bluuebunny/crossref_metadata_2025 huggingface dataset:
ATX1 and HUB1/2 promote recruitment of the transcription elongation factor VIP2 to modulate the floral transition in Arabidopsis
Authors: Lu Qianqian , Shi Wenwen , Zhang Fei , Ding Yong
Published: March 2024

Histone 2B ubiquitination (H2Bub) and trimethylation of H3 at lysine 4 (H3K4me3) are associated with transcription activation. However, the function of these modifications in transcription in plants remains largely unknown. Here, we report that coordination of H2Bub and H3K4me3 deposition with the binding of the RNA polymerase‐associated factor VERNALIZATION INDEPENDENCE2 (VIP2) to FLOWERING LOCUS C (FLC) modulates flowering time in Arabidopsis. We found that RING domain protein HISTONE MONOUBIQUITINATION1 (HUB1) and HUB2 (we refer as HUB1/2), which are responsible for H2Bub, interact with ARABIDOPSIS TRITHORAX1 (ATX1), which is required for H3K4me3 deposition, to promote the transcription of FLC and repress the flowering time. The atx1‐2 hub1‐10 hub2‐2 triple mutant in FRIGIDIA (FRI) background displayed early flowering like FRI hub1‐10 hub2‐2 and overexpression of ATX1 failed to rescue the early flowering phenotype of hub1‐10 hub2‐2. Mutations in HUB1 and HUB2 reduced the ATX1 enrichment at FLC, indicating that HUB1 and HUB2 are required for ATX1 recruitment and H3K4me3 deposition at FLC. We also found that the VIP2 directly binds to HUB1, HUB2, and ATX1 and that loss of VIP2 in FRI hub1‐10 hub2‐2 and FRI atx1‐2 plants resulted in early flowering like that observed in FRI vip2‐10. Loss of function of HUB2 and ATX1 impaired VIP2 enrichment at FLC, and reduced the transcription initiation and elongation of FLC. In addition, mutations in VIP2 reduced HUB1 and ATX1 enrichment and H2Bub and H3K4me3 levels at FLC. Together, our findings revealed that HUB1/2, ATX1, and VIP2 coordinately modulate H2Bub and H3K4me3 deposition, FLC transcription, and flowering time.
DEFLECTION AND STRAINS PERFORMANCE OF KENAF FIBRE-REINFORCED CONCRETE BEAMS
Authors: Ayeni Ige Samuel , Jamaludin Yatim Mohamad , Abdul Shukor Lim Nor Hasanah Binti
Published: March 2024

There has been a need to find a lasting means to improve beams' deflection and strain performance without necessarily increasing the beam stirrups. The limitations of steel and other synthetic fibres have reduced their application. Given its tensile strength, renewability, sustainability, and affordability compared to steel and synthetic fibres, kenaf fibre development is of great interest in Malaysia. Therefore, this research work experimentally investigated the deflection and strain performance of Kenaf Fibre Reinforced concrete beams. The volume and length of kenaf fibre used were 0.75% and 25mm, respectively.  Kenaf fibre was treated with 5% NaOH to improve its performance. The alkaline-treated and untreated kenaf fibres morphology was observed under a variable-pressure scanning electron microscope. It was discovered inclusion of kenaf fibre reduced the workability of concrete. Also, plain and KFR concrete morphology was observed under a variable-pressure scanning electron microscope. Four beams were designed to study the deflection and strain performance of the KFR concrete beam; one was well reinforced but without kenaf fibre. The stirrups spacings were increased by 25%, 50%, and 75% for the other three beams.  The beams were tested under centre loading. Deflection and concrete strain at the centre and along the beam span were measured using LVDTs and concrete strain gauges for the four beams. Furthermore, the strains on the shear and bottom flexural reinforcements at the centre of the beam were measured using steel strain gauges. It was discovered that kenaf fibre enhanced the deflection and strain performance of beams between 25% and 50% stirrups deficiency.
GASIFICATION TECHNOLOGY AND ITS FUTURE: A REVIEW
Authors: Rahim Muhammad Roslan , Trisasongko Annisa Palupi , Ab Wahid Mastura , Othman Norazila , Araibi Alaa Salahuddin , Said Mazlan
Published: March 2024

Gasification technology has the potential to revolutionise the energy industry by providing a clean and efficient way to produce energy from a variety of raw materials. This technology have the ability to produce synthesis gas from raw materials based on negative or low carbon values such as high sulphur fuel oil, petroleum coke, coal, domestic wastes, industrial and biomass wastes. The gas produced from the process is used to replace natural gas, to generate electricity, or as a basic raw material to produce chemicals and liquid fuels. Gasification is a process that uses heat, pressure, and steam to convert substances directly into gases, such as carbon monoxide and hydrogen. Gasification technology has differences in various aspects but there are four engineering factors that are the core of the gasification system such as atmospheric gasification reactor (level of oxygen or air content), internal and external heating, reactor design and operating temperature. The raw material used, prepared and introduced in dry form and small particles to the reactor chamber are called gasification. Raw materials experience heat, pressure and an environment rich or low in oxygen content in the gasification. There are three main products from the gasification process which are hydrocarbon gas (also called syngas), hydrocarbon liquid (oil) and coal (carbon black and ash). Syngas can be used as a fuel to produce electricity or steam or as a based material for many types of chemicals. When mixed with air, syngas can be used in petrol or diesel engines as a vehicle fuel with minor modifications to the engine. Gasification technology has several advantages over traditional fossil fuel-based energy production methods. It is able to produce energy from a wide range of raw materials, including waste, which reduces the need for landfills and incineration. Additionally, gasification can reduce greenhouse gas emissions by producing energy from low or negative carbon value raw materials.
NONLINEAR SIMULATIONS TO EVALUATE THE CODE-BASED RESPONSE MODIFICATION FACTOR FOR SEISMIC DESIGN OF SLAB-ON-PILE STRUCTURE
Authors: Darmawan Muhamad Fauzi , Setiawan Angga Fajar , Satyarno Iman , Awaludin Ali
Published: March 2024

