Congenital factor VII (FVII) deficiency is the commonest type of the rare bleeding disorders. Very few cases of congenital FVII deficiency developed inhibitor and liver transplant is considered as ...definitive treatment. In the literature, twelve patients with congenital FVII deficiency developed inhibitors. Two had spontaneous resolution of inhibitors and one did not respond to high dose recombinant factor VIIa (rFVIIa) and died. Regarding liver transplant in congenital FVII patients, seven patients underwent liver transplant with good prognosis. We report a 5‐year‐old girl with confirmed severe congenital FVII deficiency since neonatal period. She suffered from recurrent intracranial bleeding despite rFVIIa replacement. After auxiliary liver transplant at the age of 4, she continued to show persistent deranged clotting profile and was found to have inhibitor towards FVII. Interestingly, she was still responsive to rFVIIa replacement.
Tetrodotoxin (TTX) is a highly potent neurotoxin that selectively binds to the outer vestibule of voltage-gated sodium channels. Pufferfishes accumulate extremely high concentrations of TTX without ...any adverse effect. A nonaromatic amino acid (Asn) residue present in domain I of the pufferfish,
Takifugu pardalis, Na
v1.4 channel has been implicated in the TTX resistance of pufferfishes
1. However, the effect of this residue on TTX sensitivity has not been investigated, and it is not known if this residue is conserved in all pufferfishes. We have investigated the genetic basis of TTX resistance in pufferfishes by comparing the sodium channels from two pufferfishes (
Takifugu rubripes fugu and
Tetraodon nigroviridis) and the TTX-sensitive zebrafish. Although all three fishes contain duplicate copies of Na
v1.4 channels (Na
v1.4a and Na
v1.4b), several substitutions were found in the TTX binding outer vestibule of the two pufferfish channels. Electrophysiological studies showed that the nonaromatic residue (Asn in fugu and Cys in
Tetraodon) in domain I of Na
v1.4a channels confers TTX resistance. The Glu-to-Asp mutation in domain II of
Tetraodon channel Na
v1.4b is similar to that in the saxitoxin- and TTX-resistant Na
+ channels of softshell clams
2. Besides helping to deter predators, TTX resistance enables pufferfishes to selectively feed on TTX-bearing organisms.
Objective:
To characterize cognitive and behavioral features, physical findings, and brain atrophy patterns in pathology‐proven corticobasal degeneration (CBD) and corticobasal syndrome (CBS) with ...known histopathology.
Methods:
We reviewed clinical and magnetic resonance imaging data in all patients evaluated at our center with either an autopsy diagnosis of CBD (n = 18) or clinical CBS at first presentation with known histopathology (n = 40). Atrophy patterns were compared using voxel‐based morphometry.
Results:
CBD was associated with 4 clinical syndromes: progressive nonfluent aphasia (n = 5), behavioral variant frontotemporal dementia (n = 5), executive‐motor (n = 7), and posterior cortical atrophy (n = 1). Behavioral or cognitive problems were the initial symptoms in 15 of 18 patients; less than half exhibited early motor findings. Compared to controls, CBD patients showed atrophy in dorsal prefrontal and perirolandic cortex, striatum, and brainstem (p < 0.001 uncorrected). The most common pathologic substrates for clinical CBS were CBD (35%), Alzheimer disease (AD, 23%), progressive supranuclear palsy (13%), and frontotemporal lobar degeneration (FTLD) with TDP inclusions (13%). CBS was associated with perirolandic atrophy irrespective of underlying pathology. In CBS due to FTLD (tau or TDP), atrophy extended into prefrontal cortex, striatum, and brainstem, whereas in CBS due to AD, atrophy extended into temporoparietal cortex and precuneus (p < 0.001 uncorrected).
Interpretation:
Frontal lobe involvement is characteristic of CBD, and in many patients frontal, not parietal or basal ganglia, symptoms dominate early stage disease. CBS is driven by medial perirolandic dysfunction, but this anatomy is not specific to a single underlying histopathology. Antemortem prediction of CBD will remain challenging until clinical features of CBD are redefined, and sensitive, specific biomarkers are identified. ANN NEUROL 2011;
WUDAPT Ching, J.; Mills, G.; Bechtel, B. ...
