VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease

Kim, Jeonghan,Gupta, Rajeev,Blanco, Luz P.,Yang, Shutong,Shteinfer-Kuzmine, Anna,Wang, Kening,Zhu, Jun,Yoon, Hee Eun,Wang, Xinghao,Kerkhofs, Martijn,Kang, Hyeog,Brown, Alexandra L.,Park, Sung-Jun,Xu, American Association for the Advancement of Scienc 2019 Science Vol.366 No.6472

<P><B>VDACs are MOM's ruin</B></P><P>Mitochondrial DNA (mtDNA) is normally kept within the mitochondria. It can be released into the cytosol in response to stress and thus encounter cytosolic DNA sensors, triggering type I interferon responses. During apoptosis, mtDNA release is mediated by macropores in the mitochondrial outer membrane (MOM) created by oligomerization of the proteins BAX and BAK. Kim <I>et al.</I> found that during oxidative stress, mtDNA escapes instead through macropores formed by oligomerization of voltage-dependent anion channels (VDACs) (see the Perspective by Crow). In a mouse model of lupus, an inhibitor of VDAC oligomerization diminished mtDNA release and downstream signaling events. This treatment reduced lupus-like symptoms in the model, suggesting a potential therapeutic route for conditions mediated by mtDNA release.</P><P><I>Science</I>, this issue p. 1531; see also p. 1445</P><P>Mitochondrial stress releases mitochondrial DNA (mtDNA) into the cytosol, thereby triggering the type Ι interferon (IFN) response. Mitochondrial outer membrane permeabilization, which is required for mtDNA release, has been extensively studied in apoptotic cells, but little is known about its role in live cells. We found that oxidatively stressed mitochondria release short mtDNA fragments via pores formed by the voltage-dependent anion channel (VDAC) oligomers in the mitochondrial outer membrane. Furthermore, the positively charged residues in the N-terminal domain of VDAC1 interact with mtDNA, promoting VDAC1 oligomerization. The VDAC oligomerization inhibitor VBIT-4 decreases mtDNA release, IFN signaling, neutrophil extracellular traps, and disease severity in a mouse model of systemic lupus erythematosus. Thus, inhibiting VDAC oligomerization is a potential therapeutic approach for diseases associated with mtDNA release.</P>

Effects of Astragalus Polysaccharides, Achyranthes bidentata Polysaccharides, and Acantbepanax senticosus Saponin on the Performance and Immunity in Weaned Pigs

Kang, P.,Xiao, H.L.,Hou, Y.Q.,Ding, B.Y.,Liu, Y.L.,Zhu, H.L.,Hu, Q.Z.,Hu, Y.,Yin, Y.L. Asian Australasian Association of Animal Productio 2010 Animal Bioscience Vol.23 No.6

Two trials were conducted to study the effects of two Chinese herbal polysaccharides, Astragalus polysaccharides (APS) and Achyranthes bidentata polysaccharides (ABPS), and one Chinese herbal saponin, Acantbepanax senticosus saponin (ASS), on the immunity and growth performance of weaned pigs. Experiment 1 was a 14-day growth assay, in which 32 weaned pigs were randomly allocated to one of four dietary treatments: i) 0.05% talcum powder control; ii) 0.05% APS; iii) 0.05% mixture of APS and ASS in a 1:1 ratio by weight; and iv) 0.05% mixture of APS, ASS, and ABPS in a ratio of 1:1:1 by weight. Blood samples were collected on day 14 to determine plasma parameters. Feed intake, body weight gain, and feed efficiency were also determined. Experiment 2 was a 21-day immunity assay, in which 16 weaned pigs were randomly allotted to one of two dietary treatments: i) 0.05% talcum powder control; and ii) 0.05% mixture of APS and ASS in a 1:1 ratio by weight. On day 21, pigs were challenged with lipopolysaccharide (LPS) and 3 h later blood samples were collected and analyzed for lymphocyte proliferation as well as interleukin 6 (IL-6), insulin-like growth factor 1 (IGF-1), growth hormone (GH), and cortisol levels. In Experiment 1, feeding Chinese herbal polysaccharides and saponin increased growth performance of the pigs. The effects of the mixture of APS and ASS were especially notable, as there was a significant improvement in growth performance compared with the control (p<0.05). The plasma concentration of immunoglobulin G (IgG), nitric oxide (NO), and nitric oxide synthase (NOS) were increased in all treatments groups, with the mixture of APS and ASS increasing the level of IgG and NOS significantly (p<0.05), compared with the control. There was no difference in the NO level between the control and treatment groups (p>0.05). In Experiment 2, Chinese herbal polysaccharides and saponin showed immunostimulating effects. The level of cortisol, GH, and IGF-I were significantly increased (p>0.05), and the level of IL-6 showed a significant decrease (p<0.05) in the APS and ASS treatment after the LPS challenge. The mixture of APS and ASS could stimulate the blood lymphocyte proliferation significantly whether the LPS was injected or not (p<0.05). These results show that Chinese herbal extracts can improve growth performance and stimulate immunity of weaned pigs. A mixture of APS and ASS, compared with APS alone, could be a new kind of immunostimulant for weaned pigs, which could result in greater positive effects on their growth performance and immunity.

