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Article: Gut barrier defects, increased intestinal innate immune response, and enhanced lipid catabolism drive lethality in

Pandey, Ashutosh / Galeone, Antonio / Han, Seung Yeop / Story, Benjamin A / Consonni, Gaia / Mueller, William F / Steinmetz, Lars M / Vaccari, Thomas / Jafar-Nejad, Hamed

bioRxiv : the preprint server for biology

2023

Abstract: Intestinal barrier dysfunction leads to inflammation and associated metabolic changes. However, the relative impact of infectious versus non-infectious mechanisms on animal health in the context of barrier dysfunction is not well understood. Here, we ... ...

Abstract	Intestinal barrier dysfunction leads to inflammation and associated metabolic changes. However, the relative impact of infectious versus non-infectious mechanisms on animal health in the context of barrier dysfunction is not well understood. Here, we establish that loss of
Language	English
Publishing date	2023-04-07
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.04.07.536022
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Article ; Online: Gut barrier defects, intestinal immune hyperactivation and enhanced lipid catabolism drive lethality in NGLY1-deficient Drosophila.

Pandey, Ashutosh / Galeone, Antonio / Han, Seung Yeop / Story, Benjamin A / Consonni, Gaia / Mueller, William F / Steinmetz, Lars M / Vaccari, Thomas / Jafar-Nejad, Hamed

Nature communications

2023 Volume 14, Issue 1, Page(s) 5667

Abstract: Intestinal barrier dysfunction leads to inflammation and associated metabolic changes. However, the relative impact of gut bacteria versus non-bacterial insults on animal health in the context of barrier dysfunction is not well understood. Here, we ... ...

Abstract	Intestinal barrier dysfunction leads to inflammation and associated metabolic changes. However, the relative impact of gut bacteria versus non-bacterial insults on animal health in the context of barrier dysfunction is not well understood. Here, we establish that loss of Drosophila N-glycanase 1 (Pngl) in a specific intestinal cell type leads to gut barrier defects, causing starvation and JNK overactivation. These abnormalities, along with loss of Pngl in enterocytes and fat body, result in Foxo overactivation, leading to hyperactive innate immune response and lipid catabolism and thereby contributing to lethality. Germ-free rearing of Pngl mutants rescued their developmental delay but not lethality. However, raising Pngl mutants on isocaloric, fat-rich diets partially rescued lethality. Our data indicate that Pngl functions in Drosophila larvae to establish the gut barrier, and that the lethality caused by loss of Pngl is primarily mediated through non-bacterial induction of immune and metabolic abnormalities.
MeSH term(s)	Animals ; Drosophila/genetics ; Lipolysis ; Adipose Tissue ; Enterocytes ; Lipids
Chemical Substances	Lipids
Language	English
Publishing date	2023-09-13
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-40910-w
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Article ; Online: Improving Wastewater-Based Tobacco Use Estimates Using Anabasine.

Zheng, Qiuda / Gerber, Cobus / Steadman, Kathryn J / Lin, Chun-Yin / Tscharke, Benjamin J / O'Brien, Jake William / Hobson, Peter / Toms, Leisa-Maree / Mueller, Jochen F / Thomas, Kevin V / Thai, Phong K

Environmental science & technology

2023 Volume 57, Issue 21, Page(s) 7958–7965

Abstract: In wastewater-based epidemiology (WBE), nicotine metabolites have been used as biomarkers for monitoring tobacco use. Recently, the minor tobacco alkaloids anabasine and anatabine have been suggested as more specific biomarkers for tobacco use since ... ...

Abstract	In wastewater-based epidemiology (WBE), nicotine metabolites have been used as biomarkers for monitoring tobacco use. Recently, the minor tobacco alkaloids anabasine and anatabine have been suggested as more specific biomarkers for tobacco use since nicotine use can be from both tobacco and non-tobacco sources. This study aimed to provide an in-depth evaluation of the suitability of anabasine and anatabine as WBE biomarkers of tobacco and subsequently estimate their excretion factors for WBE applications. Pooled urine (
MeSH term(s)	Humans ; Nicotine/urine ; Anabasine/urine ; Cotinine/urine ; Wastewater ; Smoking/urine ; Tobacco Use ; Nicotiana ; Biomarkers
Chemical Substances	Nicotine (6M3C89ZY6R) ; Anabasine (LMS11II2LO) ; Cotinine (K5161X06LL) ; Wastewater ; Biomarkers
Language	English
Publishing date	2023-05-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1520-5851
ISSN (online)	1520-5851
DOI	10.1021/acs.est.3c01510
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Article: AAV9-NGLY1 gene replacement therapy improves phenotypic and biomarker endpoints in a rat model of NGLY1 Deficiency.

