Rate of mass loss from the Greenland Ice Sheet will exceed Holocene values this century.

The Greenland Ice Sheet (GIS) is losing mass at a high rate1. Given the short-term nature of the observational record, it is difficult to assess the historical importance of this mass-loss trend. Unlike records of greenhouse gas concentrations and global temperature, in which observations have been merged with palaeoclimate datasets, there are no comparably long records for rates of GIS mass change. Here we reveal unprecedented mass loss from the GIS this century, by placing contemporary and future rates of GIS mass loss within the context of the natural variability over the past 12,000 years. We force a high-resolution ice-sheet model with an ensemble of climate histories constrained by ice-core data2. Our simulation domain covers southwestern Greenland, the mass change of which is dominated by surface mass balance. The results agree favourably with an independent chronology of the history of the GIS margin3,4. The largest pre-industrial rates of mass loss (up to 6,000 billion tonnes per century) occurred in the early Holocene, and were similar to the contemporary (AD 2000-2018) rate of around 6,100 billion tonnes per century5. Simulations of future mass loss from southwestern GIS, based on Representative Concentration Pathway (RCP) scenarios corresponding to low (RCP2.6) and high (RCP8.5) greenhouse gas concentration trajectories6, predict mass loss of between 8,800 and 35,900 billion tonnes over the twenty-first century. These rates of GIS mass loss exceed the maximum rates over the past 12,000 years. Because rates of mass loss from the southwestern GIS scale linearly5 with the GIS as a whole, our results indicate, with high confidence, that the rate of mass loss from the GIS will exceed Holocene rates this century.

Effects of melt aging and off-stoichiometric melts on CsSrI3:Eu(2+) single crystal scintillators.

Ternary halide scintillators are commonly prepared from a mixture of commercially available binary halides. The initial binary halides may contain excess halogen ions or have different volatilities, which could lead to loss of stoichiometry of the resulting ternary halide crystals and potentially negatively affect optical and scintillation properties. In this work, the effects of vacuum aging of the melt (melt aging) and use of off-stoichiometric melts via introduction of excess CsI on the crystal quality and scintillation properties of CsSrI3:Eu(2+), a promising scintillator for gamma-ray detection applications, are investigated. The phase purity of the grown samples was confirmed by powder X-ray diffraction and differential scanning calorimeter measurements, and the existence of matrix composition variations is revealed by energy-dispersive X-ray spectroscopy analyses. An abnormal relationship between the full energy peak and the shaping time, i.e. full energy peak broadening or existence of two full energy peaks, in the melt-aged and off-stoichiometric samples is observed. It is ascribed to a slow scintillation decay event in a time scale between 15 and 50 µs. For the CsSrI3:Eu(2+) single crystal grown from a stoichiometric melt without melt aging treatment, an energy resolution of 5.0% at 662 keV and a light yield of 48,000 ± 2000 photons per MeV can be achieved at a size of 1.4 cm(3).

Mitotically inactivated embryonic stem cells can be used as an in vivo feeder layer to nurse damaged myocardium after acute myocardial infarction: a preclinical study.

RATIONALE: Various types of viable stem cells have been reported to result in modest improvement in cardiac function after acute myocardial infarction. The mechanisms for improvement from different stem cell populations remain unknown. OBJECTIVE: To determine whether irradiated (nonviable) embryonic stem cells (iESCs) improve postischemic cardiac function without adverse consequences. METHODS AND RESULTS: After coronary artery ligation-induced cardiac infarction, either conditioned media or male murine or male human iESCs were injected into the penumbra of ischemic myocardial tissue of female mice or female rhesus macaque monkeys, respectively. Murine and human iESCs, despite irradiation doses that prevented proliferation and induced cell death, significantly improved cardiac function and decreased infarct size compared with untreated or media-treated controls. Fluorescent in situ hybridization of the Y chromosome revealed disappearance of iESCs within the myocardium, whereas 5-bromo-2'-deoxyuridine assays revealed de novo in vivo cardiomyocyte DNA synthesis. Microarray gene expression profiling demonstrated an early increase in metabolism, DNA proliferation, and chromatin remodeling pathways, and a decrease in fibrosis and inflammatory gene expression compared with media-treated controls. CONCLUSIONS: As a result of irradiation before injection, ex vivo and in vivo iESC existence is transient, yet iESCs provide a significant improvement in cardiac function after acute myocardial infarction. The mechanism(s) of action of iESCs seems to be related to cell-cell exchange, paracrine factors, and a scaffolding effect between iESCs and neighboring host cardiomyocytes.

