Infection of Mice with the Agent of Human Granulocytic Ehrlichiosis after Different Routes of Inoculation

Population kinetics of the agent of human granulocytic ehrlichiosis (aoHGE) were examined after needle and tickborne inoculation of C3H mice. Blood, skin, lung, spleen, liver, kidney, brain, lymph node, and bone marrow samples were analyzed by using real-time polymerase chain reaction (PCR) at various intervals after inoculation, using a p44 gene target. The highest number of copies of the p44 gene target occurred in blood and bone marrow samples, emphasizing aoHGE leukocytotropism. Numbers of copies of the p44 gene target in other tissues reflected vascular perfusion rather than replication. Needle-inoculated infected mice had earlier dissemination, but kinetics of infection in both groups were parallel, with declining rates of infection by day 20 and recovery in some mice on days 20-60 after inoculation. On the basis of an aoHGE lysate ELISA, mice seroconverted by day 10 after inoculation. Therefore, real-time PCR is useful for quantitative studies with the aoHGE in experimental infections, and results showed that needle inoculation can be used to study the aoHGE infection because of its similarity to tickborne inoculatio

Using 2D and 3D pluripotent stem cell models to study neurotropic viruses

Understanding the impact of viral pathogens on the human central nervous system (CNS) has been challenging due to the lack of viable human CNS models for controlled experiments to determine the causal factors underlying pathogenesis. Human embryonic stem cells (ESCs) and, more recently, cellular reprogramming of adult somatic cells to generate human induced pluripotent stem cells (iPSCs) provide opportunities for directed differentiation to neural cells that can be used to evaluate the impact of known and emerging viruses on neural cell types. Pluripotent stem cells (PSCs) can be induced to neural lineages in either two- (2D) or three-dimensional (3D) cultures, each bearing distinct advantages and limitations for modeling viral pathogenesis and evaluating effective therapeutics. Here we review the current state of technology in stem cell-based modeling of the CNS and how these models can be used to determine viral tropism and identify cellular phenotypes to investigate virus-host interactions and facilitate drug screening. We focus on several viruses (e.g., human immunodeficiency virus (HIV), herpes simplex virus (HSV), Zika virus (ZIKV), human cytomegalovirus (HCMV), SARS-CoV-2, West Nile virus (WNV)) to illustrate key advantages, as well as challenges, of PSC-based models. We also discuss how human PSC-based models can be used to evaluate the safety and efficacy of therapeutic drugs by generating data that are complementary to existing preclinical models. Ultimately, these efforts could facilitate the movement towards personalized medicine and provide patients and physicians with an additional source of information to consider when evaluating available treatment strategies

Moving Toward, Moving Against, and Moving Away: An Interpersonal Approach to Construct Validation of the Horney–Coolidge Type Inventory

Karen Horney’s interpersonal theory of adjustment defined three different neurotic trends involving characteristic social behavior and motives: compliant (moving toward people), aggressive (moving against people), and detached (moving away from people). The Horney–Coolidge Type Inventory (HCTI) was developed to assess these trends, but has not been validated using standard methods in the interpersonal perspective. The studies reported here refined the structure of the HCTI, and utilized the structural summary method (SSM) to identify relationships of the three shortened HCTI trend scales with the interpersonal circumplex (IPC) in single university (n = 514) and multisite university (n = 3,283) samples. Results across both studies confirmed predicted interpersonal characteristics of each trend: Compliance was associated with warm submissiveness, aggression was associated with hostile dominance, and detachment was associated with hostile or cold submissiveness. However, analyses of facets within the three HCTI trend domains revealed significant differences. Results are discussed as a potential guide to further refinement of assessments of the Horney maladaptive trends, and support inclusion of Horney’s model in current interpersonal theory

WormBase 2012: more genomes, more data, new website

Since its release in 2000, WormBase (http://www.wormbase.org) has grown from a small resource focusing on a single species and serving a dedicated research community, to one now spanning 15 species essential to the broader biomedical and agricultural research fields. To enhance the rate of curation, we have automated the identification of key data in the scientific literature and use similar methodology for data extraction. To ease access to the data, we are collaborating with journals to link entities in research publications to their report pages at WormBase. To facilitate discovery, we have added new views of the data, integrated large-scale datasets and expanded descriptions of models for human disease. Finally, we have introduced a dramatic overhaul of the WormBase website for public beta testing. Designed to balance complexity and usability, the new site is species-agnostic, highly customizable, and interactive. Casual users and developers alike will be able to leverage the public RESTful application programming interface (API) to generate custom data mining solutions and extensions to the site. We report on the growth of our database and on our work in keeping pace with the growing demand for data, efforts to anticipate the requirements of users and new collaborations with the larger science community

Rheb1 mediates DISC1-dependent regulation of new neuron development in the adult hippocampus

Acknowledgments: We thank D. Weinberger, D. St. Clair and D. Valle for discussion, Jaden Shin for gene expression analyses, members of Ming and Song Laboratories for help and critical comments, L. Liu, Y. Cai, Q. Hussaini, and M. Jardine-Alborz for technical support. Funding: This work was supported by NIH (NS048271, MH105128), NARSAD, and MSCRF to G-l.M., by NIH (NS047344 and NS093772) and MSCRF to H.S., by NARSAD and NIH (NS093772) to K.C., and by NARSAD to E.K.Peer reviewedPublisher PD

