Recurrent Coupling Improves Discrimination of Temporal Spike Patterns

Despite the ubiquitous presence of recurrent synaptic connections in sensory neuronal systems, their general functional purpose is not well understood. A recent conceptual advance has been achieved by theories of reservoir computing in which recurrent networks have been proposed to generate short-term memory as well as to improve neuronal representation of the sensory input for subsequent computations. Here, we present a numerical study on the distinct effects of inhibitory and excitatory recurrence in a canonical linear classification task. It is found that both types of coupling improve the ability to discriminate temporal spike patterns as compared to a purely feed-forward system, although in different ways. For a large class of inhibitory networks, the network’s performance is optimal as long as a fraction of roughly 50% of neurons per stimulus is active in the resulting population code. Thereby the contribution of inactive neurons to the neural code is found to be even more informative than that of the active neurons, generating an inherent robustness of classification performance against temporal jitter of the input spikes. Excitatory couplings are found to not only produce a short-term memory buffer but also to improve linear separability of the population patterns by evoking more irregular firing as compared to the purely inhibitory case. As the excitatory connectivity becomes more sparse, firing becomes more variable, and pattern separability improves. We argue that the proposed paradigm is particularly well-suited as a conceptual framework for processing of sensory information in the auditory pathway

Central plasticity and dysfunction elicited by aural deprivation in the critical period

The acoustic signal is crucial for animals to obtain information from the surrounding environment. Like other sensory modalities, the central auditory system undergoes adaptive changes (i.e., plasticity) during the developmental stage as well as other stages of life. Owing to its plasticity, auditory centers may be susceptible to various factors, such as medical intervention, variation in ambient acoustic signals and lesion of the peripheral hearing organ. There are critical periods during which auditory centers are easier to suffer from abnormal experiences. Particularly in the early postnatal development period, aural inputs are essential for functional maturity of auditory centers. An aural deprivation model, which can be achieved by attenuating or blocking the peripheral acoustic afferent input to the auditory center, is ideal for investigating plastic changes of auditory centers. Generally, auditory plasticity includes structural and functional changes, and some of which can be irreversible. Aural deprivation can distort tonotopic maps, disrupt the binaural integration, reorganize the neural network and change the synaptic transmission in the primary auditory cortex or at lower levels of the auditory system. The regulation of specific gene expression and the modified signal pathway may be the deep molecular mechanism of these plastic changes. By studying this model, researchers may explore the pathogenesis of hearing loss and reveal plastic changes of the auditory cortex, which will facilitate the therapeutic advancement in patients with severe hearing loss. After summarizing developmental features of auditory centers in auditory deprived animals and discussing changes of central auditory remodeling in hearing loss patients, we are aimed at stressing the significant of an early and well-designed auditory training program for the hearing rehabilitation

Lipopolyplex for therapeutic gene delivery and its application for the treatment of Parkinson’s disease

Abstract: Lipopolyplex is a core-shell structure composed of nucleic acid, polycation and lipid. As a non-viral gene delivery vector, lipopolyplex combining the advantages of polyplex and lipoplex has shown superior colloidal stability, reduced cytotoxicity, extremely high gene transfection efficiency. Following intravenous administration, there are many strategies based on lipopolyplex to overcome the complex biological barriers in systemic gene delivery including condensation of nucleic acids into nanoparticles, long circulation, cell targeting, endosomal escape, release to cytoplasm and entry into cell nucleus. Parkinson’s disease is the second most common neurodegenerative disorder and severely influences the patients’ life quality. Current gene therapy clinical trials for Parkinson’s disease employing viral vectors didn’t achieve satisfactory efficacy. However, lipopolyplex may become a promising alternative approach owing to its stability in blood, ability to cross the blood-brain barrier and specific targeting to diseased brain cells

Rapid detection of Acinetobacter baumannii and molecular epidemiology of carbapenem-resistant A.baumannii in two comprehensive hospitals of Beijing, China

