bluuebunny/crossref_metadata_2025 huggingface dataset:
TPIA2: an updated tea plant information archive for Camellia genomics
Authors: Gao Qijuan , Tong Wei , Li Fangdong , Wang Yanli , Wu Qiong , Wan Xiaochun , Xia Enhua
Published: August 2023

The genus Camellia consists of about 200 species, which include many economically important species widely used for making tea, ornamental flowers and edible oil. Here, we present an updated tea plant information archive for Camellia genomics (TPIA2; http://tpia.teaplants.cn) by integrating more novel large-scale genomic, transcriptomic, metabolic and genetic variation datasets as well as a variety of useful tools. Specifically, TPIA2 hosts all currently available and well assembled 10 Camellia genomes and their comprehensive annotations from three major sections of Camellia. A collection of 15 million SNPs and 950 950 small indels from large-scale genome resequencing of 350 diverse tea accessions were newly incorporated, followed by the implementation of a novel ‘Variation’ module to facilitate data retrieval and analysis of the functionally annotated variome. Moreover, 116 Camellia transcriptomes were newly assembled and added, leading to a significant extension of expression profiles of Camellia genes to 13 developmental stages and eight abiotic/biotic treatments. An updated ‘Expression’ function has also been implemented to provide a comprehensive gene expression atlas for Camellia. Two novel analytic tools (e.g. Gene ID Convert and Population Genetic Analysis) were specifically designed to facilitate the data exchange and population genomics in Camellia. Collectively, TPIA2 provides diverse updated valuable genomic resources and powerful functions, and will continue to be an important gateway for functional genomics and population genetic studies in Camellia.
HapX-mediated H2B deub1 and SreA-mediated H2A.Z deposition coordinate in fungal iron resistance
Authors: Sun Kewei , Li Yiqing , Gai Yunpeng , Wang Jingrui , Jian Yunqing , Liu Xin , Wu Liang , Shim Won-Bo , Lee Yin-Won , Ma Zhonghua , Haas Hubertus , Yin Yanni
Published: August 2023

Plant pathogens are challenged by host-derived iron starvation or excess during infection, but the mechanism through which pathogens counteract iron stress is unclear. Here, we found that Fusarium graminearum encounters iron excess during the colonization of wheat heads. Deletion of heme activator protein X (FgHapX), siderophore transcription factor A (FgSreA) or both attenuated virulence. Further, we found that FgHapX activates iron storage under iron excess by promoting histone H2B deubiquitination (H2B deub1) at the promoter of the responsible gene. Meanwhile, FgSreA is shown to inhibit genes mediating iron acquisition during iron excess by facilitating the deposition of histone variant H2A.Z and histone 3 lysine 27 trimethylation (H3K27 me3) at the first nucleosome after the transcription start site. In addition, the monothiol glutaredoxin FgGrx4 is responsible for iron sensing and control of the transcriptional activity of FgHapX and FgSreA via modulation of their enrichment at target genes and recruitment of epigenetic regulators, respectively. Taken together, our findings elucidated the molecular mechanisms for adaptation to iron excess mediated by FgHapX and FgSreA during infection in F. graminearum and provide novel insights into regulation of iron homeostasis at the chromatin level in eukaryotes.
Unidirectional trans-cleaving behavior of CRISPR-Cas12a unlocks for an ultrasensitive assay using hybrid DNA reporters containing a 3′ toehold
Authors: Mohammad Noor , Talton Logan , Hetzler Zach , Gongireddy Megha , Wei Qingshan
Published: August 2023

CRISPR-Cas12a can induce nonspecific trans-cleavage of dsDNA substrate, including long and stable λ DNA. However, the mechanism behind this is still largely undetermined. In this study, we observed that while trans-activated Cas12a didn’t cleave blunt-end dsDNA within a short reaction time, it could degrade dsDNA reporters with a short overhang. More interestingly, we discovered that the location of the overhang also affected the susceptibility of dsDNA substrate to trans-activated Cas12a. Cas12a trans-cleaved 3′ overhang dsDNA substrates at least 3 times faster than 5′ overhang substrates. We attributed this unique preference of overhang location to the directional trans-cleavage behavior of Cas12a, which may be governed by RuvC and Nuc domains. Utilizing this new finding, we designed a new hybrid DNA reporter as nonoptical substrate for the CRISPR-Cas12a detection platform, which sensitively detected ssDNA targets at sub picomolar level. This study not only unfolded new insight into the trans-cleavage behavior of Cas12a but also demonstrated a sensitive CRISPR-Cas12a assay by using a hybrid dsDNA reporter molecule.
Optimisation of TP53 reporters by systematic dissection of synthetic TP53 response elements
Authors: Trauernicht Max , Rastogi Chaitanya , Manzo Stefano G , Bussemaker Harmen J , van Steensel Bas
Published: August 2023

