bluuebunny/crossref_metadata_2025 huggingface dataset:
Harnessing piezoelectric sensors for electricity generation from speed breaker
Authors: Girde A. A. , Farsole A. A. , Deshmukh H. P. , Umate M. P. , Rai N. A. , Lanjewar S. S. , Bhagat M. S.
Published: November 2024

The population of India is increasing drastically. In 2024, it has reached 140 crores, which leads to more energy consumption. The energy generated from conventional sources is limited and non-renewable. Also, due to urbanization, the energy demand is increased tremendously. So, there is a need to generate energy through renewable sources. One of the effective ways to generate renewable energy is by using piezoelectric cells. Piezoelectric cells are the cells that can generate electric charge through mechanical stress. The mechanical stress is generated on the roads, especially on the road breakers. This mechanical stress is created by vibrations of the vehicles on the speed breaker which will induce electrical energy. By installing piezoelectric cells beneath the speed breaker, the generated mechanical energy can be converted into electrical energy. The generated electricity can be utilized for street lighting, traffic signals, etc. It helps in generating clean and renewable energy from vehicular motion, leading to sustainable development.
Characterization of high-performance composite bricks fabricated from recycled HDPE/PS blends and brick powder
Authors: Moulai Arbi Youcef Seif Eddine , Bentahar Mohammed , Mahmoudi Noureddine
Published: November 2024

This study explores the feasibility and benefits of utilizing plastic waste in the production of construction materials, specifically composite bricks. The escalating accumulation of plastic waste poses significant environmental challenges, which necessitates innovative approaches for recycling and re-utilization to mitigate pollution and reduce landfill use. Our research focuses on the synthesis of bricks by incorporating high-density polyethylene (HDPE) and polystyrene (PS) with sand brick powder, utilizing a compatibilizer (SBS-g-MA) to enhance interfacial adhesion and mechanical integrity. The experimental methodology involved the preparation of composite materials through melt mixing, followed by molding to form brick specimens. These were analyzed for their mechanical properties, including tensile strength, Young’s modulus, and elongation at break, as well as thermal properties such as degradation temperature and crystallization behavior. Results showed that the inclusion of sand brick powder significantly enhances the thermal stability of the composites, as evidenced by the higher degradation temperatures observed. Specifically, the degradation temperature increased from 300.59 °C in pure HDPE/PS blends to 420.39 °C in composites with 7% brick powder, suggesting the formation of a protective barrier against thermal decomposition. Moreover, mechanical testing revealed that composites with up to 7% brick powder exhibited improved tensile strength and Young’s modulus compared to pure polymer blends.
A new method to assess the performance of anti-scatter grids in x-ray projection imaging
Authors: Monnin P
Published: November 2024

Purpose. This work proposes a new method to assess the performance of radiographic anti-scatter grids (ASGs) without the use of a narrow primary beam, which is difficult to achieve. Method. Three general purpose ASGs were evaluated, two marketed ASGs and a low frequency and high ratio prototype ASG with molybdenum lamellae. A range of high scatter x-ray beams were used in a standardized geometry, with energies ranging from 60 kV to 121 kV, for five beam sizes between 10 × 10 and 30 × 30 cm2. The scatter fraction (SF) of each beam was measured in the image plane with and without ASG using the lead beam stop method with an extrapolation function derived from the scatter point spread function (PSF). Results. The primary, scatter and total transmissions of the three ASGs measured for the different x-ray beams allowed the calculation of the grid factor, contrast improvement factor and detective quantum efficiency (DQE) as functions of the input SF. The results obtained for the three ASGs are consistent with those obtained with the standard narrow-beam method and data published in the literature, confirmed the prime importance of the ASG primary transmission and revealed important variations in ASG performance, especially as a function of the input SF and beam size. The break-even input SFs at which the imaging system efficiency was improved by the ASG ranged between 0.18 and 0.52 for the different ASGs and beam characteristics. Significance. The method is proposed as an alternative to current ASG characterization techniques.
Superdiffusive limits beyond the Marcus regime for deterministic fast-slow systems
Authors: Chevyrev Ilya , Korepanov Alexey , Melbourne Ian
Published: November 2024

We consider deterministic fast-slow dynamical systems of the form
\[
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="x Subscript k plus 1 Superscript left-parenthesis n right-parenthesis Baseline equals x Subscript k Superscript left-parenthesis n right-parenthesis Baseline plus n Superscript negative 1 Baseline upper A left-parenthesis x Subscript k Superscript left-parenthesis n right-parenthesis Baseline right-parenthesis plus n Superscript negative 1 slash alpha Baseline upper B left-parenthesis x Subscript k Superscript left-parenthesis n right-parenthesis Baseline right-parenthesis v left-parenthesis y Subscript k Baseline right-parenthesis comma y Subscript k plus 1 Baseline equals upper T y Subscript k Baseline comma">

x

k
+
1

(
n
)

=

x
k

(
n
)

+

n

−
1

A
(

x
k

(
n
)

)
+

n

−
1

/

α

B
(

x
k

(
n
)

)
v
(

y
k

)
,

y

k
+
1

=
T

y
k

,

x_{k+1}^{(n)} = x_k^{(n)} + n^{-1} A(x_k^{(n)}) + n^{-1/\alpha } B(x_k^{(n)}) v(y_k), \quad y_{k+1} = Ty_k,

\]
where

α
∈
(
1
,
2
)

\alpha \in (1,2)

and

x
k

(
n
)

∈

R

m

x_k^{(n)}\in \mathbb {R}^m

. Here,

T
T

is a slowly mixing nonuniformly hyperbolic dynamical system and the process
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="upper W Subscript n Baseline left-parenthesis t right-parenthesis equals n Superscript negative 1 slash alpha Baseline sigma-summation Underscript k equals 1 Overscript left-bracket n t right-bracket Endscripts v left-parenthesis y Subscript k Baseline right-parenthesis">

W
n

(
t
)
=

n

−
1

/

α

∑

k
=
1

[
n
t
]

v
(

y
k

)

W_n(t)=n^{-1/\alpha }\sum _{k=1}^{[nt]}v(y_k)

converges weakly to a

d
d

-dimensional

α
\alpha

-stable Lévy process

L
α

L_\alpha

.

