Genomic Epidemiology of Imported Cases of COVID-19 in Guangdong Province, China, October 2020 - May 2021 / 生物医学与环境科学（英文）

Objective@#The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been engendering enormous hazards to the world. We obtained the complete genome sequences of SARS-CoV-2 from imported cases admitted to the Guangzhou Eighth People's Hospital, which was appointed by the Guangdong provincial government to treat coronavirus disease 2019 (COVID-19). The SARS-CoV-2 diversity was analyzed, and the mutation characteristics, time, and regional trend of variant emergence were evaluated.@*Methods@#In total, 177 throat swab samples were obtained from COVID-19 patients (from October 2020 to May 2021). High-throughput sequencing technology was used to detect the viral sequences of patients infected with SARS-CoV-2. Phylogenetic and molecular evolutionary analyses were used to evaluate the mutation characteristics and the time and regional trends of variants.@*Results@#We observed that the imported cases mainly occurred after January 2021, peaking in May 2021, with the highest proportion observed from cases originating from the United States. The main lineages were found in Europe, Africa, and North America, and B.1.1.7 and B.1.351 were the two major sublineages. Sublineage B.1.618 was the Asian lineage (Indian) found in this study, and B.1.1.228 was not included in the lineage list of the Pangolin web. A reasonably high homology was observed among all samples. The total frequency of mutations showed that the open reading frame 1a (ORF1a) protein had the highest mutation density at the nucleotide level, and the D614G mutation in the spike protein was the commonest at the amino acid level. Most importantly, we identified some amino acid mutations in positions S, ORF7b, and ORF9b, and they have neither been reported on the Global Initiative of Sharing All Influenza Data nor published in PubMed among all missense mutations.@*Conclusion@#These results suggested the diversity of lineages and sublineages and the high homology at the amino acid level among imported cases infected with SARS-CoV-2 in Guangdong Province, China.

Kinetic Characteristics of Neutralizing Antibody Responses Vary among Patients with COVID-19 / 生物医学与环境科学（英文）

Objective@#The coronavirus disease 2019 (COVID-19) pandemic continues to present a major challenge to public health. Vaccine development requires an understanding of the kinetics of neutralizing antibody (NAb) responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).@*Methods@#In total, 605 serum samples from 125 COVID-19 patients (from January 1 to March 14, 2020) varying in age, sex, severity of symptoms, and presence of underlying diseases were collected, and antibody titers were measured using a micro-neutralization assay with wild-type SARS-CoV-2.@*Results@#NAbs were detectable approximately 10 days post-onset (dpo) of symptoms and peaked at approximately 20 dpo. The NAb levels were slightly higher in young males and severe cases, while no significant difference was observed for the other classifications. In follow-up cases, the NAb titer had increased or stabilized in 18 cases, whereas it had decreased in 26 cases, and in one case NAbs were undetectable at the end of our observation. Although a decreasing trend in NAb titer was observed in many cases, the NAb level was generally still protective.@*Conclusion@#We demonstrated that NAb levels vary among all categories of COVID-19 patients. Long-term studies are needed to determine the longevity and protective efficiency of NAbs induced by SARS-CoV-2.

Effects of modulation range and presentation rate of FM stimulus on auditory response properties of mouse inferior collicular neurons / 生理学报

In natural acoustical environments, most biologically related sounds containing frequency-modulated (FM) components repeat over periods of time. They are often in rapid sequence rather than in temporal isolation. Few studies examined the neuronal response patterns evoked by FM stimuli at different presentation rates (PR). In the present investigation, by using normal electrophysiological technique, we specifically studied the temporal features of response of the inferior collicular (IC) neurons to FM sweeps with different modulation ranges (MR) in conditions of distinct PR in mouse. The results showed that most of the recorded neurons responded best to narrower MRs (narrow-pass, up-sweep: 60.00%, 54/90; down-sweep: 63.33%, 57/90), while a small fraction of neurons displayed other patterns such as band-pass (up-sweep, 16.67%, 15/90; down-sweep, 18.89%, 17/90), all-pass (up-sweep, 18.89%, 17/90; down-sweep, 13.33%, 12/90) and wide-pass (up-sweep, 4.44%, 4/90; down-sweep, 4.44%, 4/90). Both the discharge rate and duration of recorded neurons decreased but the latency lengthened with increase in PR, when different PRs from 0.5/s to 10/s of FM sound were used. The percentage of total directional selective neurons, up-directional selective neurons, and down-directional selective neurons changed with the variation of PR or MR. These results indicate that temporal features of mouse midbrain neurons responding to FM sweeps are co-shaped by the MR and PR. Possible mechanisms underlying may be related to spectral and temporal integration of the FM sound by the IC neurons.