Acinetobacter baumannii is an important opportunistic pathogen associated with a variety of nosocomial infections. A rapid and sensitive molecular detection in clinical isolates is quite needed for the appropriate therapy and outbreak control of A. baumannii. Group 2 carbapenems have been considered the agents of choice for the treatment of multiple drug resistant A. baumannii. But the prevalence of carbapenem-resistant A. baumannii (CRAB) has been steadily increasing in recent years. Here, we developed a loop-mediated isothermal amplification (LAMP) assay for the rapid detection of A. baumannii in clinical samples by using high-specificity primers of the blaOXA-51 gene. Then we investigated the OXA-carbapenemases molecular epidemiology of A. baumannii isolates in 2 comprehensive hospitals in Beijing. The results showed that the LAMP assay could detect target DNA within 60 min at 65°C. The detection limit was 50 pg/μl, which was about 10-fold greater than that of PCR. Furthermore, this method could distinguish A. baumannii from the homologous A. nosocomialis and A. pittii. A total of 228 positive isolates were identified by this LAMP-based method for A. baumannii from 335 ICU patients with clinically suspected multi-resistant infections in 2 hospitals in Beijing. The rates of CRAB are on the rise and are slowly becoming a routine phenotype for A. baumannii. Among the CRABs, 92.3% harbored both the blaOXA-23 and blaOXA-51 genes. Thirty-three pulsotypes were identified by pulsed-field gel electrophoresis, and the majority belonged to clone C. In conclusion, the LAMP method developed for detecting A. baumannii was faster and simpler than conventional PCR and has great potential for both point-of-care testing and basic research. We further demonstrated a high distribution of class D carbapenemase-encoding genes, mainly OXA-23, which presents an emerging threat in hospitals in China

Overexpression of an Apocynum venetum DEAD-box helicase gene (AvDH1) in cotton confers salinity tolerance and increases yield in a saline field

Soil salinity is a major environmental stress limiting plant growth and productivity. We have reported previously the isolation of an Apocynum venetum DEAD-box helicase 1 (AvDH1) that is expressed in response to salt exposure. Here, we report that the overexpression of AvDH1 driven by a constitutive cauliflower mosaic virus-35S promoter in cotton plants confers salinity tolerance. Southern and northern blotting analyses showed that the AvDH1 gene was integrated into the cotton genome and expressed. In this study, the growth of transgenic cotton expressing AvDH1 was evaluated under saline conditions in a growth chamber and in a saline field trial. Transgenic cotton overexpressing AvDH1 was much more resistant to salt than the wild-type plants when grown in a growth chamber. The lower membrane ion leakage, along with increased activity of superoxide dismutase (SOD), in AvDH1 transgenic lines suggested that these characteristics may prevent membrane damage, which increases plant survival rates. In a saline field, the transgenic cotton lines expressing AvDH1 showed increased boll numbers, boll weights and seed cotton yields compared with wild-type plants, especially at high soil salinity levels. This study indicates that transgenic cotton expressing AvDH1 is a promising option for increasing crop productivity in saline fields

Survey and rapid detection of Klebsiella pneumoniae in clinical samples targeting the rcsA gene in Beijing, China

Klebsiella pneumoniae is a wide-spread nosocomial pathogen. A rapid and sensitive molecular method for the detection of K. pneumoniae in clinical samples is needed to guide therapeutic treatment. In this study, we first described a loop-mediated isothermal amplification (LAMP) method for the rapid detection of capsular polysaccharide synthesis regulating gene rcsA from K. pneumoniae in clinical samples by using two methods including real-time turbidity monitoring and fluorescence detection to assess the reaction. Then dissemination of K. pneumoniae strains was investigated from ICU patients in three top hospitals in Beijing, China. The results showed that the detection limit of the LAMP method was 0.115 pg/µl DNA within 60 min under isothermal conditions (61°C), a 100-fold increase in sensitivity compared with conventional PCR. All 30 non- K. pneumoniae strains tested were negative for LAMP detection, indicating the high specificity of the LAMP reaction. To evaluate the application of the LAMP assay to clinical diagnosis, of 110 clinical sputum samples collected from ICU patients with clinically suspected multi-resistant infections in China, a total of 32 K. pneumoniae isolates were identified for LAMP-based surveillance of rcsA. All isolates belonged to nine different K. pneumoniae multilocus sequence typing (MLST) groups. Strikingly, of the 32 K. pneumoniae strains, 18 contained the Klebsiella pneumoniae Carbapenemase (KPC)-encoding gene blaKPC-2 and had high resistance to β-lactam antibiotics. Moreover, K. pneumoniae WJ-64 was discovered to contain blaKPC-2 and blaNDM-1 genes simultaneously in the isolate. Our data showed the high prevalence of blaKPC-2 among K. pneumoniae and co-occurrence of many resistant genes in the clinical strains signal a rapid and continuing evolution of K. pneumoniae. In conclusion, we have developed a rapid and sensitive visual K. pneumoniae detection LAMP assay, which could be a useful tool for clinical screening, on-site diagnosis

