The Hubble Space Telescope Extragalactic Distance Scale Key Project. X. The Cepheid Distance to NGC 7331

The distance to NGC 7331 has been derived from Cepheid variables observed with HST/WFPC2, as part of the Extragalactic Distance Scale Key Project. Multi-epoch exposures in F555W (V) and F814W (I), with photometry derived independently from DoPHOT and DAOPHOT/ALLFRAME programs, were used to detect a total of 13 reliable Cepheids, with periods between 11 and 42 days. The relative distance moduli between NGC 7331 and the LMC, imply an extinction to NGC 7331 of A_V = 0.47+-0.15 mag, and an extinction-corrected distance modulus to NGC 7331 of 30.89+-0.14(random) mag, equivalent to a distance of 15.1 Mpc. There are additional systematic uncertainties in the distance modulus of +-0.12 mag due to the calibration of the Cepheid Period-Luminosity relation, and a systematic offset of +0.05+-0.04 mag if we applied the metallicity correction inferred from the M101 results of Kennicutt et al 1998.Comment: To be published in The Astrophysical Journal, 1998 July 1, v501 note: Figs 1 and 2 (JPEG files) and Fig 7 (multipage .eps file) need to be viewed/printed separatel

Bridging the Gap Between Practice Guidelines and the Therapy Room: Community-Derived Practice Adaptations for Psychological Services with Transgender and Gender Diverse Adults in the Central United States

Individuals who identify as transgender and gender diverse (TGD) are presenting at mental health clinicians’ offices with increasing frequency. Many TGD clients are seeking care related to affirming their gender identity but also may present with anxiety, depression, trauma, substance abuse, or other problems forwhich a clinician may commonly provide services. Some clinicians may hesitate to accept TGD clients into their practice if they have little specialized training to work with this population in an affirming manner, especially in more underserved areas where a generalist practice is the norm. Numerous professional associations and experts have developed guidelines for affirmative behavioral health care for TGDpeople.However, what is needed are community-informed recommendations to bridge from the official guidelines to clinicians’ in-session activities. The Trans Collaborations Practice Adaptations for Psychological Interventions for Transgender and Gender Diverse Adults are derived from iterative interviews with TGD community members and affirming mental health clinicians in the Central United States. The 12 practice adaptations are intended to guide clinicians to adapt their usual treatment approach to be TGD affirming, especially in underserved and rural areas. The practice adaptations cover numerous aspects of practice including the office setting and paperwork, understanding gender identity and incorporating it into the case conceptualization, therapist’s self-awareness, and referrals. The Trans Collaborations Practice Adaptations will help clinicians work confidently and competently with adult TGD clients, regardless of the presenting problem, to ensure TGD communities receive the best interventions for their behavioral health concerns

The Extragalactic Distance Scale Key Project. XVI. Cepheid Variables in an Inner Field of M101

We report on the identification of 255 candidate variable stars in a field located some 1.7 from the center of the late-type spiral galaxy M101 = NGC 5457, based on observations made with the Wide Field and Planetary Camera 2 on board the Hubble Space Telescope

The HST Key Project on the Extragalactic Distance Scale XIV. The Cepheids in NGC 1365

We report the detection of Cepheid variable stars in the barred spiral galaxy NGC 1365, located in the Fornax cluster, using the Hubble Space Telescope Wide Field and Planetary Camera 2. Twelve V (F555W) and four I (F814W) epochs of observation were obtained. The two photometry packages, ALLFRAME and DoPHOT, were separately used to obtain profile-fitting photometry of all the stars in the HST field. The search for Cepheid variable stars resulted in a sample of 52 variables, with periods between 14 and 60 days, in common with both datasets. ALLFRAME photometry and light curves of the Cepheids are presented. A subset of 34 Cepheids were selected on the basis of period, light curve shape, similar ALLFRAME and DoPHOT periods, color, and relative crowding, to fit the Cepheid period-luminosity relations in V and I for both ALLFRAME and DoPHOT. The measured distance modulus to NGC 1365 from the ALLFRAME photometry is 31.31 +/- 0.20 (random) +/- 0.18 (systematic) mag, corresponding to a distance of 18.3 +/- 1.7 (random) +/- 1.6 (systematic) Mpc. The reddening is measured to be E(V-I) = 0.16 +/- 0.08 mag. These values are in excellent agreement with those obtained using the DoPHOT photometry, namely a distance modulus of 31.26 +/- 0.10 mag, and a reddening of 0.15 +/- 0.10 mag (internal errors only).Comment: 48 pages, 8 tables, 8 figures, to appear in Ap