Zhu, Lei / Tan, Brandon / Dwight, Selina S / Beahm, Brendan / Wilsey, Matt / Crawford, Brett E / Schweighardt, Becky / Cook, Jennifer W / Wechsler, Thomas / Mueller, William F

Molecular therapy. Methods & clinical development

2022 Volume 27, Page(s) 259–271

Abstract: N-glycanase 1 (NGLY1) Deficiency is a progressive, ultra-rare, autosomal recessive disorder with no approved therapy and five core clinical features: severe global developmental delay, hyperkinetic movement disorder, elevated liver transaminases, ... ...

Abstract	N-glycanase 1 (NGLY1) Deficiency is a progressive, ultra-rare, autosomal recessive disorder with no approved therapy and five core clinical features: severe global developmental delay, hyperkinetic movement disorder, elevated liver transaminases, alacrima, and peripheral neuropathy. Here, we confirmed and characterized the
Language	English
Publishing date	2022-10-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2872938-9
ISSN	2329-0501 ; 2329-0501
ISSN (online)	2329-0501
ISSN	2329-0501
DOI	10.1016/j.omtm.2022.09.015
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Article: Attention, sentiments and emotions towards emerging climate technologies on Twitter.

Müller-Hansen, Finn / Repke, Tim / Baum, Chad M / Brutschin, Elina / Callaghan, Max W / Debnath, Ramit / Lamb, William F / Low, Sean / Lück, Sarah / Roberts, Cameron / Sovacool, Benjamin K / Minx, Jan C

Global environmental change : human and policy dimensions

2023 Volume 83, Page(s) 102765

Abstract: Public perception of emerging climate technologies, such as greenhouse gas removal (GGR) and solar radiation management (SRM), will strongly influence their future development and deployment. Studying perceptions of these technologies with traditional ... ...

Abstract	Public perception of emerging climate technologies, such as greenhouse gas removal (GGR) and solar radiation management (SRM), will strongly influence their future development and deployment. Studying perceptions of these technologies with traditional survey methods is challenging, because they are largely unknown to the public. Social media data provides a complementary line of evidence by allowing for retrospective analysis of how individuals share their unsolicited opinions. Our large-scale, comparative study of 1.5 million tweets covers 16 GGR and SRM technologies and uses state-of-the-art deep learning models to show how attention, and expressions of sentiment and emotion developed between 2006 and 2021. We find that in recent years, attention has shifted from general geoengineering themes to specific GGR methods. On the other hand, there is little attention to specific SRM technologies and they often coincide with conspiracy narratives. Sentiments and emotions in GGR tweets tend to be more positive, particularly for methods perceived to be natural, but are more negative when framed in the geoengineering context.
Language	English
Publishing date	2023-12-19
Publishing country	England
Document type	Journal Article
ZDB-ID	30436-0
ISSN	0959-3780 ; 1056-9367
ISSN	0959-3780 ; 1056-9367
DOI	10.1016/j.gloenvcha.2023.102765
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Article ; Online: NGLY1 deficiency: a prospective natural history study.

Tong, Sandra / Ventola, Pamela / Frater, Christina H / Klotz, Jenna / Phillips, Jennifer M / Muppidi, Srikanth / Dwight, Selina S / Mueller, William F / Beahm, Brendan J / Wilsey, Matt / Lee, Kevin J

Human molecular genetics

2023 Volume 32, Issue 18, Page(s) 2787–2796

Abstract: N-glycanase 1 (NGLY1) deficiency is a debilitating, ultra-rare autosomal recessive disorder caused by loss of function of NGLY1, a cytosolic enzyme that deglycosylates other proteins. It is characterized by severe global developmental delay and/or ... ...

Abstract	N-glycanase 1 (NGLY1) deficiency is a debilitating, ultra-rare autosomal recessive disorder caused by loss of function of NGLY1, a cytosolic enzyme that deglycosylates other proteins. It is characterized by severe global developmental delay and/or intellectual disability, hyperkinetic movement disorder, transient elevation of transaminases, (hypo)alacrima and progressive, diffuse, length-dependent sensorimotor polyneuropathy. A prospective natural history study (NHS) was conducted to elucidate clinical features and disease course. Twenty-nine participants were enrolled (15 onsite, 14 remotely) and followed for up to 32 months, representing ~29% of the ~100 patients identified worldwide. Participants exhibited profound developmental delays, with almost all developmental quotients below 20 on the Mullen Scales of Early Learning, well below the normative score of 100. Increased difficulties with sitting and standing suggested decline in motor function over time. Most patients presented with (hypo)alacrima and reduced sweat response. Pediatric quality of life was poor except for emotional function. Language/communication and motor skill problems including hand use were reported by caregivers as the most bothersome symptoms. Levels of the substrate biomarker, GlcNAc-Asn (aspartylglucosamine; GNA), were consistently elevated in all participants over time, independent of age. Liver enzymes were elevated for some participants but improved especially in younger patients and did not reach levels indicating severe liver disease. Three participants died during the study period. Data from this NHS informs selection of endpoints and assessments for future clinical trials for NGLY1 deficiency interventions. Potential endpoints include GNA biomarker levels, neurocognitive assessments, autonomic and motor function (particularly hand use), (hypo)alacrima and quality of life.
MeSH term(s)	Humans ; Child ; Prospective Studies ; Quality of Life ; Congenital Disorders of Glycosylation ; Biomarkers
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-06-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddad106
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Article ; Online: Integrating Seeding Rates and Pesticide Programs for Managing Sclerotinia Stem Rot in Glycine max with Nitrogen Fertilizer Applications

Webster, Richard W. / Mueller, Brian D. / Chilvers, Martin I. / Byrne, Adam M. / Boyse, John F. / Widdicombe, William W. / Mueller, Daren S. / Wiggs, Stith / Kandel, Yuba / Telenko, Darcy E. P. / Ravellette, Jeffrey / Shim, Su / Smith, Damon L.

