Biological Connections Research Articles

Abstract IA02: Dissection of the BRG1 and MYC/MAX biological connection and its use in lung cancer therapeutics

Abstract Lung cancer is the first cause of death due to cancer in most western countries, in part because of the low efficacy of most current therapies. In this regard, understanding the genetic architecture of lung malignancies has proven to constitute a reliable strategy to develop novel anticancer agents and foretell response to therapies. Previously, we reported that one third of the lung tumors of the non-small cell lung cancer type (NSCLC) endure inactivation of BRG1, which constitutes the fourth most commonly altered gene in this type of cancer. Interestingly, we also observed that BRG1 inactivation and MYC amplification are mutually exclusive events in lung cancer, supporting previous observations of a functional relationship between the MYC and BRG1 proteins. The BRG1 gene codes for a member of the SWI/SNF chromatin remodeling complex, and its role in cancer development is still poorly understood, which hinders its potential use in clinical settings. Here, I report our discovery on how the expression of wild type BRG1 in lung cancer cells up-regulates lung-specific transcripts, significantly restoring the gene expression signature of normal lung. Using cell lines from several cancer types we found that those lacking BRG1 do not respond to retinoic acid (RA) or glucocorticoids (GC), while restoration of BRG1 restitutes sensitivity, as determined by changes in cell morphology and gene expression. Conversely, in SH-SY5Y cells, a paradigm of RA-dependent differentiation, abrogation of BRG1 prevented the response to RA. We also demonstrated an antagonistic functional connection between BRG1 and MYC, whereby refractoriness to RA and GC by BRG1 inactivation involves deregulation of MYC activity. Mechanistically, these effects are mediated by BRG1 binding to MYC and MYC-target promoters to regulate their expression. Finally, BRG1 restoration significantly dampened invasion and progression, decreased MYC and restored responsiveness to RA in lung cancer cells orthotopically implanted in nude mice. This supports that BRG1 inactivation enables the cancer cell to sustain undifferentiated gene expression programs and prevent its response to environmental stimuli. On the other hand, small cell lung cancer (SCLC) accounts for one-fifth of lung cancer diagnoses and is a highly aggressive malignancy. However, our knowledge of small cell lung cancer (SCLC) genetics is still very limited, amplification of L-MYC, N-MYC and C-MYC being some of the well-established gene alterations. In this presentation I will also report our discovery of biallelic and tumor-specific inactivation of the MYC-associated factor X gene, MAX, in SCLC. Alterations in MAX were mutually exclusive with alterations at MYC and BRG1, the latter coding for an ATPase of the SWI/SNF complex. Taking advantage of three lung cancer cell lines lacking MAX we studied the effects of restoring MAX activity and depleting BRG1 in these cells. The current work demonstrates that BRG1 regulates the expression of MAX through direct recruitment to the MAX promoter, and that depletion of BRG1 strongly hinders cell growth, specifically in MAX-deficient cells. This heralds a synthetic lethal interaction between MAX and BRG1, and raise the possibility of developing a therapeutic strategy for patients with MAX-deficient tumors. Furthermore, it was observed that MAX requires BRG1 to activate neuroendocrine transcriptional programs and to up-regulate MYC-targets, such as glycolytic-related genes (e.g., LDHA, HK2, PDK1, PKM2, and PGK1). Finally, we also report genetic inactivation of the MAX dimerization protein, MGA, in lung cancers with wild type components of the SWI/SNF or MYC pathways. Taken together, these observations demonstrate that an aberrant SWI/SNF-MYC network is essential for lung cancer development, and opens novel therapeutic possibilities for the treatment of SCLC patients with MAX-deficient tumors. Citation Format: Montse Sanchez-Cespedes. Dissection of the BRG1 and MYC/MAX biological connection and its use in lung cancer therapeutics. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr IA02.

