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Abstract Disrupted or atypical light–dark cycles disrupts synchronization of endogenous circadian clocks to the external environment; extensive circadian rhythm desynchrony promotes adverse health outcomes. Previous studies suggest that disrupted circadian rhythms promote neuroinflammation and neuronal damage post-ischemia in otherwise healthy mice, however, few studies to date have evaluated these health risks with aging. Because most strokes occur in aged individuals, we sought to identify whether, in addition to being a risk factor for poor ischemic outcome, circadian rhythm disruption can increase risk for vascular cognitive impairment and dementia (VCID). We hypothesized that repeated 6 h phase advances (chronic jet lag; CJL) for 8 weeks alters cerebrovascular architecture leading to increased cognitive impairments in aged mice. Female CJL mice displayed impaired spatial processing during a spontaneous alternation task and reduced acquisition during auditory-cued associative learning. Male CJL mice displayed impaired retention of the auditory-cued associative learning task 24 h following acquisition. CJL increased vascular tortuosity in the isocortex, associated with increased risk for vascular disease. These results demonstrate that CJL increased sex-specific cognitive impairments coinciding with structural changes to vasculature in the brain. We highlight that CJL may accelerate aged-related functional decline and could be a crucial target against disease progression.

Abstract Despite its demonstrated biological significance, time of day is a broadly overlooked biological variable in preclinical and clinical studies. How time of day affects the influence of peripheral tumors on central (brain) function remains unspecified. Thus, we tested the hypothesis that peripheral mammary cancer tumors alter the transcriptome of immune responses in the brain and that these responses vary based on time of day; we predicted that time of day sampling bias would alter the interpretation of the results. Brain tissues collected at mid dark and mid light from mammary tumor-bearing and vehicle injected mice were analyzed using the Nanostring nCounter immune panel. Peripheral mammary tumors significantly affected expression within the brain of over 100 unique genes of the 770 represented in the panel, and fewer than 25% of these genes were affected similarly across the day. Indeed, between 65 and 75% of GO biological processes represented by the differentially expressed genes were dependent upon time of day of sampling. The implications of time-of-day sampling bias in interpretation of research studies cannot be understated. We encourage considering time of day as a significant biological variable in studies and to appropriately control for it and clearly report time of day in findings.

Aging is a risk factor for the development of breast cancer. Foundational science studies have supported associations among neuroinflammation, breast cancer, and chemotherapy, but to date, these associations are based on studies using young adult rodents. The current study examined the neuroinflammatory effects of chemotherapy in aged, tumor-naïve and tumor-bearing mice with or without social enrichment. Mice received two intravenous injections of doxorubicin (A) and cyclophosphamide (C) at a two-week interval. Brain immune cells were enriched/assessed via flow cytometry, seven days following the second chemotherapy injection. Social enrichment enhanced peripheral immune cell trafficking in aged tumor-naive mice treated with AC. Group housed aged tumor bearing mice receiving AC had reduced percentage of IL-6+ monocytes and granulocytes relative to their singly housed counterparts. Notably, group housing aged experimental mice with young cage partners significantly reduced TNF + monocytes, tumor volume, and tumor mass. These data illustrate the importance of social enrichment in attenuating neuroinflammation and are the first to demonstrate that social support with young housing partners reduces tumor growth in aged mice.

Summary: The structure and function of the cardiovascular system are modulated across the day by circadian rhythms, making this system susceptible to circadian rhythm disruption. Recent evidence demonstrated that short-term exposure to a pervasive circadian rhythm disruptor, artificial light at night (ALAN), increased inflammation and altered angiogenic transcripts in the hippocampi of mice. Here, we examined the effects of four nights of ALAN exposure on mouse hippocampal vascular networks. To do this, we analyzed 2D and 3D images of hippocampal vasculature and hippocampal transcriptomic profiles of mice exposed to ALAN. ALAN reduced vascular density in the CA1 and CA2/3 of female mice and the dentate gyrus of male mice. Network structure and connectivity were also impaired in the CA2/3 of female mice. These results demonstrate the rapid and potent effects of ALAN on cerebrovascular networks, highlighting the importance of ALAN mitigation in the context of health and cerebrovascular disease.