Effects of Dietary Chromium Methionine on Growth Performance, Carcass Composition, Meat Colour and Expression of the Colour-related Gene Myoglobin of Growing-finishing Pigs

Li, Y.S.,Zhu, N.H.,Niu, P.P.,Shi, F.X.,Hughes, C.L.,Tian, G.X.,Huang, R.H. Asian Australasian Association of Animal Productio 2013 Animal Bioscience Vol.26 No.7

To investigate the effect of dietary chromium (Cr) as Cr methionine (CrMet) on growth performance, carcass traits, pork quality, meat colour and expression of meat colour-related genes in growing-finishing pigs, 189 crossbred Duroc${\times}$(Landrace${\times}$Yorkshire) growing-finishing pigs (male, castrated, average initial BW $74.58{\pm}1.52$ kg) were selected and randomly allocated into four groups. Dietary treatments per kg of feed were as follows: 0 (CT), 0.3 mg/kg (T1), 0.6 mg/kg (T2) and 0.9 mg/kg (T3) Cr (in the form of CrMet; as-fed basis), and each treatment was replicated five times with 8 to 10 pigs per replicate pen. During the 28 d of the experiment, both the ADG and the ADFI increased linearly (p<0.05) as the level of dietary Cr increased. The F/G ratio decreased linearly (p<0.05). As dietary Cr increased, loin muscle areas (linear, p = 0.013) and average backfat thickness (linear, p = 0.072) decreased. Shear force (linear, p = 0.070) and Commission Internationale de I'$\acute{E}$clairage (CIE) redness (quadratic, p = 0.028) were increased. In addition, CIE Lightness (quadratic, p = 0.053) were decreased as dietary Cr increased. As dietary Cr increased, total myglobin (Mb) content (quadratic, p = 0.015) and the mb mRNA levels (quadratic, p = 0.046) in longissimus muscles of pigs were up-regulated. In conclusion, supplementation of dietary Cr improved growth and meat colour, but increased shear force and decreased IMF reduced palatability of longissimus muscles. Moreover, the increasing total Mb content and mb mRNA levels indicated that CrMet dietary supplementation may improve meat colour via up-regulating expression of the mb gene.

Effects of Dietary Lysine Levels on Apparent Nutrient Digestibility and Serum Amino Acid Absorption Mode in Growing Pigs

Zeng, P.L.,Yan, H.C.,Wang, X.Q.,Zhang, C.M.,Zhu, C.,Shu, G.,Jiang, Q.Y. Asian Australasian Association of Animal Productio 2013 Animal Bioscience Vol.26 No.7

Two experiments were conducted to determine the effects of different dietary lysine levels on the apparent nutrient digestibility, the serum amino acid (AA) concentration, and the biochemical parameters of the precaval and portal vein blood in growing pigs. In Experiment 1, 15 noncannulated pigs received diets with different lysine densities (0.65%, 0.95%, and 1.25% lysine) for 13 d. A total collection digestion test was performed, and blood samples were collected from the precaval vein at the end of the experiment. In Experiment 2, four cannulated pigs were fed the same diets of Experiment 1. The experiment used a self-control experimental design and was divided into three periods. On d 5 of each period, at 0.5 h before feeding and hourly up to 8 h after feeding, single blood samples were collected from catheters placed in the portal vein. In Experiment 1, some serum AAs (including lysine), serum urinary nitrogen (SUN), and total protein (TP) concentrations were significantly affected by the dietary lysine levels (p<0.05). Moreover, the 0.65% lysine treatment showed a significant lower apparent digestibility of gross energy, dry matter, crude protein, and phosphorus than the other treatments (p<0.05). In Experiment 2, serum lysine, histidine, phenylalanine, threonine, valine, isoleucine (p = 0.0588), triglyceride, and SUN (p = 0.0572) concentrations were significantly affected by the dietary lysine levels (p<0.05). Additionally, almost all of the determined serum AA and total AA concentrations reached their lowest values at 0.5 h before feeding and their highest values at 2 h after feeding (p<0.05). These findings indicate that the greatest absorption of AA occurred at 2 h after feeding and that the dynamic profile of serum AA is affected by the dietary lysine levels. Moreover, when the dietary lysine content was 0.95%, the growing pigs achieved a better nutrient digestibility and serum metabolites levels.

