Estimation of effective number of breeders and effective population size in an abundant and heavily exploited marine teleost.

Obtaining reliable estimates of the effective number of breeders (N b) and generational effective population size (N e) for fishery-important species is challenging because they are often iteroparous and highly abundant, which can lead to bias and imprecision. However, recent advances in understanding of these parameters, as well as the development of bias correction methods, have improved the capacity to generate reliable estimates. We utilized samples of both single-cohort young of the year and mixed-age adults from two geographically and genetically isolated stocks of the Australasian snapper (Chrysophrys auratus) to investigate the feasibility of generating reliable N b and N e estimates for a fishery species. Snapper is an abundant, iteroparous broadcast spawning teleost that is heavily exploited by recreational and commercial fisheries. Employing neutral genome-wide SNPs and the linkage-disequilibrium method, we determined that the most reliable N b and N e estimates could be derived by genotyping at least 200 individuals from a single cohort. Although our estimates made from the mixed-age adult samples were generally lower and less precise than those based on a single cohort, they still proved useful for understanding relative differences in genetic effective size between stocks. The correction formulas applied to adjust for biases due to physical linkage of loci and age structure resulted in substantial upward modifications of our estimates, demonstrating the importance of applying these bias corrections. Our findings provide important guidelines for estimating N b and N e for iteroparous species with large populations. This work also highlights the utility of samples originally collected for stock structure and stock assessment work for investigating genetic effective size in fishery-important species.

Learning with conviction: Exploring the relationship between criminal legal system involvement and substance use and recovery outcomes for students in collegiate recovery programs.

This study examines the association of criminal legal system involvement and age with substance use and academic related outcomes among students involved in collegiate recovery programs in the US. We examined 435 students in collegiate recovery using a national survey of college students. We computed differences between non-system-involved, system-involved with no incarceration history, and formerly incarcerated participants on relevant substance use and recovery-related outcomes. The results provide evidence that there are significant differences between those system-involved and those who are not. Specifically, we found significant differences across the outcomes of recovery capital, quality of life, hours worked per week, and substance use disorder symptoms, but after controlling for relevant covariates, only the differences between hours worked (non-system involved and system involved < formerly incarcerated) and substance use disorder symptoms (non-system involved < system involved and formerly incarcerated) remained significant. The study contributes to the literature by demonstrating that nearly half of the collegiate students in recovery in this sample have legal system-involvement and a third have been incarcerated. Further, interventions for collegiate recovery programs may need to be adjusted to account for legal system involvement among their members.

Effects of strength of relationship ties in recovery homes: A conundrum.

Recovery homes are a widespread source of support for those attempting to maintain abstinence. For those who are able to remain in these settings for at least 6 months, outcomes tend to be favorable; however, many leave prematurely. There is a need to better understand the social integration processes that play a major role in giving recovery home residents access to available recovery-related social capital that is associated with better outcomes. The current study involved Oxford House recovery homes in 3 states and examined the strength of relationship ties among house members. We found that those who associated with peers who have higher recovery scores tend to improve their own recovery scores over time. However, we also found that those with higher recovery scores tended to create "strong" ties with similarly high-scoring alters; likewise lower-scoring individuals preferentially formed strong ties with each other. These findings suggest a conundrum: recovery home residents most in need of relational support from more recovered housemates are the least likely to obtain it. We discuss possible pathways to creating more ties between high and low-recovered residents.

Workforce outcomes among substance use peer supports and their contextual determinants: A scoping review protocol.