Abstract Background Circadian rhythms are important for all aspects of biology; virtually every aspect of biological function varies according to time of day. Although this is well known, variation across the day is also often ignored in the design and reporting of research. For this review, we analyzed the top 50 cited papers across 10 major domains of the biological sciences in the calendar year 2015. We repeated this analysis for the year 2019, hypothesizing that the awarding of a Nobel Prize in 2017 for achievements in the field of circadian biology would highlight the importance of circadian rhythms for scientists across many disciplines, and improve time-of-day reporting. Results Our analyses of these 1000 empirical papers, however, revealed that most failed to include sufficient temporal details when describing experimental methods and that few systematic differences in time-of-day reporting existed between 2015 and 2019. Overall, only 6.1% of reports included time-of-day information about experimental measures and manipulations sufficient to permit replication. Conclusions Circadian rhythms are a defining feature of biological systems, and knowing when in the circadian day these systems are evaluated is fundamentally important information. Failing to account for time of day hampers reproducibility across laboratories, complicates interpretation of results, and reduces the value of data based predominantly on nocturnal animals when extrapolating to diurnal humans.

Circadian rhythms are internal manifestations of the 24-h solar day that allow for synchronization of biological and behavioral processes to the external solar day. This precise regulation of physiology and behavior improves adaptive function and survival. Chronotherapy takes advantage of circadian rhythms in physiological processes to optimize the timing of drug administration to achieve maximal therapeutic efficacy and minimize negative side effects. Chronotherapy for cancer treatment was first demonstrated to be beneficial more than five decades ago and has favorable effects across diverse cancer types. However, implementation of chronotherapy in clinic remains limited. The present review examines the evidence for chronotherapeutic treatment for solid tumors. Specifically, studies examining chrono-chemotherapy, chrono-radiotherapy, and alternative chronotherapeutics (e.g., hormone therapy, TKIs, antiangiogenic therapy, immunotherapy) are discussed. In addition, we propose areas of needed research and identify challenges in the field that remain to be addressed.

Across multiple countries the term "big ideas" of mathematics has become a construct advocated as important for teachers' mathematical knowledge. Indeed, several policy or position statement documents about math learning in the United States (U.S.) have stated that "big ideas" of math is a crucial construct for teacher knowledge. With this study we sought to determine if there was consistency about this "big idea" construct that teachers of mathematics in the U.S. are advised to know. To this end, we conducted a content analysis of resources for U.S. teachers of preschool through grade 12. We determined that few resources defined a big idea and those that did lacked agreement with each other. Although most resources delineating big ideas cited Charles (2005) as the basis of their use of the construct, our analysis of the actual big ideas in each resource revealed inconsistent implementation of Charles' theoretical perspective. Thus, to move research and practice forward by more precisely defining and prioritizing this abstract construct we (a) clarified a definition, (b) specified five criteria, and (c) constructed a scholar- and teacher-friendly framework: The Big Ideas Framework. This framework consists of three ordinal levels to distinguish and prioritize the importance of big ideas based on relative size and power: Mighty Mega Math Ideas, Power Math Ideas, and Strong Math Ideas. Moreover, the big ideas construct has focused on Mathematical Knowledge for Teaching (MKT), whereas we urge the field to shift its theoretical perspective to value the entire construct or at least the two most powerful levels of the framework as aspects of Common Content Knowledge. In other words, we urge teachers and mathematics teacher educators to foreground Mighty Mega Math Ideas and Power Math Ideas with P-12 students and families to empower those we serve. Furthermore, given the dearth of peer-reviewed research about big ideas, we encourage a new branch of scholarship to analyze the impact of the practical recommendations we offered here.