Slab on Pile (SOP) structure using concrete spun pile (CSP) is frequently constructed for highway or railway infrastructures in Indonesia. However, some previous studies showed that spun piles have low energy dissipation and ductility. Therefore, spun pile application as bridge piers, particularly in high seismic locations such as Indonesia, needs additional consideration. The response modification factor (R) in the SOP elastic seismic design needs to be carefully considered since this parameter reflects the ability of the structure to dissipate energy through inelastic behavior. The work discussed in this paper primarily concerns the evaluation of the R-value based on the Indonesia seismic bridge design code, SNI 2833-2016, which is applied to SOP seismic design. The study provided an alternative reference for engineers in the seismic design of a SOP structure. Preliminary elastic design of SOP structures demonstrated that the number of piles and structural flexibility is significantly affected by the R-values consideration. In addition, the pinching hysteresis captured from the nonlinear dynamic analysis results emphasized the limited capability of an SOP structure in dissipating energy under seismic excitation. Moreover, the spun pile concrete material, especially in the pile-to-pile head connection, was observed to have an earlier failure. This study strongly suggested using an R-value of 1.5 to achieve a high seismic performance SOP structure with little need for aftershock retrofitting, even though this would necessitate much more spun piles. However, some further research could be conducted to develop the high seismic performance but economical design of SOP structures.
CHEAT DETECTION IN ONLINE EXAMINATIONS USING ARTIFICIAL INTELLIGENCE
Authors: Gopane Santosh , Kotecha Radhika , Obhan Janhavi , Pandey Ritesh Kumar
Published: March 2024

With increasing use of ICT and technical advancements in the education sector, distant and online education as well as examinations are being carried out frequently. However, online examination, as a method of assessment offers the risk of an unmonitored setting where students have full access to external resources. Online-proctored exams are the most efficient way for educational institutions to ensure academic honesty and ethics to counteract this. Typically, proctoring requires human assistance in the form of online proctors who remotely monitor students' performance. Yet, due to the rising demand for personnel and the intrusive nature of human proctoring, it is imperative to explore other areas. To tackle this pressing issue, this research work aims to devise a novel architecture that, through the development of a robust and automated Artificial Intelligence system, enables students to take exams remotely and reduces proctor involvement. The method overcomes the shortcomings of the previous automated proctoring system by combining important components of online exam cheating detection with cost-effective and efficient hardware. By proposing a Hybrid of FaceNet Model, Lucas Kanade Algorithm, and Active Appearance Model for Face Detection and Activity Monitoring of the student, the proposed system extracts semantic indicators to evaluate whether an applicant is cheating in an online examination. The proposed Cheat Detection system's experimental results measured via an F-score of 0.94 demonstrate its efficacy, and promising performance compared to the standard baseline techniques.
HYDRODYNAMIC ASSESSMENT ALONG THE COAST OF TANJUNG SEDELI, MALAYSIA
Authors: Jamal Mohamad Hidayat , Lee Lee Hin , Othman Ilya Khairanis , Anak Benson Yannie , Wong Lavine , Mohamed Rashidi Ahmad Hadi , Abdul Shukor Lim Abd Haslim , Hamzah Saiful Bahri , Pereira Dunstan Anthony , Razali Muhammad Rizal
Published: March 2024

Tidal influence plays a significant role in coastal hydrodynamics as the impact may lead to coastal erosion. Tanjung Sedeli located on the southern coast of Malaysia is exposed to low tidal issues which disrupts the navigation of local fishermen due to the shallow river mouth in the area. This study presents the hydrodynamic processes along the shoreline of Tanjung Sedeli. BLUEKENUE was used as the pre-processor to create a bathymetry file and perform mesh generation to set up the initial model boundary which functions as input files for numerical study. TELEMAC2D further processes the hydrodynamic data (tides and currents), calibrated, and validated with the measured field data collected between 24th September to 6th October 2020 covering both spring and neap tide conditions. The nature of tides in the area was mainly mixed tides, predominantly semidiurnal tides. Modelled hydrodynamic values show good conformity with field measurements with an error of 1.4% for water level values, 10.6% and 20o for current speed and direction respectively. Water flows north into the estuary during spring tide with maximum velocity is 0.756m/s surrounding the river mouth and Pulau Tagal. Low velocity values were recorded at the left bank of the river (0.028 m/s) and Pulau Tagal (0.085 m/s) during spring tide. This study provides information on current hydrodynamic condition of the study area.
A REVIEW OF HYBRIDISED USE OF FIBRES IN SHEAR BEHAVIOUR OF FIBRE-REINFORCED CONCRETE BEAMS
Authors: Ayeni Ige Samuel , Yatim Jamaludin Mohamad , Abdul Shukor Lim Nor Hasanah , Aluko Oluwatobi Gbenga
Published: March 2024

