bluuebunny/crossref_metadata_2025 huggingface dataset:
Article 4
Authors: Lembke Ulrike
Published: November 2022

This chapter assesses Article 4 of the Convention on the Elimination of All Forms of Discrimination against Women (CEDAW). Article 4, in both its paragraphs, introduces the concept of special measures into the Convention: the first paragraph deals with temporary special measures (TSMs) to accelerate de facto or substantive equality for women and the second concerns special measures to protect maternity, which are not of a temporary nature. The measures under Article 4(1) are TSMs of compensation for, correction of and intervention into gender hierarchies that are supported by gender stereotypes and gender-segregated distribution of power and resources. Article 4(2) focuses on the issue of maternity, legitimizing protective measures for special needs that are linked to biological as well as social aspects of maternity. Thus, it can contribute to integrating maternity into public and working life, dismantle the gendered public–private divide, and support the (economic) recognition and compensation of mostly unpaid care work. Although ‘special measures’ may differ considerably in context, concept, and design, they serve the same purpose: equality for women, including formal, substantive, and transformative equality.
Article 12
Authors: Undurraga Verónica , Cook Rebecca J
Published: November 2022

This chapter discusses Article 12 of the Convention on the Elimination of All Forms of Discrimination against Women (CEDAW). It shows how the CEDAW Committee has applied Article 12 to States parties so as to identify discrimination against women in the field of health care. One pervasive form of gender-based discrimination is the denial or neglect of women’s basic health services due to the failure to take account of the socio-economic determinants of women’s ill health. A further factors of discrimination is that health-care systems are structured in ways that subordinate women and their health-care needs to those of men and deny them their agency in making their own health-care decisions and their voice in designing health systems. Article 12(2) also addresses sex-specific reproductive health-care needs by requiring appropriate services for women relating to pregnancy, confinement, and the post-natal period and adequate nutrition during pregnancy and lactation. General Recommendation No 24 requires that reports of States parties to the Committee demonstrate that their respective health legislation, plans, and policies are based on scientific and ethical research and assessment of the health status and needs of women in that country.
Article 16
Authors: Halperin-Kaddari Ruth , Freeman Marsha A
Published: November 2022

This chapter focuses on Article 16 of the Convention on the Elimination of All Forms of Discrimination against Women (CEDAW). Article 16 obligates States parties to ensure equality between women and men in all aspects of marriage and dissolution of marriage, prohibits child marriage, and obligates States parties to enact a minimum age for marriage and to require marriage registration. In conjunction with Articles 2 and 5, it requires States parties to prohibit discrimination, to eliminate discrimination in civil law and personal status laws, and to address the gender stereotyping in customary and religious law and practice that support persistent inequality within the family. The CEDAW Committee consistently reviews these three overarching requirements within the framework of Article 2 and General Recommendation No 28, commenting on States parties’ progress towards their achievement and emphasizing the areas still to be addressed. The Committee itself has expanded its understanding of the issues under Article 16 progressively, breaking new ground in the areas of the economic consequences of family relations, the connection between domestic violence and questions on child custody, the taxation of married couples, the rights of women living in de facto relationships, and more.
Article 21
Authors: Boerefijn Ineke , Fraser Julie
Published: November 2022

This chapter studies Article 21 of the Convention on the Elimination of All Forms of Discrimination against Women (CEDAW), which combines two distinct topics. First, the CEDAW Committee must report annually on its activities to the General Assembly. This clause can be found in all human rights treaties, although not all treaties include a role for the Economic and Social Council (ECOSOC). The Convention is the only treaty that also requires the Commission on the Status of Women (CSW) to receive the Committee’s annual reports, though only ‘for its information’. The second topic is the reference to ‘suggestions and general recommendations’ based on the examination of States parties’ reports. While the Committee was initially hesitant regarding its mandate under this article, its practice has evolved to include adopting specific concluding observations to State reports and general recommendations on the Convention’s implementation. These documents form part of the Committee’s jurisprudence and are essential tools for a wide variety of actors in understanding the content of Convention obligations as well as addressing obstacles in a particular State context. Over the years, the general recommendations have come to contain detailed analysis of complex situations regarding the realization of women’s rights.
Article 23
Authors: Byrnes Andrew , Anthony Dorothea
Published: November 2022

This chapter reviews Article 23 of the Convention on the Elimination of All Forms of Discrimination against Women (CEDAW). Article 23 is a savings clause, the purpose of which is to clarify the relationship between the provisions of the Convention and those contained in other treaties or national law. It is intended to ensure that the highest standard for the protection of women’s human rights is observed by a State party, whether the source of that obligation is the Convention, another treaty, or national law. Where a national law provides better protection for women’s equality than the Convention does, Article 23(a) provides that the national provision should prevail. The adoption of any new treaty often gives rise to the question of how the obligations of States parties under that treaty relate to their obligations under other conventions and which standard is to prevail if obligations under two treaties conflict. The matter is further complicated if States parties to the earlier treaty are not the same as the States parties to the later treaty. Article 23(b) addresses this issue.
Article 26
Authors: Kroworsch Susann
Published: November 2022

