Abstract While endocannabinoid modulation of both GABAergic and glutamatergic synaptic transmission and plasticity has been extensively investigated, our understanding of the role of endocannabinoids ...in protecting neurons from harmful insults remains limited. 2-Arachidonoylglycerol (2-AG), the most abundant endogenous ligand and a full agonist for cannabinoid receptors, exhibits anti-inflammatory and neuroprotective effects via a CB1 receptor (CB1R)-mediated mechanism. However, it is still not clear whether 2-AG is also able to protect neurons from β-amyloid (Aβ)-induced neurodegeneration. Here, we demonstrate that exogenous application of 2-AG significantly protected hippocampal neurons in culture against Aβ-induced neurodegeneration and apoptosis. This neuroprotective effect was blocked by SR141716 (SR-1), a selective CB1R antagonist, but not by SR144528 (SR-2), a selective CB2R antagonist, or capsazepine (CAP), a selective transient receptor potential cation channels, subfamily V, member 1 (TRPV1) receptor antagonist. To determine whether endogenous 2-AG is capable of protecting neurons from Aβ insults, hippocampal neurons in culture were treated with URB602 or JZL184, selective inhibitors of monoacylglycerol lipase (MAGL), the enzyme hydrolyzing 2-AG. MAGL inhibition that elevates endogenous levels of 2-AG also significantly reduced Aβ-induced neurodegeneration and apoptosis. The 2-AG-produced neuroprotective effects appear to be mediated via CB1R-dependent suppression of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and nuclear factor-κB (NF-κB) phosphorylation and cyclooxygenase-2 (COX-2) expression. Our results suggest that elevation of endogenous 2-AG by inhibiting its hydrolysis has potential as a novel efficacious therapeutic approach for preventing, ameliorating or treating Alzheimer's disease.
A flexible 3D porous magnet KCo7(OH)3(ip)6(H2O)4·12 H2O based on unprecedented trigonal‐prismatic heptanuclear CoII clusters (see figure) is reported to undergo a reversible ...single‐crystal‐to‐single‐crystal transformation on the desorption/adsorption of guest molecules, accompanied by reversible magnetic property changes. This might be applied for the sensing of coordinative, paramagnetic, small molecules such as O2 and NO.
Background Anchorage is one of the most important treatments for severe temporomandibular joint disorder (TMD). Anchoring nails have shown great success in clinical trials; however, they can break ...under pressure and are difficult to remove. In this study, we aimed to evaluate an improved anchoring nail and its mechanical stability. Methods The experiment consisted of two parts: a tensile test and finite element analysis (FEA). First, traditional and improved anchoring nails were implanted into the condylar cortical bone and their tensile strength was measured using a tension meter. Second, a three-dimensional finite element model of the condyles with implants was established and FEA was performed with forces from three different directions. Results The FEA results showed that the total force of the traditional and improved anchoring nails is 48.2 N and 200 N, respectively. The mean (+ or -s.d.) maximum tensile strength of the traditional anchoring nail with a 3-0 suture was 27.53 + or - 5.47 N. For the improved anchoring nail with a 3-0 suture it was 25.89 + or - 2.64 N and with a 2-0 suture it was above 50 N. The tensile strengths of the traditional and improved anchoring nails with a 3-0 suture was significantly different (P = 0.033-< 0.05). Furthermore, the difference between the traditional anchoring nail with a 3-0 suture and the improved anchoring nail with a 2-0 suture was also significantly different (P = 0.000-< 0.01). Conclusion The improved anchoring nail, especially when combined with a 2-0 suture, showed better resistance ability compared with the traditional anchoring nail. Keywords: Temporalmandibular joint disc anchorage, Mandibular condyle, Anchoring nail, Suture, Tensile test, Finite element analysis, FEA
Summary
Background
Structural variations (SVs; defined as DNA variants ≥ 50 base pairs) have been associated with various complex human diseases. However, research to screen the whole genome for SVs ...predisposing to psoriasis is lacking.
Objectives
To investigate the association of SVs and psoriasis.
Methods
Using imputation, we performed a genome‐wide screen of SVs on five independent cohorts with 45 386 participants from the Han Chinese population. Fine‐mapping analysis, genetic interaction analysis and RNA expression analysis were conducted to explore the mechanism of SVs.
Results
In total, we obtained 4535 SVs and identified two novel deletions esv3608550, odds ratio (OR) 2·73 (P < 2·00 × 10–308); esv3608542, OR 0·47 (P = 7·40 × 10–28) at 6q21·33 (major histocompatibility complex), one novel Alu element insertion esv3607339; OR 1·22 (P = 1·18 × 10–35) at 5q33·3 (IL12B) and confirmed one previously reported deletion esv3587563; OR 1·30 (P = 9·52 × 10–60) at 1q21·2 (late cornified envelope) for psoriasis. Fine‐mapping analysis including single‐nucleotide polymorphisms (SNPs) and small insertions/deletions revealed that esv3608550 and esv3608542 were independently associated with psoriasis, and a novel independent SNP rs9378188; OR, 1·65 (P = 3·46 × 10–38) was identified at 6q21·33. By genetic interaction analysis and RNA expression analysis, we speculate that the association of two deletions at 6q21·33 with psoriasis might relate to their influence on the expression of HLA‐C.
Conclusions
We have constructed the most comprehensive SV map for psoriasis thus far and enriched the genetic architecture and pathogenesis of psoriasis, and highlight the non‐negligible impact of SVs on complex diseases.
What is already known about this topic?
Single‐nucleotide polymorphism‐based association studies have uncovered hundreds of genetic variants associated with psoriasis.
However, the missing heritability and unclear underlying pathogenesis of psoriasis still exist.