Shear failure of the concrete beam is always disastrous due to unnoticed occurrences and is avoided in construction. Introducing fibres into concrete elements has provided significant shear support to reinforced concrete beam structures through stress redistribution after initial cracking and bridging mechanisms. Given their advantages over single fibre strengthening in past years, using hybrid fibres in an optimal combination as strengthening in cementitious materials has drawn much interest. However, research on this area remains inexhaustible based on the emerging various fibre combinations and the challenge of unnoticed concrete shear failure. Therefore, reviewed research articles on shear performances of Fibre Reinforced Concrete (FRC) beams considering the effect of fibre volume, lengths and orientation on the synergy. The findings reveal the possibility of synergising fibre to enhance reinforced concrete beam(RCB) shear performance for metallic-metallic, metallic-synthetic, synthetic-synthetic, and metallic-biofibre combinations, with varying performance. Using low-strength/modulus fibre with high strength has been effective for shear resistance. Also, beam type (deep/shallow), fibre type and volume fractions, length, aspect ratio, orientation and distribution remarkably affect the shear performance of RC beams.
AN INVESTIGATION ON THE USE OF T’BOLI GOLD TAILINGS FROM MINDANAO STATE UNIVERSITY – ILIGAN INSTITUTE OF TECHNOLOGY (MSU-IIT) GOLD PILOT PLANT AS TOTAL REPLACEMENT OF FINE AGGREGATES IN CEMENT MORTAR
Authors: Oculares Melito S. , Zoleta Joshua B. , C. Armodia Jioms Lee Vern , Goma Jayvee R. , Hingco Vincent C. , Quimno Jessa R. , Wasawas Marielle R. , Itao Gevelyn B. , Sayadi Nadzmi S. , Tolentino Rosavilla S.
Published: March 2024

Gold tailings are waste products produced from the extraction and recovery of gold from its ore. At present, these tailings are in large amounts and are stored in tailings storage facilities, mostly in the form of dams. These gold tailings dams could have serious consequences for the environment and humans if unfortunate events happen. Thus, it is important to utilize these wastes not only to give them value but also to lessen the environmental and human risks they bear. This study investigates the use of gold tailings produced by the Mindanao State University – Iligan Institute of Technology (MSU-IIT) gold pilot plant from the gold ore of T’Boli, South Cotabato, Philippines, as a total replacement of the sand (fine aggregates) component in cement mortar. The chemical compositions of the T’Boli gold tailings were identified using XRF and SEM-EDX analyses. It was found that SiO2, Al2O3, Fe2O3, K2O, and CaO were the major oxide minerals found in the tailings sample. To investigate the effect of the gold tailings on the mechanical property (compressive strength) of the cement mortar, two different formulations of cement and gold tailings (20:80 and 15:85), a controlled formulation with no gold tailings, and two different curing periods (7 and 14 days) were used. The result shows that the formulation of the control sample produces the highest compressive strength of 20.95 MPa at a 14-day curing period. This is followed by the cement mortar in ratios 1:4 and 1:5.7 at a 14-day curing period with a compressive strength of 9.11 MPa and 7.14 MPa, respectively. With these findings, it shows the suitability of T’Boli gold tailings (mining waste) as an alternative to fine aggregates in cement mortar.
AUTOMATION OF PETROLEUM STORAGE TANK LEAKAGE THROUGH PRODUCT TRANSFER CONTROL USING PROGRAMMABLE LOGIC CONTROLLER
Authors: Bongcales Gian Carlo M. , Cabral Charlotte , Chua Alvin
Published: March 2024

Industrial storage tanks have always been a critical part of the petrochemical industry due to their capacity to either act as a buffer to other plant processes or simply to store enormous amounts of fluids for a long period of time in a controlled environment. These petroleum storage tanks are supposedly constructed to follow specific sets of instructions guided by the American Petroleum Industry from the type of material used up to the welding procedure.  But due to inefficient construction, unmaintained and uninspected problems, welding defects, and environmental concerns among others, a leak in a storage tank can occur and will be a major problem as this can cause fire, explosion, and environmental hazards. Additionally, due to tensions between Ukraine and the Russian government and the succeeding Russian ban on oil imports, the cost of 1 barrel of oil rises at an alarming since 2020. With that in mind, an automation procedure is proposed by the researchers, to save as much of this oil from leaking and being unusable and to reduce the causes of further accidents. This paper not only seeks to use an existing tank layout, with currently installed level indicator transmitters, motor-operated control valves, and other equipment, but also to introduce flammable gas detectors that could detect the leaked petroleum on the ground and would initiate the automation procedure. The automation setup was realized by flowcharts, PLC, and ladder logic simulation using Picosoft software. Automation procedures are analyzed wherein the tanks are being filled, the trucks are being loaded, a leaking tank has its contents pumped to another tank, and a leaking tank has its contents pumped to the truck loading station. Results show that a minimum number of 8.89 barrels of oil saved could breakeven the cost of an estimated amount of $80-90 dollars per barrel of oil can be saved by the proposed automation.
IMPACT OF CLIMATE CHANGE ON INUNDATION IN THE KATINGAN TIDAL AGRICULTURAL LOWLAND, CENTRAL KALIMANTAN
Authors: Kamil Insanul , Jayadi Rachmad , Rahardjo Adam Pamudji
Published: March 2024

