bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcription factor-dependent regulatory networks of sexual reproduction in
Fusarium graminearum
Authors: Kim Wonyong , Kim Da-Woon , Wang Zheng , Liu Meng , Townsend Jeffrey P. , Trail Frances 
Published: November 2024

ABSTRACT

Transcription factors (TFs) involved in sexual reproduction in filamentous fungi have been characterized. However, we have little understanding of how these TFs synergize within regulatory networks resulting in sexual development. We investigated 13 TFs in
Fusarium graminearum
, whose knockouts exhibited abortive or arrested phenotypes during sexual development to elucidate the transcriptional regulatory cascade underlying the development of the sexual fruiting bodies. A Bayesian network of the TFs was inferred based on transcriptomic data from key stages of sexual development. We evaluated
in silico
knockout impacts to the networks of the developmental phenotypes among the TFs and guided knockout transcriptomics experiments to properly assess regulatory roles of genes with same developmental phenotypes. Additional transcriptome data were collected for the TF knockouts guided by the stage at which their phenotypes appeared and by the cognate
in silico
prediction. Global TF networks revealed that TFs within the mating-type locus (
MAT
genes) trigger a transcriptional cascade involving TFs that affected early stages of sexual development. Notably,
PNA1
, whose knockout mutants produced exceptionally small protoperithecia, was shown to be an upstream activator for
MAT
genes and several TFs essential for ascospore production. In addition, knockout mutants of
SUB1
produced excessive numbers of protoperithecia, wherein
MAT
genes and pheromone-related genes exhibited dysregulated expression. We conclude that
PNA1
and
SUB1
play central and suppressive roles in initiating sexual reproduction, respectively. This comprehensive investigation contributes to our understanding of the transcriptional framework governing the multicellular body plan during sexual reproduction in
F. graminearum
.

IMPORTANCE

Understanding transcriptional regulation of sexual development is crucial to the elucidation of the complex reproductive biology in
Fusarium graminearum
. We performed gene knockouts on 13 transcription factors (TFs), demonstrating knockout phenotypes affecting distinct stages of sexual development. Using transcriptomic data across stages of sexual development, we inferred a Bayesian network of these TFs that guided experiments to assess the robustness of gene interactions using a systems biology approach. We discovered that the mating-type locus (
MAT
genes) initiates a transcriptional cascade, with
PNA1
identified as an upstream activator essential for early sexual development and ascospore production. Conversely,
SUB1
was found to play a suppressive role, with knockout mutants exhibiting excessive protoperithecia due to abnormally high expression of
MAT
and pheromone-related genes. These findings highlight the central roles of
PNA1
and
SUB1
in regulating other gene activity related to sexual reproduction, contributing to a deeper understanding of the mechanisms of the multiple TFs that regulate sexual development.
Structure and identification of the native PLP synthase complex from
Methanosarcina acetivorans
lysate
Authors: Agnew Angela , Humm Ethan , Zhou Kang , Gunsalus Robert P. , Zhou Z. Hong 
Published: November 2024

ABSTRACT

Many protein-protein interactions behave differently in biochemically purified forms as compared to their
in vivo
states. As such, determining native protein structures may elucidate structural states previously unknown for even well-characterized proteins. Here, we apply the bottom-up structural proteomics method,
cryoID
, toward a model methanogenic archaeon. While they are keystone organisms in the global carbon cycle and active members of the human microbiome, there is a general lack of characterization of methanogen enzyme structure and function. Through the
cryoID
approach, we successfully reconstructed and identified the native
Methanosarcina acetivorans
pyridoxal 5′-phosphate (PLP) synthase (PdxS) complex directly from cryogenic electron microscopy (cryo-EM) images of fractionated cellular lysate. We found that the native PdxS complex exists as a homo-dodecamer of PdxS subunits, and the previously proposed supracomplex containing both the synthase (PdxS) and glutaminase (PdxT) was not observed in cellular lysate. Our structure shows that the native PdxS monomer fashions a single 8α/8β TIM-barrel domain, surrounded by seven additional helices to mediate solvent and interface contacts. A density is present at the active site in the cryo-EM map and is interpreted as ribose 5-phosphate. In addition to being the first reconstruction of the PdxS enzyme from a heterogeneous cellular sample, our results reveal a departure from previously published archaeal PdxS crystal structures, lacking the 37-amino-acid insertion present in these prior cases. This study demonstrates the potential of applying the
cryoID
workflow to capture native structural states at atomic resolution for archaeal systems, for which traditional biochemical sample preparation is nontrivial.

