bluuebunny/crossref_metadata_2025 huggingface dataset:
Transient Deep Ocean Cooling in the Eastern Equatorial Pacific Ocean at the Eocene‐Oligocene Transition
Authors: Taylor V. E. , Wilson P. A. , Bohaty S. M. , Meckler A. N.
Published: August 2023

At the Eocene‐Oligocene Transition (EOT), approximately 34 million years ago, Earth abruptly transitioned to a climate state sufficiently cool for Antarctica to sustain large ice sheets for the first time in tens to hundreds of millions of years. Oxygen isotope records from deep‐sea benthic foraminifera (δ18Ob) provide the foundation of our understanding of this pivot point in Cenozoic climate history. A deeper insight, however, is hindered by the paucity of independent deep‐sea temperature reconstructions and the ongoing challenge of deconvolving the temperature and continental ice volume signals embedded in δ18Ob records. Here we present records of deep‐sea temperature change from the eastern equatorial Pacific for the EOT using clumped isotope thermometry, which permits explicit temperature reconstructions independent of seawater chemistry and continental ice volume. Our records suggest that the deep Pacific Ocean cooled markedly at the EOT by 4.7 ± 0.9°C. This decrease in temperature represents the first direct and robust evidence of deep‐sea cooling associated with the inception of major Cenozoic glaciation. However, our data also indicate that this major cooling of the deep Pacific Ocean at the EOT was short‐lived (∼200 kyrs), with temperatures rebounding to values close to pre‐EOT levels by 33.6 Ma. Our calculated record of seawater δ18O suggests that this rebound in ocean temperature occurred despite the continued presence of a large‐scale Antarctic ice sheet. This finding suggests a degree of decoupling between deep ocean temperatures in the eastern equatorial Pacific Ocean and the behavior of the newly established Antarctic ice sheet.
Cohort selection and the estimation of racial disparity in mortality of extremely preterm neonates
Authors: Gould Jeffrey B. , Bennett Mihoko V. , Profit Jochen , Lee Henry C.
Published: August 2023

Background

Racial disparities in preterm neonatal mortality are long-standing. We aimed to assess how cohort selection influences mortality rates and racial disparity estimates.

Methods

With 2014–2018 California data, we compared neonatal mortality rates among Black and non-Hispanic White very low birth weight (VLBW, <1500 g) or very preterm infants (22–29 weeks gestational age). Relative risks were estimated by different cohort selection criteria. Blinder-Oaxaca decomposition quantified factors contributing to mortality differential.

Results

Depending upon standard selection criteria, mortality ranged from 6.2% (VLBW infants excluding first 12-h deaths) to 16.0% (22–29 weeks’ gestation including all deaths). Black observed neonatal mortality was higher than White infants only for delivery room deaths in VLBW infants (5.6 vs 4.2%). With risk adjustment accounting for higher rate of low gestational age, low Apgar score and other factors, White infant mortality increased from 15.9 to 16.6%, while Black infant mortality decreased from 16.7 to 13.7% in the 22–29 weeks cohort. Across varying cohort selection, risk adjusted survival advantage among Black infants ranged from 0.70 (CL 0.61–0.80) to 0.84 (CL 0.76–0.93).

Conclusions

Standard cohort selection can give markedly different mortality estimates. It is necessary to reduce prematurity rates and perinatal morbidity to improve outcomes for Black infants.

Impact

In this population-based observational cohort study that encompassed very low birth weight infant hospitalizations in California, varying standard methods of cohort selection resulted in neonatal mortality ranges from 6.2 to 16.0%.

Across all cohorts, the only significant observed Black-White disparity was for delivery room deaths in Very Low Birth Weight births (5.6 vs 4.2%).

Across all cohorts, we found a 16–30% survival advantage for Black infants.

Cohort selection can result in an almost three-fold difference in estimated mortality but did not have a meaningful impact on observed or adjusted differences in neonatal mortality outcomes by race and ethnicity.
Age-, sex-, and pathology-related variability in brain structure and cognition
Authors: Bachmann Dario , Buchmann Andreas , Studer Sandro , Saake Antje , Rauen Katrin , Zuber Isabelle , Gruber Esmeralda , Nitsch Roger M. , Hock Christoph , Gietl Anton , Treyer Valerie
Published: August 2023

This work aimed to investigate potential pathways linking age and imaging measures to early age- and pathology-related changes in cognition. We used [18F]-Flutemetamol (amyloid) and [18F]-Flortaucipir (tau) positron emission tomography (PET), structural MRI, and neuropsychological assessment from 232 elderly individuals aged 50–89 years (46.1% women, 23% APOE-ε4 carrier, 23.3% MCI). Tau-PET was available for a subsample of 93 individuals. Structural equation models were used to evaluate cross-sectional pathways between age, amyloid and tau burden, grey matter thickness and volumes, white matter hyperintensity volume, lateral ventricle volume, and cognition. Our results show that age is associated with worse outcomes in most of the measures examined and had similar negative effects on episodic memory and executive functions. While increased lateral ventricle volume was consistently associated with executive function dysfunction, participants with mild cognitive impairment drove associations between structural measures and episodic memory. Both age and amyloid-PET could be associated with medial temporal lobe tau, depending on whether we used a continuous or a dichotomous amyloid variable. Tau burden in entorhinal cortex was related to worse episodic memory in individuals with increased amyloid burden (Centiloid >12) independently of medial temporal lobe atrophy. Testing models for sex differences revealed that amyloid burden was more strongly associated with regional atrophy in women compared with men. These associations were likely mediated by higher tau burden in women. These results indicate that influences of pathological pathways on cognition and sex-specific vulnerabilities are dissociable already in early stages of neuropathology and cognitive impairment.
Preventing Post-Traumatic Stress Disorder (PTSD) in rats with pulsed 810 nm laser transcranial phototherapy
Authors: Zhao Hongyou , Li Yi , Luo Ting , Chou Wenxin , Sun Tianzhen , Liu Haolin , Qiu Haixia , Zhu Dan , Chen Defu , Gu Ying
Published: August 2023