Background: Peer recovery support services are a promising approach for improving harm reduction, treatment, and recovery-related outcomes for people who have substance use disorders. However, unique difficulties associated with the role may put peer recovery support staff (i.e., peers) at high risk for negative workforce outcomes, including burnout, vicarious trauma, and compassion fatigue, which impact one's personal recovery journey. Little is known about the extent to which peers experience such negative outcomes or the influence the service setting context has upon them. This scoping review aims to describe the nature and extent of research evidence on peers' workforce outcomes and how these outcomes might differ across service settings. Methods: A scoping review will be conducted with literature searches conducted in PsycINFO®, (EBSCO), Embase® (EBSCO), CINAHL® (EBSCO), Web of Science™ (Clarivate), and Google Scholar databases for relevant articles discussing US-based research and published in English from 1 January 1999 to 1 August 2023. The study will include peer-reviewed and grey-literature published materials describing the experiences of peers participating in recovery support services and harm reduction efforts across a variety of service settings. Two evaluators will independently review the abstracts and full-text articles. We will perform a narrative synthesis, summarizing and comparing the results across service settings. Conclusions: This review will assess the state of the literature on peer workforce-related outcomes and how outcomes might vary by service setting context. Exploration will include individual characteristics of peers that moderate workforce outcomes, and workforce outcomes that mediate personal recovery outcomes. Results will inform the field regarding future directions for research in this area. Systematic review registration: Submitted to Open Science Framework, August 22nd, 2023.

An Open-Label, Randomized Trial Comparing Fidaxomicin With Oral Vancomycin for the Treatment of Clostridioides difficile Infection in Hospitalized Patients Receiving Concomitant Antibiotics for Concurrent Infections.

BACKGROUND: Recurrent Clostridioides difficile infection (rCDI) occurs frequently, and concomitant antibiotic (CA) during the initial episode for treatment of non-CDI is a major risk factor. We sought to address the comparative efficacy of fidaxomicin versus vancomycin in the setting of CA during the initial CDI episode. METHODS: We conducted a randomized, controlled, open-label trial at 2 hospitals in Ann Arbor, Michigan. We consecutively consented and enrolled hospitalized patients ≥18 years old with diarrhea, a positive test for C. difficile, and ≥1 qualifying CA. Complicated CDI, CDI treatment for >24 hours prior to enrollment, and planned long-term (>12 weeks) CA use were notable exclusions. Clinical cure was defined as resolution of diarrhea for 2 consecutive days maintained until 2 days after therapy, and rCDI as recurrent diarrhea with positive testing ≤30 days after initial treatment. Patients were randomized to fidaxomicin or vancomycin. RESULTS: Baseline characteristics were similar in the 2 groups of 144 patients. Rates of clinical cure (73% vs 62.9%, P = .195) and rCDI (3.3% vs 4.0%; P > .99) were similar for fidaxomicin and vancomycin in the intention-to-treat and per-protocol cohorts, respectively. Only 4 patients developed rCDI. CONCLUSIONS: In this study of patients with CDI receiving CA, a numerically higher proportion were cured with fidaxomicin versus vancomycin, but this result did not reach statistical significance. Overall recurrence was lower than anticipated in both arms compared with previous studies that did not extend duration of CDI treatment during CA. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov (NCT02692651).

Fishery independent survey datasets of abalone populations on subtidal coastal reefs in southeastern Australia.

Assessing the status or exploited marine fish populations often relies on fishery dependent catch and effort data reported by licensed commercial fishers in compliance with regulations and by recreational anglers voluntarily. This invariably leads to bias towards the fraction of a fish population or community that can be legally fished i.e., the stock as defined by legal minimum lengths and spatial boundaries. Data are restricted to populations which continue to be exploited at the expense of obtaining data on previously exploited and unexploited populations [1,2], so if a fishery is contracting spatially over time, then successively less of the overall fish community is monitored with bias towards where biomass is highest or most accessible [3]. A viable alternative is to conduct population monitoring surveys independently of a fishery to obtain information that is more broadly representative of the abundance, composition and size structure of fish communities and their supporting habitats [4-6]. Whereas catch and effort data often must be de-identified and aggregated to protect the confidentiality of fishers' commercial and personal interests, this constraint does not exist for independently acquired monitoring data, collected at public expense and hence publicly available at high levels of spatial and temporal resolution. Time series underpins the utility of fishery independent survey (FIS) datasets in terms of the life histories of exploited fish species and the time frames of their responses to various combinations of fishing mortality and environmental fluctuations and trends [7]. One-off surveys can establish a baseline and spatial distribution pattern, but regular surveys conducted consistently over time are necessary to detect trends from which population status can be inferred. We present several unique datasets focused on the commercially valuable blacklip abalone (Haliotis rubra), spanning three decades of annually collected data from up to 204 locations on subtidal rocky reefs along a coastline of almost 2500 km, the State of Victoria, Australia. It is rare for data to be collected consistently at this intensity over such a long period of monitoring [2], especially with surveys conducted by small teams of highly skilled research divers, some of whom up until recently had participated in every year. The data comprises ∼28,000 records from ∼4500 site surveys conducted during 1992 to 2021 [2]. Although the fixed site design remained unchanged, the number of sites surveyed varied over time, mostly increasing in number periodically, and the survey method was refined on several occasions. We defined three different variants in the survey method due to technological advancement for both enumerating abalone abundance and measuring shell size structure [7]. The relative abundance counts were standardized using a Bayesian generalized linear mixed model (GLMM) to test for interannual trends whilst allowing for inherent differences among sites, research divers, and their interactions [8].

