bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autophagy promotes p72 degradation and capsid disassembly during the early phase of African swine fever virus infection
Authors: Song Jie , Li Jiangnan , Li Shuai , Zhao Gaihong , Li Tingting , Chen Xin , Hu Boli , Liu Jia , Lai Xinyu , Liu Sitong , Zhou Qiongqiong , Huang Li , Weng Changjiang 
Published: December 2024

ABSTRACT

During viral infections, autophagy functions as a cell-intrinsic defense mechanism by facilitating the delivery of virions or viral components to the endosomal/lysosomal pathway for degradation. In this study, we report that internalized African swine fever virus (ASFV) virions enter autolysosomes during the early phase of viral infection. Autophagy selectively targets the major capsid protein p72 within the ASFV virion. The ASFV p72 protein undergoes modification through ubiquitination at the C-terminus, a process mediated by the E3 ubiquitin ligase Stub1. Subsequently, ubiquitinated p72 is recognized by the autophagy receptor SQSTM1/p62 through its ubiquitin-binding domain. Stub1 facilitates the ubiquitination and degradation of p72 in an HSPA8-dependent manner
via
selective autophagy. Autophagy plays a critical role in disassembling ASFV virions and further promotes the release of ASFV genomic DNA. These findings support the notion that autophagy is involved in and contributes to the capsid disassembly of ASFV, providing valuable insights into this essential viral process.

IMPORTANCE

African swine fever (ASF), a highly contagious disease caused by the ASF virus (ASFV), affects domestic pigs and wild boars, with a mortality rate of up to 100%. The ASF epidemic poses a persistent threat to the global pig industry. Currently, no effective vaccines or antiviral drugs are available for prevention and control. In this study, we discovered that autophagy promotes the degradation of p72 and the disassembly of the capsid during the early phase of ASFV infection. Mechanically, Stub1 facilitates the polyubiquitination of ASFV p72 through the chaperone HSPA8. The polyubiquitinated p72 then interacts with the autophagy receptor SQSTM1/p62, leading to its degradation
via
the selective autophagy pathway. These findings reveal the mechanism of p72 degradation through autophagy and provide new insights into the capsid disassembly process of ASFV.
Sdd3 regulates the biofilm formation of
Candida albicans
via the Rho1-PKC-MAPK pathway
Authors: Pang Li Mei , Zeng Guisheng , Chow Eve Wai Ling , Xu Xiaoli , Li Ning , Kok Yee Jiun , Chong Shu Chen , Bi Xuezhi , Gao Jiaxin , Seneviratne Chaminda Jayampath , Wang Yue 
Published: December 2024

ABSTRACT

Candida albicans
, the most frequently isolated fungal pathogen in humans, forms biofilms that enhance resistance to antifungal drugs and host immunity, leading to frequent treatment failure. Understanding the molecular mechanisms governing biofilm formation is crucial for developing anti-biofilm therapies. In this study, we conducted a genetic screen to identify novel genes that regulate biofilm formation in
C. albicans
. One identified gene is
ORF19.6693
, a homolog of the
Saccharomyces cerevisiae SDD3
gene. The
sdd3
∆/∆ mutant exhibited severe defects in biofilm formation and significantly reduced chitin content in the cell wall. Overexpression of the constitutively active version of the Rho1 GTPase Rho1
G18V
, an upstream activator of the protein kinase C (PKC)-mitogen-activated protein kinase (MAPK) cell-wall integrity pathway, rescued these defects. Affinity purification, mass spectrometry, and co-immunoprecipitation revealed Sdd3’s physical interaction with Bem2, the GTPase-activating protein of Rho1. Deletion of
SDD3
significantly reduced the amount of the active GTP-bound form of Rho1, thereby diminishing PKC-MAPK signaling and downregulating chitin synthase genes
CHS2
and
CHS8
. Taken together, our studies identify a new biofilm regulator, Sdd3, in
C. albicans
that modulates Rho1 activity through its inhibitory interaction with Bem2, thereby regulating the PKC-MAPK pathway to control chitin biosynthesis, which is critical for biofilm formation. As an upstream component of the pathway and lacking a homolog in mammals, Sdd3 has the potential to serve as an antifungal target for biofilm infections.

