Plasmoid Formation and Strong Radiative Cooling in a Driven Magnetic Reconnection Experiment.

We present the first experimental study of plasmoid formation in a magnetic reconnection layer undergoing rapid radiative cooling, a regime relevant to extreme astrophysical plasmas. Two exploding aluminum wire arrays, driven by the Z machine, generate a reconnection layer (S_{L}≈120) in which the cooling rate far exceeds the hydrodynamic transit rate (τ_{hydro}/τ_{cool}>100). The reconnection layer generates a transient burst of >1 keV x-ray emission, consistent with the formation and subsequent rapid cooling of the layer. Time-gated x-ray images show fast-moving (up to 50 km s^{-1}) hotspots in the layer, consistent with the presence of plasmoids in 3D resistive magnetohydrodynamic simulations. X-ray spectroscopy shows that these hotspots generate the majority of Al K-shell emission (around 1.6 keV) prior to the onset of cooling, and exhibit temperatures (170 eV) much greater than that of the plasma inflows and the rest of the reconnection layer, thus providing insight into the generation of high-energy radiation in radiatively cooled reconnection events.

Delineating sociodemographic, medical and quality of life factors associated with psychological distress in individuals with endometriosis.

STUDY QUESTION: What is the relationship between specific quality of life domains and depression, anxiety and stress in the endometriosis population? SUMMARY ANSWER: Psychosocial domains of quality of life, such as a perception of social support and self-image, are more strongly associated with depression, anxiety and stress than pain and medical factors. WHAT IS KNOWN ALREADY: Prior research indicates a high prevalence of anxiety and depression in individuals with endometriosis. Pain is thought to be critical in the development of psychological distress, however prior research has investigated this association without consideration of psychosocial quality of life domains such as social functioning, perceived social support and self-image. STUDY DESIGN, SIZE, DURATION: This study is a cross-sectional analysis of baseline data collected in a longitudinal study exploring psychological distress in endometriosis (n = 584). PARTICIPANTS/MATERIALS, SETTING, METHODS: Individuals living with endometriosis participated in this study and were recruited via online platforms of community organizations and support groups. Demographic and medical information concerning endometriosis treatment and diagnosis was self-reported. Psychological distress and quality of life was measured using the Depression, Anxiety and Stress Scale (DASS-21), Endometriosis Health Profile-30 (EHP-30) and the Short Form Survey (SF-36v2). A series of linear regression analyses explored the relationship between specific quality of life domains and the primary outcomes of depression, anxiety and stress. MAIN RESULTS AND THE ROLE OF CHANCE: Approximately half of the participants in this sample reported moderate to severe anxiety, depression and stress. Quality of life domains, particularly perceived social support, social functioning and self-image, were more strongly associated with psychological distress than medical or demographic factors. Pain was associated with anxiety, but not depression or stress. A greater number of endometriosis symptoms was only associated with depression. LIMITATIONS, REASONS FOR CAUTION: These data are cross-sectional and, therefore, causality cannot be inferred from this analysis. Information about endometriosis diagnosis and treatment was self-reported, and not verified against medical records. WIDER IMPLICATIONS OF THE FINDINGS: This study indicates that psychosocial factors may be more salient factors underlying depression, anxiety and stress in the endometriosis population than pain and medical factors. There is a need for interventions that target psychological distress in this population with a focus on the broader impact of endometriosis beyond pain and physical symptomatology. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the Research Training Program (RTP) Scholarship awarded to C.S.M. by Macquarie University. The remaining authors have nothing to declare. TRIAL REGISTRATION NUMBER: ACTRN12619001508167.

Performance Scaling in Magnetized Liner Inertial Fusion Experiments.

We present experimental results from the first systematic study of performance scaling with drive parameters for a magnetoinertial fusion concept. In magnetized liner inertial fusion experiments, the burn-averaged ion temperature doubles to 3.1 keV and the primary deuterium-deuterium neutron yield increases by more than an order of magnitude to 1.1×10^{13} (2 kJ deuterium-tritium equivalent) through a simultaneous increase in the applied magnetic field (from 10.4 to 15.9 T), laser preheat energy (from 0.46 to 1.2 kJ), and current coupling (from 16 to 20 MA). Individual parametric scans of the initial magnetic field and laser preheat energy show the expected trends, demonstrating the importance of magnetic insulation and the impact of the Nernst effect for this concept. A drive-current scan shows that present experiments operate close to the point where implosion stability is a limiting factor in performance, demonstrating the need to raise fuel pressure as drive current is increased. Simulations that capture these experimental trends indicate that another order of magnitude increase in yield on the Z facility is possible with additional increases of input parameters.

