 18.4 MJ (gross energy per kilogram DM). Also, the suitability of the British and German NE requirement systems was assessed as alternatives used for cattle nutrition in SSA. These NE systems were implemented in the IPCC model to yield the “AFRC” and “GfE” models, respectively. The four models were then evaluated using an evaluation dataset summarizing feed quality and DM intake results from 21 studies conducted in SSA, with 125 dietary treatments, and 822 cattle observations. The relative prediction error (RPE) and concordance correlation coefficient (CCC) were used to evaluate the models’ accuracy. Only the South African model estimated the GEI in dairy cattle with an acceptable RPE (18.9%) and highest CCC (0.87), while the other three models yielded estimates with RPE > 20%. None of the four models we assessed estimated GEI for other cattle (i.e., nondairy) with an RPE < 20% or CCC > 0.30. The inaccuracy in GEI estimates suggests an error of the same magnitude in EFCH4 estimates. Therefore, a concerted effort is needed to improve the accuracy of enteric CH4 estimation models for cattle in SSA.
Inpatient Screening, Brief Intervention, and Referral to Treatment for Alcohol Use Disorder in Patients Admitted with Alcohol-associated Liver Disease Is Not Universally Implemented in Practice, But Can Reduce Readmissions for Alcohol-associated Hepatitis
Authors: Wang Dennis , Puglia Marco
Published: December 2023

Introduction

The management of alcohol-related liver disease requires a multidisciplinary approach to treat alcohol use disorder. We aimed to determine the proportion of actively drinking patients admitted for alcohol-associated hepatitis (AAH) or decompensated alcohol-related cirrhosis (DARLC) who were offered or underwent screening, brief intervention, and referral to treatment (SBIRT) for alcohol use disorder during admission and if inpatient SBIRT is associated with reduced readmissions for alcohol-related liver disease.

Methods

We conducted a retrospective cohort study of actively drinking patients admitted to our institution from January 2017 to December 2021 with AAH or DARLC. Logistic regression was used to identify factors, such as conducting SBIRT, that were associated with 30-day and 90-day readmissions for recurrent AAH or DARLC.

Results

There were 120 AAH admissions (mean age 47.7 ± 13.6 years), and 177 DARLC admissions (mean age 58.2 ± 9.5 years). SBIRT was conducted in only 51.7% of AAH admissions, and 23.7% of DARLC admissions. For AAH, conducting SBIRT was associated with significantly reduced 30-day (OR 0.098, P = 0.001, 95% CI 0.024–0.408) and 90-day (OR 0.166, P = 0.003, 95% CI 0.052–0.534) readmissions. For DARLC, there was no association between conducting SBIRT and 30-day or 90-day readmissions.

Conclusion

SBIRT was conducted with actively drinking patients in only 51.7% of AAH admissions and 23.7% of DARLC admissions. Patients admitted for AAH who received inpatient SBIRT had decreased 30-day and 90-day readmission rates for AAH or DARLC.
Exploring the cross-cancer effect of circulating proteins and discovering potential intervention targets for 13 site-specific cancers
Authors: Sun Jing , Luo Jia , Jiang Fangyuan , Zhao Jianhui , Zhou Siyun , Wang Lijuan , Zhang Dongfeng , Ding Yuan , Li Xue
Published: December 2023

Background

The proteome is an important reservoir of potential therapeutic targets for cancer. This study aimed to examine the causal associations between plasma proteins and cancer risk and to identify proteins with cross-cancer effects.

Methods

Genetic instruments for 3991 plasma proteins were extracted from a large-scale proteomic study. Summary-level data of 13 site-specific cancers were derived from publicly available datasets. Proteome-wide Mendelian randomization and colocalization analyses were used to investigate the causal effect of circulating proteins on cancers. Protein-protein interactions and druggability assessment were conducted to prioritize potential therapeutic targets. Finally, systematical Mendelian randomization analysis between healthy lifestyle factors and cancer-related proteins was conducted to identify which proteins could act as interventional targets by lifestyle changes.