Three-dimensional paper-based microfluidic device for assays of protein and glucose in urine.

The first step in curing a disease is being able to detect the disease effectively. Paper-based microfluidic devices are biodegradable and can make diagnosing diseases cost-effective and easy in almost all environments. We created a three-dimesnional (3D) paper device using wax printing fabrication technique and basic principles of origami. This design allows for a versatile fabrication technique over previously reported patterning of SU-8 photoresist on chromatography paper by employing a readily available wax printer. The design also utilizes multiple colorimetric assays that can accommodate one or more analytes including urine, blood, and saliva. In this case to demonstrate the functionality of the 3D paper-based microfluidic system, a urinalysis of protein and glucose assays is conducted. The amounts of glucose and protein introduced to the device are found to be proportional to the color change of each assay. This color change was quantified by use of Adobe Photoshop. Urine samples from participants with no pre-existing health conditions and one person with diabetes were collected and compared against synthetic urine samples with predetermined glucose and protein levels. Utilizing this method, we were able to confirm that both protein and glucose levels were in fact within healthy ranges for healthy participants. For the participant with diabetes, glucose was found to be above the healthy range while the protein level was in the healthy range.

Deep learning estimation of northern hemisphere soil freeze-thaw dynamics using satellite multi-frequency microwave brightness temperature observations.

Satellite microwave sensors are well suited for monitoring landscape freeze-thaw (FT) transitions owing to the strong brightness temperature (TB) or backscatter response to changes in liquid water abundance between predominantly frozen and thawed conditions. The FT retrieval is also a sensitive climate indicator with strong biophysical importance. However, retrieval algorithms can have difficulty distinguishing the FT status of soils from that of overlying features such as snow and vegetation, while variable land conditions can also degrade performance. Here, we applied a deep learning model using a multilayer convolutional neural network driven by AMSR2 and SMAP TB records, and trained on surface (~0-5 cm depth) soil temperature FT observations. Soil FT states were classified for the local morning (6 a.m.) and evening (6 p.m.) conditions corresponding to SMAP descending and ascending orbital overpasses, mapped to a 9 km polar grid spanning a five-year (2016-2020) record and Northern Hemisphere domain. Continuous variable estimates of the probability of frozen or thawed conditions were derived using a model cost function optimized against FT observational training data. Model results derived using combined multi-frequency (1.4, 18.7, 36.5 GHz) TBs produced the highest soil FT accuracy over other models derived using only single sensor or single frequency TB inputs. Moreover, SMAP L-band (1.4 GHz) TBs provided enhanced soil FT information and performance gain over model results derived using only AMSR2 TB inputs. The resulting soil FT classification showed favorable and consistent performance against soil FT observations from ERA5 reanalysis (mean percent accuracy, MPA: 92.7%) and in situ weather stations (MPA: 91.0%). The soil FT accuracy was generally consistent between morning and afternoon predictions and across different land covers and seasons. The model also showed better FT accuracy than ERA5 against regional weather station measurements (91.0% vs. 86.1% MPA). However, model confidence was lower in complex terrain where FT spatial heterogeneity was likely beneath the effective model grain size. Our results provide a high level of precision in mapping soil FT dynamics to improve understanding of complex seasonal transitions and their influence on ecological processes and climate feedbacks, with the potential to inform Earth system model predictions.

Mechanically ventilated COVID-19 patients admitted to the intensive care unit in the United States with or without respiratory failure secondary to COVID-19 pneumonia: a retrospective comparison of characteristics and outcomes.