Experimental displacement of longnose dace, Rhinichthys cataractae (Actinopterygii, Cyprinidae), reveals rapid fish avoidance of a stormwater drain in an urban watershed

Land-use change associated with human development can alter aquatic habitat and imperil aquatic species. Fish are challenged when urban streams are altered, for example for stormwater conveyance, but little is known about how such activities influence the space use of individual fish. Electronic tagging and experimental displacement of fish can be used to explore site fidelity and homing behaviour of fish and can therefore be useful for testing hypotheses about space use and habitat selection. In this study, we used experimental displacement to determine how longnose dace (LND, Rhinichthys cataractae) utilize reaches within a watershed that have varying degrees of degradation. LND were tagged using passive integrated transponders (PIT tags), transported upstream, and released either into the natural stream reach, impaired stormwater drain reach, or at their confluence. Fixed PIT antennas were used to monitor movement of the PIT-tagged fish among the three reaches for a period of 3 weeks. LND exhibited dramatic and rapid selection against the stormwater drain. No LND moved into the drain and 97% of fish transported to the drain left within 24 h. LND were actively avoiding the stormwater drain, emphasizing the need for enhancement work to improve the biological connectivity of the system.

Using GIS to Delineate Headwater Stream Origins in the Appalachian Coalfields of Kentucky

AbstractHeadwater streams have a significant nexus or physical, chemical, and/or biological connection to downstream reaches. Generally, defined as 1st‐3rd order with ephemeral, intermittent, or perennial flow regimes, these streams account for a substantial portion of the total stream network particularly in mountainous terrain. Due to their often remote locations, small size, and large numbers, conducting field inventories of headwater streams is challenging. A means of estimating headwater stream location and extent according to flow regime type using publicly available spatial data is needed to simplify this complex process. Using field‐collected headwater point of origin data from three control watersheds, streams were characterized according to a set of spatial parameters related to topography, geology, and soils. These parameters were (1) compared to field‐collected point of origin data listed in three nearby Jurisdictional Determinations, (2) used to develop a geographic information system (GIS)‐based stream network for identifying ephemeral, intermittent, and perennial streams, and (3) applied to a larger watershed and compared to values obtained using the high‐resolution National Hydrography Dataset (NHD). The parameters drainage area and local valley slope were the most reliable predictors of flow regime type. Results showed the high‐resolution NHD identified no ephemeral streams and 9 and 65% fewer intermittent and perennial streams, respectively, than the GIS model.

Echoes of a distant time: effects of historical processes on contemporary genetic patterns in Galaxias platei in Patagonia.

Interpreting the genetic structure of a metapopulation as the outcome of gene flow over a variety of timescales is essential for the proper understanding of how changes in landscape affect biological connectivity. Here we contrast historical and contemporary connectivity in two metapopulations of the freshwater fish Galaxias platei in northern and southernmost Patagonia where paleolakes existed during the Holocene and Pleistocene, respectively. Contemporary gene flow was mostly high and asymmetrical in the northern system while extremely reduced in the southernmost system. Historical migration patterns were high and symmetric in the northern system and high and largely asymmetric in the southern system. Both systems showed a moderate structure with a clear pattern of isolation by distance (IBD). Effective population sizes were smaller in populations with low contemporary gene flow. An approximate Bayesian computation (ABC) approach suggests a late Holocene colonization of the lakes in the northern system and recent divergence of the populations from refugial populations from east and west of the Andes. For the southern system, the ABC approach reveals that some of the extant G.platei populations most likely derive from an ancestral population inhabiting a large Pleistocene paleolake while the rest derive from a higher-altitude lake. Our results suggest that neither historical nor contemporary processes individually fully explain the observed structure and geneflow patterns and both are necessary for a proper understanding of the factors that affect diversity and its distribution. Our study highlights the importance of a temporal perspective on connectivity to analyse the diversity of spatially complex metapopulations.