How Would Low-Income Communities Prioritize Medicaid Spending?

CONTEXT: Medicaid plays a critical role in low-income, minority, and medically underserved communities, particularly in states that have expanded Medicaid under the Affordable Care Act. Yet, the voices of underresourced communities are often unheard in decisions about how to allocate Medicaid's scarce resources, and traditional methods of public engagement are poorly suited to gathering such input. We argue that deliberative public engagement can be a useful tool for involving communities in setting Medicaid priorities. METHOD: We engaged 209 residents of low-income, medically underserved Michigan communities in discussions about Medicaid spending priorities using an exercise in informed deliberation: CHAT (CHoosing All Together). Participants learned about Medicaid, deliberated in small groups, and set priorities both individually and collectively. FINDINGS: Participants prioritized broad eligibility consistent with the ACA expansion, accepted some cost sharing, and prioritized spending in areas-including mental health-that are historically underfunded. Participants allocated less funding beyond benefit coverage, such as spending on healthy communities. Participants perceived the deliberative process as fair and informative, and they supported using it in the policy-making process. CONCLUSION: The choices of participants from low-income, medically underserved communities reflect a unique set of priorities and suggest that engaging low-income communities more deeply in Medicaid policy making might result in different prioritization decisions.

Evaluating community deliberations about health research priorities.

CONTEXT: Engaging underrepresented communities in health research priority setting could make the scientific agenda more equitable and more responsive to their needs. OBJECTIVE: Evaluate democratic deliberations engaging minority and underserved communities in setting health research priorities. METHODS: Participants from underrepresented communities throughout Michigan (47 groups, n = 519) engaged in structured deliberations about health research priorities in professionally facilitated groups. We evaluated some aspects of the structure, process, and outcomes of deliberations, including representation, equality of participation, participants' views of deliberations, and the impact of group deliberations on individual participants' knowledge, attitudes, and points of view. Follow-up interviews elicited richer descriptions of these and also explored later effects on deliberators. RESULTS: Deliberators (age 18-88 years) overrepresented minority groups. Participation in discussions was well distributed. Deliberators improved their knowledge about disparities, but not about health research. Participants, on average, supported using their group's decision to inform decision makers and would trust a process like this to inform funding decisions. Views of deliberations were the strongest predictor of these outcomes. Follow-up interviews revealed deliberators were particularly struck by their experience hearing and understanding other points of view, sometimes surprised at the group's ability to reach agreement, and occasionally activated to volunteer or advocate. CONCLUSIONS: Deliberations using a structured group exercise to engage minority and underserved community members in setting health research priorities met some important criteria for a fair, credible process that could inform policy. Deliberations appeared to change some opinions, improved some knowledge, and were judged by participants worth using to inform policymakers.

Members of Minority and Underserved Communities Set Priorities for Health Research.

Policy Points Engaging and involving underrepresented communities when setting research priorities could make the scientific research agenda more equitable, more just, and more responsive to their needs and values. Groups and individuals from minority and underserved communities strongly prioritized child health and mental health research, often choosing to invest at the highest possible level. Groups consisting of predominantly Native American or Arab American participants invested in culture and beliefs research at the highest level, while many groups did not select it at all. The priority given to culture and beliefs research by these groups illustrates the importance of paying special attention to unique preferences, and not just commonly held views, when getting public input on spending priorities for research. CONTEXT: A major contributor to health disparities is the relative lack of resources-including resources for science-allocated to address the health problems of those with disproportionately greater needs. Engaging and involving underrepresented communities in setting research priorities could make the scientific research agenda more equitable, more just, and more responsive to their needs and values. We engaged minority and underserved communities in informed deliberations and report here their priorities for health research. METHODS: Academic-community partnerships adapted the simulation exercise CHAT for setting health research priorities. We had participants from minority and medically underserved communities (47 groups, n = 519) throughout Michigan deliberate about health research priorities, and we used surveys and CHAT software to collect the demographic characteristics and priorities selected by individuals and groups. FINDINGS: The participants ranged in age (18 to 88), included more women than men, and were overrepresented by minority groups. Nearly all the deliberating groups selected child health and mental health research (93.6% and 95.7%), and most invested at the highest level. Aging, access, promote health, healthy environment, and what causes disease were also prioritized by groups. Research on mental health and child health were high priorities for individuals both before and after group deliberations. Access was the only category more likely to be selected by individuals after group deliberation (77.0 vs 84.0%, OR = 1.63, p = .005), while improve research, health policy, and culture and beliefs were less likely to be selected after group deliberations (all, p < .001). However, the level of investment in many categories changed after the group deliberations. Participants identifying as Black/African American were less likely to prioritize mental health research, and those of Other race were more likely to prioritize culture and beliefs research. CONCLUSIONS: Minority and medically underserved communities overwhelmingly prioritized mental health and child health research in informed deliberations about spending priorities.

