Mapping of genetic modifiers of <Emphasis Type="Italic">Plcd1</Emphasis> in scant hair mice (<Emphasis Type="Italic">snthr</Emphasis><Superscript><Emphasis Type="Italic">1Bao</Emphasis></Superscript>)

The scant hair mutant mouse (locus symbol: snthr ^1Bao ) is a recessive mutation that originated in an ethylnitrosourea chemical carcinogenesis study using the DBA/2J inbred strain. The gene responsible for the mutation was previously determined to be phospholipase C, delta 1 (Plcd1; mutant allele symbol Plcd1 ^snthr1Bao ). To map the modifiers of Plcd1, an intercross (DBA/2J-snthr ^1Bao /snthr ^1Bao × C57BL/6J+/+) was conducted. The F2 mutant progeny exhibited a variety of alopecia phenotypes; all F2 mutants (n=507) were classified into 3 groups (mild, moderate, and severe alopecia) and genotyped based on 96 microsatellites. A major QTL was identified on mouse chromosome (mChr) 15 at 12 cM with an LOD score greater than 7 (P < 0.0001). Three minor QTLs were detected on mChr 2, 5, and 7 at 40, 84 and 48 cM, respectively. The QTLs on mChr 7 and 15 were associated with minor alopecia while the QTLs on mChr 2 and 5 were associated with moderate to severe alopecia. No antagonistic or synergistic effects among or between the 4 QTLs were found. Integrating the functions of the 4 potential regulatory QTLs and mutant Plcd1 ^snthr1Bao , we found that these QTLs might contribute to variations of scant hair severity by altering the Ca²⁺ signal pathways in mouse skin.     

New testing methodology for the quantification of rock crushability: Compressive crushing value (CCV)

Crushing is a size reduction process that plays a key role in both mineral processing and crushing-screening plant design. Investigations on rock crushability have become an important issue in mining operations and the manufacture of industrial crusher equipment. The main objective of this research is to quantify the crushability of hard rocks based on their mineralogical and mechanical properties. For this purpose, the mineralogical, physical, and mechanical properties of various hard rocks were determined. A new compressive crushing value (CCV) testing methodology was proposed. The results obtained from CCV tests were compared with those from mineralogical inspections, rock strength as well as mechanical aggregate tests. Strong correlations were found between CCV and several rock and aggregate properties such as uniaxial compressive strength (UCS), the brittleness index (S₂₀), and aggregate impact value (AIV). Furthermore, the relationship between the mineralogical properties of the rocks and their CCVs were established. It is concluded that the proposed testing methodology is simple and highly repeatable and could be utilized as a pre-design tool in the design stage of the crushing process for rock quarries.     

Liver cell therapy: is this the end of the beginning?

The prevalence of liver diseases is increasing globally. Orthotopic liver transplantation is widely used to treat liver disease upon organ failure. The complexity of this procedure and finite numbers of healthy organ donors have prompted research into alternative therapeutic options to treat liver disease. This includes the transplantation of liver cells to promote regeneration. While successful, the routine supply of good quality human liver cells is limited. Therefore, renewable and scalable sources of these cells are sought. Liver progenitor and pluripotent stem cells offer potential cell sources that could be used clinically. This review discusses recent approaches in liver cell transplantation and requirements to improve the process, with the ultimate goal being efficient organ regeneration. We also discuss the potential off-target effects of cell-based therapies, and the advantages and drawbacks of current pre-clinical animal models used to study organ senescence, repopulation and regeneration.     

Effect of hot-dip galvanizing processes on the microstructure and mechanical properties of 600-MPa hot-dip galvanized dual-phase steel

A C-Mn dual-phase steel was soaked at 800℃ for 90 s and then either rapidly cooled to 450℃ and held for 30 s (process A) or rapidly cooled to 350℃ and then reheated to 450℃ (process B) to simulate the hot-dip galvanizing process. The influence of the hot-dip galvanizing process on the microstructure and mechanical properties of 600-MPa hot-dip galvanized dual-phase steel (DP600) was investigated using optical microscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and tensile tests. The results showed that, in the case of process A, the microstructure of DP600 was composed of ferrite, martensite, and a small amount of bainite. The granular bainite was formed in the hot-dip galvanizing stage, and martensite islands were formed in the final cooling stage after hot-dip galvanizing. By contrast, in the case of process B, the microstructure of the DP600 was composed of ferrite, martensite, bainite, and cementite. In addition, compared with the yield strength (YS) of the DP600 annealed by process A, that for the DP600 annealed by process B increased by approximately 50 MPa because of the tempering of the martensite formed during rapid cooling. The work-hardening coefficient (n value) of the DP600 steel annealed by process B clearly decreased because the increase of the YS affected the computation result for the n value. However, the ultimate tensile strength (UTS) and elongation (A₈₀) of the DP600 annealed by process B exhibited less variation compared with those of the DP600 annealed by process A. Therefore, DP600 with excellent comprehensive mechanical properties (YS=362 MPa, UTS=638 MPa, A₈₀=24.3%, n=0.17) was obtained via process A.     