Energy and Standardized Ileal Amino Acid Digestibilities of Chinese Distillers Dried Grains, Produced from Different Regions and Grains Fed to Growing Pigs

Xue, P.C.,Dong, B.,Zang, J.J.,Zhu, Z.P.,Gong, L.M. Asian Australasian Association of Animal Productio 2012 Animal Bioscience Vol.25 No.1

Two experiments were conducted to determine the digestibility of crude protein (CP), amino acids and energy in three Chinese corn distillers dried grains with solubles (DDGS), one rice DDGS, one American corn DDGS and one American high protein distillers dried grains (HP-DDG). In Exp. 1, the apparent ileal digestibility (AID) and standardized ileal digestibility (SID) of CP and amino acids in the six samples were determined using cannulated barrows (initial BW: $43.3{\pm}1.7$ kg). In Exp. 2, the digestible energy (DE) and metabolizable energy (ME) content of these six samples were determined using crossbred barrows (initial BW: $46.0{\pm}2.5$ kg). The results of the two experiments indicated that Chinese corn DDGS is generally similar to American DDGS in chemical composition, digestibility of amino acids, DE and ME. However, Chinese DDGS had a lower Lys concentration (0.50% vs. 0.74%) and SID Lys (52.3% vs. 57.0%, p<0.01). The DE and ME values in Chinese corn DDGS were 3,427 and 3,306 kcal/kg, respectively. Rice DDGS had a similar DE and ME (3,363 and 3,228 kcal/kg) but higher Lys concentration (0.64% vs. 0.50%) to corn DDGS, while the SID of Lys was quite low (61.8%, p<0.01). HP-DDG had high value of SID of Lys, DE and ME (79.8%, 3,899 and 3,746 kcal/kg). In conclusion, except for a lower Lys concentrations and availability, the chemical composition, digestibility of amino acids, DE and ME values in Chinese corn DDGS are similar to American corn DDGS. Additionally, the rice DDGS had lower Lys content and digestible Lys values than that in corn DDGS. Thirdly, HP-DDG has higher levels of digestible amino acids and energy than DDGS.

Effects of Dietary Electrolyte Balance on Growth Performance, Nitrogen Metabolism and Some Blood Biochemical Parameters of Growing Rabbits

Li, J.W.,Wang, X.P.,Wang, C.Y.,Zhu, Y.L.,Li, F.C. Asian Australasian Association of Animal Productio 2013 Animal Bioscience Vol.26 No.12

The effects of different dietary electrolyte balance (DEB) on growth performance, nitrogen (N) metabolism and some blood biochemical parameters were investigated in 2 to 3 months old growing rabbits. A total of 150 growing rabbits of 2 months age were randomly divided into five groups according to average body weight, with 30 rabbits in each group. The DEB levels of the five experimental diets were -154, -3.16, +201, +347, and +500 meq/kg of dry matter (DM), respectively. There was a 7-d adaptation period and a 23-d experimental period. The results showed that the DEB levels had a quadratic affect on the average daily feed intake (ADFI) (p<0.001). The greatest ADFI was achieved when the DEB level was +201 meq/kg DM. Fecal N (FN) content linearly decreased (0.047), while digestible N (DN), retained N (RN), efficiency of intake N converted into digestible N (DN/IN) and the efficiency of intake N converted into retained N (RN/IN) linearly increased with the DEB increase (0.020, 0.004, 0.021, and 0.049, respectively). Serum phosphorus (P) ion content linearly increased with the DEB increase (p = 0.036). The DEB had a quadratic relationship with serum anion gap (AG) (p = 0.002) and serum parathyroid hormone (PTH) content (p = 0.016). The DEB levels quadratically affected base excess (BE) in the plasma (p<0.001). In conclusion, the DEB unaffected growth performance but affected feed intake, N metabolism and some blood biochemical parameters of growing rabbits.