Uncontrolled tidal overflows inundated Katingan's tidal agricultural lowland. Inundation is worsening due to the impact of climate change. This condition will decrease the productivity of paddy fields. Therefore, a study was conducted with several objectives to obtain the area, water level, and duration of inundation in paddy fields as an impact of climate change and proposed sustainable water management. The methods used are tidal measurements and hydrodynamic analysis using HEC-RAS. The highest tide was at +4.52 m, while the elevation of the paddy fields was only +3.40 m; thus, the paddy fields were inundated during the spring tide. Sea level rise and rainfall increase the area, water level, and duration of inundation. During spring tide, the inundation area is 73.42%, with a duration of inundation of 3.11 days. Under sea level rises of 25 and 50 years, the inundation area increases to 74.41% and 74.86%, while the inundation duration increases to 3.28 and 3.40 days, respectively. Under rainfall with a 5- and 25-year return period, the inundation area reaches 79.19% and 79.21%, while the duration is 3.40 and 3.48 days, respectively. Paddy fields are continuously inundated for over three days at elevations of +3.70–3.80 m. Excessive inundation during prolonged periods decreased rice production. Preventive actions due to climate change are needed to control the inundations. Inundation control can be conducted by gates, canal excavation, embankments, and drain pipes. Meanwhile, integration between government sectors and local communities is needed to support the sustainability of the Katingan tidal agricultural lowlands.
THE EFFECT OF STEEP SLOPES ON THE APPLICATION OF THE USLE, RUSLE, AND MUSLE METHODS
Authors: Romdania Yuda , Herison Ahmad
Published: March 2024

Soil erosion and ecological environmental damage cause environmental and resource problems in the Way Khilau Sub-Sub-Watershed. The purpose of the study was to compare the predictions of the soil erosion rates of the universal soil loss equation (USLE), its revised model (RUSLE), and its modified version (MUSLE). This study comprises several stages; literature review, data collection, and erosion calculations. The erosion calculations were based on 3 methods; THE USLE, RUSLE and MUSLE methods, which were then analyzed for the results of the comparison. The largest erosion values of all the methods on steep slope land (25-45%) were 526.5485 tons/Ha/th with the USLE Method, 585.3 tons/Ha/th with the RUSLE Method, and 13202.38 tons/Ha/th with the MUSLE Method. The lowest erosion values of all methods on sloping slope land (0-8%) were 0.879 tons/Ha/th with the USLE Method, 0.94 tons/Ha/th with the RUSLE Method, and 22.04 tons/Ha/th with the MUSLE Method. The results of the calculations of the average erosion per year in the Way Khilau Sub-Sub-Watershed with the USLE and RUSLE methods fall into the medium category (S), while with the MUSLE Method, it falls into the very heavy category (SB). In conclusion, the USLE and RUSLE soil erosion models had relatively similar results, yet the MUSLE model showed a higher spatial difference in erosion potential than the other models.
Perkembangan dan Proses Sintesis Tamadun Menurut Malek Bennabi (Development and Process of Synthesis of Civilization According to Malek Bennabi)
Authors: Abdul Razak Abdul Qayuum , Ab. Halim Adlina , Ahmad Zaid , Othman Normala
Published: March 2024

Malek bennabi is known as the successor to the ideas and theories of civilization in the 20th century AD after Ibn Khaldun six centuries ago. In the current context, his contribution is seen as significant in the political settings and development, economics, and social development of Muslim communities around the world. In this regard, Bennabi has succeeded in synthesizing important elements in the reconstruction of Islamic civilization. Therefore, this article aims to articulate the development and synthesis process of civilization according to Malek Bennabi. In addition, this article also discusses the idea of his civilizational thought. The methodology used is document analysis as well as historical analysis of documents which related to the scope of Bennabi civilizational thoughts. The process of synthesis of civilization can be understood through three sources namely man, land, and time. These three sources need to be well synthesized through the personal element of man that is triggered through the spirit of religion or ideology and the element of ideas that are embedded in mankind himself. In addition, this process needs to be applied by the Muslim community today because it is relevant to the situation and the development of civilization today.
Kaedah Pentaksiran Bilik Darjah (PBD) dan Kesannya Kepada Murid Tahap Satu: Analisis Subjek Pendidikan Islam/ Classroom Assessment Method (PBD) And Its Impact On Level One Pupils: Analysis Of Islamic Education Subjects
Authors: M. Mustaqim Roslan,
Published: March 2024

Teachers frequently employ testing techniques as an assessment tool. However, in October 2018, the Minister of Education stopped the evaluation using this testing technique. When parents questioned the impartiality of instructors in evaluating their children’s accomplishments, the outcomes of the removing the examination caused negative response. Additionally, they lack clarity and comprehension of the teacher’s methodologies and procedures for evaluation. This article produced to understand the Classroom Assessment Method (PBD) and how it affects level one students studying Islamic Education. The philosophy behind this study is interpretive, while the study strategy is case studies. The study also adapted qualitative design with data collection methods using a combination of document content analysis techniques and semi-structured question interviews. The content analysis approach was used in the data analysis. Thematic methods are used in this study to categorise the results. There are three methods used by teachers in assessing level one students – 1) observation 2) writing and 3) oral methods. However, the assessment using these three methods in determining the level of mastery (TP) of the pupils is very subjective. Thus, two effectswas identified on the application of PBD, namely, the reduced burden of teachers’ duties related to the examination and the occurrence of teacher injustices in the PBD process. In this context, the report recommends that the Ministry of Education’s (MOE) PBD system undergo revisions to ensure that level one students get assessed equitably. Teachers should also employ the scoring rubric while implementing the three established PBD assessment techniques. After further research on other topics, it is also appropriate to revaluate the PBD approach. In addition, the scoring rubric should be used by teachers in the implementation of PBD assessment using three predefined methods.
Extreme values of L$L$‐functions of newforms
Authors: Gun Sanoli , Lunia Rashi
Published: March 2024