Drinking to cope and coping strategies in Deaf/Hard of hearing college students.

INTRODUCTION: Deaf and hard of hearing (DHH) students experience unique stressors as a minority linguistic and cultural group that may contribute to problematic substance and alcohol use behavior. Proper coping strategies may be one protective factor to avoid reliance on alcohol as a means to reduce stress. METHODS: The current study compared the endorsement of coping strategies by DHH students and hearing individuals and their relationship to drinking to cope behavior. Data was collected among DHH (n = 126) and hearing students (n = 349) at a large university. RESULTS: While these two groups did not differ in their levels of problematic drinking behavior, there were differences observed in drinking to cope motives as well as in the levels of coping styles used. DHH students were found to endorse greater levels of emotion-oriented and task-oriented coping than hearing students. Drinking to cope motivations were also higher for DHH students, particularly those who endorsed greater emotion focused coping. CONCLUSIONS: Interventions and educational efforts involving coping skills is a potentially important area of focus for the DHH student population. Further implications for understanding drinking behavior in this population are discussed.

Spiritual Awakening in 12-Step Recovery: Impact Among Residential Aftercare Residents.

Spiritually-based interventions in the form of 12-step programs are frequently offered as a part of substance use treatment programs in the United States. Programs based in the 12 steps guarantee that by working their program, an individual will undergo a process of transformation labeled a spiritual awakening. However, the impact of this experience on recovery factors and treatment adherence is unclear. The current study investigated adult residents (n = 115) who experienced a spiritual awakening attributed to 12-step group affiliation during their stay at residential aftercare facilities for substance use disorder. Self-efficacy and hope were greater for individuals who experienced a spiritual awakening versus those persons who did not experience awakening. Awakening was associated with greater affiliation to AA and decreased negative exit from the facility. Results revealed the potential for an awakening to improve treatment behavior and outcomes in a residential environment, as well as benefit an individual's personal recovery resources. Further theoretical and clinical implications are discussed.

A substance user-self fit perception increases identification as a user of the substance.

We tested whether greater identification as a user of a substance (i.e., perceived general associations between oneself and use of the substance, the group of people who use the substance, and/or the substance itself) results from a theorized source-perceived fit between one's own identity and one's perception of the identity of being a user of the substance. We also tested whether this effect is stronger the more the group of people who use the substance is perceived as an entity and the more the prototypical user of the substance is perceived as having a favorable identity. We conducted two correlational and two (preregistered) experimental investigations of drinker identity and marijuana user identity. In all studies, substance user identity was positively associated with substance user-self fit perception. In both correlational studies, this relationship was stronger the more the group of people who use the substance was perceived as an entity. In the drinker identity correlational study, this relationship was also stronger the more it was perceived that the prototypical drinker has a favorable identity. A substance user-self fit perception could be addressed to reduce identification as a user of the substance in efforts to prevent hazardous use. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Weight gain associated with insulin detemir vs insulin glargine in clinical practice: A retrospective longitudinal cohort study.

