Pancreatic islet failure is a key characteristic of type 2 diabetes besides insulin resistance. To get molecular insights into the pathology of islets in type 2 diabetes, we developed a computational ...approach to integrating expression profiles of Goto-Kakizaki and Wistar rat islets from a designed experiment with those of the human islets from an observational study. A principal gene-eigenvector in the expression profiles characterized by up-regulated angiogenesis and down-regulated oxidative phosphorylation was identified conserved across the two species. In the case of Goto-Kakizaki versus Wistar islets, such alteration in gene expression can be verified directly by the treatment-control tests over time, and corresponds to the alteration of alpha/beta-cell distribution obtained by quantifying the islet micrographs. Furthermore, the correspondence between the dual sample- and gene-eigenvectors unveils more delicate structures. In the case of rats, the up- and down-trend of insulin mRNA levels before and after week 8 correspond respectively to the top two principal eigenvectors. In the case of human, the top two principal eigenvectors correspond respectively to the late and early stages of diabetes. According to the aggregated expression signature, a large portion of genes involved in the hypoxia-inducible factor signaling pathway, which activates transcription of angiogenesis, were significantly up-regulated. Furthermore, top-ranked anti-angiogenic genes THBS1 and PEDF indicate the existence of a counteractive mechanism that is in line with thickened and fragmented capillaries found in the deteriorated islets. Overall, the integrative analysis unravels the principal transcriptional alterations underlying the islet deterioration of morphology and insulin secretion along type 2 diabetes progression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
An in-depth annotation of the newly discovered coronavirus (2019-nCoV) genome has revealed differences between 2019-nCoV and severe acute respiratory syndrome (SARS) or SARS-like coronaviruses. A ...systematic comparison identified 380 amino acid substitutions between these coronaviruses, which may have caused functional and pathogenic divergence of 2019-nCoV.
An in-depth annotation of the newly discovered coronavirus (2019-nCoV) genome has revealed differences between 2019-nCoV and severe acute respiratory syndrome (SARS) or SARS-like coronaviruses. A systematic comparison identified 380 amino acid substitutions between these coronaviruses, which may have caused functional and pathogenic divergence of 2019-nCoV.
Objective: To fight the "silent killer" hypertension, continuous blood pressure (BP) monitoring has been one of the most desired functions in wearable electronics. However, current BP measuring ...principles and protocols either involve a vessel occlusion process with a cuff or require multiple sensing nodes on the body, which makes it difficult to implement them in compact wearable electronics like smartwatches and wristbands with long-term wearability. Methods: In this work, we proposed a highly compact multi-wavelength photoplethysmography (MWPPG) module and a depth-resolved MWPPG approach for continuous monitoring of BP and systemic vascular resistance (SVR). By associating the wavelength-dependent light penetration depth in the skin with skin vasculatures, our method exploited the pulse transit time (PTT) on skin arterioles for tracking SVR (n = 20). Then, we developed an arteriolar PTT-based method for beat-to-beat BP measurement. The BP estimation accuracy of the proposed arteriolar PTT method was validated against Finometer (n = 20) and the arterial line (n = 4). Results: The correlation between arteriolar PTT and SVR was theoretically deduced and experimentally validated on 20 human subjects performing various maneuvers. The proposed arteriolar PTT-based method outperformed the traditional arterial PTT-based method with better BP estimation accuracy and simpler measurement setup, i.e., with a single sensing node. Conclusion: The proposed depth-resolved MWPPG method can provide accurate measurements of SVR and BP, which are traditionally difficult to measure in a noninvasive or continuous fashion. Significance: This MWPPG work provides the wearable healthcare electronics of compact size with a low-cost and physiology-based solution for continuous measurement of BP and SVR.
Fe/N/C full of ultrafine Fe-based species and pores is synthesized by pyrolyzing a g-C
3
N
4
-coordinated Fe matrix embedded in carbon for oxygen reduction. Enhanced oxygen reduction activity is ...observed on Fe/N/C with higher pore volume and the Fe/N/C catalyst with the largest pore volume shows the highest half-wave potential of 0.890 V.
Fe/N/C rich in ultrafine Fe-based species and pores is synthesized and Fe/N/C with higher pore volume exhibits higher ORR activity.