Field experiences provide opportunities for early childhood and early childhood special education (EC/ECSE) educators to implement effective practices in learning settings, and are, therefore, a vital part of EC/ECSE teacher preparation. In this article, we describe field placement models from four universities in the United States: The Bridge Project, Getting Started Early, Peer Coaching to Increase Naturalistic Developmental Behavioral Interventions, and University Supervisors Coaching Teacher Candidates: Supporting Young Bi/Multilingual Children with Disabilities. Although there is variety in the settings and effective practices supported through these field placements, performance feedback and collaboration are clear themes across models.

Globalization and the call for global citizenship education have enabled virtual exchange to prepare healthcare students as emerging healthcare professionals for working in an increasingly interconnected and diverse world. Integrating virtual exchange opportunities into undergraduate curricula in higher education equips students with the knowledge, skills, and attributes needed to be responsive to global healthcare challenges. This study reports on the perceptions of undergraduate healthcare students from geographically distant locations on how (if any) participating in an international virtual exchange project fostered their intercultural competence. Anchored in social constructivism and adopting a qualitative methodology, data was collected using an online, open-ended reflective questionnaire. Findings from the thematic analysis highlight that integrating virtual exchange into curriculum design can foster intercultural competence, preparing healthcare students as emerging professionals for the world of work that necessitates an appreciation for diverse ways of knowing, being, and doing to ensure optimal healthcare.

As we consider the growing number of children from immigrant and refugee backgrounds that our schools serve, the importance of fostering anti-racist educators through teacher education is of the utmost importance. While anti-racist work can be a challenging and ongoing personal journey for every educator, engaging teacher education students with diverse children's and adolescent literature can lead to meaningful self-reflection that can foster empathy and global competence. This article shares how online university course modules were designed, with funding from the Longview Foundation, to support pre- and in-service educators to engage with children's and adolescent literature centered on the lived stories of immigrant and refugee families through scaffolded reading and thinking protocols as a model for using literature to encourage empathy and global competence with young learners. Pre- and in-service teachers reported several benefits, including an increased awareness of the importance of diverse literature, deepened self-reflection and empathy, and meaningful connections to classroom practice, thereby benefiting educators and their learners alike.

This case study focused on middle school and high school teachers in an independent school to explore their perceptions of how overparenting influenced them in the classroom. A qualitative case study was conducted within an independent school in the southeast United States. Eleven middle school and high school teachers, which represented 52% of the full-time faculty at the school, participated in an online questionnaire and follow-up interviews regarding their experiences with overparenting. Findings revealed three themes: (a) teachers overwhelmingly associated parent--teacher interactions with conflict and confrontation, (b) teachers perceived overparenting influences teacher autonomy by forcing teachers to set boundaries, and (c) teachers experienced increased workloads. This study provides insight into how overparenting influences teachers, which may help teachers, administrators, and future educators prepare for this type of parent--teacher interaction.

The twenty-eight item Sense of Online Community Scale was completed by 293 online students at a midsized southeastern United States university to ascertain community importance and activities associated with its formation and maintenance on the program and institutional level. A large majority of these students believed that a sense of community was important and that a sense of belonging, affiliation, and trust were valuable for community formation. Participants also believed that program and institutional activities, both academic and social, played key roles in community formation. However, academic activities (e.g., advising, program milestones, writing centers, library support) were rated as more influential than social activities (e.g., get-togethers, online games, institution sporting events). When demographic characteristics were considered, non-White participants rated their sense of affiliation with their program/institution higher than White participants. Participants who lived within a one-hour commute to campus (51% of our sample) rated institutional social activities higher than those who lived farther out. Doctoral students rated program activities as more conducive to community formation than masters, and graduate certificate students and undergraduate students rated affiliation to their program/institution higher than master's and graduate certificate students.

