Inflammatory signaling regulates embryonic hematopoietic stem and progenitor cell production

Identifying signaling pathways that regulate hematopoietic stem and progenitor cell (HSPC) formation in the embryo will guide efforts to produce and expand HSPCs ex vivo. Here we show that sterile tonic inflammatory signaling regulates embryonic HSPC formation. Expression profiling of progenitors with lymphoid potential and hematopoietic stem cells (HSCs) from aorta/gonad/mesonephros (AGM) regions of midgestation mouse embryos revealed a robust innate immune/inflammatory signature. Mouse embryos lacking interferon γ (IFN-γ) or IFN-α signaling and zebrafish morphants lacking IFN-γ and IFN-ϕ activity had significantly fewer AGM HSPCs. Conversely, knockdown of IFN regulatory factor 2 (IRF2), a negative regulator of IFN signaling, increased expression of IFN target genes and HSPC production in zebrafish. Chromatin immunoprecipitation (ChIP) combined with sequencing (ChIP-seq) and expression analyses demonstrated that IRF2-occupied genes identified in human fetal liver CD34⁺ HSPCs are actively transcribed in human and mouse HSPCs. Furthermore, we demonstrate that the primitive myeloid population contributes to the local inflammatory response to impact the scale of HSPC production in the AGM region. Thus, sterile inflammatory signaling is an evolutionarily conserved pathway regulating the production of HSPCs during embryonic development.     

Applied anatomy of small branches of the portal vein in transverse groove of hepatic hilum

Purpose

The objective of this study was to provide the morphological details on small branches of the portal vein in transverse groove of hepatic hilum.

Methods

According to the surgery significance, the small branches of portal vein in transverse groove of hepatic hilum were named as “Short hepatic portal veins (SHPVs)”. SHPVs were minutely dissected in 30 adult cadaveric livers. The number, diameter, length, origin points, and entering liver sites of SHPVs were explored and measured.

Results

There were 181 SHPVs in 30 liver specimens, including 46 % (83/181) from the left portal vein, 31 % (56/181) from the bifurcation, and 23 % (42/181) from the right portal vein. At the entering liver sites of SHPVs, 22 % (40/181) supplied for segment IV, 9 % (17/181) for segment V, 4 % (7/181) for segment VI, 23 % (41/181) for segment VII, and 42 % (76/181) for segment I (caudate lobe). There were 6.0 ± 2.4 branches per liver specimen with range 3–12. The mean diameter of SHPVs was 2.25 ± 0.89 mm. The average length of SHPVs was 4.86 ± 2.12 mm.

Conclusions

SHPVs widely existed in each liver specimen. The detailed anatomical study of SHPVs could be useful to avoid damaging the short portal branches during hepatic operations, such as isolated or combined caudate lobectomy.     

Multidimensional insights involving electrochemical and in silico investigation into the corrosion inhibition of newly synthesized pyrazolotriazole derivatives on carbon steel in a HCl solution

Herein, the anti-corrosion of carbon steel in 1 M HCl by two newly synthesized pyrazolotriazole derivatives, namely, 6-methyl-1H-pyrazolo[5,1-c][1,2,4]triazole-7-carbonitrile (CPT) and 1-acetyl-6-methyl-1H-pyrazolo[5,1-c][1,2,4]triazole-7-carbothioamide (MPT), was studied using electrochemical, density functional theory (DFT), and molecular dynamics (MD) simulation techniques. The experimental results showed that the concentrations of inhibitors had a significant influence on their inhibition efficiencies. Potentiodynamic polarization curves indicated that the two pyrazolotriazoles were mixed-type inhibitors. DFT calculations were employed to explore the molecular activity, and MD simulations were performed to obtain the interaction energy between the inhibitor molecules and the iron surface. The findings obtained using the theoretical calculation techniques were consistent with those obtained via experiments.

Anti-corrosion of carbon steel in 1 M HCl by 6-methyl-1H-pyrazolo[5,1-c][1,2,4]triazole-7-carbonitrile and 1-acetyl-6-methyl-1H-pyrazolo[5,1-c][1,2,4]triazole-7-carbothioamide, was studied using electrochemical, DFT and molecular dynamics simulation techniques.     

The DNA damage response induces antigen presenting cell‐like functions in fibroblasts

The DNA damage response (DDR) alerts the immune system to the danger posed by DNA damage through the induction of damage‐associated molecular pattern molecules, chemokines, and ligands for activating immune receptors such as lymphocyte function‐associated antigen 1 (LFA‐1), NKG2D, and DNAX accessory molecule 1 (DNAM‐1). Here we provide evidence that OVA^257–264‐pulsed fibroblasts gain the ability to activate naïve OT‐I CD8⁺ T cells in response to DNA damage. The ability of fibroblasts to activate OT‐I CD8⁺ T cells depended on the upregulation of ICAM‐1 on fibroblasts and DNAM‐1 expression of CD8⁺ T cells. OVA^257–264‐pulsed fibroblasts were able to induce a protective T‐cell response against B16‐OVA cells in a DDR‐dependent manner. Hence, the DDR may alert the immune system to the presence of potentially dangerous cells by upregulating the expression of ligands that can induce the activation of innate and adaptive immune cells.     

