The cellular autophagy/apoptosis checkpoint during inflammation

Cell death is a major determinant of inflammatory disease severity. Whether cells live or die during inflammation largely depends on the relative success of the pro-survival process of autophagy versus the pro-death process of apoptosis. These processes interact and influence each other during inflammation and there is a checkpoint at which cells irrevocably commit to either one pathway or another. This review will discuss the concept of the autophagy/apoptosis checkpoint and its importance during inflammation, the mechanisms of inflammation leading up to the checkpoint, and how the checkpoint is regulated. Understanding these concepts is important since manipulation of the autophagy/apoptosis checkpoint represents a novel opportunity for treatment of inflammatory diseases caused by too much or too little cell death.     

Null controllability of some degenerate wave equations

This paper is devoted to a study of the null controllability problems for one-dimensional linear degenerate wave equations through a boundary controller. First, the well-posedness of linear degenerate wave equations is discussed. Then the null controllability of some degenerate wave equations is established, when a control acts on the non-degenerate boundary. Different from the known controllability results in the case that a control acts on the degenerate boundary, any initial value in state space is controllable in this case. Also, an explicit expression for the controllability time is given. Furthermore, a counterexample on the controllability is given for some other degenerate wave equations.     

Single cell biology beyond the era of antibodies: relevance,challenges, and promises in biomedical research

Research of the past two decades has proved the relevance of single cell biology in basic research and translational medicine. Successful detection and isolation of specific subsets is the key to understand their functional heterogeneity. Antibodies are conventionally used for this purpose, but their relevance in certain contexts is limited. In this review, we discuss some of these contexts, posing bottle neck for different fields of biology including biomedical research. With the advancement of chemistry, several methods have been introduced to overcome these problems. Even though microfluidics and microraft array are newer techniques exploited for single cell biology, fluorescence-activated cell sorting (FACS) remains the gold standard technique for isolation of cells for many biomedical applications, like stem cell therapy. Here, we present a comprehensive and comparative account of some of the probes that are useful in FACS. Further, we illustrate how these techniques could be applied in biomedical research. It is postulated that intracellular molecular markers like nucleostemin (GNL3), alkaline phosphatase (ALPL) and HIRA can be used for improving the outcome of cardiac as well as bone regeneration. Another field that could utilize intracellular markers is diagnostics, and we propose the use of specific peptide nucleic acid probes (PNPs) against certain miRNAs for cancer surgical margin prediction. The newer techniques for single cell biology, based on intracellular molecules, will immensely enhance the repertoire of possible markers for the isolation of cell types useful in biomedical research.     

Routes and machinery of primary cilium biogenesis

Primary cilia are solitary, microtubule-based protrusions of the cell surface that play fundamental roles as photosensors, mechanosensors and biochemical sensors. Primary cilia dysfunction results in a long list of developmental and degenerative disorders that combine to give rise to a large spectrum of human diseases affecting almost any major body organ. Depending on the cell type, primary ciliogenesis is initiated intracellularly, as in fibroblasts, or at the cell surface, as in renal polarized epithelial cells. In this review, we have focused on the routes of primary ciliogenesis placing particular emphasis on the recently described pathway in renal polarized epithelial cells by which the midbody remnant resulting from a previous cell division event enables the centrosome for initiation of primary cilium assembly. The protein machinery implicated in primary cilium formation in epithelial cells, including the machinery best known for its involvement in establishing cell polarity and polarized membrane trafficking, is also discussed.     

Backstepping approach to the adaptive regulator design for a one-dimensional wave equation with general input harmonic disturbance

This paper considers the parameter estimation and stabilization of an unstable one-dimensional wave equation with matched general harmonic disturbance at the controlled end. The backstepping method for infinite-dimensional system is adopted in the design of the adaptive regulator. It is shown that the resulting closed-loop system is asymptotically stable. Meanwhile, the estimated parameter is shown to be convergent to the unknown parameter as time goes to infinity.     