This qualitative study aimed to gain a deeper understanding of principal practice through the voices of principal talk gathered from principals through the lens of Motivating Language Theory (MLT). A qualitative methodology was utilized to gain a deeper understanding from eight principals -- four elementary and four middle level. Data were collected from semi-structured interviews based upon questions modified from Motivating Language Theory-based quantitative protocols. The data analysis was based on observed MLT patterns and open and axial coding leading to themes. The findings of this study provide a voice to the field of MLT and illustrate principal talk as a medium of administrative practice. The findings of this study were the importance principals placed upon the communication of expectations (direction-giving language), providing encouragement and praise (empathetic language), building school culture (meaning-making language and motivating language outcome), and stressing the importance of the principal-teacher interaction (motivating language) in their work. This study extends the field of Motivating Language Theory as well as extending the field of educational leadership and principal talk.

At two higher education institutions in Kurdistan (Iraq), English as foreign language (EFL) programs aim to provide adult learners with language skills development that they need to excel in their majors and as professionals. A framework called the Community of Inquiry (COI), based on interactionist and constructivist-learning theories was used to create a needs analysis tool to inform the design, delivery, and evaluation of a collaborative mini-conference hosted by the two institutions during and post-COVID pandemic. The current study explores the use of the needs assessment, which measured instructors' beliefs following the sudden transition to online learning during the pandemic, and their awareness of principles of teaching and learning for EFL learners in particular within the context of Kurdistan Iraq. There are opportunities in and beyond the current setting to address issues of equity, capacity for integrating tech skills with pedagogy, and more empathy between public and private institutions of higher education that support EFL learners. The study gathered critical evidence through qualitative and quantitative research methods that assessed institutional, faculty, and student needs during the transition of online learning.

Objective: ADHD is subject to stigma from the general population. Exposure to stigma poses the risk of developing self-stigma of youth and parents, but few studies have focused on self-stigma of ADHD. Furthermore, parental factors have been implicated in self-stigma of youth, but no previous research has assessed the association between self-stigma of parents and youth. Therefore, the objective of this study was to better understand the experience of self-stigma of youth and their parents in the context of ADHD. Method: Fifty-five youth with ADHD (aged 8-17) and one parent reporter per youth completed surveys to report their experiences. Results: The results of this study found that both youth and parents reported significantly lower self-stigma scores compared to most previously published research. Parents of boys reported higher self-stigma scores compared to parents of girls. Youth who reported higher self-stigma also reported lower self-esteem. Self-stigma scores in youth were predicted by inattentive symptoms but not hyperactive/impulsive symptoms or parental self-stigma. Conclusion: Results emphasize the importance of understanding self-stigma of ADHD, symptom severity, and the need for interventions for families with ADHD.

Many early childhood teachers seek to promote diversity in their classrooms through the use of multicultural children's literature. While these efforts are well-intentioned, teachers may not be fully aware of the issues of culture potentially hidden within such books, nor may they have support in considering the authenticity of the texts they use. While these issues are pervasive within books representing all cultural groups, recent research by Indigenous scholars has highlighted the concerns and implications within Indigenous children's literature. This article is grounded within Indigenous ways of knowing to provide a helpful tool for supporting teachers as they seek to curate authentic Indigenous children's literature for classrooms. Resources presented within include a 3-step guide to choosing and using such books and a list of Indigenous titles recommended by members of Indigenous communities.

The purpose of this phenomenological study was to explore the ways that early childhood teachers were "making waves" as they fostered equitable classrooms through multicultural picturebooks. Through a thematic analysis of one-on-one interviews and a virtual book selection simulation, five early childhood teachers offered their insights on the potential barriers teachers may face in selecting and using such books in their classrooms, as well as their suggestions for curating classroom libraries that highlight books that serve as mirrors, windows, and doors for children. These insights have the potential to support other early childhood teachers as they make waves of their own and leverage multicultural children's literature to build equitable classrooms.

