bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diminished NAD+ levels and activation of retrotransposons promote postovulatory aged oocyte (POAO) death
Authors: Singh Ajay K. , Mohanty Aradhana , Kumar S. Lava , Kumari Anjali , Beniwal Rohit , Kumar Etikuppam Ajith , Birajdar Pravin , Mohd Athar , Prasada Rao H. B. D. 
Published: February 2024

AbstractDeath is the fate of postovulatory aged or unfertilized oocytes (POAO) in many animals. However, precise molecular mechanisms are yet to be discovered. Here, we demonstrate that increased amounts of reactive oxygen species (ROS), calcium ion (Ca+2) channels, and retrotransposon activity induce apoptosis, which in turn causes POAO death. Notably, suppression of ROS, Ca+2 channels, and retrotransposons delayed POAO death. Further, we found that the histone H4K12 and K16 acetylation increased via downregulation of NAD+ and NAD+ -dependent histone deacetylase SIRT3. Furthermore, adding NMN, sodium pyruvate, or CD38 inhibition delayed the death of postovulatory aged oocytes. Finally, we demonstrate the conservation of retrotransposon-induced DNA damage-dependent POAO death in higher-order vertebrates. Our findings suggest that POAO mortality is caused by cyclic cascade metabolic interactions in which low NAD+ levels increase histone acetylation by inhibiting histone deacetylases, resulting in an increase in retrotransposons, ROS, and Ca+2 channel activity and thus contributing to DNA damage-induced apoptosis.
Structure-function analysis of the cyclic β-1,2-glucan synthase from Agrobacterium tumefaciens
Authors: Sedzicki Jaroslaw , Ni Dongchun , Lehmann Frank , Stahlberg Henning , Dehio Christoph 
Published: February 2024

AbstractThe synthesis of complex sugars is a key aspect of microbial biology. Cyclic β-1,2-glucan (CβG) is a circular polysaccharide critical for host interactions of many bacteria, including major pathogens of humans (Brucella) and plants (Agrobacterium). CβG is produced by the cyclic glucan synthase (Cgs), a multi-domain membrane protein. So far, its structure as well as the mechanism underlining the synthesis have not been clarified. Here we use cryo-electron microscopy (cryo-EM) and functional approaches to study Cgs from A. tumefaciens. We determine the structure of this complex protein machinery and clarify key aspects of CβG synthesis, revealing a distinct mechanism that uses a tyrosine-linked oligosaccharide intermediate in cycles of polymerization and processing of the glucan chain. Our research opens possibilities for combating pathogens that rely on polysaccharide virulence factors and may lead to synthetic biology approaches for producing complex cyclic sugars.
Disentangling the multiorbital contributions of excitons by photoemission exciton tomography
Authors: Bennecke Wiebke , Windischbacher Andreas , Schmitt David , Bange Jan Philipp , Hemm Ralf , Kern Christian S. , D’Avino Gabriele , Blase Xavier , Steil Daniel , Steil Sabine , Aeschlimann Martin , Stadtmüller Benjamin , Reutzel Marcel , Puschnig Peter , Jansen G. S. Matthijs , Mathias Stefan 
Published: February 2024

AbstractExcitons are realizations of a correlated many-particle wave function, specifically consisting of electrons and holes in an entangled state. Excitons occur widely in semiconductors and are dominant excitations in semiconducting organic and low-dimensional quantum materials. To efficiently harness the strong optical response and high tuneability of excitons in optoelectronics and in energy-transformation processes, access to the full wavefunction of the entangled state is critical, but has so far not been feasible. Here, we show how time-resolved photoemission momentum microscopy can be used to gain access to the entangled wavefunction and to unravel the exciton’s multiorbital electron and hole contributions. For the prototypical organic semiconductor buckminsterfullerene (C60), we exemplify the capabilities of exciton tomography and achieve unprecedented access to key properties of the entangled exciton state including localization, charge-transfer character, and ultrafast exciton formation and relaxation dynamics.
Molecular and clinical analyses of PHF6 mutant myeloid neoplasia provide their pathogenesis and therapeutic targeting
Authors: Kubota Yasuo , Gu Xiaorong , Terkawi Laila , Bodo Juraj , Przychodzen Bartlomiej P. , Awada Hussein , Williams Nakisha , Gurnari Carmelo , Kawashima Naomi , Aly Mai , Durmaz Arda , Mori Minako , Ponvilawan Ben , Kewan Tariq , Bahaj Waled , Meggendorfer Manja , Jha Babal K. , Visconte Valeria , Rogers Heesun J. , Haferlach Torsten , Maciejewski Jaroslaw P. 
Published: February 2024