This chapter evaluates Article 26 of the Convention on the Elimination of All Forms of Discrimination against Women (CEDAW). As a ‘revision clause’, Article 26 of the Convention seeks to provide both stability of the text and the necessary flexibility for change. Other human rights treaties also provide for revision, although the procedures may differ. Article 26 provides that a revision may be requested by notification from a State party in written form addressed to the UN Secretary-General (UN SG) and empowers the UN General Assembly (UNGA) to establish the procedure for possible amendment. Where Article 26 is silent on a particular issue, the subsidiary rules of Article 40 of the 1969 Vienna Convention of the Law of Treaties (VCLT) may be applied.
Article 29
Authors: Kroworsch Susann
Published: November 2022

This chapter assesses Article 29 of the Convention on the Elimination of All Forms of Discrimination against Women (CEDAW). In contrast to other UN human rights treaties, the Convention does not provide for a special inter-State complaints mechanism. Hence, the Article 29 ‘settlement of disputes clause’ is an important tool for maintaining the integrity of the text and monitoring the implementation of the Convention. All States parties are authorized to rely on the clause. Any State party can intervene, if it considers that another State party impedes the aim of the Convention, by characterizing the issue as a matter of interpretation and application of the Convention. Article 29 favours the dispute resolution processes listed in the UN Charter Article 33—negotiation, ad hoc arbitration, and adjudication—rather than a more specific inter-State complaint procedure. Article 29 also establishes the compulsory jurisdiction of the International Court of Justice (ICJ) in accordance with Article 36(1) of its Statute if the pre-conditions of Article 29 are met.
Opening Statements
Authors: Vinson Donald E , Reichert Klaus
Published: November 2022

This chapter cites the persuasive techniques and tactical considerations that lawyers can employ for the oral hearing’s opening statement of any arbitration. In terms of arbitration, oral hearing resembles litigation in national courts. Thus, opening statements set up the stage on how and what arbitrators perceive during the hearing. The chapter also highlights the issue of the perspective of the counsel and arbitrators as they may not approach a case from the same perspective amidst the delivery of opening statements. Additionally, thematic anchors is a key psychological consideration in building persuasive opening statements as it would be the foundation of the tribunal’s final decision.
Applicable Laws
Authors: Blackaby Nigel , Partasides Constantine , Redfern Alan
Published: November 2022

This chapter covers the applicable laws imposed by arbitral tribunals for the process of international arbitration. It explains that law governs the contracts conducted in line with international arbitration. Moreover, arbitration is regulated by specific rules of procedure agreed upon by the law of the arbitration place, parties, or the arbitral tribunal. Mostly, modern laws of arbitration leave parties and arbitrators free to decide on the specificity of the procedures as long as both parties are treated equally. On the other hand, international arbitration tends to involve more than a single system of law or legal rules. The chapter also notes the laws governing the terms of arbitration and substance.
Establishment and Organisation of an Arbitral Tribunal
Authors: Blackaby Nigel , Partasides Constantine , Redfern Alan
Published: November 2022

This chapter tackles the process of establishing and organising the arbitral tribunal. An appropriate form of notice of request for arbitration must be delivered, following relevant procedural rules, in order to start an arbitration. Additionally, the rules are relevant to the rules of applicable law. The chapter expounds on the process of commencing an arbitration regarding disputes and their respective parties. On the other hand, the process of establishing a tribunal and arbitrators is known to be lengthy. Thus, institutional arbitration rules suggest the appointment of Emergency Arbitrators as an alternative for parties trying to find relief from national courts.
Conduct of the Proceedings
Authors: Blackaby Nigel , Partasides Constantine , Redfern Alan
Published: November 2022

This chapter explains the process of conducting international arbitration proceedings. Despite the possibility of conducting proceedings in various ways, institutional and ad hoc rules of arbitration often provide an outline of steps and detailed regulations agreed by parties to be followed. Moreover, the agreed regulations must comply with mandatory rules and public policy requirements. Then, party autonomy becomes the guiding principle in determining the international arbitration procedure. The basic underlying structures of international arbitration range between the international conventions, arbitration rules, and the practice of experienced arbitrators and counsel. Depending on the circumstances of a case, arbitral tribunals mostly try to ensure stop further additional hearings beyond post-hearing briefs.
Introduction
Authors: Bork Reinhard
Published: November 2022

This chapter introduces cross-border insolvency issues and their regulation under the EU Regulation 2015/848. It also tackles the role of the Court of Justice of the European Union (CJEU) on regards to European cross-border insolvency laws and the Court’s judicial activism. Cross-border insolvency cases look into which state has the jurisdiction, applicable laws, and judgement recognition on foreign law enforcement. Moreover, the regulation of cross-border insolvency issues improves the internal market while establishing a sector of freedom, security, or justice. The chapter clarifies that the cross-border issues are mostly political in nature instead of geographical. It also covers how the cross-border insolvency law of Brexit and Directive (EU) affected preventive restructuring.
Part 2 The Scope of the Occupant’s Powers and Obligations, 6 Private and Public Property and Natural Resources
Authors: Eliav Lieblich , Eyal Benvenisti
Published: November 2022

