Structural Loop Between the Cerebellum and the Superior Temporal Sulcus: Evidence from Diffusion Tensor Imaging

The cerebellum is believed to play an essential role in a variety of motor and cognitive functions through reciprocal interaction with the cerebral cortex. Recent findings suggest that cerebellar involvement in the network specialized for visual body motion processing may be mediated through interaction with the right superior temporal sulcus (STS). Yet, the underlying pattern of structural connectivity between the STS and the cerebellum remains unidentified. In the present work, diffusion tensor imaging analysis on seeds derived from functional magnetic resonance imaging during a task on point-light biological motion perception uncovers a structural pathway between the right posterior STS and the left cerebellar lobule Crus I. The findings suggest existence of a structural loop underpinning bidirectional communication between the STS and cerebellum. This connection might also be of potential value for other visual social abilitie

Stressor- and Corticotropin releasing Factor-induced Reinstatement and Active Stress-related Behavioral Responses are Augmented Following Long-access Cocaine Self-administration by Rats

Rationale Stressful events during periods of drug abstinence likely contribute to relapse in cocaine-dependent individuals. Excessive cocaine use may increase susceptibility to stressor-induced relapse through alterations in brain corticotropin-releasing factor (CRF) responsiveness. Objectives This study examined stressor- and CRF-induced cocaine seeking and other stress-related behaviors in rats with different histories of cocaine self-administration (SA). Materials and methods Rats self-administered cocaine under short-access (ShA; 2 h daily) or long-access (LgA; 6 h daily) conditions for 14 days or were provided access to saline and were tested for reinstatement by a stressor (electric footshock), cocaine or an icv injection of CRF and for behavioral responsiveness on the elevated plus maze, in a novel environment and in the light–dark box after a 14- to 17-day extinction/withdrawal period. Results LgA rats showed escalating patterns of cocaine SA and were more susceptible to reinstatement by cocaine, EFS, or icv CRF than ShA rats. Overall, cocaine SA increased activity in the center field of a novel environment, on the open arms of the elevated plus maze, and in the light compartment of a light–dark box. In most cases, the effects of cocaine SA were dependent on the pattern/amount of cocaine intake with statistically significant differences from saline self-administering controls only observed in LgA rats. Conclusions When examined after several weeks of extinction/ withdrawal, cocaine SA promotes a more active pattern of behavior during times of stress that is associated with a heightened susceptibility to stressor-induced cocaine-seeking behavior and may be the consequence of augmented CRF regulation of addiction-related neurocircuitry

Distinct Relationship Between Cognitive Flexibility and White Matter Integrity in Individuals at Risk of Parkinson’s Disease

Background and Objective: Executive dysfunction is the most common cognitive impairment in Parkinson’s disease (PD), occurring even in its early stages. In our study, we applied diffusion tensor imaging (DTI) to investigate white matter integrity and its association with a specific executive function such as cognitive flexibility in individuals with risk factors for PD. Methods: We examined 50 individuals with risk factors for developing PD and 24 healthy controls from the TREND (Tübinger Evaluation of Risk Factors for Early Detection of Neurodegeneration) study including neuropsychological evaluation and DTI. Cognitive flexibility was assessed using the trail making test (TMT). Tract based spatial statistics (TBSS) were employed to assess white matter abnormalities and their correlation with cognitive flexibility. Results: TMT performance correlated with mean and axial diffusivity in several white matter regions, predominantly in the frontoparietal white matter. These effects were stronger in PD risk persons (PD-RP) than in controls as evidenced by a significant group interaction. White matter integrity and TMT performance did not significantly differ across groups. Conclusion: Based on our results, PD-RP do no exhibit white matter changes or impaired cognitive flexibility. However, specific executive functions in PD-RP are more related to white matter alterations than in healthy older adults

Gait decline while dual-tasking is an early sign of white matter deterioration in middle-aged and older adults

Loss of white matter integrity (WMI) is associated with gait deficits in middle-aged and older adults. However, these deficits are often only apparent under cognitively demanding situations, such as walking and simultaneously performing a secondary cognitive task. Moreover, evidence suggests that declining executive functions (EF) are linked to gait decline, and their co-occurrence may point to a common underlying pathology, i.e., degeneration of shared brain regions. In this study, we applied diffusion tensor imaging (DTI) and a standardized gait assessment under single- and dual-tasking (DT) conditions (walking and subtracting) in 74 middle-aged and older adults without any significant gait or cognitive impairments to detect subtle WM alterations associated with gait decline under DT conditions. Additionally, the Trail Making Test (TMT) was used to assess EF, classify participants into three groups based on their performance, and examine a possible interaction between gait, EF, and WMI. Gait speed and subtracting speed while dual-tasking correlated significantly with the fractional anisotropy (FA) in the bilateral anterior corona radiata (highest r = 0.51/p < 0.0125 FWE-corrected). Dual-task costs (DTC) of gait speed correlated significantly with FA in widespread pathways, including the corpus callosum, bilateral anterior and superior corona radiata, as well as the left superior longitudinal fasciculus (highest r = −0.47/p < 0.0125 FWE-corrected). EF performance was associated with FA in the left anterior corona radiata (p < 0.05); however, EF did not significantly mediate the effects of WMI on DTC of gait speed. There were no significant correlations between TMT and DTC of gait and subtracting speed, respectively. Our findings indicate that gait decline under DT conditions is associated with widespread WM deterioration even in middle-aged and older adults without any significant gait or cognitive impairments