In 2008, Soundararajan showed that there exists a normalized Hecke eigenform of weight and level one such that
for sufficiently large . In this note, we show that for any and for all sufficiently large , the number of normalized Hecke eigenforms of weight and level one for which
is . For an odd fundamental discriminant , let be the set of all cuspidal normalized Hecke eigenforms of weight and level dividing . When the real primitive Dirichlet character satisfies , we investigate the number of for which takes extremal values.
Upconversion dual-photosensitizer–expressing bacteria for near-infrared monochromatically excitable synergistic phototherapy
Authors: Chen Mian , Han Qiuju , Zhang Mengmeng , Liu Ying , Wang Lu , Yang Fengmin , Li Qian , Cao Zhenping , Fan Chunhai , Liu Jinyao
Published: March 2024

Synergistic phototherapy stands for superior treatment prospects than a single phototherapeutic modality. However, the combined photosensitizers often suffer from incompatible excitation mode, limited irradiation penetration depth, and lack of specificity. We describe the development of upconversion dual-photosensitizer–expressing bacteria (UDPB) for near-infrared monochromatically excitable combination phototherapy. UDPB are prepared by integrating genetic engineering and surface modification, in which bacteria are encoded to simultaneously express photothermal melanin and phototoxic KillerRed protein and the surface primary amino groups are derived to free thiols for biorthogonal conjugation of upconversion nanoparticles. UDPB exhibit a near-infrared monochromatic irradiation-mediated dual-activation characteristic as the photothermal conversion of melanin can be initiated directly, while the photodynamic effect of KillerRed can be stimulated indirectly by upconverted visible light emission. UDPB also show living features to colonize hypoxic lesion sites and inhibit pathogens via bacterial community competition. In two murine models of solid tumor and skin wound infection, UDPB separately induce robust antitumor response and a rapid wound healing effect.
Unseen overlap between fishing vessels and top predators in the northeast Pacific
Authors: Welch Heather , Clavelle Tyler , White Timothy D. , Cimino Megan A. , Kroodsma David , Hazen Elliott L.
Published: March 2024

Accurate assessments of human-wildlife risk associated with industrial fishing are critical for the conservation of marine top predators. Automatic Identification System (AIS) data provide a means of mapping fishing and estimating human-wildlife risk; however, risk can be obscured by gaps in the AIS record due to technical issues and intentional disabling. We assessed the extent to which unseen fishing vessel activity due to AIS gaps obscured estimates of overlap between fishing vessel activity and 14 marine predators including sharks, tunas, mammals, seabirds, and critically endangered leatherback turtles. Among vessels equipped with AIS in the northeast Pacific, up to 24% of total predator overlap with fishing vessel activity was unseen, and up to 36% was unseen for some individual species. Waters near 10°N had high unseen overlap with sharks yet low reported shark catch, revealing potential discrepancies in self-reported datasets. Accounting for unseen fishing vessel activity illuminates hidden human-wildlife risk, demonstrating challenges and solutions for transparent and sustainable marine fisheries.
Regulation of phase separation and antiviral activity of Cactin by glycolytic enzyme PGK via phosphorylation in
Drosophila
Authors: Chen Dongchao , Shi Chang , Xu Wen , Rong Qiqi , Wu Qingfa
Published: March 2024

Liquid–liquid phase separation (LLPS) plays a crucial role in various biological processes in eukaryotic organisms, including immune responses in mammals. However, the specific function of LLPS in immune responses in
Drosophila melanogaster
remains poorly understood. Cactin, a highly conserved protein in eukaryotes, is involved in a non-canonical signaling pathway associated with Nuclear factor-κB (NF-κB)-related pathways in
Drosophila
. In this study, we investigated the role of Cactin in LLPS and its implications for immune response modulation. We discovered that Cactin undergoes LLPS, forming droplet-like particles, primarily mediated by its intrinsically disordered region (IDR). Utilizing immunoprecipitation and mass spectrometry analysis, we identified two phosphorylation sites at serine residues 99 and 104 within the IDR1 domain of Cactin. Co-immunoprecipitation and mass spectrometry further revealed phosphoglycerate kinase (PGK) as a Cactin-interacting protein responsible for regulating its phosphorylation. Phosphorylation of Cactin by PGK induced a transition from stable aggregates to dynamic liquid droplets, enhancing its ability to interact with other components in the cellular environment. Overexpression of PGK inhibited
Drosophila
C virus (DCV) replication, while PGK knockdown increased replication. DCV infection also increased Cactin phosphorylation. We also found that phosphorylation enhances the antiviral ability of Cactin by promoting liquid-phase droplet formation. These findings demonstrate the role of Cactin-phase separation in regulating DCV replication and highlight the modulation of its antiviral function through phosphorylation, providing insights into the interplay between LLPS and antiviral defense mechanisms.