We are interested in convergence of the

m
m

-dimensional process

X
n

(
t
)
=

x

[
n
t
]

(
n
)

X_n(t)= x_{[nt]}^{(n)}

to the solution of a stochastic differential equation (SDE)
\[

d
X
=
A
(
X
)

d
t
+
B
(
X
)

d

L
α

.

dX = A(X)\,dt + B(X)\, dL_\alpha .

\]
In the simplest cases considered in previous work, the limiting SDE has the Marcus interpretation. In particular, the SDE is Marcus if the noise coefficient

B
B

is exact or if the excursions for

W
n

W_n

converge to straight lines as

n
→
∞

n\to \infty

.

Outside these simplest situations, it turns out that typically the Marcus interpretation fails. We develop a general theory that does not rely on exactness or linearity of excursions. To achieve this, it is necessary to consider suitable spaces of “decorated” càdlàg paths and to interpret the limiting decorated SDE. In this way, we are able to cover more complicated examples such as billiards with flat cusps where the limiting SDE is typically non-Marcus for

m
≥
2

m\ge 2

.
Looking to the Past to Inform Future Simulations
Authors: Ostler Terry , Tan Kevin , Wu Chi-Fang
Published: November 2024

Chapter 2 reviews the history of simulations in social work at the University of Illinois Champaign–Urbana (UIUC). Viewed initially as a new modality of learning, master and bachelor of social work (MSW and BSW, respectively) students conducted realistic home visit assessments in a simulation house, followed by collaborative group discussions to reflect on their experiences and feelings. Doctoral (PhD) students increasingly came to take the lead in developing and implementing simulations in practice, policy, and research classes and conducted focus groups and surveys to assess student experiences. Over time, simulations became a way to deepen understanding and thought about social and racial justice, equity, diversity, and inclusion. The simulations contributed to class cohesion. Students and teachers alike became more alive to differences, experiences, and the pain of being human.
Financial and Fiscal Policies
Authors: Reddy Y V , Ray Partha , Chakraborty Pinaki
Published: November 2024

What started as a sub-prime mortgage crisis in the US in 2007 snowballed into global recession soon after. It has turned itself into an economic crisis, if not a sociopolitical one. While the period covering 2014–19 was one of return to the growth trajectory, albeit of the new normal variety, there were various headwinds affecting growth—the US-China trade war, initial confusing signals of Brexit finally culminating in the UK’s exit from the European Union—to name a few. In 2020, the world witnessed the emergence of the COVID-19 pandemic that culminated in a once-in-a-century type of human tragedy and a return to more aggressive fiscal and monetary stimuli. This book looks at the impact of the global crisis on fiscal positions and fiscal implications of the measures undertaken to deal with the situation. The authors explore cross-country experiences with special focus on the euro area economies and India. Analysing the issues relating to the interaction between monetary, fiscal, and financial policies, with emphasis on public debt management, sovereign debt restructuring, taxation, and regulation of the financial sector and sub-national finance, they present the emerging challenges. Recognizing the inter-linkages between monetary, financial, and fiscal policies against the backdrop of the global crisis, this book offers an understanding of possible institutional arrangements for the future.
The Crises and the Global Economy in the Twenty-First Century
Authors: Reddy Y V , Ray Partha , Chakraborty Pinaki
Published: November 2024

This chapter provides a synoptic view of the economic developments of the tumultuous years since 2007 covering crises such as the global financial crisis, euro area crisis, and the pandemic. To begin with, the sub-period 2007–9 saw the emergence of the sub-prime crisis in the US residential mortgage market, leading to the global financial crisis, which finally culminated in the Great Recession of 2009 (when global GDP growth, as well as the growth of both advanced economies and emerging and developing economies (EMDEs), registered a contraction). Countries all across the world have undertaken simultaneously coordinated monetary and fiscal stimulus—more so the bigger countries in G20. Consequently, growth resurfaced during 2010 with a number of countries in developing Asia (led by China) emerging as growth poles. But this resurgence of growth was transitory, uneven, and fragile. And by the end of 2010, it was apparent that the euro area would be affected by a sovereign debt crisis. Admittedly, there are various dimensions of the euro area crisis transmitted through the cross-holding of sovereign debt of the affected countries (such as Greece, Ireland, Italy, Portugal, and Spain; often referred to as GIIPS countries) by the banking sector of the core euro area economies (such as Germany, France, Belgium, or Austria) and erosion of confidence. Finally, apart from probing into the US-China Trade War and its ramifications, it looks into the economic implications of the pandemic and the Russia-Ukraine war.
Sovereign Debt Restructuring
Authors: Reddy Y V , Ray Partha , Chakraborty Pinaki
Published: November 2024