Acute coronary syndrome and depression: A review of shared pathophysiological pathways

To examine the evidence for shared pathophysiological pathways in acute coronary syndrome and major depression and to conceptualise the dynamic interplay of biological systems and signalling pathways that link acute coronary syndrome and depression within a framework of neuro-visceral integration. Relevant articles were sourced via a search of published literature from MEDLINE, EMBASE and PubMed using a variety of search terms relating to biological connections between acute coronary syndrome and depression. Additional articles from bibliographies of retrieved papers were assessed and included where relevant. Despite considerable research efforts, a clear understanding of the biological processes connecting acute coronary syndrome and depression has not been achieved. Shared abnormalities are evident across the immune, platelet/endothelial and autonomic/stress-response systems. From the available evidence, it seems unlikely that a single explanatory model could account for the complex interactions of biological pathways driving the pathophysiology of these disorders and their comorbidity. A broader conceptual framework of mind-body or neuro-visceral integration that can incorporate the existence of several causative scenarios may be more useful in directing future research and treatment approaches for acute coronary syndrome-associated depression.

Connecting SNPs in Diabetes: A Spatial Analysis of Meta-GWAS Loci.

Meta-analyses of genome-wide association studies (GWAS) have improved our understanding of the genetic foundations of a number of diseases, including diabetes. However, single nucleotide polymorphisms (SNPs) that are identified by GWAS, especially those that fall outside of gene regions, do not always clearly link to the underlying biology. Despite this, these SNPs have often been validated through re-sequencing efforts as not just tag SNPs, but as causative SNPs, and so must play a role in disease development or progression. In this study, we show how the 3D genome (spatial connections) and trans-expression Quantitative Trait Loci connect diabetes loci from different GWAS meta-analyses, informing the backbone of regulatory networks. Our findings include a three-way functional–spatial connection between the TM6SF2, CTRB1–BCAR1, and CELSR2–PSRC1 loci (rs201189528, rs7202844, and rs7202844, respectively) connected through the KCNIP3 and BCAR1/BCAR3 loci, respectively. These spatial hubs serve as an example of how loci in genes with little biological connection to disease come together to contribute to the diabetes phenotype.

Lipoprotein (a) upregulates ABCA1 in liver cells via scavenger receptor-B1 through its oxidized phospholipids

Elevated levels of lipoprotein (a) [Lp(a)] are a well-established risk factor for developing CVD. While Lp(a) levels are thought to be independent of other plasma lipoproteins, some trials have reported a positive association between Lp(a) and HDL. Whether Lp(a) has a direct effect on HDL is not known. Here we investigated to determine whether Lp(a) had any effect on the ABCA1 pathway of HDL production in liver cells. Incubation of HepG2 cells with Lp(a) upregulated the PPARγ protein by 1.7-fold and the liver X receptor α protein by 3-fold. This was accompanied by a 1.8-fold increase in ABCA1 protein and a 1.5-fold increase in cholesterol efflux onto apoA1. We showed that Lp(a) was internalized by HepG2 cells, however, the ABCA1 response to Lp(a) was mediated by the selective uptake of oxidized phospholipids (oxPLs) from Lp(a) via the scavenger receptor-B1 and not by Lp(a) internalization per se. We conclude that there is a biological connection between Lp(a) and HDL through the ability of Lp(a)’s oxPLs to upregulate HDL biosynthesis.

Implications of pleiotropy: challenges and opportunities for mining Big Data in biomedicine.