Bulletin of the American Meteorological Society,
09/2018, Letnik:
99, Številka:
9
Journal Article
Recenzirano
Odprti dostop
The World Urban Database and Access Portal Tools (WUDAPT) is an international community-based initiative to acquire and disseminate climate relevant data on the physical geographies of cities for ...modeling and analysis purposes. The current lacuna of globally consistent information on cities is a major impediment to urban climate science toward informing and developing climate mitigation and adaptation strategies at urban scales. WUDAPT consists of a database and a portal system; its database is structured into a hierarchy representing different levels of detail, and the data are acquired using innovative protocols that utilize crowdsourcing approaches, Geowiki tools, freely accessible data, and building typology archetypes. The base level of information (L0) consists of local climate zone (LCZ) maps of cities; each LCZ category is associated with a range of values for model-relevant surface descriptors (roughness, impervious surface cover, roof area, building heights, etc.). Levels 1 (L1) and 2 (L2) will provide specific intra-urban values for other relevant descriptors at greater precision, such as data morphological forms, material composition data, and energy usage. This article describes the status of the WUDAPT project and demonstrates its potential value using observations and models. As a community-based project, other researchers are encouraged to participate to help create a global urban database of value to urban climate scientists.
Global diversity and geography of soil fungi Tedersoo, Leho; Bahram, Mohammad; Põlme, Sergei ...
Science (American Association for the Advancement of Science),
11/2014, Letnik:
346, Številka:
6213
Journal Article
Recenzirano
Odprti dostop
Fungi play major roles in ecosystem processes, but the determinants of fungal diversity and biogeographic patterns remain poorly understood. Using DNA metabarcoding data from hundreds of globally ...distributed soil samples, we demonstrate that fungal richness is decoupled from plant diversity. The plant-to-fungus richness ratio declines exponentially toward the poles. Climatic factors, followed by edaphic and spatial variables, constitute the best predictors of fungal richness and community composition at the global scale. Fungi show similar latitudinal diversity gradients to other organisms, with several notable exceptions. These findings advance our understanding of global fungal diversity patterns and permit integration of fungi into a general macroecological framework. Assessing fungal diversity worldwideFungi are hyperdiverse but poorly known, despite their ecological and economic impacts. Tedersoo et al. collected nearly 15,000 topsoil samples from 365 sites worldwide and sequenced their genomes (see the Perspective by Wardle and Lindahl). Overall, they found a striking decline in fungal species richness with distance from the equator. For some specialist groups though, diversity depended more on the abundance of host plants than host diversity or geography. The findings reveal a huge gap between known and described species and the actual numbers of distinct fungi in the world's soils.Science, this issue 10.1126/science.1256688; see also p. 1052
Cardiac regeneration may revolutionize treatment for heart failure but endogenous progenitor-derived cardiomyocytes in the adult mammalian heart are few and pre-existing adult cardiomyocytes divide ...only at very low rates. Although candidate genes that control cardiomyocyte cell cycle re-entry have been implicated, expression heterogeneity in the cardiomyocyte stress-response has never been explored. Here, we show by single nuclear RNA-sequencing of cardiomyocytes from both mouse and human failing, and non-failing adult hearts that sub-populations of cardiomyocytes upregulate cell cycle activators and inhibitors consequent to the stress-response in vivo. We characterize these subgroups by weighted gene co-expression network analysis and discover long intergenic non-coding RNAs (lincRNA) as key nodal regulators. KD of nodal lincRNAs affects expression levels of genes related to dedifferentiation and cell cycle, within the same gene regulatory network. Our study reveals that sub-populations of adult cardiomyocytes may have a unique endogenous potential for cardiac regeneration in vivo.Adult mammalian cardiomyocytes are predominantly binucleated and unable to divide. Using single nuclear RNA-sequencing of cardiomyocytes from mouse and human failing and non-failing adult hearts, See et al. show that some cardiomyocytes respond to stress by dedifferentiation and cell cycle re-entry regulated by lncRNAs.