A significant fallout of the global financial crisis is expansion of liquidity facilities for economies in distress, through bilateral currency swaps, multilateral arrangements between central banks, and through IMF. Based on available data and literature, this chapter argues that the prospects for establishing orderly sovereign debt-restructuring mechanisms are very limited. Efforts at enforcing good creditor conduct and good debtor conduct for debt restructuring are bound to fail as long as creditors and debtors are located in different jurisdictions and the governing law of dominant international financial centres favours creditors. Inevitably, these pose issues of fiscal solvency or sovereign debt sustainability and sovereign debt restructuring, all of which have features very distinct from individuals and corporate entities. The conduct of fiscal policy and its constituent part, management of public debt by national authorities in future, is likely to be influenced by developments with regards to liquidity facilities available and mechanisms for debt restructuring.
Sub-national Finance and Crisis
Authors: Reddy Y V , Ray Partha , Chakraborty Pinaki
Published: November 2024

A study of sub-national finance is made difficult by the fact that data is limited, and often either incomplete or outdated. Comparisons are also difficult due to the nature of data. This chapter notes the growing importance of sub-national finance and identifies the recent trends. This is followed by exploration of the effects of the global financial crisis and pandemic on sub-national finance. The policy responses to the impact of the crisis on sub-national finances are also mentioned. The emerging issues in this regard, along with a reference to recent experience, are also discussed in this chapter.
NivobotulinumtoxinA in the Treatment of Glabellar Lines With or Without Concurrent Treatment of Lateral Canthal Lines in Two Phase 3 Clinical Trials
Authors: Coleman William , Bertucci Vince , Humphrey Shannon , Kaufman-Janette Joely , Keaney Terrence , Pariser David , Solish Nowell , Wirta David , Weiss Robert A
Published: November 2024

Background

Botulinum neurotoxins in aesthetic medicine require reconstitution before administration, which may be inconvenient and present errors among injectors.

Objectives

The aim of this study was to evaluate the efficacy and safety of ready-to-use nivobotulinumtoxinA liquid formulation for the treatment of glabellar lines (GL) with or without treatment of lateral canthal lines (LCL).

Methods

Two multicenter, phase 3, double-blind, randomized trials enrolled participants with moderate-to-severe GL (Study 001) or moderate-to-severe GL + LCL (Study 005). Participants received double-blind nivobotulinumtoxinA (20 U) or placebo (Period 1) then ≤2 open-label nivobotulinumtoxinA GL treatments (Period 2) in Study 001 or double-blind nivobotulinumtoxinA 20 U (GL), nivobotulinumtoxinA 44 U (GL + LCL), or placebo (Period 1) then ≤2 double-blind injections of the same treatment (Period 2) in Study 005. The composite primary endpoint was the proportion of participants achieving a ≥2-grade improvement on a facial wrinkle scale at maximum frown on investigator and participant assessment; coprimary endpoints were investigator- and participant-assessed FWS “none or mild” ratings.

Results

At Day 30, significantly higher responder rates were observed for the composite primary endpoint with GL treatment alone (Study 001, 46.1%; Study 005, 45.1%) and GL + LCL (Study 005, 41.3%) vs placebo (0%; all P < .001). Responder rates of “none or mild” by investigator and participant assessment, respectively, were significantly higher for GL treatment alone (Study 001, 77.2% and 65.0%; Study 005, 74.3% and 68.8%) and GL + LCL (Study 005, 74.0% and 61.2%) vs placebo (all P < .001). Adverse events were similar between treatment groups and placebo.

Conclusions

Liquid nivobotulinumtoxinA was effective and well tolerated for treating moderate-to-severe GL alone or with LCL.

Level of Evidence: 1 (Therapeutic)
Dermatopathology
Authors: Teng Yi-Shan , Sun Yng
Published: November 2024

We report a 30-year-old woman with persistent, asymptomatic whitish filiform projections on her soles and toes, which were resistant to conventional treatments.
Gestational and early postnatal protein malnutrition disrupts neurodevelopment in rhesus macaques
Authors: Karpf Joshua A , Sullivan Elinor L , Roberts Victoria H J , Studholme Colin , Roberts Charles T , Kroenke Christopher D
Published: November 2024

Adequate nutrition during gestation is critical for fetal development, and deficits in protein are associated with neurological and behavioral impairments in offspring placing a significant burden on global health. Fetal and neonatal longitudinal magnetic resonance assessments of brain development spanning mid-gestation to 11 months of age were conducted in rhesus macaque (Macaca mulatta) (n = 22; 9 females) generated from an established nonhuman primate model of gestational protein reduction to ascertain the neurodevelopmental effects of reduced maternal protein intake. Structural abnormalities were identified in two reduced diet groups, in addition to age-dependent whole-brain volume deficits in the most severely reduced (50% vs. 33% reduction) protein cohort, primarily restricted to gray matter structures; i.e. cortical/subcortical gray matter and the cerebellum. Diffusion-weighted imaging revealed widespread postnatal reductions in white matter fractional anisotropy, concentrated in the corpus callosum for both reduced protein levels relative to control diet. Despite extensive neurodevelopmental alterations detectable by longitudinal imaging, early behavioral assessments conducted at 1 month revealed minor perturbations. These results highlight differential impacts of reduced maternal and infant protein intake on gray and white matter formation and organization, with potential implications for early motor development.
Efficacy and Safety of Switching to Daily Bictegravir Plus Lenacapavir From a Complex Human Immunodeficiency Virus Treatment Regimen: A Randomized, Open-Label, Multicenter Phase 2 Study (ARTISTRY-1)
Authors: Mounzer Karam , Slim Jihad , Ramgopal Moti , Hedgcock Malcolm , Bloch Mark , Santana Jorge , Mendes Ines , Guo Ying , Arora Priyanka , Montezuma-Rusca Jairo M , Sklar Peter , Baeten Jared M , Segal-Maurer Sorana
Published: November 2024

Background

Complex antiretroviral therapy (ART) regimens, such as those requiring multiple tablets, several doses per day, or both, can negatively affect quality of life and treatment adherence among people with human immunodeficiency virus (HIV).