Pleiotropy arises when a locus influences multiple traits. Rich GWAS findings of various traits in the past decade reveal many examples of this phenomenon, suggesting the wide existence of pleiotropic effects. What underlies this phenomenon is the biological connection among seemingly unrelated traits/diseases. Characterizing the molecular mechanisms of pleiotropy not only helps to explain the relationship between diseases, but may also contribute to novel insights concerning the pathological mechanism of each specific disease, leading to better disease prevention, diagnosis and treatment. However, most pleiotropic effects remain elusive because their functional roles have not been systematically examined. A systematic investigation requires availability of qualified measurements at multilayered biological processes (e.g., transcription and translation). The rise of Big Data in biomedicine, such as high-quality multi-omics data, biomedical imaging data and electronic medical records of patients, offers us an unprecedented opportunity to investigate pleiotropy. There will be a great need of computationally efficient and statistically rigorous methods for integrative analysis of these Big Data in biomedicine. In this review, we outline many opportunities and challenges in methodology developments for systematic analysis of pleiotropy, and highlight its implications on disease prevention, diagnosis and treatment.

Osteopontin induces vascular endothelial growth factor expression in articular cartilage through PI3K/AKT and ERK1/2 signaling.

The expression of osteopontin (OPN) and vascular endothelial growth factor (VEGF) are associated with the severity of cartilage destruction in osteoarthritis. However, the biological connection between OPN and VEGF in osteoarthritis remains to be elucidated. The present study was performed to investigate the effect of OPN on VEGF expression in articular cartilage. Rat articular chondrocytes were isolated and cultured in monolayer conditions, and they were treated with OPN for different time periods (0, 2, 8, 12 or 24 h) and dosages (0, 0.1, 0.25 or 0.5 µM). VEGF expression was assessed by reverse transcription‑quantitative polymerase chain reaction and western blotting. The activation of the phosphoinositide 3‑kinase (PI3K)/AKT and extracellular signal‑regulated kinase (ERK)1/2 pathway was analyzed by detecting the expression of pPI3K, pAKT and pERK1/2. To inhibit the PI3K/AKT and ERK1/2 pathway, LY294002 and PD98059 were used, respectively or in combination. It was identified that OPN increased the expression of VEGF in a dose‑ and time‑dependent manner. The PI3K/AKT and ERK1/2 pathways were activated following OPN stimulation and the effect was concomitant with the upregulation of VEGF. Finally, the regulation of VEGF was inhibited by LY294002 and PD98059, and their combination exhibited a synergistic effect. In conclusion, these findings suggest that OPN may directly upregulate VEGF expression through the PI3K/AKT and ERK1/2 pathway. Further studies are required to reveal the mechanism of action of OPN on cartilage angiogenesis and cartilage destruction.

Cartilage regeneration for treatment of osteoarthritis: a paradigm for nonsurgical intervention.

Osteoarthritis (OA) is associated with articular cartilage abnormalities and affects people of older age: preventative or therapeutic treatment measures for OA and related articular cartilage disorders remain challenging. In this perspective review, we have integrated multiple biological, morphological, developmental, stem cell and homeostasis concepts of articular cartilage to develop a paradigm for cartilage regeneration. OA is conceptually defined as an injury of cartilage that initiates chondrocyte activation, expression of proteases and growth factor release from the matrix. This regenerative process results in the local activation of inflammatory response genes in cartilage without migration of inflammatory cells or angiogenesis. The end results are catabolic and anabolic responses, and it is the balance between these two outcomes that controls remodelling of the matrix and regeneration. A tantalizing clinical clue for cartilage regrowth in OA joints has been observed in surgically created joint distraction. We hypothesize that cartilage growth in these distracted joints may have a biological connection with the size of organs and regeneration. Therefore we propose a novel, practical and nonsurgical intervention to validate the role of distraction in cartilage regeneration in OA. The approach permits normal wake-up activity while during sleep; the index knee is subjected to distraction with a pull traction device. Comparison of follow-up magnetic resonance imaging (MRI) at 3 and 6 months of therapy to those taken before therapy will provide much-needed objective evidence for the use of this mode of therapy for OA. We suggest that the paradigm presented here merits investigation for treatment of OA in knee joints.