TP53 is a transcription factor that controls multiple cellular processes, including cell cycle arrest, DNA repair and apoptosis. The relation between TP53 binding site architecture and transcriptional output is still not fully understood. Here, we systematically examined in three different cell lines the effects of binding site affinity and copy number on TP53-dependent transcriptional output, and also probed the impact of spacer length and sequence between adjacent binding sites, and of core promoter identity. Paradoxically, we found that high-affinity TP53 binding sites are less potent than medium-affinity sites. TP53 achieves supra-additive transcriptional activation through optimally spaced adjacent binding sites, suggesting a cooperative mechanism. Optimally spaced adjacent binding sites have a ∼10-bp periodicity, suggesting a role for spatial orientation along the DNA double helix. We leveraged these insights to construct a log-linear model that explains activity from sequence features, and to identify new highly active and sensitive TP53 reporters.
Smoking Dependence, Time-Discounting, and Sustained Cessation Behavior: A Longitudinal Study of Predominantly Light Smokers
Authors: Saenz-de-Miera Belen , Lambert Victoria C , Chen Brian , Gallegos-Carrillo Katia , Barrientos-Gutierrez Inti , Arillo-Santillán Edna , Thrasher James F
Published: August 2023

Introduction

This study aimed to assess whether two established psychosocial predictors of smoking abstinence, nicotine dependence and time-discounting, also apply to a population of predominantly cigarette light smokers, which is the dominant pattern of smoking in countries like Mexico. Relatively infrequent smoking is increasingly prevalent, yet still harmful, making it important to understand the predictors of cessation in this population.

Aims and Methods

Mexican adult smokers recruited from an online consumer panel were surveyed every 4 months between November 2018 and July 2020. We considered respondents who reported a quit attempt in between surveys (n = 1288). Dependence was measured with a 10-item version of the Wisconsin Inventory of Smoking Dependence Motives (WISDM). Time-discounting was assessed with five branching questions about hypothetical reward scenarios. Logistic models regressed sustained quit attempts (≥30 days of abstinence) at time t + 1 on study variables at time t.

Results

We found strong interitem reliability (α = 0.92) and intraindividual consistency of our brief WISDM (ρ = 0.68), but moderate intraindividual consistency of the time-discounting measure (ρ = 0.48). Forty-eight percent of the sample reported sustained quit attempts, and 79% were non-daily or light daily smokers (≤5 cigarettes per day). Smokers with higher WISDM-10 had lower odds of sustained quitting and this result remained when controlling for smoking frequency and the Heaviness of Smoking Index (adjusted odds ratio [AOR] = 0.768). Time-discounting was unassociated with sustained quitting.

Conclusions

Our findings suggest that a brief, 10-item multidimensional measure of dependence is useful for predicting sustained quitting in a context of relatively light smoking; time-discounting appears less relevant, although our results are not conclusive because of the low test-retest reliability of our measure.

Implications

Given the increase in non-daily and light daily cigarette smoking in many countries, including in Mexico, and the health risks this still poses, it is important to understand the predictors of cessation among relatively light smokers. The WISDM-10 multidimensional measure seems to be a good instrument to assess dependence and predict successful quitting in this population, and possibly more appropriate than physical dependence measures. As such, it could help design and target more suitable cessation treatments for non-daily and daily light cigarette smokers. While this study did not find time-discounting to be a relevant predictor of smoking abstinence, future studies should explore other measures.
A Systematic Review of Qualitative Studies on Factors Associated With Smoking Cessation Among Adolescents and Young Adults
Authors: Bitar Sarah , Collonnaz Magali , O’Loughlin Jennifer , Kestens Yan , Ricci Laetitia , Martini Hervé , Agrinier Nelly , Minary Laetitia
Published: August 2023

Objective

To summarize findings from qualitative studies on factors associated with smoking cessation among adolescents and young adults.

Data sources

We searched Pubmed, Psychinfo, CINAHL, Embase, Web of Science, and SCOPUS databases, as well as reference lists, for peer-reviewed articles published in English or French between January 1, 2000, and November 18, 2020. We used keywords such as adolescents, determinants, cessation, smoking, and qualitative methods.

Study selection

Of 1724 records identified, we included 39 articles that used qualitative or mixed methods, targeted adolescents and young adults aged 10–24, and aimed to identify factors associated with smoking cessation or smoking reduction.

Data extraction

Two authors independently extracted the data using a standardized form. We assessed study quality using the National Institute for Health and Care Excellence checklist for qualitative studies.

Data synthesis

We used an aggregative meta-synthesis approach and identified 39 conceptually distinct factors associated with smoking cessation. We grouped them into two categories: (1) environmental factors [tobacco control policies, pro-smoking norms, smoking cessation services and interventions, influence of friends and family], and (2) individual attributes (psychological characteristics, attitudes, pre-quitting smoking behavior, nicotine dependence symptoms, and other substances use). We developed a synthetic framework that captured the factors identified, the links that connect them, and their associations with smoking cessation.

Conclusions

This qualitative synthesis offers new insights on factors related to smoking cessation services, interventions, and attitudes about cessation (embarrassment when using cessation services) not reported in quantitative reviews, supplementing limited evidence for developing cessation programs for young persons who smoke.