Children often prefer nonfiction to fiction books but historically, teachers have neglected nonfiction books during reads alouds. The present study examined how young readers collectively make meaning of nonfiction picturebooks with the help of the teacher and their peers during a whole group interactive read-aloud in one kindergarten classroom. Using Bakhtin's dialogism and Rosenblatt's reader response theory, this study captured videos of nonfiction read-alouds, interviews, and formal observations to examine how children make sense of nonfiction picturebooks during whole group read-alouds. This study exposes the social nature of learning. Findings indicate that readers of nonfiction consider the responses of those around them in their takeaways, that making sense of nonfiction is a continual and discursive process, and that children used nonfiction books as a way to connect with one another. Implications for conducting nonfiction read-alouds with young children are discussed. This research exposes the power and potential for interactive read-alouds using nonfiction picturebooks with kindergarteners.

Teachers are returning to schools during the COVID-19 pandemic under the weight of unprecedented stressors to engage a student body that has also experienced stress and trauma. In this study, we examined how confident 454 teachers (55% Black) from 41 charter schools in New Orleans, Louisiana, were in their ability to address students' social-emotional needs upon their return to school. Results showed that Black teachers were more likely to report a greater sense of efficacy in addressing students' needs. Both Black and White teachers identified the top three resources needed to assist students: mental health supports, trainings, and in-class resources.

This paper compares website usability--specifically library users' understanding of library terms--for fifty-one original research studies between 2012-2021, with the findings of John Kupersmith's 2011 white paper "Library Terms That Users Understand." Studies reported approximately twice as many terms that users didn't understand than terms users did understand, with some terms appearing in both categories. Analysis of the findings suggests a majority of Kupersmith's guidelines remain applicable to today's online environment, with some adjustments related to technology advances. We propose an additional guideline that acknowledges the role non-library websites play in guiding how users interact with library terminology.

The evolution of artificial intelligence (AI) technology offers promising solutions to underserved populations in the United States. AI tools can reduce college access and academic barriers for low-income students, first-generation college students, racial and ethnic minorities, individuals with disabilities, and students living in rural areas. While AI tools offer support to college students from all demographics, they offer uniquely individualized assistance to underserved students to overcome the complex postsecondary schooling challenges they face. Examples of the nuanced, often complex, obstacles faced by these vulnerable students are discussed along with brief descriptions of AI tools that can help. AI tools leverage the power of high-speed computing, expansive access to information, machine learning capabilities, and natural language processing. Utilizing the power of AI tools, vulnerable learners can increase their access to financial, academic, and social resources needed to attend and be successful in postsecondary education. AI tools also help close opportunity gaps as they provide means by which college students gain increased independence and control over their educational and career journeys. Note that the AI tools referenced in this article are included as examples only. We encourage ongoing discussion of AI-powered tools and solutions to help underserved students gain more access to higher education and get individualized support for vulnerable learners.

In terms of instructional sequencing and cognitive load research, it remains unclear what effect different instructional sequences have on cognitive load and how to use problem-solving support within instructional sequences to reduce cognitive load. The current study examines how instructional sequencing and problem-solving support interact with different types of cognitive load and learner performance. University students (n = 254) were randomly assigned to one of three conditions: an explicit instruction first sequence, an unsupported problem-solving first sequence, and a supported problem-solving first sequence. Results show that intrinsic load did not differ across the three conditions, extraneous load was lowest in the explicit instruction first and supported problem-solving first conditions, germane load was highest in the supported problem-solving first condition, and performance was highest in the explicit instruction first condition. Providing insight into specific ways instructional sequencing and problem-solving support can reduce cognitive load; results suggest that either problem-solving activities need support or explicit instruction is needed before problem-solving.