Relative effects of geographically isolated wetlands on streamflow: a watershed‐scale analysis

AbstractGeographically isolated wetlands (GIWs) are characterized as ‘isolated’ because they are embedded by uplands, though they potentially exhibit a gradient of hydrologic, biological, or chemical connections to other surface waters. In fact, recent field studies have begun to elucidate that GIWs exhibit varying degrees of hydrologic connectivity. In this study, we examine the influence of GIWs on streamflow, a potential indicator of GIW hydrologic connectivity with surface waters. We assess annual and seasonal spatially based statistical relationships between GIW characteristics (e.g. volume and extent) and streamflow across a dense network of subbasins using a hybrid modeling approach. Our method involves the Spatial Stream Network (SSN) model, which considers spatial autocorrelation of model covariates explicitly, and the Soil and Water Assessment Tool (SWAT), which predicts streamflow across a network of 579 subbasins in the lower Neuse River Basin, North Carolina, USA. Our study results suggest that GIWs, to some extent, influence streamflow. The further GIWs are from a stream, the greater their capacity to increase streamflow due to the physiographic setting, hypothesized transit times, and sequencing of watershed hydrologic connectivity in the study area. However, as the combined extent of GIWs and non‐GIWs increases in subbasins, seasonal and annual streamflow decreases. Results also suggest that other landscape indicators of watershed‐scale hydrology can, in aggregate with GIWs and non‐GIWs, explain variations in seasonal and annual simulated streamflow. Our study findings begin to elucidate the aggregate influence of GIWs on streamflow, providing insights for future decision‐making on GIW protection and management. Copyright © 2015 John Wiley & Sons, Ltd.

Di-(2-ethylhexyl) phthalate metabolites in urine show age-related changes and associations with adiposity and parameters of insulin sensitivity in childhood.

ObjectivesPhthalates might be implicated with obesity and insulin sensitivity. We evaluated the levels of primary and secondary metabolites of Di-(2-ethylhexyl) phthalate (DEHP) in urine in obese and normal-weight subjects both before and during puberty, and investigated their relationships with auxological parameters and indexes of insulin sensitivity.Design and MethodsDEHP metabolites (MEHP, 6-OH-MEHP, 5-oxo-MEHP, 5-OH-MEHP, and 5-CX-MEHP), were measured in urine by RP-HPLC-ESI-MS. Traditional statistical analysis and a data mining analysis using the Auto-CM analysis were able to offer an insight into the complex biological connections between the studied variables.ResultsThe data showed changes in DEHP metabolites in urine related with obesity, puberty, and presence of insulin resistance. Changes in urine metabolites were related with age, height and weight, waist circumference and waist to height ratio, thus to fat distribution. In addition, clear relationships in both obese and normal-weight subjects were detected among MEHP, its products of oxidation and measurements of insulin sensitivity.ConclusionIt remains to be elucidated whether exposure to phthalates per se is actually the risk factor or if the ability of the body to metabolize phthalates is actually the key point. Further studies that span from conception to elderly subjects besides further understanding of DEHP metabolism are warranted to clarify these aspects.

Bayesian graphical network analyses reveal complex biological interactions specific to Alzheimer's disease.

With different approaches to finding prognostic or diagnostic biomarkers for Alzheimer's disease (AD), many studies pursue only brief lists of biomarkers or disease specific pathways, potentially dismissing information from groups of correlated biomarkers. Using a novel Bayesian graphical network method, with data from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, the aim of this study was to assess the biological connectivity between AD associated blood-based proteins. Briefly, three groups of protein markers (18, 37, and 48 proteins, respectively) were assessed for the posterior probability of biological connection both within and between clinical classifications. Clinical classification was defined in four groups: high performance healthy controls (hpHC), healthy controls (HC), participants with mild cognitive impairment (MCI), and participants with AD. Using the smaller group of proteins, posterior probabilities of network similarity between clinical classifications were very high, indicating no difference in biological connections between groups. Increasing the number of proteins increased the capacity to separate both hpHC and HC apart from the AD group (0 for complete separation, 1 for complete similarity), with posterior probabilities shifting from 0.89 for the 18 protein group, through to 0.54 for the 37 protein group, and finally 0.28 for the 48 protein group. Using this approach, we identified beta-2 microglobulin (β2M) as a potential master regulator of multiple proteins across all classifications, demonstrating that this approach can be used across many data sets to identify novel insights into diseases like AD.