This chapter addresses the protections of private and public property under the law of occupation, including their exceptions. Additionally, it discusses the protection of natural resources in occupied territories. In the context of private property, the chapter deals with issues such confiscation, pillage, and destruction; requisitions, expropriation, and seizure—as well as the protection of foreign property and investments. Regarding public property, it addresses mainly state funds and movables. The chapter then moves to analyze the protection of state real estate and natural resources. Doing so, it expounds the concept of usufruct, as well as the various dilemmas that it raises.
RCSB Protein Data Bank (RCSB.org): delivery of experimentally-determined PDB structures alongside one million computed structure models of proteins from artificial intelligence/machine learning
Authors: Burley Stephen K , Bhikadiya Charmi , Bi Chunxiao , Bittrich Sebastian , Chao Henry , Chen Li , Craig Paul A , Crichlow Gregg V , Dalenberg Kenneth , Duarte Jose M , Dutta Shuchismita , Fayazi Maryam , Feng Zukang , Flatt Justin W , Ganesan Sai , Ghosh Sutapa , Goodsell David S , Green Rachel Kramer , Guranovic Vladimir , Henry Jeremy , Hudson Brian P , Khokhriakov Igor , Lawson Catherine L , Liang Yuhe , Lowe Robert , Peisach Ezra , Persikova Irina , Piehl Dennis W , Rose Yana , Sali Andrej , Segura Joan , Sekharan Monica , Shao Chenghua , Vallat Brinda , Voigt Maria , Webb Ben , Westbrook John D , Whetstone Shamara , Young Jasmine Y , Zalevsky Arthur , Zardecki Christine
Published: November 2022

The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), founding member of the Worldwide Protein Data Bank (wwPDB), is the US data center for the open-access PDB archive. As wwPDB-designated Archive Keeper, RCSB PDB is also responsible for PDB data security. Annually, RCSB PDB serves >10 000 depositors of three-dimensional (3D) biostructures working on all permanently inhabited continents. RCSB PDB delivers data from its research-focused RCSB.org web portal to many millions of PDB data consumers based in virtually every United Nations-recognized country, territory, etc. This Database Issue contribution describes upgrades to the research-focused RCSB.org web portal that created a one-stop-shop for open access to ∼200 000 experimentally-determined PDB structures of biological macromolecules alongside >1 000 000 incorporated Computed Structure Models (CSMs) predicted using artificial intelligence/machine learning methods. RCSB.org is a ‘living data resource.’ Every PDB structure and CSM is integrated weekly with related functional annotations from external biodata resources, providing up-to-date information for the entire corpus of 3D biostructure data freely available from RCSB.org with no usage limitations. Within RCSB.org, PDB structures and the CSMs are clearly identified as to their provenance and reliability. Both are fully searchable, and can be analyzed and visualized using the full complement of RCSB.org web portal capabilities.
A large-scale benchmark study of tools for the classification of protein-coding and non-coding RNAs
Authors: Singh Dalwinder , Roy Joy
Published: November 2022

Identification of protein-coding and non-coding transcripts is paramount for understanding their biological roles. Computational approaches have been addressing this task for over a decade; however, generalized and high-performance models are still unreliable. This benchmark study assessed the performance of 24 tools producing >55 models on the datasets covering a wide range of species. We have collected 135 small and large transcriptomic datasets from existing studies for comparison and identified the potential bottlenecks hampering the performance of current tools. The key insights of this study include lack of standardized training sets, reliance on homogeneous training data, gradual changes in annotated data, lack of augmentation with homology searches, the presence of false positives and negatives in datasets and the lower performance of end-to-end deep learning models. We also derived a new dataset, RNAChallenge, from the benchmark considering hard instances that may include potential false alarms. The best and least well performing models under- and overfit the dataset, respectively, thereby serving a dual purpose. For computational approaches, it will be valuable to develop accurate and unbiased models. The identification of false alarms will be of interest for genome annotators, and experimental study of hard RNAs will help to untangle the complexity of the RNA world.
Baseline Neutrophil-to-Eosinophil Ratio Is Associated with Outcomes in Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors
Authors: Zhuang Tony Z , Ravindranathan Deepak , Liu Yuan , Martini Dylan J , Brown Jacqueline T , Nazha Bassel , Russler Greta , Yantorni Lauren B , Caulfield Sarah , Carthon Bradley C , Kucuk Omer , Master Viraj A , Bilen Mehmet Asim
Published: November 2022

Background

Biomarkers have the potential to guide treatment selection and clinical care in metastatic renal cell carcinoma (mRCC) in an expanding treatment landscape. We report baseline neutrophil-to-eosinophil ratios (NER) in patients with mRCC treated with immune checkpoint inhibitors (CPIs) and their association with clinical outcomes.

Methods

We conducted a retrospective review of patients with mRCC treated with CPIs at Winship Cancer Institute from 2015 to 2020 in the United States of America (USA). Demographics, disease characteristics, and laboratory data, including complete blood counts (CBC) were described at the initiation of CPIs. Clinical outcomes were measured as overall survival (OS), progression-free survival (PFS), and clinical benefit (CB) associated with baseline lab values.