BACKGROUND: There is increasing heterogeneity in the clinical phenotype of patients admitted to the intensive care unit (ICU) with coronavirus disease 2019 (COVID-19,) and reasons for mechanical ventilation are not limited to COVID pneumonia. We aimed to compare the characteristics and outcomes of intubated patients admitted to the ICU with the primary diagnosis of acute hypoxemic respiratory failure (AHRF) from COVID-19 pneumonia to those patients admitted for an alternative diagnosis. METHODS: Retrospective cohort study of adults with confirmed SARS-CoV-2 infection admitted to nine ICUs between March 18, 2020, and April 30, 2021, at an urban university institution. We compared characteristics between the two groups using appropriate statistics. We performed logistic regression to identify risk factors for death in the mechanically ventilated COVID-19 population. RESULTS: After exclusions, the final sample consisted of 319 patients with respiratory failure secondary to COVID pneumonia and 150 patients intubated for alternative diagnoses. The former group had higher ICU and hospital mortality rates (57.7% vs. 36.7%, P<0.001 and 58.9% vs. 39.3%, P<0.001, respectively). Patients with AHRF secondary to COVID-19 pneumonia also had longer ICU and hospital lengths-of-stay (12 vs. 6 days, P<0.001 and 20 vs. 13.5 days, P=0.001). After risk-adjustment, these patients had 2.25 times higher odds of death (95% confidence interval, 1.42-3.56; P=0.001). CONCLUSIONS: Mechanically ventilated COVID-19 patients admitted to the ICU with COVID-19-associated respiratory failure are at higher risk of hospital death and have worse ICU utilization outcomes than those whose reason for admission is unrelated to COVID pneumonia.

Genotyping single nucleotide polymorphisms (SNPs) across species in Old World Monkeys.

The development of DNA markers is becoming increasingly useful in the field of primatology for studies on paternity, population history, and biomedical research. In this study, we determine the efficacy of using cross-species amplification to identify single nucleotide polymorphisms (SNPs) in closely related species. The DNA of 93 individuals representing seven Old World Monkey species was analyzed to identify SNPs using cross-species amplification and genotyping. The loci genotyped were 653 SNPs identified and validated in rhesus macaques. Of the 653 loci analyzed, 27% were estimated to be polymorphic in the samples studied. SNPs identified at the same locus among different species (coincident SNPs) were found in six of the seven species studied with longtail macaques exhibiting the highest number of coincident SNPs (84). The distribution of coincident SNPs among species is not biased based on proximity to genes in the samples studied. In addition, the frequency of coincident SNPs is not consistent with expectations based on their phylogenetic relationships. This study demonstrates that cross-species amplification and genotyping using the Illumina Golden Gate Array is a useful method to identify a large number of SNPs in closely related species, although issues with ascertainment bias may limit the type of studies where this method can be applied.

Mid-Miocene cooling and the extinction of tundra in continental Antarctica.

A major obstacle in understanding the evolution of Cenozoic climate has been the lack of well dated terrestrial evidence from high-latitude, glaciated regions. Here, we report the discovery of exceptionally well preserved fossils of lacustrine and terrestrial organisms from the McMurdo Dry Valleys sector of the Transantarctic Mountains for which we have established a precise radiometric chronology. The fossils, which include diatoms, palynomorphs, mosses, ostracodes, and insects, represent the last vestige of a tundra community that inhabited the mountains before stepped cooling that first brought a full polar climate to Antarctica. Paleoecological analyses, (40)Ar/(39)Ar analyses of associated ash fall, and climate inferences from glaciological modeling together suggest that mean summer temperatures in the region cooled by at least 8 degrees C between 14.07 +/- 0.05 Ma and 13.85 +/- 0.03 Ma. These results provide novel constraints for the timing and amplitude of middle-Miocene cooling in Antarctica and reveal the ecological legacy of this global climate transition.

Brief communication: mitochondrial haplotype C4c confirmed as a founding genome in the Americas.

Mitochondrial DNA analysis of 31 unrelated Shuswap speakers from a previously poorly sampled region of North America revealed two individuals with haplogroups rarely found in the Americas, C4c and C1d. Comparison of the complete genomes of the two individuals with others found in the literature confirms that C4c is a founding haplotype and gives insight into the evolution of the C1d haplotype. This study demonstrates the importance of collecting and analyzing data from Native North Americans when addressing hypotheses about the peopling of the Americas.

Extensive phylogenetic analysis of a soil bacterial community illustrates extreme taxon evenness and the effects of amplicon length, degree of coverage, and DNA fractionation on classification and ecological parameters.

To thoroughly investigate the bacterial community diversity present in a single composite sample from an agricultural soil and to examine potential biases resulting from data acquisition and analytical approaches, we examined the effects of percent G+C DNA fractionation, sequence length, and degree of coverage of bacterial diversity on several commonly used ecological parameters (species estimation, diversity indices, and evenness). We also examined variation in phylogenetic placement based on multiple commonly used approaches (ARB alignments and multiple RDP tools). The results demonstrate that this soil bacterial community is highly diverse, with 1,714 operational taxonomic units demonstrated and 3,555 estimated (based on the Chao1 richness estimation) at 97% sequence similarity using the 16S rRNA gene. The results also demonstrate a fundamental lack of dominance (i.e., a high degree of evenness), with 82% of phylotypes being encountered three times or less. The data also indicate that generally accepted cutoff values for phylum-level taxonomic classification might not be as applicable or as general as previously assumed and that such values likely vary between prokaryotic phyla or groups.