Intimate Associations: The Law and Culture of American Families by J. Herbie DiFonzo and Ruth C. Stern, University of Michigan Press

The authors set out on a deceptively simple mission. They cull the extensive literature on modern family structures and lay out its “social, legal and economic implications” for the current practice of law. What is deceptive is that there is nothing simple about this undertaking: the body of knowledge that has accumulated is robust, it is located in a variety of disciplinary journals and books, and it is laced with political commentary and nuance. What the authors accomplish is laudatory. They define and explain nontraditional family structures that courts and the legal profession are confronted with every day and highlight the families’ strengths and vulnerabilities arising from their nontraditional structures. They go on to question how the legal world is doing in protecting children from these various family structures when the unions part ways legally, emotionally, and structurally. And their premise is that the legal profession is not doing as well as it could by these children and families. And they offer a way to higher ground. They begin with a well-researched premise that, although social science data show that the “prime components of well-functioning families are. . .live-in parents, stability, and a measure of economic stability” (p. 43), that does not accurately describe most contemporary families. They articulate the dilemma that the legal profession faces as one of how to strengthen families without perpetuating dysfunctional practices that undermine child well-being, such as serial childbirths with different partners—none of whom have any interest in parenting. The authors consider newer forms of family structures in a way that does not sweep under the carpet their vulnerability relative to the wellfunctioning norm, but also recognizes these newer forms as valid and deserving of equal status in society, if not in the eyes of the law. The authors are clear that the judiciary as it currently functions reflects outdated rules of law that privilege marital and biological connections, which no longer constitute the majority of American families. They lay out how the structures of contemporary families are vulnerable to dissolution, in large part because of the legal and structural impediments blocking their path to legitimacy and the entitlements and benefits—legal and economic—withheld from them as a result. The authors take a position that it is not their (or anyone’s) place to judge how and why families get into the vulnerable position of turning on each other in ways that undermine what they are trying to achieve in terms of acceptance from society. However, when the judiciary does not deal head-on with the conundrums such a stance poses, it serves only to further undermine intimate relationships and the children born to them. The authors call upon the judiciary to make difficult decisions based on functional rather than biological ties, because they recognize that these are vulnerable and seemingly less desirable family forms in which to raise children and because they pragmatically espouse that these forms are here to stay and need to be supported rather than ignored. The book begins with an historical look at marriage, focusing on when and how it became optional. They then move into various expressions of parenthood that have emerged as products and producers of new family forms, particularly surrogacy and other relationships involved in reproductive

Restoring motor function with bidirectional neural interfaces.

Closed-loop brain-computer interfaces have bidirectional connections that allow activity-dependent stimulation of the brain, spinal cord, or muscles. Such bidirectional brain-computer interfaces (BBCI) have three major applications that can be used to restore lost motor function. First, the brain could learn to incorporate a long-term artificial recurrent connection into normal behavior, exploiting the brain's ability to adapt to consistent sensorimotor conditions. The obvious clinical application for restoring motor function is to use an artificial recurrent connection to bridge a lost biological connection. Second, activity-dependent stimulation can generate synaptic plasticity on the cellular level. The corresponding clinical application is to strengthen weakened neural connections, such as occur in stroke. A third application involves delivery of activity-dependent deep brain stimulation at subcortical reward sites, which can operantly reinforce the activity that generates the stimulation. The BBCI paradigm has numerous specific applications, depending on the source of the signals and the stimulated targets.