We explored how teachers perceived challenging behavior in contrast to behaviors that exemplify social-emotional competence, and how descriptions of behavior varied based on child demographics such as gender, race/ethnicity, and disability status. Using a DisCrit lens, we conducted this study under the assumption that perceptions of behavior may be informed by teachers' implicit biases. Fourteen preschool teachers shared their perspectives on behaviors they saw in the classroom, as exemplified by descriptions of the two children they considered the most socially-emotionally successful, A/Z, and the two they considered the most challenging, C/E. Children in the A/Z group were 54% female, 46% male, 54% White, 29% Black, and 82% did not receive special education services or need screening. Children in the C/E group were 86% male, 14% female, 46% Black, 36% White, and 75% were either receiving special education services or identified by teachers as needing a referral for screening. Positive A/Z behaviors included being a model, leader, or helper; having good play skills, manners, and verbal skills; and loving to learn. The challenging behaviors for C/E students included being hard to connect with; engaging in physical aggression and defiance; and having communication difficulties and poor self-regulation skills. These findings help us understand the role of implicit bias, systems issues, and the importance of culturally responsive practices in early childhood settings.

Recovery from substance use disorder (SUD) is a personal journey that includes connection with self and others, including animals – known as the human-animal bond (HAB). Research shows that canines are the most common type of animal integrated into animal-assisted interventions to support people with SUD. Yet, to our knowledge, there has been no review of the evidence on the role of canines in SUD recovery. The scoping review’s objective was to examine the literature on the human-canine bond’s role in recovery from SUD among adolescents and adults, including how the bond may help or hinder recovery. The review considered records that described the human-canine bond with respect to recovery in any recovery- or therapy-related setting globally. Eleven databases were searched, and 32 sources met inclusion criteria that involved companion dogs, therapy dogs, service/assistance, dogs and others. The thematic analysis across records identified three key benefits of the human-canine bond in SUD recovery: (1) a source of social connection and a conduit for human-to-human social connection, (2) a calming and comforting effect on individuals with SUD that can reduce stress and anxiety, and (3) the human-canine bond as a motivating factor for positive change. Through these themes, the bond may help divert substance use-related thoughts and reduce cravings, bolster engagement in treatment and recovery, and help to decrease and prevent substance use. However, a few articles found no role or a limited role of the human-canine bond in recovery, and challenges and considerations were reported, particularly for marginalized populations (e.g., related to obtaining and maintaining housing, employment, and SUD treatment). Most of the records discussed canine welfare in some capacity. Calls were also made for improved policy, public awareness, and animal welfare.

The enamel proteome includes a range of proteins that are well-preserved in archaeological settings but have so far received less study than those associated with sex-estimation of enamel. We look beyond sex-specific sequencing of amelogenin to investigate the potential of several serum proteins, including immunoglobulin gamma (IgG), the major immunoglobulin found in blood serum, and C-reactive protein (CRP), which is associated with inflammatory response, to provide insight into the health and stresses experienced by individuals in the past. We apply this approach to enamel samples from Mission-Period ancestral Ohlone interred at Asistencia San Pedro y San Pablo (CA-SMA-71/H; n = 11). For comparison, we also examine enamel from historic-period European-Americans interred in the City Cemetery in San Francisco (n = 12), and extracted third molars from present-day military cadets (n = 8). Results indicate that IgG is elevated among individuals at the asistencia relative to samples from present-day military cadets, and historic City Cemetery individuals (ANOVA with post-hoc Tukey Kramer tests, p < .02). Further, the inflammatory protein CRP, normally expressed at much lower levels than IgG, was present in 55% (6 of 11) of the asistencia samples, and in 17% (2 of 12) of the historic City Cemetery samples, but was not detected in enamel samples from present-day military cadets. While more studies are needed, we argue that the difference in IgG could reflect higher levels of chronic diseases such as tuberculosis among Ohlone living within the Mission system, and the presence of measurable amounts of CRP could relate to higher degrees of physical, social, and emotional stresses. To our knowledge, this is the first paleoproteomic study of immune proteins in tooth enamel. The ability to track immune responses during tooth formation could provide valuable and high-resolution information on ancient health and disease at the level of the individual over archaeological time-scales.