Methods

ARTISTRY-1 is a phase 2/3, operationally seamless, randomized, open-label, multicenter, active-controlled study (GS-US-621-6289; NCT05502341). Phase 2 of the study enrolled adults with plasma HIV-1 RNA <50 copies/mL receiving a complex ART regimen for ≥6 months. Efficacy and safety outcomes were evaluated after a switch to bictegravir (BIC) (75-mg) + lenacapavir (LEN) (25- or 50-mg) regimens, compared with continuing on a complex ART regimen through 24 weeks.

Results

Overall, 128 participants were assigned randomly to begin BIC 75 mg + LEN 25 mg (n = 51) or BIC 75 mg + LEN 50 mg (n = 52) or continue on their complex ART regimen (n = 25). At week 24, HIV-1 RNA was ≥50 copies/mL in 0 of 51, 1 of 52 (1.9%), and 0 of 25 participants in the 3 groups, respectively. CD4 cell counts and percentages remained stable through week 24; the median change from baseline in CD4 cell count (interquartile range) was 18 (−39 to 70), −16 (−80 to 93), and 42 (−36 to 90) cells/µL, respectively. There were no study discontinuations due to a serious adverse event through week 24. Both BIC + LEN dosing regimens were well tolerated, with similar safety profiles observed between groups.

Conclusions

These data support the continued evaluation of the combination of BIC and LEN to optimize treatment in people with HIV and virologic suppression who are receiving complex ART regimens.
Multiple Displacement Amplification Facilitates SMRT Sequencing of Microscopic Animals and the Genome of the Gastrotrich Lepidodermella squamata (Dujardin 1841)
Authors: Roberts Nickellaus G , Gilmore Michael J , Struck Torsten H , Kocot Kevin M
Published: November 2024

Obtaining adequate DNA for long-read genome sequencing remains a roadblock to producing contiguous genomes from small-bodied organisms, hindering understanding of phylogenetic relationships and genome evolution. Multiple displacement amplification leverages Phi29 DNA polymerase to produce micrograms of DNA from picograms of input. However, multiple displacement amplification's inherent biases in amplification related to guanine and cytosine (GC) content, repeat content and chimera production are a problem for long-read genome assembly, which has been little investigated. We explored the utility of multiple displacement amplification for generating template DNA for High Fidelity (HiFi) sequencing directly from living cells of Caenorhabditis elegans (Nematoda) and Lepidodermella squamata (Gastrotricha) containing one order of magnitude less DNA than required for the PacBio Ultra-Low DNA Input Workflow. High Fidelity sequencing of libraries prepared from multiple displacement amplification products resulted in highly contiguous and complete genomes for both C. elegans (102 Mbp assembly; 336 contigs; N50 = 868 kbp; L50 = 39; BUSCO_nematoda_nucleotide: S:96.1%, D:2.8%) and L. squamata (122 Mbp assembly; 157 contigs; N50 = 3.9 Mbp; L50 = 13; BUSCO_metazoa_nucleotide: S:80.8%, D:2.8%). Coverage uniformity for reads from multiple displacement amplification DNA (Gini Index: 0.14, normalized mean across all 100 kbp blocks: 0.49) and reads from pooled nematode DNA (Gini Index: 0.16, normalized mean across all 100 kbp blocks: 0.49) proved similar. Using this approach, we sequenced the genome of the microscopic invertebrate L. squamata (Gastrotricha), the first of its phylum. Using the newly sequenced genome, we infer Gastrotricha's long-debated phylogenetic position as the sister taxon of Platyhelminthes and conduct a comparative analysis of the Hox cluster.
De novo assembly and characterization of a highly degenerated ZW sex chromosome in the fish Megaleporinus macrocephalus
Authors: Souza-Borges Carolina Heloisa , Utsunomia Ricardo , Varani Alessandro M , Uliano-Silva Marcela , Lira Lieschen Valeria G , Butzge Arno J , Gomez Agudelo John F , Manso Shisley , Freitas Milena V , Ariede Raquel B , Mastrochirico-Filho Vito A , Penaloza Carolina , Barria Agustín , Porto-Foresti Fábio , Foresti Fausto , Hattori Ricardo , Guiguen Yann , Houston Ross D , Hashimoto Diogo Teruo
Published: November 2024

Background

Megaleporinus macrocephalus (piauçu) is a Neotropical fish within Characoidei that presents a well-established heteromorphic ZZ/ZW sex determination system and thus constitutes a good model for studying W and Z chromosomes in fishes. We used PacBio reads and Hi-C to assemble a chromosome-level reference genome for M. macrocephalus. We generated family segregation information to construct a genetic map, pool sequencing of males and females to characterize its sex system, and RNA sequencing to highlight candidate genes of M. macrocephalus sex determination.

Results

The reference genome of M. macrocephalus is 1,282,030,339 bp in length and has a contig and scaffold N50 of 5.0 Mb and 45.03 Mb, respectively. In the sex chromosome, based on patterns of recombination suppression, coverage, FST, and sex-specific SNPs, we distinguished a putative W-specific region that is highly differentiated, a region where Z and W still share some similarities and is undergoing degeneration, and the PAR. The sex chromosome gene repertoire includes genes from the TGF-β family (amhr2, bmp7) and the Wnt/β-catenin pathway (wnt4, wnt7a), some of which are differentially expressed.