IMPORTANCE

The human fungal pathogen
Candida albicans
is categorized as a critical priority pathogen on the World Health Organization’s Fungal Priority Pathogens List. A key virulence attribute of this pathogen is its ability to form biofilms on the surfaces of indwelling medical devices. Fungal cells in biofilms are highly resistant to antifungal drugs and host immunity, leading to treatment failure. This study conducted a genetic screen to discover novel genes that regulate biofilm formation. We found that deletion of the
SDD3
gene caused severe biofilm defects. Sdd3 negatively regulates the Rho1 GTPase, an upstream activator of the protein kinase C-mitogen-activated protein kinase pathway, through direct interaction with Bem2, the GTPase-activating protein of Rho1, resulting in a significant decrease in chitin content in the fungal cell wall. This chitin synthesis defect leads to biofilm formation failure. Given its essential role in biofilm formation, Sdd3 could serve as an antifungal target for biofilm infections.
Improved genome sequence of
Geobacillus kaustophilus
GBlys, a lysogenic strain by lysogenic phage phiOH2
Authors: Tanaka Rihito , Imbe Soki , Fujino Yasuhiro , Hiromasa Yasuaki , Mori Kazuki , Tashiro Kosuke , Doi Katsumi 
Published: December 2024

ABSTRACT

Geobacillus kaustophilus
GBlys is a lysogenic strain of the temperate phage phiOH2, which is 3,644,428 bp long, has a GC content of 52%, and contains 3,595 predicted protein-coding genes. Here, we report a resequenced GBlys genome obtained by deep sequencing with long and short reads.
The probability of detecting host-specific microbial source tracking markers in surface waters was strongly associated with method and season
Authors: Murphy Claire M. , Weller Daniel L. , Love Tanzy M. T. , Danyluk Michelle D. , Strawn Laura K. 
Published: December 2024

ABSTRACT

Fecal contamination of surface waters presents significant human health and environmental risks. While many methods for understanding fecal contamination cannot differentiate between human and animal sources, microbial source tracking (MST) marker methods are used to identify fecal sources. To understand how to best employ MST marker data for managing fecal contamination risks, the present study compiled previously collected MST marker data (
N
= 12,878 samples) from across North America; each sample in the data set had been tested for fecal contamination from one or more of five sources (avian, canine, human, ruminant, swine). Using these data, this study aimed to characterize associations between non-methodological and methodological factors and detection of host-specific MST markers and determine how methodological differences may complicate the interpretation of these associations between studies. Variance partitioning analysis was used to quantify the variance in host-specific MST marker detection attributable to non-methodological and methodological factors. Conditional forest and regression analysis were utilized to assess the association between detection and select non-methodological and methodological factors. Between 10% (canine) and 38% (human) of total variance was uniquely attributable to non-methodological factors for any of the fecal sources considered, while between 50% (human) and 84% (canine) of variance could not be attributed to either methodological or non-methodological factors. This highlights the need for standardization of methods for MST marker detection across studies but also suggests that other factors, beyond those non-methodological variables considered here, influenced variation in the likelihood of MST marker detection.

IMPORTANCE
This study underscores complications associated with comparing findings from studies that used different methodologies to detect the same fecal targets and highlights the difficulties associated with using non-comparable data to generalize findings and develop science-based risk management plans. These findings highlight the need for standardization of sampling and laboratory methods across microbial source tracking marker studies. Our findings build on previous research to suggest that one-size-fits-all approaches to managing fecal hazards in surface waterways may not be appropriate; instead, strategies tailored to specific water sources and conditions at the time of water use may be more effective.
The Resident European River Lamprey Lampetra fluviatilis (Petromyzontidae) and its Habitat Conditions in the Upper Reaches of Tributaries of the Pola and Msta Rivers
Authors: Kolotei A. V. , Kucheryavyy A. V. , Zvezdin A. O. , Pavlov D. S. 
Published: December 2024

Abstract—
The results of the study of local populations of the resident form of the European river lamprey Lampetra fluviatilis in medium and small watercourses (tributaries of the Pola and Msta rivers), located at a distance of ~700 km from the sea, in the native part of the species range, are presented. Such populations are still poorly studied, despite the fact that they ensure the preservation of the range under conditions of fragmentation of river system. The captured adults are typical representatives of the resident form, with a slight variation in the dentition. The population density of lamprey larvae in most of the studied habitats is low and average in a small part of them. The habitat conditions of ammocoetes are determined to be optimal, however, due to the peculiarities of small watercourses, their habitats are vulnerable to the negative effects of environmental factors.
Cosmic Polarization Rotation from CMB data: A review for GR110
Authors: Gruppuso Alessandro , di Serego Alighieri Sperello 
Published: December 2024