Results

A total of 184 patients were included with a median follow-up time of 25.4 months. Patients with baseline NER were categorized into high or low subgroups; high group was defined as NER >49.2 and low group was defined as NER <49.2 with 25% of patients in the high NER group. Univariate analyses (UVA) and multivariable analyses (MVA) identified decreased overall survival (OS) associated with elevated NER. In MVA, patients with a high baseline NER group had a hazard ratio (HR) of 1.68 (95%CI, 1.01-2.82, P = .048) for OS; however, there was no significant difference between groups for PFS. Clinical benefit was seen in 47.3% of patients with low baseline NER and 40% with high NER.

Conclusions

We conclude that elevated baseline NER may be associated with worse clinical outcomes in mRCC. Although results require further validation, NER is a feasible biomarker in patients with CPI-treated mRCC.
It’s What’s True
Authors: Sievers Benjamin L
Published: November 2022

A cancer survivor describes the journey from healthy student through diagnosis and treatment for thyroid cancer and back again
Plant lineage-specific PIKMIN1 drives APC/CCCS52A2 E3-ligase activity-dependent cell division
Authors: Willems Alex , Liang Yuanke , Heyman Jefri , Depuydt Thomas , Eekhout Thomas , Canher Balkan , Van den Daele Hilde , Vercauteren Ilse , Vandepoele Klaas , De Veylder Lieven
Published: November 2022

The anaphase-promoting complex/cyclosome (APC/C) marks key cell cycle proteins for proteasomal breakdown, thereby ensuring unidirectional progression through the cell cycle. Its target recognition is temporally regulated by activating subunits, one of which is called CELL CYCLE SWITCH 52 A2 (CCS52A2). We sought to expand the knowledge on the APC/C by using the severe growth phenotypes of CCS52A2-deficient Arabidopsis (Arabidopsis thaliana) plants as a readout in a suppressor mutagenesis screen, resulting in the identification of the previously undescribed gene called PIKMIN1 (PKN1). PKN1 deficiency rescues the disorganized root stem cell phenotype of the ccs52a2-1 mutant, whereas an excess of PKN1 inhibits the growth of ccs52a2-1 plants, indicating the need for control of PKN1 abundance for proper development. Accordingly, the lack of PKN1 in a wild-type background negatively impacts cell division, while its systemic overexpression promotes proliferation. PKN1 shows a cell cycle phase-dependent accumulation pattern, localizing to microtubular structures, including the preprophase band, the mitotic spindle, and the phragmoplast. PKN1 is conserved throughout the plant kingdom, with its function in cell division being evolutionarily conserved in the liverwort Marchantia polymorpha. Our data thus demonstrate that PKN1 represents a novel, plant-specific protein with a role in cell division that is likely proteolytically controlled by the CCS52A2-activated APC/C.
ASSESSMENT OF GAMMA DOSE AND ANNUAL EFFECTIVE DOSE RATE FOR COMMONLY USED FERTILIZER SAMPLES IN AGRICULTURE FIELD WITH A STATISTICAL APPROACH
Authors: Tamilarasi Azhagesan , Sathish Vilvanathan , Chandrasekaran Ananthanarayanan
Published: November 2022

In this present study, the activity concentration of the naturally occurring radionuclides 238U, 232Th and 40K have been measured in commonly used chemical fertilizers for agriculture by using gamma-ray spectrometry with NaI (TI) detector. Radiological hazard parameters have been calculated for samples. The mean specific activity concentration of the 238U, 232Th and 40K is 176, 5.75 and 4136 Bq kg−1, respectively. Particularly, the mean value of 238U, as well as 40K, is higher than the world recommended value. Also, the average value of radium equivalent activity is 503 Bq kg−1 and the absorbed dose rate (DR) is 282.93 nGyh−1, which is greater than the permissible limit, whereas the annual effective dose rate (AEDR) is 0.316 mSvy−1, which is lower than the world recommended value. Therefore, collected fertilizer samples significantly increase the activity concentration of natural radionuclides in the agricultural soils. Multivariate statistical techniques such as Pearson correlation and factor analysis are carried out for radioactive variables to understand the existing relationship between them. From obtained results reveals that these fertilizer samples increases the probability of adverse health effects due to natural radioactivity.
ARTIFICIAL NEURAL NETWORK MODELS FOR ESTIMATION OF ELECTRIC FIELD INTENSITY AND MAGNETIC FLUX DENSITY IN THE PROXIMITY OF OVERHEAD TRANSMISSION LINE
Authors: Turajlic Emir , Alihodzic Ajdin , Mujezinovic Adnan
Published: November 2022

This paper considers the application of artificial neural network (ANN) models for electric field intensity and magnetic flux density estimation in the proximity of overhead transmission lines. Specifically, two distinct ANN models are used to facilitate independent estimation of electric field intensity and magnetic flux density in the proximity of overhead transmission lines. The considered ANN approach is systematically evaluated under different scenarios. An example of an overhead transmission line with horizontal phase conductor configuration is used to enable a direct comparison of the electric field intensity and magnetic flux density estimates generated by the two ANN models to measurement results obtained over the lateral profile. Further investigation of ANN models involves an extensive study whereby 13 different overhead transmission lines of horizontal configurations are used as the basis for comparing measurement results to estimates provided by the ANN models. In this study, the performance analysis of the ANN models was evaluated using coefficient of determination and root mean square error. The obtained results demonstrate that the considered ANN approach can be used to estimate the electric field intensity and magnetic flux density in the proximity of overhead transmission lines.
BAICALEIN RELIEVES BRAIN INJURY VIA INHIBITING FERROPTOSIS AND ENDOPLASMIC RETICULUM STRESS IN A RAT MODEL OF CARDIAC ARREST
Authors: Ye Zhou , Zhang Fan , Wang Peng , Ran Yingqi , Liu Cong , Lu Jinming , Zhang Mingtao , Yao Lan
Published: November 2022

