Elevated serum lipoprotein (a) levels associated with ulcerative colitis in a young Japanese patient

Thromboembolism has been shown to play a role in the pathogenesis of inflammatory bowel disease (IBD). A possibility exists that lipoprotein (a) [Lp(a)], a newly-discovered prothrombotic factor, also participates in the development of at least some cases of IBD. Marked elevation of serum Lp(a) levels was observed in a young patient with ulcerative colitis. A biopsy specimen of the rectal mucosa showed findings compatible with ulcerative colitis, as well as small vessel thrombus occurring within the muscularis mucosa in the rectum. Serum Lp(a) levels were markedly elevated on admission (71 mg/dl), with a gradual decrease to 46 mg/dl on discharge. Moreover, serum Lp(a) levels decreased in parallel with clinical improvement. In the quiescent clinical stage, no small vessel thrombus was observed in the mucosa on follow-up colonoscopy. The association between IBD and hyper-Lp(a)-emia would be presumable but it has been, to our knowledge, previously unreported. The case reported here would be the first young patient, suggesting the presence of hyper-Lp(a)-emia and small vessel thrombus formation occurring in association with the development of ulcerative colitis.     

An Engineered Biliverdin-Compatible Cyanobacteriochrome Enables a Unique Ultrafast Reversible Photoswitching Pathway

Cyanobacteriochromes (CBCRs) are promising optogenetic tools for their diverse absorption properties with a single compact cofactor-binding domain. We previously uncovered the ultrafast reversible photoswitching dynamics of a red/green photoreceptor AnPixJg2, which binds phycocyanobilin (PCB) that is unavailable in mammalian cells. Biliverdin (BV) is a mammalian cofactor with a similar structure to PCB but exhibits redder absorption. To improve the AnPixJg2 feasibility in mammalian applications, AnPixJg2_BV4 with only four mutations has been engineered to incorporate BV. Herein, we implemented femtosecond transient absorption (fs-TA) and ground state femtosecond stimulated Raman spectroscopy (GS-FSRS) to uncover transient electronic dynamics on molecular time scales and key structural motions responsible for the photoconversion of AnPixJg2_BV4 with PCB (Bpcb) and BV (Bbv) cofactors in comparison with the parent AnPixJg2 (Apcb). Bpcb adopts the same photoconversion scheme as Apcb, while BV4 mutations create a less bulky environment around the cofactor D ring that promotes a faster twist. The engineered Bbv employs a reversible clockwise/counterclockwise photoswitching that requires a two-step twist on ~5 and 35 picosecond (ps) time scales. The primary forward P_fr → P_o transition displays equal amplitude weights between the two processes before reaching a conical intersection. In contrast, the primary reverse P_o → P_fr transition shows a 2:1 weight ratio of the ~35 ps over 5 ps component, implying notable changes to the D-ring-twisting pathway. Moreover, we performed pre-resonance GS-FSRS and quantum calculations to identify the Bbv vibrational marker bands at ~659,797, and 1225 cm⁻¹. These modes reveal a stronger H-bonding network around the BV cofactor A ring with BV4 mutations, corroborating the D-ring-dominant reversible photoswitching pathway in the excited state. Implementation of BV4 mutations in other PCB-binding GAF domains like AnPixJg4, AM1_1870g3, and NpF2164g5 could promote similar efficient reversible photoswitching for more directional bioimaging and optogenetic applications, and inspire other bioengineering advances.     

Negation-Limited Complexity of Parity and Inverters

In negation-limited complexity, one considers circuits with a limited number of NOT gates, being motivated by the gap in our understanding of monotone versus general circuit complexity, and hoping to better understand the power of NOT gates. We give improved lower bounds for the size (the number of AND/OR/NOT) of negation-limited circuits computing Parity and for the size of negation-limited inverters. An inverter is a circuit with inputs x ₁,…,x _n and outputs ¬ x ₁,…,¬ x _n . We show that: (a) for n=2 ^r ?1, circuits computing Parity with r?1 NOT gates have size at least 6n?log?₂(n+1)?O(1), and (b) for n=2 ^r ?1, inverters with r NOT gates have size at least 8n?log?₂(n+1)?O(1). We derive our bounds above by considering the minimum size of a circuit with at most r NOT gates that computes Parity for sorted inputs x ₁≥???≥x _n . For an arbitrary r, we completely determine the minimum size. It is 2n?r?2 for odd n and 2n?r?1 for even n for ?log?₂(n+1)??1≤r≤n/2, and it is ?3n/2??1 for r≥n/2. We also determine the minimum size of an inverter for sorted inputs with at most r NOT gates. It is 4n?3r for ?log?₂(n+1)?≤r≤n. In particular, the negation-limited inverter for sorted inputs due to Fischer, which is a core component in all the known constructions of negation-limited inverters, is shown to have the minimum possible size. Our fairly simple lower bound proofs use gate elimination arguments in a somewhat novel way.     