Post-traumatic stress disorder (PTSD) is a debilitating condition that occurs following exposure to traumatic events. Current treatments, such as psychological debriefing and pharmacotherapy, often have limited efficacy and may result in unwanted side effects, making early intervention is a more desirable strategy. In this study, we investigated the efficacy of a single dose of pulsed (10 Hz) 810 nm laser-phototherapy (P-PT) as an early intervention for preventing PTSD-like comorbidities in rats induced by single inescapable electric foot shock following the single prolonged stress (SPS&S). As indicated by the results of the open filed test, elevated plus maze test, and contextual fear conditioning test, P-PT prevented the development of anxiety and freezing behaviors in rats exposed to the SPS&S. We also compared the effects of P-PT and continuous wave 810 nm laser-phototherapy (CW-PT) in preventing PTSD-like comorbidities in rats. The results revealed that P-PT was effective in preventing both freezing and anxiety behavior in stressed rats. In contrast, CW-PT only had a preventive effect on freezing behavior but not anxiety. Additionally, P-PT significantly reduced the c-fos expression in cingulate cortex area 1(Cg1) and infralimbic cortex (IL) of stressed rats, while CW-PT had no significant effects on c-fos expression. Taken together, our results demonstrate that P-PT is a highly effective strategy for preventing the occurrence of PTSD-like comorbidities in rats.
The diversified role of mitochondria in ferroptosis in cancer
Authors: Liu Yu’e , Lu Shiping , Wu Lei-lei , Yang Liang , Yang Lixue , Wang Jinghan
Published: August 2023

Ferroptosis is a form of regulated cell death induced by iron-dependent lipid peroxidation, and it has been studied extensively since its discovery in 2012. Induced by iron overload and ROS accumulation, ferroptosis is modulated by various cellular metabolic and signaling pathways. The GSH-GPX4 pathway, the FSP1-CoQ10 pathway, the GCH1-BH4 pathway, the DHODH-CoQH2 system and the sex hormones suppress ferroptosis. Mitochondrial iron metabolism regulates ferroptosis and mitochondria also undergo a morphological change during ferroptosis, these changes include increased membrane density and reduced mitochondrial cristae. Moreover, mitochondrial energy metabolism changes during ferroptosis, the increased oxidative phosphorylation and ATP production rates lead to a decrease in the glycolysis rate. In addition, excessive oxidative stress induces irreversible damage to mitochondria, diminishing organelle integrity. ROS production, mitochondrial membrane potential, mitochondrial fusion and fission, and mitophagy also function in ferroptosis. Notably, some ferroptosis inhibitors target mitochondria. Ferroptosis is a major mechanism for cell death associated with the progression of cancer. Metastasis-prone or metastatic cancer cells are more susceptible to ferroptosis. Inducing ferroptosis in tumor cells shows very promising potential for treating drug-resistant cancers. In this review, we present a brief retrospect of the discovery and the characteristics of ferroptosis, then we discuss the regulation of ferroptosis and highlight the unique role played by mitochondria in the ferroptosis of cancer cells. Furthermore, we explain how ferroptosis functions as a double-edged sword as well as novel therapies aimed at selectively manipulating cell death for cancer eradication.
Systematic review of cnidarian microbiomes reveals insights into the structure, specificity, and fidelity of marine associations
Authors: McCauley M. , Goulet T. L. , Jackson C. R. , Loesgen S.
Published: August 2023

Microorganisms play essential roles in the health and resilience of cnidarians. Understanding the factors influencing cnidarian microbiomes requires cross study comparisons, yet the plethora of protocols used hampers dataset integration. We unify 16S rRNA gene sequences from cnidarian microbiome studies under a single analysis pipeline. We reprocess 12,010 cnidarian microbiome samples from 186 studies, alongside 3,388 poriferan, 370 seawater samples, and 245 cultured Symbiodiniaceae, unifying ~6.5 billion sequence reads. Samples are partitioned by hypervariable region and sequencing platform to reduce sequencing variability. This systematic review uncovers an incredible diversity of 86 archaeal and bacterial phyla associated with Cnidaria, and highlights key bacteria hosted across host sub-phylum, depth, and microhabitat. Shallow (< 30 m) water Alcyonacea and Actinaria are characterized by highly shared and relatively abundant microbial communities, unlike Scleractinia and most deeper cnidarians. Utilizing the V4 region, we find that cnidarian microbial composition, richness, diversity, and structure are primarily influenced by host phylogeny, sampling depth, and ocean body, followed by microhabitat and sampling date. We identify host and geographical generalist and specific Endozoicomonas clades within Cnidaria and Porifera. This systematic review forms a framework for understanding factors governing cnidarian microbiomes and creates a baseline for assessing stress associated dysbiosis.
Ultra-resilient multi-layer fluorinated diamond like carbon hydrophobic surfaces
Authors: Hoque Muhammad Jahidul , Li Longnan , Ma Jingcheng , Cha Hyeongyun , Sett Soumyadip , Yan Xiao , Rabbi Kazi Fazle , Ho Jin Yao , Khodakarami Siavash , Suwala Jason , Yang Wentao , Mohammadmoradi Omid , Ince Gozde Ozaydin , Miljkovic Nenad
Published: August 2023

