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Authors explore recent education policies that ban the teaching of critical race theory, restrict teaching race-related topics, prohibit conversations about divisive concepts, and problematize their impact in further silencing (and potentially erasing) complex issues about race and racism and other forms of oppression in historical and sociocultural contexts. This article highlights legislative efforts and examines findings and implications from a study designed to explore perceptions of educators related to the anti-critical race theory bills. [ABSTRACT FROM AUTHOR]

This article presents a study that explored how race and racism impact teaching and learning and how civic education can be employed to promote racial justice. We argue the need to examine educators' perspectives on how increased awareness of existing inequities coupled with ongoing professional development can better equip them to understand their identity, engage in meaningful dialogue, and teach in culturally responsive ways. The paper concludes with a brief discussion of teaching implications related to self-assessment, disruptive discourse, and inclusive practices. [ABSTRACT FROM AUTHOR]

Drug-resistant forms of acute lymphoblastic leukaemia ( ALL) are a leading cause of death from disease in children. Up to 25% of patients with T-cell ALL (T- ALL) develop resistance to chemotherapeutic agents, particularly to glucocorticoids ( GCs), a class of drug to which resistance is one of the strongest indicators of poor clinical outcome. Despite their clinical importance, the molecular mechanisms that underpin GC resistance and leukaemia relapse are not well understood. Recently, we demonstrated that GC-resistance is associated with a proliferative metabolism involving the up-regulation of glycolysis, oxidative phosphorylation and cholesterol biosynthesis. Here we confirm that resistance is directly associated with a glycolytic phenotype and show that GC-resistant T- ALL cells are able to shift between glucose bioenergetic pathways. We evaluated the potential for targeting these pathways in vitro using a glycolysis inhibitor, 2-deoxyglucose (2 DG), and the oxidative phosphorylation inhibitor oligomycin in combination with methylprednisolone ( MPRED). We found that oligomycin synergized with MPRED to sensitize cells otherwise resistant to GCs. Similarly we observed synergy between MPRED and simvastatin, an inhibitor of cholesterol metabolism. Collectively, our findings suggest that dual targeting of bioenergetic pathways in combination with GCs may offer a promising therapeutic strategy to overcome drug resistance in ALL. [ABSTRACT FROM AUTHOR]

Background: Pre-clinical models that effectively recapitulate human disease are critical for expanding our knowledge of cancer biology and drug resistance mechanisms. For haematological malignancies, the non-obese diabetic/severe combined immunodeficient (NOD/SCID) mouse is one of the most successful models to study paediatric acute lymphoblastic leukaemia (ALL). However, for this model to be effective for studying engraftment and therapy responses at the whole genome level, careful molecular characterisation is essential. Results: Here, we sought to validate species-specific gene expression profiling in the high engraftment continuous ALL NOD/SCID xenograft. Using the human Affymetrix whole transcript platform we analysed transcriptional profiles from engrafted tissues without prior cell separation of mouse cells and found it to return highly reproducible profiles in xenografts from individual mice. The model was further tested with experimental mixtures of human and mouse cells, demonstrating that the presence of mouse cells does not significantly skew expression profiles when xenografts contain 90% or more human cells. In addition, we present a novel in silico and experimental masking approach to identify probes and transcript clusters susceptible to cross-species hybridisation. Conclusions: We demonstrate species-specific transcriptional profiles can be obtained from xenografts when high levels of engraftment are achieved or with the application of transcript cluster masks. Importantly, this masking approach can be applied and adapted to other xenograft models where human tissue infiltration is lower. This model provides a powerful platform for identifying genes and pathways associated with ALL disease progression and response to therapy in vivo. [ABSTRACT FROM AUTHOR]