Ecological genetics in the North Atlantic: environmental gradients and adaptation at specific loci

The North Atlantic intertidal community provides a rich set of organismal and environmental material for the study of ecological genetics. Clearly defined environmental gradients exist at multiple spatial scales: there are broad latitudinal trends in temperature, meso-scale changes in salinity along estuaries, and smaller scale gradients in desiccation and temperature spanning the intertidal range. The geology and geography of the American and European coasts provide natural replication of these gradients, allowing for population genetic analyses of parallel adaptation to environmental stress and heterogeneity. Statistical methods have been developed that provide genomic neutrality tests of population differentiation and aid in the process of candidate gene identification. In this paper, we review studies of marine organisms that illustrate associations between an environmental gradient and specific genetic markers. Such highly differentiated markers become candidate genes for adaptation to the environmental factors in question, but the functional significance of genetic variants must be comprehensively evaluated. We present a set of predictions about locus-specific selection across latitudinal, estuarine, and intertidal gradients that are likely to exist in the North Atlantic. We further present new data and analyses that support and contradict these simple selection models. Some taxa show pronounced clinal variation at certain loci against a background of mild clinal variation at many loci. These cases illustrate the procedures necessary for distinguishing selection driven by internal genomic vs. external environmental factors. We suggest that the North Atlantic intertidal community provides a model system for identifying genes that matter in ecology due to the clarity of the environmental stresses and an extensive experimental literature on ecological function. While these organisms are typically poor genetic and genomic models, advances in comparative genomics have provided access to molecular tools that can now be applied to taxa with well-defined ecologies. As many of the organisms we discuss have tight physiological limits driven by climatic factors, this synthesis of molecular population genetics with marine ecology could provide a sensitive means of assessing evolutionary responses to climate change

Electrophysiological Characterization of The Cerebellum in the Arterially Perfused Hindbrain and Upper Body of The Rat

In the present study, a non-pulsatile arterially perfused hindbrain and upper body rat preparation is described which is an extension of the brainstem preparation reported by Potts et al., (Brain Res Bull 53(1):59–67), 1. The modified in situ preparation allows study of cerebellar function whilst preserving the integrity of many of its interconnections with the brainstem, upper spinal cord and the peripheral nervous system of the head and forelimbs. Evoked mossy fibre, climbing fibre and parallel fibre field potentials and EMG activity elicited in forelimb biceps muscle by interpositus stimulation provided evidence that both cerebellar inputs and outputs remain operational in this preparation. Similarly, the spontaneous and evoked single unit activity of Purkinje cells, putative Golgi cells, molecular interneurones and cerebellar nuclear neurones was similar to activity patterns reported in vivo. The advantages of the preparation include the ability to record, without the complications of anaesthesia, stabile single unit activity for extended periods (3 h or more), from regions of the rat cerebellum that are difficult to access in vivo. The preparation should therefore be a useful adjunct to in vitro and in vivo studies of neural circuits underlying cerebellar contributions to movement control and motor learning

Increased CD8+ T cell responses to apoptotic T cell-associated antigens in multiple sclerosis.