Background: Cardiac arrest (CA) is one of the leading causes of death worldwide. Endoplasmic reticulum (ER) stress and ferroptosis are proven pathological mechanisms implicated in neuronal damage. Baicalein, a ferroptosis Inhibitor, improved outcomes after traumatic brain injury. We aimed to explore the effects of baicalein on brain injury via ferroptosis and ER stress in a rat model of CA.
Methods: Cardiac arrest models were established in Sprague-Dawley (SD) rats. The sham group (n = 6) was untreated with inducing ventricular fibrillation to cardiac arrest and cardiopulmonary resuscitation (CPR). Survival rats were randomly divided into five groups (n = 6). Ferroptosis inhibitor and ER stress agonist were administered separately and together in three groups. There was no drug intervention in the remaining group. The neurological deficit scores were recorded. Characteristics of ferroptosis were observed. And the associated protein of ferroptosis and ER stress were determined by Western blot. Cerebral ROS production was measured by using 2′,7′-dichlorofluorescein diacetate as the oxidative fluorescent probe. Results: Baicalein treatment improved neurological outcomes and decreased neurocyte injuries compared with CPR group. The changes of ferroptosis, more specifically, iron content, glutathione peroxidase 4 (GPX4), reactive oxygen species (ROS), arachidonate 15-lipoxygenase (ALOX15) and mitochondrial characteristics, were observed in brain tissue after ROSC. ALOX15 was lower in baicalein group than in CPR group. The morphology and structure of mitochondria in baicalein group were better than in CPR group. The ER stress markers, glucose-regulated protein 78, activating Transcription Factor 4 and C/EBP homologous protein was lower in baicalein group compared with CPR group. ROS in tunicamycin group was higher than in CPR group. And ROS in baicalein +tunicamycin group was lower than in tunicamycin group. Conclusion: Ferroptosis and ER stress are both involved in brain injury after ROSC. Baicalein alleviates brain injury via suppressing the ferroptosis and ER stress, and reduces ROS partly through inhibiting ER stress. Baicalein is a potential drug to relieve brain injury after ROSC.
Computationally designed sensors for endogenous Ras activity reveal signaling effectors within oncogenic granules
Authors: Zhang Jason Z. , Nguyen William H. , Greenwood Nathan , Rose John C. , Ong Shao-En , Maly Dustin J. , Baker David
Published: November 2022

Genetically encoded biosensors have accelerated biological discovery, however many important targets such as active Ras (Ras-GTP) are difficult to sense as strategies to match a sensor’s sensitivity to the physiological range of target are lacking. Here, we use computational protein design to generate and optimize intracellular sensors of Ras activity (LOCKR-basedSensor forRasactivity: Ras-LOCKR-S) and proximity labelers of the signaling environment of Ras (LOCKR-based,Rasactivity-dependentProximityLabeler: Ras-LOCKR-PL). We demonstrate that our tools can measure endogenous Ras activity and environment at subcellular resolution. We illustrate the application of these tools by using them to identify Ras effectors, notably Src-Associated in Mitosis 68 kDa protein (SAM68), enriched in oncogenic EML4-Alk granules. Localizing these sensors to these granules revealed that SAM68 enhances Ras activity specifically at the granules, and SAM68 inhibition sensitizes EML4-Alk-driven cancer cells to existing drug therapies, suggesting a possible therapeutic strategy.
The dynamic relationship between COVID-19 cases and SARS-CoV-2 wastewater concentrations across time and space: considerations for model training data sets
Authors: Schill Rebecca , Nelson Kara L. , Harris-Lovett Sasha , Kantor Rose S.
Published: November 2022

During the COVID-19 pandemic, wastewater-based surveillance has been used alongside diagnostic testing to monitor infection rates. With the decline in cases reported to public health departments due to at-home testing, wastewater data may serve as the primary input for epidemiological models, but training these models is not straightforward. We explored factors affecting noise and bias in the ratio between wastewater and case data collected in 26 sewersheds in California from October 2020 to March 2022. The strength of the relationship between wastewater and case data appeared dependent on sampling frequency and population size, but was not increased by wastewater normalization to flow rate or case count normalization to testing rates. Additionally, the lead and lag times between wastewater and case data varied over time and space, and the ratio of log-transformed individual cases to wastewater concentrations changed over time. This ratio increased sequentially in the Epsilon/Alpha, Delta, and Omicron BA.1 variant surges of COVID-19 and was also related to the diagnostic testing rate. Based on this analysis, we present a framework of scenarios describing the dynamics of the case to wastewater ratio to aid in data handling decisions for ongoing modeling efforts.
Common and Rare Variants Associated with Cardiometabolic Traits across 98,622 Whole-Genome Sequences in theAll of UsResearch Program
Authors: Wang Xin , Ryu Justine , Kim Jihoon , Ramirez Andrea , Mayo Kelsey R. ,   All of Us Research Program, Condon Henry , Vaitinadin Nataraja Sarma , Ohno-Machado Lucila , Talavera Greg A. , Ellinor Patrick T. , Lubitz Steven A. , Choi Seung Hoan
Published: November 2022

