Motor abnormalities, depression risk, and clinical course in adolescence.

Background Motor abnormalities, such as psychomotor agitation and retardation, are widely recognized as core features of depression. However, it is not currently known if motor abnormalities connote risk for depression. Methods Using data from the Adolescent Brain Cognitive Development (ABCD) Study, a nationally representative sample of youth (n=10,835, 9-11 years old), the present paper examines whether motor abnormalities are associated with (a) depression symptoms in early adolescence, (b) familial risk for depression (familial risk loading), and (c) future depression symptoms. Motor abnormalities measures included traditional (DSM) motor signs such as psychomotor agitation and retardation as well as other motor domains such as developmental motor delays and dyscoordination. Results Traditional motor abnormalities were less prevalent (agitation=3.2%, retardation=0.3%) than non-traditional domains (delays=13.79%, coordination=35.5%) among adolescents. Motor dysfunction was associated with depression symptoms (Cohen's ds=0.02 to 0.12). Familial risk for depression was related to motor abnormalities (Cohen's ds=0.08 to 0.27), with the exception of motor retardation. Family vulnerability varied in sensitivity to depression risk (e.g., retardation: .53%; dyscoordination: 32.05%). Baseline endorsement of motor abnormalities predicted future depression symptoms at one-year follow-up. Conclusions These findings suggest that motor signs reflect a novel, promising future direction for examining vulnerability to depression risk in early adolescence

Overview of MPLNET Version 3 Cloud Detection

The National Aeronautics and Space Administration Micro Pulse Lidar Network, version 3, cloud detection algorithm is described and differences relative to the previous version are highlighted. Clouds are identified from normalized level 1 signal profiles using two complementary methods. The first method considers vertical signal derivatives for detecting low-level clouds. The second method, which detects high-level clouds like cirrus, is based on signal uncertainties necessitated by the relatively low signal-to-noise ratio exhibited in the upper troposphere by eye-safe network instruments, especially during daytime. Furthermore, a multitemporal averaging scheme is used to improve cloud detection under conditions of a weak signal-to-noise ratio. Diurnal and seasonal cycles of cloud occurrence frequency based on one year of measurements at the Goddard Space Flight Center (Greenbelt, Maryland) site are compared for the new and previous versions. The largest differences, and perceived improvement, in detection occurs for high clouds (above 5 km, above MSL), which increase in occurrence by over 5%. There is also an increase in the detection of multilayered cloud profiles from 9% to 19%. Macrophysical properties and estimates of cloud optical depth are presented for a transparent cirrus dataset. However, the limit to which the cirrus cloud optical depth could be reliably estimated occurs between 0.5 and 0.8. A comparison using collocated CALIPSO measurements at the Goddard Space Flight Center and Singapore Micro Pulse Lidar Network (MPLNET) sites indicates improvements in cloud occurrence frequencies and layer heights

Hand gesture performance is impaired in major depressive disorder: A matter of working memory performance?

OBJECTIVE Individuals with depression exhibit numerous interpersonal deficits. As effective use of gestures is critical for social communication, it is possible that depressed individuals' interpersonal deficits may be due to deficits in gesture performance. The present study thus compared gesture performance of depressed patients and controls and examined whether these deficits relate to cognitive and other domains of dysfunction. METHODS Gesture performance was evaluated in 30 depressed patients and 30 controls using the Test of Upper Limb Apraxia (TULIA). Clinical rating scales were assessed to determine if gesture deficits were associated with motor, cognitive or functional outcomes. RESULTS Compared to controls, depressed patients exhibited impaired gesture performance with 2/3 of the patients demonstrating gesture deficits. Within depressed patients, gesture performance was highly correlated with working memory abilities. In contrast, no association between gesture performance and gestural knowledge, psychomotor retardation, depression severity, or frontal dysfunction was observed in patients. LIMITATIONS This is a cross-sectional study and a larger size would have allowed for confident detection of more subtle, but potentially relevant effects. CONCLUSION Gesture performance is impaired in depressed patients, and appears to be related to poor working memory abilities, suggesting a disruption in the retrieval of gestural cues indicative of a distinct clinical phenomenon that might be related to social functioning

Stress Resistance and Longevity Are Not Directly Linked to Levels of Enzymatic Antioxidants in the Ponerine Ant Harpegnathos saltator