BACKGROUND: Here, we evaluated the hypothesis that CD8(+) T cell responses to caspase-cleaved antigens derived from effector T cells undergoing apoptosis, may contribute to multiple sclerosis (MS) immunopathology. METHODS: The percentage of autoreactive CD8(+) T effector cells specific for various apoptotic T cell-associated self-epitopes (apoptotic epitopes) were detected in the peripheral blood and cerebrospinal fluid (CSF) by both enzyme-linked immunospot and dextramers of class I molecules complexed with relevant apoptotic epitopes. Moreover, the capacity of dextramer(+) CD8(+) T cells to produce interferon (IFN)-γ and/or interleukin (IL)-17 in response to the relevant apoptotic epitopes was evaluated by the intracellular cytokine staining. Cross-presentation assay of apoptotic T cells by dendritic cells was also evaluated ex vivo. RESULTS: We found that polyfunctional (IFN-γ and/or IL-17 producing) autoreactive CD8(+) T cells specific for apoptotic epitopes were represented in MS patients with frequencies significantly higher than in healthy donors. These autoreactive CD8(+) T cells with a strong potential to produce IFN-γ or IL-17 in response to the relevant apoptotic epitopes were significantly accumulated in the CSF from the same patients. In addition, the frequencies of these autoreactive CD8(+) T cells correlated with the disease disability. Cross-presentation assay revealed that caspase-cleaved cellular proteins are required to activate apoptotic epitope-specific CD8(+) T cells ex vivo. CONCLUSION: Taken together, these data indicate that apoptotic epitope-specific CD8(+) T cells with strong inflammatory potential are recruited at the level of the inflammatory site, where they may be involved in MS immunopathology through the production of high levels of inflammatory cytokines

Polyfunctional Type-1, -2, and -17 CD8+ T Cell Responses to Apoptotic Self-Antigens Correlate with the Chronic Evolution of Hepatitis C Virus Infection

Caspase-dependent cleavage of antigens associated with apoptotic cells plays a prominent role in the generation of CD8+ T cell responses in various infectious diseases. We found that the emergence of a large population of autoreactive CD8+ T effector cells specific for apoptotic T cell-associated self-epitopes exceeds the antiviral responses in patients with acute hepatitis C virus infection. Importantly, they endow mixed polyfunctional type-1, type-2 and type-17 responses and correlate with the chronic progression of infection. This evolution is related to the selection of autoreactive CD8+ T cells with higher T cell receptor avidity, whereas those with lower avidity undergo prompt contraction in patients who clear infection. These findings demonstrate a previously undescribed strict link between the emergence of high frequencies of mixed autoreactive CD8+ T cells producing a broad array of cytokines (IFN-γ, IL-17, IL-4, IL-2…) and the progression toward chronic disease in a human model of acute infection

Whole-genome sequencing of acral melanoma reveals genomic complexity and diversity

To increase understanding of the genomic landscape of acral melanoma, a rare form of melanoma occurring on palms, soles or nail beds, whole genome sequencing of 87 tumors with matching transcriptome sequencing for 63 tumors was performed. Here we report that mutational signature analysis reveals a subset of tumors, mostly subungual, with an ultraviolet radiation signature. Significantly mutated genes are BRAF, NRAS, NF1, NOTCH2, PTEN and TYRP1. Mutations and amplification of KIT are also common. Structural rearrangement and copy number signatures show that whole genome duplication, aneuploidy and complex rearrangements are common. Complex rearrangements occur recurrently and are associated with amplification of TERT, CDK4, MDM2, CCND1, PAK1 and GAB2, indicating potential therapeutic options.This work was supported by a National Health and Medical Research Council of Australia (NHMRC) Program Grant (1093017, G.J.M., R.A.S., N.H., G.V.L., J.F.T.), an NHMRC project grant (APP1123217) and NHMRC Fellowship grants (R.A.S., N.K.H. - APP1139071, G.VL.). G.V.L is supported by an NHMRC Practitioner Fellowship and the University of Sydney Medical Foundation. R.A.S is supported by an NHMRC Practitioner Fellowship. J.S.W. is supported by a NHMRC early career fellowship (1111678). N.W. is supported by an NHMRC Senior Research Fellowship (1139071). N.K.H. is supported by an NHMRC Senior Principal Research Fellowship (1117663). P.M.F. was supported by the Deborah and John McMurtrie MIA Pathology Fellowship. T.J.D. was supported by the Jani Haenke Melanoma Pathology Fellowship. Support from Melanoma Institute Australia, the Royal Prince Alfred Hospital and New South Wales Health Pathology is also gratefully acknowledged