Implications

Using an aggregative meta-synthesis approach, this study identified 39 conceptually distinct factors grouped into two categories: Environmental factors and individual attributes. These findings highlight the importance of considering both environmental and individual factors when developing smoking cessation programs for young persons who smoke. The study also sheds light on self-conscious emotions towards cessation, such as embarrassment when using cessation services, which are often overlooked in quantitative reviews. Overall, this study has important implications for developing effective smoking cessation interventions and policies that address the complex factors influencing smoking behavior among young persons.
Human infections by the rat tapeworm Hymenolepis diminuta in China
Authors: Yao Chaoqun
Published: August 2023

The rat tapeworm Hymenolepis diminuta is a parasite that usually uses rats as a definitive host. It also infects humans and non-human primates. Human infections have been reported in 80 countries worldwide, including China. Nevertheless, nearly all the literature on human infections in China by the rat tapeworm is in Chinese journals, which are very difficult to access by readers outside China. The main aim of the current manuscript was to systematically review human infections by the rat tapeworm in China for readers inside and outside the country. Chinese characters for H. diminuta were used to search several databases, including Google Scholar. In total, 511 infections were reported in 24 Chinese provinces/autonomous regions, which surpassed 320 in Costa Rica as the country with the highest number of infections. Furthermore, three nationwide surveys on parasitic infections in the past 3 decades revealed detailed prevalence of this parasite along with that of roundworm, whipworm, hookworm and pinworm in Chinese populations. These data contribute to better understanding of this greatly neglected zoonosis in the world’s most populated country.
Mucosal melanoma: from molecular landscape to current treatment strategies
Authors: Mattei Jane , Trindade Eduardo N. , Chedid Marcio F.
Published: August 2023

Mucosal melanoma (MM) is an aggressive tumor originating from melanocytes located in the respiratory, gastrointestinal, and urogenital tract with clinical and pathologic characteristics distinct from cutaneous melanoma. In addition, MMs have a unique biology that contributes to delayed diagnosis and, therefore an adverse prognosis. The factors all contribute to a treatment paradigm unique from its more studied cutaneous brethren. Due to the rarity of this disease, well-established protocols for the treatment of this pathology have yet to be established. The use of immune checkpoint inhibitors patterned after cutaneous melanoma has become the de facto primary therapeutic approach; however, cytotoxic strategies and pathway-targeted therapies have a defined role in treatment. Judicious use of these approaches can give rise to durable unmaintained disease responses.
Direct early growth response-1 knockdown decreases melanoma viability independent of mitogen-activated extracellular signal-related kinase inhibition
Authors: Miley David R. , Andrews-Pfannkoch Cynthia M. , Pulido Jose S. , Erickson Samantha A. , Vile Richard G. , Fautsch Michael P. , Marmorstein Alan D. , Dalvin Lauren A.
Published: August 2023

To investigate downstream molecular changes caused by mitogen-activated protein kinase (MEK) inhibitor treatment and further explore the impact of direct knockdown of early growth response-1 (EGR1) in melanoma cell culture. RNA-sequencing (RNA-Seq) was performed to determine gene expression changes with MEK inhibitor treatment. Treatment with MEK inhibitor (trametinib) was then assessed in two cutaneous (MEL888, MEL624) and one conjunctival (YUARGE 13-3064) melanoma cell line. Direct knockdown of EGR1 was accomplished using lentiviral vectors containing shRNA. Cell viability was measured using PrestoBlueHS Cell Viability Reagent. Total RNA and protein were assessed by qPCR and SimpleWestern. RNA-Seq demonstrated a profound reduction in EGR1 with MEK inhibitor treatment, prompting further study of melanoma cell lines. Following trametinib treatment of melanoma cells, viability was reduced in both cutaneous (MEL888 26%, P < 0.01; MEL624 27%, P < 0.001) and conjunctival (YUARGE 13-3064 33%, P < 0.01) melanoma compared with DMSO control, with confirmed EGR1 knockdown to 0.04-, 0.01-, and 0.16-fold DMSO-treated levels (all P < 0.05) in MEL888, MEL624, and YUARGE 13-3064, respectively. Targeted EGR1 knockdown using shRNA reduced viability in both cutaneous (MEL624 78%, P = 0.05) and conjunctival melanoma (YUARGE-13-3064 67%, P = 0.02). RNA-Sequencing in MEK inhibitor-treated cells identified EGR1 as a candidate effector molecule of interest. In a malignant melanoma cell population, MEK inhibition reduced viability in both cutaneous and conjunctival melanoma with a profound downstream reduction in EGR1 expression. Targeted knockdown of EGR1 reduced both cutaneous and conjunctival melanoma cell viability independent of MEK inhibition, suggesting a key role for EGR1 in melanoma pathobiology.
Microbial Infections After Boston Keratoprosthesis: A Case Series
Authors: Xu Yuwei , Zeng Liangbo , Zhang Yuying , Chen Miao , Ou Zhancong , Zhou Jin , Zhuo Kaichen , Chen Jiaqi , Lin Lixia , Gu Jianjun
Published: August 2023

Purpose:

This article presents a case series of microbial keratitis in eyes that underwent Boston keratoprosthesis implantation.

Methods:

A thorough examination of medical records and microbiology results was conducted for patients who experienced microbial keratitis subsequent to Boston keratoprosthesis (KPro) implantation from July 2019 to July 2023.

Results:

The review included 3 eyes of 3 distinct patients. In case 1, a patient with a history of chemical burns in the right eye underwent type I KPro implantation. Infectious keratitis, caused by Corynebacterium amycolatum, developed 9 years post-implantation. Despite the keratitis, the KPro remained in place, and treatment with vancomycin and ceftazidime agents, along with a C-collar full-thickness corneal graft for corneal melt, was administered. In case 2, Streptococcus pneumoniae-induced keratitis occurred 2 months following a type I KPro implantation. The infiltration resolved entirely after 4 weeks of topical and systemic antimicrobial treatment. Case 3 involved a patient with a history of Stevens-Johnson syndrome who underwent type II KPro implantation with autologous auricular cartilage reinforcement in the left eye. Bacterial keratitis and endophthalmitis caused by Streptococcus mitis/oralis developed 2 years after the surgery, ultimately resulting in phthisis.

