Bis[hexa­amminecobalt(III)] penta­chloride nitrate

The title compound, [Co(NH3)6]2Cl5(NO3), was obtained under hydro­thermal conditions. The asymmetric unit contains three Co3+ ions, one lying on an inversion center and the other two located at 2/m positions. All Co3+ ions are six-coordinated by NH3 mol­ecules, forming [Co(NH3)6]3+ octahedra, with Co—N distances in the range 1.945 (4)–1.967 (3) Å. The nitrate N atom and one of the O atoms lie at a mirror plane. Among the Cl− anions, one lies in a general position, one on a twofold axis and two on a mirror plane. N—H⋯O and N—H⋯Cl hydrogen bonds link the cations and anions into a three-dimensional network

NetMoST: A network-based machine learning approach for subtyping schizophrenia using polygenic SNP allele biomarkers

Subtyping neuropsychiatric disorders like schizophrenia is essential for improving the diagnosis and treatment of complex diseases. Subtyping schizophrenia is challenging because it is polygenic and genetically heterogeneous, rendering the standard symptom-based diagnosis often unreliable and unrepeatable. We developed a novel network-based machine-learning approach, netMoST, to subtyping psychiatric disorders. NetMoST identifies polygenic risk SNP-allele modules from genome-wide genotyping data as polygenic haplotype biomarkers (PHBs) for disease subtyping. We applied netMoST to subtype a cohort of schizophrenia subjects into three distinct biotypes with differentiable genetic, neuroimaging and functional characteristics. The PHBs of the first biotype (36.9% of all patients) were related to neurodevelopment and cognition, the PHBs of the second biotype (28.4%) were enriched for neuroimmune functions, and the PHBs of the third biotype (34.7%) were associated with the transport of calcium ions and neurotransmitters. Neuroimaging patterns provided additional support to the new biotypes, with unique regional homogeneity (ReHo) patterns observed in the brains of each biotype compared with healthy controls. Our findings demonstrated netMoST's capability for uncovering novel biotypes of complex diseases such as schizophrenia. The results also showed the power of exploring polygenic allelic patterns that transcend the conventional GWAS approaches.Comment: 21 pages,4 figure

An improved positioning algorithm in a long-range asymmetric perimeter security system

In this paper, an improved positioning algorithm is proposed for a long-range asymmetric perimeter security system. This algorithm employs zero-crossing rate to detect the disturbance starting point, and then utilizes an improved empirical mode decomposition to obtain the effective time-frequency distribution of the extracted signal. In the end, a cross-correlation is used to estimate the time delay of the effective extracted signal. The scheme is also verified and analyzed experimentally. The field test results demonstrate that the proposed scheme can achieve a detection of 96.60% of positioning errors distributed within the range of 0-±20 m at the sensing length of 75 km, which significantly improves the positioning accuracy for the long-range asymmetric fence perimeter application

Carcinoma Initiation via Rb Tumor Suppressor Inactivation: A Versatile Approach to Epithelial Subtype-Dependent Cancer Initiation in Diverse Tissues

Carcinomas arise in a complex microenvironment consisting of multiple distinct epithelial lineages surrounded by a variety of stromal cell types. Understanding cancer etiologies requires evaluating the relationship among cell types during disease initiation and through progression. Genetically engineered mouse (GEM) models facilitate the prospective examination of early oncogenic events, which is not possible in humans. Since most solid tumors harbor aberrations in the RB network, we developed an inducible GEM approach for the establishment and assessment of carcinoma initiation in a diverse range of epithelial tissues and subtypes upon inactivation of RB-mediated tumor suppression (RB-TS). The system allows independent assessment of epithelial subtypes that express either cytokeratins (K) 18 or 19. By Cre-dependent expression of a protein that dominantly inactivates RB and functionally redundant proteins p107 and p130, neoplasia could be initiated in either K18 or K19 expressing cells of numerous tissues. By design, because only a single pathway aberration was engineered, carcinomas developed stochastically only after long latency. Hence, this system, which allows for directed cell type-specific carcinoma initiation, facilitates further definition of events that can progress neoplasms to aggressive cancers via engineered, carcinogen-induced and/or spontaneous evolution

Rare solid and cystic presentation of hemangiopericytoma/ solitary fibrous tumor: A case report

