Molecular characterization of a Chinese variant of the Flury-LEP strain

The entire genome of rabies virus vaccine strain Flury-LEP-C, a Chinese variant of the rabies virus vaccine strain Flury-LEP, was sequenced. The overall length of the genome of Flury-LEP-C strain was 11 924 nucleotides (nt), comprising a leader sequence of 58 nt, nucleoprotein (N) gene of 1353 nt, phosphoprotein (P) gene of 894 nt, matrix protein (M) gene of 609 nt, glycoprotein (G) gene of 1575 nt, RNA-dependent RNA polymerase (RdRp, L) gene of 6384 nt, and a trailer region of 70 nt. There was TGAAAAAAA (TGA7) consensus sequence in the end of each gene in Flury-LEP-C genome, except G gene which had a GAGAAAAAAA sequence in the end of the non-coding G-L region. There were AACAYYYCT consensus start signal close to the TGA7. Flury-LEP-C has 310 nucleotides more than HEP-Flury in G-L intergenic region. The analysis showed that the residue at 333 of the mature G protein was Arg, which was reported to be related to pathogenicity. Compared with FluryLEP, there were 19 different amino acids (AAs) in five proteins of Flury-LEP-C, including 15 AAs which were identical with corresponding residues of Hep-Flury, and 4 AAs which were neither identical with the residues of FluryLEP nor with the residues of Hep-Flury. The results showed the topology of the phylogenetic trees generated by two protein sequences were similar. It was demonstrated that HN10, BD06, FJ009, FJ008, D02, D01, F04, F02 have a close relationship to CTN-1 and CTN181, and MRV was closely related to Flury-LEP, HEP-Flury and Flury-LEP-C

New fossils of Australopithecus sediba reveal a nearly complete lower back

Abstract: Adaptations of the lower back to bipedalism are frequently discussed but infrequently demonstrated in early fossil hominins. Newly discovered lumbar vertebrae contribute to a near-complete lower back of Malapa Hominin 2 (MH2), offering additional insights into posture and locomotion in Australopithecus sediba. We show that MH2 demonstrates a lower back consistent with human-like lumbar lordosis and other adaptations to bipedalism, including an increase in the width of intervertebral articular facets from the upper to lower lumbar column (“pyramidal configuration”). This contrasts with recent work on lordosis in fossil hominins, where MH2 was argued to demonstrate no appreciable lordosis (“hypolordosis”) similar to Neandertals. Our three-dimensional geometric morphometric (3D GM) analyses show that MH2’s nearly complete middle lumbar vertebra is human-like in shape but bears large, cranially-directed transverse processes, implying powerful trunk musculature. We interpret this combination of features to indicate that A. sediba used its lower back in both human-like bipedalism and ape-like arboreal positional behaviors, as previously suggested based on multiple lines of evidence from other parts of the skeleton and reconstructed paleobiology of A. sediba

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Juvenile hormone potentiates ecdysone receptor-dependent transcription in a mammalian cell culture system

Juvenile hormone potentiates ecdysone receptor-dependent transcription in a mammalian cell culture system. Insect Biochem. Mol. Biol., 33, 1239-1247. DOI: 10.1016/j.ibmb.2003 Insect development is guided by the combined actions of ecdysteroids and juvenile hormones (JHs). The transcriptional effects of ecdysteroids are mediated by a protein complex consisting of the ecdysone receptor (EcR) and its heterodimeric partner, Ultraspiracle (USP), but a corresponding JH receptor has not been defined conclusively. Given that the EcR ligand binding domain (LBD) is similar to that of the JH-responsive rat farnesoid-X-activated receptor (FXR), we sought to define experimental conditions under which EcR-dependent transcription could be promoted by JH. Chinese hamster ovary (CHO) cells were transfected with a plasmid carrying an ecdysteroid-inducible reporter gene, a second plasmid expressing one of the three amino-terminal variants of Drosophila EcR or an EcR chimera, and a third plasmid expressing either the mouse retinoid X receptor (RXR), or its insect orthologue, USP. Each of the EcR variants responded to the synthetic ecdysteroid, muristerone A (murA), but a maximal response to 20-hydroxyecdysone (20E) was achieved only for specific EcR combinations with its heterodimeric partner. Notably, the Drosophila EcR isoforms were responsive to 20E only when paired with USP, and only EcRB2 activity was further potentiated by JHIII in the presence of 20E. EcR chimeras that fuse the activator domains from VP16 or the glucocorticoid receptor to the Drosophila EcR DNA-binding and ligand-binding domains were responsive to ecdysteroids. Again, the effects of JHIII and 20E were associated with specific partners of the chimeric EcRs. In all experiments, the LBD of EcR proved to be the prerequisite component for potentiation by JHIII, and in this conformation may resemble the FXR LBD. Our results indicate that EcR responsiveness is influenced by the heterodimeric partner and that both the Nterminal domain of EcR and the particular ecdysteroid affect JHIII potentiation