All of Usis a biorepository aiming to advance biomedical research by providing various types of data in diverse human populations. Here we present a demonstration project validating the program’s genomic data in 98,622 participants. We sought to replicate known genetic associations for three diseases (atrial fibrillation [AF], coronary artery disease, type 2 diabetes [T2D]) and two quantitative traits (height and low-density lipoprotein [LDL]) by conducting common and rare variant analyses. We identified one known risk locus for AF, five loci for T2D, 143 loci for height, and nine loci for LDL. In gene-based burden tests for rare loss-of-function variants, we replicated associations betweenTTNand AF,GIGYF1and T2D,ADAMTS17, ACAN, NPR2and height,APOB, LDLR, PCSK9and LDL. Our results are consistent with previous literature, indicating that theAll of Usprogram is a reliable resource for advancing the understanding of complex diseases in diverse human populations.
miR-210 expression is strongly hypoxia-induced in anaplastic thyroid cancer cell lines and is associated with extracellular vesicles & Argonaute-2
Authors: Powell Bonita H. , Turchinovich Andrey , Wang Yongchun , Gololobova Olesia , Buschmann Dominik , Zeiger Martha A. , Umbricht Christopher B. , Witwer Kenneth W.
Published: November 2022

Hypoxia, or low oxygen tension, is frequently found in highly proliferative solid tumors such as anaplastic thyroid carcinoma (ATC) and is believed to promote resistance to chemotherapy and radiation. Identifying hypoxic cells for targeted therapy may thus be an effective approach to treating aggressive cancers. Here, we explore the potential of the well-known hypoxia-responsive microRNA (miRNA) miR-210-3p as a cellular and extracellular biological marker of hypoxia. We compare miRNA expression across several ATC and papillary thyroid cancer (PTC) cell lines. In the ATC cell line SW1736, miR-210-3p expression levels indicate hypoxia during exposure to low oxygen conditions (2% O2). Furthermore, when released by SW1736 cells into the extracellular space, miR-210-3p is associated with RNA carriers such as extracellular vesicles (EVs) and Argonaute-2 (AGO2), making it a potential extracellular marker for hypoxia.
Plasticity in centromere organization: Holocentromeres can consist of merely a few megabase-sized satellite arrays
Authors: Kuo Yi-Tzu , Câmara Amanda Souza , Schubert Veit , Neumann Pavel , Macas Jiří , Melzer Michael , Chen Jianyong , Fuchs Jörg , Abel Simone , Klocke Evelyn , Huettel Bruno , Himmelbach Axel , Demidov Dmitri , Dunemann Frank , Mascher Martin , Ishii Takayoshi , Marques André , Houben Andreas
Published: November 2022

The centromere is the chromosome region where the microtubules attach during cell division. In contrast to monocentric chromosomes with one centromere location, holocentric species usually distribute hundreds of centromere units along the entire chromatid. We assembled the chromosome-scale reference genome and analyzed the holocentromere and (epi)genome organization of the lilioidChionographis japonica.Remarkably, each of its holocentric chromatids consists of only 7 to 11 evenly-spaced megabase-sized centromere-specific histone H3-positive units. These units contain satellite arrays of 23 and 28 bp-long monomers capable of forming palindromic structures. Like monocentric species,C. japonicaforms distinctly clustered centromeres in chromocenters at interphase. Additionally, the large-scale eu- and heterochromatin arrangement differs betweenC. japonicaand other known holocentric species. Using polymer simulations, we modeled the formation of prometaphase line-like holocentromeres from interphase centromere clusters. Our findings broaden the knowledge about the diversity of centromere organization, showing that holocentricity is not restricted to species with numerous and small centromere units.
Machine learning analysis of the T cell receptor repertoire identifies sequence features that predict self-reactivity
Authors: Textor Johannes , Buytenhuijs Franka , Rogers Dakota , Gauthier Ève Mallet , Sultan Shabaz , Wortel Inge M. N. , Kalies Kathrin , Fähnrich Anke , Pagel René , Melichar Heather J. , Westermann Jürgen , Mandl Judith N.
Published: November 2022

