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The circadian clock enables anticipation of the day/night cycle in animals ranging from cnidarians to mammals. Circadian rhythms are generated through a transcription-translation feedback loop (TTFL or pacemaker) with CLOCK as a conserved positive factor in animals. However, CLOCK's functional evolutionary origin and mechanism of action in basal animals are unknown. In the cnidarian Nematostella vectensis , pacemaker gene transcript levels, including NvClk (the Clock ortholog), appear arrhythmic under constant darkness, questioning the role of NvCLK. Utilizing CRISPR/Cas9, we generated a NvClk allele mutant ( NvClk Δ ), revealing circadian behavior loss under constant dark (DD) or light (LL), while maintaining a 24 hr rhythm under light-dark condition (LD). Transcriptomics analysis revealed distinct rhythmic genes in wild-type (WT) polypsunder LD compared to DD conditions. In LD, NvClk Δ/Δ polyps exhibited comparable numbers of rhythmic genes, but were reduced in DD. Furthermore, under LD, the NvClk Δ/Δ polyps showed alterations in temporal pacemaker gene expression, impacting their potential interactions. Additionally, differential expression of non-rhythmic genes associated with cell division and neuronal differentiation was observed. These findings revealed that a light-responsive pathway can partially compensate for circadian clock disruption, and that the Clock gene has evolved in cnidarians to synchronize rhythmic physiology and behavior with the diel rhythm of the earth's biosphere., Competing Interests: RA, MR, NS, TD, LA, OL No competing interests declared, (© 2023, Aguillon et al.)

The detection of microsatellite instability (MSI) and mismatch repair (MMR) deficiency has become mandatory for most tumors in recent years, owing to the development of immune checkpoint inhibitors as a highly effective therapy for MMR deficiency/MSI tumors. The timely and efficient detection of MSI is valuable, and new methods are increasingly being developed. To date, MMR assessment has been performed using immunohistochemistry of the 4 MMR proteins and/or microsatellite stability/MSI using PCR, mostly using the pentaplex panel. The implementation of next-generation sequencing (NGS) for MSI analysis would improve the effectiveness at a lower cost and in less time. This study describes the development of 8 new microsatellites combined with a classification algorithm, termed "Octaplex CaBio-MSID" (for Cancérologie Biologique MSI Detection tool), to assess MSI using NGS. A series of 303 colorectal cancer and 88 endometrial cancer samples were assessed via MSI testing using NGS using the Octaplex CaBio-MSID algorithm. The sensitivity and specificity of Octaplex CaBio-MSID were 98.4% and 98.4% for colorectal cancers, and 89.3% and 100% for endometrial cancers, respectively. This new NGS-based MSI detection method outperforms previously published methods (ie, Idylla [Biocartis], OncoMate MSI Dx [Promega], and Foundation One CDx [Roche Foundation Medicine]). Although highly efficient, Octaplex CaBio-MSID requires validation in a larger independent series of different tumor types., (Copyright © 2023. Published by Elsevier Inc.)

