cAMP Pulsing of Denuded Mouse Oocytes Increases Meiotic Resumption Via Activation of AMP-activated Protein Kinase

cAMP plays a critical role in the control of oocyte maturation, as a high level of cAMP maintains oocyte arrest at the first meiotic prophase. Yet this study shows that pulsing meiotically arrested denuded oocytes (DO) with cAMP induces oocyte maturation through the activation of AMP-activated protein kinase (PRKA). Short-term (3 h) pulsing of meiotically arrested oocytes with forskolin, an adenyl cyclase (AC) activator, increased oocyte cAMP, led to elevated AMP, and induced oocyte meiotic resumption compared to oocytes continuously cultured in the control medium with or without forskolin. Western analysis showed that germinal vesicle (GV)-stage oocytes after forskolin pulsing contained increased levels of phospho-acetyl CoA carboxylase (pACACA), a primary substrate of PRKA. Pulsing oocytes with the phosphodiesterase (PDE)-sensitive cAMP analog, 8-bromo-cAMP (8-Br-cAMP), also increased pACACA and pPRKA levels in GV-stage oocytes and induced oocyte meiotic resumption. Moreover, the PRKA inhibitors, compound C and araA, prevented 8-Br-cAMP pulsing-induced maturation. The lack of effect on meiotic induction and PRKA activation when oocytes were pulsed with the PDE-resistant activators of cAMP-dependent protein kinase, Sp-cAMP-AM and Sp-5,6-DCI-cBIMPS, suggests that cAMP degradation is required for pulsing-induced maturation. Pulsing oocytes with the exchange protein directly activated by cAMP (Epac)-specific activator, 8-CPT-2′-O-Me-cAMP, had no stimulatory effect on oocyte maturation, suggesting Epac is not involved in the pulsing-induced maturation. Taken together, these data support the idea that a transient increase in oocyte cAMP can induce meiotic resumption via activation of PRKA

The Brown Dwarf Kinematics Project I. Proper motions and tangential velocities for a large sample of late-type M, L, and T dwarfs

We report proper-motion measurements for 427 late-type M, L, and T dwarfs, 332 of which have been measured for the first time. Combining these new proper motions with previously published measurements yields a sample of 841 M7-T8 dwarfs. We combined parallax measurements or calculated spectrophotometric distances, and computed tangential velocities for the entire sample. We find that kinematics for the full and volume-limited 20 pc samples are consistent with those expected for the Galactic thin disk, with no significant differences between late-type M, L, and T dwarfs. Applying an age-velocity relation we conclude that the average kinematic age of the 20 pc sample of ultracool dwarfs is older than recent kinematic estimates and more consistent with age results calculated with population synthesis models. There is a statistically distinct population of high tangential velocity sources (V tan > 100 km s^–1) whose kinematics suggest an even older population of ultracool dwarfs belonging to either the Galactic thick disk or halo. We isolate subsets of the entire sample, including low surface gravity dwarfs, unusually blue L dwarfs, and photometric outliers in J – Ks color and investigate their kinematics. We find that the spectroscopically distinct class of unusually blue L dwarfs has kinematics clearly consistent with old age, implying that high surface gravity and/or low metallicity may be relevant to their spectral properties. The low surface gravity dwarfs are kinematically younger than the overall population, and the kinematics of the red and blue ultracool dwarfs suggest ages that are younger and older than the full sample, respectively. We also present a reduced proper-motion diagram at 2MASS (Two Micron All Sky Survey) Ks for the entire population and find that a limit of HKs > 18 excludes M dwarfs from the L and T dwarf population regardless of near-infrared color, potentially enabling the identification of the coldest brown dwarfs in the absence of color information

