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FcγRIIb mediates amyloid-β neurotoxicity and memory impairment in Alzheimer's disease.
Kam, Tae-In,Song, Sungmin,Gwon, Youngdae,Park, Hyejin,Yan, Ji-Jing,Im, Isak,Choi, Ji-Woo,Choi, Tae-Yong,Kim, Jeongyeon,Song, Dong-Keun,Takai, Toshiyuki,Kim, Yong-Chul,Kim, Key-Sun,Choi, Se-Young,Choi, American Society for Clinical Investigation 2013 The Journal of clinical investigation Vol.123 No.7
<P>Amyloid-β (Aβ) induces neuronal loss and cognitive deficits and is believed to be a prominent cause of Alzheimer's disease (AD); however, the cellular pathology of the disease is not fully understood. Here, we report that IgG Fcγ receptor II-b (FcγRIIb) mediates Aβ neurotoxicity and neurodegeneration. We found that FcγRIIb is significantly upregulated in the hippocampus of AD brains and neuronal cells exposed to synthetic Aβ. Neuronal FcγRIIb activated ER stress and caspase-12, and Fcgr2b KO primary neurons were resistant to synthetic Aβ-induced cell death in vitro. Fcgr2b deficiency ameliorated Aβ-induced inhibition of long-term potentiation and inhibited the reduction of synaptic density by naturally secreted Aβ. Moreover, genetic depletion of Fcgr2b rescued memory impairments in an AD mouse model. To determine the mechanism of action of FcγRIIb in Aβ neurotoxicity, we demonstrated that soluble Aβ oligomers interact with FcγRIIb in vitro and in AD brains, and that inhibition of their interaction blocks synthetic Aβ neurotoxicity. We conclude that FcγRIIb has an aberrant, but essential, role in Aβ-mediated neuronal dysfunction.</P>
Gwon, Youngdae,Kam, Tae-In,Kim, Seo-Hyun,Song, Sungmin,Park, Hyejin,Lim, Bitna,Lee, Haneul,Lee, Weontae,Jo, Dong-Gyu,Jung, Yong-Keun Society for Neuroscience 2018 The Journal of neuroscience Vol.38 No.42
<P>Emerging evidences suggest that intraneuronal A beta correlates with the onset of Alzheimer's disease (AD) and highly contributes to neurodegeneration. However, critical mediator responsible for A beta uptake in AD pathology needs to be clarified. Here, we report that Fc gamma RIIb2, a variant of Fc gamma-receptor IIb (Fc gamma RIIb), functions in neuronal uptake of pathogenic A beta. Cellular accumulation of oligomeric A beta(1-42), not monomeric A beta(1-42) or oligomeric A beta(1-40), was blocked by Fcgr2b knock-out in neurons and partially in astrocytes. A beta(1-42) internalization was Fc gamma RIIb2 di-leucine motif-dependent and attenuated by TOM1, a Fc gamma RIIb2-binding protein that repressed the receptor recycling. TOM1 expression was downregulated in the hippocampus of male 3xTg-AD mice and AD patients, and regulated by miR-126-3p in neuronal cells after exposure to A beta(1-42). In addition, memory impairments in male 3xTg-AD mice were rescued by the lentiviral administration of TOM1 gene. Augmented A beta uptake into lysosome caused its accumulation in cytoplasm and mitochondria. Moreover, neuronal accumulation of A beta in both sexes of 3xTg-AD mice and memory deficits in male 3xTg-AD mice were ameliorated by forebrain-specific expression of A beta-uptake-defective Fcgr2b mutant. Our findings suggest that Fc gamma RIIb2 is essential for neuropathic uptake of A beta in AD.</P>
OCIAD2 activates γ-secretase to enhance amyloid β production by interacting with nicastrin
Han, Jonghee,Jung, Sunmin,Jang, Jiyeon,Kam, Tae-In,Choi, Hyunwoo,Kim, Byung-Ju,Nah, Jihoon,Jo, Dong-Gyu,Nakagawa, Toshiyuki,Nishimura, Masaki,Jung, Yong-Keun Springer-Verlag 2014 Cellular and molecular life sciences Vol.71 No.13
Direct-fed Microbials for Ruminant Animals
Seo, Ja-Kyeom,Kim, Seon-Woo,Kim, Myung-Hoo,Upadhaya, Santi D.,Kam, Dong-Keun,Ha, Jong-K. Asian Australasian Association of Animal Productio 2010 Animal Bioscience Vol.23 No.12
