The Neuronal EGF-Related Gene Nell2 Interacts with Macf1 and Supports Survival of Retinal Ganglion Cells after Optic Nerve Injury

Nell2 is a neuron-specific protein containing six epidermal growth factor-like domains. We have identified Nell2 as a retinal ganglion cell (RGC)-expressed gene by comparing mRNA profiles of control and RGC-deficient rat retinas. The aim of this study was to analyze Nell2 expression in wild-type and optic nerve axotomized retinas and evaluate its potential role in RGCs. Nell2-positive in situ and immunohistochemical signals were localized to irregularly shaped cells in the ganglion cell layer (GCL) and colocalized with retrogradely-labeled RGCs. No Nell2-positive cells were detected in 2 weeks optic nerve transected (ONT) retinas characterized with approximately 90% RGC loss. RT-PCR analysis showed a dramatic decrease in the Nell2 mRNA level after ONT compared to the controls. Immunoblot analysis of the Nell2 expression in the retina revealed the presence of two proteins with approximate MW of 140 and 90 kDa representing glycosylated and non-glycosylated Nell2, respectively. Both products were almost undetectable in retinal protein extracts two weeks after ONT. Proteome analysis of Nell2-interacting proteins carried out with MALDI-TOF MS (MS) identified microtubule-actin crosslinking factor 1 (Macf1), known to be critical in CNS development. Strong Macf1 expression was observed in the inner plexiform layer and GCL where it was colocalizied with Thy-1 staining. Since Nell2 has been reported to increase neuronal survival of the hippocampus and cerebral cortex, we evaluated the effect of Nell2 overexpression on RGC survival. RGCs in the nasal retina were consistently more efficiently transfected than in other areas (49% vs. 13%; n = 5, p<0.05). In non-transfected or pEGFP-transfected ONT retinas, the loss of RGCs was approximately 90% compared to the untreated control. In the nasal region, Nell2 transfection led to the preservation of approximately 58% more cells damaged by axotomy compared to non-transfected (n = 5, p<0.01) or pEGFP-transfected controls (n = 5, p<0.01)

Network analysis of human glaucomatous optic nerve head astrocytes

<p>Abstract</p> <p>Background</p> <p>Astrocyte activation is a characteristic response to injury in the central nervous system, and can be either neurotoxic or neuroprotective, while the regulation of both roles remains elusive.</p> <p>Methods</p> <p>To decipher the regulatory elements controlling astrocyte-mediated neurotoxicity in glaucoma, we conducted a systems-level functional analysis of gene expression, proteomic and genetic data associated with reactive optic nerve head astrocytes (ONHAs).</p> <p>Results</p> <p>Our reconstruction of the molecular interactions affected by glaucoma revealed multi-domain biological networks controlling activation of ONHAs at the level of intercellular stimuli, intracellular signaling and core effectors. The analysis revealed that synergistic action of the transcription factors AP-1, vitamin D receptor and Nuclear Factor-kappaB in cross-activation of multiple pathways, including inflammatory cytokines, complement, clusterin, ephrins, and multiple metabolic pathways. We found that the products of over two thirds of genes linked to glaucoma by genetic analysis can be functionally interconnected into one epistatic network via experimentally-validated interactions. Finally, we built and analyzed an integrative disease pathology network from a combined set of genes revealed in genetic studies, genes differentially expressed in glaucoma and closely connected genes/proteins in the interactome.</p> <p>Conclusion</p> <p>Our results suggest several key biological network modules that are involved in regulating neurotoxicity of reactive astrocytes in glaucoma, and comprise potential targets for cell-based therapy.</p

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Long-term results after a triple arthrodesis of the hindfoot: function and satisfaction in 36 patients

The long-term functional results of a triple arthrodesis of the hindfoot are not well known. In this retrospective cohort study we therefore investigated pain, function and aligment of the tibiotalar joint, patient satisfaction with the procedure and the prevalence of osteoarthritis (OA) of the tibiotalar joint after a median follow-up of six years. We also aimed to investigate whether there are patient and surgical characteristics associated with the outcome. Patients who underwent a triple arthrodesis for OA between January 1992 and July 2002 were invited to participate. A clinical examination was performed, the Ankle-Hindfoot Scale was completed, and radiographs were taken. Patient characteristics (e.g., age, gender and the indication for operation) and surgical characteristics (e.g., fixation material and use of bone graft) were collected. Sixty-one percent (22 patients) of the patients had a good total score on the Ankle-Hindfoot Scale. Nineteen patients (53%) were satisfied with the result of the operation and 47% of the patients had radiographic OA of the tibiotalar joint. In a univariate regression analysis, male gender and the score on the Ankle-Hindfoot Scale were significantly associated with radiographic OA. Patient satisfaction was significantly associated with a higher score on the Ankle-Hindfoot Scale and better dorsi–flexion of the ankle. Our study shows that 61% of the procedures in 36 patients with a triple arthrodesis for OA had a good score on the Ankle-Hindfoot Scale. Radiographic OA of the ankle was present in 47% of the cases and was not related to patient satisfaction. No patient characteristics or surgical characteristics were associated with the score on the Ankle-Hindfoot Scale

Patterns of pollen and nectar foraging specialization by bumblebees over multiple timescales using RFID

The ecological success of social insects is frequently ascribed to improvements in task performance due to division of labour amongst workers. While much research has focused on improvements associated with lifetime task specialization, members of colonies can specialize on a given task over shorter time periods. Eusocial bees in particular must collect pollen and nectar rewards to survive, but most workers appear to mix collection of both rewards over their lifetimes. We asked whether bumblebees specialize over timescales shorter than their lifetime. We also explored factors that govern such patterns, and asked whether reward specialists made more foraging bouts than generalists. In particular, we described antennal morphology and size of all foragers in a single colony and related these factors to each forager's complete foraging history, obtained using radio frequency identification (RFID). Only a small proportion of foragers were lifetime specialists; nevertheless, >50% of foragers specialized daily on a given reward. Contrary to expectations, daily and lifetime reward specialists were not better foragers (being neither larger nor making more bouts); larger bees with more antennal olfactory sensilla made more bouts, but were not more specialized. We discuss causes and functions of short and long-term patterns of specialization for bumblebee colonies.University of Arizona Graduate & Professional Student Council; University of Arizona Center for Insect Science; National Science Foundation [IOS-0921280]This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]