Comparative analysis of physiologic rest position of the mandible with twins

Identical twins are multidisciplinary phenomenon, a miracle of fetal biology, medical reproductive challenge, the closest and most enduring biological connection. The aim of the research is a comparative analysis of physiologic rest of the mandible identical twins. This longitudinal oral epidemiological survey was conducted in a randomized sample of 30 pairs of identical twins, of equal gender representation and chronological age from 20 to 40 years. Based on the statistical parameters evaluated the position of physiologic rest and made a comparative analysis, that a certain degree of intra pairs similarities and differences among members of the same pair and a degree inter pairs similarities and differences among the members of different pairs of monozygotic twins. An evaluation comparing the position of physiologic rest, identical twins, t-test no significant difference in physiological rest, in the area of the front teeth. Concordance or conformity final ioshoda is proven among members of the same and different pairs. The difference was not observed, even compared to a gender. Comparing valuables of physiologic rest position, no significant intra pairs not inter pairs difference between members of the same and different MZ twin pairs.

Comparison intercuspal mandible position twins

The twins are the miracle of fetal biology, medical reproductive challenge, the closest and most durable biological connection. The aim is to identify, evaluate and compare the type, number and location interjaw functional contacts in the intercuspal position of the mandible, with MZ monozygotic (identical) twins. Analysis of occlusal relationships in the most stable-intercuspal comparison was done on a sample of 60 identical twins, by 15 female and 15 male pairs, chronological ages 18 to 40, in which the means of articulation papers specific localization and distribution of contact relationships, in the region of the lateral teeth. Results of this study showed that in the lateral region, 57 respondents or 95%, has the modalities of occlusal relationships lump-ridges-marginal edge. Average more occlusal contacts identified in males (25.1) than in female twin pairs (19.1). Also, in male couples registered more three points (M: F = 7: 1), two points by gender is equal 24:12, and contacts at one point they outnumber men (22), compared to female respondents (18). Less Similarities than expected sameness, proving that the number, distribution and intensity of occlusal contacts in the mandible vary individually.

Book Review: I Could Not Call Her Mother: The Stepmother in American Popular Culture, 1750-1960

Rebecca Jo Plant, review of Leslie J. Lindenauer, I Could Not Call Her Mother: The Stepmother in American Popular Culture, 1750-1960 (Lanham: Lexington Books, 2013). Forthcoming in the Journal of Family History. Scholars have devoted a great deal of attention to the history of mothers and motherhood in recent years. Whereas this literature encompasses numerous works on adoptive mothers, another group of non-biological mothers—stepmothers—has been largely overlooked. Leslie J. Lindenauer seeks to remedy this neglect by tracing the cultural history of the stepmother as revealed primarily by popular fiction, advice literature and film. She not only seeks to show how representations of stepmothers varied over time, but also to demonstrate how the figure of the stepmother served as “a lens on the changing constructions of motherhood itself over time.” (xxi) While the book meets the former objective with verve, it is not wholly successful in achieving the latter. The book’s first chapter charts a shift from the widespread demonization of stepmothers in the late 18 th and early 19 th centuries toward more ambiguous and positive portrayals beginning in the mid-19 th century. The wicked stepmother loomed large in the cultural landscape of the Revolutionary and early national periods, serving as a counterpoint for the emergent ideal of the Republican mother. Lindenauer astutely notes the role that the political context played in shaping depictions of stepmothers, who were deemed “tyrannical, corrupt, avaricious, selfish” and “unnatural”—terms that reflected the ascendant language of republicanism and natural rights (21). Indeed, so resonant was the image of the wicked stepmother that rebellious colonists readily employed it to describe the deteriorating relationship with England; as one critic of the Stamp Act wrote, the once “beloved Mother country” had become a “cruel step-mother, unbounded in her malice.” (8) By the mid-19 th century, however, the privileging of “natural” motherhood diminished somewhat, as the intense cultural idealization of motherhood expanded so as to encompass stepmothers as well. In fact, some writers represented stepmothers as the ideal exemplars of mother love, for they gave selflessly even in the absence of a biological connection. In the period from 1860 to 1890—an era Lindenauer characterizes as witnessing the “redemption of the stepmother”—popular magazines ran numerous stories that portrayed stepmothers winning over initially suspicious and resentful stepchildren through patience and love. Other vignettes challenged the stereotype of the cold and greedy stepmother who connived to snare a widower by featuring virtuous women lured into loveless marriages by widowers who wanted only their domestic labor. While Lindenauer ably sketches this shift, the reasons why the stereotype of the evil stepmother waned remain somewhat murky. She suggests that large-scale shifts in the economy that threatened to destabilize the family, combined with the rise of advanced education for women and their increasing forays into public and political realms, led to efforts to shore up the familial ideal, lest women abandon domesticity. But this argument seems quite general. Could changing demographics (the fact that stepmothers became less common as the average life span rose) have played a role? Did it matter that, by the mid-19 th century, that women themselves were writing many of the popular stories featuring stepmothers? Or might actual changes in parental practices, such as the decline in the apprenticing of children and corporal punishment, somehow have rendered stepmothers less objectionable? While the reasons underlying cultural transformation