Results

Genetically determined circulating levels of 58 proteins were statistically significantly associated with 7 site-specific cancers. A total of 39 proteins were prioritized by colocalization, of them, 11 proteins (ADPGK, CD86, CLSTN3, CSF2RA, CXCL10, GZMM, IL6R, NCR3, SIGLEC5, SIGLEC14, and TAPBP) were observed to have cross-cancer effects. Notably, 5 of these identified proteins (CD86, CSF2RA, CXCL10, IL6R, and TAPBP) have been targeted for drug development in cancer therapy; 8 proteins (ADPGK, CD86, CXCL10, GZMM, IL6R, SIGLEC5, SIGLEC14, TAPBP) could be modulated by healthy lifestyles.

Conclusion

Our study identified 39 circulating protein biomarkers with convincing causal evidence for 7 site-specific cancers, with 11 proteins demonstrating cross-cancer effects, and prioritized the proteins as potential intervention targets by either drugs or lifestyle changes, which provided new insights into the etiology, prevention, and treatment of cancers.
Development of local-power-free, remote α-particle detection using optical fibers
Authors: Pfeifer Kent B , Weber Thomas M , Martin James E
Published: December 2023

We demonstrate the application of fluorescence optical fiber coupled to a telecom grade fiber as a sensor for alpha particles using alpha-specific ZnS(Ag) scintillation materials whose wavelength is down-shifted into a low-loss region of the telecom grade fiber transmission band. Telecom-grade fiber optics offer a solution for sensing alpha radiation in deep repositories and cask storage for radioactive materials due to the stability of SiO2 under normal environmental conditions and its relative radiation hardness at low radiation doses. Long-term nuclear waste storage facilities require sensors for the detection of leakage of radioactive materials that are maintenance-free, do not require power and can survive with no ‘wear out’ mechanisms for decades. By accomplishing the wavelength transformation, we maximize efficiencies in the detection of α-particles and signal transport and can detect alpha scintillation at distances on the order of >1 km with a sensor that is ~3% efficient and can be easily scaled as a sensor array. This paper describes the construction and testing of the sensor including manufacture of the controlled thickness films, verification of the wavelength shift from 450 to 620 nm and optimization of the sensitivity as a function of thickness. We also model the relative sensitivity of the film as a function of film thickness, and we demonstrate a signal-to-noise ratio of 10 at a range of greater than 1 km.
Barely a passing resemblance: Why women's football stands out from the crowd
Authors: Marks Joanna , Penn Matthew J
Published: December 2023

Many of us find women's football more exciting to watch than the men's game. But why? A statistical analysis by Matthew J. Penn and Joanna Marks provides some answers
Unique cases of large and small bowel obstruction in intraperitoneal renal transplantations: a case series and review of literature
Authors: Yu Zirong , Ong Ferdinand , Kanagarajah Vijay
Published: December 2023

Bowel obstruction is a common cause for the acute abdomen with different aetiologies that shapes subsequent management plans. Small bowel obstruction often develop due to intra-abdominal adhesions in patients with prior abdominal surgery and for large bowel obstructions, more commonly due to tumours and lesions. Disruptions to normal intra-abdominal anatomy as seen in pancreatic–kidney transplantation or kidney transplant alone can result in increased risk of bowel obstruction—especially if the donor graft is implanted within the intraperitoneal plane. We present two patients from separate institutions with history of simultaneous pancreas–kidney (SPK) transplantation (Patient 1) and intraperitoneal renal (Patient 2) transplant whom both presented with bowel obstruction requiring surgical intervention. Given the specificity and operative intricacies of our cases, we aim to present our findings and surgical management of these rare presentations in hopes of increasing awareness to this uncommon but significant cause of bowel obstruction in a transplant patient.
Involvement of brassinosteroids and abscisic acid in spikelet degeneration in rice under soil drying during meiosis
Authors: Zhang Weiyang , Wu Mengyin , Zhong Xiaohan , Liu Ying , Yang Xinxin , Cai Wei , Zhu Kuanyu , Zhang Hao , Gu Junfei , Wang Zhiqin , Liu Lijun , Zhang Jianhua , Yang Jianchang
Published: December 2023