AbstractPHF6 mutations (PHF6MT) are identified in various myeloid neoplasms (MN). However, little is known about the precise function and consequences of PHF6 in MN. Here we show three main findings in our comprehensive genomic and proteomic study. Firstly, we show a different pattern of genes correlating with PHF6MT in male and female cases. When analyzing male and female cases separately, in only male cases, RUNX1 and U2AF1 are co-mutated with PHF6. In contrast, female cases reveal co-occurrence of ASXL1 mutations and X-chromosome deletions with PHF6MT. Next, proteomics analysis reveals a direct interaction between PHF6 and RUNX1. Both proteins co-localize in active enhancer regions that define the context of lineage differentiation. Finally, we demonstrate a negative prognostic role of PHF6MT, especially in association with RUNX1. The negative effects on survival are additive as PHF6MT cases with RUNX1 mutations have worse outcomes when compared to cases carrying single mutation or wild-type.
An atlas of epithelial cell states and plasticity in lung adenocarcinoma
Authors: Han Guangchun , Sinjab Ansam , Rahal Zahraa , Lynch Anne M. , Treekitkarnmongkol Warapen , Liu Yuejiang , Serrano Alejandra G. , Feng Jiping , Liang Ke , Khan Khaja , Lu Wei , Hernandez Sharia D. , Liu Yunhe , Cao Xuanye , Dai Enyu , Pei Guangsheng , Hu Jian , Abaya Camille , Gomez-Bolanos Lorena I. , Peng Fuduan , Chen Minyue , Parra Edwin R. , Cascone Tina , Sepesi Boris , Moghaddam Seyed Javad , Scheet Paul , Negrao Marcelo V. , Heymach John V. , Li Mingyao , Dubinett Steven M. , Stevenson Christopher S. , Spira Avrum E. , Fujimoto Junya , Solis Luisa M. , Wistuba Ignacio I. , Chen Jichao , Wang Linghua , Kadara Humam 
Published: February 2024

AbstractUnderstanding the cellular processes that underlie early lung adenocarcinoma (LUAD) development is needed to devise intervention strategies1. Here we studied 246,102 single epithelial cells from 16 early-stage LUADs and 47 matched normal lung samples. Epithelial cells comprised diverse normal and cancer cell states, and diversity among cancer cells was strongly linked to LUAD-specific oncogenic drivers. KRAS mutant cancer cells showed distinct transcriptional features, reduced differentiation and low levels of aneuploidy. Non-malignant areas surrounding human LUAD samples were enriched with alveolar intermediate cells that displayed elevated KRT8 expression (termed KRT8+ alveolar intermediate cells (KACs) here), reduced differentiation, increased plasticity and driver KRAS mutations. Expression profiles of KACs were enriched in lung precancer cells and in LUAD cells and signified poor survival. In mice exposed to tobacco carcinogen, KACs emerged before lung tumours and persisted for months after cessation of carcinogen exposure. Moreover, they acquired Kras mutations and conveyed sensitivity to targeted KRAS inhibition in KAC-enriched organoids derived from alveolar type 2 (AT2) cells. Last, lineage-labelling of AT2 cells or KRT8+ cells following carcinogen exposure showed that KACs are possible intermediates in AT2-to-tumour cell transformation. This study provides new insights into epithelial cell states at the root of LUAD development, and such states could harbour potential targets for prevention or intervention.
Anti-TIGIT antibody improves PD-L1 blockade through myeloid and Treg cells
Authors: Guan Xiangnan , Hu Ruozhen , Choi Yoonha , Srivats Shyam , Nabet Barzin Y. , Silva John , McGinnis Lisa , Hendricks Robert , Nutsch Katherine , Banta Karl L. , Duong Ellen , Dunkle Alexis , Chang Patrick S. , Han Chia-Jung , Mittman Stephanie , Molden Nandini , Daggumati Pallavi , Connolly Wendy , Johnson Melissa , Abreu Delvys Rodriguez , Cho Byoung Chul , Italiano Antoine , Gil-Bazo Ignacio , Felip Enriqueta , Mellman Ira , Mariathasan Sanjeev , Shames David S. , Meng Raymond , Chiang Eugene Y. , Johnston Robert J. , Patil Namrata S. 
Published: February 2024