Glutenin macropolymer particles size distribution of six wheat varieties in eastern China

Size distribution of glutenin macropolymer(GMP) particles significantly affects the quality of final products in wheat. Six wheat varieties in eastern China were used for investigating the GMP content, particle size distribution and their relation. The results showed that the particle diameter of GMP changed from 0.38 μm to 269 μm. A typical bimodal curve of volume distribution of particles with peak values ranged from 4.44 μm to 5.36 μm and from 45.76 μm to 116.30 μm, respectively. Number distribution of particles showed the typical population with peak values in the range of 0.57-1.00 μm. Proportions of granules 12 μm, 12-80 μm and 80 μm were in the range of 17.1%-47.8%, 32.1%-50.3% and 10.2%-38.1% of total volume, respectively. The content of GMP was negatively correlated with the volume of GMP particles 12 μm, but positively correlated with the volume of particles 80 μm. The results suggested that the greater percentage of larger GMP particles is, the more GMP content there is in wheat grain.     

Telomerase and drug resistance in cancer

It is well known that a decreased expression or inhibited activity of telomerase in cancer cells is accompanied by an increased sensitivity to some drugs (e.g., doxorubicin, cisplatin, or 5-fluorouracil). However, the mechanism of the resistance resulting from telomerase alteration remains elusive. There are theories claiming that it might be associated with telomere shortening, genome instability, hTERT translocation, mitochondria functioning modulation, or even alterations in ABC family gene expression. However, association of those mechanisms, i.e., drug resistance and telomerase alterations, is not fully understood yet. We review the current theories on the aspect of the role of telomerase in cancer cells resistance to therapy. We believe that revealing/unravelling this correlation might significantly contribute to an increased efficiency of cancer cells elimination, especially the most difficult ones, i.e., drug resistant.     

Alzheimer’s disease and CADASIL are heritable,adult-onset dementias that both involve damaged small blood vessels

This essay explores an alternative pathway to Alzheimer’s dementia that focuses on damage to small blood vessels rather than late-stage toxic amyloid deposits as the primary pathogenic mechanism that leads to irreversible dementia. While the end-stage pathology of AD is well known, the pathogenic processes that lead to disease are often assumed to be due to toxic amyloid peptides that act on neurons, leading to neuronal dysfunction and eventually neuronal cell death. Speculations as to what initiates the pathogenic cascade have included toxic abeta peptide aggregates, oxidative damage, and inflammation, but none explain why neurons die. Recent high-resolution NMR studies of living patients show that lesions in white matter regions of the brain precede the appearance of amyloid deposits and are correlated with damaged small blood vessels. To appreciate the pathogenic potential of damaged small blood vessels in the brain, it is useful to consider the clinical course and the pathogenesis of CADASIL, a heritable arteriopathy that leads to damaged small blood vessels and irreversible dementia. CADASIL is strikingly similar to early onset AD in that it is caused by germ line mutations in NOTCH 3 that generate toxic protein aggregates similar to those attributed to mutant forms of the amyloid precursor protein and presenilin genes. Since NOTCH 3 mutants clearly damage small blood vessels of white matter regions of the brain that lead to dementia, we speculate that both forms of dementia may have a similar pathogenesis, which is to cause ischemic damage by blocking blood flow or by impeding the removal of toxic protein aggregates by retrograde vascular clearance mechanisms.     

Transient pressure analysis for the reactor core and containment of a HTGR after a primary loop pressure boundary break accident

The pressure variances in the reactor core and containment of a High Temperature Gas-cooled Reactor (HTGR) after a primary loop pressure boundary break accident determine the structural integrity and safety of the reactor. Based on mass conservation, energy conservation and state equations, explicit formulae for the transient pressure and temperature variances in the pressure vessels were deduced, and a set of differential equations for the transient pressure and temperature variances in the containment were developed. Numerical simulation was also conducted to investigate the transient pressure and temperature variances in the pressure vessels and containment. The results show that energy transformation due to expansion work cannot be neglected. The maximum pressure in the containment could increase by 40 percent due to blockage caused by air in the containment. Detailed numerical simulations of the transient pressure and temperature variance in the reactor core flow passages were also conducted. The results show that the pressures acting on the reactor core and containment are below acceptable values.