Feedback Regulation and its Efficiency in Biochemical Networks

Intracellular biochemical networks fluctuate dynamically due to various internal and external sources of fluctuation. Dissecting the fluctuation into biologically relevant components is important for understanding how a cell controls and harnesses noise and how information is transferred over apparently noisy intracellular networks. While substantial theoretical and experimental advancement on the decomposition of fluctuation was achieved for feedforward networks without any loop, we still lack a theoretical basis that can consistently extend such advancement to feedback networks. The main obstacle that hampers is the circulative propagation of fluctuation by feedback loops. In order to define the relevant quantity for the impact of feedback loops for fluctuation, disentanglement of the causally interlocked influence between the components is required. In addition, we also lack an approach that enables us to infer non-perturbatively the influence of the feedback to fluctuation as the dual reporter system does in the feedforward network. In this work, we resolve these problems by extending the work on the fluctuation decomposition and the dual reporter system. For a single-loop feedback network with two components, we define feedback loop gain as the feedback efficiency that is consistent with the fluctuation decomposition for feedforward networks. Then, we clarify the relation of the feedback efficiency with the fluctuation propagation in an open-looped FF network. Finally, by extending the dual reporter system, we propose a conjugate feedback and feedforward system for estimating the feedback efficiency only from the statistics of the system non-perturbatively

Experiments on Rockfall Protection Embankments with Geogrids and Cushions

There are various protection measures against rockfalls. An embankment is effective in rockfall hazard mitigation at a dangerous slope end. The slope rockfall tests on full-scale embankments have been carried out. These embankments are made of sandy soil reinforced with geogrids. The cushioning layers which are made of geocells filled with crushed stones of 5-13 mm in diameter are also placed on the mountain side of the embankment. A boulder, i.e., RC block rolls down the test-site slope, and hits against the embankment. A new system of measuring instruments is employed in order to evaluate the impact force and the impact energy. One of important observations is a possibility that a rolling boulder carries it toward the top of an embankment because of its rolling momentum. The experimental results, especially the relationship between impact force and impact energy is discussed in this paper. © 2011, International Journal of GEOMATE

Experiments on pocket-type rockfall protective nets at a real slope

Although pocket-type rockfall protective nets are more economical and easier to install, the amount of rockfall energy they can absorb and the locations where they can be used are limited. Because of this, in recent years, a new rockfall protective net, which has built-in shock absorbers to prevent anchor rods from breaking and to absorb considerable rockfall energy due to their function, has been designed. This study was conducted to determine the effective range of implementation for a new pocket-type rockfall protective net, and to confirm the net\u27s reaction and energy absorption capacity upon the introduction of rotational energy approximating the actual behavior of a rockfall

Experiments on pocket-type rockfall protective nets at a real slope

Although pocket-type rockfall protective nets are more economical and easier to install, the amount of rockfall energy they can absorb and the locations where they can be used are limited. Because of this, in recent years, a new rockfall protective net, which has built-in shock absorbers to prevent anchor rods from breaking and to absorb considerable rockfall energy due to their function, has been designed. This study was conducted to determine the effective range of implementation for a new pocket-type rockfall protective net, and to confirm the net\u27s reaction and energy absorption capacity upon the introduction of rotational energy approximating the actual behavior of a rockfall

Hairball-Like Migration of “Onyx Threads” into the Draining Vein during Transarterial Embolization of a Dural Arteriovenous Fistula: A Case Report and Experimental Validation

Transarterial embolization using Onyx is a well-established treatment for dural arteriovenous fistulas (DAVFs). However, complications can arise when Onyx migrates into the venous side, impairing the draining veins. We encountered a case where Onyx, injected through the arterial side, strayed into the jugular vein, forming a hairball-like structure. Our study aimed to investigate the underlying mechanism of this unusual phenomenon. We postulated that Onyx precipitates into thread-like shapes when passing through extremely narrow openings. To test this, we extruded Onyx from a syringe through a 27-gauge needle into a silicone tube with flowing water. By varying the flow speed, we observed the hardening behavior of Onyx. Under slow flow, the extruded Onyx quickly solidified at the needle tip, forming a round mass. Conversely, high-speed flow resulted in Onyx being dispersed as small pieces. We successfully replicated the formation of “Onyx threads” under continuous slow flow conditions, similar to our case. This phenomenon occurs when Onyx unexpectedly migrates to the draining vein through a tiny opening during transarterial embolization for arteriovenous shunt diseases. Early recognition and appropriate measures are necessary to prevent occlusive complications in the draining veins and the pulmonary system

Macrophage centripetal migration drives spontaneous healing process after spinal cord injury.