Insights into the mechanism of cell death induced by saporin delivered into cancer cells by an antibody fusion protein targeting the transferrin receptor 1

We previously developed an antibody-avidin fusion protein (ch128.1Av) that targets the human transferrin receptor 1 (TfR1) and exhibits direct cytotoxicity against malignant B cells in an iron-dependent manner. ch128.1Av is also a delivery system and its conjugation with biotinylated saporin (b-SO6), a plant ribosome-inactivating toxin, results in a dramatic iron-independent cytotoxicity, both in malignant cells that are sensitive or resistant to ch128.1Av alone, in which the toxin effectively inhibits protein synthesis and triggers caspase activation. We have now found that the ch128.1Av/b-SO6 complex induces a transcriptional response consistent with oxidative stress and DNA damage, a response that is not observed with ch128.1Av alone. Furthermore, we show that the antioxidant N-acetylcysteine partially blocks saporin-induced apoptosis suggesting that oxidative stress contributes to DNA damage and ultimately saporin-induced cell death. Interestingly, the toxin was detected in nuclear extracts by immunoblotting, suggesting the possibility that saporin might induce direct DNA damage. However, confocal microscopy did not show a clear and consistent pattern of intranuclear localization. Finally, using the long-term culture-initiating cell assay we found that ch128.1Av/b-SO6 is not toxic to normal human hematopoietic stem cells suggesting that this critical cell population would be preserved in therapeutic interventions using this immunotoxin.Fil: Daniels Wells, Tracy R.. University of California; Estados Unidos de América;Fil: Helguera, Gustavo Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. University of California; Estados Unidos de América;Fil: Rodríguez, José A.. University of California; Estados Unidos de América;Fil: Leoh, Lai Sum. University of California; Estados Unidos de América;Fil: Erb, Michael A.. University of California; Estados Unidos de América;Fil: Diamante, Graciel. University of California; Estados Unidos de América;Fil: Casero, David. University Of California; Estados Unidos de América;Fil: Pellegrini, Mateo. University of California; Estados Unidos de América;Fil: Martinez Maza, Otoniel. University of California; Estados Unidos de América;Fil: Penichet, Manuel L.. University of California; Estados Unidos de América

Hubble Space Telescope WFC3 Early Release Science: Emission-Line Galaxies from Infrared Grism Observations

We present grism spectra of emission-line galaxies (ELGs) from 0.6-1.6 microns from the Wide Field Camera 3 on the Hubble Space Telescope. These new infrared grism data augment previous optical Advanced Camera for Surveys G800L 0.6-0.95 micron grism data in GOODS-South from the PEARS program, extending the wavelength covereage well past the G800L red cutoff. The ERS grism field was observed at a depth of 2 orbits per grism, yielding spectra of hundreds of faint objects, a subset of which are presented here. ELGs are studied via the Ha, [OIII], and [OII] emission lines detected in the redshift ranges 0.2<z<1.4, 1.2<z<2.2 and 2.0<z<3.3 respectively in the G102 (0.8-1.1 microns; R~210) and G141 (1.1-1.6 microns; R~130) grisms. The higher spectral resolution afforded by the WFC3 grisms also reveals emission lines not detectable with the G800L grism (e.g., [SII] and [SIII] lines). From these relatively shallow observations, line luminosities, star-formation rates, and grism spectroscopic redshifts are determined for a total of 48 ELGs to m(AB)~25 mag. Seventeen GOODS-South galaxies that previously only had photometric redshifts now have new grism-spectroscopic redshifts, in some cases with large corrections to the photometric redshifts (Delta(z)~0.3-0.5). Additionally, one galaxy had no previously-measured redshift but now has a secure grism-spectroscopic redshift, for a total of 18 new GOODS-South spectroscopic redshifts. The faintest source in our sample has a magnitude m(AB)=26.9 mag. The ERS grism data also reflect the expected trend of lower specific star formation rates for the highest mass galaxies in the sample as a function of redshift, consistent with downsizing and discovered previously from large surveys. These results demonstrate the remarkable efficiency and capability of the WFC3 NIR grisms for measuring galaxy properties to faint magnitudes and redshifts to z>2.Comment: Accepted for publication in AJ. Updated to include referee comments. Updated sample using improved reduction contains 23 new galaxies (Table 1; Figures 2 & 3