We provide an update to S. di Serego Alighieri, Int. J. Mod. Phys. D 24 (2015) 1530016, arXiv:1501.06460 [astro-ph.CO], focusing on recent developments regarding constraints on Cosmic Polarization Rotation (CPR), also known as Cosmic Birefringence (CB), derived from Cosmic Microwave Background (CMB) polarization data.
Preformation of alpha particles in superheavy nuclei within an improved coulomb and proximity potential model
Authors: Shahana Aysha , Damodaran Lisha , Suresh T. P. , Prathapan K. 
Published: December 2024

The alpha decay half-life and alpha preformation factor in superheavy elements are investigated within the framework of an improved Coulomb and proximity potential model (ICPPM). The CPPM is improved by including a more accurate expression for the diffuseness parameter (b) in the proximity potential. The alpha decay half-lives are calculated by inputting the experimental Q-values and the preformation probability is extracted. It is noteworthy that computed half-lives for alpha decay for superheavy nuclei by using the improved CPPM can accurately replicate experimental data and considerably minimize discrepancies. The estimated alpha decay half-lives are compared with the predictions of the universal decay law (UDL), 1 the Akrawy–Poenaru (AP) formula 2 and the prediction of the modified formula of Santhosh et al. suggested by Luo et al. 3 The hindrance factor (HF) is also calculated for the alpha decays considered in this study. Low values of the HF indicate the high accuracy of the predictions of the ICPPM.
Memory Checking Requires Logarithmic Overhead
Authors: Boyle Elette , Komargodski Ilan , Vafa Neekon 
Published: December 2024

We study the complexity of memory checkers with computational security and prove the first general tight lower bound.

Memory checkers, first introduced over 30 years ago by Blum, Evans, Gemmel, Kannan, and Naor (FOCS ’91, Algorithmica ’94), allow a user to store and maintain a large memory on a remote and unreliable server by using small trusted local storage. The user can issue instructions to the server and after every instruction, obtain either the correct value or a failure (but not an incorrect answer) with high probability. The main complexity measure of interest is the size of the local storage and the number of queries the memory checker makes upon every logical instruction. The most efficient known construction has query complexity
O
(log
n
/log log
n
) and local space proportional to a computational security parameter, assuming one-way functions, where
n
is the logical memory size. Dwork, Naor, Rothblum, and Vaikuntanathan (TCC ’09) showed that for a restricted class of “deterministic and non-adaptive” memory checkers, this construction is optimal, up to constant factors. However, going beyond the small class of deterministic and non-adaptive constructions has remained a major open problem.

In this work, we fully resolve the complexity of memory checkers by showing that
any
construction with local space
p
and query complexity
q
must satisfy

\[
p \ge \frac{n}{(\log n)^{O(q)}} \;.
\]

This implies, as a special case, that
q
≥
Ω
(log
n
/log log
n
) in any scheme, assuming that
p
≤
n
1 − ε
for ε > 0. The bound applies to any scheme with computational security, completeness 2/3, and inverse polynomial in
n
soundness (all of which make our lower bound only stronger). We further extend the lower bound to schemes where the read complexity

q
r

and write complexity

q
w

differ. For instance, we show the tight bound that if

q
r

=
O
(1) and
p
≤
n
1 − ε
for ε > 0, then

q
w

≥
n

Ω
(1)

. This is the first lower bound, for any non-trivial class of constructions, showing a read-write query complexity trade-off.

