Genetic and genomic studies have advanced our knowledge of inherited Parkinson's disease (PD), however, the etiology and pathophysiology of idiopathic PD remain unclear. Herein, we perform a ...meta-analysis of 8 PD postmortem brain transcriptome studies by employing a multiscale network biology approach to delineate the gene-gene regulatory structures in the substantia nigra and determine key regulators of the PD transcriptomic networks. We identify STMN2, which encodes a stathmin family protein and is down-regulated in PD brains, as a key regulator functionally connected to known PD risk genes. Our network analysis predicts a function of human STMN2 in synaptic trafficking, which is validated in Stmn2-knockdown mouse dopaminergic neurons. Stmn2 reduction in the mouse midbrain causes dopaminergic neuron degeneration, phosphorylated α-synuclein elevation, and locomotor deficits. Our integrative analysis not only begins to elucidate the global landscape of PD transcriptomic networks but also pinpoints potential key regulators of PD pathogenic pathways.
In this article, a new type of Vivaldi antenna with heat dissipation enhancement is proposed and manufactured based on 3-D printing and printed circuit board (PCB) technologies. A longitudinal slot ...on substrate integrated waveguide (SIW) is employed to feed Vivaldi radiation structure, which replaces the balun structure of traditional Vivaldi antennas. The measured 10 dB bandwidth of antenna element reaches up to 34.48% (21.77-30.39 GHz) and the in-band realized boresight gain is 6.5-8.8 dBi. The <inline-formula> <tex-math notation="LaTeX">1\times 4 </tex-math></inline-formula> Vivaldi antenna array with 28.72% (21.63-28.81 GHz) bandwidth and a gain range of 10.5-12.5 dBi is achieved. The fin-shaped structure of the antenna array further enhances the heat dissipation while increasing the gain up to the range of 13.4-15.5 dBi. The measured results are in good agreement with the simulated ones. The proposed antenna array has important application potential in 5G millimeter-wave systems.
A miniaturized laminated resonator antenna (LRA) array with periodic irises is proposed in this article. By means of the distinguished slow wave property of the periodic iris-loaded waveguide (IWG), ...a compact LRA element with a dimension of only <inline-formula> <tex-math notation="LaTeX">0.36\lambda _{0} \times 0.26\lambda _{0} \times 0.08\lambda _{0} </tex-math></inline-formula> is designed, where <inline-formula> <tex-math notation="LaTeX">\lambda _{0} </tex-math></inline-formula> is the wavelength in the free space at 60 GHz. The small transverse size makes it possible to construct an antenna array with the element spacing of less than <inline-formula> <tex-math notation="LaTeX">0.5\lambda _{0} </tex-math></inline-formula>, which is rather beneficial to the scanning arrays and multiple-input-multiple-output (MIMO) systems. For demonstration, a series-fed <inline-formula> <tex-math notation="LaTeX">1\times6 </tex-math></inline-formula> antenna array in the E-plane with the element spacing of <inline-formula> <tex-math notation="LaTeX">0.38\lambda _{0} </tex-math></inline-formula> is designed and fabricated with the low-temperature co-fired ceramic (LTCC) process. The measured relative impedance bandwidth is 9.2% (from 56.3 to 61.8 GHz). The measured peak gain and 3-dB gain bandwidth are 10.6 dBi and 5.3 GHz, respectively. Furthermore, the scanning arrays are fabricated to demonstrate the scanning performance, with an element spacing of <inline-formula> <tex-math notation="LaTeX">0.45\lambda _{0} </tex-math></inline-formula> in the H-plane. They support a measured maximum scanning angle of 43° while the gain drop is within 2.5 dB.
Fungi are key components of microbial communities in mangrove wetlands, with important roles in the transformation of nutrients and energy. However, existing studies typically focus on cultivable ...fungi and seldom on the structure and driving factors of entire fungal communities. The compositions, community assembly, and interaction patterns of mangrove fungal communities on a large scale remain elusive. Here, biogeography, assembly, and co-occurrence patterns of fungal communities in mangroves across eastern to southern China were systematically analyzed by targeting the entire internal transcribed spacer (ITS) region with high-throughput Pacific Biosciences single-molecule real-time sequencing. The analysis revealed a high level of fungal diversity, including a number of basal fungal lineages not previously reported in mangroves, such as
and
. Beta nearest-taxon index analyses suggested a determinant role of dispersal limitation on fungal community in overall and most individual mangroves, with support from the strong distance-decay patterns of community similarity. Further, nonmetric multidimensional scaling analyses revealed similar biogeographies of dominant and rare fungal communities. A minor role of environmental selection on the fungal community was noted, with geographical location and sediment depth as crucial factors driving the distribution of both, the dominant and rare taxa. Finally, network analysis revealed high modularized co-occurrence patterns of fungal community in mangrove sediments, and the keystone taxa might play important roles in microbial interactions and ecological functions. The investigation expands our understanding of biogeography, assembly patterns, driving factors, and co-occurrence relationships of mangrove fungi and will spur the further functional exploration and protection of fungal resources in mangroves.