Supplemental programs for enhanced recovery of data from the DOTUR application.

In order to retrieve phylogenetic information from distance matrices generated from large-scale clone libraries, and to explore OTU distribution among them, we have developed downstream applications for use with the already available DOTUR program. These programs enhance and ease data extraction, providing phylogeny to the already generated distance data.

Acute and Chronic Increases of Circulating FSTL1 Normalize Energy Substrate Metabolism in Pacing-Induced Heart Failure.

BACKGROUND: FSTL1 (follistatin-like protein 1) is an emerging cardiokine/myokine that is upregulated in heart failure (HF) and is found to be cardioprotective in animal models of cardiac injury. We tested the hypothesis that circulating FSTL1 can affect cardiac function and metabolism under baseline physiological conditions and in HF. METHODS AND RESULTS: FSTL1 was acutely (10 minutes) or chronically (2 weeks) infused to attain clinically relevant blood levels in conscious dogs with cardiac tachypacing-induced HF. Dogs with no cardiac pacing and FSTL1 infusion served as control. 3H-oleate and 14C-glucose were infused to track the metabolic fate of free fatty acids and glucose. Cardiac uptake of lactate and ketone bodies and systemic respiratory quotient were also measured. HF caused a shift from prevalent cardiac and systemic fat to carbohydrate oxidation. Although acute FSTL1 administration caused minimal hemodynamic changes at baseline, in HF dogs it enhanced cardiac oxygen consumption and transiently reversed the changes in free fatty acid and glucose oxidation and systemic respiratory quotient. In HF, chronic FSTL1 infusion stably normalized cardiac free fatty acid, glucose, ketone body consumption, and systemic respiratory quotient, while moderately improving diastolic and contractile function. Consistently, FSTL1 prevented the downregulation of medium-chain acyl-CoA dehydrogenase-a representative enzyme of the free fatty acid oxidation pathway. Complementary in vitro experiments in primary cardiac and skeletal muscle myocytes showed that FSTL1 stimulated oxygen consumption through AMPK (AMP-activated kinase) activation. CONCLUSIONS: These findings support a novel function for FSTL1 and provide the first direct evidence that a circulating cardiokine/myokine can alter myocardial and systemic energy substrate metabolism, in vivo.

Closed solutions to a differential-difference equation and an associated plate solidification problem.

Two distinct and novel formalisms for deriving exact closed solutions of a class of variable-coefficient differential-difference equations arising from a plate solidification problem are introduced. Thereupon, exact closed traveling wave and similarity solutions to the plate solidification problem are obtained for some special cases of time-varying plate surface temperature.

Effects on stereotypy and other challenging behavior of matching rates of instruction to free-operant rates of responding.

Research has shown that when individuals are in situations that do not occasion one form of motoric responding, they will engage in another so that the overall level of motoric responding is homeostatic. The purpose of this study was to test whether students would substitute task-related behaviors for stereotypic or other challenging behaviors when the opportunity for active responding did or did not match the level of motoric responding in a free-operant baseline. Four students with mental retardation participated. Results showed that they did substitute behaviors, with stereotypic and other challenging behaviors occurring 1.5-14 times as much in the Non-matched condition for the four students. Further analysis showed considerably more of these behaviors in passive than in active tasks (by a factor up to 21 times as much). Results were discussed in terms of homeostasis, functional assessment, and opportunities to improve educational behaviors.

Discrimination training: a comparison of two procedures for presenting multiple examples within a fading and non-fading paradigm.