Seventy percent of global electricity is generated by steam-cycle power plants. A hydrophobic condenser surface within these plants could boost overall cycle efficiency by 2%. In 2022, this enhancement equates to an additional electrical power generation of 1000 TWh annually, or 83% of the global solar electricity production. Furthermore, this efficiency increase reduces CO2 emissions by 460 million tons /year with a decreased use of 2 trillion gallons of cooling water per year. However, the main challenge with hydrophobic surfaces is their poor durability. Here, we show that solid microscale-thick fluorinated diamond-like carbon (F-DLC) possesses mechanical and thermal properties that ensure durability in moist, abrasive, and thermally harsh conditions. The F-DLC coating achieves this without relying on atmospheric interactions, infused lubricants, self-healing strategies, or sacrificial surface designs. Through tailored substrate adhesion and multilayer deposition, we develop a pinhole-free F-DLC coating with low surface energy and comparable Young’s modulus to metals. In a three-year steam condensation experiment, the F-DLC coating maintains hydrophobicity, resulting in sustained and improved dropwise condensation on multiple metallic substrates. Our findings provide a promising solution to hydrophobic material fragility and can enhance the sustainability of renewable and non-renewable energy sources.
Cellular profiling of a recently-evolved social behavior in cichlid fishes
Authors: Johnson Zachary V. , Hegarty Brianna E. , Gruenhagen George W. , Lancaster Tucker J. , McGrath Patrick T. , Streelman Jeffrey T.
Published: August 2023

Social behaviors are diverse in nature, but it is unclear how conserved genes, brain regions, and cell populations generate this diversity. Here we investigate bower-building, a recently-evolved social behavior in cichlid fishes. We use single nucleus RNA-sequencing in 38 individuals to show signatures of recent behavior in specific neuronal populations, and building-associated rebalancing of neuronal proportions in the putative homolog of the hippocampal formation. Using comparative genomics across 27 species, we trace bower-associated genome evolution to a subpopulation of glia lining the dorsal telencephalon. We show evidence that building-associated neural activity and a departure from quiescence in this glial subpopulation together regulate hippocampal-like neuronal rebalancing. Our work links behavior-associated genomic variation to specific brain cell types and their functions, and suggests a social behavior has evolved through changes in glia.
GATA2 mitotic bookmarking is required for definitive haematopoiesis
Authors: Silvério-Alves Rita , Kurochkin Ilia , Rydström Anna , Vazquez Echegaray Camila , Haider Jakob , Nicholls Matthew , Rode Christina , Thelaus Louise , Lindgren Aida Yifter , Ferreira Alexandra Gabriela , Brandão Rafael , Larsson Jonas , de Bruijn Marella F. T. R. , Martin-Gonzalez Javier , Pereira Carlos-Filipe
Published: August 2023

In mitosis, most transcription factors detach from chromatin, but some are retained and bookmark genomic sites. Mitotic bookmarking has been implicated in lineage inheritance, pluripotency and reprogramming. However, the biological significance of this mechanism in vivo remains unclear. Here, we address mitotic retention of the hemogenic factors GATA2, GFI1B and FOS during haematopoietic specification. We show that GATA2 remains bound to chromatin throughout mitosis, in contrast to GFI1B and FOS, via C-terminal zinc finger-mediated DNA binding. GATA2 bookmarks a subset of its interphase targets that are co-enriched for RUNX1 and other regulators of definitive haematopoiesis. Remarkably, homozygous mice harbouring the cyclin B1 mitosis degradation domain upstream Gata2 partially phenocopy knockout mice. Degradation of GATA2 at mitotic exit abolishes definitive haematopoiesis at aorta-gonad-mesonephros, placenta and foetal liver, but does not impair yolk sac haematopoiesis. Our findings implicate GATA2-mediated mitotic bookmarking as critical for definitive haematopoiesis and highlight a dependency on bookmarkers for lineage commitment.
Enantioconvergent construction of stereogenic silicon via Lewis base-catalyzed dynamic kinetic silyletherification of racemic chlorosilanes
Authors: Hu Tianbao , Zhao Chen , Zhang Yan , Kuang Yuzhong , Gao Lu , Wang Wanshu , Su Zhishan , Song Zhenlei
Published: August 2023

Organosilanes possessing an enantioenriched stereogenic silicon center are important in many branches of chemistry, yet they remain challenging to synthesize in a practical and scalable way. Here we report a dynamic kinetic silyletherification process of racemic chlorosilanes with (S)-lactates using 4-aminopyridine as a Lewis base catalyst. This enantioconvergent approach asymmetrically constructs the stereogenic silicon center in a different manner from traditional resolution or desymmetrization. A range of silylethers have been prepared with high diastereoselectivity on up to 10 g-scale, allowing the practical synthesis of diverse enantioenriched organosilane analogs.
Programming conformational cooperativity to regulate allosteric protein-oligonucleotide signal transduction
Authors: Liang Yuan , Qie Yunkai , Yang Jing , Wu Ranfeng , Cui Shuang , Zhao Yuliang , Anderson Greg J. , Nie Guangjun , Li Suping , Zhang Cheng
Published: August 2023