PURPOSE: In comparative randomized studies, use of insulin detemir has been consistently demonstrated to be associated with less weight gain than the industry standard, insulin glargine. However, the magnitude of the relative reduction in weight gain with use of insulin determir vs insulin glargine in regulatory studies (reported values ranged from 0.77 kg to 3.6 kg) may not be generalizable to patients in real-world practice conditions. A study was conducted to substantiate detemir's purported weight-sparing advantage over insulin glargine in newly treated patients with type 2 diabetes mellitus under the conditions found in a clinical practice setting. METHODS: A retrospective longitudinal cohort study design was applied in reviewing electronic medical records to identify insulin-naive, overweight patients with type 2 diabetes who received insulin detemir or insulin glargine therapy continued for up to 1 year. Patient weights at baseline and at each subsequent clinic visit after treatment initiation were identified. The primary outcome was the maximum weight increase from baseline after exposure to insulin detemir or glargine. The difference-in-differences (DiD) mean total body weight change was tested by analysis of covariance (ANCOVA). RESULTS: One hundred nine patient records (56 of patients who received insulin glargine and 53 of patients who received insulin detemir) met study criteria and underwent full abstraction. The covariate-adjusted estimated mean change in body weight associated with use of insulin detemir vs insulin glargine was -1.5 kg (95% CI, -2.89 to -0.12 kg; P = 0.04). CONCLUSION: The mean weight gain associated with detemir use was significantly less than the mean weight change observed with glargine use. The magnitude of weight change was consistent with that demonstrated in randomized controlled trials. These results further substantiate detemir's purported comparative weight-sparing properties under conditions found in a real-world practice setting.

Publisher Correction: Crystal structure of a lipin/Pah phosphatidic acid phosphatase.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Crystal structure of human PLD1 provides insight into activation by PI(4,5)P2 and RhoA.

The signal transduction enzyme phospholipase D1 (PLD1) hydrolyzes phosphatidylcholine to generate the lipid second-messenger phosphatidic acid, which plays roles in disease processes such as thrombosis and cancer. PLD1 is directly and synergistically regulated by protein kinase C, Arf and Rho GTPases, and the membrane lipid phosphatidylinositol-4,5-bisphosphate (PIP2). Here, we present a 1.8 Å-resolution crystal structure of the human PLD1 catalytic domain, which is characterized by a globular fold with a funnel-shaped hydrophobic cavity leading to the active site. Adjacent is a PIP2-binding polybasic pocket at the membrane interface that is essential for activity. The C terminus folds into and contributes part of the catalytic pocket, which harbors a phosphohistidine that mimics an intermediate stage of the catalytic cycle. Mapping of PLD1 mutations that disrupt RhoA activation identifies the RhoA-PLD1 binding interface. This structure sheds light on PLD1 regulation by lipid and protein effectors, enabling rationale inhibitor design for this well-studied therapeutic target.

Crystal structure of a lipin/Pah phosphatidic acid phosphatase.

Lipin/Pah phosphatidic acid phosphatases (PAPs) generate diacylglycerol to regulate triglyceride synthesis and cellular signaling. Inactivating mutations cause rhabdomyolysis, autoinflammatory disease, and aberrant fat storage. Disease-mutations cluster within the conserved N-Lip and C-Lip regions that are separated by 500-residues in humans. To understand how the N-Lip and C-Lip combine for PAP function, we determined crystal structures of Tetrahymena thermophila Pah2 (Tt Pah2) that directly fuses the N-Lip and C-Lip. Tt Pah2 adopts a two-domain architecture where the N-Lip combines with part of the C-Lip to form an immunoglobulin-like domain and the remaining C-Lip forms a HAD-like catalytic domain. An N-Lip C-Lip fusion of mouse lipin-2 is catalytically active, which suggests mammalian lipins function with the same domain architecture as Tt Pah2. HDX-MS identifies an N-terminal amphipathic helix essential for membrane association. Disease-mutations disrupt catalysis or destabilize the protein fold. This illustrates mechanisms for lipin/Pah PAP function, membrane association, and lipin-related pathologies.