As key components of microbial community in mangroves, fungi have important ecological functions. However, the fungal community in mangroves on a large scale is generally elusive, and mangroves are declining rapidly due to climate change and anthropogenic activities. This work provides an overview of fungal community structure and biogeography in mangrove wetlands along a >9,000-km coastline across eastern to southern China. Our study observed a high number of basal fungal lineages, such as
and
, in mangrove sediments. In addition, our results highlight a crucial role of dispersal limitation and a minor role of environmental selections on fungal communities in mangrove sediments. These novel findings add important knowledge about the structure, assembly processes, and driving factors of fungal communities in mangrove sediments.
Parkinson's disease (PD) is characterized pathologically by the selective loss of substantia nigra (SN) dopaminergic (DAergic) neurons. Recent evidence has suggested a role of LRRK2, linked to the ...most frequent familial PD, in regulating synaptic vesicle (SV) trafficking. However, the mechanism whereby LRRK2 mutants contribute to nigral vulnerability remains unclear. Here we show that the most common PD mutation
impairs SV endocytosis in ventral midbrain (MB) neurons, including DA neurons, and the slowed endocytosis can be rescued by inhibition of LRRK2 kinase activity. A similar endocytic defect, however, was not observed in LRRK2 mutant neurons from the neocortex (hereafter, cortical neurons) or the hippocampus, suggesting a brain region-specific vulnerability to the G2019S mutation. Additionally, we found MB-specific impairment of SV endocytosis in neurons carrying heterozygous deletion of
(
), a gene that is associated with recessive Parkinsonism. Combining
and
does not exacerbate SV endocytosis but impairs sustained exocytosis in MB neurons and alters specific motor functions of 1-year-old male mice. Interestingly, we show that LRRK2 directly phosphorylates synaptojanin1
, resulting in the disruption of endophilin-synaptojanin1 interaction required for SV endocytosis. Our work suggests a merge of
and
pathogenic pathways in deregulating SV trafficking in MB neurons as an underlying molecular mechanism of early PD pathogenesis.
Understanding midbrain dopaminergic (DAergic) neuron-selective vulnerability in PD is essential for the development of targeted therapeutics. We report, for the first time, a nerve terminal impairment in SV trafficking selectively in MB neurons but not cortical neurons caused by two PARK genes:
(PARK8) and
(PARK20). We demonstrate that the enhanced kinase activity resulting from the most frequent
mutation in
is the key to this impairment. We provide evidence suggesting that
and
loss of function share a similar pathogenic pathway in deregulating DAergic neuron SV endocytosis and that they play additive roles in facilitating each other's pathogenic functions in PD.
A grid array antenna is presented in this paper with sub grid arrays and multiple feed points, showing enhanced radiation characteristics and sufficient design flexibility. For instance, the grid ...array antenna can be easily designed as a linearly- or circularly-polarized, unbalanced or balanced antenna. A design example is given for a linearly-polarized unbalanced grid array antenna in Ferro A6M low temperature co-fired ceramic technology for 60-GHz radios to operate from 57 to 66 GHz (≈ 14.6% at 61.5 GHz ). It consists of 4 sub grid arrays and 4 feed points that are connected to a single-ended 50-Ω source by a quarter-wave matched T-junction network. The simulated results indicate that the grid array antenna has the maximum gain of 17.7 dBi at 59 GHz , an impedance bandwidth (| S 11 | ≤ -10 dB) nearly from 56 to 67.5 GHz (or 18.7%), a 3-dB gain bandwidth from 55.4 to 66 GHz (or 17.2%), and a vertical beam bandwidth in the broadside direction from 57 to 66 GHz (14.6%). The measured results are compared with the simulated ones. Discrepancies and their causes are identified with a tolerance analysis on the fabrication process.
Global surface evapotranspiration is one of the most significant components of the response of the water cycle to a warming climate. However, trends in surface evapotranspiration differ considerably ...from the trend in climate warming according to recent studies, with some studies even showing an opposing trend. The reason for this difference in the response of surface evapotranspiration to climate warming is still not completely understood. We validated the gridded FLUXNET evapotranspiration dataset and the Global Land Surface Assimilation Dataset (GLDAS) against evapotranspiration data observed in northern China using the eddy covariance system. The response of surface evapotranspiration to an increase in temperature varied with the type of climate (classified by the amount of precipitation) and the trend of surface evapotranspiration with warming showed similar features to the transitions between these climate types. The climate type with precipitation in the range of 250–350 mm was the most sensitive to the effects of warming on evapotranspiration. In more humid climates, surface evapotranspiration increased with increasing temperature, whereas in drier climates surface evapotranspiration decreased with increasing temperature. A similar response of evapotranspiration to increasing temperatures was also observed elsewhere in regions of climate transition. There are two main mechanisms of evapotranspiration: (1) an increase in temperature resulting in a direct increase in potential evapotranspiration; and (2) an increase in temperature resulting in a loss of soil moisture due to the increase in evapotranspiration, which in turn will indirectly suppress surface evapotranspiration due to the loss of vegetation.