Hemangiopericytoma/Solitary Fibrous Tumor (HPC/SFT) is a rare fibroblastic sarcoma characterized by hyper-vasculature and STAT6 trans-nuclear localization. Cystic HPC/SFT is extremely rare. Due to the scarcity of cystic HPC/SFT cases, diagnostic and treatment guidelines are not well established. To our knowledge, we present the first case of cystic HPC/SFT observed in the liver. In addition, the patient had over 6 years of recurrent hypervascular solid HPC/SFT in the brain, bone, leptomeninges, liver and lung prior to developing a cystic HPC/SFT. Briefly, a 37-year-old Caucasian female with a history of HPC/SFT presented with several enlarging cystic hepatic lesions on surveillance MRI. The cystic/nonenhancing nature of these liver metastases were confirmed by contrast-enhanced ultrasound. Due to diagnostic uncertainty, two of these hepatic cysts were removed laparoscopically and pathology confirmed cystic HPC/SFT with a high MIB-1 index. Previously, in 2014, the patient was diagnosed with solid intracranial grade III pseudopapillary mesenchymal HPC/SFT in the posterior fossa and underwent subtotal resection followed by external beam radiation. In 2017, she had recurrent intracranial, vertebral, and intraspinal intradural extramedullary HPC/SFTs followed by surgery, proton therapy, and SRS radiotherapy. In 2019, after an uneventful pregnancy and birth, routine surveillance revealed metastases in the liver requiring an extended right hepatectomy. In 2020-2021 two solid hypervascular hepatic HPC/SFT were found and treated with microwave ablation. Shortly afterwards, several rapidly growing hepatic cystic HPC/SFT lesions developed. Of note, she has not taken any systemic therapy, indicating the cystic tumors are from metastases rather than cystic degradation as a sequela of therapy. Overall, this case highlights that cystic metastasis are a potential clinical manifestation of solid HPC/SFT. Moreover, cystic HPC/SFT can co-exist with the more typical primary solid hypervascular HPC/SFTs in the same patient. Lastly, in this case cystic HPC/SFT had a higher growth rate and propensity to metastasize as compared to the solid equivalent.Peer reviewe

Vitamin B12 modulates Parkinson’s disease LRRK2 kinase activity through allosteric regulation and confers neuroprotection

Missense mutations in Leucine-Rich Repeat Kinase 2 (LRRK2) cause the majority of familial and some sporadic forms of Parkinson’s disease (PD). The hyperactivity of LRRK2 kinase induced by the pathogenic mutations underlies neurotoxicity, promoting the development of LRRK2 kinase inhibitors as therapeutics. Many potent and specific small molecule LRRK2 inhibitors have been reported with promise. However, nearly all inhibitors are ATP competitive – some with unwanted side effects and unclear clinical outcome - alternative types of LRRK2 inhibitors are lacking. Herein we find 5’-deoxyadenosylcobalamin (AdoCbl), a physiological form of the essential micronutrient vitamin B12 as a mixed-type allosteric inhibitor of LRRK2 kinase activity. Multiple assays show that AdoCbl directly binds LRRK2, leading to the alterations of protein conformation and ATP binding in LRRK2. STD-NMR analysis of a LRRK2 homologous kinase reveals the contact sites in AdoCbl that interface with the kinase domain. Furthermore, we provide evidence that AdoCbl modulates LRRK2 activity through disruption of LRRK2 dimerization. Treatment with AdoCbl inhibits LRRK2 kinase activity in cultured cells and brain tissue, and importantly prevents neurotoxicity in primary rodent cultures as well as in transgenic C. elegans and D. melanogaster expressing LRRK2 disease variants. Finally, AdoCbl alleviates deficits in dopamine release sustainability caused by LRRK2 disease variants in mouse models. Our study uncovers vitamin B12 as a novel class of LRRK2 kinase modulator with a distinct mechanism, which can be harnessed to develop new LRRK2-based PD therapeutics in the futur

Development of multifunctional unmanned aerial vehicles versus ground seeding and outplanting: What is more effective for improving the growth and quality of rice culture?