Conformational cooperativity is a universal molecular effect mechanism and plays a critical role in signaling pathways. However, it remains a challenge to develop artificial molecular networks regulated by conformational cooperativity, due to the difficulties in programming and controlling multiple structural interactions. Herein, we develop a cooperative strategy by programming multiple conformational signals, rather than chemical signals, to regulate protein-oligonucleotide signal transduction, taking advantage of the programmability of allosteric DNA constructs. We generate a cooperative regulation mechanism, by which increasing the loop lengths at two different structural modules induced the opposite effects manifesting as down- and up-regulation. We implement allosteric logic operations by using two different proteins. Further, in cell culture we demonstrate the feasibility of this strategy to cooperatively regulate gene expression of PLK1 to inhibit tumor cell proliferation, responding to orthogonal protein-signal stimulation. This programmable conformational cooperativity paradigm has potential applications in the related fields.
Toll-like receptor 4 and macrophage scavenger receptor 1 crosstalk regulates phagocytosis of a fungal pathogen
Authors: Onyishi Chinaemerem U. , Desanti Guillaume E. , Wilkinson Alex L. , Lara-Reyna Samuel , Frickel Eva-Maria , Fejer Gyorgy , Christophe Olivier D. , Bryant Clare E. , Mukhopadhyay Subhankar , Gordon Siamon , May Robin C.
Published: August 2023

The opportunistic fungal pathogen Cryptococcus neoformans causes lethal infections in immunocompromised patients. Macrophages are central to the host response to cryptococci; however, it is unclear how C. neoformans is recognised and phagocytosed by macrophages. Here we investigate the role of TLR4 in the non-opsonic phagocytosis of C. neoformans. We find that loss of TLR4 function unexpectedly increases phagocytosis of non-opsonised cryptococci by murine and human macrophages. The increased phagocytosis observed in Tlr4−/− cells was dampened by pre-treatment of macrophages with oxidised-LDL, a known ligand of scavenger receptors. The scavenger receptor, macrophage scavenger receptor 1 (MSR1) (also known as SR-A1 or CD204) was upregulated in Tlr4−/− macrophages. Genetic ablation of MSR1 resulted in a 75% decrease in phagocytosis of non-opsonised cryptococci, strongly suggesting that it is a key non-opsonic receptor for this pathogen. We go on to show that MSR1-mediated uptake likely involves the formation of a multimolecular signalling complex involving FcγR leading to SYK, PI3K, p38 and ERK1/2 activation to drive actin remodelling and phagocytosis. Altogether, our data indicate a hitherto unidentified role for TLR4/MSR1 crosstalk in the non-opsonic phagocytosis of C. neoformans.
Efficient electrospray deposition of surfaces smaller than the spray plume
Authors: Park Sarah H. , Lei Lin , D’Souza Darrel , Zipkin Robert , DiMartini Emily T. , Atzampou Maria , Lallow Emran O. , Shan Jerry W. , Zahn Jeffrey D. , Shreiber David I. , Lin Hao , Maslow Joel N. , Singer Jonathan P.
Published: August 2023

Electrospray deposition (ESD) is a promising technique for depositing micro-/nano-scale droplets and particles with high quality and repeatability. It is particularly attractive for surface coating of costly and delicate biomaterials and bioactive compounds. While high efficiency of ESD has only been successfully demonstrated for spraying surfaces larger than the spray plume, this work extends its utility to smaller surfaces. It is shown that by architecting the local “charge landscape”, ESD coatings of surfaces smaller than plume size can be achieved. Efficiency approaching 100% is demonstrated with multiple model materials, including biocompatible polymers, proteins, and bioactive small molecules, on both flat and microneedle array targets. UV-visible spectroscopy and high-performance liquid chromatography measurements validate the high efficiency and quality of the sprayed material. Here, we show how this process is an efficient and more competitive alternative to other conformal coating mechanisms, such as dip coating or inkjet printing, for micro-engineered applications.
Identification of gene function based on models capturing natural variability of Arabidopsis thaliana lipid metabolism
Authors: Córdoba Sandra Correa , Tong Hao , Burgos Asdrúbal , Zhu Feng , Alseekh Saleh , Fernie Alisdair R. , Nikoloski Zoran
Published: August 2023

Lipids play fundamental roles in regulating agronomically important traits. Advances in plant lipid metabolism have until recently largely been based on reductionist approaches, although modulation of its components can have system-wide effects. However, existing models of plant lipid metabolism provide lumped representations, hindering detailed study of component modulation. Here, we present the Plant Lipid Module (PLM) which provides a mechanistic description of lipid metabolism in the Arabidopsis thaliana rosette. We demonstrate that the PLM can be readily integrated in models of A. thaliana Col-0 metabolism, yielding accurate predictions (83%) of single lethal knock-outs and 75% concordance between measured transcript and predicted flux changes under extended darkness. Genome-wide associations with fluxes obtained by integrating the PLM in diel condition- and accession-specific models identify up to 65 candidate genes modulating A. thaliana lipid metabolism. Using mutant lines, we validate up to 40% of the candidates, paving the way for identification of metabolic gene function based on models capturing natural variability in metabolism.
Exo84c interacts with VAP27 to regulate exocytotic compartment degradation and stigma senescence
Authors: Zhang Tong , Li Yifan , Li Chengyang , Zang Jingze , Gao Erlin , Kroon Johan T. , Qu Xiaolu , Hussey Patrick J. , Wang Pengwei
Published: August 2023