IMPORTANCE

Liquid–liquid phase separation (LLPS) plays an integral role in various biological processes in eukaryotic organisms. Although several studies have highlighted its crucial role in modulating immune responses in mammals, its function in immune responses in
Drosophila melanogaster
remains poorly understood. Our study investigated the role of Cactin in LLPS and its implications for immune response modulation. We identified that phosphoglycerate kinase (PGK), an essential enzyme in the glycolytic pathway, phosphorylates Cactin, facilitating its transition from a relatively stable aggregated state to a more dynamic liquid droplet phase during the phase separation process. This transformation allows Cactin to rapidly interact with other cellular components, enhancing its antiviral properties and ultimately inhibiting virus replication. These findings expand our understanding of the role of LLPS in the antiviral defense mechanism, shedding light on the intricate mechanisms underlying immune responses in
D. melanogaster
.
The antagonistic transcription factors, EspM and EspN, regulate the ESX-1 secretion system in
M. marinum
Authors: Nicholson Kathleen R. , Cronin Rachel M. , Prest Rebecca J. , Menon Aruna R. , Yang Yuwei , Jennisch Madeleine K. , Champion Matthew M. , Tobin David M. , Champion Patricia A.
Published: March 2024

Bacterial pathogens use protein secretion systems to transport virulence factors and regulate gene expression. Among pathogenic mycobacteria, including
Mycobacterium tuberculosis
and
Mycobacterium marinum
, the ESAT-6 system 1 (ESX-1) secretion is crucial for host interaction. Secretion of protein substrates by the ESX-1 secretion system disrupts phagosomes, allowing mycobacteria cytoplasmic access during macrophage infections. Deletion or mutation of the ESX-1 system attenuates mycobacterial pathogens. Pathogenic mycobacteria respond to the presence or absence of the ESX-1 system in the cytoplasmic membrane by altering transcription. Under laboratory conditions, the EspM repressor and WhiB6 activator control transcription of specific ESX-1-responsive genes, including the ESX-1 substrate genes. However, deleting the
espM
or
whiB6
gene does not phenocopy the deletion of the ESX-1 substrate genes during macrophage infection by
M. marinum
. In this study, we identified EspN, a critical transcription factor whose activity is masked by the EspM repressor under laboratory conditions. In the absence of EspM, EspN activates transcription of
whiB6
and ESX-1 genes during both laboratory growth and macrophage infection. EspN is also independently required for
M. marinum
growth within and cytolysis of macrophages, similar to the ESX-1 genes, and for disease burden in a zebrafish larval model of infection. These findings suggest that EspN and EspM coordinate to counterbalance the regulation of the ESX-1 system and support mycobacterial pathogenesis.

IMPORTANCE

Pathogenic mycobacteria, which are responsible for tuberculosis and other long-term diseases, use the ESX-1 system to transport proteins that control the host response to infection and promote bacterial survival. In this study, we identify an undescribed transcription factor that controls the expression of ESX-1 genes and is required for both macrophage and animal infection. However, this transcription factor is not the primary regulator of ESX-1 genes under standard laboratory conditions. These findings identify a critical transcription factor that likely controls expression of a major virulence pathway during infection, but whose effect is not detectable with standard laboratory strains and growth conditions.
Genome sequences of actinobacteriophages JorRay, Blocker23, Nibbles, and OlgasClover
Authors: Baumgartner Breanna M. , Bono Kayla A. , McIntosh Dawn R. , Vu Anna M. , Adams Chanel F. , Benik Brooklyn C. , Chavez Jessica , Gresky Samantha J. , Sotelo Andres , Ray Jordan I. , Peister Alexandra , Kimberley Kendra W. , McKenna Chelsey C. , Theoret James R. , Yoon Earl J. , Windsor Erin J.
Published: March 2024

JorRay, Blocker23, Nibbles, and OlgasClover are actinobacteriophages belonging to clusters G1, B2, CT, and DJ, respectively. JorRay and Blocker23 were identified in host bacterium

Mycobacterium smegmatis mc
2
155

. Nibbles and OlgasClover were identified in host bacterium
Gordonia rubripertincta
NRRL B-16540.
Evaluation of three protocols for direct susceptibility testing for Gram-negative rods from flagged positive blood culture bottles
Authors: Khan Salman , Das Arghya , Mishra Anwita , Vidyarthi Ashima Jain , Nandal Mukesh , Yadav Himanshu , Roy Shayak , Singh Mahipal
Published: March 2024

Bloodstream infections are associated with high mortality, which can be reduced by targeted antibiotic therapy in the early stages of infection. Direct antibiotic susceptibility testing (AST) from flagged positive blood cultures may facilitate the administration of early effective antimicrobials much before the routine AST. This study aimed to evaluate three different direct AST protocols for Gram-negative rods from flagged positive blood culture broths. Blood culture broths showing Gram-negative rods only were subjected to direct AST by Clinical and Laboratory Standards Institute-recommended direct disk diffusion (protocol A). Additionally, automated AST (protocol B) and Kirby-Bauer disk diffusion (protocol C) were performed with standard inoculum prepared from bacterial pellets obtained by centrifuging blood culture broths in serum separator vials. For comparison, conventional AST of isolates from solid media subculture was also performed with Kirby-Bauer disk diffusion (reference standard) and the automated method. Overall, categorical agreements of protocols A, B, and C were 97.6%, 95.7%, and 95.9%, respectively. Among Enterobacterales, minor error, major error, and very major error rates of protocol B were 3.5%, 0.36%, and 0.43%, respectively, whereas minor error, major error, and very major error rates of protocol C were 3.4%, 0.72%, and 0.21%, respectively, and among non-fermenters, protocol B had a minor error rate of 6.5%, and protocol C had a minor error rate of 4.1% and major error rate of 1.9%. All three direct AST protocols demonstrated excellent categorical agreements with the reference method. Performance of protocols B and C between Enterobacterales and non-fermenters was not statistically different.