Abstract
The intrinsic statistical properties and correlations of short gamma-ray bursts (SGRBs) have not been fully determined, due to the limitations of observations. In this paper, we compile a ...more extensive sample of 82 SGRBs with measured redshifts and present a comprehensive study of their intrinsic characteristics. We obtain the median values of the intrinsic duration (
T
90,z
), peak energy (
E
p,z
), isotropic energy (
E
iso
), and peak luminosity (
L
iso
) as 0.47 s, 466 keV, 8.21 ×10
50
erg, and 3.22 × 10
51
erg s
−1
, respectively. We update the spectrum–energy correlations, and report
E
p
,
z
∝
E
iso
0.36
±
0.05
and
E
p
,
z
∝
L
iso
0.33
±
0.04
, which further confirm the previous results that the
E
p,z
–
E
iso
correlations of SGRBs and long gamma-ray bursts (LGRBs) are different and that this correlation can be used to distinguish GRB types. We report for the first time that there is a tighter correlation between the isotropic energy of the prompt emission of SGRBs and the star formation rate of their host galaxies, which reads
sSFR
∝
E
iso
0.38
±
0.11
. Using the measured jet break time (
t
jet
) of 11 SGRBs, we tentatively investigate the
E
iso
–
E
p,z
–
t
jet,z
and
L
iso
–
E
p,z
–
t
jet,z
correlations of SGRBs and find that three-parameter correlations of SGRBs also exist and are different from those of LGRBs. Based on the
E
iso
–
E
p,z
–
t
jet,z
correlation, we estimate the
t
jet,z
values of other SGRBs and calculate the opening angles of SGRBs. We find that the median value of the SGRB opening angle is 7.°5, which is larger than that of LGRBs.
The influenza virus (IV) triggers a series of signalling events inside host cells and induces complex cellular responses. Studies have suggested that host factors play an essential role in IV ...replication. MicroRNAs (miRNAs) represent a class of small non‐coding RNAs that target mRNAs, triggering either translation repression or RNA degradation. Emerging research suggests that host‐derived cellular miRNAs are involved in mediating the host–IV interaction. Using miRNA microarrays, we identified several miRNAs aberrantly expressed in IV‐infected human lung epithelial cells (A549). Specifically, miR‐let‐7c was highly up‐regulated in IV‐infected A549 cells. PITA and miRanda database screening indicated that the let‐7c seed sequence is a perfect complementary sequence match to the 3′ untranslated region (UTR) of viral gene M1 (+) cRNA, but not to PB2 and PA. As detected by a luciferase reporter system, let‐7c directly targeted the 3′‐UTR of M1 (+) cRNA, but not PB2 and PA. To experimentally identify the function of cellular let‐7c, precursor let‐7c was transfected into A549 cells. Let‐7c down‐regulated IV M1 expression at both the (+) cRNA and protein levels. Furthermore, transfection with a let‐7c inhibitor enhanced the expression of M1. Therefore, let‐7c may reduce IV replication by degrading M1 (+) cRNA. This is the first report indicating that cellular miRNA regulates IV replication through the degradation of viral gene (+) cRNA by matching the 3′‐UTR of the viral cRNA. These findings suggest that let‐7c plays a role in protecting host cells from the virus in addition to its known cellular functions.
Behavioral observations suggest a connection between anxiety and predator defense, but the underlying neural mechanisms remain unclear. Here we examine the role of the anterior hypothalamic nucleus ...(AHN), a node in the predator defense network, in anxiety-like behaviors. By in vivo recordings in male mice, we find that activity of AHN GABAergic (AHN
) neurons shows individually stable increases when animals approach unfamiliar objects in an open field (OF) or when they explore the open-arm of an elevated plus-maze (EPM). Moreover, object-evoked AHN activity overlap with predator cue responses and correlate with the object and open-arm avoidance. Crucially, exploration-triggered optogenetic inhibition of AHN
neurons reduces object and open-arm avoidance. Furthermore, retrograde viral tracing identifies the ventral subiculum (vSub) of the hippocampal formation as a significant input to AHN
neurons in driving avoidance behaviors in anxiogenic situations. Thus, convergent activation of AHN
neurons serves as a shared mechanism between anxiety and predator defense to promote behavioral avoidance.