BACKGROUND: The molecular mechanisms of variations in individual longevity are not well understood, even though longevity can be increased substantially by means of diverse experimental manipulations. One of the factors supposed to be involved in the increase of longevity is a higher stress resistance. To test this hypothesis in a natural system, eusocial insects such as bees or ants are ideally suited. In contrast to most other eusocial insects, ponerine ants show a peculiar life history that comprises the possibility to switch during adult life from a normal worker to a reproductive gamergate, therewith increasing their life expectancy significantly. RESULTS: We show that increased resistance against major stressors, such as reactive oxygen species and infection accompanies the switch from a life-history trait with normal lifespan to one with a longer life expectancy. A short period of social isolation was sufficient to enhance stress resistance of workers from the ponerine ant species Harpegnathos saltator significantly. All ant groups with increased stress resistances (reproducing gamergates and socially isolated workers) have lower catalase activities and glutathione levels than normal workers. Therewith, these ants resemble the characteristics of the youngest ants in the colony. CONCLUSIONS: Social insects with their specific life history including a switch from normal workers to reproducing gamergates during adult life are well suited for ageing research. The regulation of stress resistance in gamergates seemed to be modified compared to foraging workers in an economic way. Interestingly, a switch towards more stress resistant animals can also be induced by a brief period of social isolation, which may already be associated with a shift to a reproductive trajectory. In Harpegnathos saltator, stress resistances are differently and potentially more economically regulated in reproductive individuals, highlighting the significance of reproduction for an increase in longevity in social insects. As already shown for other organisms with a long lifespan, this trait is not directly coupled to higher levels of enzymatic and non-enzymatic antioxidants

RARγ is critical for maintaining a balance between hematopoietic stem cell self-renewal and differentiation

Hematopoietic stem cells (HSCs) sustain lifelong production of all blood cell types through finely balanced divisions leading to self-renewal and differentiation. Although several genes influencing HSC self-renewal have been identified, to date no gene has been described that, when activated, enhances HSC self-renewal and, when activated, promotes HSC differentiation. We observe that the retinoic acid receptor (RAR)γ is selectively expressed in primitive hematopoietic precursors and that the bone marrow of RARγ knockout mice exhibit markedly reduced numbers of HSCs associated with increased numbers of more mature progenitor cells compared with wild-type mice. In contrast, RARα is widely expressed in hematopoietic cells, but RARα knockout mice do not exhibit any HSC or progenitor abnormalities. Primitive hematopoietic precursors overexpressing RARα differentiate predominantly to granulocytes in short-term culture, whereas those overexpressing RARγ exhibit a much more undifferentiated phenotype. Furthermore, loss of RARγ abrogated the potentiating effects of all-trans retinoic acid on the maintenance of HSCs in ex vivo culture. Finally, pharmacological activation of RARγ ex vivo promotes HSC self-renewal, as demonstrated by serial transplant studies. We conclude that the RARs have distinct roles in hematopoiesis and that RARγ is a critical physiological and pharmacological regulator of the balance between HSC self-renewal and differentiation

Behavioral and Other Phenotypes in a Cytoplasmic Dynein Light Intermediate Chain 1 Mutant Mouse

The cytoplasmic dynein complex is fundamentally important to all eukaryotic cells for transporting a variety of essential cargoes along microtubules within the cell. This complex also plays more specialized roles in neurons. The complex consists of 11 types of protein that interact with each other and with external adaptors, regulators and cargoes. Despite the importance of the cytoplasmic dynein complex, we know comparatively little of the roles of each component protein, and in mammals few mutants exist that allow us to explore the effects of defects in dynein-controlled processes in the context of the whole organism. Here we have taken a genotype-driven approach in mouse (Mus musculus) to analyze the role of one subunit, the dynein light intermediate chain 1 (Dync1li1). We find that, surprisingly, an N235Y point mutation in this protein results in altered neuronal development, as shown from in vivo studies in the developing cortex, and analyses of electrophysiological function. Moreover, mutant mice display increased anxiety, thus linking dynein functions to a behavioral phenotype in mammals for the first time. These results demonstrate the important role that dynein-controlled processes play in the correct development and function of the mammalian nervous system

