Pathway to Totipotency: Lessons from Germ Cells

Oocytes and sperm are some of the most differentiated cells in our bodies, yet they generate all cell types after fertilization. Accumulating evidence suggests that this extraordinary potential is conferred to germ cells from the time of their formation during embryogenesis. In this Review, we describe common themes emerging from the study of germ cells in vertebrates and invertebrates. Transcriptional repression, chromatin remodeling, and an emphasis on posttranscriptional gene regulation preserve the totipotent genome of germ cells through generations

Brief mindfulness training enhances cognitive control in socioemotional contexts: Behavioral and neural evidence.

In social contexts, the dynamic nature of others' emotions places unique demands on attention and emotion regulation. Mindfulness, characterized by heightened and receptive moment-to-moment attending, may be well-suited to meet these demands. In particular, mindfulness may support more effective cognitive control in social situations via efficient deployment of top-down attention. To test this, a randomized controlled study examined effects of mindfulness training (MT) on behavioral and neural (event-related potentials [ERPs]) responses during an emotional go/no-go task that tested cognitive control in the context of emotional facial expressions that tend to elicit approach or avoidance behavior. Participants (N = 66) were randomly assigned to four brief (20 min) MT sessions or to structurally equivalent book learning control sessions. Relative to the control group, MT led to improved discrimination of facial expressions, as indexed by d-prime, as well as more efficient cognitive control, as indexed by response time and accuracy, and particularly for those evidencing poorer discrimination and cognitive control at baseline. MT also produced better conflict monitoring of behavioral goal-prepotent response tendencies, as indexed by larger No-Go N200 ERP amplitudes, and particularly so for those with smaller No-Go amplitude at baseline. Overall, findings are consistent with MT's potential to enhance deployment of early top-down attention to better meet the unique cognitive and emotional demands of socioemotional contexts, particularly for those with greater opportunity for change. Findings also suggest that early top-down attention deployment could be a cognitive mechanism correspondent to the present-oriented attention commonly used to explain regulatory benefits of mindfulness more broadly

ADAD1 and ADAD2, testis-specific adenosine deaminase domain-containing proteins, are required for male fertility.

Adenosine-to-inosine RNA editing, a fundamental RNA modification, is regulated by adenosine deaminase (AD) domain containing proteins. Within the testis, RNA editing is catalyzed by ADARB1 and is regulated in a cell-type dependent manner. This study examined the role of two testis-specific AD domain proteins, ADAD1 and ADAD2, on testis RNA editing and male germ cell differentiation. ADAD1, previously shown to localize to round spermatids, and ADAD2 had distinct localization patterns with ADAD2 expressed predominantly in mid- to late-pachytene spermatocytes suggesting a role for both in meiotic and post-meiotic germ cell RNA editing. AD domain analysis showed the AD domain of both ADADs was likely catalytically inactive, similar to known negative regulators of RNA editing. To assess the impact of Adad mutation on male germ cell RNA editing, CRISPR-induced alleles of each were generated in mouse. Mutation of either Adad resulted in complete male sterility with Adad1 mutants displaying severe teratospermia and Adad2 mutant germ cells unable to progress beyond round spermatid. However, mutation of neither Adad1 nor Adad2 impacted RNA editing efficiency or site selection. Taken together, these results demonstrate ADAD1 and ADAD2 are essential regulators of male germ cell differentiation with molecular functions unrelated to A-to-I RNA editing

Supernova Remnants in the Fossil Starburst in M82

We report the discovery of ten compact H-alpha-bright sources in the post-starburst region northeast of the center of M82, ``M82 B.'' These objects have H alpha luminosities and sizes consistent with Type II supernova remnants (SNRs). They fall on the same H alpha surface brightness-diameter (Sigma-D) relation defined by SNRs in other nearby star-forming galaxies, with the M82 candidates lying preferentially at the small diameter end. These are the first candidates for optically-visible SNRs in M82 outside the heavily obscured central starburst within ~250 pc from the galactic center. If these sources are SNRs, they set an upper limit to the end of the starburst in region ``B2,'' about 500 pc from the galaxy's core, of ~50 Myr. Region ``B1,'' about 1000 pc from the core, lacks good SNR candidates and is evidently somewhat older. This suggests star formation in the galaxy has propagated inward toward the present-day intense starburst core.Comment: Re-submitted to AJ, referee's comments taken into account, 15 pages LaTeX preprint style, 4 postscript figures; full-resolution figures available from http://www.astro.virginia.edu/~rd7a/snrs/ Changes: minor textual changes and orientation/axes of Fig.

Brightly Luminescent Platinum Complexes of N∧C–∧N Ligands Forming Six-Membered Chelate Rings: Offsetting Deleterious Ring Size Effects Using Site-Selective Benzannulation