Akt is frequently hyperactivated in human cancers and is targeted for cancer therapy. However, the physiological consequences of systemic Akt isoform inhibition were not fully explored. We showed ...that while combined Akt1 and Akt3 deletion in adult mice is tolerated, combined Akt1 and Akt2 deletion induced rapid mortality. Akt2−/− mice survived hepatic Akt1 deletion but all developed spontaneous hepatocellular carcinoma (HCC), which is associated with FoxO-dependent liver injury and inflammation. The gene expression signature of HCC-bearing livers is similar to aggressive human HCC. Consistently, neither Akt1−/− nor Akt2−/− mice are resistant to diethylnitrosamine-induced hepatocarcinogenesis, and Akt2−/− mice display a high incidence of lung metastasis. Thus, in contrast to other cancers, hepatic Akt inhibition induces liver injury that could promote HCC.
Display omitted
•Early onset of HCC after hepatic deletion of Akt1 in Akt2−/− mice•The HCC is preceded by liver injury and inflammation in a FoxO1-dependent manner•Akt2 deficiency promotes lung metastasis after hepatocarcinogenesis•Akt is required for hepatic STAT5 phosphorylation and IGF1 expression
Wang et al. show that systemic deletion of Akt1 and Akt2 is lethal while hepatic deletion leads to hepatocellular carcinoma (HCC) with complete penetrance in a FoxO1-dependent manner. Deletion of either Akt1 or Akt2 did not inhibit diethylnitrosamine-induced HCC, but Akt2 loss increased metastasis.
Reconstructing mitochondrial genomes of angiosperms is extremely intricate due to frequent recombinations which give rise to varied sized in Dendrobium mitogenomes and their structural variations, ...even in most orchid species. In this study, we first sequenced two complete and five draft mitochondrial genomes of Dendrobium using next‐generation and third‐generation sequencing technologies. The mitochondrial genomes were 420 538–689 048 bp long, showing multipartite (multichromosomal) structures that consisted of variably sized circular or linear‐mapping isoforms (chromosomes). The comparison of mitochondrial genomes showed frequent gene losses in Dendrobium species. To explore structure variations of mitochondrial genomes in vivo, we quantified copy numbers of five mitochondrial genes and DNA contents per mitochondrion. The gene copy numbers and the DNA contents showed extreme differences during Dendrobium development, suggesting dynamic structures of mitochondrial genomes. Furthermore, phylogenetic relationships of 97 accessions from 39 Dendrobium species were constructed based on 12 nuclear single‐copy genes and 15 mitochondrial genes. We discovered obvious discordance between the nuclear and mitochondrial trees. Reticulate evolution was inferred from the species network analysis in Dendrobium. Our findings revealed the rapid structural evolution of Dendrobium mitochondrial genomes and the existence of hybridization events in Dendrobium species, which provided new insights into in vivo structural variations of plant mitochondrial genomes and the strong potential of mitochondrial genes in deciphering plant evolution history.
Mitochondrial genomes of Dendrobium showed multichromosomal structures with variably sized circular or linear isoforms. Mitochondrial protein‐coding genes underwent frequent lost events in Dendrobium species. The structures of mitochondrial genomes were dynamic during Dendrobium development. The mitochondrial tree and the nuclear tree displayed obvious phylogenetic discordances in Dendrobium.
The house mouse or Mus musculus has become a premier mammalian model for genetic research due to its genetic and physiological similarities to humans. It brought mechanistic insights into numerous ...human diseases and has been routinely used to assess drug efficiency and toxicity, as well as to predict patient responses. To facilitate molecular mechanism studies in mouse, we present the Mouse Interactome Database (MID, Version 1), which includes 155,887 putative functional associations between mouse protein-coding genes inferred from functional association evidence integrated from 9 public databases. These putative functional associations are expected to cover 19.32% of all mouse protein interactions, and 26.02% of these function associations may represent protein interactions. On top of MID, we developed a gene set linkage analysis (GSLA) web tool to annotate potential functional impacts from observed differentially expressed genes. Two case studies show that the MID/GSLA system provided precise and informative annotations that other widely used gene set annotation tools, such as PANTHER and DAVID, did not. Both MID and GSLA are accessible through the website http://mouse.biomedtzc.cn.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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