AbstractTiragolumab, an anti-TIGIT antibody with an active IgG1κ Fc, demonstrated improved outcomes in the phase 2 CITYSCAPE trial (ClinicalTrials.gov: NCT03563716) when combined with atezolizumab (anti-PD-L1) versus atezolizumab alone1. However, there remains little consensus on the mechanism(s) of response with this combination2. Here we find that a high baseline of intratumoural macrophages and regulatory T cells is associated with better outcomes in patients treated with atezolizumab plus tiragolumab but not with atezolizumab alone. Serum sample analysis revealed that macrophage activation is associated with a clinical benefit in patients who received the combination treatment. In mouse tumour models, tiragolumab surrogate antibodies inflamed tumour-associated macrophages, monocytes and dendritic cells through Fcγ receptors (FcγR), in turn driving anti-tumour CD8+ T cells from an exhausted effector-like state to a more memory-like state. These results reveal a mechanism of action through which TIGIT checkpoint inhibitors can remodel immunosuppressive tumour microenvironments, and suggest that FcγR engagement is an important consideration in anti-TIGIT antibody development.
Multisensory gamma stimulation promotes glymphatic clearance of amyloid
Authors: Murdock Mitchell H. , Yang Cheng-Yi , Sun Na , Pao Ping-Chieh , Blanco-Duque Cristina , Kahn Martin C. , Kim TaeHyun , Lavoie Nicolas S. , Victor Matheus B. , Islam Md Rezaul , Galiana Fabiola , Leary Noelle , Wang Sidney , Bubnys Adele , Ma Emily , Akay Leyla A. , Sneve Madison , Qian Yong , Lai Cuixin , McCarthy Michelle M. , Kopell Nancy , Kellis Manolis , Piatkevich Kiryl D. , Boyden Edward S. , Tsai Li-Huei 
Published: February 2024

AbstractThe glymphatic movement of fluid through the brain removes metabolic waste1–4. Noninvasive 40 Hz stimulation promotes 40 Hz neural activity in multiple brain regions and attenuates pathology in mouse models of Alzheimer’s disease5–8. Here we show that multisensory gamma stimulation promotes the influx of cerebrospinal fluid and the efflux of interstitial fluid in the cortex of the 5XFAD mouse model of Alzheimer’s disease. Influx of cerebrospinal fluid was associated with increased aquaporin-4 polarization along astrocytic endfeet and dilated meningeal lymphatic vessels. Inhibiting glymphatic clearance abolished the removal of amyloid by multisensory 40 Hz stimulation. Using chemogenetic manipulation and a genetically encoded sensor for neuropeptide signalling, we found that vasoactive intestinal peptide interneurons facilitate glymphatic clearance by regulating arterial pulsatility. Our findings establish novel mechanisms that recruit the glymphatic system to remove brain amyloid.
Quantitative risk factor analysis of prior disease condition and socioeconomic status with the multiple myeloma development: nationwide cohort study
Authors: Choi Suein , Kim Eunjin , Jung Jinhee , Park Sung-Soo , Min Chang-Ki , Han Seunghoon 
Published: February 2024

