Gene regulatory factors of the sea urchin embryo. II. Two dissimilar proteins, P3A1 and P3A2, bind to the same target sites that are required for early territorial gene expression

Previous work demonstrated that a negative regulatory interaction mediated by factor(s) termed 'P3A' is required for correct territory-specific gene expression in the sea urchin embryo. A probe derived from a P3A target site in the skeletogenic SM50 gene of Strongylocentrotus purpuratus was used to isolate a cDNA clone coding for a factor that binds specifically to this site. This factor, called P3A1, contains two sequence elements that belong to the Zn finger class of DNA-binding motifs, and in these regions is most closely similar to the Drosophila hunchback factor. The P3A1 factor also binds to a similar target sequence in a second gene, CyIIIa, expressed in embryonic aboral ectoderm. Another sea urchin embryo protein factor, P3A2, has been isolated by affinity chromatography and cloned, as described in Calzone et al. Development 112, 335-350 (1991). P3A2 footprints the same target sites in the SM50 and CyIIIa genes as does P3A1, but lacks the Zn finger sequence motifs and in amino acid sequence is almost entirely dissimilar to P3A1. A deletion analysis of P3A2 delimited the DNA-binding region, revealing that five specific amino acids in the first P3A1 finger region and four in the second P3A1 finger region are also present in equivalent positions in P3A2. The P3A1 and P3A2 factors could function as regulatory antagonists, having evolved similar target specificities from dissimilar DNA-binding domains

Screening for Gynecologic Conditions With Pelvic Examination US Preventive Services Task Force Recommendation Statement

IMPORTANCE Many conditions that can affect women\u27s health are often evaluated through pelvic examination. Although the pelvic examination is a common part of the physical examination, it is unclear whether performing screening pelvic examinations in asymptomatic women has a significant effect on disease morbidity and mortality. OBJECTIVE To issue a new US Preventive Services Task Force(USPSTF) recommendation on screening for gynecologic conditions with pelvic examination for conditions other than cervical cancer, gonorrhea, and chlamydia, for which the USPSTF has already made specific recommendations. EVIDENCE REVIEW The USPSTF reviewed the evidence on the accuracy, benefits, and potential harms of performing screening pelvic examinations in asymptomatic, nonpregnant adult women 18 years and older who are not at increased risk for any specific gynecologic condition. FINDINGS Overall, the USPSTF found inadequate evidence on screening pelvic examinations for the early detection and treatment of a range of gynecologic conditions in asymptomatic, nonpregnant adult women. CONCLUSIONS AND RECOMMENDATION The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of performing screening pelvic examinations in asymptomatic, nonpregnant adult women. (I statement) This statement does not apply to specific disorders for which the USPSTF already recommends screening (ie, screening for cervical cancer with a Papanicolaou smear, screening for gonorrhea and chlamydia)

Developmental Effector Gene Regulation: Multiplexed Strategies for Functional Analysis

The staggering complexity of the genome controls for developmental processes is revealed through massively parallel cis-regulatory analysis using new methods of perturbation and readout. The choice of combinations of these new methods is tailored to the system, question and resources at hand. Our focus is on issues that include the necessity or sufficiency of given cis-regulatory modules, cis-regulatory function in the normal spatial genomic context, and easily accessible high throughput and multiplexed analysis methods. In the sea urchin embryonic model, recombineered BACs offer new opportunities for consecutive modes of cis-regulatory analyses that answer these requirements, as we here demonstrate on a diverse suite of previously unstudied sea urchin effector genes expressed in skeletogenic cells. Positively active cis-regulatory modules were located in single Nanostring experiments per BAC containing the gene of interest, by application of our previously reported “barcode” tag vectors of which> 100 can be analyzed at one time. Computational analysis of DNA sequences that drive expression, based on the known skeletogenic regulatory state, then permitted effective identification of functional target site clusters. Deletion of these sub-regions from the parent BACs revealed module necessity, as simultaneous tests of the same regions in short constructs revealed sufficiency. Predicted functional inputs were then confirmed by site mutations, all generated and tested in multiplex formats. There emerged the simple conclusion that each effector gene utilizes a small subset of inputs from the skeletogenic GRN. These inputs may function to only adjust expression levels or in some cases necessary for expression. Since we know the GRN architecture upstream of the effector genes, we could then conceptually isolate and compare the wiring of the effector gene driver sub-circuits and identify the inputs whose removal abolish expression