Brightly emissive platinum(II) complexes (λemission,max = 607–612 nm) of the type RLPtCl are reported, where RL is a cyclometalated N∧C–∧N-coordinating ligand derived from 1,3-di(2-trifluoromethyl-4-phenanthridinyl)benzene (CF3LH) or 1,3-di(2-tert-butyl-4-phenanthridinyl)benzene (tBuLH). Metathesis of the chlorido ligand can be achieved under mild conditions, enabling isolation of ionic compounds with the formula [CF3LPtL′]PF6 where L′ = pyridine or (4-dimethylamino)pyridine (DMAP), as well as the charge-neutral species tBuLPt(C≡C─C6H4─tBu) (C≡C─C6H4─tBu = 4-tert-butylphenylacetylido). Compared with N∧N∧N-ligated Pt(II) complexes that form 5-membered chelates, these compounds all contain 6-membered rings. Expanding the chelate ring size from 5 to 6 has been previously demonstrated to enhance emission in some N∧N∧N-coordinated Pt(II) species─for example, in complexes of 2,6-di(8-quinolinyl)pyridine vs those of 2,2′:6′,2″-terpyridine─but in related N∧C–∧N-coordinated species, luminescence quantum yields are significantly lower for the 6-membered chelate ring complexes. Here, we demonstrate that site-selective benzannulation of the quinolinyl side-arms can offset the deleterious effect of changing the chelate ring-size and boost photophysical properties such as the quantum yield. Density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations suggest that benzannulation counterintuitively destabilizes the emissive triplet states compared to the smaller π-system, with the “imine-bridged biphenyl” form of the phenanthridinyl arm helping to buffer against larger molecular distortions, enhancing photoluminescence quantum yields up to 0.09 ± 0.02. The spontaneous formation under aerated conditions of a Pt(IV) derivative (CF3LPtCl3) is also reported, together with its molecular structure in the solid state

Spectrophotometry of HII Regions, Diffuse Ionized Gas and Supernova Remnants in M31: The Transition from Photo- to Shock-Ionization

We present results of KPNO 4-m optical spectroscopy of discrete emission-line nebulae and regions of diffuse ionized gas (DIG) in M31. Long-slit spectra of 16 positions in the NE half of M31 were obtained over a 5-15 kpc range in radial distance from the center of the galaxy. The spectra have been used to confirm 16 supernova remnant candidates from the Braun & Walterbos (1993) catalog. The slits also covered 46 HII regions which show significant differences among the various morphological types (center-brightened, diffuse, rings). Radial gradients in emission-line ratios such as [OIII]/H$\beta$ and [OII]/[OIII] are observed most prominently in the center-brightened HII regions. These line ratio trends are either much weaker or completely absent in the diffuse and ring nebulae. The line ratio gradients previously seen in M31 SNRs (Blair, Kirshner, & Chevalier 1981; 1982) are well reproduced by our new data. The spectra of center-brightened HII regions and SNRs confirm previous determinations of the radial abundance gradient in M31. We use diagnostic diagrams which separate photoionized gas from shock-ionized gas to compare the spectral properties of HII regions, SNRs and DIG. This analysis strengthens earlier claims (Greenawalt, Walterbos, & Braun 1997) that the DIG in the disk of M31 is photoionized by a dilute radiation field.Comment: 45 pages, 9 figures, 7 tables, to appear in the Astronomical Journal (December 1999

Identification of EOMES-expressing spermatogonial stem cells and their regulation by PLZF.

Long-term maintenance of spermatogenesis in mammals is supported by GDNF, an essential growth factor required for spermatogonial stem cell (SSC) self-renewal. Exploiting a transgenic GDNF overexpression model, which expands and normalizes the pool of undifferentiated spermatogonia between Plzf +/+ and Plzf lu/lu mice, we used RNAseq to identify a rare subpopulation of cells that express EOMES, a T-box transcription factor. Lineage tracing and busulfan challenge show that these are SSCs that contribute to steady state spermatogenesis as well as regeneration following chemical injury. EOMES+ SSCs have a lower proliferation index in wild-type than in Plzf lu/lu mice, suggesting that PLZF regulates their proliferative activity and that EOMES+ SSCs are lost through proliferative exhaustion in Plzf lu/lu mice. Single cell RNA sequencing of EOMES+ cells from Plzf +/+ and Plzf lu/lu mice support the conclusion that SSCs are hierarchical yet heterogeneous

Development of an Attribution of Racial/Ethnic Health Disparities Scale

The purpose of this study was to develop an Attribution of Racial/Ethnic Health Disparities (AREHD) scale. A convenience sample of undergraduate college students (n = 423) at four Midwestern universities was recruited to respond to the survey. A pilot test with undergraduate students (n = 23) found the survey had good acceptability and readability level (SMOG = 11th grade). Using exploratory factor analysis we found the two a priori subscales were confirmed: individual responsibility and social determinants. Internal reliabilities of the subscales were: individual responsibility (alpha = 0.87) and social determinants (alpha = 0.90). Test–retest stability reliabilities were: individual responsibility (r = 0.72) and social determinants (r = 0.69). The AREHD subscales are satisfactory for assessing college student’s AREHD

GDNF promotes hair formation and cutaneous wound healing by targeting bulge stem cells.

Glial-cell-derived neurotrophic factor (GDNF) is a well-studied neuroregenerative factor; however, the degree to which it supports hair formation and skin wound repair is not known. By using a Gfra1 (GDNF family receptor alpha 1) knock-in reporter mouse line, GDNF signaling was found to occur within hair bulge stem cells (BSCs) during the initiation of the hair cycle and early stages of hair formation after depilation. Both recombinant and transgene overexpression of GDNF promoted BSC colony growth, hair formation, and skin repair after wounding through enhanced self-renewal of BSCs and commitment of BSC-derived progenitors into becoming epidermal cells at the injury site. Conditional ablation of Gfra1 among BSCs impaired the onset of the hair cycle, while conditional ablation of the GDNF family member signal transducer, Ret, within BSCs prevented the onset of the hair cycle and depilation-induced anagen development of hair follicles. Our findings reveal that GDNF promotes hair formation and wound repair and that bulge stem cells are critical mediators of both