IMPORTANCE

Bloodstream infections are associated with high mortality that can be reduced by targeted antibiotic therapy in the early stages of infection. Direct antibiotic susceptibility testing (AST) from flagged positive blood cultures may facilitate the administration of early effective antimicrobials much before the routine AST. Clinical and Laboratory Standards Institute-recommended direct AST can be performed with a limited number of antibiotic disks only. On the other hand, using an automated system for direct AST will not only allow effective laboratory workflow with reduced turnaround time but also provide the minimum inhibitory concentration values of tested antibiotics. However, using expensive automated systems for direct AST may not be feasible for resource-limited laboratories. Therefore, in this study, we aimed to evaluate the CLSI-recommended method and two other direct AST protocols (one with an automated system and the other with disk diffusion) for Gram-negative rods from flagged positive blood cultures.
Integrative metabolomics highlights gut microbiota metabolites as novel NAFLD-related candidate biomarkers in children
Authors: Luo Jiayou , Luo Miyang , Kaminga Atipatsa C. , Wei Jia , Dai Wen , Peng Yunlong , Zhao Kunyan , Duan Yamei , Xiao Xiang , Ouyang SiSi , Yao Zhenzhen , Liu Yixu , Pan Xiongfeng
Published: March 2024

Altered gut microbiota and metabolites are important for non-alcoholic fatty liver disease (NAFLD) in children. We aimed to comprehensively examine the effects of gut metabolites on NAFLD progression. We performed integrative metabolomics (untargeted discovery and targeted validation) analysis of non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), and obesity in children. Fecal samples were collected from 75 subjects in the discovery cohort (25 NAFL, 25 NASH, and 25 obese control children) and 145 subjects in an independent validation cohort (53 NAFL, 39 NASH, and 53 obese control children). Among 2,491 metabolites, untargeted metabolomics revealed a complete NAFLD metabolic map containing 318 increased and 123 decreased metabolites. Then, machine learning selected 65 important metabolites that can distinguish the severity of the NAFLD. Furthermore, precision-targeted metabolomics selected 5 novel gut metabolites from 20 typical metabolites. The functionality of candidate metabolites was validated in hepatocyte cell lines. In the end, this study annotated two novel elevated pathogenic metabolites (dodecanoic acid and creatinine) and a relationship between depleted protective gut microbiota (
Butyricicoccus
and
Alistipes
), increased inflammation (IL-1β), lipid metabolism (TG), and liver function (ALT and AST). This study demonstrates the role of novel gut metabolites (dodecanoic acid and creatinine), as the fatty acid metabolism regulator contributing to NAFLD development through its influence on inflammation and liver function.

IMPORTANCE

Altered gut microbiota and metabolites are a major cause of non-alcoholic fatty liver disease (NAFLD) in children. This study demonstrated a complete gut metabolic map of children with NAFLD, containing 318 increased and 123 decreased metabolites by untargeted metabolomic. Multiple validation approaches (machine learning and targeted metabolomic) selected five novel gut metabolites for targeted metabolomics, which can distinguish NAFLD status and severity. The gut microbiota (
Butyricicoccus
and
Alistipes
) and metabolites (creatinine and dodecanoic acid) were novel biomarkers associated with impaired liver function and inflammation and validated by experiments of hepatocyte cell lines. The data provide a better understanding of the importance of gut microbiota and metabolite alterations in NAFLD, which implies that the altered gut microbiota and metabolites may represent a potential target to prevent NAFLD development.
Middle–Late Jurassic subduction erosion caused by intra-oceanic arc subduction in central Tibet
Authors: Zhang Bo-Chuan , Fan Jian-Jun , Luo An-Bo , Sun Si-Lin , Bai Jia-Wei
Published: March 2024

Subduction erosion is crucial in crustal material recycling. However, subduction erosion caused by intra-oceanic arc subduction has not been sufficiently investigated. In this study, we provide new geological, geochronological, geochemical, and isotopic data from Dongco granodiorites in the central Bangong–Nujiang suture zone of central Tibet to explore subduction erosion caused by intra-oceanic arc subduction. Analysis shows that the ca. 158–155 Ma Dongco granodiorites originated from the subducted oceanic plate, and they were contaminated with accretionary wedge when they intruded the Dongco ophiolite. This suggests that the Dongco ophiolite was emplaced in the subducted accretionary wedge before the Late Jurassic. Based on the intra-oceanic arc affinity and lack of volcanic rocks of Middle Jurassic Dongco ophiolite and other regional data, we believe that the main body of the central intra-oceanic arcs and a portion of the western intra-oceanic arcs in the Meso-Tethys Ocean subducted beneath the southern Qiangtang terrane during the Middle–Late Jurassic. In addition, the different degree absence of the Jurassic accretionary wedge, forearc region, and arc magmatic rocks in the southern Qiangtang terrane indicate that the central and western parts of the southern Qiangtang terrane experienced both vigorous and relatively weak subduction erosion during the Middle–Late Jurassic, respectively. Thus, there is a significant spatiotemporal coupling between subduction erosion of the southern Qiangtang terrane and intra-oceanic arc subduction. Based on these studies and the research on subduction erosion, we suggest that subduction of the main body of the central intra-oceanic arcs and partial subduction of the western intra-oceanic arcs in the Meso-Tethys Ocean caused both vigorous and relatively weak subduction erosion of the southern Qiangtang terrane during the Middle–Late Jurassic, respectively. In addition, the increase in subduction rate also promoted Middle–Late Jurassic subduction erosion of the southern Qiangtang terrane.
An ongoing lithospheric dripping process beneath northeast China and its impact on intraplate volcanism
Authors: Lin Feiyu , Qi Liang , Zhang Nan , Guo Zhen
Published: March 2024