In plants, exocyst subunit isoforms exhibit significant functional diversity in that they are involved in either protein secretion or autophagy, both of which are essential for plant development and survival. Although the molecular basis of autophagy is widely reported, its contribution to plant reproduction is not very clear. Here, we have identified Exo84c, a higher plant-specific Exo84 isoform, as having a unique function in modulating exocytotic compartment degradation during stigmatic tissue senescence. This process is achieved through its interaction with the ER localised VAP27 proteins, which regulate the turnover of Exo84c through the autophagy pathway. VAP27 recruits Exo84c onto the ER membrane as well as numerous ER-derived autophagosomes that are labelled with ATG8. These Exo84c/exocyst and VAP27 positive structures are accumulated in the vacuole for degradation, and this process is partially perturbed in the exo84c knock-out mutants. Interestingly, the exo84c mutant showed a prolonged effective pollination period with higher seed sets, possibly because of the delayed stigmatic senescence when Exo84c regulated autophagy is blocked. In conclusion, our studies reveal a link between the exocyst complex and the ER network in regulating the degradation of exocytosis vesicles, a process that is essential for normal papilla cell senescence and flower receptivity.
Bacteroides uniformis-induced perturbations in colonic microbiota and bile acid levels inhibit TH17 differentiation and ameliorate colitis developments
Authors: Yan YiTing , Lei Yu , Qu Ying , Fan Zhen , Zhang Ting , Xu Yangbin , Du Qian , Brugger Daniel , Chen Yulin , Zhang Ke , Zhang Enping
Published: August 2023

Inflammatory bowel disease (IBD) is associated with gut dysbiosis and can lead to colitis-associated malignancies. Bacteroides uniformis (Bu) regulates animal intestinal homeostasis; however, the mechanism by which it alleviates colitis in mice remains unknown. We investigated the effects of B. uniformis JCM5828 and its metabolites on female C57BL/6J mice with dextran sulfate sodium salt (DSS) induced colitis. Treatment with Bu considerably alleviated colitis progression and restored the mechanical and immune barrier protein expression. Additionally, Bu increased the abundance of the symbiotic bacteria Bifidobacterium and Lactobacillus vaginalis while decreasing that of pathogenic Escherichia-Shigella, and modulated intestinal bile acid metabolism. Bu largely regulated the expression of key regulatory proteins of the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways in colonic tissues and the differentiation of TH17 cells. However, Bu could not directly inhibit TH17 cell differentiation in vitro; it modulated the process in the lamina propria by participating in bile acid metabolism and regulating key metabolites (alpha-muricholic, hyodeoxycholic, and isolithocholic acid), thereby modulating the intestinal immune response. Our findings suggest that Bu or bile acid supplements are potential therapies for colitis and other diseases associated with intestinal barrier dysfunction.
IHH enhancer variant within neighboring NHEJ1 intron causes microphthalmia anophthalmia and coloboma
Authors: Wormser Ohad , Perez Yonatan , Dolgin Vadim , Kamali Bahman , Tangeman Jared A. , Gradstein Libe , Yogev Yuval , Hadar Noam , Freund Ofek , Drabkin Max , Halperin Daniel , Irron Inbar , Grajales-Esquivel Erika , Del Rio-Tsonis Katia , Birnbaum Ramon Y. , Akler Gidon , Birk Ohad S.
Published: August 2023

Genomic sequences residing within introns of few genes have been shown to act as enhancers affecting expression of neighboring genes. We studied an autosomal recessive phenotypic continuum of microphthalmia, anophthalmia and ocular coloboma, with no apparent coding-region disease-causing mutation. Homozygosity mapping of several affected Jewish Iranian families, combined with whole genome sequence analysis, identified a 0.5 Mb disease-associated chromosome 2q35 locus (maximal LOD score 6.8) harboring an intronic founder variant in NHEJ1, not predicted to affect NHEJ1. The human NHEJ1 intronic variant lies within a known specifically limb-development enhancer of a neighboring gene, Indian hedgehog (Ihh), known to be involved in eye development in mice and chickens. Through mouse and chicken molecular development studies, we demonstrated that this variant is within an Ihh enhancer that drives gene expression in the developing eye and that the identified variant affects this eye-specific enhancer activity. We thus delineate an Ihh enhancer active in mammalian eye development whose variant causes human microphthalmia, anophthalmia and ocular coloboma. The findings highlight disease causation by an intronic variant affecting the expression of a neighboring gene, delineating molecular pathways of eye development.
Metallurgical pathways of lead leaching from brass
Authors: Zhu Te , Li Wei , Kwok Jonathan Chun Ming , Siu Kai Wing , Yin Lu , Ngan Alfonso Hing Wan
Published: August 2023

Leaded (Pb) brass components used in water pipeworks are prone to lead leaching following soldering or brazing during installation. Synchrotron radiation X-ray imaging shows that in the initial state of potable-water grade brass samples, Pb exists mainly as isolated or linked-together particles from sub-micron to several microns large. On heating to the usual soldering temperature of ~200 °C, the Pb contents surface rapidly via diffusion pathways involving an interpenetrating Pb–brass structure with orientation relationship (11$$\bar{1}$$

1

̅

)α-brass//(220)Pb; [011]α-brass//[$$\bar{1}$$

1

̅

13]Pb. On heating to the usual brazing temperature of 700 °C, the Pb particles melt and expand in volume, with the Pb content forced into the brass lattice preferentially along {101}α-brass planes, forming Pb phase of low sphericity or even large sheets. On immersion in water, the surfaced Pb particles are oxidized to form PbO needles along the normal direction of {$$\bar{2}\bar{2}2$$

2

̅

2

̅

2

}PbO planes, which are then easily washed away to cause Pb leaching.
Three-dimensional neutron far-field tomography of a bulk skyrmion lattice
Authors: Henderson M. E. , Heacock B. , Bleuel M. , Cory D. G. , Heikes C. , Huber M. G. , Krzywon J. , Nahman-Levesqué O. , Luke G. M. , Pula M. , Sarenac D. , Zhernenkov K. , Pushin D. A.
Published: August 2023