Effects of Inclusion Levels of Wheat Bran and Body Weight on Ileal and Fecal Digestibility in Growing Pigs

Q. Huang,Y.B. Su,D.F. Li,L. Liu,C.F. Huang,Z.P. Zhu,C.H. Lai 아세아·태평양축산학회 2015 Animal Bioscience Vol.28 No.6

The objective of this study was to determine the effects of graded inclusions of wheat bran (0%, 9.65%, 48.25% wheat bran) and two growth stages (from 32.5 to 47.2 kg and 59.4 to 78.7 kg, respectively) on the apparent ileal digestibility (AID), apparent total tract digestibility (ATTD) and hindgut fermentation of nutrients and energy in growing pigs. Six light pigs (initial body weight [BW] 32.5±2.1 kg) and six heavy pigs (initial BW 59.4±3.2 kg) were surgically prepared with a T-cannula in the distal ileum. A difference method was used to calculate the nutrient and energy digestibility of wheat bran by means of comparison with a basal diet consisting of corn-soybean meal (0% wheat bran). Two additional diets were formulated by replacing 9.65% and 48.25% wheat bran by the basal diet, respectively. Each group of pigs was allotted to a 6×3 Youden square design, and pigs were fed to three experimental diets during three 11-d periods. Hindgut fermentation values were calculated as the differences between ATTD and AID values. For the wheat bran diets, the AID and ATTD of dry matter (DM), ash, organic matter (OM), carbohydrates (CHO), gross energy (GE), and digestible energy (DE) decreased with increasing inclusion levels of wheat bran (p<0.05). While only AID of CHO and ATTD of DM, ash, OM, CHO, GE, and DE content differed (p<0.05) when considering the BW effect. For the wheat bran ingredient, there was a wider variation effect (p<0.01) on the nutrient and energy digestibility of wheat bran in 9.65% inclusion level due to the coefficient of variation (CV) of the nutrient and energy digestibility being higher at 9.65% compared to 48.25% inclusion level of wheat bran. Digestible energy content of wheat bran at 48.25% inclusion level (4.8 and 6.7 MJ/kg of DM, respectively) fermented by hindgut was significantly higher (p<0.05) than that in 9.65% wheat bran inclusion level (2.56 and 2.12 MJ/kg of DM, respectively), which was also affected (p<0.05) by two growth stages. This increase in hindgut fermentation caused the difference in ileal DE (p<0.05) to disappear at total tract level. All in all, increasing wheat bran levels in diets negatively influences the digestibility of some nutrients in pigs, while it positively affects the DE fermentation in the hindgut.

Expression Profiles of Cellular Retinol-binding Protein, Type II (CRBP II) in Erlang Mountainous Chickens

Yin, H.D.,Tian, K.,Li, D.Y.,Gilbert, E.R.,Xiao, L.H.,Chen, S.Y.,Wang, Y.,Liu, Y.P.,Zhao, X.L.,Zhu, Q. Asian Australasian Association of Animal Productio 2014 Animal Bioscience Vol.27 No.3

Cellular retinol-binding protein II (CRBP II) belongs to the family of cellular retinol-binding proteins and plays a major role in absorption, transport, and metabolism of vitamin A. In addition, because vitamin A is correlated with reproductive performance, we measured CRBP II mRNA abundance in erlang mountainous chickens by real-time PCR using the relative quantification method. The expression of CRBP II showed a tissue-specific pattern and egg production rate-dependent changes. The expression was very high (p<0.05) in jejunum and liver, intermediate in kidney, ovary, and oviduct, and lowest (p<0.05) in heart, hypothalamus, and pituitary. In the hypothalamus, oviduct, ovary, and pituitary, CRBP II mRNA abundance were correlated to egg production rate, which increased from 12 wk to 32 wk, peaked at 32 wk relative to the other time points, and then decreased from 32 wk to 45 wk. In contrast, the expression of CRBP II mRNA in heart, jejunum, kidney, and liver was not different at any of the ages evaluated in this study. These data may help to understand the genetic basis of vitamin A metabolism, and suggest that CRBP II may be a candidate gene to affect egg production traits in chickens.