IMPORTANCE
Archaea are one of the three domains of life, classified as a phylogenetically distinct lineage. There is a paucity of known enzyme structures from organisms of this domain, and this is often exacerbated by characteristically difficult growth conditions and a lack of readily available molecular biology toolkits to study proteins in archaeal cells. As a result, there is a gap in knowledge concerning the mechanisms governing archaeal protein behavior and their impacts on both the environment and human health; case in point, the synthesis of the widely utilized cofactor pyridoxal 5′-phosphate (PLP; a vitamer of vitamin B6, which humans cannot produce). By leveraging the power of single-particle cryo-EM and map-to-primary sequence identification, we determine the native structure of PLP synthase from cellular lysate. Our workflow allows the (i) rapid examination of new or less characterized systems with minimal sample requirements and (ii) discovery of structural states inaccessible by recombinant expression.
Permanent draft genome sequences of cadmium-resistant isolates of
Cupriavidus
from soils within the Tar Creek Superfund site
Authors: Winn Jordon N. , Wedlock Emily A. , McHugh Emily P. , Monismith, Jr. David , Campbell James H. , Campbell Alisha G. 
Published: November 2024

ABSTRACT

Soil samples taken near the abandoned town of Picher, OK, USA, were used to enrich and isolate bacteria in the presence of cadmium. Isolates reported belong to the genus
Cupriavidus
. Here, we report their permanent draft sequences with an emphasis on genes conferring resistance to cadmium.
Complete genome of
Xanthomonas citri
pv.
anacardii
strain CCRMTAQ13 (causal agent of angular leaf spot in cashew) from Brazil using long-read Nanopore technology
Authors: Silva Hiago Antonio Oliveira da , de Abreu Lucas Magalhaes , da Gama Marco Aurelio Siqueira , Huguet-Tapia Jose , Zhang Peiqi , Buttros Victor Hugo , Mukesh Jain , White Frank , Martins Samuel J. 
Published: November 2024

ABSTRACT

Here, we present a single contiguous genome sequence of
Xanthomonas citri
pv.
anacardii
(
Xca
; strain CCRMTAQ13), the causal agent of angular leaf spot in cashew, an important commodity crop in Brazil. Oxford Nanopore Sequencing Technology was used to assemble the genome of the
Xca
in a single contig of 5,086,757 bp with a 64.53% GC content. This genome sequence will provide a useful resource for studies on virulence mechanisms, including the identification of a single transcription activator-like effector gene of 3,359 bp.
Impact of exercise training in combination with dapagliflozin on physical function in adults with type 2 diabetes mellitus: study protocol for the Dapagliflozin, Exercise Training and physicAl function (DETA) randomised controlled trial
Authors: Sargeant Jack A , Ahmad Ehtasham , James Emily , Baker Luke , Bilak Joanna M , Coull Nicole A , Gulsin Gaurav Singh , King James A , Khunti Kamlesh , Redman Emma , Rowlands Alex , Watson Emma , Wormleighton Joanne V , McCann Gerry P , Yates Thomas , Davies Melanie J 
Published: November 2024

IntroductionSodium-glucose co-transporter 2 inhibitors (SGLT2i) are associated with weight loss, diverse cardiorenal benefits and improved glycaemic control. However, the effects of SGLT2i on physical function and fitness are uncertain. The Dapagliflozin, Exercise Training and physicAl function trial investigates whether the SGLT2i dapagliflozin, alone or in combination with structured exercise training, improves physical function compared with diet-induced weight loss in adults with type 2 diabetes mellitus (T2DM), overweight/obesity and impaired physical function.Methods and analysisThis single-centre randomised controlled trial will assign 1:1:1, 135 adults with T2DM and low physical function to receive one of three treatments: (1) dapagliflozin (10 mg once-daily) alone, (2) dapagliflozin (10 mg once-daily) plus structured exercise training or (3) diet control (where participants are supported to achieve 3% weight loss, equivalent to estimated weight loss with dapagliflozin treatment). Primary and secondary outcomes will be assessed at baseline, 12 and 24 weeks. The primary outcome is the difference in physical function, assessed using the modified Physical Performance Test, between the treatment groups and diet control at 24 weeks. Secondary outcomes include MRI-measured cardiac structure and function, maximal aerobic capacity, resting metabolic rate, device-measured physical activity and sleep, body composition, haemoglobin A1c and cardiovascular risk markers.Ethics and disseminationThe Heath Research Authority (HRA) and the Medicines and Healthcare Products Regulatory Authority (MHRA) Research Ethics Committee have approved the study. The findings of the study will be published in peer-reviewed journals.Trial registration numberISRCTN11459997.EudraCT number2019-004586-41.
Brown rice attenuates iron-induced Parkinson’s disease phenotypes in male wild-type drosophila: insights into antioxidant and iron metabolism modulation
Authors: Yankuzo Hassan Muhammad , Sulaiman Ismail , Muhammad Suleiman Alhaji , Raji Abdullahi Abdullahi , Uthman Yaaqub Abiodun , Imam Mustapha Umar 
Published: November 2024