AbstractEarly diagnosis and following management are important determinants of the prognosis of multiple myeloma (MM). However, screening for MM is not routinely performed because it is rare disease. In this study, we evaluated the association of prior disease condition and socioeconomic status (SES) with MM diagnosis and developed a simple predictive model that can identify patients at high risk of developing MM who may need screening using nationwide database from South Korea. According to multivariate logistic regression analysis, eight prior disease conditions and SES before diagnosis were shown to be predictors of MM development and selected for score development. Total prediction scores were categorized into four groups: patients without any risk (≤ 0) intermediate-1 (0.5–9), intermediate-2 (9–14), and high risk (> 14). The odds ratios for developing MM in the intermediate-1, intermediate-2, and high-risk groups were 1.29, 3.07, and 4.62, respectively. The association of prior disease conditions and SES with MM diagnosis were demonstrated and the simple scoring system to predict the MM risk was developed. This scoring system is also provided by web-based application and could be a useful tool to support clinicians in identifying potential candidates for MM screening.
Conjugating uncoupler compounds with hydrophobic hydrocarbon chains to achieve adipose tissue selective drug accumulation
Authors: Ng Mei Ying , Song Zhi Jian , Venkatesan Gopalakrishnan , Rodriguez-Cuenca Sergio , West James A. , Yang Shili , Tan Choon Hong , Ho Paul Chi-Lui , Griffin Julian L. , Vidal-Puig Antonio , Bassetto Marcella , Hagen Thilo 
Published: February 2024

AbstractOne potential approach for treating obesity is to increase energy expenditure in brown and white adipose tissue. Here we aimed to achieve this outcome by targeting mitochondrial uncoupler compounds selectively to adipose tissue, thus avoiding side effects from uncoupling in other tissues. Selective drug accumulation in adipose tissue has been observed with many lipophilic compounds and dyes. Hence, we explored the feasibility of conjugating uncoupler compounds with a lipophilic C8-hydrocarbon chain via an ether bond. We found that substituting the trifluoromethoxy group in the uncoupler FCCP with a C8-hydrocarbon chain resulted in potent uncoupling activity. Nonetheless, the compound did not elicit therapeutic effects in mice, likely as a consequence of metabolic instability resulting from rapid ether bond cleavage. A lipophilic analog of the uncoupler compound 2,6-dinitrophenol, in which a C8-hydrocarbon chain was conjugated via an ether bond in the para-position (2,6-dinitro-4-(octyloxy)phenol), exhibited increased uncoupling activity compared to the parent compound. However, in vivo pharmacokinetics studies suggested that 2,6-dinitro-4-(octyloxy)phenol was also metabolically unstable. In conclusion, conjugation of a hydrophobic hydrocarbon chain to uncoupler compounds resulted in sustained or improved uncoupling activity. However, an ether bond linkage led to metabolic instability, indicating the need to conjugate lipophilic groups via other chemical bonds.
High rate of species misidentification reduces the taxonomic certainty of European biodiversity databases of ivies (Hedera L.)
Authors: Coca-de-la-Iglesia Marina , Gallego-Narbón Angélica , Alonso Alejandro , Valcárcel Virginia 
Published: February 2024