BackgroundIt is unknown if early COVID-19 monoclonal antibody (mAb) therapy can reduce risk of Long COVID. The mAbs amubarvimab/romlusevimab were previously demonstrated to reduce risk of hospitalization/death by 79%. This study assessed the impact of amubarvimab/romlusevimab on late outcomes, including Long COVID.MethodsNon-hospitalized high-risk adults within 10 days of COVID-19 symptom onset enrolled in a randomized, double-blind, placebo-controlled phase 2/3 trial of amubarvimab/romlusevimab for COVID-19 treatment. Late symptoms, assessed using a participant-completed symptom diary, were a pre-specified exploratory endpoint. The primary outcome for this analysis was the composite of Long COVID by participant self-report (presence of COVID-19 symptoms as recorded in the diary at week 36) or hospitalization or death by week 36. Inverse probability weighting (IPW) was used to address incomplete outcome ascertainment, giving weighted risk ratios (wRR) comparing amubarvimab/romlusevimab to placebo.FindingsParticipants received amubarvimab/romlusevimab (n = 390) or placebo (n = 390) between January and July 2021. Median age was 49 years, 52% were female, 18% Black/African American, 49% Hispanic/Latino, and 9% COVID-19-vaccinated at entry. At week 36, 103 (13%) had incomplete outcome ascertainment, and 66 (17%) on amubarvimab/romlusevimab and 92 (24%) on placebo met the primary outcome (wRR = 0.70, 95% confidence interval (CI) 0.53-0.93). The difference was driven by fewer hospitalizations/deaths with amubarvimab/romlusevimab (4%) than placebo (13%). Among 652 participants with available diary responses, 53 (16%) on amubarvimab/romlusevimab and 44 (14%) on placebo reported presence of Long COVID.InterpretationAmubarvimab/romlusevimab treatment, while highly effective in preventing hospitalizations/deaths, did not reduce risk of Long COVID. Additional interventions are needed to prevent Long COVID.FundingNational Institute of Allergy and Infectious Diseases of the National Institutes of Health. Amubarvimab and romlusevimab supplied by Brii Biosciences.

Exoplanet discoveries have revealed a dramatic diversity of planet sizes across a vast array of orbital architectures. Sub-Neptunes are of particular interest; due to their absence in our own solar system, we rely on demographics of exoplanets to better understand their bulk composition and formation scenarios. Here, we present the discovery and characterization of TOI-1437 b, a sub-Neptune with a 18.84 day orbit around a near-solar analog (M⋆ = 1.10 ± 0.10 M☉, R⋆=1.17 ± 0.12 R☉). The planet was detected using photometric data from the Transiting Exoplanet Survey Satellite (TESS) mission and radial velocity (RV) follow-up observations were carried out as a part of the TESS-Keck Survey using both the HIRES instrument at Keck Observatory and the Levy Spectrograph on the Automated Planet Finder telescope. A combined analysis of these data reveal a planet radius of Rp = 2.24 ± 0.23 R⊕ and a mass measurement of Mp = 9.6 ± 3.9 M⊕). TOI-1437 b is one of few (∼50) known transiting sub-Neptunes orbiting a solar-mass star that has a RV mass measurement. As the formation pathway of these worlds remains an unanswered question, the precise mass characterization of TOI-1437 b may provide further insight into this class of planet.

The California Pipevine, Aristolochia californica Torr., is the only endemic California species within the cosmopolitan birthwort family Aristolochiaceae. It occurs as an understory vine in riparian and chaparral areas and in forest edges and windrows. The geographic range of this plant species almost entirely overlaps with that of its major specialized herbivore, the California Pipevine Swallowtail Butterfly Battus philenor hirsuta. While this species pair is a useful, ecologically well-understood system to study co-evolution, until recently, genomic resources for both have been lacking. Here, we report a new, chromosome-level assembly of A. californica as part of the California Conservation Genomics Project (CCGP). Following the sequencing and assembly strategy of the CCGP, we used Pacific Biosciences HiFi long reads and Hi-C chromatin proximity sequencing technology to produce a de novo assembled genome. Our genome assembly, the first for any species in the genus, contains 531 scaffolds spanning 661 megabase (Mb) pairs, with a contig N50 of 6.53 Mb, a scaffold N50 of 42.2 Mb, and BUSCO complete score of 98%. In combination with the recently published B. philenor hirsuta reference genome assembly, the A. californica reference genome assembly will be a powerful tool for studying co-evolution in a rapidly changing California landscape.