Parkinson’s disease (PD) is a progressive movement disorder associated with brain iron (Fe) accumulation and free radicals. Brown rice (BR) is antioxidant-rich and has been shown to ameliorate oxidative stress-induced damage. The aim of this study was to investigate the effects of BR compared to white rice (WR) on Fe-induced PD in a fruit fly model. Three-day-old male adult flies were divided into two groups: one on a normal diet and the other on Fe-diet (1 mmol/L) for 10 days to induce PD. After 10 days, the Fe-fed flies were redistributed into four groups: one on normal diet (Fe group), while the others were treated with BR (Fe + BR group), WR (Fe + WR group), or L-3,4-dihydroxyphenylalanine (L-dopa) (Fe + L-dopa group) for 5 days. Similarly, the flies initially on a normal diet were separated into four groups: one on normal diet (Control group), while the others were treated with BR (BR group), WR (WR group), or L-dopa (L-dopa group) for 5 days. Finally, Fe levels, dopamine, malonaldehyde (MDA), and antioxidant enzymes were measured, and the mRNA levels of antioxidant and Fe metabolism genes were assessed. BR significantly improved motor and cognitive functions, decreased fly head MDA and Fe levels, and increased antioxidant enzyme levels in comparison to the Fe and WR groups. Similarly, BR upregulated the mRNA levels of antioxidant genes: catalase, GPx, Nrf2, and DJ-1. The results suggest that BR could potentially reduce morbidities associated with PD possibly due to its bioactive compounds compared to WR.
Evaluation of a CBT‐Based Program for Mental Health in the General Population During the COVID‐19 Pandemic: A Stepped‐Care Approach Using a Chatbot and Digitized Group Intervention
Authors: Langhammer Till , Hilbert Kevin , Wasenmueller Robert , Praxl Berit , Ertle Andrea , Asbrand Julia , Lueken Ulrike 
Published: November 2024

Background: The COVID‐19 pandemic exposed a substantial portion of society to multiple stressors, while access to mental health care was limited. To address this, we introduced a digital stepped‐care program rooted in cognitive–behavioral therapy (CBT) principles, aiming to alleviate mental health distress among the general public seeking help.Methods: The program comprises a 4‐week digital application using “Aury” the chatbot, followed by an optional 6‐week online group session for those still symptomatic. A 4‐week waiting period separated these steps. Participants entered based on self‐identified mental health concerns. Interventions addressed prevalent pandemic mental health issues: sleep disturbances, anxiety, depression, worry/rumination, interpersonal issues, and resource mobilization. Outcomes focused on depressive, anxiety, and somatic symptoms, assessed by the Patient Health Questionnaire (PHQ).Results: Of the 1261 initial participants, postchatbot results (N = 142) indicated small to medium effects (d = 0.412 to d = 0.523). Those finishing the entire program (N = 41) saw substantial symptom decline with medium to large effects (d = 0.757 to d = 0.818). No shifts were seen in the waiting phase. At follow‐up 6 months after baseline, both groups—those who only used the chatbot (N = 60; d = 0.284 to d = 0.416) and those who completed the entire program (N = 27; d = 0.854 to d = 0.926)—showed sustained symptom reduction. Comparing groups that received no intervention, used the chatbot only, and completed the entire program, we observed a dose–response effect.Conclusions: This resource‐efficient and adaptable digital approach effectively reduced pandemic‐induced mental health issues, indicating its potential in crisis periods with limited health resources. Randomized controlled trials are recommended for further validation.Trial Registration: Clinical Trial Registry identifier: DRKS00023220.
Aspergillus Tracheobronchitis With Mediastinal Lymphadenopathy in a Patient With Well‐Controlled HIV Infection
Authors: Singhatiraj Ekachai , Tiengburanatarm Korsin , Pongpirul Krit 
Published: November 2024

