vania-janet/multiturn-rag-retrieval-data huggingface dataset:
Lake Victoria’s Falling Waters
When water levels on Lake Victoria plunged at the end of 2005, news media began reporting that water officials and environmental groups had accused the power authority that operates the dam of taking more water than the policy allowed. According to news reports in January 2006, Uganda’s Directorate of Water Development (DWD) reported that the primary cause for falling lake waters was the power company’s failure to adhere to the 1954 water release policy, but other government officials later denied these allegations, saying that the drought was the only reason water levels were falling.
Regardless of the cause, the drop in water levels means that those who rely on the lake face some difficult choices. “Reservoirs have multi-uses, and economic value can be placed on these different uses,” says Reynolds. “You have to decide which economic use is going to take highest priority during dry periods.” With Lake Victoria, the choice is complicated. The lake is a crucial resource to the more than 30 million people in Uganda, Tanzania, and Kenya who live near its shoreline. It provides an inexpensive way to transport goods between the three countries. Its fish are an important source of food, and the lure of the lake, the evasive source of the Nile, draws tourists to its shores.
 
Nalubaale Dam regulates the flow of water out of Lake Victoria and into the Nile River. Increased discharges of water from the dam for power production may be causing the water level of Lake Victoria to drop. (Photograph courtesy USDA Foreign Agricultural Service.)
 

Though the lake has long served these purposes, the extent to which people are relying on the lake is unprecedented. Since 1960, when water levels on the lake jumped due to heavy rains, the population surrounding the lake has sky-rocketed. The Lake Victoria region has the densest rural population in the world, and population growth around the lake continues to increase faster than anywhere else in Africa. The current economy—fisheries, transport, resorts, and even the Nalubaale Dam Complex—has developed to operate around a much fuller Lake Victoria.
 
Declining water levels in Lake Victoria are disrupting shoreline infrastructure like this small dock. (Photograph courtesy USDA Foreign Agricultural Service.)
Ablation of amyloid precursor protein increases insulin-degrading enzyme levels and activity in brain and peripheral tissues - PubMed
B: App−/− primary astrocyte cultures (n = 4/condition) were treated with bacterial recombinant sAPPα, sAPPβ, mutant N-terminal sAPPα, or eukaryotic-derived sAPPα695 and 751. IDE protein was measured and significance (P < 0.05) was determined by 1-way ANOVA. C: App−/− astrocyte primary cultures (n = 6/condition) were transfected with APP695, APP751, or green fluorescent protein (GFP) plasmids or mock transfected. IDE protein was measured and significance (P < 0.05) was determined by 1-way ANOVA. Data are graphed as means ± SE.

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Ablation of amyloid precursor protein increases insulin-degrading enzyme levels and activity in brain and peripheral tissues - PubMed
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Joshua A Kulas et al.

 Am J Physiol Endocrinol Metab.

2019.

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 . 2019 Jan 1;316(1):E106-E120.

 doi: 10.1152/ajpendo.00279.2018.
 

 Epub 2018 Nov 13.
 

 Authors
 

Joshua A Kulas 
 1
 , Whitney F Franklin 
 2
 , Nicholas A Smith 
 3
 , Gunjan D Manocha 
 1
 , Kendra L Puig 
 1
 , Kumi Nagamoto-Combs 
 3
 , Rachel D Hendrix 
 4
 , Giulio Taglialatela 
 5
 , Steven W Barger 
 6
  
 7
 , Colin K Combs 
 1
 

 Affiliations
 

1 Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences , Grand Forks, North Dakota.
2 Department of Neuroscience and Cell Biology, University of Texas Medical Branch , Galveston, Texas.
3 Department of Pathology, University of North Dakota School of Medicine and Health Sciences , Grand Forks, North Dakota.
4 Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences , Little Rock Arkansas.
5 Department of Neurology, University of Texas Medical Branch , Galveston, Texas.
6 Department of Geriatrics, University of Arkansas for Medical Sciences , Little Rock Arkansas.
7 Geriatric Research, Education and Clinical Center, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas.

 
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 Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254, 1976. doi:10.1016/0003-2697(76)90527-3.
 
 
 
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 Bush AI, Pettingell WH Jr, de Paradis M, Tanzi RE, Wasco W. The amyloid beta-protein precursor and its mammalian homologues. Evidence for a zinc-modulated heparin-binding superfamily. J Biol Chem 269: 26618–26621, 1994.
 
 
 
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 . 2019 Jan 1;316(1):E106-E120.

 doi: 10.1152/ajpendo.00279.2018.
 

 Epub 2018 Nov 13.
 

 
 
 
 
 
 
 Ablation of amyloid precursor protein increases insulin-degrading enzyme levels and activity in brain and peripheral tissues

 
 

Joshua A Kulas 
 1
 , Whitney F Franklin 
 2
 , Nicholas A Smith 
 3
 , Gunjan D Manocha 
 1
 , Kendra L Puig 
 1
 , Kumi Nagamoto-Combs 
 3
 , Rachel D Hendrix 
 4
 , Giulio Taglialatela 
 5
Ablation of amyloid precursor protein increases insulin-degrading enzyme levels and activity in brain and peripheral tissues - PubMed
This regulation of IDE by APP was widespread across numerous tissues, including liver, skeletal muscle, and brain as well as cell types within neural tissue, including neurons, astrocytes, and microglia. RNA interference-mediated knockdown of APP in the SIM-A9 microglia cell line elevated IDE levels. Fasting levels of blood insulin were lower in App-/- than App+/+ mice, but the former showed a larger increase in response to glucose. These low basal levels may enhance peripheral insulin sensitivity, as App-/- mice failed to develop impairment of glucose tolerance on a high-fat, high-sucrose ("Western") diet. Insulin levels and insulin signaling were also lower in the App-/- brain; synaptosomes prepared from App-/- hippocampus showed diminished insulin receptor phosphorylation compared with App+/+ mice when stimulated ex vivo. These findings represent a new molecular link connecting APP to metabolic homeostasis and demonstrate a novel role for APP as an upstream regulator of IDE in vivo.
 