Keeping the global food supply safe necessitates international collaborations between countries. Health and regulatory agencies routinely communicate during foodborne illness outbreaks, allowing partners to share investigational evidence. A 2016-2020 outbreak of Listeria monocytogenes infections linked to imported enoki mushrooms required a multinational collaborative investigation among the United States, Canada, Australia, and France. Ultimately, this outbreak included 48 ill people, 36 in the United States and 12 in Canada, and was linked to enoki mushrooms sourced from one manufacturer located in the Republic of Korea. Epidemiologic, laboratory, and traceback evidence led to multiple regulatory actions, including extensive voluntary recalls by three firms in the United States and one firm in Canada. In the United States and Canada, the Korean manufacturer was placed on import alert while other international partners provided information about their respective investigations and advised the public not to eat the recalled enoki mushrooms. The breadth of the geographic distribution of this outbreak emphasizes the global reach of the food industry. This investigation provides a powerful example of the impact of national and international coordination of efforts to respond to foodborne illness outbreaks and protect consumers. It also demonstrates the importance of fast international data sharing and collaboration in identifying and stopping foodborne outbreaks in the global community. Additionally, it is a meaningful example of the importance of food sampling, testing, and integration of sequencing results into surveillance databases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Abstract: During spring 2018, the U.S. Food and Drug Administration (FDA), Centers for Disease Control and Prevention, and state and local public health agencies responded to a multistate outbreak of gastrointestinal illnesses caused by multiple Salmonella serovars and associated with consumption of kratom, a product harvested from a tropical tree native to Southeast Asia. The outbreak included 199 case-patients reported by 41 U.S. states, with illness onset dates ranging 11 from January 2017 to 8 May 2018, leading to 54 hospitalizations and no deaths. Case-patients reported purchasing kratom products from physical and online retail points of service (POSs). Products distributed to 16 POSs where 24 case-patients from 17 states purchased kratom were selected for traceback investigation. Traceback revealed that the kratom was imported from several countries, the most common being Indonesia. Local and state officials collected product samples from case-patients and retail POSs. The FDA collected 76 product samples from POSs and distributors, of which 42 (55%) tested positive for Salmonella. The positive samples exhibited a range of pulsed-field gel electrophoresis patterns and whole genome sequence genetic heterogeneity, and 25 (60%) of 42 samples yielded at least one isolate indistinguishable from one or more outbreak-related clinical isolates. Although it does not exclude a possibility of a single contamination source, the extent of genetic diversity exhibited by the Salmonella isolates recovered from product samples and a lack of traceback convergence suggested that kratom was widely contaminated across multiple sites from which it was grown, harvested, and packaged. As a result of the contamination, kratom products were recalled by numerous firms (both voluntarily and mandatory). Epidemiologic, traceback, and laboratory evidence supported the conclusion that kratom products were associated with illnesses., (Published 2022 by the International Association for Food Protection. Not subject to U.S. Copyright.)

Sense organs acquire their distinctive shapes concomitantly with the differentiation of sensory cells and neurons necessary for their function. Although our understanding of the mechanisms controlling morphogenesis and neurogenesis in these structures has grown, how these processes are coordinated remains largely unexplored. Neurogenesis in the zebrafish olfactory epithelium requires the bHLH proneural transcription factor Neurogenin 1 (Neurog1). To address whether Neurog1 also controls morphogenesis, we analysed the migratory behaviour of early olfactory neural progenitors in neurog1 mutant embryos. Our results indicate that the oriented movements of these progenitors are disrupted in this context. Morphogenesis is similarly affected by mutations in the chemokine receptor gene, cxcr4b , suggesting it is a potential Neurog1 target gene. We find that Neurog1 directly regulates cxcr4b through an E-box cluster located just upstream of the cxcr4b transcription start site. Our results suggest that proneural transcription factors, such as Neurog1, directly couple distinct aspects of nervous system development., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

The zebrafish olfactory epithelium comprises a variety of neuronal populations, which are thought to have distinct embryonic origins. For instance, while ciliated sensory neurons arise from preplacodal ectoderm (PPE), previous lineage tracing studies suggest that both Gonadotropin releasing hormone 3 (Gnrh3) and microvillous sensory neurons derive from cranial neural crest (CNC). We find that the expression of Islet1/2 is restricted to Gnrh3 neurons associated with the olfactory epithelium. Unexpectedly, however, we find no change in Islet1/2+ cell numbers in sox10 mutant embryos, calling into question their CNC origin. Lineage reconstruction based on backtracking in time-lapse confocal datasets, and confirmed by photoconversion experiments, reveals that Gnrh3 neurons derive from the anterior PPE. Similarly, all of the microvillous sensory neurons we have traced arise from preplacodal progenitors. Our results suggest that rather than originating from separate ectodermal populations, cell-type heterogeneity is generated from overlapping pools of progenitors within the preplacodal ectoderm.