Conclusions

The chromosome-level genome of piauçu exhibits high quality, establishing a valuable resource for advancing research within the group. Our discoveries offer insights into the evolutionary dynamics of Z and W sex chromosomes in fish, emphasizing ongoing degenerative processes and indicating complex interactions between Z and W sequences in specific genomic regions. Notably, amhr2 and bmp7 are potential candidate genes for sex determination in M. macrocephalus.
Successful collaborative trials of simple gear modifications to reduce entanglement of whales and other megafauna in Scotland’s static pot (creel) fisheries
Authors: Calderan Susannah , Cisternino Bianca , De Noia Michele , Leaper Russell , MacLennan Ellie , Philp Bally
Published: November 2024

Entanglement in ropes associated with static fishing gear (pots/traps/creels) is a welfare and conservation concern for minke whales (Balaenoptera acutorostrata), humpback whales (Megaptera novaeangliae), basking sharks (Cetorhinus maximus), and other megafauna in Scottish waters. The Scottish Entanglement Alliance estimated that six humpback whales and 30 minke whales become entangled annually. Where entanglement type was known, 83% of minke whales, 50% of humpback whales, and 76% of basking sharks were caught in floating groundlines between pots. We collaborated with fishers on Scotland’s west coast to trial sinking groundline (which lies on the seabed) to assess its practicality. A total of 15 Nephrops (langoustine) and crab fishers re-roped 61 sets of creel gear and fished the gear for ∼15 months, reporting on each haul. Over 1500 hauls were reported; the fishers encountered few problems, in some cases preferring the modified gear. We also deployed depth sensors/accelerometers and filmed a range of sinking and floating rope configurations with a Remotely Operated Vehicle (ROV) to collect data on performance underwater. This project is encouraging, both because of its results—that there may be a simple option to greatly reduce entanglement risk—and because of the successful, bottom-up, partnership approach with Scottish creel fishers.
The relative importance of host phylogeny and dietary convergence in shaping the bacterial communities hosted by several Sonoran Desert Drosophila species
Authors: DuBose James G , Crook Thomas Blake , Matzkin Luciano M , Haselkorn Tamara S
Published: November 2024

Complex eukaryotes vary greatly in the mode and extent that their evolutionary histories have been shaped by the microbial communities that they host. A general understanding of the evolutionary consequences of host–microbe symbioses requires that we understand the relative importance of host phylogenetic divergence and other ecological processes in shaping variation in host-associated microbial communities. To contribute to this understanding, we described the bacterial communities hosted by several Drosophila species native to the Sonoran Desert of North America. Our sampling consisted of four species that span multiple dietary shifts to cactophily, as well as the dietary generalist D. melanogaster, allowing us to partition the influences of host phylogeny and extant ecology. We found that bacterial communities were compositionally indistinguishable when considering incidence only but varied when considering the relative abundances of bacterial taxa. Variation in community composition was not explained by host phylogenetic divergence but could be partially explained by dietary variation. In support of the important role of diet as a source of ecological selection, we found that specialist cactophilic Drosophila deviated more from neutral predictions than dietary generalists. Overall, our findings provide insight into the evolutionary and ecological factors that shape host-associated microbial communities in a natural context.
COCONUT 2.0: a comprehensive overhaul and curation of the collection of open natural products database
Authors: Chandrasekhar Venkata , Rajan Kohulan , Kanakam Sri Ram Sagar , Sharma Nisha , Weißenborn Viktor , Schaub Jonas , Steinbeck Christoph
Published: November 2024

The COCONUT (COlleCtion of Open Natural prodUcTs) database was launched in 2021 as an aggregation of openly available natural product datasets and has been one of the biggest open natural product databases since. Apart from the chemical structures of natural products, COCONUT contains information about names and synonyms, species and organism parts in which the natural product has been found, geographic information about where the respective sample has been collected and literature references, where available. COCONUT is openly accessible at https://coconut.naturalproducts.net. Users can search textual information and perform structure, substructure, and similarity searches. The data in COCONUT are available for bulk download as SDF, CSV and a database dump. The web application for accessing the data is open-source. Here, we describe COCONUT 2.0, for which the web application has been completely rewritten, and the data have been newly assembled and extensively curated. New features include data submissions by users and community curation facilitated in various ways.
Phosphorylation-mediated disassembly of C-terminal binding protein 2 tetramer impedes epigenetic silencing of pluripotency in mouse embryonic stem cells
Authors: Lee Han-Teo , Kim Young Ah , Lee Sangho , Jung Ye-Eun , Kim Hanbyeol , Kim Tae Wan , Kwak Sojung , Kim Jaehyeon , Lee Chul-Hwan , Cha Sun-Shin , Choi Jinmi , Cho Eun-Jung , Youn Hong-Duk
Published: November 2024

Cells need to overcome both intrinsic and extrinsic threats. Although pluripotency is associated with damage responses, how stem cells respond to DNA damage remains controversial. Here, we elucidate that DNA damage activates Chk2, leading to the phosphorylation of serine 164 on C-terminal binding protein 2 (Ctbp2). The phosphorylation of Ctbp2 induces the disruption of Ctbp2 tetramer, weakening interactions with zinc finger proteins, leading to the dissociation of phosphorylated Ctbp2 from chromatin. This transition to a monomeric state results in the separation of histone deacetylase 1 from Ctbp2, consequently slowing the rate of H3K27 deacetylation. In contrast to the nucleosome remodeling and deacetylase complex, phosphorylated Ctbp2 increased binding affinity to polycomb repressive complex (PRC)2, interacting through the N-terminal domain of Suz12. Through this domain, Ctbp2 competes with Jarid2, inhibiting the function of PRC2. Thus, the phosphorylation of Ctbp2 under stress conditions represents a precise mechanism aimed at preserving stemness traits by inhibiting permanent transcriptional shutdown.
The Natural Products Atlas 3.0: extending the database of microbially derived natural products
Authors: Poynton Ella F , van Santen Jeffrey A , Pin Matthew , Contreras Marla Macias , McMann Emily , Parra Jonathan , Showalter Brandon , Zaroubi Liana , Duncan Katherine R , Linington Roger G
Published: November 2024