Conclusions:

Both C. amycolatum and S. mitis/oralis can breach commensalism barriers, leading to opportunistic infections in eyes with implanted keratoprosthesis and compromised ocular surfaces. Post-keratoprosthesis microbial keratitis remains a significant concern and is often associated with adverse outcomes.
Levomethadone Therapeutic Drug Monitoring to Aid Opioid Withdrawal Therapy: A Short Communication
Authors: Pfeifer Philippe , Hildebrand Kathrin , Angelov Andreas , Havemann-Reinecke Ursula , Böttcher Michael , Hiemke Christoph , Prentice Tatjana , Roll Sibylle C.
Published: August 2023

Background:

Therapeutic drug monitoring (TDM) is recommended for opioid maintenance therapy with levomethadone. However, TDM has not yet been applied to monitor opioid withdrawal therapy clinically, although tools to improve it are required.

Methods:

In this observational cohort study, repeated TDM with levomethadone was performed according to a prospective opioid withdrawal study protocol. Objective and subjective opioid withdrawal symptoms were measured using validated rating scales and correlated to levomethadone plasma concentrations. Plasma levels were measured using high-pressure liquid chromatography with column switching and spectroscopic detection of methadone and its major metabolite.

Results:

This study included 31 opioid-dependent patients who participated in standardized opioid withdrawal therapy. The serum levels of levomethadone were found to be highly variable and below the recommended therapeutic reference range of 250 ng/mL for maintenance therapy. These serum levels were positively correlated with dosage (r = 0.632; P < 0.001) and inversely correlated with subjective (r = −0.29; P = 0.011) and objective (r = −0.28; P = 0.014) withdrawal symptoms.

Conclusions:

The evidence provided sheds light on how to improve levomethadone withdrawal therapy in patients with opioid dependence. It seems likely that higher initial doses at the beginning and lower dose reductions would have been advantageous. TDM can enhance the safety of opioid withdrawal therapies, minimize withdrawal symptoms, and reduce dropout rates.
A NEW PHENOTYPE OR RETINAL INVOLVEMENT IN STEINERT DISEASE: A CASE REPORT
Authors: Bottazzi Leonardo , Sacconi Riccardo , Alessi Salvatore , Martorana Charles Anthony , Francesco Bandello , Querques Giuseppe
Published: August 2023

Purpose:

The purpose of this article was to report a case illustrating the association of Steinert disease with peripheral retinal nonperfusion areas and epiretinal membrane.

Methods:

This was a case report.

Results:

A 47-year-old White woman diagnosed with Steinert disease was referred for blurred vision in her right eye. She presented bilateral ptosis with deficit of elevator muscle. Dilated fundus examination revealed altered macular reflex, peripheral vascular alterations, and ghost vessels bilaterally. Structural spectral domain optical coherence tomography showed an epiretinal membrane with a partial alteration of the foveal profile in the right eye. Optical coherence tomography angiography images revealed no evidence of neovascular membrane in the macular region. Fluorescein angiography showed retinal peripheral nonperfusion areas and leakage in the late phases of the examination.

Conclusion:

Any retinal alteration should be considered during the ophthalmological examination of patients suffering from type 1 myotonic dystrophy. Optical coherence tomography and fluorescein angiography should be performed evaluating the patient with Steinert disease who complains about visual impairment.
The future of artificial intelligence in clinical nutrition
Authors: Singer Pierre , Robinson Eyal , Raphaeli Orit
Published: August 2023

Purpose of review

Artificial intelligence has reached the clinical nutrition field. To perform personalized medicine, numerous tools can be used. In this review, we describe how the physician can utilize the growing healthcare databases to develop deep learning and machine learning algorithms, thus helping to improve screening, assessment, prediction of clinical events and outcomes related to clinical nutrition.

Recent findings

Artificial intelligence can be applied to all the fields of clinical nutrition. Improving screening tools, identifying malnourished cancer patients or obesity using large databases has been achieved. In intensive care, machine learning has been able to predict enteral feeding intolerance, diarrhea, or refeeding hypophosphatemia. The outcome of patients with cancer can also be improved. Microbiota and metabolomics profiles are better integrated with the clinical condition using machine learning. However, ethical considerations and limitations of the use of artificial intelligence should be considered.

Artificial intelligence is here to support the decision-making process of health professionals. Knowing not only its limitations but also its power will allow precision medicine in clinical nutrition as well as in the rest of the medical practice.
Effect of early ultrasound-guided femoral nerve block on preoperative opioid consumption in emergency patients with hip fracture: a randomized trial
Authors: Gerlier Camille , Mijahed Rami , Fels Audrey , Bekka Samir , Courseau Romain , Singh Anne-Lyse , Ganansia Olivier , Chatellier Gilles
Published: August 2023

Background and importance

Ultrasound-guided femoral nerve block (FNB) could be used as part of a multimodal preoperative pain management for patients with hip fracture. Evidence of the effects of its early implementation in the emergency room as an immediate alternative to intravenous morphine titration is sparse.

Objective

To investigate the effect of an early ultrasound-guided FNB performed by emergency physicians on preoperative opioid consumption, compared to standard pain management.