When teaching discriminations, many researchers and practitioners recommend presenting multiple examples of both the correct and incorrect stimuli. To test this suggestion, we compared two procedures for presenting multiple examples. In one, multiple examples across trials (ME, Across), one correct (S+) and one incorrect (S-) stimulus were presented each trial; examples then changed across trials. In another procedure, multiple examples within trials (ME, Within), three stimuli (either 2 S+'s and 1 S-, or 1 S+ and 2 S-'s) were presented each trial; examples again changed across trials. Two experiments were conducted to test these procedures. The first procedure used a non-fading program to teach discrimination; the second used a fading procedure. In the first experiment, we taught 10 persons to identify words under these two procedures. The former procedure was superior in acquisition; the latter procedure, however, was better under generalization for most participants. In the second experiment, we presented the two procedures within a fading paradigm. The results replicated those in Experiment 1: ME, Across was better for acquisition, but ME, Within was better for generalization. Results were discussed and follow-up studies suggested.

Ancient DNA analysis of mid-holocene individuals from the Northwest Coast of North America reveals different evolutionary paths for mitogenomes.

To gain a better understanding of North American population history, complete mitochondrial genomes (mitogenomes) were generated from four ancient and three living individuals of the northern Northwest Coast of North America, specifically the north coast of British Columbia, Canada, current home to the indigenous Tsimshian, Haida, and Nisga'a. The mitogenomes of all individuals were previously unknown and assigned to new sub-haplogroup designations D4h3a7, A2ag and A2ah. The analysis of mitogenomes allows for more detailed analyses of presumed ancestor-descendant relationships than sequencing only the HVSI region of the mitochondrial genome, a more traditional approach in local population studies. The results of this study provide contrasting examples of the evolution of Native American mitogenomes. Those belonging to sub-haplogroups A2ag and A2ah exhibit temporal continuity in this region for 5000 years up until the present day. Of possible associative significance is that archaeologically identified house structures in this region maintain similar characteristics for this same period of time, demonstrating cultural continuity in residence patterns. The individual dated to 6000 years before present (BP) exhibited a mitogenome belonging to sub-haplogroup D4h3a. This sub-haplogroup was earlier identified in the same general area at 10300 years BP on Prince of Wales Island, Alaska, and may have gone extinct, as it has not been observed in any living individuals of the Northwest Coast. The presented case studies demonstrate the different evolutionary paths of mitogenomes over time on the Northwest Coast.

The effect of SNP discovery method and sample size on estimation of population genetic data for Chinese and Indian rhesus macaques (Macaca mulatta).

This study was designed to address issues regarding sample size and marker location that have arisen from the discovery of SNPs in the genomes of poorly characterized primate species and the application of these markers to the study of primate population genetics. We predict the effect of discovery sample size on the probability of discovering both rare and common SNPs and then compare this prediction with the proportion of common and rare SNPs discovered when different numbers of individuals are sequenced. Second, we examine the effect of genomic region on estimates of common population genetic data, comparing markers from both coding and non-coding regions of the rhesus macaque genome and the population genetic data calculated from these markers, to measure the degree and direction of bias introduced by SNPs located in coding versus non-coding regions of the genome. We found that both discovery sample size and genomic region surveyed affect SNP marker attributes and population genetic estimates, even when these are calculated from an expanded data set containing more individuals than the original discovery data set. Although none of the SNP detection methods or genomic regions tested in this study was completely uninformative, these results show that each has a different kind of genetic variation that is suitable for different purposes, and each introduces specific types of bias. Given that each SNP marker has an individual evolutionary history, we calculated that the most complete and unbiased representation of the genetic diversity present in the individual can be obtained by incorporating at least 10 individuals into the discovery sample set, to ensure the discovery of both common and rare polymorphisms.

CT lower extremity venography in suspected pulmonary embolism in the ED.

The purpose of this study was to evaluate the added benefit of computed tomography lower extremity venography (CTLV)--performed following CT pulmonary angiography (CTPA)--in the emergency department (ED) patient suspected of pulmonary embolism (PE). A retrospective review of 427 consecutive patients having both CTPA and CTLV performed to evaluate patients suspected of PE at two community hospitals was conducted. Three-month follow-up was performed on all patients to ensure that no case of PE or deep venous thrombosis (DVT) was missed. Forty patients were positive for PE, and 11 were positive for DVT. There were 6 CTPA studies read as indeterminate for PE and 11 CTLV studies indeterminate for DVT. Only 1 patient was positive for DVT, who did not have a concurrent PE identified by CTPA. The estimated charges for detecting the single case of isolated DVT was 206,400 US dollars. In our ED setting, the additional benefit of adding CTLV to the standard ED work-up of PE was minimal.

Phase 2 enzyme induction by the major metabolite of oltipraz.