The Natural Products Atlas is a database of microbially derived natural products that contains structures, producing organism taxonomy, biosynthetic and chemical ontology classifications, grouping by compound classes and cross-links to a suite of other natural product-related data resources. The database is supported by a web server that includes functionality to browse the collection, search the database using both chemical structures and text/numerical terms and visualize the chemical diversity it contains using interactive dashboards. In the current database release, we have curated 1347 papers, increasing the number of compounds to 36 545. In addition, we have initiated a large-scale effort to incorporate data from papers reporting structural reassignments and revisions to previously published structures. This effort led to the incorporation of 590 corrections to existing entries, significantly improving the accuracy of the dataset. The Natural Products Atlas may be accessed at www.npatlas.org.
STK39-mediated amplification of γ-H2A.X promotes homologous recombination and contributes to PARP inhibitor resistance
Authors: Xu Yi , Li Changying , Yin Huan , Nowsheen Somaira , Xu Xin , Kang Wenjuan , Liu Xin , Chen Lifeng , Lou Zhenkun , Yi Junlin , Deng Min
Published: November 2024

The phosphorylation of histone H2A.X into γH2A.X is a crucial early event in the DNA damage response, marking DNA damage sites and initiating repair processes. While ATM kinase is traditionally recognized as the primary mediator of H2A.X phosphorylation, our study identifies serine/threonine kinase 39 (STK39) as a novel enhancer of this critical signaling pathway. We demonstrate that after DNA damage, STK39 undergoes phosphorylation by the ATM kinase, facilitating its interaction with the Mre11-Rad50-Nbs1 complex and subsequent recruitment to chromatin. This recruitment enables STK39 to further phosphorylate H2A.X, thus amplifying γH2A.X production and promoting homologous recombination repair. Notably, we observe a significant upregulation of STK39 in pancreatic adenocarcinoma (PAAD) tissues, correlating with heightened resistance to PARPi therapy. Furthermore, we demonstrate the synergistic efficacy of combining STK39 inhibition with PARP inhibitors in suppressing and reversing PAAD growth. This study not only provides new insights into the molecular dynamics of H2A.X phosphorylation but also highlights the therapeutic potential of targeting STK39 to enhance PARPi sensitivity in PAAD (created with BioRender).
Circular oligomeric particles formed by Ros/MucR family members mediate DNA organization in α-proteobacteria
Authors: Chaves-Sanjuan Antonio , D’Abrosca Gianluca , Russo Veronica , van Erp Bert , Del Cont-Bernard Alessandro , Capelli Riccardo , Pirone Luciano , Slapakova Martina , Sgambati Domenico , Fattorusso Roberto , Isernia Carla , Russo Luigi , Barton Ian S , Roop Roy Martin , Pedone Emilia M , Bolognesi Martino , Dame Remus T , Pedone Paolo V , Nardini Marco , Malgieri Gaetano , Baglivo Ilaria
Published: November 2024

The transcriptional regulator MucR from Brucella species controls the expression of many genes, including those involved in virulence, by binding AT-rich DNA regions. MucR and its homologs belong to the Ros/MucR family, whose members occur in α-proteobacteria. MucR is a recent addition to the family of histone-like nucleoid structuring (H-NS) proteins. Indeed, despite the lack of sequence homology, MucR bears many functional similarities with H-NS and H-NS-like proteins, structuring the bacterial genome and acting as global regulators of transcription. Here we present an integrated cryogenic electron microscopy (cryo-EM), nuclear magnetic resonance, modeling and biochemical study shedding light on the functional architecture of MucR from Brucella abortus and its homolog Ml5 from Mesorhizobium loti. We show that MucR and Ml5 fold in a circular quaternary assembly, which allows it to bridge and condense DNA by binding AT-rich sequences. Our results show that Ros/MucR family members are a novel type of H-NS-like proteins and, based on previous studies, provide a model connecting nucleoid structure and transcription regulation in α-proteobacteria.
Chemotherapeutic agents and leucine deprivation induce codon-biased aberrant protein production in cancer
Authors: Kochavi Adva , Nagel Remco , Körner Pierre-Rene , Bleijerveld Onno B , Lin Chun-Pu , Huinen Zowi , Malka Yuval , Proost Natalie , van de Ven Marieke , Feng Xiaodong , Navarro Jasmine Montenegro , Pataskar Abhijeet , Peeper Daniel S , Champagne Julien , Agami Reuven
Published: November 2024