Design, setting, and participants

This open randomized controlled trial was conducted in the Emergency Department of a French hospital with patients with neck or trochanteric femoral fracture who had a pain score ≥7 out of 10 points at triage.

Intervention

Patients were randomized to receive an initial analgesia with an early ultrasound-guided FNB or with standard pain management. The continuation of pain treatment followed standardized pain control guidelines until hospital discharge in both groups.

Outcome measure and analysis

The primary outcome was preoperative opioid consumption truncated 48h after triage time, and converted in morphine milligram intravenous equivalents (MME). Secondary outcomes were time to pain relief, time for regaining walk, opioid consumption and occurrence of opioid and FNB adverse effects during the hospital stay. Exploratory outcomes included ease and duration of the procedure.

Main results

We randomized 35 patients: 17 to standard pain management and 18 to ultrasound-guided FNB, among whom 30 patients completed the protocol. The median of preoperative opioid consumption was reduced by 60% in the ultrasound-guided FNB group compared to standard group [6 MME (3–9) vs. 15 MME (11–18)], with a consumption difference of 9 MME (95% CI: 3–14, P < 0.001). Throughout hospital stay, opioid consumption was reduced by 56% in the ultrasound-guided FNB group compared to standard group, with a consumption difference of 11.5 MME (95% CI: 0.5–22).Times to pain relief and for regaining walk did not differ between groups. Opioid adverse events occurrence were reduced by 40% (95% CI: 5.1–74.9) in the ultrasound-guided FNB group compared to standard group. No adverse effects of FNB have been detected.

Conclusion

Early ultrasound-guided FNB resulted in reducing preoperative opioid consumption, without delaying time to pain relief.
Differential survival of Brazilian patients with diffuse large B-cell lymphoma with and without HIV infection
Authors: Ferreira Mariana P. , Thuler Luiz Claudio S. , Bergmann Anke , Soares Esmeralda A. , Soares Marcelo A.
Published: August 2023

Objective:

Combinatorial antiretroviral therapy provided improvement of HIV patients’ immune function and a decrease in the incidence of non-Hodgkin lymphoma (NHL). Diffuse large B-cell lymphoma (DLBCL) is one of the most common NHL forms affecting HIV+ patients. The present study aimed to evaluate the impact of HIV infection on the prognosis of patients treated for DLBCL in a reference cancer treatment center in Brazil.

Methods:

A retrospective case–control study was developed with patients followed-up at the Brazilian National Cancer Institute, in which 243 DLBCL patients (91 HIV+ and 152 HIV−) were enrolled. HIV− controls were matched to HIV+ according to date of cancer diagnosis, clinical staging, primary cancer treatment and date of birth. Sociodemographic and cancer treatment data were extracted from medical charts. Kaplan-Meier analyses were carried out to estimate survival, while univariate and multiple Cox regression analyses were used to determine factors associated with mortality.

Results:

A total of 98 deaths were observed in a 5-year period after cancer diagnosis. A negative association of HIV infection with both overall and disease-specific survival 1 year after cancer diagnosis was observed [hazard ratio (HR) = 1.98 and 1.96, respectively]. The negative association with HIV infection with disease-specific survival remained significant for a 5-year period after cancer diagnosis (HR = 1.53). HIV viral load above 1000 copies/ml at study entry was also associated with shorter overall and cancer-specific survival.

Conclusions:

HIV infection negatively impacted prognosis and mortality of DLBCL patients irrespective of cancer-related clinical factors.
A novel chimeric vaccine candidate for porcine reproductive and respiratory syndrome virus (PRRSV) I and II elicits neutralizing antibodies against both types
Authors: Cha Sang-Ho , Hyun Bang-Hun , Lee Hyang-Sim , Kang Seok-Jin , You Su-Hwa , Jeong Jiwoon , Park Chang-Joo , Lee Myung-Shin , Park Changhoon
Published: August 2023

Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important virus within the swine industry. The virus causes respiratory disease and reproductive failure. Two species of PRRSV-I and II are co-dominant, yet no effective vaccination strategy has been developed to protect against these two types. With an aim to develop a chimeric vaccine strain to protect against both types, in this study, a chimeric porcine reproductive and respiratory syndrome virus (PRRSV) type I and II was rescued using reverse genetics for the first time. Four chimeric infectious clones were designed based on the genomic arrangement of the structural proteins. However, only the clone carrying the transcriptional regulatory sequence (TRS) and ORF6 of a PRRSV-I and ORF6 of a PRRSV-II generated a viable recombinant virus, suggesting that concurrent expression of ORF6 from both parental viruses is essential for the recovery of type I and II chimeric PRRSV. The chimeric virus showed significantly lower replication ability than its parental strainsin vitro, which was improved by serial passaging.In vivo, groups of pigs were inoculated with either the chimeric virus, one of the parental strains, or PBS. The chimeric virus replicated in pig tissue and was detected in serum 7 days post-inoculation. Serum neutralization tests indicated that pigs inoculated with the chimeric virus elicited neutralizing antibodies that inhibited infection with strains of both species and with greater coverage than the parental viruses. In conclusion, the application of this technique to construct a chimeric PRRSV holds promise for the development of a highly effective modified live vaccine candidate. This is particularly significant since there are currently no approved commercial divalent vaccines available to combat PRRSV-I and II co-infections.
MEX-PD: A National Network for the Epidemiological & Genetic Research of Parkinson’s Disease
Authors: Lázaro-Figueroa Alejandra , Reyes-Pérez Paula , Morelos-Figaredo Eugenia , Guerra-Galicia Carlos M. , Estrada-Bellmann Ingrid , Salinas-Barboza Karla , Matuk-Pérez Yamil , Gandarilla-Martínez Nadia A. , Caballero-Sánchez Ulises , Flores-Ocampo Victor , Montés-Alcántara Pablo , Espinosa-Méndez Ian M. , Zayas-Del Moral Alejandra , Gaspar-Martínez Edith , Vazquez-Guevara Damaris , Rodríguez-Violante Mayela , Inca-Martinez Miguel , Mata Ignacio F. , Alcauter Sarael , Rentería Miguel E. , Medina-Rivera Alejandra , Ruiz-Contreras Alejandra E.
Published: August 2023