Evidence for implicit self-positivity bias: an event-related brain potential study

We investigated the processing of self-related information under the prime paradigm using event-related potentials (ERPs) to provide evidence for implicit self-positivity bias in Chinese individuals. Reaction times and ERPs were recorded when participants made positive/negative emotional judgments to personality-trait adjectives about themselves or others. Faster responses occurred to self-related positive adjectives and other-related negative adjectives, indicating implicit self-positivity bias at the behavioral level. ERPs showed an interaction between prime and emotion at the P300 amplitude, with larger P300 amplitudes for words within the self-positivity bias, indicating that self-related information occupied more attentional resources. Larger N400 amplitudes elicited by words that were inconsistent with the self-positivity bias, suggesting that accessing non-self-relevant information is more difficult than self-relevant information. Thus, P300 and N400 could be used as neuro-indexes of the implicit self-positivity bias.     

Analysis of ASPM in an ethnically diverse cohort of 400 patient samples: perspectives of the molecular diagnostic laboratory

Primary Autosomal Recessive Microcephaly (MCPH) is characterized by congenital microcephaly usually without additional clinical findings. The most common gene implicated in MCPH is ASPM and a large percentage of mutations described have been homozygous and in consanguineous families primarily of East Asian and Middle Eastern origin. ASPM sequencing was performed on 400 patients between the years 2009 and 2012. Seventy of the patient samples were also analyzed for copy number changes in the ASPM gene. Forty protein truncating mutations, including 29 novel mutations, were identified in 39 patients with MCPH. Approximately one third of patients were compound heterozygotes, indicative of non‐consanguinity in these patients. In addition, 46 non‐synonymous variants were identified and interpreted as variants of uncertain significance. No deletion/duplication in ASPM was identified in the patients analyzed. A wide ethnic distribution was observed, including the first reported patients with ASPM‐related MCPH of Hispanic descent. Clinical information was collected for 26 of the ASPM‐positive patients and 41 of the ASPM‐negative patients. As more individuals are identified with MCPH, we anticipate that we will continue to identify ASPM mutation‐positive patients from all ethnic origins supporting the occurrence of this genetic condition beyond that of consanguineous families of certain ethnic populations.     

Xenophagy in Helicobacter pylori‐ and Epstein–Barr virus‐induced gastric cancer

Helicobacter pylori and Epstein–Barr virus (EBV) account for roughly 80% and 10%, respectively, of gastric carcinomas worldwide. Autophagy is an evolutionarily conserved and intricately regulated cellular process that involves the sequestration of cytoplasmic proteins and organelles into double‐membrane autophagosomes that eventually fuse with lysosomes for degradation of the engulfed content. Emerging evidence indicates that xenophagy, a form of selective autophagy, plays a crucial role in the pathogenesis of H. pylori‐ and EBV‐induced gastric cancer. Xenophagy specifically recognizes intracellular H. pylori and EBV and physically targets these pathogens to the autophagosomal–lysosomal pathway for degradation. In this connection, H. pylori or EBV‐induced dysregulation of autophagy may be causally linked to gastric tumourigenesis and therefore can be exploited as therapeutic targets. This review will discuss how H. pylori and EBV infection activate autophagy and how these pathogens evade recognition and degradation by the autophagic pathway. Elucidating the molecular aspects of H. pylori‐ and EBV‐induced autophagy will help us better understand the pathogenesis of gastric cancer and promote the development of autophagy modulators as antimicrobial agents. Published by John Wiley & Sons, Ltd     

Influence of oscillating uniform magnetic field and iron supplementation on quality of freeze-thawed surimi

An oscillating uniform magnetic field was applied during the freezing of surimi. Samples were placed at the central zone of a pair of Helmholtz coils (acting as the freezing chamber, guaranteeing a 99% magnetic field homogeneity) during freeze-thawing. The magnetic field parameters were 4 mT and 50 Hz. After treatments, the physicochemical properties of the samples were immediately investigated. The magnetic field decreased the amount of thawing loss and strengthened the water-holding capacity of the surimi compared to the control. The denaturation temperature, denaturation enthalpy, and protein stability increased as the magnetic field was applied. The addition of ferrous ions (15 mg Fe per kg surimi, ferrous citrate) enhanced the molecular current under the field due to electromagnetic induction. Morphological observation of the surimi revealed that ferrous ions significantly influenced its structure after freeze-thawing, yielding the smallest pores among the sample groups. These findings indicate that the quality of freeze-thawed surimi product could be improved by using an oscillating uniform magnetic field combined with iron supplementation.

An oscillating uniform magnetic field was applied during the freezing of surimi.     

A one-pot synthesis of N2,6-diaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines and systematic evaluation of their ability to host ethanol in crystals

A convenient one-pot method for the preparation of N²,6-diaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines was developed using a three-component synthesis of 1,6-diaryl-1,6-dihydro-1,3,5-triazine-2,4-diamines followed by their Dimroth rearrangement to the desired products. The prepared compounds crystallized from ethanol as ethanol clathrates (1 : 1). X-ray crystallography on several products confirmed the adoption of 5,6-dihydro-tautomer. The thermal analysis and powder X-ray diffraction experiments on selected compounds suggested that thermal desolvation of crystals was irreversible.

One-pot synthesis and analysis of stable dihydrotriazine-EtOH clathrates.