PurposeThe purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC).Experimental designRB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes. Using CRISPR-Cas9, we deleted RB1 in HGSC cells with and without BRCA1 alterations to model co-loss with treatment response. We performed whole-genome and transcriptome data analyses on 126 patients with primary HGSC to characterize tumors with concurrent BRCA deficiency and RB1 loss.ResultsRB1 loss was associated with longer OS in HGSC but with poorer prognosis in endometrioid ovarian carcinoma. Patients with HGSC harboring both RB1 loss and pathogenic germline BRCA variants had superior OS compared with patients with either alteration alone, and their median OS was three times longer than those without pathogenic BRCA variants and retained RB1 expression (9.3 vs. 3.1 years). Enhanced sensitivity to cisplatin and paclitaxel was seen in BRCA1-altered cells with RB1 knockout. Combined RB1 loss and BRCA deficiency correlated with transcriptional markers of enhanced IFN response, cell-cycle deregulation, and reduced epithelial-mesenchymal transition. CD8+ lymphocytes were most prevalent in BRCA-deficient HGSC with co-loss of RB1.ConclusionsCo-occurrence of RB1 loss and BRCA deficiency was associated with exceptionally long survival in patients with HGSC, potentially due to better treatment response and immune stimulation.

HER2, encoded by the ERBB2 gene, is an important druggable driver of human cancer gaining increasing importance as a therapeutic target in urothelial carcinoma (UC). The genomic underpinnings of HER2 overexpression in ERBB2 nonamplified UC are poorly defined. To address this knowledge gap, we investigated 172 UC tumors from patients treated at the University of California San Francisco, using immunohistochemistry and next-generation sequencing. We found that GATA3 and PPARG copy number gains individually predicted HER2 protein expression independently of ERBB2 amplification. To validate these findings, we interrogated the Memorial Sloan Kettering/The Cancer Genome Atlas (MSK/TCGA) dataset and found that GATA3 and PPARG copy number gains individually predicted ERBB2 mRNA expression independently of ERBB2 amplification. Our findings reveal a potential link between the luminal marker HER2 and the key transcription factors GATA3 and PPARG in UC and highlight the utility of examining GATA3 and PPARG copy number states to identify UC tumors that overexpress HER2 in the absence of ERBB2 amplification. In summary, we found that an increase in copy number of GATA3 and PPARG was independently associated with higher ERBB2 expression in patient samples of UC. This finding provides a potential explanation for HER2 overexpression in UC tumors without ERBB2 amplification and a way to identify these tumors for HER2-targeted therapies.

Accompanying the climate crisis is the more enigmatic biodiversity crisis. Rapid reorganization of biodiversity due to global environmental change has defied prediction and tested the basic tenets of conservation and restoration. Conceptual and practical innovation is needed to support decision making in the face of these unprecedented shifts. Critical questions include: How can we generalize biodiversity change at the community level? When are systems able to reorganize and maintain integrity, and when does abiotic change result in collapse or restructuring? How does this understanding provide a template to guide when and how to intervene in conservation and restoration? To this end, we frame changes in community organization as the modulation of external abiotic drivers on the internal topology of species interactions, using plant-plant interactions in terrestrial communities as a starting point. We then explore how this framing can help translate available data on species abundance and trait distributions to corresponding decisions in management. Given the expectation that community response and reorganization are highly complex, the external-driver internal-topology (EDIT) framework offers a way to capture general patterns of biodiversity that can help guide resilience and adaptation in changing environments.