AMPK Regulation of Mouse Oocyte Meiotic Resumption in Vitro

We have previously shown that the adenosine analog 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR), an activator of AMP-activated protein kinase (AMPK), stimulates an increase in AMPK activity and induces meiotic resumption in mouse oocytes [Downs, S.M., Hudson, E.R., Hardie, D.G., 2002. A potential role for AMP-activated protein kinase in meiotic induction in mouse oocytes. Dev. Biol, 245, 200–212]. The present study was carried out to better define a causative role for AMPK in oocyte meiotic maturation. When microinjected with a constitutively active AMPK, about 20% of mouse oocytes maintained in meiotic arrest with dibutyryl cAMP (dbcAMP) were stimulated to undergo germinal vesicle breakdown (GVB), while there was no effect of catalytically dead kinase. Western blot analysis revealed that germinal vesicle (GV)-stage oocytes cultured in dbcAMP-containing medium plus AICAR possessed elevated levels of active AMPK, and this was confirmed by AMPK assays using a peptide substrate of AMPK to directly measure AMPK activity. AICAR-induced meiotic resumption and AMPK activation were blocked by compound C or adenine 9-beta-d-arabinofuranoside (araA, a precursor of araATP), both inhibitors of AMPK. Compound C failed to suppress adenosine uptake and phosphorylation, indicating that it did not block AICAR action by preventing its metabolism to the AMP analog, ZMP. 2′-Deoxycoformycin (DCF), a potent adenosine deaminase inhibitor, reversed the inhibitory effect of adenosine on oocyte maturation by modulating intracellular AMP levels and activating AMPK. Rosiglitazone, an anti-diabetic agent, stimulated AMPK activation in oocytes and triggered meiotic resumption. In spontaneously maturing oocytes, GVB was preceded by AMPK activation and blocked by compound C. Collectively, these results support the proposition that active AMPK within mouse oocytes provides a potent meiosis-inducing signal in vitro

The Brown Dwarf Kinematics Project (BDKP). II. Details on Nine Wide Common Proper Motion Very Low-Mass Companions to Nearby Stars

We report on nine wide common proper motion systems containing late-type M, L, or T companions. We confirm six previously reported companions, and identify three new systems. The ages of these systems are determined using diagnostics for both stellar primaries and low--mass secondaries and masses for the secondaries are inferred using evolutionary models. Of our three new discoveries, the M3+T6.5 pair G 204-39 and SDSS J1758+4633 has an age constrained to 0.5-1.5 Gyr making the secondary a potentially useful brown dwarf benchmark. The G5+L4 pair G 200-28 and SDSS J1416+5006 has a projected separation of ~25,000 AU making it one of the widest and lowest binding energy systems known to date. The system containing NLTT 2274 and SDSS J0041+1341 is an older M4+L0 (>4.5 Gyr) pair which shows Halpha activity in the secondary but not the primary making it a useful tracer of age/mass/activity trends. We find a resolved binary frequency for widely-separated (> 100 AU) low--mass companions (i.e. at least a triple system) which is at least twice the frequency found for the field ultracool dwarf population. The ratio of triples to binaries and quadruples to binaries is also high for this sample: 3:5 and 1:4, respectively, compared to 8-parsec sample values of 1:4 and 1:26. The additional components in these wide companion systems indicates a formation mechanism that requires a third or fourth component to maintain gravitational stability or facilitate the exchange of angular momentum. The binding energies for the nine multiples discussed in this text are among the lowest known for wide low-mass systems, suggesting that weakly bound, low--to--intermediate mass (0.2M_sun < M_tot <1.0M_sun) multiples can form and survive to exist in the field (1-8 Gyr).Comment: 62 pages, 12 figures, 11 Tables, AJ accepted for publicatio

Discovery of a 66 mas Ultracool Binary with Laser Guide Star Adaptive Optics

We present the discovery of 2MASS J21321145+1341584AB as a closely separated (0.066") very low-mass field dwarf binary resolved in the near-infrared by the Keck II Telescope using laser guide star adaptive optics. Physical association is deduced from the angular proximity of the components and constraints on their common proper motion. We have obtained a near-infrared spectrum of the binary and find that it is best described by an L5+/-0.5 primary and an L7.5+/-0.5 secondary. Model-dependent masses predict that the two components straddle the hydrogen burning limit threshold with the primary likely stellar and the secondary likely substellar. The properties of this sytem - close projected separation (1.8+/-0.3 AU) and near unity mass ratio - are consistent with previous results for very low-mass field binaries. The relatively short estimated orbital period of this system (~7-12 yr) makes it a good target for dynamical mass measurements. Interestingly, the system's angular separation is the tightest yet for any very low-mass binary published from a ground-based telescope and is the tightest binary discovered with laser guide star adaptive optics to date.Comment: 10 pages, 3 figures; accepted for publication to A