Changes in Quality of Life following Buprenorphine Treatment: Relationship with Treatment Retention and Illicit Opioid Use.

Studies of substance abuse treatment outcomes that give priority to cessation of all drug use may obscure other tangible benefits of treatment that are important to patients. The aim of this study was to examine the association between changes in quality of life (QoL) and: (1) retention in treatment; and (2) opioid use as measured by self-report and urine testing. Participants were 300 African American men and women starting outpatient buprenorphine treatment. Participants completed assessments at baseline, three and six months consisting of the World Health Organization's Quality of Life brief scale, Addiction Severity Index, and urine testing for opioids. There were statistically significant increases over time across all four QoL domains: physical, psychological, environmental, and social. Self-reported frequency of opioid use was negatively associated with psychological QoL, but opioid urine test results were not significantly associated with any QoL domains. Continued treatment enrollment was significantly associated with higher psychological QoL and environmental QoL. Patients entering buprenorphine treatment experience improvements in QoL, which are amplified for patients who remain in treatment. Point-prevalence opiate urine test results obtained at each assessment were not associated with any of the QoL domains and may not accurately reflect improvements perceived by patients receiving buprenorphine treatment.

The CRAFFT cut-points and DSM-5 criteria for alcohol and other drugs: a reevaluation and reexamination.

BACKGROUND: The CRAFFT, previously validated against DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) diagnostic criteria, is the most widely used screening instrument for alcohol and other substance misuse in adolescents. The present secondary analysis study sought to compare the CRAFFT with the new DSM-5 diagnostic criteria in order to assess the CRAFFT's psychometric properties and determine the optimal cut-point for identifying adolescents in need of further assessment. METHODS: Participants were primary care patients aged 12-17 (N = 525) who were recruited while waiting for a medical appointment in an urban federally qualified health center in Baltimore, Maryland, USA. Participants were administered the CRAFFT and the Composite International Diagnostic Interview, second edition, modified to include the new DSM-5 craving item. The authors examined the performance of the CRAFFT in identifying any problem use (defined as 1 or more DSM-5 criteria) and any DSM-5 substance use disorder (2 or more DSM-5 criteria) for alcohol or drugs other than tobacco. The authors examined sensitivity, specificity, and receiver operating characteristic areas under the curve (AUC) to determine the optimal CRAFFT cut-point(s) for predicting any problem use and any DSM-5 substance use disorder (SUD). RESULTS: Examining the CRAFFT as a continuous measure, AUC values were 0.93 for problem use or higher and 0.97 for DSM-5 SUD. Consistent with previously recommended cut-points for the CRAFFT, the cut-point of 2 performed optimally for identifying adolescents both exhibiting problem use of alcohol or drugs and meeting DSM-5 SUD criteria for alcohol or other drugs. CONCLUSIONS: Despite changes in the DSM substance use diagnostic criteria, the CRAFFT continues to demonstrate excellent sensitivity and specificity at its established cut-point of 2. Additional studies examining the CRAFFT in light of the new DSM-5 diagnostic criteria with more diverse populations are warranted.

Open timelike curves violate Heisenberg's uncertainty principle.

Toy models for quantum evolution in the presence of closed timelike curves have gained attention in the recent literature due to the strange effects they predict. The circuits that give rise to these effects appear quite abstract and contrived, as they require nontrivial interactions between the future and past that lead to infinitely recursive equations. We consider the special case in which there is no interaction inside the closed timelike curve, referred to as an open timelike curve (OTC), for which the only local effect is to increase the time elapsed by a clock carried by the system. Remarkably, circuits with access to OTCs are shown to violate Heisenberg's uncertainty principle, allowing perfect state discrimination and perfect cloning of coherent states. The model is extended to wave packets and smoothly recovers standard quantum mechanics in an appropriate physical limit. The analogy with general relativistic time dilation suggests that OTCs provide a novel alternative to existing proposals for the behavior of quantum systems under gravity.

