bluuebunny/crossref_metadata_2025_split huggingface dataset:
Growth-phase-dependent control of rRNA synthesis in
Saccharomyces cerevisiae
Authors: Mendes Felgueira Catarina A. , Schneider David A. 
Published: October 2024

ABSTRACT

Saccharomyces cerevisiae
is one of the most well-studied model organisms used in the scientific community. Its ease of manipulation, accessible growth conditions, short life cycle, and conserved eukaryotic metabolic pathways make it a useful model organism. Consequently, yeast has been used to investigate a myriad of phenomena, from microbial to human studies. Most of the research performed using this model organism utilizes yeast cell populations when they are growing exponentially, a growth phase aptly termed exponential or log phase. However, log phase encompasses several yeast generations and ranges several hours of yeast growth, meaning that there is a potential for variability during this “homogenous” growth phase. Cells in log phase require robust ribosome biogenesis to support their rapid growth and cell division. Interestingly, during log phase, ribosomal RNA (rRNA) synthesis (which is the first and rate limiting step in ribosome biosynthesis) has been shown to decrease prior to growth rate decline in stationary phase. In this study, we utilized several genomic and biochemical methods to elucidate the relationship between subphases of log phase and rRNA synthesis. Our results indicate that as yeast cells progress through subphases of log growth, both polymerase I transcription and rRNA processing are repressed. Overall, this study establishes a growth-phase-dependent control of rRNA synthesis that unexpectedly begins prior to the switch to stationary phase (i.e., pre-diauxic shift) as a putative mechanism of anticipating nutrient starvation.

IMPORTANCE

Saccharomyces cerevisiae
is a ubiquitously used model organism in a wide range of scientific research fields. The conventional practice when performing yeast studies is to investigate its properties during logarithmic growth phase. This growth phase is defined as the period during which the cell population doubles at regular intervals, and nutrients are not limiting. However, this growth phase lasts hours and encompasses several yeast cell generations which consequently introduce heterogeneity to log growth phase depending on their time of harvest. This study reveals significant changes in the transcriptomic landscape even in early stages of exponential growth. The overall significance of this work is the revelation that even the seemingly homogenous log growth phase is far more diverse than was previously believed.
Discovery of benzo[c]phenanthridine derivatives with potent activity against multidrug-resistant
Mycobacterium tuberculosis
Authors: Liang Yi Chu , Sun Zhiqi , Lu Chen , Lupien Andréanne , Xu Zhongliang , Berton Stefania , Xu Peng , Behr Marcel A. , Yang Weibo , Sun Jim 
Published: October 2024

ABSTRACT

Mycobacterium tuberculosis
(Mtb), the pathogen responsible for tuberculosis (TB), is the leading cause of bacterial disease-related death worldwide. Current antibiotic regimens for the treatment of TB remain dated and suffer from long treatment times as well as the development of drug resistance. As such, the search for novel chemical modalities that have selective or potent anti-Mtb properties remains an urgent priority, particularly against multidrug-resistant (MDR) Mtb strains. Herein, we design and synthesize 35 novel
b
enzo[c]
p
henanthridine
d
erivatives (BPDs). The two most potent compounds, BPD-6 and BPD-9, accumulated within the bacterial cell and exhibited strong inhibitory activity (MIC
90
~2 to 10 µM) against multiple
Mycobacterium
strains while remaining inactive against a range of other Gram-negative and Gram-positive bacteria. BPD-6 and BPD-9 were also effective in reducing Mtb survival within infected macrophages, and BPD-9 reduced the burden of
Mycobacterium bovis
BCG in the lungs of infected mice. The two BPD compounds displayed comparable efficacy to rifampicin (RIF) against non-replicating Mtb (NR-Mtb). Importantly, BPD-6 and BPD-9 inhibited the growth of multiple MDR Mtb clinical isolates. Generation of BPD-9-resistant mutants identified the involvement of the Mmr efflux pump as an indirect resistance mechanism. The unique specificity of BPDs to
Mycobacterium
spp. and their efficacy against MDR Mtb isolates suggest a potential novel mechanism of action. The discovery of BPDs provides novel chemical scaffolds for anti-TB drug discovery.