“Hitting the wall”: Lived experiences of mental health crises

Background : As Norway moves toward the provision of home-based crisis response, knowledge is needed about understandings of mental health crisis and effective ways of addressing crises within the home. Objective : To elicit and learn from service users’ experiences about the subjective meanings of crisis and what kind of help will be most effective in resolving mental health crises. Theoretical : A phenomenological-hermeneutic cooperative inquiry method was used to elicit and analyse focus group responses from mental health service users who had experienced crises. Results : Findings clustered into three themes: (1) Crisis as multifaceted and varied experiences; (2) losing the skills and structure of everyday life; and (3) complexities involved in family support. Conclusion : Several aspects of crises require an expansion of the biomedical model of acute intervention to include consideration of the personal and familial meaning of the crisis, attention to the home context, and activities of daily living that are disrupted by the crisis, and ways for the person and the family to share in and learn from resolution of the crisis

Screening for Impaired Visual Acuity in Older Adults: US Preventive Services Task Force Recommendation Statement

DESCRIPTION: Update of the US Preventive Services Task Force (USPSTF) recommendation on screening for impaired visual acuity in older adults. METHODS: The USPSTF reviewed the evidence on screening for visual acuity impairment associated with uncorrected refractive error, cataracts, and age-related macular degeneration among adults 65 years or older in the primary care setting; the benefits and harms of screening; the accuracy of screening; and the benefits and harms of treatment of early vision impairment due to uncorrected refractive error, cataracts, and age-related macular degeneration. POPULATION: This recommendation applies to asymptomatic adults 65 years or older who do not present to their primary care clinician with vision problems. RECOMMENDATION: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for impaired visual acuity in older adults. (I statement)

The prevalence and incidence of mental ill-health in adults with autism and intellectual disabilities

The prevalence, and incidence, of mental ill-health in adults with intellectual disabilities and autism were compared with the whole population with intellectual disabilities, and with controls, matched individually for age, gender, ability-level, and Down syndrome. Although the adults with autism had a higher point prevalence of problem behaviours compared with the whole adult population with intellectual disabilities, compared with individually matched controls there was no difference in prevalence, or incidence of either problem behaviours or other mental ill-health. Adults with autism who had problem behaviours were less likely to recover over a two-year period than were their matched controls. Apparent differences in rates of mental ill-health are accounted for by factors other than autism, including Down syndrome and ability level

Screening for Syphilis Infection in Nonpregnant Adults and Adolescents: US Preventive Services Task Force Recommendation Statement

Clinical Review & Education US Preventive Services Task Force | RECOMMENDATION STATEMENT Screening for Syphilis Infection in Nonpregnant Adults and Adolescents US Preventive Services Task Force Recommendation Statement US Preventive Services Task Force (USPSTF) Editorial page 2281 IMPORTANCE In 2014, 19 999 cases of syphilis were reported in the United States. Left untreated, syphilis can progress to late-stage disease in about 15% of persons who are infected. Late-stage syphilis can lead to development of inflammatory lesions throughout the body, which can lead to cardiovascular or organ dysfunction. Syphilis infection also increases the risk for acquiring or transmitting HIV infection. OBJECTIVE To update the 2004 US Preventive Services Task Force (USPSTF) recommendation on screening for syphilis infection in nonpregnant adults. Screening for syphilis in pregnant women was updated in a separate recommendation statement in 2009 (A recommendation). EVIDENCE REVIEW The USPSTF reviewed the evidence on screening for syphilis infection in asymptomatic, nonpregnant adults and adolescents, including patients coinfected with other sexually transmitted infections (such as HIV). Author Audio Interview at jama.com Related article page 2328 and JAMA Patient Page page 2367 CME Quiz at jamanetworkcme.com and CME Questions page 2342 Related articles at jamadermatology.com, jamaneurology.com, jamapediatrics.com FINDINGS The USPSTF found convincing evidence that screening for syphilis infection in asymptomatic, nonpregnant persons at increased risk for infection provides substantial benefit. Accurate screening tests are available to identify syphilis infection in populations at increased risk. Effective treatment with antibiotics can prevent progression to late-stage disease, with small associated harms, providing an overall substantial health benefit. CONCLUSIONS AND RECOMMENDATION The USPSTF recommends screening for syphilis infection in persons who are at increased risk for infection. (A recommendation) Authors/Group Information: The USPSTF members are listed at the end of the article. JAMA. 2016;315(21):2321-2327. doi:10.1001/jama.2016.5824 Corresponding Author: Kirsten Bibbins-Domingo, PhD, MD, MAS ([email protected]). T he US Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific preventive care services for patients without obvious related signs or symptoms. It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the bal- ance. The USPSTF does not consider the costs of providing a ser- vice in this assessment. The USPSTF recognizes that clinical decisions involve more con- siderations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clini- cal benefits and harms. Summary of Recommendation and Evidence The USPSTF recommends screening for syphilis infection in per- sons who are at increased risk for infection. (A recommendation) (Figure 1) jama.com See the Clinical Considerations section later in this article for in- formation on risk factors for infection. Rationale Importance The number of cases of primary and secondary syphilis have been in- creasing since 2000. In 2014, 19 999 cases (6.3 cases per 100 000 persons)ofprimaryandsecondarysyphiliswerereportedintheUnited States. 1 Left untreated, syphilis can progress to late-stage disease in approximately 15% of persons who are infected. 2 Consequences of late-stage syphilis include development of inflammatory lesions throughout the body (eg, aortitis, gummatous lesions, and osteitis), which can lead to cardiovascular or organ dysfunction. Syphilis in- fection of the central nervous system (neurosyphilis) can occur at any stage of disease and can result in blindness, paresis, tabes dor- salis, and dementia. Syphilis infection also increases the risk for ac- quiring or transmitting HIV infection. The USPSTF addresses screening for syphilis in pregnant women in a separate recommendation statement. 3 (Reprinted) JAMA June 7, 2016 Volume 315, Number 21 Copyright 2016 American Medical Association. All rights reserved. Downloaded From: http://jamanetwork.com/ by a University of California - Los Angeles User on 09/21/201