Spikelet degeneration in rice (Oryza sativa L.) is a serious physiological defect, and can be regulated by soil moisture status and phytohormones. This study investigated the possibility that brassinosteroids (BRs) in collaboration with abscisic acid (ABA) are involved in mediating the effect of soil drying during meiosis on spikelet degeneration in rice. Three rice cultivars were field grown and three irrigation regimes including well watered (WW), moderate soil drying (MD), and severe soil drying (SD) were imposed during meiosis. MD significantly decreased spikelet degeneration in comparison with WW, due mainly to the alleviation in oxidative damage via enhancing ascorbate–glutathione (AsA–GSH) cycle activity in young panicles, and SD exhibited the opposite effects. Enhanced AsA–GSH cycle strength, decreased oxidative stress, and spikelet degeneration rate were closely associated with the synergistically elevated BR and ABA levels in young panicles in MD. In contrast, low BR and excessive ABA levels led to an increase in spikelet degeneration in SD. The three cultivars exhibited the same tendencies. The intrinsic link among AsA-GSH cycle, oxidative stress, spikelet degeneration rate, and BR and ABA levels was further verified by using transgenic rice lines and chemical regulators. BRs or ABA play a unique role in regulating spikelet degeneration. Synergistically increased BR and ABA levels in MD could work together to strengthen AsA–GSH cycle activity, leading to a reduction in oxidative damage and spikelet degeneration. On the other hand, a severe imbalance between low BR and excessive ABA levels may have contributed to the opposite effects in SD.
A case of cryopyrin-associated periodic syndrome due to somatic mosaic mutation complicated with recurrent circinate erythematous psoriasis
Authors: Ando Taiki , Abe Yoshiyuki , Yamaji Ken , Nishikomori Ryuta , Tamura Naoto
Published: December 2023

Cryopyrin-associated periotic syndrome (CAPS) is a rare autoinflammatory disease caused by genetic variants in innate immunity genes. Autoinflammatory diseases, including CAPS, mediate proinflammatory cytokines such as interleukin (IL)-1 and IL-18 and result in severe systemic inflammation. A gain-of-function mutation in the NLR family pyrin domain-containing 3 (NLRP3) gene, which encodes the protein cryopyrin, was identified to be responsible for CAPS in 2001, and since then several additional pathogenic mutations have been found. Moreover, other phenotypes have been identified based on severity and symptomatology, including familial cold autoinflammatory syndrome, Muckle–Wells syndrome, and neonatal-onset multisystem inflammatory disease/chronic neurologic cutaneous articular syndrome. Prompt diagnosis of CAPS remains challenging, however, due to unspecific, extensive clinical signs, and delayed diagnosis and treatment targeting IL-1 lead to multiorgan damage. Another factor complicating diagnosis is the existence of somatic mosaic mutations in the NLRP3 gene in some cases, resulting in symptoms and clinical courses that are atypical. The frequency of somatic mosaic mutations in CAPS was estimated to be 19% in a systematic review. Psoriasis is a chronic inflammatory skin disease that affects ∼3% of the global population. Although no reports have shown complication between CAPS and psoriasis, these diseases have several similarities and potential relationships, for instance activation of T helper 17 cells in the dermis and increased NLRP3 gene expression in psoriatic skin compared with normal skin. Here, we report a case of CAPS due to a somatic mosaic mutation with recurrent circinate erythematous psoriasis.
MAE-seq refines regulatory elements across the genome
Authors: Zhu Xiusheng , Huang Qitong , Huang Lei , Luo Jing , Li Qing , Kong Dashuai , Deng Biao , Gu Yi , Wang Xueyan , Li Chenying , Kong Siyuan , Zhang Yubo
Published: December 2023