The endemic and endangered Maugean Skate (Zearaja maugeana) exhibits short-term severe hypoxia tolerance.

The endangered and range-restricted Maugean skate (Zearaja maugeana) is subjected to large environmental variability coupled with anthropogenic stressors in its endemic habitat, Macquarie Harbour, Tasmania. However, little is known about the basic biology/physiology of this skate, or how it may respond to future environmental challenges predicted from climate change and/or increases in human activities such as aquaculture. These skate live at a preferred depth of 5-15 m where the dissolved oxygen (DO) levels are moderate (~55% air saturation), but can be found in areas of the Harbour where DO can range from 100% saturation to anoxia. Given that the water at their preferred depth is already hypoxic, we sought to investigate their response to further decreases in DO that may arise from potential increases in anthropogenic stress. We measured oxygen consumption, haematological parameters, tissue-enzyme capacity and heat shock protein (HSP) levels in skate exposed to 55% dissolved O2 saturation (control) and 20% dissolved O2 saturation (hypoxic) for 48 h. We conclude that the Maugean skate appears to be an oxyconformer, with a decrease in the rate of O2 consumption with increasing hypoxia. Increases in blood glucose and lactate at 20% O2 suggest that skate are relying more on anaerobic metabolism to tolerate periods of very low oxygen. Despite these metabolic shifts, there was no difference in HSP70 levels between groups, suggesting this short-term exposure did not elicit a cellular stress response. The metabolic state of the skate suggests that low oxygen stress for longer periods of time (i.e. >48 h) may not be tolerable and could potentially result in loss of habitat or shifts in their preferred habitat. Given its endemic distribution and limited life-history information, it will be critical to understand its tolerance to environmental challenges to create robust conservation strategies.

Trans individuals' experiences in primary care.

OBJECTIVE: To explore past experiences and describe the expectations of members of the trans community regarding the delivery of primary care by their family physicians. DESIGN: Qualitative phenomenologic approach. SETTING: Kingston, Ont, which has a population of approximately 123 000. PARTICIPANTS: A convenience sample of 11 individuals older than 18 years of age who self-identified as trans was recruited through community agencies and family medicine clinics. METHODS: Semistructured interviews were recorded and transcribed verbatim, and thematic analysis of transcripts was carried out by 2 independent researchers using NVivo. MAIN FINDINGS: Eleven interviews took place between September and November 2016; 4 individuals identified as trans men, 6 as trans women, and 1 as gender nonconforming. Themes identified included perceived physician knowledge of trans identities, patient self-advocacy, discrimination, positive spaces, and expectations of ideal care. The expected role of the family physician for trans patients includes hormone assessment and prescription and referrals for gender-affirming surgeries. CONCLUSION: The trans community has several physical and mental health needs that are not being met by the current health care system. Family physicians need to be empowered to provide services such as hormone initiation and gender-affirming surgery referrals. Although other specialists might have a role for some patients, most trans people expect care to be delivered by family physicians whenever possible.

Post-Capture Survival and Implications for By-Catch in a Multi-Species Coastal Gillnet Fishery.

As fisheries shift towards ecosystem-based management, the need to reduce impacts on by-catch has been increasingly recognised. In this study the catch composition, discard rate, and post-capture survival of species caught by gillnets in Tasmania, Australia, was investigated. Over half the commercial gillnet catch was discarded, with discard rates of ~20% for target and >80% for non-target species. Capture condition, including initial mortality, was assessed using simple criteria for a range of species and related to soak duration. Delayed mortality was also assessed using tank trials and related to capture condition. By combining initial and delayed mortality rates post-capture survival was estimated. Longer soak durations generally resulted in slight, but significant, declines in capture condition and lower initial survival. Nonetheless, when combined with delayed survival, four of the five most commonly caught species (Cheilodactylus spectabilis, Latridopsis forsteri, Aplodactylus arctidens, Cephaloscyllium laticeps) exhibited high post-capture survival (83-100%) for soak durations within the maximum regulated range. Post-capture survival of the one remaining commonly caught species, Notolabrus tetricus, (typically discarded) declined with increased soak duration from 84% to 62%, suggesting that this species would benefit from a further reduction in maximum soak duration. Initial and delayed survival rates for the species retained for tank trials exhibited a significant linear relationship, which was used to estimate delayed survival rates for the rarer species. This method enabled the estimation of potential post-capture survival rates for a diverse range of species and may have application in other data-limited situations where the relationships between fishing practices and by-catch survival are uncertain. Overall, our results suggest that soak duration regulation has been effective in reducing by-catch mortality for many species, noting that some species have low survival rates regardless of soak duration.