Body image, self-compassion, and sexual distress in individuals living with endometriosis.

OBJECTIVE: Extensive psychological burden is associated with the experience of living with endometriosis, including negative changes to body image and sexual functioning. Emerging evidence suggests that potential protective factors such as body appreciation and self-compassion may help mitigate these adverse impacts of endometriosis. This study aimed to investigate the association of body image, both positive (body appreciation) and negative (body image disturbance) dimensions, with sexual distress and the potential buffering effect of self-compassion on the body image-sexual distress link. METHODS: Data were collected via an online cross-sectional survey (N = 471) assessing body image disturbance, body appreciation, self-compassion and sexual distress in individuals with endometriosis. A series of hierarchical linear regression analyses were conducted to explore the relationship between key variables. RESULTS: >80% of the sample reported clinically significant sexual distress and high levels of body image disturbance. Regression analyses indicated a moderate positive effect of body image disturbance with sexual distress, and a weaker inverse effect of self-compassion with sexual distress. Body appreciation was not associated with sexual distress, and no moderating effects of self-compassion were evident. CONCLUSION: The high prevalence of sexual distress identified in this sample, along with the finding that body image disturbance was strongly associated with sexual distress, suggest that psychosocial interventions addressing body image may help ameliorate sexual distress in individuals with endometriosis.

Quantitative study of guide-field effects on Hall reconnection in a laboratory plasma.

The effect of guide field on magnetic reconnection is quantitatively studied by systematically varying an applied guide field in the Magnetic Reconnection Experiment (MRX). The quadrupole field, a signature of two-fluid reconnection at zero guide field, is altered by a finite guide field. It is shown that the reconnection rate is significantly reduced with increasing guide field, and this dependence is explained by a combination of local and global physics: locally, the in-plane Hall currents are reduced, while globally guide field compression produces an increased pressure both within and downstream of the reconnection region.

AC compensation of 3D magnetic diagnostic signals in DIII-D and National Spherical Torus Experiment-Upgrade (NSTX-U) for real-time application.

A time domain algorithm has been developed to remove the vacuum pickup generated by both coil current (DC) and induced vessel current (AC) in real time from three dimensional (3D) magnetic diagnostic signals in the National Spherical Torus Experiment-Upgrade (NSTX-U) and DIII-D tokamaks. The possibility of detecting 3D plasma perturbations in real time is essential in modern and future tokamaks to avoid and control MHD instabilities. The presence of vacuum field pickup, due to toroidally asymmetric (3D) coils or to misalignment between sensors and axisymmetric (2D) coils, pollutes the measured plasma 3D field, making the detection of the magnetic field produced by the plasma challenging. Although the DC coupling between coils and sensors can be easily calculated and removed, the AC part is more difficult. An algorithm based on a layered low-pass filter approach for the AC compensation and its application for DIII-D and NSTX-U data is presented, showing that this method reduces the vacuum pickup to the noise level. Comparison of plasma response measurements with and without vacuum compensation shows that accurate mode locking detection and plasma response identification require precise AC and DC compensations.

The impact of substance abuse on osteoporosis screening and risk of osteoporosis in women with psychotic disorders.