Background

Parkinson’s Disease (PD) has a complex etiology, involving genetic and environmental factors. Most of our current understanding of the disease comes from studies in populations with mostly European ancestry, representing challenges in generalizing findings to other populations with different genetic, social, and environmental contexts. There are scarce studies focused in Latin American populations. The Mexican population is genetically diverse because its admixture from Native American, European, and African ancestries, coupled with the unique environmental conditions, stressing the relevance of establishing genetic studies in this population. Thus, we have established theMexican Parkinson’s Research Network(MEX-PD), a consortium to research the clinical, genetical, environmental, and neurophysiological bases of the phenotypic diversity in Mexican PD patients.

Objectives

Describing how MEX-PD was established, the methods and instruments and presenting the first results.

Methods

Patients and controls were recruited from medical centers in 20 states of Mexico. Initial recruitment included neurological evaluation, cognitive assessment, and DNA collection.

Results

MEX-PD has registered 302 controls and 262 PD patients with a mean age of diagnosis of 61 years (SD=10.86). There were 19.8% PD patients identified with early onset. Levodopa was the most common pharmacological treatment.

Conclusions

MEX-PD contributes to understand PD nationally. The information gathered here will allow us to understand the prevalence of mental health, neurological symptoms, and cognitive function in the PD Mexican population and how genetical and environmental factors contributes to those outcomes. These will advocate for personalized treatments and improving quality of life in the Mexican population.
Sparse Modeling of Genomic Landscape Identifies Pathogenic Processes and Therapeutic Targets in Metastatic Breast Cancer
Authors: Pu Mengchen , Tian Kai , Zheng Weisheng , Li Xiaorong , Fan Keyue , Zheng Liang , Zhou Jielong , Zhang Yingsheng
Published: August 2023

Breast cancer is a heterogeneous disease and ranks as one of the most lethal and frequently detected disease in the world. It poses significant challenges for precision therapy. To better decipher the patterns of heterogeneous nature in human genome and converge them into common functionals, mutational signatures are introduced to define the types of DNA damage, repair and replicative mechanisms that shape the genomic landscape of each cancer patient.

In this study, we developed a deep learning (DL) model, MetaWise 2.0, based on pruning technology that improved model generalization with deep sparsity. We applied it to patient samples from multiple sequencing studies, and identified statistically significant mutational signatures associated with metastatic progression using Shapley additive explanations (SHAP). We also employed gene cumulative contribution abundance analysis to link the mutational signatures with relevant genes, which could unearth the shared molecular mechanisms behind tumorigenesis and metastasis of each patient and lead to novel therapeutic target identification.

Our study illustrates that MetaWise 2.0 is an effective DL tool for discovering clinically meaningful mutational signatures in metastatic breast cancer (MBC) and relating them directly to relevant biological functions and gene targets. These findings could facilitate the development of novel therapeutic strategies and improve the clinical outcomes for individual patients.
Spatiotemporal development of the human T follicular helper cell response to Influenza vaccination
Authors: Schattgen Stefan A , Turner Jackson S. , Ghonim Mohamed A , Crawford Jeremy Chase , Schmitz Aaron J. , Kim Hyunjin , Zhou Julian Q. , Awad Walid , Kim Wooseob , McIntire Katherine M. , Haile Alem , Klebert Michael K. , Suessen Teresa , Middleton William D. , Teefey Sharlene A. , Presti Rachel M. , Ellebedy Ali H. , Thomas Paul G.
Published: August 2023

We profiled blood and draining lymph node (LN) samples from human volunteers after influenza vaccination over two years to define evolution in the T follicular helper cell (TFH) response. We show LN TFH cells expanded in a clonal-manner during the first two weeks after vaccination and persisted within the LN for up to six months. LN and circulating TFH (cTFH) clonotypes overlapped but had distinct kinetics. LN TFH cell phenotypes were heterogeneous and mutable, first differentiating into pre-TFH during the month after vaccination before maturing into GC and IL-10+ TFH cells. TFH expansion, upregulation of glucose metabolism, and redifferentiation into GC TFH cells occurred with faster kinetics after re-vaccination in the second year. We identified several influenza-specific TFH clonal lineages, including multiple responses targeting internal influenza proteins, and show each TFH state is attainable within a lineage. This study demonstrates that human TFH cells form a durable and dynamic multi-tissue network.
qMaLioffG: A single green fluorescent protein FLIM indicator enabling quantitative imaging of endogenous ATP
Authors: Arai Satoshi , Itoh Hideki , Vu Cong Quang , Nakayama Mizuho , Oshima Masanobu , Morita Atsuya , Okamoto Kazuko , Okuda Satoru , Teranishi Aki , Osawa Madori , Tamura Yoshiteru , Nonoyama Shigeaki , Takuma Megumi , Fujie Toshinori , Sarker Satya Ranjan , Sudhaharan Thankiah , Kiya Taketoshi , Lane E. Birgitte , Kitaguchi Tetsuya
Published: August 2023