Magnetic skyrmions are localized non-collinear spin textures, characterized by an integer topological charge. Commonly observed in thin systems as two-dimensional sheets, in three dimensions skyrmions form tubes that are thought to nucleate and annihilate along their depth on points of vanishing magnetization. However, a lack of techniques that can probe the bulk of the material has made it difficult to perform experimental visualizations of skyrmion lattices and their stabilization through defects. Here we present three-dimensional visualizations of a bulk Co8Zn8Mn4 skyrmion lattice through a tomographic algorithm applied to multiprojection small-angle neutron scattering measurements. Reconstructions of the sample show a disordered skyrmion lattice exhibiting three-dimensional topological transitions through emergent (anti)monopole branching and segmentation defect pathways. Our technique provides insights into skyrmion stabilization and topological transition pathways in a bulk skyrmion lattice, guiding the future development and manipulation of skyrmion materials for spintronic applications.
Short-term dietary changes can result in mucosal and systemic immune depression
Authors: Siracusa Francesco , Schaltenberg Nicola , Kumar Yogesh , Lesker Till R. , Steglich Babett , Liwinski Timur , Cortesi Filippo , Frommann Laura , Diercks Björn-Phillip , Bönisch Friedericke , Fischer Alexander W. , Scognamiglio Pasquale , Pauly Mira J. , Casar Christian , Cohen Yotam , Pelczar Penelope , Agalioti Theodora , Delfs Flemming , Worthmann Anna , Wahib Ramez , Jagemann Bettina , Mittrücker Hans-Willi , Kretz Oliver , Guse Andreas H. , Izbicki Jakob R. , Lassen Kara G. , Strowig Till , Schweizer Michaela , Villablanca Eduardo J. , Elinav Eran , Huber Samuel , Heeren Joerg , Gagliani Nicola
Published: August 2023

Omnivorous animals, including mice and humans, tend to prefer energy-dense nutrients rich in fat over plant-based diets, especially for short periods of time, but the health consequences of this short-term consumption of energy-dense nutrients are unclear. Here, we show that short-term reiterative switching to ‘feast diets’, mimicking our social eating behavior, breaches the potential buffering effect of the intestinal microbiota and reorganizes the immunological architecture of mucosa-associated lymphoid tissues. The first dietary switch was sufficient to induce transient mucosal immune depression and suppress systemic immunity, leading to higher susceptibility to Salmonella enterica serovar Typhimurium and Listeria monocytogenes infections. The ability to respond to antigenic challenges with a model antigen was also impaired. These observations could be explained by a reduction of CD4+ T cell metabolic fitness and cytokine production due to impaired mTOR activity in response to reduced microbial provision of fiber metabolites. Reintroducing dietary fiber rewired T cell metabolism and restored mucosal and systemic CD4+ T cell functions and immunity. Finally, dietary intervention with human volunteers confirmed the effect of short-term dietary switches on human CD4+ T cell functionality. Therefore, short-term nutritional changes cause a transient depression of mucosal and systemic immunity, creating a window of opportunity for pathogenic infection.
Fanconi anemia DNA crosslink repair factors protect against LINE-1 retrotransposition during mouse development
Authors: Bona Nazareno , Crossan Gerry P.
Published: August 2023

Long interspersed nuclear element 1 (LINE-1) is the only autonomous retrotransposon in humans and new integrations are a major source of genetic variation between individuals. These events can also lead to de novo germline mutations, giving rise to heritable genetic diseases. Recently, a role for DNA repair in regulating these events has been identified. Here we find that Fanconi anemia (FA) DNA crosslink repair factors act in a common pathway to prevent retrotransposition. We purify recombinant SLX4-XPF-ERCC1, the crosslink repair incision complex, and find that it cleaves putative nucleic acid intermediates of retrotransposition. Mice deficient in upstream crosslink repair signaling (FANCA), a downstream component (FANCD2) or the nuclease XPF-ERCC1 show increased LINE-1 retrotransposition in vivo. Organisms limit retrotransposition through transcriptional silencing but this protection is attenuated during early development leaving the zygote vulnerable. We find that during this window of vulnerability, DNA crosslink repair acts as a failsafe to prevent retrotransposition. Together, our results indicate that the FA DNA crosslink repair pathway acts together to protect against mutation by restricting LINE-1 retrotransposition.
Mutational analysis of hemoglobin genes and functional characterization of detected variants, through in-silico analysis, in Pakistani beta-thalassemia major patients
Authors: Ejaz Samina , Abdullah Iqra , Usman Muhammad , Iqbal Muhammad Arslan , Munawar Sidra , Khan Muhammad Irfan , Imtiaz Nagina , Tahir Hanniah , Bari Muhammad Ihsan , Rasool Tayyaba , Fatima Aneeza , Anwar Ramsha , Durrani Ayman , Hameed Yasir
Published: August 2023