Sulfate transporters involved in sulfate secretion in the kidney are localized in the renal proximal tubule II of the elephant fish (Callorhinchus milii).

Most vertebrates, including cartilaginous fishes, maintain their plasma SO4 (2-) concentration ([SO4 (2-)]) within a narrow range of 0.2-1 mM. As seawater has a [SO4 (2-)] about 40 times higher than that of the plasma, SO4 (2-) excretion is the major role of kidneys in marine teleost fishes. It has been suggested that cartilaginous fishes also excrete excess SO4 (2-) via the kidney. However, little is known about the underlying mechanisms for SO4 (2-) transport in cartilaginous fish, largely due to the extraordinarily elaborate four-loop configuration of the nephron, which consists of at least 10 morphologically distinguishable segments. In the present study, we determined cDNA sequences from the kidney of holocephalan elephant fish (Callorhinchus milii) that encoded solute carrier family 26 member 1 (Slc26a1) and member 6 (Slc26a6), which are SO4 (2-) transporters that are expressed in mammalian and teleost kidneys. Elephant fish Slc26a1 (cmSlc26a1) and cmSlc26a6 mRNAs were coexpressed in the proximal II (PII) segment of the nephron, which comprises the second loop in the sinus zone. Functional analyses using Xenopus oocytes and the results of immunohistochemistry revealed that cmSlc26a1 is a basolaterally located electroneutral SO4 (2-) transporter, while cmSlc26a6 is an apically located, electrogenic Cl(-)/SO4 (2-) exchanger. In addition, we found that both cmSlc26a1 and cmSlc26a6 were abundantly expressed in the kidney of embryos; SO4 (2-) was concentrated in a bladder-like structure of elephant fish embryos. Our results demonstrated that the PII segment of the nephron contributes to the secretion of excess SO4 (2-) by the kidney of elephant fish. Possible mechanisms for SO4 (2-) secretion in the PII segment are discussed.

Fukushima derived radiocesium in subsistence-consumed northern fur seal and wild celery.

In July 2014, our investigative team traveled to St. Paul Island, Alaska to measure concentrations of radiocesium in wild-caught food products, primarily northern fur seal (Callorhinus ursinus). The 2011 Fukushima Daiichi Nuclear Power Plant accident released radiocesium into the atmosphere and into the western Pacific Ocean; other investigators have detected Fukushima-derived radionuclides in a variety of marine products harvested off the western coast of North America. We tested two subsistence-consumed food products from St. Paul Island, Alaska for Fukushima-derived radionuclides: 54 northern fur seal, and nine putchki (wild celery, Angelica lucida) plants. Individual northern fur seal samples were below minimum detectable activity concentrations of (137)Cs and (134)Cs, but when composited, northern fur seal tissues tested positive for trace quantities of both isotopes. Radiocesium was detected at an activity concentration of 37.2 mBq (134)Cs kg(-1) f.w. (95% CI: 35.9-38.5) and 141.2 mBq (137)Cs kg(-1) f.w. (95% CI: 135.5-146.8). The measured isotopic ratio, decay-corrected to the date of harvest, was 0.26 (95% CI: 0.25-0.28). The Fukushima nuclear accident released (134)Cs and (137)Cs in roughly equal quantities, but by the date of harvest in July 2014, this ratio was 0.2774, indicating that this population of seals has been exposed to small quantities of Fukushima-derived radiocesium. Activity concentrations of both (134)Cs and (137)Cs in putchki were below detection limits, even for composited samples. Northern fur seal is known to migrate between coastal Alaska and Japan and the trace (134)Cs in northern fur seal tissue suggests that the population under study had been minimally exposed Fukushima-derived radionuclides. Despite this inference, the radionuclide quantities detected are small and no impact is expected as a result of the measured radiation exposure, either in northern fur seal or human populations consuming this species.