Studies evaluating effects of human activity on wildlife typically emphasize short-term behavioral responses from which it is difficult to infer biological significance or formulate plans to mitigate harmful impacts. Based on decades of detailed behavioral records, we evaluated long-term impacts of vessel activity on bottlenose dolphins (Tursiops sp.) in Shark Bay, Australia. We compared dolphin abundance within adjacent 36-km2 tourism and control sites, over three consecutive 4.5-year periods wherein research activity was relatively constant but tourism levels increased from zero, to one, to two dolphin-watching operators. A nonlinear logistic model demonstrated that there was no difference in dolphin abundance between periods with no tourism and periods in which one operator offered tours. As the number of tour operators increased to two, there was a significant average decline in dolphin abundance (14.9%; 95% CI =−20.8 to −8.23), approximating a decline of one per seven individuals. Concurrently, within the control site, the average increase in dolphin abundance was not significant (8.5%; 95% CI =−4.0 to +16.7). Given the substantially greater presence and proximity of tour vessels to dolphins relative to research vessels, tour-vessel activity contributed more to declining dolphin numbers within the tourism site than research vessels. Although this trend may not jeopardize the large, genetically diverse dolphin population of Shark Bay, the decline is unlikely to be sustainable for local dolphin tourism. A similar decline would be devastating for small, closed, resident, or endangered cetacean populations. The substantial effect of tour vessels on dolphin abundance in a region of low-level tourism calls into question the presumption that dolphin-watching tourism is benign. [ABSTRACT FROM AUTHOR]

We documented immediate, behavioural responses of Indo-Pacific bottlenose dolphins (Tursiops sp.) to experimental vessel approaches in regions of high and low vessel traffic in Shark Bay, Western Australia. Experimental vessel approaches elicited significant changes in the behaviour of targeted dolphins when compared with their behaviour before and after approaches. During approaches, focal dolphin groups became more compact, had higher rates of change in membership and had more erratic speeds and directions of travel. Dolphins in the region of low vessel traffic (control site) had stronger and longer-lasting responses than did dolphins in the region of high vessel traffic (impact site). In the absence of additional information, the moderated behavioural responses of impact-site dolphins probably would be interpreted to mean that long-term vessel activity within a region of tourism had no detrimental effect on resident dolphins. However, another study showed that dolphin-watching tourism in Shark Bay has contributed to a long-term decline in dolphin abundance within the impact site (Bejder et al., in press, Conservation Biology). Those findings suggest that we documented moderated responses not because impact-site dolphins had become habituated to vessels but because those individuals that were sensitive to vessel disturbance left the region before our study began. This reinterpretation of our findings led us to question the traditional premise that short-term behavioural responses are sufficient indicators of impacts of anthropogenic disturbance on wildlife. [Copyright &y& Elsevier]

Abstract: We report on a study that extended mitochondrial transcript information from a recent EST project to obtain complete mitochondrial genome sequence for 5 tiger salamander complex species (Ambystoma mexicanum, A. t. tigrinum, A. andersoni, A. californiense, and A. dumerilii). We describe, for the first time, aspects of mitochondrial transcription in a representative amphibian, and then use complete mitochondrial sequence data to examine salamander phylogeny at both deep and shallow levels of evolutionary divergence. The available mitochondrial ESTs for A. mexicanum (N=2481) and A. t. tigrinum (N=1205) provided 92% and 87% coverage of the mitochondrial genome, respectively. Complete mitochondrial sequences for all species were rapidly obtained by using long distance PCR and DNA sequencing. A number of genome structural characteristics (base pair length, base composition, gene number, gene boundaries, codon usage) were highly similar among all species and to other distantly related salamanders. Overall, mitochondrial transcription in Ambystoma approximated the pattern observed in other vertebrates. We inferred from the mapping of ESTs onto mtDNA that transcription occurs from both heavy and light strand promoters and continues around the entire length of the mtDNA, followed by post-transcriptional processing. However, the observation of many short transcripts corresponding to rRNA genes indicates that transcription may often terminate prematurely to bias transcription of rRNA genes; indeed an rRNA transcription termination signal sequence was observed immediately following the 16S rRNA gene. Phylogenetic analyses of salamander family relationships consistently grouped Ambystomatidae in a clade containing Cryptobranchidae and Hynobiidae, to the exclusion of Salamandridae. This robust result suggests a novel alternative hypothesis because previous studies have consistently identified Ambystomatidae and Salamandridae as closely related taxa. Phylogenetic analyses of tiger salamander complex species also produced robustly supported trees. The D-loop, used in previous molecular phylogenetic studies of the complex, was found to contain a relatively low level of variation and we identified mitochondrial regions with higher rates of molecular evolution that are more useful in resolving relationships among species. Our results show the benefit of using complete genome mitochondrial information in studies of recently and rapidly diverged taxa. [Copyright &y& Elsevier]