Unusually Deep Wintertime Cirrus Clouds Observed over the Alaskan Sub-Arctic

Unusually deep wintertime cirrus clouds at altitudes exceeding 13.0 km above mean sea level (AMSL) were observed at Fairbanks, Alaska (64.86 N, 147.85 W, 0.300 km AMSL) over a twelve hour period, beginning near 1200 UTC 1 January 2017. Such elevated cirrus cloud heights are far more typical of warmer latitudes, and in many instances associated with convective outflow, as opposed to early winter over the sub-Arctic on a day featuring barely four hours of local sunlight. In any other context, they could have been confused for polar stratospheric clouds, which are a more common regional/seasonal occurrence at elevated heights. The mechanics of this unique event are documented, including the thermodynamic and synoptic environments that nurtured and sustained cloud formation. The impact of an unusually deep and broad anticyclone over the wintertime Alaskan sub-Arctic is described. Comparisons with climatological datasets illustrate how unusual these events are regionally and seasonally. The event proves a relatively uncharacteristic confluence of circulatory and dynamic features over the wintertime Alaskan sub-Arctic. Our goal is to document the occurrence of this event within the context of a growing understanding for how cirrus cloud incidence and their physical characteristics vary globally. Cirrus clouds are unique within the earth-atmosphere system. Formed by the freezing of submicron haze particles in the upper troposphere, they are the last primary cloud mechanism contributing to the large scale exchange of the terrestrial water cycle. Accordingly, cirrus clouds are observed globally at all times of the year, exhibiting an instantaneous global occurrence rate near 40%. Radiatively, however, they are even more distinct. During daylight hours, cirrus are the only cloud genus that can induce either positive or negative top-of-the-atmosphere forcing (i.e., heating or cooling; all other clouds induce a negative sunlit cooling effect). Though diffuse compared with low-level liquid water clouds, their significance radiatively and thus within climate, is borne out of their overwhelming relative occurrence rate. This emerging recognition makes understanding cirrus cloud occurrence and physical cloud properties an innovative and exciting element of current climate study. The observations described here contribute to this knowledge, and the apparent potential for anomalous wintertime radiative characteristics exhibited along sub-Arctic latitudes

Deficiency of the zinc finger protein ZFP106 causes motor and sensory neurodegeneration

Acknowledgements We are indebted to Jim Humphries, JennyCorrigan, LizDarley, Elizabeth Joynson, Natalie Walters, Sara Wells and the whole necropsy, histology, genotyping and MLC ward 6 teams at MRC Harwell for excellent technical assistance. We thank the staff of the WTSI Illumina Bespoke Team for the RNA-seq data, the Sanger Mouse Genetics Project for the initial mouse characterization and Dr David Adams for critical reading of the manuscript. We also thank KOMP for the mouse embryonic stem cells carrying the knockout first promoter-less allele (tm1a(KOMP)Wtsi) within Zfp016. Conflict of Interest statement. None declared. Funding This work was funded by the UK Medical Research Council (MRC) to A.A.-A. and a Motor Neurone Disease Association (MNDA) project grant to A.A.-A. and EMCF. D.L.H.B. is a Wellcome Trust Senior Clinical Scientist Fellow and P.F. is a MRC/MNDA Lady Edith Wolfson Clinician Scientist Fellow. Funding to pay the Open Access publication charges for this article was provided by the MRC grant number: MC_UP_A390_1106.Peer reviewedPublisher PD

Most viral peptides displayed by class I MHC on infected cells are immunogenic

CD8+ T cells are essential effectors in antiviral immunity, recognizing short virus-derived peptides presented by MHC class I (pMHCI) on the surface of infected cells. However, the fraction of viral pMHCI on infected cells that are immunogenic has not been shown for any virus. To approach this fundamental question, we used peptide sequencing by high-resolution mass spectrometry to identify more than 170 vaccinia virus pMHCI presented on infected mouse cells. Next, we screened each peptide for immunogenicity in multiple virus-infected mice, revealing a wide range of immunogenicities. A surprisingly high fraction (>80%) of pMHCI were immunogenic in at least one infected mouse, and nearly 40% were immunogenic across more than half of the mice screened. The high number of peptides found to be immunogenic and the distribution of responses across mice give us insight into the specificity of antiviral CD8+ T cell responses.This work was supported by a Project Grant from the National Health and Medical Research Council Australia (NHMRC) (APP1084283) (to D.C.T., A.W.P., and N.P.C.); an NHMRC Senior Research Fellowship (APP1104329) (to D.C.T.); an NHMRC Principal Research Fellowship (APP1137739) (to A.W.P.); and a Viertel Fellowship, ARC Future Fellowship, and NHMRC Program Grant (APP1071916) (to N.L.L.G.)