Spin-orbit torque (SOT) is an emerging technology that enables the efficient manipulation of spintronic devices. The initial processes of interest in SOTs involved electric fields, spin-orbit ...coupling, conduction electron spins, and magnetization. More recently, interest has grown to include a variety of other processes that include phonons, magnons, or heat. Over the past decade, many materials have been explored to achieve a larger SOT efficiency. Recently, holistic design to maximize the performance of SOT devices has extended material research from a nonmagnetic layer to a magnetic layer. The rapid development of SOT has spurred a variety of SOT-based applications. In this article, we first review the theories of SOTs by introducing the various mechanisms thought to generate or control SOTs, such as the spin Hall effect, the Rashba-Edelstein effect, the orbital Hall effect, thermal gradients, magnons, and strain effects. Then, we discuss the materials that enable these effects, including metals, metallic alloys, topological insulators, 2-D materials, and complex oxides. We also discuss the important roles in SOT devices of different types of magnetic layers, such as magnetic insulators, antiferromagnets, and ferrimagnets. Afterward, we discuss device applications utilizing SOTs. We discuss and compare three- and two-terminal SOT-magnetoresistive random access memories (MRAMs); we mention various schemes to eliminate the need for an external field. We provide technological application considerations for SOT-MRAM and give perspectives on SOT-based neuromorphic devices and circuits. In addition to SOT-MRAM, we present SOT-based spintronic terahertz generators, nano-oscillators, and domain-wall and skyrmion racetrack memories. This article aims to achieve a comprehensive review of SOT theory, materials, and applications, guiding future SOT development in both the academic and industrial sectors.
Circular RNA (circRNA) is a newly validated class of single-stranded RNA, ubiquitously expressed in mammalian tissues and possessing key functions including acting as microRNA sponges and as ...transcriptional regulators by binding to RNA-binding proteins. While independent studies confirm the expression of circRNA in various tissue types, genome-wide circRNA expression in the heart has yet to be described in detail.
We performed deep RNA-sequencing on ribosomal-depleted RNA isolated from 12 human hearts, 25 mouse hearts and across a 28-day differentiation time-course of human embryonic stem cell-derived cardiomyocytes. Using purpose-designed bioinformatics tools, we uncovered a total of 15 318 and 3017 cardiac circRNA within human and mouse, respectively. Their abundance generally correlates with the abundance of their cognate linear RNA, but selected circRNAs exist at disproportionately higher abundance. Top highly expressed circRNA corresponded to key cardiac genes including Titin (TTN), RYR2, and DMD. The most abundant cardiac-expressed circRNA is a cytoplasmic localized single-exon circSLC8A1-1. The longest human transcript TTN alone generates up to 415 different exonic circRNA isoforms, the majority (83%) of which originates from the I-band domain. Finally, we confirmed the expression of selected cardiac circRNA by RT-PCR, Sanger sequencing and single molecule RNA-fluorescence in situ hybridization.
Our data provide a detailed circRNA expression landscape in hearts. There is a high-abundance of specific cardiac-expressed circRNA. These findings open up a new avenue for future investigation into this emerging class of RNA.
The stability of model nanostructured Cu
90Mo
10 and Cu
90W
10 alloys during irradiation with 1.8
MeV Kr
+ at very high temperatures was investigated. Significant coarsening occurs only above ∼0.6
T
...m in Cu
90Mo
10 and ∼0.8
T
m in Cu
90W
10 (
T
m is the melting point of Cu). Below these temperatures, nanoprecipitates nucleate and grow to a saturation diameter of ∼4
nm. These very small nanoprecipitates confer remarkable microstructural stability, with the Cu grain size remaining below 40
nm. Computer simulations help to explain why these nanostructures are so stable.
To elucidate the pathogenesis of vein of Galen malformations (VOGMs), the most common and most severe of congenital brain arteriovenous malformations, we performed an integrated analysis of 310 VOGM ...proband-family exomes and 336,326 human cerebrovasculature single-cell transcriptomes. We found the Ras suppressor p120 RasGAP (RASA1) harbored a genome-wide significant burden of loss-of-function de novo variants (2042.5-fold, p = 4.79 x 10
). Rare, damaging transmitted variants were enriched in Ephrin receptor-B4 (EPHB4) (17.5-fold, p = 1.22 x 10
), which cooperates with p120 RasGAP to regulate vascular development. Additional probands had damaging variants in ACVRL1, NOTCH1, ITGB1, and PTPN11. ACVRL1 variants were also identified in a multi-generational VOGM pedigree. Integrative genomic analysis defined developing endothelial cells as a likely spatio-temporal locus of VOGM pathophysiology. Mice expressing a VOGM-specific EPHB4 kinase-domain missense variant (Phe867Leu) exhibited disrupted developmental angiogenesis and impaired hierarchical development of arterial-capillary-venous networks, but only in the presence of a "second-hit" allele. These results illuminate human arterio-venous development and VOGM pathobiology and have implications for patients and their families.
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