Proper cell fate determination relies on precise spatial and temporal genome-wide cooperation between regulatory elements (REs) and their targeted genes. However, the lengths of REs defined using different methods vary, which indicates that there is sequence redundancy and that the context of the genome may be unintelligible. We developed a method called MAE-seq (Massive Active Enhancers by Sequencing) to experimentally identify functional REs at a 25-bp scale. In this study, MAE-seq was used to identify 626879, 541617 and 554826 25-bp enhancers in mouse embryonic stem cells (mESCs), C2C12 and HEK 293T, respectively. Using ∼1.6 trillion 25 bp DNA fragments and screening 12 billion cells, we identified 626879 as active enhancers in mESCs as an example. Comparative analysis revealed that most of the histone modification datasets were annotated by MAE-Seq loci. Furthermore, 33.85% (212195) of the identified enhancers were identified as de novo ones with no epigenetic modification. Intriguingly, distinct chromatin states dictate the requirement for dissimilar cofactors in governing novel and known enhancers. Validation results show that these 25-bp sequences could act as a functional unit, which shows identical or similar expression patterns as the previously defined larger elements, Enhanced resolution facilitated the identification of numerous cell-specific enhancers and their accurate annotation as super enhancers. Moreover, we characterized novel elements capable of augmenting gene activity. By integrating with high-resolution Hi-C data, over 55.64% of novel elements may have a distal association with different targeted genes. For example, we found that the Cdh1 gene interacts with one novel and two known REs in mESCs. The biological effects of these interactions were investigated using CRISPR-Cas9, revealing their role in coordinating Cdh1 gene expression and mESC proliferation. Our study presents an experimental approach to refine the REs at 25-bp resolution, advancing the precision of genome annotation and unveiling the underlying genome context. This novel approach not only advances our understanding of gene regulation but also opens avenues for comprehensive exploration of the genomic landscape.
TaCRTISO dosage modulates plant height and spike number per plant in wheat
Authors: Yan Qiang , Lu Yue , Pang Yunlong , Zhao Hailiang , Liu Jingxian , Liu Mingyu , Zhu Huaqiang , Zhang Ziliang , Li Genying , Wu Yuye , Liu Shubing
Published: December 2023

An allelic variation of TaCRTISO is valuable in adjusting spike number per plant and plant height in wheat breeding.
R-SNARE protein YKT61 mediates root apical meristem cell division via BRASSINOSTEROID-INSENSITIVE1 recycling
Authors: Ma Ting , Tan Jun-Ru , Zhang Yan , Li Sha
Published: December 2023

Root growth is sustained by cell division and differentiation of the root apical meristem (RAM), in which brassinosteroid (BR) signaling mediated via the dynamic targeting of BRASSINOSTEROID-INSENSITIVE1 (BRI1) plays complex roles. BRI1 is constitutively secreted to the plasma membrane (PM), internalized, and recycled or delivered into vacuoles, whose PM abundance is critical for BR signaling. Vesicle–target membrane fusion is regulated by heterotetrameric SNARE complexes. SNARE proteins have been implicated in BRI1 targeting, but how SNAREs affect RAM development is unclear. We report that Arabidopsis (Arabidopsis thaliana) YKT61, an atypical R-SNARE protein, is critical for BR-controlled RAM development through the dynamic targeting of BRI1. Functional loss of YKT61 is lethal for both male and female gametophytes. By using weak mutant alleles of YKT61, ykt61-partially complemented (ykt61-pc), we show that YKT61 knockdown results in a reduction of RAM length due to reduced cell division, similar to that in bri1-116. YKT61 physically interacts with BRI1 and is critical for the dynamic recycling of BRI1 to the PM. We further determine that YKT61 is critical for the dynamic biogenesis of vacuoles, for the maintenance of Golgi morphology, and for endocytosis, which may have a broad effect on development. Endomembrane compartments connected via vesicular machinery, such as SNAREs, influence nuclear-controlled cellular activities such as division and differentiation by affecting the dynamic targeting of membrane proteins, supporting a retro-signaling pathway from the endomembrane system to the nucleus.
Oomycete pathogen pectin acetylesterase targets host lipid transfer protein to reduce salicylic acid signaling
Authors: Situ Junjian , Song Yu , Feng Dinan , Wan Lang , Li Wen , Ning Yue , Huang Weixiong , Li Minhui , Xi Pinggen , Deng Yizhen , Jiang Zide , Kong Guanghui
Published: December 2023