Several structural variations (SVs) associated with psoriasis have been reported, but they only cover a small proportion of the missing heritability and the recruited sample size was limited.
What does this study add?
We report the most comprehensive SV map of psoriasis so far, with a large sample size.
We undertook a genome‐wide screen of SVs in five independent Han Chinese cohorts with a total of 45 386 participants.
We identified two novel SVs at the major histocompatibility complex, one novel SV at IL12B and confirmed one previously reported SV at the late cornified envelope gene cluster for psoriasis.
What is the translational message?
A full understanding of the mechanisms contributing to psoriasis risk at established susceptibility loci should take SVs into account.
The associated SVs identified will provide novel targets for diagnosis and treatment.
Linked Comment: N. Dand. Br J Dermatol 2022; 186:210–211.
Plain language summary available online
Electron flux measurements outside geosynchronous orbit (GSO) obtained by the BeiDa Imaging Electron Spectrometer instrument on board a 55° inclined GSO satellite and inside GSO obtained by the Van ...Allen Probes are analyzed to investigate the temporal and spatial evolutions of the substorm injection region. In 1 year data started from October 2015, 63 injection events are identified. First, our study shows that the injection signatures can be detected in a large radial extent in one single event, for example, from L ∼ 4.1 to L ∼ 9.3. Second, injection onset times are derived from the energy dispersion of particle injection signatures of each satellite. The difference of the onset times among satellites reveals that the injection boundary, termed as “injection front” in this paper, can propagate both earthward and tailward with a speed varying from a few km/s to ∼100 km/s. Third, evolutions of the upper‐cutoff magnetic moments (μuc) of injected electrons are analyzed, upon which the injection events are classified into two categories. In one category, the μuc observed by two radially separated satellites are equal taking into account the error caused by the finite width of energy channels, whereas in the other category, μuc at lower L shells are smaller than those at higher L shells.
Key Points
Substorm injection front can propagate both earthward (34 cases) and tailward (49 cases), with a speed varying from a few km/s to ∼100 km/s
Studies on the upper‐cutoff magnetic moment indicate that substorm injections may be divided into two types: adiabatic and nonadiabatic injection
Statistical study is conducted on 63 substorm injection events from L ∼ 4 to L ∼ 10, which are identified from 1 year flux measurements
Sex controls have been performed in some farmed fish species because of significant growth differences between females and males. In yellow catfish (Pelteobagrus fulvidraco), adult males are three ...times larger than female adults. In this study, six Y- and X-linked amplified fragment length polymorphism fragments were screened by sex-genotype pool bulked segregant analysis and individual screening. Interestingly, sequence analysis identified two pairs of allelic genes, Pf33 and Pf62. Furthermore, the cloned flanking sequences revealed several Y- and X-specific polymorphisms, and four Y-linked or X-linked sequence characterized amplified region (SCAR) primer pairs were designed and converted into Y- and X-linked SCAR markers. Consequently, these markers were successfully used to identify genetic sex and YY super-males, and applied to all-male population production. Thus, we developed a novel and simple technique to help commercial production of YY super-males and all-male populations in the yellow catfish.
In this paper, we propose a hierarchical bidirectional Gated Recurrent Unit (GRU) network with attention for human emotion classification from continues electroencephalogram (EEG) signals. The ...structure of the model mirrors the hierarchical structure of EEG signals, and the attention mechanism is used at two levels of EEG samples and epochs. By paying different levels of attention to content with different importance, the model can learn more significant feature representation of EEG sequence which highlights the contribution of important samples and epochs to its emotional categories. We conduct the cross-subject emotion classification experiments on DEAP data set to evaluate the model performance. The experimental results show that in valence and arousal dimensions, our model on 1-s segmented EEG sequences outperforms the best deep baseline LSTM model by 4.2% and 4.6%, and outperforms the best shallow baseline model by 11.7% and 12% respectively. Moreover, with increase of the epoch's length of EEG sequences, our model shows more robust classification performance than baseline models, which demonstrates that the proposed model can effectively reduce the impact of long-term non-stationarity of EEG sequences and improve the accuracy and robustness of EEG-based emotion classification.
During the process of aging, especially for postmenopausal females, the cell lineage commitment of mesenchymal stem cells (MSCs) shift to adipocyte in bone marrow, resulting in osteoporosis. However, ...the cell-intrinsic mechanism of this cell lineage commitment switch is poorly understood. As the post-transcription regulation by microRNAs (miRNAs) has a critical role in MSCs differentiation and bone homeostasis, we performed comprehensive miRNAs profiling and found miR-705 and miR-3077-5p were significantly enhanced in MSCs from osteoporosis bone marrow. Both miR-705 and miR-3077-5p acted as inhibitors of MSCs osteoblast differentiation and promoters of adipocyte differentiation, by targeting on the 3'untranslated region (3'UTR) of HOXA10 and RUNX2 mRNA separately. Combined inhibition of miR-705 and miR-3077-5p rescued the cell lineage commitment disorder of MSCs through restoring HOXA10 and RUNX2 protein level. Furthermore, we found excessive TNFα and reactive oxygen species caused by estrogen deficiency led to the upregulation of both miRNAs through NF-κB pathway. In conclusion, our findings showed that redundant miR-705 and miR-3077-5p synergistically mediated the shift of MSCs cell lineage commitment to adipocyte in osteoporosis bone marrow, providing new insight into the etiology of osteoporosis at the post-transcriptional level. Moreover, the rescue of MSCs lineage commitment disorder by regulating miRNAs expression suggested a novel potential therapeutic target for osteoporosis as well as stem cell-mediated regenerative medicine.
PDF