Direct-fed microbials (DFM) are dietary supplements that inhibit gastrointestinal infection and provide optimally regulated microbial environments in the digestive tract. As the use of antibiotics in ruminant feeds has been banned, DFM have been emphasized as antimicrobial replacements. Microorganisms that are used in DFM for ruminants may be classified as lactic acid producing bacteria (LAB), lactic acid utilizing bacteria (LUB), or other microorganisms including species of Lactobacillus, Bifidobacterium, Enterococcus, Streptococcus, Bacillus and Propionibacterium, strains of Megasphaera elsdenii and Prevotella bryantii and yeast products containing Saccharomyces and Aspergillus. LAB may have beneficial effects in the intestinal tract and rumen. Both LAB and LUB potentially moderate rumen conditions and improve feed efficiency. Yeast DFM may reduce harmful oxygen, prevent excess lactate production, increase feed digestibility, and improve fermentation in the rumen. DFM may also compete with and inhibit the growth of pathogens, stimulate immune function, and modulate microbial balance in the gastrointestinal tract. LAB may regulate the incidence of diarrhea, and improve weight gain and feed efficiency. LUB improved weight gain in calves. DFM has been reported to improve dry matter intake, milk yield, fat corrected milk yield and milk fat content in mature animals. However, contradictory reports about the effects of DFM, dosages, feeding times and frequencies, strains of DFM, and effects on different animal conditions are available. Cultivation and preparation of ready-to-use strict anaerobes as DFM may be cost-prohibitive, and dosing methods, such as drenching, that are required for anaerobic DFM are unlikely to be acceptable as general on-farm practice. Aero-tolerant rumen microorganisms are limited to only few species, although the potential isolation and utilization of aero-tolerant ruminal strains as DFM has been reported. Spore forming bacteria are characterized by convenience of preparation and effectiveness of DFM delivery to target organs and therefore have been proposed as DFM strains. Recent studies have supported the positive effects of DFM on ruminant performance.
( Seoyoung Jeon ),( Mingyung Lee ),( Jakyeom Seo ),( Jeong-hoon Kim ),( Dong-Keun Kam ),( Seongwon Seo ) 한국축산학회 2021 한국축산학회지 Vol.63 No.5
Recently, a high level of dietary crude protein (CP) has become of interest as a possible practice to improve the carcass quality of beef cattle, and its level has been increasing in the field. However, there is little scientific evidence that supports this. This study was conducted to test whether a high dietary CP level would improve growth performance, body metabolism, and carcass traits in Hanwoo beef cattle. A total of 32 Hanwoo finishing beef cattle (18 multiparous cows, six heifers, and eight steers) participated in a 12-weeks feeding trial. Two kinds of total mixed rations were prepared to contain two different CP; 156 g/kg for the control (CON) and 173 g/kg of CP for the treatment (HCP), while maintaining a similar level of metabolizable energy. The experiment was ended when more than half of the steers reached the target body weight (730 kg). Blood was collected at the end of the experiment. After harvesting, the carcass trait was evaluated at the slaughterhouse according to Korean standards. The carcass yield score and grade were also calculated based on revised criteria. Overall, dry matter intake, average daily gain, blood metabolites concentration, and the carcass traits, except for backfat thickness and the yield score, did not differ between the treatments. The HCP had lower backfat thickness than those of CON. There was no difference in the carcass yield grade, but the yield score was higher in the HCP treatment. According to the newly revised carcass grading criteria, both yield score and grade were higher in HCP than in CON. Increasing CP supply decreased the carcass’s backfat thickness without altering growth performance and body metabolism, resulting in improved yield score and grade. Therefore, feeding a high CP diet may be beneficial in the farm income, although it may also increase feed cost and nitrogen excretion to the environment.