Messenger RNA (mRNA) translation is a tightly controlled process frequently deregulated in cancer. Key to this deregulation are transfer RNAs (tRNAs), whose expression, processing and post-transcriptional modifications are often altered in cancer to support cellular transformation. In conditions of limiting levels of amino acids, this deregulated control of protein synthesis leads to aberrant protein production in the form of ribosomal frameshifting or misincorporation of non-cognate amino acids. Here, we studied leucine, an essential amino acid coded by six different codons. Surprisingly, we found that leucine deprivation leads to ribosomal stalling and aberrant protein production in various cancer cell types, predominantly at one codon, UUA. Similar effects were observed after treatment with chemotherapeutic agents, implying a shared mechanism controlling the downstream effects on mRNA translation. In both conditions, a limitation in the availability of tRNALeu(UAA) for protein production was shown to be the cause for this dominant effect on UUA codons. The induced aberrant proteins can be processed and immune-presented as neoepitopes and can direct T-cell killing. Altogether, we uncovered a novel mode of interplay between DNA damage, regulation of tRNA availability for mRNA translation and aberrant protein production in cancer that could be exploited for anti-cancer therapy.
High-throughput capture of transcription factor-driven epigenome dynamics using PHILO ChIP-seq
Authors: Choudhary Aanchal , Ammari Moonia , Yoon Hyuk Sung , Zander Mark
Published: November 2024

Assessing the dynamics of chromatin features and transcription factor (TF) binding at scale remains a significant challenge in plants. Here, we present PHILO (Plant HIgh-throughput LOw input) ChIP-seq, a high-throughput ChIP-seq platform that enables the cost-effective and extensive capture of TF binding and genome-wide distributions of histone modifications. The PHILO ChIP-seq pipeline is adaptable to many plant species, requires very little starting material (1mg), and provides the option to use MNase (micrococcal nuclease) for chromatin fragmentation. By employing H3K9ac PHILO ChIP-seq on eight Arabidopsis thaliana jasmonic acid (JA) pathway mutants, with the simultaneous processing of over 100 samples, we not only recapitulated but also expanded the current understanding of the intricate interplay between the master TFs MYC2/3/4 and various chromatin regulators. Additionally, our analyses brought to light previously unknown histone acetylation patterns within the regulatory regions of MYC2 target genes in Arabidopsis, which is also conserved in tomato (Solanum lycopersicum). In summary, our PHILO ChIP-seq platform demonstrates its high effectiveness in investigating TF binding and chromatin dynamics on a large scale in plants, paving the way for the cost-efficient realization of complex experimental setups.
Implications of sociodemographic and clinical factors on symptom burden: Age-specific survivorship care in the primary central nervous system tumor population
Authors: Robins Kimberly R , Kunst Tricia , Reyes Jennifer , Acquaye-Mallory Alvina , Grajkowska Ewa , Ozer Byram H , Penas-Prado Marta , Wu Jing , Burton Eric , Boris Lisa , Panzer Marissa , Pillai Tina , Polskin Lily , Gilbert Mark R , Vera Elizabeth , Armstrong Terri S
Published: November 2024

Background

This analysis aims to provide insight into differences in symptom burden and general health status between young adults (YA; 18–39 years old) and older adults (OA; ≥40 years old) with primary central nervous system tumors.

Methods

Data were retrospectively analyzed from the National Cancer Institute Neuro-Oncology Branch’s Natural History Study (NCT02851706 PI: T.S. Armstrong) to determine differences in patient-reported outcomes (general health status [EQ-5D-3L], symptom burden [MDASI-BT and MDASI-SP], anxiety/depression [Patient-Reported Outcomes Measurement Information System], and perceived cognition [Neuro-QOL]) and demographic and clinical data using chi-square, one-way ANOVA, and Student’s t-tests. Linear regression with backward elimination determined which characteristics impacted perceived symptom burden and general health status.

Results

The sample included 271 YA (82% with a primary brain tumor (PBT); median age 31 [range, 18–39]) and 516 OA (88% with a PBT; median age 54 [range, 40–85]). YA were more likely to be single (P < .001), employed (P < .001), and make < $50 000 per year (P = .014). More YA reported pain (P = .008), nausea (P < .001), drowsiness (P = .043), and vomiting (P = .001) than OA. Among demographic and clinical characteristics, when controlling for age, Karnofsky Performance Scale score (P < .001) and employment status (P < .001) were predictors of symptom interference, activity- and mood-related interference in patients with PBTs. Compared to OA with spinal tumors, YA reported more moderate-severe anxiety (P = .050) and moderate-severe perceived cognitive deficits (P = .023).

Conclusions

Significant differences in characteristics and symptom burden exist between YA and OA. Developmentally tailored survivorship programs providing additional psychosocial support and resources to address symptom presentation in YA are needed.
Effectiveness of the 2023–2024 Omicron XBB.1.5-containing mRNA COVID-19 Vaccine (mRNA-1273.815) in Preventing COVID-19–related Hospitalizations and Medical Encounters Among Adults in the United States
Authors: Kopel Hagit , Araujo Andre B , Bogdanov Alina , Zeng Ni , Winer Isabelle , Winer-Jones Jessamine P , Lu Tianyi , Marks Morgan A , Bonafede Machaon , Nguyen Van Hung , Martin David , Mansi James A
Published: November 2024

Background

This study aimed to evaluate the vaccine effectiveness (VE) of mRNA-1273.815, a 2023–2024 Omicron XBB.1.5-containing mRNA COVID-19 vaccine, at preventing COVID-19–related hospitalizations and any medically attended COVID-19 in adults.

Methods

In a linked electronic health record–claims dataset, we identified US adults (≥18 years) who received the mRNA-1273.815 vaccine (exposed cohort) between 12 September and 15 December 2023, matched 1:1 to individuals who did not receive a 2023–2024 updated COVID-19 vaccine (unexposed cohort). Cohorts were balanced using inverse probability of treatment weighting on demographics, vaccination and infection history, and underlying medical conditions. Study cohorts were followed until 31 December 2023 for COVID-19–related hospitalizations and medically attended COVID-19. Cox regression was used to estimate hazard ratios and VE. Subgroup analyses were performed for adults ≥50 years, adults ≥65 years, and individuals with underlying medical conditions.