IMPORTANCE

The emergence of drug-resistant tuberculosis (TB) is a serious global health threat. There remains an urgent need to discover new antibiotics with unique mechanisms of action that are effective against drug-resistant
Mycobacterium tuberculosis
(Mtb). This study shows that novel semi-synthetic compounds can be derived from natural compounds to produce potent activity against Mtb. Importantly, the identified compounds have narrow spectrum activity against
Mycobacterium
species, including clinical multidrug-resistant (MDR) strains, are effective in infected macrophages and against non-replicating Mtb (NR-Mtb), and show anti-mycobacterial activity in mice. These new compounds provide promising chemical scaffolds to develop potent anti-Mtb drugs of the future.
Trench-parallel mid-ocean ridge subduction driven by along-strike transmission of slab pull
Authors: Cui Qihua , Li Zhong-Hai 
Published: October 2024

Abstract
Trench-parallel mid-ocean ridge (MOR) subduction is observed and/or predicted on the present Earth and during geological history. Slab break-off normally occurs after such a MOR subduction, leading to an absence of local slab pull. The driving force of such MOR subduction is a puzzling issue. We realize that the MOR is generally dislocated by transform faults, which means that the MOR does not enter the trench simultaneously along strike. In this case, the slab pull does not vanish simultaneously along the entire subduction zone. Consequently, the trench-parallel MOR subduction may be driven by along-strike transmission of neighboring slab pull. We tested this idea using a series of 3-D, high-resolution numerical models. The results indicate that the transform fault (TF) and fracture zone (FZ) should not be too weak in order for the lateral transmission of slab pull. Such rheological strength of a TF/FZ is consistent with observation-based inferences and rheological analyses. In addition, the thermal structure and strength of oceanic plates neighboring the MOR also affect the MOR subduction: faster spreading MOR in a younger plate leads to easier subduction. Based on the model results and geological constraints, we propose a self-driven MOR subduction model, which highlights the role of along-strike transmission of slab pull during diachronic entry of MOR into the trench.
Early Pleistocene glacier ice preserved in permafrost in the eastern Canadian Arctic
Authors: Coulombe Stéphanie , Fortier D. , Lacelle D. , St-Onge G. , Guertin-Pasquier A. 
Published: October 2024

Abstract
Extensive amounts of glacier ice can be buried and preserved in the permafrost for thousands to millions of years under favorable conditions. Here, we combine sedimentological, cryostratigraphic, and geochemical techniques together with radiocarbon and paleomagnetic dating to show that relict early Pleistocene glacier ice was preserved in the permafrost on Bylot Island (Nunavut). The buried glacial ice sits on top of a 2.8–2.4 Ma fossil forest deposit, and the glacio-fluvial sediments overlying the ice has normal-reversed-normal magnetic polarities, suggesting that the ice was in place since at least 0.773 Ma. As such, this represents the oldest glacier ice preserved in Arctic permafrost landscapes and the earliest evidence of a Pleistocene glaciation in the eastern Canadian Arctic. The findings highlight the resiliency of ice-rich permafrost to degradation; however, the ongoing climate warming and/or recent geomorphic disturbances have now exposed the early Pleistocene age buried glacial ice to melting.
XY-VBS phase boundary for the square-lattice $$J_1$$-$$J_2$$ XXZ model with the ring exchange
Authors: Nishiyama Yoshihiro 
Published: October 2024

Abstract
The square-lattice $$J_1$$

J
1

-$$J_2$$

J
2

XXZ model with the ring-exchange interaction K was investigated numerically. As for the hard-core-boson model with the nearest-neighbor hopping $$J_1/2$$

J
1

/
2

, namely, the $$J_1$$

J
1

-KXY model, it has been reported that the ring exchange leads to a variety of exotic phases such as the valence-bond-solid (VBS) phase. In this paper, we extend the parameter space to investigate the phase boundary between the XY (superfluid) and VBS phases. A notable feature is that the phase boundary terminates at the fully frustrated point, $$J_2/J_1 \rightarrow 0.5^-$$

J
2

/

J
1

→
0
.

5
-

. As a scaling parameter for the multi-criticality, the distance from the multi-critical point $$\delta (\ge 0)$$

δ
(
≥
0
)

is introduced. To detect the phase transition, we employed the high-order fidelity susceptibility $$\chi ^{(3)}_F$$

χ
F

(
3
)

, which is readily evaluated via the exact-diagonalization scheme. As a demonstration, for a fixed value of $$\delta $$
δ
, the XY-VBS criticality was analyzed by the probe $$\chi ^{(3)}_F$$

χ
F

(
3
)

. Thereby, with properly scaling $$\delta $$
δ
, the $$\chi ^{(3)}_F$$

χ
F

(
3
)

data were cast into the crossover-scaling formula to determine the multi-criticality.