Thalassemia is one of the most prevalent genetic disorders worldwide. The present study aimed to explore the mutational spectrum of all hemoglobin (HB) encoding genes and to identify the potentially damaging and pathogenic variants in the beta (β)-thalassemia major patients and thalassemia minor carriers of Southern Punjab, Pakistan. A total of 49 β-thalassemia major patients and 49 carrier samples were screened for the identification of HBA1, HBA2, HBB, HBD, HBE1, HBG1 and HBG2 variants by NGS. PCR was performed for the amplification of HB encoding genes and the amplified product of 13 patients and 7 carrier samples were processed for the Sanger sequencing. Various bioinformatics tools and databases were employed to reveal the functional impact and pathogenicity potential of the observed variants. Results depicted a total of 20 variants of HB-related genes by NGS and 5 by Sanger sequencing in thalassemia patients. While 20 variants by NGS and 3 by Sanger were detected in carriers. Few known genetic variants of HB-encoding genes are being reported for the first time in Pakistani thalassemia patients and carriers. However, two novel HBB variants c.375A>C (p.P125P) and c.*61T>G and a novel variant of HBE1 (c.37A>T (p.T13S)) were also documented. Pathogenicity analysis predicted the pathogenic potential of HBB variants (c.47G>A (p.W16*), c.27-28insG (p. S10fs), and c.92+5G>C) for β thalassemia. The study of functional impact indicated that these HBB variants result in the premature termination of translation leading to the loss of functional β-globin protein. It is therefore suggested that the pathogenic HBB variants, identified during present study, can be employed for the diagnosis, carrier screening, and planning therapy of thalassemia.
Diffusion law of coal gangue slurry and the application of fluidized filling technology of gangue in caving area
Authors: Zhang Ji-qiang , He Xiang , Yang Ke , Wei Zhen , Zhao Xin-Yuan , Fang Jue-jing
Published: August 2023

In order to deeply study the basic characteristics, diffusion laws, and flow laws of coal gangue and coal gangue slurry, the basic characteristic parameters of coal gangue and coal gangue slurry were obtained through particle size distribution test, electron microscope scanning test, X-ray diffraction test, X-ray fluorescence spectrum test, and angle of repose test. The conveying performance test of coal gangue slurry was carried out, and based on this, a simulation test of coal gangue slurry caving areas was designed. The diffusion and flow laws of coal gangue slurry under the same inclination angle were summarized, and the field test of fluidization filling in the caving areas was conducted. The results show that: (1) The water-to-gangue ratio was the main controlling factor for the conveying performance of coal gangue slurry. The extensibility, slump, and bleeding rate of the coal gangue slurry increased with the increase of the water-to-gangue ratio. (2) The diffusion profile of coal gangue slurry at different dip angles was arc-shaped, and the diffusion distance of slurry increased with the increase of infiltration time. However, there were differences in the sustained diffusion ability of different dip angles. (3) At the same time interval, the spatial accumulation patterns of scattered gangue in different regions will lead to differences in the diffusion speed of the slurry. (4) Both burying and hanging pipes in the falling area can safely and efficiently fill the gangue slurry. The diffusion distance of the caving areas in the test working face was basically consistent with the diffusion distance of the slurry in the simulation test of the coal gangue slurry caving areas.
Iridescent biofilms of Cellulophaga lytica are tunable platforms for scalable, ordered materials
Authors: Sullivan Claretta J. , Brown Kennedy , Hung Chia-Suei , Tang Joseph Kuo-Hsiang , DeSimone Mark , Chen Vincent , Lloyd Pamela F. , Gupta Maneesh , Juhl Abby , Crookes-Goodson Wendy , Vasudev Milana , Dennis Patrick B. , Kelley-Loughnane Nancy
Published: August 2023

Nature offers many examples of materials which exhibit exceptional properties due to hierarchical assembly of their constituents. In well-studied multi-cellular systems, such as the morpho butterfly, a visible indication of having ordered submicron features is given by the display of structural color. Detailed investigations of nature’s designs have yielded mechanistic insights and led to the development of biomimetic materials at laboratory scales. However, the manufacturing of hierarchical assemblies at industrial scales remains difficult. Biomanufacturing aims to leverage the autonomy of biological systems to produce materials at lower cost and with fewer carbon emissions. Earlier reports documented that some bacteria, particularly those with gliding motility, self-assemble into biofilms with polycrystalline structures and exhibit glittery, iridescent colors. The current study demonstrates the potential of using one of these bacteria, Cellulophaga lytica, as a platform for the large scale biomanufacturing of ordered materials. Specific approaches for controlling C. lytica biofilm optical, spatial and temporal properties are reported. Complementary microscopy-based studies reveal that biofilm color variations are attributed to changes in morphology induced by cellular responses to the local environment. Incorporation of C. lytica biofilms into materials is also demonstrated, thereby facilitating their handling and downstream processing, as would be needed during manufacturing processes. Finally, the utility of C. lytica as a self-printing, photonic ink is established by this study. In summary, autonomous surface assembly of C. lytica under ambient conditions and across multiple length scales circumvent challenges that currently hinder production of ordered materials in industrial settings.
Muscle power-related parameters in middle-aged and older Brazilian women: a cross-sectional study
Authors: Coelho-Júnior Hélio José , de Oliveira Gonçalves Ivan , Landi Francesco , Calvani Riccardo , Tosato Matteo , Picca Anna , Marzetti Emanuele
Published: August 2023