Peripheral sensory organs and ganglia found in the vertebrate head arise during embryonic development from distinct ectodermal thickenings, called cranial sensory placodes (adenohypophyseal, olfactory, lens, trigeminal, epibranchial, and otic). A series of patterning events leads to the establishment of these placodes. Subsequently, these placodes undergo specific morphogenetic movements and cell-type specification in order to shape the final placodal derivatives and to produce differentiated cell types necessary for their function. In this chapter, we will focus on recent studies in the zebrafish that have advanced our understanding of cranial sensory placode development. We will summarize the signaling events and their molecular effectors guiding the formation of the so-called preplacodal region, and the subsequent subdivision of this region along the anteroposterior axis that gives rise to specific placode identities as well as those controlling morphogenesis and neurogenesis. Finally, we will highlight the approaches used in zebrafish that have been established to precisely label cell populations, to follow their development, and/or to characterize cell fates within a specific placode., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Ad-ISF35, an adenovirus vector encoding a membrane-bound engineered CD154 chimeric protein (ISF35), induces complete A20 lymphoma tumor regression in mice after intratumoral direct injection (IDI). Ad-ISF35 induced durable local and systemic antitumor responses associated with a rapid tumor infiltration of macrophages and neutrophils as well as increased levels of proinflammatory cytokines in the tumor microenvironment. Ad-ISF35 IDI transduced preferentially fibroblasts and macrophages present in the tumor microenvironment, and ISF35 protein expression was observed in only 0.25% of cells present in the tumor. Moreover, Ad-ISF35 IDI induced upregulation of CD40 in tumor and immune regulatory cells, including those that did not express ISF35, suggesting the presence of a strong bystander effect. These responses resulted in the generation of IFN-γ-secreting cytotoxic lymphocytes and the production of specific cytotoxic antibodies against lymphoma cells. Overall, cellular immune therapy based on ISF35 induced phenotypic changes in the tumor cells and tumor microenvironment that were associated with a break in tumor immune tolerance and a curative antitumor effect in this lymphoma mouse model. Our data highlight the potential activity that modulation of costimulatory signaling has in cancer therapy.

Background: Latina intimate partner violence (IPV) survivors often face great barriers to depression care. We sought to use a community-based participatory research (CBPR) approach to create and evaluate a community-based depression care program for Latina IPV survivors., Methods: We created a multifaceted, culturally tailored intervention, based on principles of chronic illness management. A promotora provided case management services and led 12 weekly group sessions. Participants completed surveys at baseline and 6 months and participated in open-ended exit interviews., Results: Ten Spanish-speaking Latina women participated in the intervention. The program had excellent attendance, with 100% of women attending at least 10 group sessions, and high satisfaction. We found a large decrease in depression severity (Patient Health Questionnaire [PHQ]-9, 17.3-7.2; p = .001), as well as improvements in depression self-efficacy, self-esteem, and stress., Conclusion: This study offers promising preliminary data to support the use of community-based approaches to reducing depression disparities in Latina IPV survivors.

Few studies have examined Latinos' beliefs about the Pap smear or what uses they attribute to the procedure. We conducted qualitative interviews with 28 Mexican immigrant women and 23 Mexican immigrant men recruited through snowball sampling. We found that individuals learned about the Pap smear from a wide variety of sources and often understood the exam to be a screening test for sexually transmitted infections in general. They also related the need for Pap smears and the development of cervical cancer to high risk sexual behaviors. Finally, participants considered men to have a significant role as vectors for disease and as barriers to screening. Our results suggest that interventions to improve cervical cancer prevention among Mexican immigrants may be most effective if they include both men and women and if they recognize and address concerns about STI spread and prevention. Furthermore, interventions must recognize that even when women know how to prevent disease, they may feel disempowered with regard to making behavioral changes that will decrease their risk for STIs or cancer.

Background: Latina immigrants from Mexico suffer significantly increased morbidity and mortality from cervical cancer when compared with non-Hispanic White women, largely owing to lack of screening and appropriate treatment., Objectives: To demonstrate that by combining the tools of community-based participatory research (CBPR) with the tools of interpretive inquiry, it is possible to address explicit community concerns surrounding a particular problem such as cervical cancer while also examining what other, perhaps less immediately visible, matters consume the time and attention of community members., Methods: We first briefly discuss and compare CBPR as an approach to research and interpretive inquiry as a qualitative research method. We then provide a case study from our own research using a CBPR approach to examine beliefs and attitudes about cervical cancer prevention among Oregon Latinos. Methods in that study included extensive discussions with our community advisory board (CAB) and promotores (community health workers) regarding barriers to cervical cancer screening for Latinas and community health concerns in general, and in-depth interviews with more than 50 Latino immigrants., Conclusion: Combining the tools of CBPR with the tools of interpretive qualitative inquiry may allow researchers to address explicit community concerns while also examining what other, less immediately visible, issues consume the time and attention of community members. In our specific case, combining the insights of our community partners with the results of our interpretive analysis helped us shift the focus from cervical cancer alone to a focus on gender relations and family health as we design future interventions.