Phosphorylation of the neurofilament proteins of high and medium relative molecular mass, as well as of the Alzheimer's tau protein, is thought to be catalysed by a protein kinase with Cdc2-like substrate specificity. We have purified a novel Cdc2-like kinase from bovine brain capable of phosphorylating both the neurofilament proteins and tau. The purified enzyme is a heterodimer of cyclin-dependent kinase 5 (Cdk5) and a novel regulatory subunit, p25 (ref. 8). When overexpressed and purified from Escherichia coli, p25 can activate Cdk5 in vitro. Unlike Cdk5, which is ubiquitously expressed in human tissue, the p25 transcript is expressed only in brain. A full-length complementary DNA clone showed that p25 is a truncated form of a larger protein precursor, p35, which seems to be the predominant form of the protein in crude brain extract. Cdk5/p35 is the first example of a Cdc2-like kinase with neuronal function.

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In this study, we determined and genetically characterized three fowl adenoviruses isolated from chickens with inclusion body hepatitis (IBH) and hydropericardium syndrome (HPS) in China and assessed their pathogenicity. The full genome of HBQ12, BJH13 and JSJ13 was found to be 44,081, 43,966 and 43,756 nucleotides long, respectively. Sequence alignment and phylogenetic analysis revealed that strain HBQ12 and BJH13 were clustered together belonging to fowl adenoviruses D species and serotyped as FAdV-11, whereas strain JSJ13 was classified into fowl adenoviruses C species and serotyped as FAdV-4. To our knowledge, this is the first report of FAdV-4 strain circulating in China. The pathogenicity test showed that mortality for chickens infected with HBQ12 and JSJ13 within 21 days post infection (dpi) was 8.6% and 28.6%, respectively. Necropsy displayed mild or severe hepatitis and hydropericardium at 3 and 5 dpi as well as dead chickens. Viral DNA was detected in almost all tissues sampled from dead chickens. These results revealed that fowl adenovirus strains HBQ12 and JSJ13 are capable of causing IBH and HPS in chickens, indicating that preventive measures against FAdV infection on poultry farms should be implemented in China.

Background: The safety of performing spinal anaesthesia for both patients and anaesthetists alike in the presence of active infection with the novel coronavirus disease 2019 (COVID-19) is unclear. Here, we report the clinical characteristics and outcomes for both patients with COVID-19 and the anaesthetists who provided their spinal anaesthesia. Methods: Forty-nine patients with radiologically confirmed COVID-19 for Caesarean section or lower-limb surgery undergoing spinal anaesthesia in Zhongnan Hospital, Wuhan, China participated in this retrospective study. Clinical characteristics and perioperative outcomes were recorded. For anaesthesiologists exposed to patients with COVID-19 by providing spinal anaesthesia, the level of personal protective equipment (PPE) used, clinical outcomes (pulmonary CT scans), and confirmed COVID-19 transmission rates (polymerase chain reaction [PCR]) were reviewed. Results: Forty-nine patients with COVID-19 requiring supplementary oxygen before surgery had spinal anaesthesia (ropivacaine 0.75%), chiefly for Caesarean section (45/49 [91%]). Spinal anaesthesia was not associated with cardiorespiratory compromise intraoperatively. No patients subsequently developed severe pneumonia. Of 44 anaesthetists, 37 (84.1%) provided spinal anaesthesia using Level 3 PPE. Coronavirus disease 2019 infection was subsequently confirmed by PCR in 5/44 (11.4%) anaesthetists. One (2.7%) of 37 anaesthetists who wore Level 3 PPE developed PCR-confirmed COVID-19 compared with 4/7 (57.1%) anaesthetists who had Level 1 protection in the operating theatre (relative risk reduction: 95.3% [95% confidence intervals: 63.7e99.4]; P<0.01). Conclusions: Spinal anaesthesia was delivered safely in patients with active COVID-19 infection, the majority of whom had Caesarean sections. Level 3 PPE appears to reduce the risk of transmission to anaesthetists who are exposed to mildly symptomatic surgical patients.