Perception and selectivity of sound duration in the central auditory midbrain / 生理学报

Sound duration plays important role in acoustic communication. Information of acoustic signal is mainly encoded in the amplitude and frequency spectrum of different durations. Duration selective neurons exist in the central auditory system including inferior colliculus (IC) of frog, bat, mouse and chinchilla, etc., and they are important in signal recognition and feature detection. Two generally accepted models, which are "coincidence detector model" and "anti-coincidence detector model", have been raised to explain the mechanism of neural selective responses to sound durations based on the study of IC neurons in bats. Although they are different in details, they both emphasize the importance of synaptic integration of excitatory and inhibitory inputs, and are able to explain the responses of most duration-selective neurons. However, both of the hypotheses need to be improved since other sound parameters, such as spectral pattern, amplitude and repetition rate, could affect the duration selectivity of the neurons. The dynamic changes of sound parameters are believed to enable the animal to effectively perform recognition of behavior related acoustic signals. Under free field sound stimulation, we analyzed the neural responses in the IC and auditory cortex of mouse and bat to sounds with different duration, frequency and amplitude, using intracellular or extracellular recording techniques. Based on our work and previous studies, this article reviews the properties of duration selectivity in central auditory system and discusses the mechanisms of duration selectivity and the effect of other sound parameters on the duration coding of auditory neurons.

Selectivity for the rate of frequency-modulated sweeps and its affecting factors in the inferior collicular neurons of mouse / 生理学报

Both animal communication sounds and human speech contain frequency-modulated (FM) sweeps. Although the selectivity for the rate of FM sweeps in neurons has been found in many kinds of animals at different levels of the central auditory structures, the underlying neural mechanism is still not clear. Using extracellular single unit recording techniques, we examined the selectivity for the rate of FM sweeps in the inferior colliculus (IC) neurons of the Kunming mouse (Mus musculus, Km) in the free-field stimulation conditions and determined its affecting factors. Totally, 102 neurons were recorded successfully, among which 42 neurons (41.2%) displayed a duration tuning pattern under pure tone (PT) stimulus. The percentages of short-pass, band-pass, and long-pass neurons were 22.6% (23/10), 8.8% (9/102), 9.8% (10/102), respectively. The other 60 neurons (58.8%) did not show any duration tuning features. Under FM stimulus, the majority of duration tuning neurons (78.6%, 33/42) showed the selectivity for the rate of FM sweeps. For these neurons, the type of rate selectivity was determined by the duration tuning features, but it was not related to the modulation range (MR) of FM. In a small fraction of duration tuning neurons (21.4%, 9/42), the rate selectivity was correlated with the MR, but uncorrelated with the duration tuning features. On the other hand, more than half of the non-duration tuning neurons (53.3%, 32/60) exhibited the rate selectivity under FM stimulus, and almost all of them (31/32) showed fast-rate selectivity. Nevertheless, there were 8 neurons (in 32) displaying the same best rate at different MR, indicating that they were real rate-selective neurons. Our results indicate that the selectivity for the rate of FM sweeps is co-determined by duration tuning features and sweep bandwidth. Only a few of inferior colliculus neurons belong to real rate-selectivity neurons in the mouse.

Different forward masking patterns of sustained noise burst and segmental noise burst in the inferior collicular neurons of the mouse / 生理学报

Although there has been a growing body of literature showing the neural correlation of forward masking caused by a pure tone masker in the auditory neurons, relative few studies have addressed the description of how the forward masking caused by a noise burst, especially a sequence of noise burst, is transformed into neuronal representation in the central auditory system. Using a noise forward masking paradigm under free field stimuli conditions, this in vivo study was devoted to exploring it in the inferior collicular (IC) neurons of the mouse (Mus musculus KM). A total of 96 IC neurons were recorded. Rate-intensity functions (RIFs) with and without the presentation of masker, sustained noise burst (SNB) or segmental noise burst (SGNB), were measured in 51 neurons. We found that the relative masker intensities were distributed over a wide range between 21 dB below the minimum threshold (MT) and 19 dB above the MT of the corresponding probe tone. The masking effect of the SGNB on firing rate in nearly half of neurons (type I, 45.10%) was stronger than that of the SNB (P<0.001), whereas in a smaller fraction of neurons (type III, 17.65%), it was weaker than that of the SNB (P<0.001). There was no significant difference in masking effect between the SNB and SGNB in type II neurons (37.25%, P>0.05). Irrespective of type I or type III neurons, the inhibitory effects of both kinds of maskers were all greater at lower probe intensities but decreased significantly with the increase of probe intensity (P<0.001). Interestingly, as the probe intensity increased, the difference of masking effect between the SNB and SGNB disappeared (P>0.05). In addition, we observed that temporal masking pattern could be transformed when the masker was changed from the SNB to SGNB. The main type of this transformation was from early-inhibition to proportional-inhibition pattern (53.85%, 7/13). Our data provide the evidence that the inhibitory effects of these two maskers have differential weights over time and intensity domains of the IC neurons responding to a pure tone. This suggests that the forward masking of noise is by no means the source of simply suppression in neuronal firing rate. There might be a few of active neural modulating ways in which the coding of temporal acoustical information can be operated.