K2 Discovers a Busy Bee: An Unusual Transiting Neptune Found in the Beehive Cluster

Open clusters have been the focus of several exoplanet surveys but only a few planets have so far been discovered. The \emph{Kepler} spacecraft revealed an abundance of small planets around small, cool stars, therefore, such cluster members are prime targets for exoplanet transit searches. Kepler's new mission, K2, is targeting several open clusters and star-forming regions around the ecliptic to search for transiting planets around their low-mass constituents. Here, we report the discovery of the first transiting planet in the intermediate-age (800 Myr) Beehive cluster (Praesepe). K2-95 is a faint ($\mathrm{Kp = 15.5\,mag}$) $\mathrm{M3.0\pm0.5}$ dwarf from K2's Campaign 5 with an effective temperature of $\mathrm{3471 \pm 124\,K}$, approximately solar metallicity and a radius of $\mathrm{0.402 \pm 0.050 \,R_\odot}$. We detected a transiting planet with a radius of $\mathrm{3.47^{+0.78}_{-0.53} \, R_\oplus}$ and an orbital period of 10.134 days. We combined photometry, medium/high-resolution spectroscopy, adaptive optics/speckle imaging and archival survey images to rule out any false positive detection scenarios, validate the planet, and further characterize the system. The planet's radius is very unusual as M-dwarf field stars rarely have Neptune-sized transiting planets. The comparatively large radius of K2-95b is consistent with the other recently discovered cluster planets K2-25b (Hyades) and K2-33b (Upper Scorpius), indicating systematic differences in their evolutionary states or formation. These discoveries from K2 provide a snapshot of planet formation and evolution in cluster environments and thus make excellent laboratories to test differences between field-star and cluster planet populations.Comment: 14 pages, 8 figues. Accepted for publication in A

Brain-specific Crmp2 deletion leads to neuronal development deficits and behavioural impairments in mice

Acknowledgements: This work was supported by grants from NSF (31430037/31271156/ 31270826) and MOST (2014CB942801/2012CB517904/2012YQ03026006) to Z.X.; from NIH (NS048271, MH105128) to G.-l.M., from NIH (NS047344) to H.S., and from NRASAD to E.K. and K.M.C. Author notes: Hongsheng Zhang, Eunchai Kang and Yaqing Wang: These authors contributed equally to this work.Peer reviewedPublisher PD

ICA model order selection of task co-activation networks

Independent component analysis (ICA) has become a widely used method for extracting functional networks in the brain during rest and task. Historically, preferred ICA dimensionality has widely varied within the neuroimaging community, but typically varies between 20 and 100 components. This can be problematic when comparing results across multiple studies because of the impact ICA dimensionality has on the topology of its resultant components. Recent studies have demonstrated that ICA can be applied to peak activation coordinates archived in a large neuroimaging database (i.e., BrainMap Database) to yield whole-brain task-based co-activation networks. A strength of applying ICA to BrainMap data is that the vast amount of metadata in BrainMap can be used to quantitatively assess tasks and cognitive processes contributing to each component. In this study, we investigated the effect of model order on the distribution of functional properties across networks as a method for identifying the most informative decompositions of BrainMap-based ICA components. Our findings suggest dimensionality of 20 for low model order ICA to examine large-scale brain networks, and dimensionality of 70 to provide insight into how large-scale networks fractionate into sub-networks. We also provide a functional and organizational assessment of visual, motor, emotion, and interoceptive task co-activation networks as they fractionate from low to high model-orders

Induction of Group IVC Phospholipase A2 in Allergic Asthma: Transcriptional Regulation by TNF-α in Bronchoepithelial Cells

Airway inflammation in allergen-induced asthma is associated with eicosanoid release. These bioactive lipids exhibit anti- and pro-inflammatory activities with relevance to pulmonary pathophysiology. We hypothesized that sensitization/challenge using an extract from the ubiquitous fungus, Aspergillus fumigatus (Af), in a mouse model of allergic asthma would result in altered phospholipase gene expression, thus modulating the downstream eicosanoid pathway. We observed the most significant induction in the group IVC phospholipase A2 (cPLA2γ or PLA2G4C). Our results infer that Af extract can induce cPLA2γ levels directly in eosinophils while induction in lung epithelial cells is most likely a consequence of TNF-α secretion by Af-activated macrophages. The mechanism of TNF-α-dependent induction of cPLA2γ gene expression was elucidated through a combination of promoter deletions, ChIP and overexpression studies in human bronchoepithelial cells, leading to the identification of functionally relevant CRE, NF-κB and E-box promoter elements. ChIP analysis demonstrated that RNA polymerase II, c-Jun/ATF-2, p65/p65 and USF1/USF2 complexes are recruited to the cPLA2γ enhancer/promoter in response to TNF-α with overexpression and dominant negative studies implying a strong level of cooperation and interplay between these factors. Overall, our data link cytokine-mediated alterations in cPLA2γ gene expression with allergic asthma and outline a complex regulatory mechanism