Summary
We explored the prognostic factors for children with very high‐risk (VHR) Philadelphia chromosome (Ph) negative B‐cell acute lymphoblastic leukaemia (B‐ALL) and compared the therapeutic ...effects of intensive chemotherapy and unmanipulated haploidentical haematopoietic stem cell transplantation (haplo‐HSCT) as post‐remission treatment in these patients undergoing first complete remission (CR1). A total of 104 paediatric patients with VHR B‐ALL in CR1 were retrospectively enrolled in this study, including 42 receiving unmanipulated haplo‐HSCT (Group A) and 62 receiving ongoing chemotherapy (Group B). Estimated 3‐year overall survival (OS), disease‐free survival (DFS) and cumulative incidence of relapse (CIR) at 36·2 months median follow‐up were 69·5 ± 4·7%, 63·5 ± 4·8% and 32·4 ± 4·7%, respectively. Maintenance of persistent positive or conversion from negative to positive of measurable residual disease (MRD) and chemotherapy were independent risk factors associated with inferior long‐term survival and higher CIR. OS, DFS, and CIR differed significantly between the groups in patients with persistent positive or negative‐to‐positive MRD. Haplo‐HSCT may be an option for children with VHR Ph‐negative B‐ALL in CR1, especially for patients with persistent positive or negative‐to‐positive MRD, and could achieve better survival than intensive chemotherapy as post‐remission treatment.
Soil salinization is a growing environmental problem caused by both natural and human activities. Excessive salinity in soil suppresses growth, decreases species diversity, and alters the community ...composition of plants; however, the effect of salinity on soil microbial communities is poorly understood. Here, we characterize the soil microbial community along a natural salinity gradient in Gurbantunggut Desert, Northwestern China. Microbial diversity linearly decreased with increases in salinity, and community dissimilarity significantly increased with salinity differences. Soil salinity showed a strong effect on microbial community dissimilarity, even after controlling for the effects of spatial distance and other environmental variables. Microbial phylotypes (
= 270) belonging to
,
,
,
, and
showed a high-salinity niche preference. Out of nine potential phenotypes predicted by BugBase, oxygen-related phenotypes showed a significant relationship with salinity content. To explore the community assembly processes, we used null models of within-community (nearest-taxon index NTI) and between-community (βNTI) phylogenetic composition. NTI showed a significantly negative relationship with salinity, suggesting that the microbial community was less phylogenetically clustered in more-saline soils. βNTI, the between-community analogue of NTI, showed that deterministic processes have overtaken stochastic processes across all sites, suggesting the importance of environmental filtering in microbial community assembly. Taken together, these results suggest the importance of salinity in soil microbial community composition and assembly processes in a desert ecosystem.
Belowground microorganisms are indispensable components for nutrient cycling in desert ecosystems, and understanding how they respond to increased salinity is essential for managing and ameliorating salinization. Our sequence-based data revealed that microbial diversity decreased with increasing salinity, and certain salt-tolerant phylotypes and phenotypes showed a positive relationship with salinity. Using a null modeling approach to estimate microbial community assembly processes along a salinity gradient, we found that salinity imposed a strong selection pressure on the microbial community, which resulted in a dominance of deterministic processes. Studying microbial diversity and community assembly processes along salinity gradients is essential in understanding the fundamental ecological processes in desert ecosystems affected by salinization.
Pediatric acute myeloid leukemia (AML) with t(8;21) (q22;q22) is classified as a low-risk group. However, relapse is still the main factor affecting survival. We aimed to investigate the effect of ...allogeneic hematopoietic stem cell transplantation (allo-HSCT) on reducing recurrence and improving the survival of high-risk pediatric t(8;21) AML based on minimal residual disease (MRD)-guided treatment, and to further explore the prognostic factors to guide risk stratification treatment and identify who will benefit from allo-HSCT.
Overall, 129 newly diagnosed pediatric t(8;21) AML patients were included in this study. Patients were divided into high-risk and low-risk group according to RUNX1-RUNX1T1 transcript levels after 2 cycles of consolidation chemotherapy. High-risk patients were divided into HSCT group and chemotherapy group according to their treatment choices. The characteristics and outcomes of 125 patients were analyzed.
For high-risk patients, allo-HSCT could improve 5-year relapse-free survival (RFS) rate compared to chemotherapy (87.4% vs. 61.9%; P = 0.026). Five-year overall survival (OS) rate in high-risk HSCT group had a trend for better than that in high-risk chemotherapy group (82.8% vs. 71.4%; P = 0.260). The 5-year RFS rate of patients with a c-KIT mutation in high-risk HSCT group had a trend for better than that of patients with a c-KIT mutation in high-risk chemotherapy group (82.9% vs. 75%; P = 0.400). Extramedullary infiltration (EI) at diagnosis was associated with a high cumulative incidence of relapse for high-risk patients (50% vs. 18.4%; P = 0.004); allo-HSCT can improve the RFS (P = 0.009).
allo-HSCT can improve the prognosis of high-risk pediatric t(8;21) AML based on MRD-guided treatment. Patients with a c-KIT mutation may benefit from allo-HSCT. EI is an independent prognostic factor for high-risk patients and allo-HSCT can improve the prognosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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