The T cell receptor (TCR) determines the specificity and affinity for both foreign and self-peptides presented by MHC. It is established that self-pMHC reactivity impacts T cell function, but it has been challenging to identify TCR sequence features that predict T cell fate. To discern patterns distinguishing TCRs from naïve CD4+T cells with low versus high self-pMHC reactivity, we used data from 42 mice to train a machine learning (ML) algorithm that predicts self-reactivity directly from TCRβ sequences. This approach revealed that n-nucleotide additions and acidic amino acids weaken self-reactivity. We tested our ML predictions of TCRβ sequence self-reactivity using retrogenic mice. Extrapolating our analyses to independent datasets, we found high predicted self-reactivity for regulatory CD4+T cells and low predicted self-reactivity for T cells responding to chronic infection. Our analyses suggest a potential trade-off between repertoire diversity and self-reactivity intrinsic to the architecture of a TCR repertoire.
ExposomeX: Integrative Exposomic Platform Expediates Discovery of “Exposure-Biology-Disease” Nexus
Authors: Wang Bin , Lan Changxin , Zhang Guohuan , Ren Mengyuan , Feng Yanqiu , Gao Ning , Lin Weinan , Jiangtulu Bahabake , Liu Zhijian , Shao Xuqiang , Su Shu , Wang Yuting , Wang Han , Zhao Fanrong , Peng Bo , Ji Xiaotong , Chen Xiaojia , Nian Min , Fang Mingliang
Published: November 2022

Exposome has become the hotspot of next-generation health studies. To date, there is no available effective platform to standardize the analysis of exposomic data. In this study, we aim to propose one new framework of exposomic analysis and build up one novel integrated platform “ExposomeX” to expediate the discovery of the “Exposure-Biology-Disease” nexus. We have developed 13 standardized modules to accomplish six major functions including statistical learning (E-STAT), exposome database search (E-DB), mass spectrometry data processing (E-MS), meta-analysis (E-META), biological link via pathway integration and protein-protein interaction (E-BIO) and data visualization (E-VIZ). Using ExposomeX, we can effectively analyze the multiple-dimensional exposomics data and investigate the “Exposure-Biology-Disease” nexus by exploring mediation and interaction effects, understanding statistical and biological mechanisms, strengthening prediction performance, and automatically conducting meta-analysis based on well-established literature databases. The performance of ExposomeX has been well validated by re-analyzing two previous multi-omics studies. Additionally, ExposomeX can efficiently help discover new associations, as well as relevant in-depth biological pathways via protein-protein interaction and gene ontology network analysis. In sum, we have proposed a novel framework for standardized exposomic analysis, which can be accessed using both R and online interactive platform (http://www.exposomex.cn/).
A new Paleogene fossil and a new dataset for waterfowl (Aves: Anseriformes) clarify phylogeny, ecological evolution, and avian evolution at the K-Pg Boundary
Authors: Musser Grace , Clarke Julia A.
Published: November 2022

Abstract

Despite making up one of the most ecologically diverse groups of living birds, comprising soaring, diving and giant flightless taxa, the evolutionary relationships and ecological evolution of Anseriformes (waterfowl) remain unresolved. Although Anseriformes have a comparatively rich, global Cretaceous and Paleogene fossil record, morphological datasets for this group that include extinct taxa report conflicting relationships for all known extinct taxa. Correct placement of extinct taxa is necessary to understand whether ancestral anseriform feeding ecology was more terrestrial or one of a set of diverse aquatic ecologies and to better understand avian evolution around the K-T boundary. Here, we present a new morphological dataset for Anseriformes that includes more extant and extinct taxa than any previous anseriform-focused dataset and describe a new anseriform species from the early Eocene Green River Formation of North America. The new taxon has a mediolaterally narrow bill which is not known in any previously described anseriform fossils other than portions of the pseudotoothed Pelagornithidae. The matrix created to assess the placement of this taxon comprises 41 taxa and 719 discrete morphological characters describing skeletal morphology, musculature, syringeal morphology, ecology, and behavior. We additionally combine the morphological dataset with published sequences using Bayesian methods and perform ancestral state reconstruction for ecological and behavioral characters. We recover the new Eocene taxon as a stem anseranatid across all analyses, and find that the new taxon represents a novel ecology within known Anseriformes and the Green River taxa. Results indicate that Anseriformes were likely ancestrally aquatic herbivores with rhamphothecal lamellae and provide insight into avian evolution during and following the K-Pg mass extinction.
A three-dimensional, discrete-continuum model of blood pressure in microvascular networks
Authors: Sweeney Paul W. , Walsh Claire , Walker-Samuel Simon , Shipley Rebecca J.
Published: November 2022

We present a 3D discrete-continuum model to simulate blood pressure in large microvascular tissues in the absence of known capillary network architecture. Our hybrid approach combines a 1D Poiseuille flow description for large, discrete arteriolar and venular networks coupled to a continuum-based Darcy model, point sources of flux, for transport in the capillary bed. We evaluate our hybrid approach using a vascular network imaged from the mouse brain medulla/pons using multi-fluorescence high-resolution episcopic microscopy (MF-HREM). We use the fully-resolved vascular network to predict the hydraulic conductivity of the capillary network and generate a fully-discrete pressure solution to benchmark against. Our results demonstrate that the discrete-continuum methodology is a computationally feasible and effective tool for predicting blood pressure in real-world microvascular tissues when capillary microvessels are poorly defined.
BLEND: A Fast, Memory-Efficient, and Accurate Mechanism to Find Fuzzy Seed Matches in Genome Analysis
Authors: Firtina Can , Park Jisung , Alser Mohammed , Kim Jeremie S. , Cali Damla Senol , Shahroodi Taha , Ghiasi Nika Mansouri , Singh Gagandeep , Kanellopoulos Konstantinos , Alkan Can , Mutlu Onur
Published: November 2022

Generating the hash values of short subsequences, called seeds, enables quickly identifying similarities between genomic sequences by matching seeds with a single lookup of their hash values. However, these hash values can be used only for finding exact-matching seeds as the conventional hashing methods assign distinct hash values for different seeds, including highly similar seeds. Finding only exact-matching seeds causes either 1) increasing the use of the costly sequence alignment or 2) limited sensitivity.