The widespread use of fluorescence lifetime imaging microscopy (FLIM) for quantitative imaging is hindered by the limited availability of a FLIM-based genetically encoded indicator using a conventional 488 nm laser. Here, we present qMaLioffG, a single green fluorescent protein FLIM indicator showing a fluorescence lifetime change in ATP concentration within the physiological range. This allows quantitative imaging of endogenous ATP to investigate cellular energy status of different cell types.
Decoding the Influence of Central LEAP2 on Hedonic Food Intake and its association with Dopaminergic Reward Pathways
Authors: Tufvesson-Alm Maximilian , Zhang Qian , Aranäs Cajsa , Blid Sköldheden Sebastian , Edvardsson Christian E , Jerlhag Elisabet
Published: August 2023

The gut-brain peptide ghrelin and its receptor (GHSR) are established as a regulator of hunger and reward-processing. However, the recently recognized GHSR inverse agonist, liver-expressed antimicrobial peptide 2 (LEAP2), is less characterized. Given the role of GHSR in many central processes, and in particular reward, understanding the central effects of LEAP2 is of high interest to understand reward-related behaviors and disorders, including hedonic feeding in eating disorders. The present study aimed to elucidate LEAP2s central effect on reward-related behaviors through hedonic feeding and its mechanism. LEAP2 was administrated centrally in male mice and effectively reduced hedonic feeding but had no or little effect on homeostatic chow intake when a more palatable option was available. Strikingly, the effect on hedonic feeding was correlated to the preference of the palatable food option, where peanut butter showed the highest preference and the greatest reduction by LEAP2. Further, LEAP2 reduced the rewarding memory of high-preference foods, as well as attenuated the accumbal dopamine release associated with peanut butter exposure and eating. Interestingly, LEAP2 was widely expressed in the brain, and in particular in reward-related brain areas such as the laterodorsal tegmental area (LDTg). The expression in this area was also markedly altered when given free access to peanut butter. Accordingly, infusion of LEAP2 into the LDTg was sufficient to attenuate acute peanut butter eating. Taken together, the present results show that central LEAP2 has a profound effect on central dopaminergic reward signaling and affects several aspects of hedonic eating. The present study highlights LEAP2s effect on reward, which may have application not only for hedonic feeding, but for other reward-related psychiatric disorders as well.
An efficient and robust ABC approach to infer the rate and strength of adaptation
Authors: Murga-Moreno Jesús , Casillas Sònia , Barbadilla Antonio , Uricchio Lawrence , Enard David
Published: August 2023

Inferring the effects of positive selection on genomes remains a critical step in characterizing the ultimate and proximate causes of adaptation across species, and quantifying positive selection remains a challenge due to the confounding effects of many other evolutionary processes. Robust and efficient approaches for adaptation inference could help characterize the rate and strength of adaptation in non-model species for which demographic history, mutational processes, and recombination patterns are not currently well-described. Here, we introduce an efficient and user-friendly extension of the McDonald-Kreitman test (ABC-MK) for quantifying long-term protein adaptation in specific lineages of interest. We characterize the performance of our approach with forward simulations and find that it is robust to many demographic perturbations and positive selection configurations, demonstrating its suitability for applications to non-model genomes. We apply ABC-MK to the human proteome and a set of known Virus Interacting Proteins (VIPs) to test the long-term adaptation in genes interacting with viruses. We find substantially stronger signatures of positive selection on RNA-VIPs than DNA-VIPs, suggesting that RNA viruses may be an important driver of human adaptation over deep evolutionary time scales.
Metabolites with benzene ring from sugarcane leaf play important role in plant-Spodoptera frugiperdainteraction
Authors: Su Liangyinan , Hu Chunyu , Wang Chaoqi , Chen Baoshan , Zhao Yang
Published: August 2023

Secondary metabolism plays important role in plant growth and development, however, the relationship between secondary metabolism and adaptive plant-insect communication is largely unknown. The present study used sugarcane line highly susceptible toSpodoptera frugiperdaand sister line with medium resistance to analyze the role of plant non-volatile organic compounds (NOCs) and volatile organic compounds (VOCs) in sugarcane-S. frugiperdainteraction. A total of 46 plant NOCs and 15 plant VOCs significantly different between resistant and susceptible lines and were continuously up-regulated and down-regulated at different time points before/afterS.frugiperdatreatment were screened. Phenolic acids containing benzene ring accounted for the largest proportion of differential NOCs. Levels of 66.7% of these phenolic acids were higher in susceptible line. Feeding supplemented with NOCs showed that phenoxyacetic acid (phenolic acid) and 4-methoxybenzaldehyde (aromatic phenolic acid) both increased the male-to-female ratio ofS. frugiperda. Aromatics containing benzene ring, accounted for the largest of differential VOCs in susceptible line. Two aromatics,p-cymene and benzene and 1-ethenyl-4-methoxy-, with higher level in susceptible line, were attractive toS. frugiperda. Terpenoids, aldehyde, and esters accounted for most of higher-in-resistant VOCs, with most tested to be repellent toS. frugiperda. Furthermore, transcriptome analysis ofS. frugiperdafeeding on susceptible and resistant lines combined with feeding assays revealed that tryptophan, as a precursor of aromatic compounds that also contains benzene ring, could promote the growth and development ofS. frugiperdain nutritional deficiency condition. These findings together suggested that benzene-ring containing compounds play a critical role in plant-Spodoptera frugiperdainteraction.
Social learning of a challenging two-step action sequence fulfils key criteria of cumulative culture in an insect
Authors: Bridges Alice D. , Royka Amanda , Wilson Tara , Chittka Lars
Published: August 2023