During initial stages of microbial invasion, the extracellular space (apoplast) of plant cells is a vital battleground between plants and pathogens. The oomycete plant pathogens secrete an array of apoplastic carbohydrate active enzymes, which are central molecules for understanding the complex plant–oomycete interactions. Among them, pectin acetylesterase (PAE) plays a critical role in the pathogenesis of plant pathogens including bacteria, fungi, and oomycetes. Here, we demonstrated that Peronophythora litchii (syn. Phytophthora litchii) PlPAE5 suppresses litchi (Litchi chinensis) plant immunity by interacting with litchi lipid transfer protein 1 (LcLTP1). The LcLTP1-binding activity and virulence function of PlPAE5 depend on its PAE domain but not on its PAE activity. The high expression of LcLTP1 enhances plant resistance to oomycete and fungal pathogens, and this disease resistance depends on BRASSINOSTEROID INSENSITIVE 1–associated receptor kinase 1 (BAK1) and Suppressor of BIR1 (SOBIR1) in Nicotiana benthamiana. LcLTP1 activates the plant salicylic acid (SA) signaling pathway, while PlPAE5 subverts the LcLTP1-mediated SA signaling pathway by destabilizing LcLTP1. Conclusively, this study reports a virulence mechanism of oomycete PAE suppressing plant LTP-mediated SA immune signaling and will be instrumental for boosting plant resistance breeding.
Integrative multiomics profiling of passion fruit reveals the genetic basis for fruit color and aroma
Authors: Zheng Yu-Yu , Chen Lin-Hua , Fan Bing-Liang , Xu Zhenni , Wang Qiuxia , Zhao Bo-Yuan , Gao Min , Yuan Min-Hui , Tahir ul Qamar Muhammad , Jiang Yuanyuan , Yang Liu , Wang Lingqiang , Li Weihui , Cai Wenguo , Ma Chongjian , Lu Li , Song Jia-Ming , Chen Ling-Ling
Published: December 2023

Passion fruit (Passiflora edulis) possesses a complex aroma and is widely grown in tropical and subtropical areas. Here, we conducted the de novo assembly, annotation, and comparison of PPF (P. edulis Sims) and YPF (P. edulis f. flavicarpa) reference genomes using PacBio, Illumina, and Hi-C technologies. Notably, we discovered evidence of recent whole-genome duplication events in P. edulis genomes. Comparative analysis revealed 7.6∼8.1 million single nucleotide polymorphisms, 1 million insertions/deletions, and over 142 Mb presence/absence variations among different P. edulis genomes. During the ripening of yellow passion fruit, metabolites related to flavor, aroma, and color were substantially accumulated or changed. Through joint analysis of genomic variations, differentially expressed genes, and accumulated metabolites, we explored candidate genes associated with flavor, aroma, and color distinctions. Flavonoid biosynthesis pathways, anthocyanin biosynthesis pathways, and related metabolites are pivotal factors affecting the coloration of passion fruit, and terpenoid metabolites accumulated more in PPF. Finally, by heterologous expression in yeast (Saccharomyces cerevisiae), we functionally characterized 12 terpene synthases. Our findings revealed that certain TPS homologs in both YPF and PPF varieties produce identical terpene products, while others yield distinct compounds or even lose their functionality. These discoveries revealed the genetic and metabolic basis of unique characteristics in aroma and flavor between the 2 passion fruit varieties. This study provides resources for better understanding the genome architecture and accelerating genetic improvement of passion fruits.
OROSOMUCOID PROTEIN 1 regulation of sphingolipid synthesis is required for nodulation in Aeschynomene evenia
Authors: Nouwen Nico , Pervent Marjorie , El M’Chirgui Franck , Tellier Frédérique , Rios Maëlle , Horta Araújo Natasha , Klopp Christophe , Gressent Frédéric , Arrighi Jean-François
Published: December 2023

Legumes establish symbiotic interactions with nitrogen-fixing rhizobia that are accommodated in root-derived organs known as nodules. Rhizobial recognition triggers a plant symbiotic signaling pathway that activates 2 coordinated processes: infection and nodule organogenesis. How these processes are orchestrated in legume species utilizing intercellular infection and lateral root base nodulation remains elusive. Here, we show that Aeschynomene evenia OROSOMUCOID PROTEIN 1 (AeORM1), a key regulator of sphingolipid biosynthesis, is required for nodule formation. Using A. evenia orm1 mutants, we demonstrate that alterations in AeORM1 function trigger numerous early aborted nodules, defense-like reactions, and shorter lateral roots. Accordingly, AeORM1 is expressed during lateral root initiation and elongation, including at lateral root bases where nodule primordium form in the presence of symbiotic bradyrhizobia. Sphingolipidomics revealed that mutations in AeORM1 lead to sphingolipid overaccumulation in roots relative to the wild type, particularly for very long-chain fatty acid-containing ceramides. Taken together, our findings reveal that AeORM1-regulated sphingolipid homeostasis is essential for rhizobial infection and nodule organogenesis, as well as for lateral root development in A. evenia.
Decellularized extracellular matrix-based composite scaffolds for tissue engineering and regenerative medicine
Authors: Xu Peiyao , Kankala Ranjith Kumar , Wang Shibin , Chen Aizheng
Published: December 2023