The present study was conducted to provide normative values for lower-limb muscle power estimated through equations based on the 5 times sit-to-stand (5STS) test in Brazilian older women. In addition, we investigated the association between muscle power parameters and age. The study followed a cross-sectional design. Participants were community-dwelling women. Candidates were considered eligible if they were 18 years or older, lived independently, and possessed sufficient physical and cognitive abilities to perform all measurements required by the protocol. The 5STS test was performed as fast as possible using a standard protocol. Absolute, relative, and allometric muscle power measures were estimated using 5STS-based equations. Two thousand four-hundred seventy-one women participated in the present study. Results indicated that muscle power-related parameters decreased linearly with age. Women 60–69 years showed a marginal reduction in absolute (− 5.2%), relative (− 7.9%), and allometric (− 4.0%) muscle power. A larger reduction was observed in those 70–79 years and reached ¼ of loss in participants ≥ 80, in comparison to middle-aged participants. Pearson’s correlation and linear regression analyses indicated that power-related parameters were negatively associated with age. In conclusion, data of the present study provide normative values for lower-limb muscle power parameters according to 5STS-based equations. We observed that muscle power-related parameters declined with age, such that participants 60–69, 70–79, and ≥ 80 years displayed lower absolute and relative muscle power compared middle-aged women. A later decline was observed in allometric muscle power. Relative muscle power declined to a greater extent than other parameters, suggesting a possible window of opportunity for interventions.
Eschar dissolution and the immunoregulator effect of keratinase on burn wounds
Authors: Xu Yan , Hu Kai , Liu Chenyang , Du Pan , Zhou Feifan , Lu Yichi , Fu Qiuyan , Xu Jianmin , Lyu Guozhong
Published: August 2023

At present, enzyme debridement preparation has shown a good curative effect on eschar removal of burn wounds. Keratinase has shown great potential in enzymatic debridement because of its good fibrin-degrading ability. In this study, the debridement of keratinase was examined by using a third degree burn wound model in rats. We observed the wound, and keratinase shortened the time of eschar dissolution after debridement. Histopathology and immunofluorescence staining showed that the eschar in the keratinase group became thinner, inflammatory cell infiltration in the wound increased, the fluorescence intensity of the macrophage surface marker CD68 increased, and the CD163/CD86 ratio increased. In bone marrow-derived macrophages (BMDMs), there was no significant difference in the activity of CCK-8 in cells in the keratinase group compared with the control group. The fluorescence intensity of the keratinase group was higher than that of the control group. At 12 h, the cell scratches were obviously closed. The number of migrated Transwell cells increased. Flow cytometry and immunofluorescence analysis showed increased expression of CD206 and Arg-1 and decreased expression of CD86 and iNOS. The gene expression of the Arg-1, iNOS and IL-10 was increased, as shown by qPCR. The secretion of IL-10 was increased and TNF-α was decreased, as shown by ELISA. We concluded that keratinase dissolution of eschar not only has a hydrolytic effect on eschar but may also affect immune regulation to enhance the migration and phagocytosis of macrophages, promote the polarization of macrophages, and further enhance the effect of eschar dissolution. Therefore, keratinase may have good prospects for the debridement of burn wounds.
Impact of health disparities on national breast cancer screening participation rates in South Korea
Authors: Nari Fatima , Park Juwon , Kim Nayeon , Kim Dong Jin , Jun Jae Kwan , Choi Kui Son , Suh Mina
Published: August 2023

Socioeconomic barriers to cancer screening exist at a regional level. The deprivation index is used to estimate socioeconomic gradients and health disparities across different geographical regions. We aimed to examine the impact of deprivation on breast cancer screening participation rates among South Korean women. Municipal breast cancer screening participation rates in women were extracted from the National Cancer Screening Information System and linked to the Korean version of the deprivation index constructed by the Korea Institute for Health and Social Affairs. A generalised linear mixed model was employed to investigate the association between the deprivation index and age-standardised breast cancer screening participation rates in 2005, 2012, and 2018. Participation rates increased gradually across all age groups from 2005 to 2018. Participants in their 60 s consistently had one of the highest participation rates (2005: 30.37%, 2012: 61.57%, 2018: 65.88%). In 2005, the most deprived quintile had a higher estimate of breast cancer screening participation than the least deprived quintile (2nd quintile; estimate: 1.044, p = 0.242, 3rd quintile; estimate: 1.153, p = 0.192, 4th quintile; estimate: 3.517, p = 0.001, 5th quintile; estimate: 6.913, p =  < 0.0001). In 2012, the participation rate also increased as the level of deprivation increased. There were no statistically meaningful results in 2018. Regions with high deprivation have a higher participation rate in breast cancer screening. The role of health disparities in determining cancer outcomes among women in Korea requires further examination.
Identification of tumor-related genes via RNA sequencing of tumor tissues in Xenopus tropicalis
Authors: Kitamura Kazuki , Yamamoto Takayoshi , Ochi Haruki , Suzuki Makoto , Suzuki Nanoka , Igawa Takeshi , Yoshida Tadashi , Futakuchi Mitsuru , Ogino Hajime , Michiue Tatsuo
Published: August 2023

Cancer treatment is still challenging because the disease is often caused by multiple mutations. Although genomic studies have identified many oncogenes and tumor suppressor genes, gene sets involved in tumorigenesis remain poorly understood. Xenopus, a genus of aquatic frogs, is a useful model to identify gene sets because it can be genetically and experimentally analyzed. Here, we analyzed gene expression in tumor tissues of three individuals in Xenopus tropicalis and identified 55 differentially expressed genes (DEGs). Gene ontology (GO) analysis showed that the upregulated genes in the tumor tissues were enriched in GO terms related to the extracellular matrix and collagen fibril organization. Hierarchical clustering showed that the gene expression patterns of tumor tissues in X. tropicalis were comparable to those of human connective, soft, and subcutaneous tissue-derived cancers. Additionally, pathway analysis revealed that these DEGs were associated with multiple pathways, including the extracellular matrix, collagen fibril organization, MET signaling, and keratan sulfate. We also found that the expression tendency of some DEGs that have not been well analyzed in the cancer field clearly determines the prognosis of human cancer patients. This study provides a remarkable reference for future experimental work on X. tropicalis to identify gene sets involved in human cancer.