Discovery of conventional prolactin from the holocephalan elephant fish, Callorhinchus milii.

The conventional prolactin (PRL), also known as PRL1, is an adenohypophysial hormone that critically regulates various physiological events in reproduction, metabolism, growth, osmoregulation, among others. PRL1 shares its evolutionary origin with PRL2, growth hormone (GH), somatolactin and placental lactogen, which together form the GH/PRL hormone family. Previously, several bioassays implied the existence of PRL1 in elasmobranch pituitaries. However, to date, all attempts to isolate PRL1 from chondrichthyans have been unsuccessful. Here, we cloned PRL1 from the pituitary of the holocephalan elephant fish, Callorhinchus milii, as the first report of chondrichthyan PRL1. The putative mature protein of elephant fish PRL1 (cmPRL1) consists of 198 amino acids, containing two conserved disulfide bonds. The orthologous relationship of cmPRL1 to known vertebrate PRL1s was confirmed by the analyses of molecular phylogeny and gene synteny. The cmPRL1 gene was similar to teleost PRL1 genes in gene synteny, but was distinct from amniote PRL1 genes, which most likely arose in an early amphibian by duplication of the ancestral PRL1 gene. The mRNA of cmPRL1 was predominantly expressed in the pituitary, but was considerably less abundant than has been previously reported for bony fish and tetrapod PRL1s; the copy number of cmPRL1 mRNA in the pituitary was less than 1% and 0.1% of that of GH and pro-opiomelanocortin mRNAs, respectively. The cells expressing cmPRL1 mRNA were sparsely distributed in the rostral pars distalis. Our findings provide a new insight into the studies on molecular and functional evolution of PRL1 in vertebrates.

Validation of 64Cu-ATSM damaging DNA via high-LET Auger electron emission.

Radioactive copper (II) (diacetyl-bis N4-methylthiosemicarbazone) (Cu-ATSM) isotopes were originally developed for the imaging of hypoxia in tumors. Because the decay of a (64)Cu atom is emitting not only positrons but also Auger electrons, this radionuclide has great potential as a theranostic agent. However, the success of (64)Cu-ATSM internal radiation therapy would depend on the contribution of Auger electrons to tumor cell killing. Therefore, we designed a cell culture system to define the contributions to cell death from Auger electrons to support or refute our hypothesis that the majority of cell death from (64)Cu-ATSM is a result of high-LET Auger electrons and not positrons or other low-LET radiation. Chinese hamster ovary (CHO) wild type and DNA repair-deficient xrs5 cells were exposed to (64)Cu-ATSM during hypoxic conditions. Surviving fractions were compared with those surviving gamma-radiation, low-LET hadron radiation, and high-LET heavy ion exposure. The ratio of the D(10) values (doses required to achieve 10% cell survival) between CHO wild type and xrs5 cells suggested that (64)Cu-ATSM toxicity is similar to that of high-LET Carbon ion radiation (70 keV/µm). γH2AX foci assays confirmed DNA double-strand breaks and cluster damage by high-LET Auger electrons from (64)Cu decay, and complex types of chromosomal aberrations typical of high-LET radiation were observed after (64)Cu-ATSM exposure. The majority of cell death was caused by high-LET radiation. This work provides strong evidence that (64)Cu-ATSM damages DNA via high-LET Auger electrons, supporting further study and consideration of (64)Cu-ATSM as a cancer treatment modality for hypoxic tumors.