Unique intraplate volcano eruptions and westward volcano migration since the Oligocene have been observed in northeast China, where an overriding continental zone is tectonically controlled by the subduction of the northwestern Pacific plate and the opening of Japan Sea. Interestingly, these intraplate magmatic events occur around a subsiding basin (the Songliao Basin), but no volcanic activity has been observed within the Songliao Basin. The geodynamic mechanism responsible for these volcanoes remains unclear. To address the geodynamic process beneath northeast China, we conducted numerical models constrained by data from regional reconstruction and seismic and volcanic studies. The vertical velocity field of mantle convection and lithospheric partial melting structures derived from our models show that mantle upwelling and melting centers migrate from east to west in northeast China with the westward propagation of the sub-horizontal slab in the transition zone, leading to the observed volcano migration. Also, with the subduction retreat of the northwestern region of the Pacific plate and the opening of the Japan Sea, significant lithospheric thickness differences developed between the Changbaishan-Mudanjiang region and the Songliao Basin, leading to lithospheric unstable dripping. This dripping structure prevents the partial melting of the lithosphere but facilitates the subsidence of the Songliao Basin. Moreover, the lithospheric dripping model successfully predicts upper mantle structures consistent with the proposed tomography model, the observed Moho depth, and surface topography variations. Thus, lithospheric dripping induced by lithospheric thickness differences and the retreating subduction of the Pacific slab provides a robust mechanism for the unique geodynamic processes in northeast China.
Information in summaries of product characteristics about use in children is limited and needs standardisation: a systematic analysis in Switzerland
Authors: Tilen Romy , Berger Christoph , Allemann Samuel , Meyer zu Schwabedissen Henriette
Published: March 2024

Background

A considerable proportion of drugs administered to children are not authorised for this purpose, and consequently off-label use is common in paediatric care. Our aims were to quantify systematically the number of drugs authorised in Switzerland for use in children based on their current summary of product characteristics (SmPC) and to assess the quality of this information.

Methods

We used natural language processing to screen all Swiss SmPCs, available in German language in the open-source drug database, for information about use in children. Based on the SmPCs of the most frequently used drugs in Swiss children’s hospitals, 10 search terms were defined to retrieve this information.

Results

Of the analysed 4214 drugs corresponding to 1553 active substances, 2322 (55.1%) drugs were authorised for use in children. In only 639 (15.2%) SmPCs, information about authorisation for children was found in the section ‘Therapeutic indications’. 320 (13.8%) SmPCs of drugs authorised for use in children contained only verbal age indications such as ‘children’ and ‘adolescents’ without a clear definition of the age or an age range.

Conclusions

Most Swiss SmPCs contain information about children, but only a minority refer to an official indication. Even if some SmPCs clearly indicate that use in children is authorised, a clear statement of the age at which the drug may be administered is missing. Standardisation of information about use in children in SmPCs is needed.
Can critical care transport be safely reduced in children intubated during emergency management of status epilepticus in the United Kingdom: a national audit with case–control analysis
Authors: Knight Philip , Norman Victoria , Gully Rochelle , Wood Dora , Raffaj Dusan , Riddick Laura , Hancock Stephen , Revanna Sanjay , Uvaise Mohammed , Herring Sasha , Worrall Mark , Daye Ashley , Terris Mark , O'Brien Cormac , Kumar Ananth , Scott Sophie , Pritchard Lisa , Palaniappan Srinivasan , Hughes Charlotte , Griksaitis Michael J , Riphagen Shelley , Ramnarayan Padmanabhan
Published: March 2024

Objective

This study describes the baseline clinical characteristics, predictors of successful extubation at referring hospitals and short-term outcomes of children intubated for status epilepticus and referred to United Kingdom (UK) paediatric critical care transport teams (PCCTs).

Design

Multicentre audit with case–control analysis, conducted between 1 September 2018 and 1 September 2020.

Setting

This study involved 10 UK PCCTs.

Patients

Children over 1 month of age intubated during emergency management for status epilepticus (SE), referred to UK PCCTs. Patients with trauma, requiring time-critical neurosurgical intervention or those with a tracheostomy were excluded.

Interventions

No interventions were implemented.

Measurements and main results

Out of the 1622 referrals for SE, 1136 (70%) were intubated at referral. The median age was 3 years (IQR 1.25–6.54 years). Among the intubated children, 396 (34.8%) were extubated locally by the referring team, with 19 (4.8%) requiring reintubation. Therefore, the overall rate of successful extubation was 33% (377/1136). There was significant variation between PCCTs, with local extubation rates ranging from 2% to 74%. Multivariable analyses showed region/PCCT, contributing diagnosis, acute changes on CT, preceding encephalopathy and type of continuous sedation (midazolam) used postintubation were significantly associated with transfer to a critical care unit.

Conclusion

This study highlights wide regional variation in early extubation practices. Regions with high successful extubation rates have established extubation guidelines from PCCTs. Successful extubation represents critical care transports that have been avoided.