Male members of a group of captive Macaca radiata at the California Primate Research Center held and carried infants as they approached or were approached by higher-ranking males and as they were threatened by other males. Male infants between the ages of 25 and 84 weeks were involved in triadic interactions more frequently than were female infants of any age or male infants of other ages. That males were less likely to be harassed while huddling with or embracing infants suggested that infants provided an effective buffer against aggression. [ABSTRACT FROM AUTHOR]

Background: Thyroid hormones (TH) induce gene expression programs that orchestrate amphibian metamorphosis. In contrast to anurans, many salamanders do not undergo metamorphosis in nature. However, they can be induced to undergo metamorphosis via exposure to thyroxine (T4). We induced metamorphosis in juvenile Mexican axolotls (Ambystoma mexicanum) using 5 and 50 nM T4, collected epidermal tissue from the head at four time points (Days 0, 2, 12, 28), and used microarray analysis to quantify mRNA abundances. Results: Individuals reared in the higher T4 concentration initiated morphological and transcriptional changes earlier and completed metamorphosis by Day 28. In contrast, initiation of metamorphosis was delayed in the lower T4 concentration and none of the individuals completed metamorphosis by Day 28. We identified 402 genes that were statistically differentially expressed by ≥ two-fold between T4 treatments at one or more non-Day 0 sampling times. To complement this analysis, we used linear and quadratic regression to identify 542 and 709 genes that were differentially expressed by ≥ two-fold in the 5 and 50 nM T4 treatments, respectively. Conclusion: We found that T4 concentration affected the timing of gene expression and the shape of temporal gene expression profiles. However, essentially all of the identified genes were similarly affected by 5 and 50 nM T4. We discuss genes and biological processes that appear to be common to salamander and anuran metamorphosis, and also highlight clear transcriptional differences. Our results show that gene expression in axolotls is diverse and precise, and that axolotls provide new insights about amphibian metamorphosis. [ABSTRACT FROM AUTHOR]

Abstract: Ambystomatid salamanders offer several advantages for endocrine disruption research, including genomic and bioinformatics resources, an accessible laboratory model (Ambystoma mexicanum), and natural lineages that are broadly distributed among North American habitats. We used microarray analysis to measure the relative abundance of transcripts isolated from A. mexicanum epidermis (skin) after exogenous application of thyroid hormone (TH). Only one gene had a >2-fold change in transcript abundance after 2 days of TH treatment. However, hundreds of genes showed significantly different transcript levels at days 12 and 28 in comparison to day 0. A list of 123 TH-responsive genes was identified using statistical, BLAST, and fold level criteria. Cluster analysis identified two groups of genes with similar transcription patterns: up-regulated versus down-regulated. Most notably, several keratins exhibited dramatic (1000 fold) increases or decreases in transcript abundance. Keratin gene expression changes coincided with morphological remodeling of epithelial tissues. This suggests that keratin loci can be developed as sensitive biomarkers to assay temporal disruptions of larval-to-adult gene expression programs. Our study has identified the first collection of loci that are regulated during TH-induced metamorphosis in a salamander, thus setting the stage for future investigations of TH disruption in the Mexican axolotl and other salamanders of the genus Ambystoma. [Copyright &y& Elsevier]