The agronomic processes are complex in rice production. The mechanization efficiency is low in seeding, fertilization, and pesticide application, which is labor-intensive and time-consuming. Currently, many kinds of research focus on the single operation of UAVs on rice, but there is a paucity of comprehensive applications for the whole process of seeding, fertilization, and pesticide application. Based on the previous research synthetically, a multifunctional unmanned aerial vehicle (mUAV) was designed for rice planting management based on the intelligent operation platform, which realized three functions of seeding, fertilizer spreading, and pesticide application on the same flight platform. Computational fluid dynamics (CFD) simulations were used for machine design. Field trials were used to measure operating parameters. Finally, a comparative experimental analysis of the whole process was conducted by comparing the cultivation patterns of mUAV seeding (T1) with mechanical rice direct seeder (T2), and mechanical rice transplanter (T3). The comprehensive benefit of different rice management processes was evaluated. The results showed that the downwash wind field of the mUAV fluctuated widely from 0 to 1.5 m, with the spreading height of 2.5 m, and the pesticide application height of 3 m, which meet the operational requirements. There was no significant difference in yield between T1, T2, and T3 test areas, while the differences in operational efficiency and input labor costs were large. In the sowing stage, T1 had obvious advantages since the working efficiency was 2.2 times higher than T2, and the labor cost was reduced by 68.5%. The advantages were more obvious compared to T3, the working efficiency was 4 times higher than in T3, and the labor cost was reduced by 82.5%. During the pesticide application, T1 still had an advantage, but it was not a significant increase in advantage relative to the seeding stage, in which operating efficiency increased by 1.3 times and labor costs were reduced by 25%. However, the fertilization of T1 was not advantageous due to load and other limitations. Compared to T2 and T3, operational efficiency was reduced by 80% and labor costs increased by 14.3%. It is hoped that this research will provide new equipment for rice cultivation patterns in different environments, while improving rice mechanization, reducing labor inputs, and lowering costs

Evenness mediates the global relationship between forest productivity and richness

1. Biodiversity is an important component of natural ecosystems, with higher species richness often correlating with an increase in ecosystem productivity. Yet, this relationship varies substantially across environments, typically becoming less pronounced at high levels of species richness. However, species richness alone cannot reflect all important properties of a community, including community evenness, which may mediate the relationship between biodiversity and productivity. If the evenness of a community correlates negatively with richness across forests globally, then a greater number of species may not always increase overall diversity and productivity of the system. Theoretical work and local empirical studies have shown that the effect of evenness on ecosystem functioning may be especially strong at high richness levels, yet the consistency of this remains untested at a global scale. 2. Here, we used a dataset of forests from across the globe, which includes composition, biomass accumulation and net primary productivity, to explore whether productivity correlates with community evenness and richness in a way that evenness appears to buffer the effect of richness. Specifically, we evaluated whether low levels of evenness in speciose communities correlate with the attenuation of the richness–productivity relationship. 3. We found that tree species richness and evenness are negatively correlated across forests globally, with highly speciose forests typically comprising a few dominant and many rare species. Furthermore, we found that the correlation between diversity and productivity changes with evenness: at low richness, uneven communities are more productive, while at high richness, even communities are more productive. 4. Synthesis. Collectively, these results demonstrate that evenness is an integral component of the relationship between biodiversity and productivity, and that the attenuating effect of richness on forest productivity might be partly explained by low evenness in speciose communities. Productivity generally increases with species richness, until reduced evenness limits the overall increases in community diversity. Our research suggests that evenness is a fundamental component of biodiversity–ecosystem function relationships, and is of critical importance for guiding conservation and sustainable ecosystem management decisions

Native diversity buffers against severity of non-native tree invasions

Determining the drivers of non-native plant invasions is critical for managing native ecosystems and limiting the spread of invasive species$^{1,2}$. Tree invasions in particular have been relatively overlooked, even though they have the potential to transform ecosystems and economies$^{3,4}$. Here, leveraging global tree databases$^{5,6,7}$, we explore how the phylogenetic and functional diversity of native tree communities, human pressure and the environment influence the establishment of non-native tree species and the subsequent invasion severity. We find that anthropogenic factors are key to predicting whether a location is invaded, but that invasion severity is underpinned by native diversity, with higher diversity predicting lower invasion severity. Temperature and precipitation emerge as strong predictors of invasion strategy, with non-native species invading successfully when they are similar to the native community in cold or dry extremes. Yet, despite the influence of these ecological forces in determining invasion strategy, we find evidence that these patterns can be obscured by human activity, with lower ecological signal in areas with higher proximity to shipping ports. Our global perspective of non-native tree invasion highlights that human drivers influence non-native tree presence, and that native phylogenetic and functional diversity have a critical role in the establishment and spread of subsequent invasions