We introduceBLEND,the first efficient and accurate mechanism that can identifybothexact-matching and highly similar seeds with a single lookup of their hash values, called fuzzy seed matches. BLEND 1) utilizes a technique called SimHash, that can generate the same hash value for similar sets, and 2) provides the proper mechanisms for using seeds as sets with the SimHash technique to find fuzzy seed matches efficiently.

We show the benefits of BLEND when used in read overlapping and read mapping. For read overlapping, BLEND is faster by2.4×−83.9×(on average19.3×),has a lower memory footprint by0.9×−14.1 ×(on average3.8×),and finds higher quality overlaps leading to accuratede novoassemblies than the state-of-the-art tool, minimap2. For read mapping, BLEND is fasterby0.8×−4.1×(on average1.7×)than minimap2. Source code is available athttps://github.com/CMU-SAFARI/BLEND.
Deep-learning-assisted Sort-Seq enables high-throughput profiling of gene expression characteristics with high precision
Authors: Feng Huibao , Li Fan , Wang Tianmin , Xing Xin-hui , Zeng An-ping , Zhang Chong
Published: November 2022

As an essential physiological process, gene expression determines the function of each cell. However, owing to the complex nondeterministic and nonlinear nature of gene expression, the steady-state intracellular protein abundance of a clonal population forms a distribution. The characteristics of this distribution, including expression strength and noise, are closely related to cellular behavior. Therefore, quantitative description of these characteristics is an important goal in biology. This task, however, has so far relied on arrayed methods, which are time-consuming and labor-intensive. To address this issue, we propose a deep-learning-assisted Sort-Seq approach (dSort-Seq) in this work, enabling high-throughput profiling of expression properties with high precision. We demonstrated the validity of dSort-Seq for large-scale assaying of the dose–response relationships of biosensors. In addition, we comprehensively investigated the contribution of transcription and translation to noise production inE. coli, from which we discovered that the expression noise is strongly coupled with the mean expression level instead of translation strength, even in the case of weak transcription. We also discovered that the transcriptional interference caused by overlapping RpoD-binding sites contributes to noise production, which suggested the existence of a simple and feasible noise control strategy inE. coli. Overall, dSort-Seq is able to efficiently determine the strength-noise landscape, which has promising applications in studies related to gene expression.
Evaluating spatially variable gene detection methods for spatial transcriptomics data
Authors: Chen Carissa , Kim Hani Jieun , Yang Pengyi
Published: November 2022

The identification of genes that vary across spatial domains in tissues and cells is an essential step for spatial transcriptomics data analysis. Given the critical role it serves for downstream data interpretations, various methods for detecting spatially variable genes (SVGs) have been proposed. The availability of multiple methods for detecting SVGs bears questions such as whether different methods select a similar set of SVGs, how reliable is the reported statistical significance from each method, how accurate and robust is each method in terms of SVG detection, and how well the selected SVGs perform in downstream applications such as clustering of spatial domains. Besides these, practical considerations such as computational time and memory usage are also crucial for deciding which method to use. In this study, we address the above questions by systematically evaluating a panel of popular SVG detection methods on a large collection of spatial transcriptomics datasets, covering various tissue types, biotechnologies, and spatial resolutions. Our results shed light on the performance of each method from multiple aspects and highlight the discrepancy among different methods especially on calling statistically significant SVGs across datasets. Taken together, our work provides useful considerations for choosing methods for identifying SVGs and serves as a key reference for the future development of such methods.
Dopamine neurons that informDrosophilaolfactory memory have distinct, acute functions driving attraction and aversion
Authors: Mohammad Farhan , Mai Yishan , Ho Joses , Zhang Xianyuan , Ott Stanislav , Stewart James Charles , Claridge-Chang Adam
Published: November 2022

The brain must guide immediate responses to beneficial and harmful stimuli while simultaneously writing memories for future reference. While both immediate actions and reinforcement learning are instructed by dopamine, how dopaminergic systems maintain coherence between these two reward functions is unknown. Through optogenetic activation experiments, we showed that the dopamine neurons that inform olfactory memory inDrosophilahave a distinct, parallel function driving attraction and aversion (valence). Sensory neurons required for olfactory memory were dispensable to dopaminergic valence. A broadly projecting set of dopaminergic cells had valence that was dependent on dopamine, glutamate, and octopamine. Similarly, a more restricted dopaminergic cluster with attractive valence was reliant on dopamine and glutamate; flies avoided opto-inhibition of this narrow subset, indicating the role of this cluster in controlling ongoing behavior. Dopamine valence was distinct from output-neuron opto-valence in locomotor pattern, strength, and polarity. Overall our data suggest that dopamine’s acute effect on valence provides a mechanism by which a dopaminergic system can coherently write memories to influence future responses while guiding immediate attraction and aversion.