 Keywords:
 
 
 Alzheimer’s disease; amyloid precursor protein; insulin; insulin-degrading enzyme; microglia.
 

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No conflicts of interest, financial or otherwise, are declared by the authors.

 Figures
 

 Fig. 1. 

 Insulin-degrading enzyme (IDE) was increased… 

 Fig. 1. 

 Insulin-degrading enzyme (IDE) was increased in App −/− tissues. A–C : IDE protein… 

 Fig. 1.
 
Insulin-degrading enzyme (IDE) was increased in App−/− tissues. A–C: IDE protein was measured in liver (n = 7), gastrocnemius (n = 6), and hippocampal tissue (n = 6–7) by Western blotting and normalized to GAPDH as a loading control. Normalized optical density is graphed as mean values ± SE.
Ablation of amyloid precursor protein increases insulin-degrading enzyme levels and activity in brain and peripheral tissues - PubMed
Ablation of amyloid precursor protein increases insulin-degrading enzyme levels and activity in brain and peripheral tissues - PubMed

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Ablation of amyloid precursor protein increases insulin-degrading enzyme levels and activity in brain and peripheral tissues - PubMed
Ablation of amyloid precursor protein increases insulin-degrading enzyme levels and activity in brain and peripheral tissues

 
 

Joshua A Kulas 
 1
 , Whitney F Franklin 
 2
 , Nicholas A Smith 
 3
 , Gunjan D Manocha 
 1
 , Kendra L Puig 
 1
 , Kumi Nagamoto-Combs 
 3
 , Rachel D Hendrix 
 4
 , Giulio Taglialatela 
 5
 , Steven W Barger 
 6
  
 7
 , Colin K Combs 
 1
 

 

 
 Affiliations
 

 
 

 Expand
 

 Affiliations
 

1 Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences , Grand Forks, North Dakota.
2 Department of Neuroscience and Cell Biology, University of Texas Medical Branch , Galveston, Texas.
3 Department of Pathology, University of North Dakota School of Medicine and Health Sciences , Grand Forks, North Dakota.
4 Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences , Little Rock Arkansas.
5 Department of Neurology, University of Texas Medical Branch , Galveston, Texas.
6 Department of Geriatrics, University of Arkansas for Medical Sciences , Little Rock Arkansas.
7 Geriatric Research, Education and Clinical Center, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas.

 
 PMID:
 
 
30422705

 
 PMCID:
 
 

 PMC6417684
 

 
 DOI:
 
 

 10.1152/ajpendo.00279.2018
 

 Item in Clipboard

 
 
 
 
 
 
 Ablation of amyloid precursor protein increases insulin-degrading enzyme levels and activity in brain and peripheral tissues

 
 

Joshua A Kulas et al.

 Am J Physiol Endocrinol Metab.

2019.

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 Am J Physiol Endocrinol Metab
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 . 2019 Jan 1;316(1):E106-E120.
Ablation of amyloid precursor protein increases insulin-degrading enzyme levels and activity in brain and peripheral tissues - PubMed
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Ablation of amyloid precursor protein increases insulin-degrading enzyme levels and activity in brain and peripheral tissues - PubMed
High-fat diet induced discrepant peripheral and central nervous systems insulin resistance in APPswe/PS1dE9 and wild-type C57BL/6J mice.
 
 

Guo Y, Ma X, Li P, Dong S, Huang X, Ren X, Yuan L.
Guo Y, et al.
Aging (Albany NY). 2020 Dec 3;13(1):1236-1250. doi: 10.18632/aging.202262. Epub 2020 Dec 3.
Aging (Albany NY). 2020.
PMID: 33291072
Free PMC article.

 
 Cerebrolysin decreases amyloid-beta production by regulating amyloid protein precursor maturation in a transgenic model of Alzheimer's disease.
 
 

Rockenstein E, Torrance M, Mante M, Adame A, Paulino A, Rose JB, Crews L, Moessler H, Masliah E.
Rockenstein E, et al.
J Neurosci Res. 2006 May 15;83(7):1252-61. doi: 10.1002/jnr.20818.
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PMID: 16511867

 
 The effects of insulin and insulin-like growth factor I on amyloid precursor protein phosphorylation in in vitro and in vivo models of Alzheimer's disease.
 
 

Kim B, Elzinga SE, Henn RE, McGinley LM, Feldman EL.
Kim B, et al.
Neurobiol Dis. 2019 Dec;132:104541. doi: 10.1016/j.nbd.2019.104541. Epub 2019 Jul 23.
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 Insulin, insulin-degrading enzyme and amyloid-beta peptide in Alzheimer's disease: review and hypothesis.
 
 

Qiu WQ, Folstein MF.
Qiu WQ, et al.