Background: Aspergillus tracheobronchitis (AT) is an uncommon yet severe form of invasive pulmonary aspergillosis, with a notably low incidence among individuals living with HIV infection—accounting for merely 4.5% (7 out of 156 cases) in recent reviews. The advent of modern antiretroviral therapy (ART) has significantly altered the landscape of opportunistic infections in HIV, rendering conditions like AT rare in well‐controlled cases.Case Presentation: We present the case of a woman in her mid‐20s with well‐managed HIV infection who experienced a 4‐week history of fever and dyspnea. Diagnostic procedures, including bronchoscopy, revealed granulation tissue obstructing her right main bronchus. Cultures confirmed infection with Aspergillus fumigatus, leading to a diagnosis of AT. Despite initial positive response to voriconazole treatment, the patient developed severe hemoptysis and unfortunately succumbed to the complication.Conclusion: This case underscores the critical need for healthcare providers to consider AT in the differential diagnosis of respiratory symptoms in HIV‐positive patients, even when HIV is well‐controlled with ART. Early recognition and prompt antifungal therapy are essential for improving outcomes. Clinicians should remain vigilant for severe complications like hemoptysis, which can occur despite appropriate therapy. This report highlights the ongoing necessity for vigilance and proactive intervention in the care of individuals living with HIV.
A Potent, Selective, Small-Molecule Inhibitor of DHX9 Abrogates Proliferation of Microsatellite Instable Cancers with Deficient Mismatch Repair
Authors: Castro Jennifer , Daniels Matthew H. , Brennan David , Johnston Brian , Gotur Deepali , Lee Young-Tae , Knockenhauer Kevin E. , Lu Chuang , Wu Jie , Nayak Sunaina , Collins Cindy , Bansal Rishabh , Buker Shane M. , Case April , Liu Julie , Yao Shihua , Sparling Brian A. , Sickmier E. Allen , Silver Serena J. , Blakemore Stephen J. , Boriack-Sjodin P. Ann , Duncan Kenneth W. , Ribich Scott , Copeland Robert A. 
Published: November 2024

Abstract
DHX9 is a multifunctional DExH-box RNA helicase with important roles in the regulation of transcription, translation, and maintenance of genome stability. Elevated expression of DHX9 is evident in multiple cancer types, including colorectal cancer. Microsatellite instable–high (MSI-H) tumors with deficient mismatch repair (dMMR) display a strong dependence on DHX9, making this helicase an attractive target for oncology drug discovery. In this report, we show that DHX9 knockdown increased RNA/DNA secondary structures and replication stress, resulting in cell-cycle arrest and the onset of apoptosis in cancer cells with MSI-H/dMMR. ATX968 was identified as a potent and selective inhibitor of DHX9 helicase activity. Chemical inhibition of DHX9 enzymatic activity elicited similar selective effects on cell proliferation as seen with genetic knockdown. In addition, ATX968 induced robust and durable responses in an MSI-H/dMMR xenograft model but not in a microsatellite stable/proficient MMR model. These preclinical data validate DHX9 as a target for the treatment of patients with MSI-H/dMMR. Additionally, this potent and selective inhibitor of DHX9 provides a valuable tool with which to further explore the effects of inhibition of DHX9 enzymatic activity on the proliferation of cancer cells in vitro and in vivo.
Significance: DHX9 is required in cancer cells with deficient mismatch repair and can be inhibited by ATX968, providing a promising strategy for the development of precision cancer therapeutics.
An Accessible, Browser-Based Gestural Controller for Web Audio, MIDI, and Open Sound Control
Authors: Lim Monica , Kotsani Natalia 
Published: November 2024