Culture in non-human animals refers to behaviour that is socially learned and persists within a population over time. Human culture is notable in that it iscumulative: new innovations have built on previous ones over thousands of years. As a result, what is acquired via social learning often goes far beyond the capacity of any individual to independently discover it during their lifetime1–3. To date, no previous study has convincingly demonstrated this phenomenon in a non-human animal. Here, we show that bumblebees can learn from a trained demonstrator to open a novel, 3D-printed two-step puzzle box to obtain food rewards, even though they fail to do so independently. Experimenters were unable to train demonstrators to perform the unrewarded first step of the behaviour without providing a temporary reward linked to this action: the reward then being removed during later stages of training. However, a third of naïve observers learned to open the two-step box from these demonstrators, without ever having been rewarded after the first step. This suggested that social learning might permit the acquisition of behaviours too complex to “re-innovate” via individual learning. Furthermore, naïve bees failed to open the box despite extended exposure over the course of 12 days. The temporal and spatial distance of the unrewarded first step from the reward appeared to inhibit acquisition of two-step box-opening via individual associative learning, but this limitation was overcome by the presence of a trained conspecific. To our knowledge, these results make bumblebees the first animal to demonstrate the ability to socially learn a behaviour that is beyond their ability to innovate individually. This finding challenges the prevailing opinion of the field, which generally considers cumulative culture, which is built on this capacity, to be unique to humans.
Lignin, glutathione and kinases play important roles inPaspalum regnelliidefense against spittlebug (Mahanarva spectabilis) attack
Authors: Begnami Isabela dos Santos , Aono Alexandre Hild , Graciano Diego da Silva , Carmello-Guerreiro Sandra Maria , Ferreira Rebecca Caroline Ulbricht , Malagó Wilson , Gusmão Marcos Rafael , de Souza Anete Pereira , Vigna Bianca Baccili Zanotto
Published: August 2023

Spittlebugs cause large production losses that affect agribusiness worldwide. Understanding plant-herbivore interactions at molecular level may be the key to developing resistant cultivars.

We assembled ade novotranscriptome for elucidate the roots response from twoPaspalum regnelliigenotypes (BGP 248 and 344) to spittlebug (Mahanarva spectabilis)nymph attack, integrating differential expression analysis and complex network modeling, supplemented by a resistance field experiment and root anatomical analysis.

GO terms related to different stress responses were enriched in BGP 248, such as salicylic acid catabolic process, while some specific to spittlebugs like response to herbivores were enriched in BP 344. KEGG enriched pathways were related to structural differences between genotypes, for example, cutin, suberin and wax biosynthesis. BP 344 also presented pathways related to induced defense, such as glutathione metabolism. Metabolic networks highlighted kinases, and coexpression networks demonstrated a greater complexity in their response cascade, which includes lncRNAs.

This study provides the first molecular insights into the defense mechanisms ofP. regnelliiagainstM. spectabilis.It was identified that the genotype with the highest nymph mortality (BGP 344) has constitutive barriers, such as lignin, which delay the attack. In addition to presenting a glutathione pathway enriched and greater presence of kinases.
Lymphatic vessel transit seeds precursors to cytotoxic resident memory T cells in skin draining lymph nodes
Authors: Heim Taylor A. , Schultz Austin C. , Delclaux Ines , Cristaldi Vanessa , Churchill Madeline J. , Lund Amanda W.
Published: August 2023

Resident memory T cells (TRM) provide rapid, localized protection in peripheral tissues to pathogens and cancer. While TRMare also found in lymph nodes (LN), how they develop during primary infection and their functional significance remains largely unknown. Here, we track the anatomical distribution of anti-viral CD8+T cells as they simultaneously seed skin and LN TRMusing a model of skin infection with restricted antigen distribution. We find exquisite localization of LN TRMto the draining LN of infected skin. LN TRMformation depends on lymphatic transport and specifically egress of effector CD8+T cells that appear poised for residence as early as 12 days post infection. Effector CD8+T cell transit through skin is necessary and sufficient to populate LN TRMin draining LNs, a process reinforced by antigen encounter in skin. Importantly, we demonstrate that LN TRMare sufficient to provide protection against pathogenic rechallenge. These data support a model whereby a subset of tissue infiltrating CD8+T cells egress during viral clearance, and establish regional protection in the draining lymphatic basin as a mechanism to prevent pathogen spread.

One Sentence Summary

T cell egress out of virally infected skin via afferent lymphatic vessels seeds CD8+resident memory T cells in the draining lymph node.