Graphic abstract
Fabrication of Die Sink Electrochemical Machining Tools Using Low Melting Fusible Alloy and Polymer Based Additive Manufacturing
Authors: Rajakumaran Maran , Dvivedi Akshay 
Published: October 2024

The present work introduces a novel approach to fabricating die-sink tools for electrochemical machining (ECM) using low-melting fusible alloy and additive manufacturing. Three methods are proposed, each bettering the previous in manufacturing sustainability. The versatility of the process enables the fabrication of die-sink ECM tools that are hitherto considered challenging to fabricate. Finite element analysis was used to simulate the temperature rise of the low-melting (50 °C) tool due to Joule heating, accounting for electrolyte flow under various process parameters. A novel validation method employed a thermostat temperature probe as a cathode. Experiments based on the simulation data revealed that for a 4 mm tool diameter, the tool is unlikely to melt at 3 A current, 200 μm inter-electrode gap, 11.97 S m−1 electrolyte conductivity, and 1.7 m s−1 electrolyte velocity. A pulsed power supply was subsequently used to improve heat dissipation, and ECM was successfully carried out using tools of various shapes, demonstrating the effectiveness of the developed fabrication methods.
Genotype/Phenotype Relationship: Lessons From 137 Patients With PMM2‐CDG
Authors: Pajusalu Sander , Vals Mari-Anne , Serrano Mercedes , Witters Peter , Cechova Anna , Honzik Tomáš , Edmondson Andrew C. , Ficicioglu Can , Barone Rita , De Lonlay Pascale , Bérat Claire-Marine , Vuillaumier-Barrot Sandrine , Lam Christina , Patterson Marc C. , Janssen Mirian C. H. , Martins Esmeralda , Quelhas Dulce , Sykut-Cegielska Jolanta , Mousa Jehan , Urreizti Roser , McWilliams Peter , Vernhes Frederique , Plotkin Horacio , Morava Eva , Õunap Katrin 
Published: October 2024

We report on the largest single dataset of patients with PMM2‐CDG enrolled in an ongoing international, multicenter natural history study collecting genetic, clinical, and biological information to evaluate similarities with previous studies, report on novel findings, and, additionally, examine potential genotype/phenotype correlations. A total of 137 participants had complete genotype information, representing 60 unique variants, of which the most common were found to be p.Arg141His in 58.4% (n = 80) of participants, followed by p.Pro113Leu (21.2%, n = 29), and p.Phe119Leu (12.4%, n = 17), consistent with previous studies. Interestingly, six new variants were reported, comprised of five missense variants (p.Pro20Leu, p.Tyr64Ser, p.Phe68Cys, p.Tyr76His, and p.Arg238His) and one frameshift (c.696del p.Ala233Argfs∗100). Patient phenotypes were characterized via the Nijmegen Progression CDG Rating Scale (NPCRS), together with biochemical parameters, the most consistently dysregulated of which were coagulation factors, specifically antithrombin (below normal in 79.5%, 93 of 117), in addition to Factor XI and protein C activity. Patient genotypes were classified based upon the predicted pathogenetic mechanism of disease‐associated mutations, of which most were found in the catalysis/activation, folding, or dimerization regions of the PMM2 enzyme. Two different approaches were used to uncover genotype/phenotype relationships. The first characterized genotype only by the predicted pathogenic mechanisms and uncovered associated changes in biochemical parameters, not apparent using only NPCRS, involving catalysis/activation, dimerization, folding, and no protein variants. The second approach characterized genotype by the predicted pathogenic mechanism and/or individual variants when paired with a subset of severe nonfunctioning variants and uncovered correlations with both NPCRS and biochemical parameters, demonstrating that p.Cys241Ser was associated with milder disease, while p.Val231Met, dimerization, and folding variants with more severe disease. Although determining comprehensive genotype/phenotype relationships has previously proven challenging for PMM2‐CDG, the larger sample size, plus inclusion of biochemical parameters in the current study, has provided new insights into the interplay of genetics with disease.Trial Registration:NCT03173300.
Identification of High-Incidence Populations in the United States for Anti–Epstein-Barr Virus Serologic Screening for Nasopharyngeal Carcinoma
Authors: Clark Payton E. , Taparra Kekoa , Miller Jacob A. 
Published: October 2024

Abstract

Background:
In the United States, Epstein-Barr virus (EBV)–associated nasopharyngeal carcinoma (NPC) disproportionately impacts Asian Americans (AA) and Native Hawaiians and other Pacific Islanders (NHPI) who have no access to screening. EBV-based screening trials in Asia have detected most cases at early stages. We sought to identify a US target population for NPC screening and hypothesized that once-lifetime screening could be cost-effective.

