The ancestors of marine mammals once roamed the land and independently committed to an aquatic lifestyle. These macroevolutionary transitions have intrigued scientists for centuries. Here, we ...generated high-quality genome assemblies of 17 marine mammals (11 cetaceans and six pinnipeds), including eight assemblies at the chromosome level. Incorporating previously published data, we reconstructed the marine mammal phylogeny and population histories and identified numerous idiosyncratic and convergent genomic variations that possibly contributed to the transition from land to water in marine mammal lineages. Genes associated with the formation of blubber (
), vascular development (
), and heat production by brown adipose tissue (
) had unique changes that may contribute to marine mammal thermoregulation. We also observed many lineage-specific changes in the marine mammals, including genes associated with deep diving and navigation. Our study advances understanding of the timing, pattern, and molecular changes associated with the evolution of mammalian lineages adapting to aquatic life.
To explore the efficacy and safety of using thrombolysis in patients with wake-up stroke (WUS).
The serum IL-6 and hs-CRP levels of the patients in both the experimental group and the standard group ...were measured before thrombolysis and at 1 and 24 h afterwards. National Institute of Health Stroke Scale (NIHHS) scores were also recorded at the same time points as well as at 10 and 90 d after thrombolysis, and modified Rankin Scale (mRS) scores were calculated before thrombolysis and at 10 and 90 d afterwards. The differences in all these observations before and after thrombolysis were then investigated.
(1) The levels of serum IL-6 and hs-CRP in the experimental group and the standard group were higher than those in the healthy control group before thrombolysis (P < 0.05), indicating that higher levels of hs-CRP and IL-6 are risk factors for WUS (P < 0.05). (2) There were no significant differences in the serum hs-CRP and IL-6 levels of the patients in the experimental and standard groups before thrombolysis (P > 0.05). (3) The serum IL-6 and hs-CRP levels were positively correlated with the NIHHS scores in both the experimental group and the standard group (P < 0.05), and they correlated with the mRS scores at 90 d.
Interleukin-6 and hs-CRP can be used as biological indicators of inflammatory injury and diagnosis of stroke, and the combined detection of IL-6 and hs-CRP is of importance in predicting a deterioration in stroke patients.
•To explore the efficacy and safety of using thrombolysis in patients with wake-up stroke (WUS).•Interleukin-6 and hs-CRP can be used as biological indicators of inflammatory injury and diagnosis of stroke.•Combined detection of IL-6 and hs-CRP is of importance in predicting a deterioration in stroke patients.
Deep brain stimulation (DBS) is a widely used neurosurgical approach to treating tremor and other movement disorders. In addition, the use of DBS in a number of psychiatric diseases, including ...obsessive-compulsive disorders and depression, is currently being tested. Despite the rapid increase in the number of individuals with surgically implanted stimulation electrodes, the cellular pathways involved in mediating the effects of DBS remain unknown. Here we show that DBS is associated with a marked increase in the release of ATP, resulting in accumulation of its catabolic product, adenosine. Adenosine A1 receptor activation depresses excitatory transmission in the thalamus and reduces both tremor- and DBS-induced side effects. Intrathalamic infusion of A1 receptor agonists directly reduces tremor, whereas adenosine A1 receptor-null mice show involuntary movements and seizure at stimulation intensities below the therapeutic level. Furthermore, our data indicate that endogenous adenosine mechanisms are active in tremor, thus supporting the clinical notion that caffeine, a nonselective adenosine receptor antagonist, can trigger or exacerbate essential tremor. Our findings suggest that nonsynaptic mechanisms involving the activation of A1 receptors suppress tremor activity and limit stimulation-induced side effects, thereby providing a new pharmacological target to replace or improve the efficacy of DBS.
The aim of the present study was to discuss the clinical features of intracranial vestibular schwannomas and to evaluate the symptoms and signs as well as their correlation with tumor extension. The ...records of 1,009 patients who were treated in Shanghai Huashan Hospital were reviewed retrospectively. According to the Samii classification of 1997, the patients were grouped into a T3 and a T4 group based on the radiological findings. We focused our analysis on the incidence of subjective disturbances versus objective morbidity, and symptomatology versus tumor size and extension. Of the 1,009 cases, 424 patients (42.0%) were defined as T3 while 585 patients (58%) were defined as T4. The most frequent clinical symptoms were hearing loss (85.8%), facial numbness (48.9%), ataxia (44.6%), tinnitus (40.1%), deafness (26.3%) and facial paralysis (21.1%). The ratios of gender, vertigo and facial paralysis were significantly different between the T3 and T4 groups (P<0.05); however, none of the clinical symptoms had a positive likelihood ratio (PLR) greater than 10 for T4 prediction. The most frequent cranial nerve disturbance was associated with the cochlear nerve (92.6%) and trigeminal nerve (53.5%). Disturbance of the facial nerve was more severe in T3 than T4 patients (P<0.05). Hearing deficit, facial paresthesia, ataxia and tinnitus are key symptoms of huge vestibular schwannomas. Cochlear, trigeminal and facial nerves were the most commonly affected cranial nerves in cases of large tumors. Gender and tumor size were associated with tumor extension. Although the predictive value was limited, the symptoms of vertigo, facial paralysis and hearing loss may be indicators of tumor growth.