Traumatic spinal cord injury (SCI) brings numerous inflammatory cells, including macrophages, from the circulating blood to lesions, but pathophysiological impact resulting from spatiotemporal dynamics of macrophages is unknown. Here, we show that macrophages centripetally migrate toward the lesion epicenter after infiltrating into the wide range of spinal cord, depending on the gradient of chemoattractant C5a. However, macrophages lacking interferon regulatory factor 8 (IRF8) cannot migrate toward the epicenter and remain widely scattered in the injured cord with profound axonal loss and little remyelination, resulting in a poor functional outcome after SCI. Time-lapse imaging and P2X/YRs blockade revealed that macrophage migration via IRF8 was caused by purinergic receptors involved in the C5a-directed migration. Conversely, pharmacological promotion of IRF8 activation facilitated macrophage centripetal movement, thereby improving the SCI recovery. Our findings reveal the importance of macrophage centripetal migration via IRF8, providing a novel therapeutic target for central nervous system injury

Dynamic modification of sphingomyelin in lipid microdomains controls development of obesity, fatty liver, and type 2 diabetes

Susumu Mitsutake, Kota Zama, Hazuki Yokota, Tetsuya Yoshida, Miki Tanaka, Masaru Mitsui, Masahito Ikawa, Masaru Okabe, Yoshikazu Tanaka, Tadashi Yamashita, Hiroshi Takemoto, Toshiro Okazaki, Ken Watanabe, Yasuyuki Igarashi, Dynamic Modification of Sphingomyelin in Lipid Microdomains Controls Development of Obesity, Fatty Liver, and Type 2 Diabetes, Journal of Biological Chemistry, Volume 286, Issue 32, 2011, Pages 28544-28555, ISSN 0021-9258, https://doi.org/10.1074/jbc.M111.255646

A Case of Endoscopic Mucosal Resection of Carcinoma in Adenoma at the Minor Duodenal Papilla

Here, we describe a case of minor papillary adenocarcinoma in adenoma that was treated with endoscopic mucosal resection (EMR). In a 67-year-old woman, sigmoid colon cancer was incidentally detected on preoperative upper gastrointestinal endoscopy. Endoscopy revealed a slightly elevated lesion at the minor duodenal papilla. The findings of a histopathologic examination were suggestive of adenocarcinoma. Computed tomography and magnetic resonance images identified a minute tumor, whereas endoscopic ultrasonography revealed that the tumor did not spread to the pancreas. We performed EMR of this lesion. There were no complications, and relapse has not occurred in 3 years. Cases of minor papillary adenocarcinoma treated with EMR are quite rare

Significance of Trans Fatty Acids and Omega-3 Fatty Acids in Japanese Men with Coronary Heart Disease

Trans fatty acids (TFA) are found naturally in ruminant foods (R-TFA) by biohydrogenation in ruminant animals or industrially produced oils (IP-TFA) by partial hydrogenation of vegetable or fish oils. The intake of TFA mainly IP-TFA is associated with an elevated risk of coronary heart disease (CHD), while some prospective cohort studies showed that R-TFA were associated with a lower risk for sudden cardiac death (SCD). Our case-control study showed that trans-C18:2 isomers (IP-TFA) were significantly higher, and palmitelaidic acid (R-TFA) levels were lower in patients with acute coronary syndrome (ACS) compared with healthy men. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have different effects on cardiometabolic risk factors. Delta-5 desaturase (D5D) is a key enzyme in the conversion of linoleic acid and alpha-linoleneic acid to arachidonic acid (AA) and EPA, respectively. Previous studies reported that low D5D estimated from the ratio of AA to dihomo-gamma linolenic acid predicts the incident cardiovascular disease. In our cross-sectional study with 436 men with ACS, various atherogenic lipid markers such as small dense LDL cholesterol and malondialdehyde-modified LDL were significantly inversely associated with D5D activity. We found that the EPA/AA may be a superior risk marker than DHA/AA in terms of correlation with atherogenic lipid profiles