Despite the considerable advancements in fabricating polymeric-based scaffolds for tissue engineering, the clinical transformation of these scaffolds remained a big challenge because of the difficulty of simulating native organs/tissues’ microenvironment. As a kind of natural tissue-derived biomaterials, decellularized extracellular matrix (dECM)-based scaffolds have gained attention due to their unique biomimetic properties, providing a specific microenvironment suitable for promoting cell proliferation, migration, attachment and regulating differentiation. The medical applications of dECM-based scaffolds have addressed critical challenges, including poor mechanical strength and insufficient stability. For promoting the reconstruction of damaged tissues or organs, different types of dECM-based composite platforms have been designed to mimic tissue microenvironment, including by integrating with natural polymer or/and syntenic polymer or adding bioactive factors. In this review, we summarized the research progress of dECM-based composite scaffolds in regenerative medicine, highlighting the critical challenges and future perspectives related to the medical application of these composite materials.
Turmeric (Curcuma longa): an alternative to antibiotics in poultry nutrition
Authors: Aderemi Foluke Abimbola , Alabi Olufemi Mobolaji
Published: December 2023

Turmeric, a common spice in many countries has been used for centuries in traditional medicine for its antimicrobial properties. Recent research has shown that turmeric can be a viable alternative to antibiotics in poultry production. Antibiotic overuse in poultry has led to the development of antibiotic-resistant bacteria, which poses a threat to both animal and human health. Turmeric contains curcumin, a compound that has been shown to have antimicrobial activity against a wide range of bacteria, including those resistant to antibiotics. In addition, turmeric has anti-inflammatory and immunomodulatory properties, which can help boost the immune system of poultry and reduce the need for antibiotics. Studies have shown that turmeric can improve growth performance, and gut health, and reduce the incidence of disease in poultry. Therefore, the use of turmeric as an alternative to antibiotics in poultry production has the potential to not only improve animal health and welfare but also contribute to the fight against antibiotic resistance. This review aims to provide an overview of the recent knowledge on the use of these plant extracts in poultry feeds as feed additives and their effects on poultry performance.
Safety of dietary nitrate supplementation by calcium nitrate for finishing pigs as measured by methemoglobin and serum and tissue nitrate levels
Authors: Sheppard Amy M , van de Ligt Jennifer L G , Pillai Padmakumar , Crincoli Christine M , Faris Richard J , McGhee Molly L , Frederick Brent R
Published: December 2023

Nitrate supplementation has been studied as a beneficial constituent of the human diet, particularly for its effects on vascular health through vasodilation. Recent studies have focused on the benefits of nitrate supplementation in animals, especially in swine. Up to 1,200 mg/kg dietary nitrate supplementation from Ca nitrate was beneficial in farrowing and lactating sows and their offspring, and up to 6,000 mg/kg supplemental nitrate showed no adverse health effects in sows or piglets. Controlled study data evaluating the safety of nitrate supplementation to growing swine of any weight class is scant. Therefore, an experiment was conducted to test the hypothesis that increased inclusion rates of dietary nitrate through the addition of Ca nitrate in diets would not influence concentrations of nitrate or nitrite in serum and tissue, nor blood hemoglobin and methemoglobin. Forty-eight individually housed pigs (initial weight 119.1 ± 5.3 kg) were randomly allotted to four dietary treatments containing 0, 500, 1,000, or 2,000 mg/kg dietary nitrate and fed experimental diets for 28 d. Growth performance was not influenced (P > 0.10) by dietary treatment. The most sensitive safety endpoint, methemoglobin, did not change (P > 0.10) with dietary nitrate exposure up to 2,000 mg/kg. Serum and tissue nitrate and nitrite levels, myoglobin, and hemoglobin were not adversely affected (P > 0.10). Total myoglobin in the loin linearly increased (P < 0.05) with greater dietary nitrate in the diet, which is correlated with the red color of meat. This work established the safety of up to 2,000 mg/kg dietary nitrate from Ca nitrate as an ingredient in food for finishing pigs.
Jumbo quail responses to diets containing raw or heat-treated Marama bean (Tylosema esculentum) meal
Authors: Fatoki Mary F , Kiarie Elijah G , Mnisi Caven M
Published: December 2023