Astrocytes in hippocampal slices can dynamically regulate synaptic transmission in a process mediated by increases in intracellular Ca(2+). However, it is debated whether astrocytic Ca(2+) signals ...result in release of glutamate. We here compared astrocytic Ca(2+) signaling triggered by agonist exposure versus photolysis side by side. Using transgenic mice in which astrocytes selectively express the MrgA1 receptor, we found that receptor-mediated astrocytic Ca(2+) signaling consistently triggered neuronal hyperpolarization and decreased the frequency of miniature excitatory postsynaptic currents (EPSCs). In contrast, photolysis of caged Ca(2+) (o-nitrophenyl-EGTA) in astrocytes led to neuronal depolarization and increased the frequency of mEPSCs through a metabotropic glutamate receptor-mediated pathway. Analysis of transgenic mice in which astrocytic vesicular release is suppressed (dominant-negative SNARE mice) and pharmacological manipulations suggested that glutamate is primarily released by opening of anion channels rather than exocytosis. Combined, these studies show that photolysis but not by agonists induced astrocytic Ca(2+) signaling triggers glutamate release.
Spinal cord intramedullary cavernous malformation (SICM) is kind of rare vascular disease, and the therapeutic strategy is still under debate. The purpose of this article is to analyze outcome of ...SICM surgical resection and to find the possible factors indicating a better outcome.
A retrospective analysis of 83 patients with SICM in a single center from 2005 to 2017 was performed. Neurologic status was assessed using the McCormick Scale. Clinical information was collected and analyzed using multivariate logistic regression analysis.
Eighty patients with SICM were included, 48% of whom were male (n = 40). The mean age was 39.0 years; 7% of patients (n = 6) had a family history and 4% of patients (n = 3) had multiple lesions; and 41% (n = 34) were found with definite hemorrhage. Before surgery, neurologic status of the patients was 43.4%, 31.3%, 13.3%, and 12.0% in grades I (n = 36), II (n = 26), III (n = 11), and IV (n = 10), respectively. Sixty-three patients received long-term follow-up, of whom 19 improved, 39 remained in stable condition, and 5 deteriorated. Patients with duration of symptoms less than 3 months showed a higher improved outcome rate than those with duration longer than 3 months.
The finding suggests that if total resection of SICM is achievable, surgical therapy could be considered to avoid risks of severe complications followed by lesion bleeding. Early microsurgical resection (usually within 3 months) for patients with SICM can lead to better clinical outcomes.
•Surgical resection of SICM within 3 months led to better clinical outcomes.•Surgical therapy was recommended for asymptomatic patients.•McCormick Scale grade III and IV patients show improved outcome after surgical therapy.
Key message
We provided a chromosome-length assembly of
B. nigra
and show the comprehensive chromosome-scale variations among Brassica genomes.
Chromosome-level assembly of the Brassica species, ...which include many important crops, is essential for the agricultural and evolutionary studies. While the present
B. nigra
chromosomes was connected with genetic map of
B. juncea
, hindering the comparative analysis of the B chromosomes. Here we present a chromosome-length
B. nigra
assembly constructed with Hi-C connections and its variations on chromosome level compared with other Brassica species. We produced an assembly of 484 Mb annotated with 51,829 genes, of which 393 Mb were anchored onto 8 chromosomes, taking 81.26% of the assembly. Comparison of the B chromosomes shows high concordance of the two
B. nigra
assemblies and reveals comprehensive variations of the B chromosomes after polyploidization and gene loss in syntenic regions. Chromosome blocks with variations have lower gene density and higher TE content. Furthermore, we compared the chromosomes of the three major Brassica diploids, which showed that most of the variations between B and A/C had completed before A/C divergence and there are more variations on C chromosomes after their divergence. In summary, our work presents a chromosome-length assembly of
B. nigra
and comprehensive comparative analysis of the Brassica chromosomes, which provides a useful reference for other studies and comprehensive information of Brassica chromosome evolution.
Hypersynchronous neuronal firing is a hallmark of epilepsy, but the mechanisms underlying simultaneous activation of multiple neurons remains unknown. Epileptic discharges are in part initiated by a ...local depolarization shift that drives groups of neurons into synchronous bursting. In an attempt to define the cellular basis for hypersynchronous bursting activity, we studied the occurrence of paroxysmal depolarization shifts after suppressing synaptic activity using tetrodotoxin (TTX) and voltage-gated Ca(2+) channel blockers. Here we report that paroxysmal depolarization shifts can be initiated by release of glutamate from extrasynaptic sources or by photolysis of caged Ca(2+) in astrocytes. Two-photon imaging of live exposed cortex showed that several antiepileptic agents, including valproate, gabapentin and phenytoin, reduced the ability of astrocytes to transmit Ca(2+) signaling. Our results show an unanticipated key role for astrocytes in seizure activity. As such, these findings identify astrocytes as a proximal target for the treatment of epileptic disorders.
Abstract
In plants, parasitism triggers the reductive evolution of plastid genomes (plastomes). To disentangle the molecular evolutionary associations between feeding on other plants below- or ...aboveground and general transitions from facultative to obligate parasitism, we analyzed 34 complete plastomes of autotrophic, root- and stem-feeding hemiparasitic, and holoparasitic Santalales. We observed inexplicable losses of housekeeping genes and tRNAs in hemiparasites and dramatic genomic reconfiguration in holoparasitic Balanophoraceae, whose plastomes have exceptionally low GC contents. Genomic changes are related primarily to the evolution of hemi- or holoparasitism, whereas the transition from a root- to a stem-feeding mode plays no major role. In contrast, the rate of molecular evolution accelerates in a stepwise manner from autotrophs to root- and then stem-feeding parasites. Already the ancestral transition to root-parasitism coincides with a relaxation of selection in plastomes. Another significant selectional shift in plastid genes occurs as stem-feeders evolve, suggesting that this derived form coincides with trophic specialization despite the retention of photosynthetic capacity. Parasitic Santalales fill a gap in our understanding of parasitism-associated plastome degeneration. We reveal that lifestyle-genome associations unfold interdependently over trophic specialization and feeding mode transitions, where holoparasitic Balanophoraceae provide a system for exploring the functional realms of plastomes.
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