Our proof is via a delicate compression argument showing that a “too good to be true” memory checker can be used to compress random bits of information. We draw inspiration from tools recently developed for lower bounds for relaxed locally decodable codes. However, our proof itself significantly departs from these works, necessitated by the differences between settings.
Epidemiology and Clinical Outcomes of Childhood Central Nervous System Cancers in a Large Low/Middle-Income Country Pediatric Oncology Center: A Report on 5,051 Kids
Authors: Maher Eslam , Kamal Mohamed , El-Ayadi Moatasem , Refaat Amal , Enayet Abdelrahman , El-Beltagy Mohamed , Eldebawy Eman , Taha Hala , Awad Madiha , Zaghloul Mohamed S. 
Published: December 2024

Abstract

Background:
Central nervous system (CNS) tumors are the leading cause of cancer-related deaths in children. Although most cases come from low- and middle-income countries (LMIC) where their prognosis is worse, few epidemiologic studies are conducted in these regions.

Methods:
We conducted a registry-based cohort study for childhood CNS tumors at Children’s Cancer Hospital, Egypt, over 15 years. Unified treatment protocols were implemented. Survival analyses were conducted using the Kaplan–Meier function. Cases were additionally annotated using the International Classification of Childhood Cancer-3 classification.

Results:
In total, 5,051 children ≤18 years of age were identified, accounting for 20% of all childhood cancers treated at Children’s Cancer Hospital, Egypt. The most common tumor sites were the posterior fossa (36.8%) and brainstem (17.7%). Pathologies were predominantly astrocytic (n = 1,360; 26.9%) and embryonal (n = 1,003; 19.9%) in origin. The 5-year overall survival (OS) and event-free survival for all cases were 64.6% and 51.8%, respectively. More specifically, 1,421 low-grade gliomas were identified, with a 5-year OS of 91.1%. Medulloblastoma (n = 801) recorded a 5-year OS of 66%. The entity with the worst prognosis was diffuse intrinsic pontine glioma (n = 633), with a 5-year OS of 3.2%.

Conclusions:
We report on a large number of childhood CNS tumors from an LMIC. This study underscores the need to understand the burden of childhood brain tumors and its outcomes in resource-constrained settings.

Impact:
This study reports on the epidemiology and clinical outcomes of 5,000+ children with CNS tumors from a specialized LMIC center. Despite the lack of many sophisticated and advanced facilities, LMICs can improve the clinical end-results with experience and augmented efforts.
Circulating Tumor DNA Dynamics and Clinical Outcome in Metastatic Colorectal Cancer Patients Undergoing Front-Line Chemotherapy
Authors: Ghidini Michele , Hahne Jens Claus , Senti Chiara , Heide Timon , Proszek Paula Z. , Shaikh Ridwan , Carter Paul , Hubank Mike , Trevisani Francesco , Garrone Ornella , Cappelletti Maria Rosa , Generali Daniele , Cattaneo Monica , Gnocchi Nicoletta , Donati Gianvito , Gobbi Angela , Grizzi Giulia , Lampis Andrea , Elghadi Raghad , Tanzi Giulia , Tomasello Gianluca , Ratti Margherita , Pinato David J. , Fassan Matteo , Vlachogiannis Georgios , Sottoriva Andrea , Cortellini Alessio , Passalacqua Rodolfo , Valeri Nicola 
Published: December 2024

Abstract

Purpose:
We tested whether circulating tumor DNA (ctDNA) changes may be used to assess early response and clinical outcomes in patients with metastatic colorectal cancer (mCRC) undergoing first-line systemic anticancer therapy (SACT).

Experimental Design:
Eight hundred sixty-two plasma samples were collected 4-weekly from baseline (BL) until disease progression in patients with mCRC receiving first-line SACT. ctDNA was tested using tissue-agnostic next-generation sequencing panels. ctDNA normalization was defined as ≥99% clearance after 1 month of therapy (Mo1) in the three variants with the highest allele frequency in BL ctDNA.

Results:
Eighty-three paired samples from 75 patients were available for analysis. Twelve pairs (14.4%) showed no variants in either BL or Mo1. In the remaining 71 comparisons (65 patients), 37 (52.1%) showed ctDNA normalization at Mo1. Patients who cleared ctDNA had significantly longer overall (45.6 months) and progression-free survival (13.9 months) compared with nonnormalized patients [overall survival = 22.6 months (log-rank P = 0.01) and progression-free survival = 10.7 months (log-rank P = 0.036), respectively]. In addition, a higher response rate was observed in patients with ctDNA clearance (72.9%) compared with nonnormalized cases (38.2%). Longitudinal sequencing of at least four time points in patients with a progression-free survival of &gt;10 months showed emerging variants in 47.8% of cases; in all these patients, the trajectory of these new “outlier” variants seemed in stark contrast with the clinical–radiological course of disease and the trend in other mutations.