Growth performance, apparent retention (AR) of amino acids (AA), blood, and meat quality parameters were determined in grower Jumbo quail-fed diets containing raw or heat-treated marama bean (Tylosema esculentum) meal (MBM). The experimental diets were formulated to contain 99.98 g/kg of raw (MBMR), cooked (MBMC), autoclaved (MBMA), and toasted MBM (MBMT) in a standard grower diet (CON). A total of 306, 7-d-old Jumbo quail chicks (30.97 ± 1.79 g live weight) were placed in 35 cages (8/9 birds per cage). The five diets were allocated to the cages to give seven replicates per diet. The diets had varied responses (P < 0.05) on AR of lysine, methionine, and threonine, among others. The CON diet promoted the highest (P < 0.05) overall feed intake (FI) followed by MBMC and MBMA, and the lowest overall FI was from MBMR and MBMT. Quail-fed MBMR and MBMT diets had the least (P < 0.05) overall body weight gain and final body weights than those fed with the CON, MBMC, and MBMA diets. Moreover, quail on MBMR diet had the lowest (P < 0.05) overall gain-to-feed ratio (G:F) than those reared on the other diets, whose G:F values were statistically similar (P > 0.05). Similarly, quail on MBMR diet had the highest (P < 0.05) concentration of serum lipase and the heaviest gizzard than quail fed the other diets. However, quail-fed MBMT diet had heavier (P < 0.05) relative proventriculus weight compared to quail-fed other diets. Heavier (P < 0.05) relative spleen weights were observed for the MBMT and MBMR groups compared to the other groups. The CON diet had higher (P < 0.05) hematocrits and 1-h breast meat redness compared to the other diets. However, CON, MBMC, and MBMA diets increased (P < 0.05) 24-h breast meat redness than MBMR and MBMT diets. In conclusion, feeding diets with cooked or autoclaved marama bean meal resulted in an improvement in AA utilization, growth performance, and indices of carcass quality. However, raw and toasted marama beans had negative effects on performance parameters suggesting that optimal thermal treatment is critical for marama bean utilization.
Evaluation and Control of Fusarium acuminatum Causing Leaf Spot in Saposhnikovia divaricata in Northeast China
Authors: Jiang Yanyan , Zhang Lili , Wang Shuni , Li Yonggang , Bai Yunlong , Cao Liping
Published: December 2023

Saposhnikovia divaricata is an authentic Chinese herbal medicine in Northeast China named Guanfangfeng, which is made from very high-quality plants for sufficient efficacy. However, leaf spot causes a very large reduction in the yield and quality of S. divaricata in Shuangyashan (46.58°N, 131.28°E), Northeast China. A total of 18 isolates were isolated from the diseased leaves of S. divaricata, following Koch’s postulates, and identified as Fusarium acuminatum based on morphological, molecular biological, and phylogenetic tree analyses. To the authors’ knowledge, this is the first report of F. acuminatum causing S. divaricata leaf spot in China. F. acuminatum infected perilla and mung beans but not foxtail millet, peanuts, wheat, peas, rye, red beans, or sorghum. Susceptibility assessment of F. acuminatum to fungicides using the mycelial growth rate method showed that isolates of F. acuminatum were most sensitive to prochloraz, with effective concentration values of 0.0005413 to 0.0009523 μg/ml. In the two field experiments, the average control efficacy of prochloraz at 0.450 g/liter on S. divaricata leaf spot caused by F. acuminatum was 75.42%. Therefore, nonhost plant rotation or intercropping with suitable chemical fungicides may be used to control S. divaricata leaf spot. This study’s results provide a theoretical basis for controlling S. divaricata leaf spot and will facilitate the development of effective disease management programs.
Combined Use of Phenotype-Based and Genome-Informed Approaches Identified a Unique Fusarium oxysporum f. sp. cubense Isolate in Hawaii
Authors: Shipman Aaron , Tian Miaoying
Published: December 2023