Methods:
We obtained NPC incidence data from the Surveillance, Epidemiology, and End Results Asian and Pacific Islander datasets. We estimated the number needed to screen (NNS), mortality reduction, and resource utilization using a validated model and performance data from trials. Six evaluated strategies incorporated serology, nasopharyngeal swab PCR, and endoscopy or MRI.

Results:
Intermediate-incidence and high-incidence populations accounted for 10.7% of US person-years yet 42.7% of cases. Anti-BNLF2b screening with selective endoscopy was the preferred strategy. In high-incidence populations, the median NNS to detect one case was 1,992, with a median of 7.12 NPC deaths averted per 100,000 screened. Screening met the willingness-to-pay threshold in all five high-incidence populations (median incremental cost-effectiveness ratio/gross domestic product, 0.82) and among men in intermediate-incidence populations.

Conclusions:
Nearly half of NPC in the United States arises among the 10% with AA or NHPI ethnicity. A suitable target population for US screening trials would be men and women aged 35 to 65 years of Chinese, Sāmoan, or Southeast Asian ethnicity, or men aged 35 to 60 years of Guamanian/Chamorro, Filipino, or Native Hawaiian ethnicity. Once-lifetime anti-BNLF2b screening could be cost-effective.

Impact:
These data may aid the design of US screening trials. Targeted NPC screening might mitigate health disparities.
Cancer Mortality among Hispanic Groups in the United States by Birthplace (2003–2017)
Authors: He Yuelin , Pinheiro Paulo S. , Tripathi Osika , Nguyen Helen , Srinivasan Malathi , Palaniappan Latha P. , Thompson Caroline A. 
Published: October 2024

Abstract

Background:
The Hispanic population is the second largest racial/ethnic group in the United States, consisting of multiple distinct ethnicities. Ethnicity-specific variations in cancer mortality may be attributed to countries of birth, so we aimed to understand differences in cancer mortality among disaggregated Hispanics by nativity (native- or foreign-born vs. US-born) over 15 years.

Methods:
A total of 228,197 Hispanic decedents (Mexican, Puerto Rican, Cuban, and Central or South American) with cancer-related deaths from US death certificates (2003–2017) were analyzed. Seven cancers that contribute significantly to Hispanic male (lung and bronchus, colon and rectum, liver, prostate, and pancreas cancers) and female (lung and bronchus, liver, pancreas, colon and rectum, female breast, and ovary cancers) mortality were selected for analysis. 5-year age-adjusted mortality rates [(95% confidence interval); per 100,000] and standardized mortality ratios (95% confidence interval) using foreign-born as the reference group were calculated. Joinpoint regression analysis was used to model cancer-related mortality trends.

Results:
Puerto Rico–born Puerto Ricans, Cuba-born Cubans, and US-born Mexicans had some of the highest cancer death rates among all the Hispanic groups. In general, foreign-born Hispanics had higher cancer mortality rates than US-born Hispanics, except Mexicans. Overall, US-born and non–US-born (i.e., native- or foreign-born) Hispanic groups experienced decreasing rates of cancer deaths over the years.

Conclusions:
We noted vast heterogeneity in mortality rates by nativity across Hispanic groups, a fast-growing diverse US population.

Impact:
Understanding disaggregated patterns and trends in cancer burden can motivate deeper discussion around community health resources, which may improve the health of Hispanics across the United States.
Social Determinants of Breast Cancer Screening: A Multilevel Analysis of Proximal and Distal Factors Related to the Practice of Mammography
Authors: Sarmiento Daiana Denis , Tumas Natalia , Pereyra Sofia Aynelen , Scruzzi Graciela Fabiana , Pou Sonia Alejandra 
Published: October 2024

Abstract

Background:
Mammography is crucial for early breast cancer detection. In Latin America, Argentina faces a significant breast cancer burden, with varying mammography rates. The social factors influencing mammography practices remain unclear. This study aimed to identify the proximal and distal social determinants of this practice among Argentinean women using a multilevel approach.

Methods:
This nationwide cross-sectional study included 4,924 women, ages 50 to 70, participating in the 2018 National Risk Factor Survey of Argentina. Two-level logistic models were used to estimate measures of association (ORs) between timely mammography practice (within the last 2 years) and selected covariates (sociodemographics, proximal environment, and distal-level variables). The intraclass correlation coefficient and proportional change in variance were calculated.