Interferon lambda protects the female reproductive tract against Zika virus infection

Zika virus infections can cause devastating congenital birth defects but the underlying interactions with the host immune system are not well understood. Here, the authors examine the immune basis of vaginal protection and susceptibility to Zika viral infection, and identify a hormonal dependent role for interferon-lambda-mediated protection against disease

The Brown Dwarf Kinematics Project (BDKP). III. Parallaxes for 70 Ultracool Dwarfs

We report parallax measurements for 70 ultracool dwarfs (UCDs). Using both literature values and our sample, we report new polynomial relations between spectral type and M$_{JHK}$. Including resolved L/T transition binaries in the relations, we find no reason to differentiate between a "bright" (unresolved binary) and "faint" (single source) sample across the L/T boundary. Isolating early T dwarfs, we find that the brightening of T0-T4 sources is prominent in M$_{J}$ where there is a [1.2 - 1.4] magnitude difference. A similar yet dampened brightening of [0.3 - 0.5] magnitude happens at M$_{H}$ and a plateau or dimming of [-0.2 - -0.3] magnitude is seen in M$_{K}$. Comparing with evolutionary models that vary gravity, metallicity, and cloud thickness we find that a near constant temperature of 1200 $\pm$100 K along a narrow spectral subtype of T0-T4 is required to account for the brightening and color magnitude diagram of the L-dwarf/T-dwarf transition. Furthermore, there is a significant population of both L and T dwarfs which are red or potentially "ultra-cloudy" compared to the models, many of which are known to be young indicating a correlation between enhanced photospheric dust and youth. For the low surface-gravity or young companion L dwarfs we find that 8 out of 10 are at least [0.2-1.0] magnitude underluminous in M$_{JH}$ and/or M$_{K}$ compared to equivalent spectral type objects. We speculate that this is a consequence of increased dust opacity and conclude that low-surface gravity L dwarfs require a completely new spectral-type/absolute magnitude polynomial for analysis.Comment: 65 pages, Accepted for publication to Ap

Magnetism in the Brown Dwarf Regime

A suite of discoveries in the last two decades demonstrate that we are now at a point where incorporating magnetic behavior is key for advancing our ability to characterize substellar and planetary systems. The next decade heralds the exciting maturation of the now-burgeoning field of brown dwarf magnetism, and investing now in brown dwarf magnetism will provide a key platform for exploring exoplanetary magnetism and habitability beyond the solar system. We anticipate significant discoveries including: the nature of substellar and planetary magnetic dynamos, the characterization of exo-aurora physics and brown dwarf magnetospheric environments, and the role of satellites in manifestations of substellar magnetic activity. These efforts will require significant new observational capabilities at radio and near infrared wavelengths, dedicated long-term monitoring programs, and committed support for the theoretical modeling efforts underpinning the physical processes of the magnetic phenomenaComment: Decadal 2020 science white pape

Caffeinated Alcoholic Beverages – An Emerging Trend in Alcohol Abuse

Alcohol use disorders are pervasive in society and their impact affects quality of life, morbidity and mortality, as well as individual productivity. Alcohol has detrimental effects on an individual’s physiology and nervous system, and is associated with disorders of many organ and endocrine systems impacting an individual’s health, behavior, and ability to interact with others. Youth are particularly affected. Unfortunately, adolescent usage also increases the probability for a progression to dependence. Several areas of research indicate that the deleterious effects of alcohol abuse may be exacerbated by mixing caffeine with alcohol. Some behavioral evidence suggests that caffeine increases alcohol drinking and binge drinking episodes, which in turn can foster the development of alcohol dependence. As a relatively new public health concern, the epidemiological focus has been to establish a need for investigating the effects of caffeinated alcohol. While the trend of co-consuming these substances is growing, knowledge of the central mechanisms associated with caffeinated ethanol has been lacking. Research suggests that caffeine and ethanol can have additive or synergistic pharmacological actions and neuroadaptations, with the adenosine and dopamine systems in particular implicated. However, the limited literature on the central effects of caffeinated ethanol provides an impetus to increase our knowledge of the neuroadaptive effects of this combination and their impact on cognition and behavior. Research from our laboratories indicates that an established rodent animal model of alcoholism can be extended to investigate the acute and chronic effects of caffeinated ethanol