Patients relapsing with T-cell acute lymphoblastic leukemia (T-ALL) face a dismal outcome. The aim of this study was to identify new markers of drug resistance and clinical response in T-ALL. We measured gene expression and drug sensitivity in 15 pediatric T-ALL cell lines to find signatures predictive of resistance to 10 agents used in therapy. These were used to generate a model for outcome prediction in patient cohorts using microarray data from diagnosis specimens. In three independent T-ALL cohorts, the 10-drug model was able to accurately identify patient outcome, indicating that the --derived drug--gene profiles were clinically in vitro relevant. Importantly, predictions of outcome within each cohort were linked to distinct drugs, suggesting that different mechanisms contribute to relapse. Sulfite oxidase expression and the drug-transporter SUOX ABCC1 (MRP1) were linked to thiopurine sensitivity, suggesting novel pathways for targeting resistance. This study advances our understanding of drug resistance in T-ALL and provides newmarkers for patient stratification. The results suggest potential benefit from the earlier use of 6-mercaptopurine in T-ALL therapy or the development of adjuvants that may sensitize blasts to this drug. The methodology developed in this study could be applied to other cancers to achieve patient stratification at the time of diagnosis. [ABSTRACT FROM AUTHOR]

Background: Rearrangement of the mixed-lineage leukemia gene (MLL) is found in 80% of infant acute lymphoblastic leukemia (ALL) and is associated with poor prognosis and resistance to glucocorticoids (GCs). We have recently observed that GC resistance in T-ALL cell lines is associated with a proliferative metabolism and reduced expression of MLL. In this study we have further explored the relationship between MLL status and GC sensitivity. Results: Negative correlation of MLL expression with GC resistance in 15 T-ALL cell lines was confirmed by quantitative RT-PCR. The absence of MLL-rearrangements suggested that this relationship represented expression of wild-type MLL. Analysis of MLL expression patterns revealed a negative relationship with cellular metabolism, proliferation and anti-apoptotic transcriptional networks. In silico analysis of published data demonstrated that reduced levels of MLL mRNA are associated with relapse and prednisolone resistance in T-ALL patients and adverse clinical outcome in children with MLL-rearranged ALL. RNAi knockdown of MLL expression in T-ALL cell lines significantly increased resistance to dexamethasone and gamma irradiation indicating an important role for wildtype MLL in the control of cellular apoptosis. Conclusions: The data suggests that reduced expression of wild-type MLL can contribute to GC resistance in ALL patients both with and without MLL-translocations. [ABSTRACT FROM AUTHOR]

Salamanders of the genus Ambystoma are a unique model organism system because they enable natural history and biomedical research in the laboratory or field. We developed Sal-Site to integrate new and existing ambystomatid salamander research resources in support of this model system. Sal-Site hosts six important resources: 1) Salamander Genome Project: an information-based web-site describing progress in genome resource development, 2) Ambystoma EST Database: a database of manually edited and analyzed contigs assembled from ESTs that were collected from A. tigrinum tigrinum and A. mexicanum, 3) Ambystoma Gene Collection: a database containing full-length protein-coding sequences, 4) Ambystoma Map and Marker Collection: an image and database resource that shows the location of mapped markers on linkage groups, provides information about markers, and provides integrating links to Ambystoma EST Database and Ambystoma Gene Collection databases, 5) Ambystoma Genetic Stock Center: a website and collection of databases that describe an NSF funded salamander rearing facility that generates and distributes biological materials to researchers and educators throughout the world, and 6) Ambystoma Research Coordination Network: a web-site detailing current research projects and activities involving an international group of researchers. Sal-Site is accessible at http://www.ambystoma.org. [ABSTRACT FROM AUTHOR]

Reports that male humpback whales modify their sexual display when exposed to man-made noise. Concerns about the effects of man-made noise on marine life, in particular marine mammals that use sound to communicate, navigate and detect predators and prey; Study conducted in cooperation with the United States Navy that showed that the singing behavior of male humpback whales was altered when they were exposed to low-frequency active sonar.