Treatment for 48 h of murine Hepa 1c1c7 cells in culture with the cancer chemopreventive oltipraz (1) followed by addition of CD(3)I and immediate cell lysis yields, by LC/MS analysis, three isotopomers of the methylated pyrrolopyrazine (2), a known human metabolite of oltipraz. The major isotopomer (58%) is the one containing two CD(3)- groups attached to the pendant sulfur atoms of the pyrrolopyrazine ring, the others containing one CD(3)- and one CH(3)- group or two CH(3)- groups. It is concluded from this that the unmethylated pyrrolopyrazine (4) is the major metabolite of oltipraz. Prodrugs 5 and 6, which have been shown to rapidly generate 4 in the presence of GSH at physiological pH, induce the phase 2 enzyme NQO1 in Hepa 1c1c7 cells with potencies on par with oltipraz itself: CD(NQO1) = 14.4 +/- 1.3, 20.1 +/- 4.6, and 23.6 +/- 1.6 microM for oltipraz, 5, and 6, respectively. Pretreatment of oltipraz, 5, and 6 in cell culture media with 1 mM GSH, which is shown to immediately convert 5 and 6 to 4, followed by incubation with Hepa 1c1c7 cells shows similar potencies for oltipraz and the (decomposed) produrgs, with CD(NQO1) = 18.0 +/- 4.4 microM for 5, 17.8 +/- 0.2 microM for 6, and 13.5 +/- 1.4 microM for oltipraz. Treatment with compound 6 of murine hepatoma cells containing a luciferase gene under the control of the antioxidant response element (ARE) from the mouse heme oxygenase (ho-1) gene elicits induction of luciferase activity, CD = 35.8 +/- 2.8 microM, somewhat greater than the potency than oltipraz itself. Western blots of nuclear proteins isolated from Hepa 1c1c7 cells and probed with anti-Nrf2 indicate that as compared to vehicle DMSO, compound 6 stimulates nuclear translocation of Nrf2 from the cytosol. From this study, it is concluded that the major metabolite of the cancer chemopreventive oltipraz is a phase 2 enzyme inducer of comparable potency that activates the ARE and initiates nuclear translocation of transcription factor Nrf 2.

Identification of aflatoxin M1-N7-guanine in liver and urine of tree shrews and rats following administration of aflatoxin B1.

Epidemiological studies have shown that exposure to aflatoxin B(1) (AFB(1)) and concurrent infection with hepatitis B lead to a multiplicative risk of developing liver cancer. This chemical-viral interaction can be recapitulated in the tree shrew (Tupia belangeri chinensis). As an initial characterization of this model, the metabolism of AFB(1) in tree shrews has been examined and compared to a sensitive bioassay species, the rat. Utilizing LC/MS/MS, an unreported product, aflatoxin M(1)-N(7)-guanine (AFM(1)-N(7)-guanine), was detected in urine and hepatic DNA samples 24 h after administration of 400 microg/kg AFB(1). In hepatic DNA isolated from tree shrews, AFM(1)-N(7)-guanine was the predominant adduct, 0.74 +/- 0.14 pmol/mg DNA, as compared to 0.37 +/- 0.07 pmol/mg DNA of AFB(1)-N(7)-guanine. Conversely, in rat liver, 6.56 +/- 2.41 pmol/mg DNA of AFB(1)-N(7)-guanine and 0.42 +/- 0.13 pmol/mg DNA of AFM(1)-N(7)-guanine were detected. Rats excreted 1.00 +/- 0.21 pmol AFB(1)-N(7)-guanine/mg creatinine and 0.29 +/- 0.10 pmol AFM(1)-N(7)-guanine/mg creatinine as compared to 0.60 +/- 0.12 pmol AFB(1)-N(7)-guanine/mg creatinine and 0.69 +/- 0.16 pmol AFM(1)-N(7)-guanine/mg creatinine excreted by the tree shrew. Furthermore, tree shrew urine contained 40 times more of the hydroxylated metabolite, AFM(1), than was excreted by rats. In vitro experiments confirmed this difference in oxidative metabolism. Hepatic microsomes isolated from tree shrews failed to produce aflatoxin Q(1) or aflatoxin P(1) but formed a significantly greater amount of AFM(1) than rat microsomes. Bioassays indicated that the tree shrew was considerably more resistant than the rat to AFB(1) hepatocarcinogenesis, which may reflect the significant differences in metabolic profiles of the two species.