Bacterial synthesis of a novel human leukocyte interferon.

A novel human leukocyte interferon cDNA clone (LeIF B) was identified in a cDNA library prepared using polyadenylated mRNA of a myeloblastoid cell line. The nucleotide sequence of LeIF B differs significantly from other published leukocyte interferon cDNA sequences. An expression plasmid was constructed which directs the synthesis in E. coli of 8 x 10(7) interferon units per liter of culture. LeIF B exhibits markedly different specificities from another bacterially synthesized human leukocyte interferon, LeIF A

Biologic response to complex blast waves

Small, bare charges were detonated inside an M59 armored personnel carrier (APC) in an attempt to simulate the complex blast waves generated by the jets from shaped-charge warheads penetrating into armored vehicles. Anesthetized sheep were placed inside the APC at 92- and 122-cm ranges from 57- or 113-g pentolite charges. Pressure-time was measured by pressure transducers either mounted on the animals or free standing at comparable ranges on the opposite side of the vehicle. In general, the waveforms were characterized by an initial shock wave of less than 1-msec duration followed by repeated reflections of decreasing magnitude. No deaths nor lung hemorrhages were observed, but all the animals sustained severe ear injury. Animals subjected to peak overpressures of 1.2 to 2.3 bar from the 113-g explosions also received slight non-auditory blast injuries to the upper respiratory and gastrointestinal tracts; those exposed to peak overpressures of just under 1 bar from the 57-g charges did not. The non-auditory blast injuries inside the APC were more severe than those sustained by sheep at comparable distances from 113-g charges in the open. The results suggested that the biological consequences of a complex wave of the type encountered in this study can be equated approximately to a Friedlander wave with a peak overpressure equal to that of the complex wave and with a total impulse equal to the impulse over the first 2 to 3 msec of the complex wave. 9 refs., 7 figs., 1 tab

Time-Varying Insomnia Symptoms and Incidence of Cognitive Impairment and Dementia among Older US Adults

There is conflicting evidence regarding the association between insomnia and the onset of mild cognitive impairment (MCI) or dementia. This study aimed to evaluate if time-varying insomnia is associated with the development of MCI and dementia. Data from the Health and Retirement Study (n = 13,833) from 2002 to 2014 were used (59.4% female). The Brief Insomnia Questionnaire was used to identify insomnia symptoms which were compiled in an insomnia severity index, ranging from 0 to 4. In analysis, participants’ symptoms could vary from wave-to-wave. Dementia was defined using results from the Health and Retirement Study (HRS) global cognitive assessment tool. Respondents were classified as either having dementia, MCI, or being cognitively healthy. Cox proportional hazards models with time-dependent exposure using the counting process (start-stop time) were used for analysis. For each one-unit increase in the insomnia symptom index, there was a 5-percent greater hazard of MCI (HR = 1.05; 95% CI: 1.04–1.06) and dementia (HR = 1.05; 95% CI: 1.03–1.05), after fully adjusting. Using a nationally representative sample of adults age 51 and older, this study found that time-varying insomnia symptoms are associated with risk of MCI and dementia. This highlights the importance of identifying sleep disturbances and their change over time as potentially important risk factors for MCI and dementia