β-Mannanase (CTCZYME<SUP>®</SUP>) 첨가가 어린 송아지의 성장에 미치는 영향
이세영(Se-Young Lee),이상문(Sang-Moon Lee),김종형(Jong-Hyeong Kim),기광석(Kwang-Seok Ki),김현섭(Hyeon-Shup Kim),감동근(Dong-Keun Kam),이재환(Jae-Hwan Lee),이정진(Jung-Jin Lee),배귀석(Gui-Seck Bae),서성원(Seongwon Seo) 충남대학교 농업과학연구소 2010 농업과학연구 Vol.37 No.2
The objective of this study was to evaluate effects of supplementation of β-mannanase (CTCZYME<SUP>ⓡ</SUP>, CTCBIO, Inc.) on feed intake, growth performance and fecal health of calves fed two levels (3% vs. 8%) of palm kernel meal (PKM). A total of nine Holstein calves were divided into three groups, and fed a conventional starter containing 3% PKM (CON), CON+ 0.1% CTCZYME <SUP>ⓡ</SUP> (TRT1), or a starter containing 8% PKM+ 0.1% CTCZYME<SUP>ⓡ</SUP> (TRT2). No clinical symptom of calves was observed through the trial. We did not find significant differences among the treatments on mean feed intake, growth performance, or fecal health during the four-week experimental period. Feed efficiency tended to be improved by adding CTCZYME<SUP>ⓡ</SUP> (0.46, 0.87 and 0.52 for CON, TRT1 and TRT2, respectively). Compared with CON (921 g/d and 786 g/d), TRT2 had lower feed intake (727 g/d) and average daily gain (ADG, 631 g/d) before weaning. However, feed intake (2300 g/d) and ADG (1012 g/d) were similar or even higher in TRT2 than CON (2269 g/d and 560 g/d) after weaning. This was probably due to the effect of a large amount of mannan-oligosaccharide released from PKM by β-mannanase. Salmonella was not detected any fecal samples. No significant difference was observed in the number of fecal E. coli or fecal properties including color, smell, and watery indexes among the treatments. We conclude that a calf starter containing 8% PKM with 0.1% CTCZYME<SUP>ⓡ</SUP> is comparable with a conventional starter in feed intake and growth performance of calf, which is beneficial in terms of reduction in feed cost.
${\beta}$-Mannanase (CTCZYME$^{(R)}$) 첨가가 어린 송아지의 성장에 미치는 영향
이세영,이상문,김종형,기광석,김현섭,감동근,이재환,이정진,배귀석,서성원,Lee, Se-Young,Lee, Sang-Moon,Kim, Jong-Hyeong,Ki, Kwang-Seok,Kim, Hyeon-Shup,Kam, Dong-Keun,Lee, Jae-Hwan,Lee, Jung-Jin,Bae, Gui-Seck,Seo, Seong-Won 충남대학교 농업과학연구소 2010 농업과학연구 Vol.37 No.2
The objective of this study was to evaluate effects of supplementation of ${\beta}$-mannanase (CTCZYME$^{(R)}$, CTCBIO, Inc.) on feed intake, growth performance and fecal health of calves fed two levels (3% vs. 8%) of palm kernel meal (PKM). A total of nine Holstein calves were divided into three groups, and fed a conventional starter containing 3% PKM (CON), CON+0.1% CTCZYME$^{(R)}$ (TRT1), or a starter containing 8% PKM+0.1% CTCZYME$^{(R)}$ (TRT2). No clinical symptom of calves was observed through the trial. We did not find significant differences among the treatments on mean feed intake, growth performance, or fecal health during the four-week experimental period. Feed efficiency tended to be improved by adding CTCZYME$^{(R)}$ (0.46, 0.87 and 0.52 for CON, TRT1 and TRT2, respectively). Compared with CON (921 g/d and 786 g/d), TRT2 had lower feed intake (727 g/d) and average daily gain (ADG, 631 g/d) before weaning. However, feed intake (2300 g/d) and ADG (1012 g/d) were similar or even higher in TRT2 than CON (2269 g/d and 560 g/d) after weaning. This was probably due to the effect of a large amount of mannan-oligosaccharide released from PKM by ${\beta}$-mannanase. Salmonella was not detected any fecal samples. No significant difference was observed in the number of fecal E. coli or fecal properties including color, smell, and watery indexes among the treatments. We conclude that a calf starter containing 8% PKM with 0.1% CTCZYME$^{(R)}$ is comparable with a conventional starter in feed intake and growth performance of calf, which is beneficial in terms of reduction in feed cost.