Results

Overall, 859 335 matched pairs of mRNA-1273.815 recipients and unexposed adults were identified. The mean (standard deviation) age was 63 (16) years. More than 60% of individuals in both cohorts had an underlying medical condition. Among the overall adult population, VE was 60.2% (95% confidence interval, 53.4–66.0) against COVID-19–related hospitalization and 33.1% (30.2–35.9) against medically attended COVID-19 over a median follow-up of 63 (interquartile range: 44–78) days. VE estimates by age and underlying medical conditions were similar.

Conclusions

These results demonstrate the significant protection provided by mRNA-1273.815 against COVID-19–related hospitalizations and any medically attended COVID-19 in adults, regardless of vaccination history, and support Centers for Disease Control and Prevention recommendations to stay up-to-date with COVID-19 vaccination to prevent COVID-19–related outcomes, including hospitalizations.
Maize unstable factor for orange1 encodes a nuclear protein that affects redox accumulation during kernel development
Authors: Chatterjee Debamalya , Zhang Ziru , Lin Pei-Yu , Wang Po-Hao , Sidhu Gurpreet K , Yennawar Neela H , Hsieh Jo-Wei Allison , Chen Pao-Yang , Song Rentao , Meyers Blake C , Chopra Surinder
Published: November 2024

The basal endosperm transfer layer (BETL) of the maize (Zea mays L.) kernel is composed of transfer cells for nutrient transport to nourish the developing kernel. To understand the spatiotemporal processes required for BETL development, we characterized 2 unstable factor for orange1 (Zmufo1) mutant alleles. The BETL defects in these mutants were associated with high levels of reactive oxygen species, oxidative DNA damage, and cell death. Interestingly, antioxidant supplementation in in vitro cultured kernels alleviated the cellular defects in mutants. Transcriptome analysis of the loss-of-function Zmufo1 allele showed differential expression of tricarboxylic acid cycle, redox homeostasis, and BETL-related genes. The basal endosperms of the mutant alleles had high levels of acetyl-CoA and elevated histone acetyltransferase activity. The BETL cell nuclei showed reduced electron-dense regions, indicating sparse heterochromatin distribution in the mutants compared with wild-type. Zmufo1 overexpression further reduced histone methylation marks in the enhancer and gene body regions of the pericarp color1 (Zmp1) reporter gene. Zmufo1 encodes an intrinsically disordered nuclear protein with very low sequence similarity to known proteins. Yeast two-hybrid and luciferase complementation assays established that ZmUFO1 interacts with proteins that play a role in chromatin remodeling, nuclear transport, and transcriptional regulation. This study establishes the critical function of Zmufo1 during basal endosperm development in maize kernels.
WD40 protein OsTTG1 promotes anthocyanin accumulation and CBF transcription factor-dependent pathways for rice cold tolerance
Authors: Zhu Chenli , Yang Xinghai , Chen Weiwei , Xia Xiuzhong , Zhang Zhongqiong , Qing Dongjin , Nong Baoxuan , Li Jingcheng , Liang Shuhui , Luo Shuangshuang , Zhou Weiyong , Yan Yong , Dai Gaoxing , Li Danting , Deng Guofu
Published: November 2024

Temperature is a critical abiotic factor affecting rice (Oryza sativa L.) yields, and cold stress at the seedling stage can inhibit plant growth or even be fatal. Antioxidants such as anthocyanins accumulate in a variety of plants during cold stress, but the underlying mechanisms are not well understood. Here, we report that rice TRANSPARENT TESTA GLABRA 1 (OsTTG1), a major regulator of anthocyanin biosynthesis in rice, responds to short- and long-term cold stress at both the transcriptional and protein levels. Metabolomic and transcriptomic data indicate that OsTTG1 activates the expression of anthocyanidin synthase (OsANS) genes under cold stress. Our data also suggest that OsTTG1 forms a MYB–bHLH–WD (MBW) complex with Basic helix-loop-helix 148 (OsbHLH148) and Myb-related S3 (OsMYBS3), and this complex activates the expression of Dehydration-responsive element-binding protein 1 (OsDREB1) and OsANS genes. Together, our findings reveal the mechanisms by which OsTTG1 coordinates both anthocyanin biosynthesis and the expression of cold-responsive genes in colored rice, providing genetic resources for future cold resistance breeding in rice.
Sources of bias in studies reporting birth prevalence of congenital anomalies: a scoping review and reporting checklist
Authors: Dharmarajan Sumedha , Bhide Prajkta , Kar Anita
Published: November 2024

Background

Data on the birth prevalence of congenital anomalies in low- and middle-income countries report wide variations in prevalence estimates. We conducted a scoping review to identify the sources of bias in studies reporting birth prevalence of congenital anomalies in World Health Organization South-East Asia region (SEAR) countries.

Methods

PubMed and Google Scholar databases were screened for relevant literature. Data on study characteristics and sources of bias was extracted. A narrative synthesis of the data is reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. A checklist for reporting studies on birth prevalence of congenital anomalies (CD-Checklist) was developed.

Results

The literature search retrieved 47 articles. Birth prevalence varied from 0.21% to 9.68%. Sampling bias was evident as studies were single hospital studies, lacked relevant description of sample, did not justify sample size or describe the process of sampling. Information bias was identified as studies did not mention classification system used, and failed to clearly distinguish between number of malformations and babies with malformations. Observer and reporting bias were noted.

Conclusions

Several sources of bias introduce variations in birth prevalence reports of congenital anomalies in SEAR countries. A checklist (CD-Checklist) has been suggested which can guide investigators to minimize the risk of bias in studies.