Supersymmetric interpretation of high--Q2Q^2 HERA events and other related issues

In the framework of the minimal supersymmetric standard model (MSSM) with $R-$parity violation, the high--$Q^2$ HERA events can be interpreted as the $s-$channel production of a single stop of $M_{\tilde{t}_1} \approx 200$ GeV, whose dominant decay modes are assumed to be the $R-$parity violating $e^+ + d$ and the $R-$parity conserving $\chi^+ + b$. Assuming only one coupling $\bar{\lambda_{131}^{'}}$ is nonzero of order $\sim 0.04-0.12$, we find that (i) the high$-Q^2$ HERA events can be understood as an $s-$channel stop production with a subsequent decay into $e^+ + (single ~jet)$, and (ii) the ALEPH 4-jet events can be understood in the scenario suggested by Carena et al.. We briefly discuss other physics signals of this scenario at other places such as HERA, LEP200 and Tevatron. The best test for our scenario is to observe the stop decay into $\chi^+ + b$ followed by $\chi^+ \to \tilde{e}^+ + \nu_e$ and $\tilde{e}^+ \to q + \bar{q}^{'}$ via the $R-$parity violating coupling.Comment: version published in Phys. Rev. D. 57 (1998) 489-49

The fatty acid binding protein 7 (FABP7) is involved in proliferation and invasion of melanoma cells

<p>Abstract</p> <p>Background</p> <p>The molecular mechanisms underlying melanoma tumor development and progression are still not completely understood. One of the new candidates that emerged from a recent gene expression profiling study is <it>fatty acid-binding protein 7 </it>(<it>FABP7)</it>, involved in lipid metabolism, gene regulation, cell growth and differentiation.</p> <p>Methods</p> <p>We studied the functional role of FABP7 in human melanoma cell lines and using immunohistochemistry analyzed its expression pattern and clinical role in 11 nevi, 149 primary melanomas and 68 metastases.</p> <p>Results</p> <p>FABP7 mRNA and protein level is down-regulated following treatment of melanoma cell lines with a PKC activator (PMA) or MEK1 inhibitor (PD98059). Down-regulation of FABP7 using siRNA decreased cell proliferation and invasion but did not affect apoptosis. In clinical specimens, FABP7 was expressed in 91% of nevi, 71% of primary melanomas and 70% of metastases, with a cytoplasmic and/or nuclear localization. FABP7 expression was associated with tumor thickness in superficial spreading melanoma (P = 0.021). In addition, we observed a trend for an association between FABP7 expression and Ki-67 score (P = 0.070) and shorter relapse-free survival (P = 0.069) in this group of patients.</p> <p>Conclusion</p> <p>Our data suggest that FABP7 can be regulated by PKC and the MAPK/ERK1/2 pathway through independent mechanisms in melanoma cell lines. Furthermore, FABP7 is involved in cell proliferation and invasion <it>in vitro</it>, and may be associated with tumor progression in melanoma.</p