UNLABELLED: Review of the 1-year prevalence of screening for osteoporosis and of osteoporosis or idiopathic fracture in Maryland Medicaid administrative records found that screening rates did not differ among women in the control population, women with psychosis, and women with major mood disorders, but were reduced compared to controls in women with substance use disorder, with or without psychosis. Prevalence of osteoporosis was increased compared to controls in women with major mood disorders or women over 55 dually diagnosed with psychosis and substance use disorder. INTRODUCTION: Osteoporosis is a major public health concern. Substance abuse and psychosis may be risk factors, however, frequency of screening and disease risk in women with psychotic disorders and substance use disorder (SUD) remains unknown. METHODS: This study examined rates (FY 2005) of osteoporosis screening and disease risk in Medicaid enrolled women aged 50 to 64 (N = 18,953). Four diagnostic groups were characterized: (1) psychosis, (2) SUD, (3) major mood disorder, and (4) controls. The interaction of psychosis and SUD on screening and disease prevalence of osteoporosis was tested. RESULTS: The prevalence of osteoporosis across the entire population was 6.7%. Four percent of those without an osteoporosis diagnosis received osteoporosis screening with no notable differences between psychosis and controls. Those with SUD, however, had a significant reduction in screening compared to controls (OR = 0.61, 95% CI = 0.40-0.91, p = 0.016). Women with a major mood disorder were more likely to have osteoporosis in their administrative record (OR = 1.32, 95% CI = 1.03-1.70, p = 0.028) compared to controls. Those who were dually diagnosed (SUD and psychosis) in the oldest ages (55-64 years) had a markedly higher prevalence of osteoporosis compared to controls (OR = 6.4 CI = 1.51-27.6, p = 0.012), whereas this interaction (SUD and psychosis) was not significant in the entire population over age 49. CONCLUSIONS: Osteoporosis screening in the Medicaid population is significantly lower for women with SUD, after adjusting for age, race, and Medicaid enrollment category. The prevalence of osteoporosis appears markedly elevated in those with major mood disorders and those over age 55 dually diagnosed with schizophrenia and SUD.

Relationship of anterior knee laxity to knee translations during drop landings: a bi-plane fluoroscopy study.

PURPOSE: Passive anterior knee laxity has been linked to non-contact ACL injury risk. High deceleration movements have been implicated in the non-contact ACL injury mechanism, and evidence suggests that greater anterior tibial translations (ATT) may occur in healthy knees that are lax compared to a tight knee. The purpose of this study was to determine the relationship between anterior knee laxity scores and ATT during drop landings using biplane fluoroscopy. METHODS: Sixteen healthy adults (10 women; 6 men) performed stiff drop landings (40 cm) while being filmed using a high-speed, biplane fluoroscopy system. Initial, peak and excursions for rotations and translations were calculated and regression analysis used to determine the 6DoF kinematic relationships with KT1000 scores with peak ATT occurring during the landing. RESULTS: KT1000 values were (+) correlated with peak ATT values for group (r = 0.89; P < 0.0001) and both genders (males, r = 0.97; P = 0.0003; females, r = 0.93; P = < 0.0001). Regression analysis yielded a significant linear fit for the group (r (2) = 0.80; Y (ATT-group) = - 0.516 + 1.2 × X (KT1000-group)) and for each gender (females: r(2) = 0.86; Y (ATT-females) = 0.074 + 1.2 × X (KT1000-females) and males: r (2) = 0.94; Y (ATT-males) = - 0.79 + 1.2 × X (KT1000-males)). CONCLUSION: A strong relationship was observed between passive anterior knee laxity measured via KT1000 and peak ATT experienced during dynamic activity in otherwise healthy persons performing a stiff drop-landing motion.

Quantitative fine-tuning of photoreceptor cis-regulatory elements through affinity modulation of transcription factor binding sites.

Given the remarkable recent progress in gene therapy-based treatments for retinal disease, there is an urgent need for the development of new approaches to quantitative design and analysis of photoreceptor-specific promoters. In this study, we determined the relative binding affinity of all single-nucleotide variants of the consensus binding site of the mammalian photoreceptor transcription factor, Crx. We then showed that it is possible to use these data to accurately predict the relative binding affinity of Crx for all possible 8 bp sequences. By rationally adjusting the binding affinity of three Crx sites, we were able to fine-tune the expression of the rod-specific Rhodopsin promoter over a 225-fold range in living retinas. In addition, we showed that it is possible to fine-tune the activity of the rod-specific Gnat1 promoter over ∼275-fold range by modulating the affinity of a single Crx-binding site. We found that the action of individual binding sites depends on the precise promoter context of the site and that increasing binding affinity does not always equate with increased promoter output. Despite these caveats, this tuning approach permits quantitative engineering of photoreceptor-specific cis-regulatory elements, which can be used as drivers in gene therapy vectors for the treatment of blindness.

Serological, biochemical, and functional identity of B cell-stimulatory factor 1 and B cell differentiation factor for IgG1.