Father Involvement, Dating Violence, and Sexual Risk Behaviors Among a National Sample of Adolescent Females

This study explored the relationship between the involvement of biological fathers and the sexual risk behaviors and dating violence/victimization and/or perpetration of adolescent girls. The data used in this cross-sectional analysis were drawn from the second wave of the public release of the National Longitudinal Study of Adolescent Health. Only adolescents who reported their biological sex as female, reported a history of being sexually active, and reported having a romantic partner in the previous 18 months were selected (N = 879). This study focused on overall positive sexual behaviors and use of contraception. Structural equation modeling (SEM) was used to best utilize capacity for dealing with latent variables and to test for possible mediation effects. The analysis demonstrated main effects of dating violence and father involvement on sexual behaviors. The more dating violence an adolescent girl experiences, the less likely she is to engage in healthy sexual behaviors. Likewise, the more involvement the biological father has in a woman's life, the more likely she is to engage in positive sexual behaviors. Perceived father involvement was associated with risky sexual behaviors among sexually experienced adolescent girls. Dating violence was directly associated with risky sexual behaviors among sexually experienced adolescent girls, particularly non-White girls. Future studies should use longitudinal models and test theoretically and empirically guided potential mediators. Future studies should also consider father figures such as step-fathers and grandfathers in addition to biological fathers, as having a father figure may be a stronger predictor of adolescent sexual behaviors than having a biological connection.

NeurOS™ and NeuroBlocks™ a neural/cognitive operating system and building blocks

Abstract NeurOS is an open platform for accelerating research, development and hosting execution of intelligent applications. A NeurOS application is a directed “neural graph” of modular components connected by signal paths, similar to biological brain connectivity and functional block diagrams of neural pathways. Built-in reusable modules (NeuroBlocks) provide a wide range of general- and special-purpose capabilities: inputs/senses, outputs/effectors, processing, memory, pattern learning and recognition, visualization/instrumentation, custom module development, integrating external intelligence capabilities, and sub-graph reuse. NeurOS sub-graph assemblies address neural/cognitive functions including perception, pattern learning and recognition, working memory, imagination, prediction, context priming, attention, abstraction, classification, associational thinking and behavior. NeurOS applications are inherently portable, scalable, networkable, extensible and embeddable. NeurOS development tools provide simple intuitive graphical drag and drop application assembly from components without programming, along with testing, debugging, monitoring and visualization. Prototype NeurOS applications have begun to explore a wide range of intelligent functions in diverse areas, including aspects of pattern recognition, vision, music, reading, puzzle solving, reasoning, behavior. Building working intelligent systems using NeurOS and NeuroBlocks lets researchers and developers focus on their core functions and rapidly iterate and instrument working models, fostering both analytical and biological insight as well as usable systems.