Local Lyman Break Galaxy Analogs: The Impact of Massive Star-forming Clumps on the Interstellar Medium and the Global Structure of Young, Forming Galaxies

We present HST UV/optical imaging, Spitzer mid-IR photometry, and optical spectroscopy of a sample of 30 low-redshift (z=0.1-0.3) galaxies chosen from SDSS/GALEX to be accurate local analogs of the high-z Lyman Break Galaxies. The Lyman Break Analogs (LBAs) are similar in mass, metallicity, dust, SFR, size and gas velocity dispersion, thus enabling a detailed investigation of processes that are important at high-z. The optical emission line properties of LBAs are also similar to those of LBGs, indicating comparable conditions in their ISM. In the UV, LBAs are characterized by complexes of massive star-forming "clumps", while in the optical they most often show evidence for (post-)mergers/interactions. In 6 cases, we find an extremely massive (>10^9 Msun) compact (R~100 pc) dominant central object (DCO). The DCOs are preferentially found in LBAs with the highest mid-IR luminosities and correspondingly high SFRs (15-100 Msun/yr). We show that the massive SF clumps (including the DCOs) have masses much larger than the nuclear super star clusters seen in normal late type galaxies. However, the DCOs have masses, sizes, and densities similar to the excess-light/central-cusps seen in typical elliptical galaxies with masses similar to the LBA galaxies. We suggest that the DCOs form in present-day examples of the dissipative mergers at high redshift that are believed to have produced the central-cusps in local ellipticals. More generally, the properties of the LBAs are consistent with the idea that instabilities in a gas-rich disk lead to very massive star-forming clumps that eventually coalesce to form a spheroid. We speculate that the DCOs are too young at present to be growing a supermassive black hole because they are still in a supernova-dominated outflow phase.Comment: The Astrophysical Journal, In Press (22 pages, 16 figures). For the full version with high-resolution colour figures, see: http://www.mpa-garching.mpg.de/~overzier/Overzier_LBApaper09.pd

Additions to the Last Millennium Reanalysis Multi-Proxy Database

Progress in paleoclimatology increasingly occurs via data syntheses. We describe additions to a collection prepared for use in paleoclimate state estimation, specifically the Last Millennium Reanalysis (LMR). The 2290 additional series include 2152 tree ring chronologies and 138 other series. They supplement the collection used previously and together form a database titled LMRdb 1.0.0. The additional data draws from lake core, ice core, coral, speleothem, and tree ring archives, using published data primarily from the NOAA Paleoclimatology archive and a set of tree ring width chronologies standardized from raw International Tree Ring Data Bank ring width series. In contrast to many previous paleo compilations, the data were not selected (screened) on the basis of their environmental correlation, multi-century length, or other attributes. The inclusion of proxies sensitive to moisture and other environmental variables expands their use in data assimilation. A preliminary calibration using linear regression with mean annual temperature reveals characteristics of the proxy series and their relationship to temperature, as well as the noise and error characteristics of the records. The additional records are structured as individual files in the NOAA Paleoclimatology format and archived at NOAA Paleoclimatology (Anderson et al. 2018) and will continue to be improved and expanded as part of the LMR Project. The additions represent a four-fold increase in the number of records available for assimilation, provide expanded geographic coverage, and add additional proxy variables. Applications include data assimilation, proxy system model development, and paleoclimate reconstruction using climate field reconstruction and other methods

The Epoch of Disk Settling: z~1 to Now

We present evidence from a sample of 544 galaxies from the DEEP2 Survey for evolution of the internal kinematics of blue galaxies with stellar masses ranging 8.0 < log M* (M_Sun) < 10.7 over 0.2<z<1.2. DEEP2 provides galaxy spectra and Hubble imaging from which we measure emission-line kinematics and galaxy inclinations, respectively. Our large sample allows us to overcome scatter intrinsic to galaxy properties in order to examine trends in kinematics. We find that at a fixed stellar mass galaxies systematically decrease in disordered motions and increase in rotation velocity and potential well depth with time. Massive galaxies are the most well-ordered at all times examined, with higher rotation velocities and less disordered motions than less massive galaxies. We quantify disordered motions with an integrated gas velocity dispersion corrected for beam smearing (sigma_g). It is unlike the typical pressure-supported velocity dispersion measured for early type galaxies and galaxy bulges. Because both seeing and the width of our spectral slits comprise a significant fraction of the galaxy sizes, sigma_g integrates over velocity gradients on large scales which can correspond to non-ordered gas kinematics. We compile measurements of galaxy kinematics from the literature over 1.2<z<3.8 and do not find any trends with redshift, likely for the most part because these datasets are biased toward the most highly star-forming systems. In summary, over the last ~8 billion years since z=1.2, blue galaxies evolve from disordered to ordered systems as they settle to become the rotation-dominated disk galaxies observed in the Universe today, with the most massive galaxies being the most evolved at any time.Comment: submitted to ApJ and responded to referee repor