AbstractThe digitization of natural history specimens and the popularization of citizen science are creating an unprecedented availability of large amounts of biodiversity data. These biodiversity inventories can be severely affected by species misidentification, a source of taxonomic uncertainty that is rarely acknowledged in biodiversity data management. For these reasons, taxonomists debate the use of online repositories to address biological questions at the species level. Hedera L. (ivies) provides an excellent case study as it is well represented in both herbaria and online repositories with thousands of records likely to be affected by high taxonomic uncertainty. We analyze the sources and extent of taxonomic errors in the identification of the European ivy species by reviewing herbarium specimens and find a high misidentification rate (18% on average), which varies between species (maximized in H. hibernica: 55%; H. azorica: 48%; H. iberica: 36%) and regions (maximized in the UK: 38% and Spain: 27%). We find a systematic misidentification of all European ivies with H. helix behind the high misidentification rates in herbaria and warn of even higher rates in online records. We compile a spatial database to overcome the large discrepancies we observed in species distributions between online and morphologically reviewed records.
Interaction between body mass index and family history of cancer on the risk of female breast cancer
Authors: Cao Jiamin , Li Jun , Zhang Zuofeng , Qin Guoyou , Pang Yi , Wu Mengyin , Gu Kai , Xu Huilin 
Published: February 2024

AbstractBoth body mass index (BMI) and family history of cancer are established risk factors for female breast cancer. However, few studies explored the potential interaction between both factors. We assessed the association of BMI and its interaction with family cancer history on the risk of female breast cancer in Shanghai, China. Based on a population-based prospective cohort study started from 2008 to 2012 with 15,055 Chinese female participants in Minhang district, Shanghai. Cox regression models were used to estimate the association of BMI and its interaction with a family history of cancer on breast cancer risk. The additive interaction was evaluated by the relative excess risk due to interaction (RERI) and the attributable proportion due to interaction (AP), and the multiplicative interaction was assessed by the product term (BMI* family history of cancer) in the Cox regression model. Compared with BMI of < 24 kg/m2 and no family history of cancer, women with BMI of ≥ 24 kg/m2 and a family history of cancer had a higher risk for breast cancer with HR 2.06 (95% CI 1.39, 3.06). There was an additive interaction between BMI and family history of cancer on breast cancer incidence, with the RERI being 0.29 (95% CI 0.08, 0.51) and the AP being 0.37 (95% CI 0.08, 0.66). The coexistence of obesity and cancer family history may exacerbate breast cancer incidence risk, highlighting the importance of weight management in women with a family history of cancer.
Cytotoxic and antiviral activities of Jatropha variegata and Jatropha spinosa in relation to their metabolite profile
Authors: Shari Khawlah , Mohamed Osama G. , Meselhy Khaled M. , Tripathi Ashootosh , Khaleel Amal E. , Abdel-Sattar Essam , Gedaily Rania A. El 
Published: February 2024

AbstractJatropha variegata and Jatropha spinosa (family: Euphorbiaceae) are utilized in Yemeni traditional medicine to treat respiratory tract infection and in different skin conditions such as wound healing, as antibacterial and hemostatic. In this study, we evaluated the cytotoxicity and the antiviral activities of the methanolic J. variegata (leaves: Ext-1, stems: Ext-2, and roots: Ext-3), and J. spinosa extracts (aerial parts: Ext-4 and roots: Ext-5), in addition to their methylene chloride fractions of roots extracts (F-6 and F-7, respectively). All samples were tested against three human cancer cell lines in vitro (MCF-7, HepG2, and A549) and two viruses (HSV-2 and H1N1). Both plants showed significant cytotoxicity, among them, the methylene chloride fractions of roots of J. variegata (F-6) and J. spinosa roots (F-7) showed the highest activity on MCF-7 (IC50 = 1.4 and 1 μg/mL), HepG2 (IC50 = 0.64 and 0.24 μg/mL), and A549 (IC50 = 0.7 and 0.5 μg/mL), respectively, whereas the IC50 values of the standard doxorubicin were (3.83, 4.73, and 4.57 μg/mL) against MCF-7, HepG2, and A549, respectively. These results revealed that the roots of both plants are potential targets for cytotoxic activities. The in vitro results revealed potential antiviral activity for each of Ext-3, Ext-5, F-6, and F-7 against HVS-2 with IC50 of 101.23, 68.83, 4.88, 3.24 μg/mL and against H1N1 with IC50 of 51.29, 27.92, 4.24, and 3.06 μg/mL respectively, whereas the IC50 value of the standard acyclovir against HVS-2 was 83.19 μg/mL and IC50 value of the standard ribavirin against H1N1 was 52.40 μg/mL .The methanol extracts of the roots (Ext-3 and Ext-5) of both plants were characterized using UPLC/MS. A total of 73 metabolites were annotated, including fourteen diterpenoids, eleven flavonoids, ten phenolic acid conjugates, twelve fatty acids and their conjugates, five triterpenes and steroids, two sesquiterpenes, and six coumarins. The cytotoxicity and antiviral activities determined in the present work are explained by the existence of flavonoids, coumarins and diterpenes with commonly known cytotoxicity and antiviral activities.
Production of iron enriched Saccharomyces boulardii: impact of process variables
Authors: Tafazzoli Kiyana , Ghavami Mehrdad , Khosravi-Darani Kianoush 
Published: February 2024