By three criteria, we have demonstrated that B cell stimulatory factor (BSF-1) and B cell differentiation factor (BCDF-gamma) are the same lymphokine. Highly purified preparations of high performance liquid chromatography-purified or affinity-purified BSF-1 had BCDF-gamma activity but not BCDF-mu activity. A monoclonal anti-BSF-1 antibody coupled to Sepharose depleted both BSF-1 and BCDF-gamma activity but not BCDF-mu activity from two different T cell supernatants. Soluble monoclonal anti-BSF-1 blocked the BSF-1 and BCDF-gamma but not the BCDF-mu responses. These results suggest that BSF-1 acts on both resting and activated B cells to induce different effects.

The immunosuppressive fungal metabolite gliotoxin specifically inhibits transcription factor NF-kappaB.

Opportunistic infections, such as aspergillosis, are among the most serious complications suffered by immunocompromised patients. Aspergillus fumigatus and other pathogenic fungi synthesize a toxic epipolythiodioxopiperazine metabolite called gliotoxin. Gliotoxin exhibits profound immunosuppressive activity in vivo. It induces apoptosis in thymocytes, splenocytes, and mesenteric lymph node cells and can selectively deplete bone marrow of mature lymphocytes. The molecular mechanism by which gliotoxin exerts these effects remains unknown. Here, we report that nanomolar concentrations of gliotoxin inhibited the activation of transcription factor NF-kappaB in response to a variety of stimuli in T and B cells. The effect of gliotoxin was specific because, at the same concentrations, the toxin did not affect activation of the transcription factor NF-AT or of interferon-responsive signal transducers and activators of transcription. Likewise, the activity of the constitutively DNA-binding transcription factors Oct-1 and cyclic AMP response element binding protein (CREB), as well as the activation of protein tyrosine kinases p56lck and p59fyn, was not altered by gliotoxin. Very high concentrations of gliotoxin prevented NF-kappaB DNA binding in vitro. However, in intact cells, inhibition of NF-kappaB did not occur at the level of DNA binding; rather, the toxin appeared to prevent degradation of IkappaB-alpha, NF-kappaB's inhibitory subunit. Our data raise the possibility that the immunosuppression observed during aspergillosis results in part from gliotoxin-mediated NF-kappaB inhibition.

Does Group Deliberation Mobilize? The Effect of Public Deliberation on Willingness to Participate in Politics.

Proponents of public deliberation suggest that engaging in deliberation increases deliberators' subsequent participation in other forms of politics. We evaluate this "deliberative participation hypothesis" using data drawn from a deliberative field experiment in which members of medically underserved communities in Michigan deliberated in small groups about the design of that state's Medicaid program. Participants were randomly assigned to deliberate about the program in a group or to think about the decision individually, and then completed a post-survey that included measures of willingness to engage in a variety of political acts. We measured willingness to engage in common forms of political participation, as well as willingness to participate in particularistic resistance to adverse decisions by insurance bureaucracies. Contrary to the claims of much of the existing literature, we find no impact of deliberation on willingness to engage in political participation. These results suggest that the ability of public deliberation to increase broader political engagement may be limited or may only occur in particularly intensive, directly empowered forms of public deliberation.

The design of a line velocity interferometer for any reflector for inertial confinement experiments on the Z-machine.

A line VISAR (Velocity Interferometer System for Any Reflector) has been designed and commissioned at the Sandia National Laboratory's Z-machine. The instrument consists of an F/2 collection system, beam transport, and an interferometer table that contains two Mach-Zehnder type interferometers and an eight channel Gated Optical Imaging (GOI) system. The VISAR probe laser operates at the 532 nm wavelength, and the GOI bandpass is 540-600 nm. The output of each interferometer is passed to an optical streak camera with four selectable sweep speeds. The system is designed with three interchangeable optics modules to select a full field of view of 1 mm, 2 mm, or 4 mm. The optical beam transport system connects the target image plane to the interferometers and the gated optical imagers. The target is integrated into a sacrificial final optics assembly that is integral to the transport beamline.

From laminin to lamin: regulation of tissue-specific gene expression by the ECM.

Mammary epithelial cells need a laminin-rich extracellular matrix (ECM) to achieve a functionally differentiated phenotype that includes secretion of milk-specific proteins such as beta-casein. There is good evidence that ECM-induced expression of beta-casein involves an 'ECM-response element' in the promoter of the casein gene that is activated by integrin-mediated signalling. This article proposes that ECM-induced structural changes in the cytoskeleton, histone organization and the nuclear matrix contribute to this tissue-specific gene expression.