Results:
Of the total participants, 62.8% of women underwent timely mammography. Age [OR = 0.96; 95% confidence interval (CI), 0.94–0.97], health insurance (OR = 2.22; 95% CI, 1.87–2.63), education (OR = 2.1; 95% CI, 1.74–2.64), and income (OR = 1.56; 95% CI, 1.23–1.97) were associated with mammography practice. Women in nonmarital (OR = 0.61; 95% CI, 0.52–0.72) or larger households (OR = 0.61; 95% CI, 0.51–0.63) were less likely to have timely mammography; living in a larger city was positively associated with timely mammography (OR = 1.28; 95% CI, 1.12–1.46). Women in provinces with higher physician density (OR = 1.06; 95% CI, 1.01–1.11) and lower maternal mortality ratio (OR = 0.9; 95% CI, 0.87–0.96) had higher chances of timely mammography. The intraclass correlation coefficient and proportional change in variance suggested that the explored healthcare indicators largely explained the macro-contextual effect.

Conclusions:
Multilevel factors influenced mammography practices in Argentina. The results highlight disparities linked to sociodemographic characteristics and healthcare resources.

Impact:
Efforts to address social inequalities in breast cancer screening must consider multilevel determinants, including in healthcare settings.
Acetaminophen Overdose Reveals PAR4 as a Low-Expressing but Potent Receptor on the Hepatic Endothelium in Mice
Authors: Rajala Rahul , Cleuren Audrey C.A. , Griffin Courtney T. 
Published: October 2024

BACKGROUND:
The protease thrombin, which elicits multiple physiological and pathological effects on vascular endothelial cells (ECs), can signal through PARs (protease-activated receptors) 1 and 4. PAR1 is a high-affinity thrombin receptor known to signal on ECs, whereas PAR4 is a low-affinity thrombin receptor, and evidence for its expression and function on ECs is mixed. This study aims to exploit the high levels of thrombin generation and hepatic vascular dysfunction that occur during acetaminophen (APAP) overdose to determine (1) whether hepatic endothelial PAR4 is a functional receptor, and (2) the endothelial-specific functions for PAR1 and PAR4 in a high thrombin and pathological setting.

METHODS:

We generated mice with conditional deletion of
Par1/Par4
in ECs and overdosed them with APAP. Hepatic vascular permeability, erythrocyte accumulation in the liver, thrombin generation, and liver function were assessed following overdose. Additionally, we investigated the expression levels of endothelial PARs and how they influence transcription in APAP-overdosed liver ECs using endothelial translating ribosome affinity purification followed by next-generation sequencing.

RESULTS:

We found that mice deficient in high-expressing endothelial
Par1
or low-expressing
Par4
had equivalent reductions in APAP-induced hepatic vascular instability, although mice deficient for both receptors had lower vascular permeability at an earlier timepoint after APAP overdose than either of the single mutants. Additionally, mice with loss of both endothelial
Par1
and
Par4
had reduced thrombin generation after APAP overdose, suggesting decreased hypercoagulability. Last, we found that endothelial PAR1—but not PAR4—can regulate transcription in hepatic ECs.

CONCLUSIONS:
Low-expressing PAR4 can react similarly to high-expressing PAR1 in APAP-overdosed hepatic ECs, demonstrating that PAR4 is a potent thrombin receptor. Additionally, these receptors are functionally redundant but act divergently in their expression and ability to influence transcription in hepatic ECs.
Ironic Lynchings and Embodied Crucifixions in Morrison’s Paradise
Authors: Little Brent 
Published: October 2024

Abstract
This article explores how the womanist theology of M. Shawn Copeland illuminates the theological dimensions of Toni Morrison’s 1997 novel, Paradise. With reference to Copeland’s thought, I argue that Morrison re-imagines the crucifixion anew during the novel’s climax, in which five socially marginalized and racially diverse women are scapegoated and murdered by male leaders of the all-black town, Ruby. Drawing upon the thought of James Cone and observations by Morrison herself, I further describe these women’s murders as a kind of lynching. Morrison thus demonstrates how racism’s logic of domination becomes internalized and replicated by Ruby’s male-power structure. The lynching of the women thereby emerges as ironic, for the men’s intentions to create an all-black paradise unconsciously imitate the oppression and perverse theology of white supremacy. Morrison’s novel thus encourages readers to re-imagine the cross so as to reject exclusionary forms of Christianity.
Dialectics of Deduction and Divination
Authors: Leubner Ben 
Published: October 2024

Abstract
This article seeks to demonstrate the heretofore unnoted influence of Arthur Conan Doyle on the poetry of James Merrill, most notably in both Merrill’s famous lyric, “Lost in Translation,” and his epic trilogy, The Changing Light at Sandover. In particular, the article seeks to show how Merrill saw as proximal to each other what many Conan Doyle experts and Sherlockians have seen as befuddlingly exclusive: the skepticism of Sherlock Holmes and the spiritualism of his creator, Conan Doyle.