Increased migration of olfactory ensheathing cells secreting the Nogo receptor ectodomain over inhibitory substrates and lesioned spinal cord

Olfactory ensheathing cell (OEC) transplantation emerged some years ago as a promising therapeutic strategy to repair injured spinal cord. However, inhibitory molecules are present for long periods of time in lesioned spinal cord, inhibiting both OEC migration and axonal regrowth. Two families of these molecules, chondroitin sulphate proteoglycans (CSPG) and myelin-derived inhibitors (MAIs), are able to trigger inhibitory responses in lesioned axons. Mounting evidence suggests that OEC migration is inhibited by myelin. Here we demonstrate that OEC migration is largely inhibited by CSPGs and that inhibition can be overcome by the bacterial enzyme Chondroitinase ABC. In parallel, we have generated a stable OEC cell line overexpressing the Nogo receptor (NgR) ectodomain to reduce MAI-associated inhibition in vitro and in vivo. Results indicate that engineered cells migrate longer distances than unmodified OECs over myelin or oligodendrocyte-myelin glycoprotein (OMgp)-coated substrates. In addition, they also show improved migration in lesioned spinal cord. Our results provide new insights toward the improvement of the mechanisms of action and optimization of OEC-based cell therapy for spinal cord lesion.     

Abnormal kynurenine pathway of tryptophan catabolism in cardiovascular diseases

Kynurenine pathway (KP) is the primary path of tryptophan (Trp) catabolism in most mammalian cells. The KP generates several bioactive catabolites, such as kynurenine (Kyn), kynurenic acid (KA), 3-hydroxykynurenine (3-HK), xanthurenic acid (XA), and 3-hydroxyanthranilic acid (3-HAA). Increased catabolite concentrations in serum are associated with several cardiovascular diseases (CVD), including heart disease, atherosclerosis, and endothelial dysfunction, as well as their risk factors, including hypertension, diabetes, obesity, and aging. The first catabolic step in KP is primarily controlled by indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO). Following this first step, the KP has two major branches, one branch is mediated by kynurenine 3-monooxygenase (KMO) and kynureninase (KYNU) and is responsible for the formation of 3-HK, 3-HAA, and quinolinic acid (QA); and another branch is controlled by kynurenine amino-transferase (KAT), which generates KA. Uncontrolled Trp catabolism has been demonstrated in distinct CVD, thus, understanding the underlying mechanisms by which regulates KP enzyme expression and activity is paramount. This review highlights the recent advances on the effect of KP enzyme expression and activity in different tissues on the pathological mechanisms of specific CVD, KP is an inflammatory sensor and modulator in the cardiovascular system, and KP catabolites act as the potential biomarkers for CVD initiation and progression. Moreover, the biochemical features of critical KP enzymes and principles of enzyme inhibitor development are briefly summarized, as well as the therapeutic potential of KP enzyme inhibitors against CVD is briefly discussed.     

Investigation of an energy nonadditivity for nonextensive systems

We investigate the energy nonadditivity relationship E(AαB) = E(A) + E(B) + αE(A)E(B) which is often considered in the development of the statistical physics of nonextensive systems. It was recently found that α in this equation was not constant for a given system in a given situation and could not characterize nonextensivity for that system. In this work, we select several typical nonextensive systems and compute the behavior of α when a system changes its size or is divided into subsystems in different fashions. Three kinds of interactions are considered. It is found by a thought experiment that α depends on the system size and the interaction as expected and on the way we divide the system. However, one of the major results of this work is that, for given system, α has a minimum with respect to division position. Around this position, there is a zone in which α is more or less constant, a situation where the sizes of the subsystems are comparable. The width of this zone depends on the interaction and on the system size. We conclude that if α is considered approximately constant in this zone, the two mathematical difficulties raised in previous studies are solved, meaning that the nonadditive relationship can characterize the nonadditivity of the system as an approximation. In all the cases, α tends to zero in the thermodynamic limit (N→∞) as expected.     

A comparative study of magnetic properties between whole cells and isolated magnetosomes of <Emphasis Type="Italic">Magnetospirillum magneticum</Emphasis> AMB-1

The magnetic properties of magnetosome magnetite are of interdisciplinary interest because magnetosomes are potential carriers of natural remanent magnetization and paleoenvironment, as well as novel nano-biomaterials in biotechnological and biomedical applications. We carried out magnetic and electron transmission microscopy analyses of fresh Magnetospirillum magneticum AMB-1 whole cells and isolated magnetosomes. Results revealed that AMB-1 synthesized single-domain magnetite magneto-somes, which are arra...     

AUTOMATIC DECISION-MAKING： NEURAL FIRING AND RESPONSE

1. Introduction This is the fourth exposition on theAnalytic Hierarchy Process. It is true thatmany decisions we make subconsciously ariseout of our physical and biological needs andderive from the pressure to survive physically.We also make subconsciou…