Background: Establishing genomic resources for closely related species will provide comparative insights that are crucial for understanding diversity and variability at multiple levels of biological organization. We developed ESTs for Mexican axolotl (Ambystoma mexicanum) and Eastern tiger salamander (A. tigrinum tigrinum), species with deep and diverse research histories. Results: Approximately 40,000 quality cDNA sequences were isolated for these species from various tissues, including regenerating limb and tail. These sequences and an existing set of 16,030 cDNA sequences for A. mexicanum were processed to yield 35,413 and 20,599 high quality ESTs for A. mexicanum and A. t. tigrinum, respectively. Because the A. t. tigrinum ESTs were obtained primarily from a normalized library, an approximately equal number of contigs were obtained for each species, with 21,091 unique contigs identified overall. The 10,592 contigs that showed significant similarity to sequences from the human RefSeq database reflected a diverse array of molecular functions and biological processes, with many corresponding to genes expressed during spinal cord injury in rat and fin regeneration in zebrafish. To demonstrate the utility of these EST resources, we searched databases to identify probes for regeneration research, characterized intra- and interspecific nucleotide polymorphism, saturated a human - Ambystoma synteny group with marker loci, and extended PCR primer sets designed for A. mexicanum / A. t. tigrinum orthologues to a related tiger salamander species. Conclusions: Our study highlights the value of developing resources in traditional model systems where the likelihood of information transfer to multiple, closely related taxa is high, thus simultaneously enabling both laboratory and natural history research. [ABSTRACT FROM AUTHOR]

The neuromotor conservatism hypothesis predicts that neuromotor patterns in homologous tetrapod muscles are conserved evolutionarily despite the musculoskeletal modifications of vertebrate limbs. A complete description of the anatomical organization of the neurons innervating homologous limb muscles is a prerequisite to any test of the neuromotor conservatism hypothesis. This study uses the retrograde neuronal tracer WGA-HRP to selectively label the motor neuron pools of seven homologous forelimb muscles in mice (Mus musculus) and iguanas (Iguana iguana): Mm. pectoralis, spinodeltoideus, biceps brachii, lateral and long heads of triceps brachii, and the supraspinatus and infraspinatus (in mice) or their reptilian homolog, the supracoracoideus (in iguanas). In vertebrates, motoneurons are arranged in longitudinal columns of cells in the ventral horn of the spinal cord. Mouse motor pools average 1,952 μm in length, except the pectoralis pool which averaged 2,949 μm in length. Iguana pools average 3,196 μm in length. The number of neurons per pool ranged from 70–199 in mice and from 58–114 neurons in iguanas. In both iguanas and mice the motor pools for the spinodeltoids, biceps, and the supracoracoideus (or its mammalian homologs) lie anterior to the pectoralis and triceps motor pools. In the transverse plane, the pectoralis pool lies medial to those of the triceps. The pools of the biceps and spinodeltoids are located dorsal and lateral to those of the pectoralis and supracoracoideus (or its homologs in mammals). The resulting motor pool maps support the hypothesis that the anatomical organization of motoneurons in ancestral reptiles has been retained in these two tetrapod descendents. [ABSTRACT FROM AUTHOR]

We have developed a phosphotyrosine-specific yeast two-hybrid system and used it to identify molecules that interact with phosphorylated substrates of Src family kinases (SFK). Using this method has resulted in the identification of new SFK regulatory mechanisms and novel pathways that emanate from SFKs such as the family member Lyn. We show that the Lyn substrate Csk binding protein (Cbp) binds Lyn via a high affinity pY-SH2 interaction. Lyn phosphorylates Cbp after activation on multiple sites, including a site that recruit Lyn's negative site Y508 phosphorylating kinase, Csk/Ctk, allowing down regulation of Lyn's kinase activity. We also identified the SH2 domain of suppressor of cytokine signaling-1 (SOCS1) as binding specifically to phosphorylated Y314 of Cbp. We show SOCS1, which is transcriptionally induced by Lyn kinase activity, associates with Cbp to allow the ubiquitination and subsequent proteasomal degradation of Lyn. Further, other pY-motifs of Cbp interact with SH2 containing mediators of the Akt/PKB pathway. Our system has also identified novel oncogenic substrates of Lyn (Lyn associated cytoskeletal modulator, LACM) that link into the Vav and Nck pathways leading to major changes in cell shape. This new method is amenable to a high throughput screening strategy to identify pathways intersected by all the 120 SH2 domains present in the mammalian genome. [ABSTRACT FROM AUTHOR]