Effects of Inclusion Levels of Wheat Bran and Body Weight on Ileal and Fecal Digestibility in Growing Pigs

Huang, Q.,Su, Y.B.,Li, D.F.,Liu, L.,Huang, C.F.,Zhu, Z.P.,Lai, C.H. Asian Australasian Association of Animal Productio 2015 Animal Bioscience Vol.28 No.6

The objective of this study was to determine the effects of graded inclusions of wheat bran (0%, 9.65%, 48.25% wheat bran) and two growth stages (from 32.5 to 47.2 kg and 59.4 to 78.7 kg, respectively) on the apparent ileal digestibility (AID), apparent total tract digestibility (ATTD) and hindgut fermentation of nutrients and energy in growing pigs. Six light pigs (initial body weight [BW] $32.5{\pm}2.1kg$) and six heavy pigs (initial BW $59.4{\pm}3.2kg$) were surgically prepared with a T-cannula in the distal ileum. A difference method was used to calculate the nutrient and energy digestibility of wheat bran by means of comparison with a basal diet consisting of corn-soybean meal (0% wheat bran). Two additional diets were formulated by replacing 9.65% and 48.25% wheat bran by the basal diet, respectively. Each group of pigs was allotted to a $6{\times}3$ Youden square design, and pigs were fed to three experimental diets during three 11-d periods. Hindgut fermentation values were calculated as the differences between ATTD and AID values. For the wheat bran diets, the AID and ATTD of dry matter (DM), ash, organic matter (OM), carbohydrates (CHO), gross energy (GE), and digestible energy (DE) decreased with increasing inclusion levels of wheat bran (p<0.05). While only AID of CHO and ATTD of DM, ash, OM, CHO, GE, and DE content differed (p<0.05) when considering the BW effect. For the wheat bran ingredient, there was a wider variation effect (p<0.01) on the nutrient and energy digestibility of wheat bran in 9.65% inclusion level due to the coefficient of variation (CV) of the nutrient and energy digestibility being higher at 9.65% compared to 48.25% inclusion level of wheat bran. Digestible energy content of wheat bran at 48.25% inclusion level (4.8 and 6.7 MJ/kg of DM, respectively) fermented by hindgut was significantly higher (p<0.05) than that in 9.65% wheat bran inclusion level (2.56 and 2.12 MJ/kg of DM, respectively), which was also affected (p<0.05) by two growth stages. This increase in hindgut fermentation caused the difference in ileal DE (p<0.05) to disappear at total tract level. All in all, increasing wheat bran levels in diets negatively influences the digestibility of some nutrients in pigs, while it positively affects the DE fermentation in the hindgut.

Temperature-Dependent Photoluminescence from ZnO/Zn0.85Mg0.15O Heterostructure Grown on Si(111) Substrates

L. P. Zhu,X. Q. Gu,H. P. He,F. Huang,M. X. Qiu,Z. Z. Ye,Y. Z. Zhang,B. H. Zhao 한국물리학회 2008 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.53 No.5

A ZnO/Zn0.85Mg0.15O single quantum well (SQW) was fabricated on a Si(111) substrate by using a pulsed laser deposition (PLD) technique. Photoluminescence (PL) measurements were carried out in the range of 10 − 290 K in order to investigate the mechanism of carrier dynamics. At 10 K, the sample exhibited two predominant ultraviolet emissions, one at 3.57 eV and the other at 3.38 eV, which were attributed to recombinations of localized excitons (LE band) in the barrier and the well layers, respectively. The quantum well emission showed a blue shift of nearly 20 meV with respect to the epitaxial ZnO films. We also observed that the carrier localization resulted in an “S-shaped” red-blue-red shift of the ∽3.38 eV emission with increasing temperature. A ZnO/Zn0.85Mg0.15O single quantum well (SQW) was fabricated on a Si(111) substrate by using a pulsed laser deposition (PLD) technique. Photoluminescence (PL) measurements were carried out in the range of 10 − 290 K in order to investigate the mechanism of carrier dynamics. At 10 K, the sample exhibited two predominant ultraviolet emissions, one at 3.57 eV and the other at 3.38 eV, which were attributed to recombinations of localized excitons (LE band) in the barrier and the well layers, respectively. The quantum well emission showed a blue shift of nearly 20 meV with respect to the epitaxial ZnO films. We also observed that the carrier localization resulted in an “S-shaped” red-blue-red shift of the ∽3.38 eV emission with increasing temperature.