Conclusions:
ctDNA clearance represents an early indicator of benefit from SACT in patients with mCRC; serial tracking of multiple variants is warranted to improve specificity and avoid misleading information due to the emergence of mutations of unknown clinical significance.
TEAD-Independent Cell Growth of Hippo-Inactive Mesothelioma Cells: Unveiling Resistance to TEAD Inhibitor K-975 through MYC Signaling Activation
Authors: Akao Ken , Sato Tatsuhiro , Mishiro-Sato Emi , Mukai Satomi , Ghani Farhana Ishrat , Kondo-Ida Lisa , Imaizumi Kazuyoshi , Sekido Yoshitaka 
Published: December 2024

Abstract
Inactivation of tumor-suppressive Hippo signaling pathway is frequently observed in mesothelioma, which leads to the activation of yes-associated protein (YAP) and TAZ (also known as WW domain–containing transcription regulator 1; YAP/TAZ) transcriptional coactivators. YAP/TAZ form complexes with TEAD family members, DNA-binding proteins, to activate transcription, which promotes cancer cell growth and proliferation. Recently developed TEAD inhibitors exhibit antitumor activity by inhibiting the formation of the transcription complex through binding to TEAD; however, the antitumor activity of TEAD inhibitors against mesothelioma remains to be fully elucidated. Here, we show that the TEAD inhibitor K-975 acts as a pan-TEAD inhibitor and selectively inhibits the binding of TEAD-binding proteins, especially YAP/TAZ, in mesothelioma cells. In studies using a panel of mesothelioma cell lines, K-975 showed a significant growth inhibitory effect on Hippo-inactivated mesothelioma cells, but some of these cell lines exhibited primary resistance to K-975. Differential gene expression analysis revealed that cells resistant to K-975 exhibited activation of MYC signaling in the presence of K-975, and cells overexpressed with MYC showed strong drug resistance, in vitro and in vivo. Our study revealed the features of a subset of mesothelioma cells that proliferate in a TEAD-independent manner and provides important insights for the successful development of therapeutic strategies for mesothelioma with Hippo pathway inactivation.
Native Valve and Native Neo-Sinus Remodeling Following Transcatheter Aortic Valve Replacement
Authors: Yoon Joshua , Gill Hacina , Jelisejevas Julius , Lai Althea , Khan Jaffar M. , Payne Geoffrey W. , Webb John G. , Sathananthan Janarthanan , Seidman Michael A. , Meier David , Sellers Stephanie L. 
Published: December 2024

BACKGROUND:
Transcatheter aortic valve replacement (TAVR) pushes aside the diseased native aortic valve and creates a native neo-sinus bordered by the aortic root wall and the displaced native valve. There are limited data on the progression of native valve disease post-TAVR and no previous analysis of the native neo-sinus.

METHODS:
Native aortic valves and native neo-sinus explants obtained post-TAVR were evaluated histologically (hematoxylin and eosin, Movat pentachrome, and Martius Scarlet Blue stains) and by immunohistochemistry (TGF-β1 [transforming growth factor-beta 1], FAP [fibroblast activation protein], and ALP [alkaline phosphatase]) to assess disease mechanisms.

RESULTS:
Native aortic valves were obtained from 20 patients from 0 to 2583 days (7.08 years) post-TAVR. Native leaflets showed persistent calcific aortic stenosis-like disease activity with positivity for ALP and FAP. Native valve remodeling was observed as changes in architecture evident in explants >1.5 years, which was observed as crumpling of the leaflets. Disease activity was also present in native neo-sinuses with transcatheter heart valve implant durations >1 year with positive staining for TGF-β1, FAP, and ALP. Extensive native neo-sinus remodeling occurred with replacement and filling-in of this space with contiguous extracellular matrix, calcific deposits, and microvessels.

CONCLUSIONS:
Following TAVR, there is ongoing calcific aortic stenosis-like disease with architectural changes to native leaflets and extensive remodeling of the native neo-sinus, evidenced by replacement and contiguous filling-in of the native neo-sinus blood pool space with increasing implant duration. The dynamic nature of these tissues has potential implications for neo-sinus flow, valve degeneration, and re-intervention.