Mirror neuron system based therapy for aphasia rehabilitation

Objective: To investigate the effect of hand action observation training, i.e. mirror neuron system (MNS) based training, on language function of aphasic patients after stroke. In addition, to reveal the tentative mechanism underlying this effect.Methods: Six aphasic patients after stroke, meeting the criteria, undergo three weeks’ training protocol (30 min per day, 6 days per week). Among them, four patients accepted an ABA training design, i.e. they implemented Protocol A (hand action observation combined with repetition) in the first and third weeks while carried out Protocol B (static objects observation combined with repetition) in the second week. Conversely, for the other two patients, BAB training design was adopted, i.e. patients took Protocol B in the first and the third weeks and accepted Protocol A in the second week. Picture naming test, western aphasia battery (WAB) and Token Test were applied to evaluate the changes of language function before and after each week’s training. Furthermore, two subjects (one aphasic patient and one healthy volunteer) attended a functional MRI (fMRI) experiment, by which we tried to reveal the mechanism underlying possible language function changes after training.Results: Compared with static objects observation and repetition training (Protocol B), hand action observation and repetition training (Protocol A) effectively improved most aspects of the language function in all six patients, as demonstrated in the picture naming test, subtests of oral language and aphasia quotient(AQ) of WAB. In addition, the fMRI experiment showed that Protocol A induced more activations in the MNS of two participants when compared to Protocol B. Conclusion: The mirror neuron based therapy may facilitate the language recovery for aphasic patients and this to some extent provides a novel direction of rehabilitation for aphasia patients

Prevalence and Detection of Stenotrophomonas maltophilia Carrying Metallo-β-lactamase blaL1 in Beijing, China

Intrinsic β-lactam resistance in Stenotrophomonas maltophilia S. maltophilia is caused by blaL1 and/or blaL2, a kind of metallo-β-lactamase with a broad substrate spectrum including carbapenems. A rapid and sensitive molecular method for the detection of blaL1 in clinical samples is needed to guide therapeutic treatment. In present study, we first described a loop-mediated isothermal amplification (LAMP) method for the rapid detection of blaL1 in clinical samples by using two methods including a chromogenic method using calcein/Mn2+ complex and the real-time turbidity monitoring to assess the reaction. Then dissemination of L1-producing S. maltophilia was investigated from ICU patients in three top hospital in Beijing, China. The results showed that both methods detected the target DNA within 60 min under 65°C. The detection limit of LAMP was 3.79 pg/µl DNA, and its sensitivity 100-fold greater than that of conventional PCR. All 21 test strains except for S. maltophilia were negative for blaL1, indicative of the high-specificity of the primers for the blaL1. A total of 22 L1-positive isolates were identified for LAMP-based surveillance of blaL1 from 105 ICU patients with clinically suspected multi-resistant infections. The sequences of these blaL1 genes were conservative with only a few sites mutated, and the strains had highly resistant to β-lactam antibiotics. The MLST recovered that 22 strains belonged to seven different ST types. Furthermore, co-occurrence of blaL1 and blaL2 genes were detected in all of isolates. Strikingly, S. maltophilia DCPS-01 was recovered to contain blaL1, blaL2, and blaNDM‑1 genes, possessing an ability to hydrolyse all β-lactams antibiotics. Our data showed the diversity types of S. maltophilia carrying blaL1 and co-occurrence of many resistant genes in the clinical strains signal an ongoing and fast evolution of S. maltophilia resulting from their wide spread in the respiratory infections, and therefore will be difficult to control