Fusarium wilt of banana, caused by Fusarium oxysporum f. sp. cubense (Foc), is a serious disease that threatens banana production worldwide. It is a long-standing problem in Hawaii, but previously, there was little knowledge of the causal pathogen. We isolated a strain of Foc, named Foc-UH, from a field experiencing the disease epidemic in Hawaii. Infection assays of a diverse panel of 26 banana clones, including varieties used for differentiating pathogen races and fruit production, revealed that Foc-UH has a race 1 pathogenic phenotype with an intermediate race 2 virulence and revealed the differential resistance of varieties to infection. Separate phylogenetic analyses using the barcoding regions of three nuclear genes, seven complete nuclear genes, and single-nucleotide polymorphisms within conserved whole-genome protein coding sequences placed Foc-UH into recently proposed taxonomic frameworks relevant to Foc and the F. oxysporum species complex. Screening of the 99.7% complete draft genome identified five secreted in xylem ( SIX) gene homologs: SIX1d, SIX1f, SIX9a, SIX9b, and SIX13a. This profile is similar to that of several race 1 isolates except for the absence of SIX4 and SIX6. Foc-UH was morphologically dissimilar to the nearest related isolates. Altogether, this study identified a unique isolate that causes banana Fusarium wilt, which represents the first characterization of the causal pathogen in Hawaii. The findings and genomic resources generated in this study are expected to guide banana breeding and cultivar deployment in Hawaii and beyond and contribute to further understanding of the pathogenicity and evolutionary systematics of Foc.
Tristetraprolin regulates the skeletal phenotype and osteoclastogenic potential through monocytic myeloid‐derived suppressor cells
Authors: Zhang Lixia , Kwack Kyu Hwan , Thiyagarajan Ramkumar , Mullaney Kylie K. , Lamb Natalie A. , Bard Jonathan E. , Sohn Jiho , Seldeen Kenneth L. , Arao Yukitomo , Blackshear Perry J. , Abrams Scott I. , Troen Bruce R. , Kirkwood Keith L.
Published: December 2023

Tristetraprolin (TTP; also known as NUP475, GOS24, or TIS11), encoded by Zfp36, is an RNA‐binding protein that regulates target gene expression by promoting mRNA decay and preventing translation. Although previous studies have indicated that TTP deficiency is associated with systemic inflammation and a catabolic‐like skeletal phenotype, the mechanistic underpinnings remain unclear. Here, using both TTP‐deficient (TTPKO) and myeloid‐specific TTPKO (cTTPKO) mice, we reveal that global absence or loss of TTP in the myeloid compartment results in a reduced bone microarchitecture, whereas gain‐of‐function TTP knock‐in (TTPKI) mice exhibit no significant loss of bone microarchitecture. Flow cytometry analysis revealed a significant immunosuppressive immune cell phenotype with increased monocytic myeloid‐derived suppressor cells (M‐MDSCs) in TTPKO and cTTPKO mice, whereas no significant changes were observed in TTPKI mice. Single‐cell transcriptomic analyses of bone marrow myeloid progenitor cell populations indicated a dramatic increase in early MDSC marker genes for both cTTPKO and TTPKO bone marrow populations. Consistent with these phenotypic and transcriptomic data, in vitro osteoclastogenesis analysis of bone marrow M‐MDSCs from cTTPKO and TTPKO displayed enhanced osteoclast differentiation and functional capacity. Focused transcriptomic analyses of differentiated M‐MDSCs showed increased osteoclast‐specific transcription factors and cell fusion gene expression. Finally, functional data showed that M‐MDSCs from TTP loss‐of‐function mice were capable of osteoclastogenesis and bone resorption in a context‐dependent manner. Collectively, these findings indicate that TTP plays a central role in regulating osteoclastogenesis through multiple mechanisms, including induction of M‐MDSCs that appear to regulate skeletal phenotype.