Abstract
Handmate is a browser-based hand gestural controller for Web Audio, MIDI, and Open Sound Control (OSC), using open-source pose-estimation technology from Google MediaPipe. The Web browser was chosen as the platform to execute all computational processes so that users could access the latest computer vision technology for music-making without requiring any specialized hardware, software, or technical expertise. By combining preexisting technologies in a browser environment, we enable accessible, interactive sound-making using hand movement. Three controllers are described: (1) Handmate Effects, which receives microphone or user sound input and provides a choice of audio effects that can be controlled by hand movement; (2) Handmate MIDI, which outputs MIDI notes or control values; and (3) Handmate OSC, which outputs OSC messages for users to access hand-movement data in other applications.
Vibrational signals differ between contests and copulatory courtship in the red milkweed beetle Tetraopes tetrophthalmus (Coleoptera: Cerambycidae)
Authors: DeLong Sage A. , Desjonquères Camille , Cirino Lauren A. 
Published: November 2024

Abstract
Substrate-borne vibrational communication is commonly used by herbivorous insects to communicate intraspecific information. This form of communication is underexplored and many discoveries of the form and functional significance of these vibrations have yet to be made. Here, we add red milkweed beetles, Tetraopes tetrophthalmus (Coleoptera: Cerambycidae) to the record of arthropods that communicate with these plant-borne vibrations. Red milkweed beetles, like other cerambycids, commonly use stridulation to produce audible squeaks when in stressful situations and can also produce plant-borne vibrations when in contact with conspecifics. These beetles engage in fights for territory which ultimately results in mating opportunities (i.e., contests). We placed beetles into three sex-ratio treatments: male–male (contests), male–female (copulatory courtship), or male–male–female (contests and copulatory courtship). We first describe contests and copulatory courtship behaviours. We then used laser vibrometry and found that red milkweed beetles communicate by producing plant-borne vibrational signals composed of low-frequency rumbles and high-frequency clacks during male–male contests and copulatory courtship. We compared the spectral and temporal features of the vibrations between the two pre-copulatory contexts. We found that vibrational signals were shorter and had a higher fundamental and dominant frequencies when beetles engaged in contests compared to copulatory courtship behaviours. Our results show that these beetles use plant-borne vibrations as context-dependent signals that communicate different information under these two pre-copulatory scenarios. Our data suggests that these context-dependent signals may help beetles gain access to mates and prolong copulation.
Agrippa’s First Letter in Context (Jos. Vita 365)
Authors: Eilers Claude 
Published: November 2024

Abstract
Josephus quotes a letter of Agrippa II at Vita 365 as proof of the superiority of his account of the Judean revolt as presented in the Bellum Judaicum to that of his rival, Justus of Tiberias. The article considers how Josephus has crafted the argument in preparation for this letter. Some have noted a similarity of language between Agrippa’s letter and Josephus’ preparatory text and raised the question of authenticity. There are, however, also dissimilarities, and this note argues that Josephus has crafted his argument leading to this letter in a way that might lead a reader to misread it as a criticism of Justus.
Carl Anton Martini and Natural Law at the University of Vienna after 1752
Authors: Cerman Ivo 
Published: November 2024

Abstract
Natural law as a discipline was definitively institutionalized at universities in the Habsburg monarchy during the reforms of Maria Theresia after 1752. The guiding principles of these reforms were set in the instruction for the chair of natural law in Vienna which was given to Carl Anton Martini. It was Catholic in conception, but it ordered the professor to draw on Grotius. Our article reconstructs the elementary structure of Martini’s theory of natural law with a focus on his conception of state. The article proves that Martini did not adopt Wolff’s conception of deducing duties and obligations from the highest principle for that would conflict with the Catholic emphasis on freedom of will. Instead of that, Martini derived duties and rights from the three God-given ends. Martini perceived the state as based on social contract, after the model of Christian Wolff. However, it seems that Martini rejected the two-contract model and acknowledged only the contract of submission as binding. Martini sought to hold the middle ground between Machiavellians arguing that the subjects lose all rights after the social contract, and radical ‘monarchomachs’ who believe that the ‘populus’ retains the supreme power. Martini argues that the ruler is limited by natural laws; the subjects retain rights to life and to property, but they are denied any right to resistance. Since Martini derived the monarch’s powers from the unlimited duty to guarantee security, he admitted even encroachments on religious freedom. He admitted coercion in matters that would threaten salus civitatis, but respected the inner libertas conscientiae. He also acknowledged a peculiar division of powers differentiating between a legislative, an inspectorial and an executive power. Even though the aim of this division was not a system of checks and balances, a precise description of the scope of the executive power helped to delimit a sphere of individual freedom.