AbstractAbout half of the 1.62 billion cases of anemia are because of poor diet and iron deficiency. Currently, the use of iron-enriched yeasts can be used as the most effective and possible way to prevent and treat anemia due to the ability of biotransformation of mineral compounds into the organic form. In this research, for the first time, Saccharomyces (S.) boulardii was used for iron enrichment with the aim that the probiotic properties of yeast provide a potential iron supplement besides improving the bioavailability of iron. Also, due to its higher resistance than other Saccharomyces strains against stresses, it can protect iron against processing temperatures and stomach acidic-enzymatic conditions. So, the effect of three important variables, including concentration of iron, molasses and KH2PO4 on the growth and biotransformation of yeast was investigated by the Box-Behnken design (BBD). The best conditions occurred in 3 g/l KH2PO4, 20 g/l molasses and 12 mg/l FeSO4 with the highest biotransformation 27 mg Fe/g dry cell weight (DCW) and 6 g/l biomass weight. Such yeast can improve fermented products, provide potential supplement, and restore the lost iron of bread, which is a useful iron source, even for vegetarians-vegans and play an important role in manage with anemia. It is recommended that in future researches, attention should be paid to increasing the iron enrichment of yeast through permeabilizing the membrane and overcoming the structural barrier of the cell wall.
Assessing the perceived effect of non-pharmaceutical interventions on SARS-Cov-2 transmission risk: an experimental study in Europe
Authors: Veltri Giuseppe Alessandro , Steinert Janina Isabel , Sternberg Henrike , Galizzi Matteo M. , Fasolo Barbara , Kourtidis Ploutarchos , Büthe Tim , Gaskell George 
Published: February 2024

AbstractWe conduct a large (N = 6567) online experiment to measure the features of non-pharmaceutical interventions (NPIs) that citizens of six European countries perceive to lower the risk of transmission of SARS-Cov-2 the most. We collected data in Bulgaria (n = 1069), France (n = 1108), Poland (n = 1104), Italy (n = 1087), Spain (n = 1102) and Sweden (n = 1097). Based on the features of the most widely adopted public health guidelines to reduce SARS-Cov-2 transmission (mask wearing vs not, outdoor vs indoor contact, short vs 90 min meetings, few vs many people present, and physical distancing of 1 or 2 m), we conducted a discrete choice experiment (DCE) to estimate the public’s perceived risk of SARS-CoV-2 transmission in scenarios that presented mutually exclusive constellations of these features. Our findings indicate that participants’ perception of transmission risk was most influenced by the NPI attributes of mask-wearing and outdoor meetings and the least by NPI attributes that focus on physical distancing, meeting duration, and meeting size. Differentiating by country, gender, age, cognitive style (reflective or intuitive), and perceived freight of COVID-19 moreover allowed us to identify important differences between subgroups. Our findings highlight the importance of improving health policy communication and citizens’ health literacy about the design of NPIs and the transmission risk of SARS-Cov-2 and potentially future viruses.