Acetaminophen-Induced Rat Hepatotoxicity Based on M1/M2-Macrophage Polarization,in Possible Relation to Damage-Associated Molecular Patterns and Autophagy

Overdose of acetaminophen (APAP), an antipyretic drug, is an important cause of liver injury. However, the mechanism in the rat model remains undetermined. We analyzed APAP-induced hepatotoxicity using rats based on M1/M2-macrophage functions in relation to damage-associated molecular patterns (DAMPs) and autophagy. Liver samples from six-week-old rats injected with APAP (1000 mg/kg BW, ip, once) after 15 h fasting were collected at hour 10, and on days 1, 2, 3, and 5. Liver lesions consisting of coagulation necrosis and inflammation were seen in the affected centrilobular area on days 1 and 2, and then, recovered with reparative fibrosis by day 5. Liver exudative enzymes increased transiently on day 1. CD68⁺ M1-macrophages increased significantly on days 1 and 2 with increased mRNAs of M1-related cytokines such as IFN-γ and TNF-α, whereas CD163⁺ M2-macrophages appeared later on days 2 and 3. Macrophages reacting to MHC class II and Iba1 showed M1-type polarization, and CD204⁺ macrophages tended to be polarized toward M2-type. At hour 10, interestingly, HMGB1 (representative DAMPs) and its related signals, TLR-9 and MyD88, as well as LC3B⁺ autophagosomes began to increase. Collectively, the pathogenesis of rat APAP hepatotoxicity, which is the first, detailed report for a rat model, might be influenced by macrophage functions of M1 type for tissue injury/inflammation and M2-type for anti-inflammatory/fibrosis; particularly, M1-type may function in relation to DAMPs and autophagy. Understanding the interplayed mechanisms would provide new insight into hepato-pathogenesis and contribute to the possible development of therapeutic strategies.     

How to identify water from thickener aqueous solutions by touch

Water detection is one of the most crucial psychological processes for many animals. However, nobody knows the perception mechanism of water through our tactile sense. In the present study, we found that a characteristic frictional stimulus with large acceleration is one of the cues to differentiate water from water contaminated with thickener. When subjects applied small amounts of water to a glass plate, strong stick-slip phenomena with a friction force of 0.46 ± 0.30 N and a vertical force of 0.57 ± 0.36 N were observed at the skin surface, as shown in previous studies. Surprisingly, periodic shears with acceleration seven times greater than gravitational acceleration occurred during the application process. Finite-element analyses predicted that these strong stimuli could activate tactile receptors: Meissner''s corpuscle and Pacinians. When such stimuli were applied to the fingertips by an ultrasonic vibrator, a water-like tactile texture was perceived by some subjects, even though no liquid was present between the fingertip and the vibrator surface. These findings could potentially be applied in the following areas: materials science, information technology, medical treatment and entertainment.     

Tocopherol Content and Fatty Acid Distribution of Peas (<Emphasis Type="Italic">Pisum sativum</Emphasis> L.)

The positional distribution of fatty acids (FA) of triacylglycerols (TAG) and major phospholipids (PL) prepared from four cultivars of peas (Pisum sativum L.) were investigated as well as their tocopherol contents. The lipids extracted from these peas were separated by thin-layer chromatography (TLC) into seven fractions. The major lipid components were PL (52.2–61.3%) and TAG (31.2–40.3%), while the other components were also present in minor proportions (5.6–9.2%). γ-Tocopherol was present in the highest concentration, and α- and δ-tocopherols were very small amounts. The main PL components isolated from the four cultivars were phosphatidylcholine (42.3–49.2%), followed by phosphatidylinositol (23.3–25.2%) and then phosphatidylethanolamine (17.7–20.5%). Small but significant differences (P < 0.05) in FA distribution existed when different pea cultivars were determined. However, the principal characteristics of the FA distribution in the TAG and the three PL were evident among the four cultivars; unsaturated FA were predominantly located in the sn-2 position, and saturated FA primary occupied the sn-1 or sn-3 position in the oils of the peas. These results suggest that the regional distribution of tocopherols and fatty acids in peas is not dependent on the climatic conditions and the soil characteristics of the cultivation areas during the growing season.     

Lipid components,fatty acid distributions of triacylglycerols and phospholipids in rice brans

Endogenous tocochromanols in extracted lipids from rice brans of the five cultivars were determined by high-performance liquid chromatography, and were investigated in relation to the fatty acid (FA) distribution of triacylglycerols (TAG) and phospholipids (PL). The dominant tocols were α-tocopherol and γ-tocotrienol, followed by α-tocotrienol and with much smaller amounts of γ-tocopherol and δ-tocotrienol. The lipids of these rice brans comprised mainly TAG (80.6–86.0 wt.%), free FA (4.2–9.0 wt.%), and phospholipids (5.5–6.7 wt.%), whilst other components were also detected in minor proportions (0.2–2.1 wt.%). The PL components included phosphatidyl choline (31.8–46.8 wt.%), phosphatidyl ethanolamine (25.0–38.9 wt.%) and phosphatidyl inositol (20.2–23.2 wt.%). Comparison of these different cultivars showed, with a few exceptions, no significant differences (P > 0.05) in FA distribution. FA distribution of TAG among the five cultivars was evident in the rice brans: unsaturated FA were predominantly concentrated at the sn-2 position and saturated FA primarily occupying the sn-1 or sn-3 position. These results suggest that the tocopherol content, lipid component, and FA distribution in rice brans are not dependent on the cultivation areas during the growing season.