Neuronal Cdc2-like kinase is a heterodimer of Cdk5 and a 25-kDa subunit which is derived from a brain-specific 35-kDa novel protein, p35 (Lew, J., Huang, Q.-Q., Qi, Z., Winkfein, R. J., Aebersold, R., Hunt, T., and Wang, J. H. (1994) Nature 371, 423-426). Three truncated forms of p35 including the one corresponding to the 25-kDa subunit of the kinase have been expressed in Escherichia coli and shown to activate a bacteria-expressed Cdk5 with equal efficacy. The shortest truncated form of p35, p21, spanning amino acid residues 88 to 291, has been used to reconstitute active Cdk5 kinase and to characterize the activation reaction. The purified kinase displays similar specific enzyme activity and similar phosphorylation site specificity as the neuronal Cdc2-like kinase purified from bovine brain. Bovine brain extract contains Cdk5 uncomplexed with p35 or p25 which has also been found to be activated by p21 or p25. The results substantiate the previous suggestion that p35 is a specific Cdk5 activator. Several observations suggest that, unlike other well characterized Cdc2-like kinases whose activities depend on the phosphorylation of the catalytic subunits at a specific site by a distinct kinase, the reconstituted Cdk5/p21 does not depend on the phosphorylation of Cdk5 for activity. The reconstitution of the highly active Cdk5 kinase was achieved without requiring any other kinase in the reconstitution reaction. The possibility of autophosphorylation of Cdk5 on the putative activation site has been ruled out as no phosphorylation occurred on Cdk5 during the enzyme reaction. The rate and extent of the kinase reconstitution were not significantly affected by Mg2+ ATP.

The nucleocapsid (N) protein of SARS-coronavirus (SARS-CoV) is the key protein for the formation of the helical nucleocapsid during virion assembly. This protein is believed to be more conserved than other proteins of the virus, such as spike and membrane glycoprotein. In this study, the N protein of SARS-CoV was expressed in Escherichia coli DH5alpha and identified with pooled sera from patients in the convalescence phase of SARS. A plasmid pCI-N, encoding the full-length N gene of SARS-CoV, was constructed. Expression of the N protein was observed in COS1 cells following transfection with pCI-N. The immune responses induced by intramuscular immunization with pCI-N were evaluated in a murine model. Serum anti-N immunoglobulins and splenocytes proliferative responses against N protein were observed in immunized BALB/c mice. The major immunoglobulin G subclass recognizing N protein was immunoglobulin G2a, and stimulated splenocytes secreted high levels of gamma interferon and IL-2 in response to N protein. More importantly, the immunized mice produced strong delayed-type hypersensitivity (DTH) and CD8(+) CTL responses to N protein. The study shows that N protein of SARS-CoV not only is an important B cell immunogen, but also can elicit broad-based cellular immune responses. The results indicate that the N protein may be of potential value in vaccine development for specific prophylaxis and treatment against SARS.

Exceptional points (EPs) are singularities that arise in non-Hermitian physics. Current research efforts focus only on systems supporting isolated EPs characterized by increased sensitivity to external perturbations, which makes them potential candidates for building next generation optical sensors. On the downside, this feature is also the Achilles heel of these devices: they are very sensitive to fabrication errors and experimental uncertainties. To overcome this problem, we introduce a new design concept for implementing photonic EPs that combine the robustness required for practical use together with their hallmark sensitivity. Particularly, our proposed structure exhibits a hypersurface of Jordan EPs (JEPs) embedded in a larger space, and having the following peculiar features: (1) A large class of undesired perturbations shift the operating point along the exceptional surface (ES), thus leaving the system at another EP which explains the robustness;(2) Perturbations due to back reflection/scattering force the operating point out of the ES, leading to enhanced sensitivity. Importantly, our proposed geometry is relatively easy to implement using standard photonics components and the design concept can be extended to other physical platforms such as microwave or acoustics. * ganainy@mtu.edu 1 arXiv:1810.09417v1 [physics.optics]

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