Plant Health Progress. 2023 Oct., v. 24, no. 3 p.320-325

2023

Abstract: Soybean production in the Upper Midwest region of the United States is consistently limited by the disease Sclerotinia stem rot (SSR). To control SSR, multiple management practices have been studied and implemented to reduce SSR development and preserve ... ...

Abstract	Soybean production in the Upper Midwest region of the United States is consistently limited by the disease Sclerotinia stem rot (SSR). To control SSR, multiple management practices have been studied and implemented to reduce SSR development and preserve yield. This study examined the effects of integrating soybean seeding rates and pesticide programs under nitrogen fertilizer applications in the form of urea (46-0-0) that may occur due to management of other crops, such as corn. From 10 site-years between 2020 and 2021, low seeding rates decreased SSR development while also decreasing yields and partial profits. The effect of pesticide applications on SSR development was influenced by both seeding rates and nitrogen applications. Consistently, applications of the fungicide Endura reduced SSR to the lowest levels while also maintaining the highest yields and partial profits. Soybeans grown with nitrogen applications experienced increased SSR development and decreased yields and partial profits. Overall, this work suggests that using low seeding rates and fungicides improves the management of SSR, and using nitrogen fertilizer applications can result in greater SSR development and decreased economic returns, especially in fields with a history of SSR.
Keywords	Glycine max ; Sclerotinia ; corn ; fungicides ; nitrogen ; nitrogen fertilizers ; soybeans ; stem rot ; urea ; Midwestern United States ; integrated pest management ; soybean ; white mold
Language	English
Dates of publication	2023-10
Size	p. 320-325.
Publishing place	The American Phytopathological Society
Document type	Article ; Online
ISSN	1535-1025
DOI	10.1094/PHP-10-22-0102-RS
Database	NAL-Catalogue (AGRICOLA)

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Article: Fabrication Methods and Chronic In Vivo Validation of Mechanically Adaptive Microfluidic Intracortical Devices.

Kim, Youjoung / Mueller, Natalie N / Schwartzman, William E / Sarno, Danielle / Wynder, Reagan / Hoeferlin, George F / Gisser, Kaela / Capadona, Jeffrey R / Hess-Dunning, Allison

Micromachines

2023 Volume 14, Issue 5

Abstract: Intracortical neural probes are both a powerful tool in basic neuroscience studies of brain function and a critical component of brain computer interfaces (BCIs) designed to restore function to paralyzed patients. Intracortical neural probes can be used ... ...

Abstract	Intracortical neural probes are both a powerful tool in basic neuroscience studies of brain function and a critical component of brain computer interfaces (BCIs) designed to restore function to paralyzed patients. Intracortical neural probes can be used both to detect neural activity at single unit resolution and to stimulate small populations of neurons with high resolution. Unfortunately, intracortical neural probes tend to fail at chronic timepoints in large part due to the neuroinflammatory response that follows implantation and persistent dwelling in the cortex. Many promising approaches are under development to circumvent the inflammatory response, including the development of less inflammatory materials/device designs and the delivery of antioxidant or anti-inflammatory therapies. Here, we report on our recent efforts to integrate the neuroprotective effects of both a dynamically softening polymer substrate designed to minimize tissue strain and localized drug delivery at the intracortical neural probe/tissue interface through the incorporation of microfluidic channels within the probe. The fabrication process and device design were both optimized with respect to the resulting device mechanical properties, stability, and microfluidic functionality. The optimized devices were successfully able to deliver an antioxidant solution throughout a six-week in vivo rat study. Histological data indicated that a multi-outlet design was most effective at reducing markers of inflammation. The ability to reduce inflammation through a combined approach of drug delivery and soft materials as a platform technology allows future studies to explore additional therapeutics to further enhance intracortical neural probes performance and longevity for clinical applications.
Language	English
Publishing date	2023-05-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2620864-7
ISSN	2072-666X
ISSN	2072-666X
DOI	10.3390/mi14051015
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Article ; Online: Nomadic ungulate movements under threat: Declining mobility of Mongolian gazelles in the Eastern Steppe of Mongolia

Mendgen, Philipp / Dejid, Nandintsetseg / Olson, Kirk / Buuveibaatar, Bayarbaatar / Calabrese, Justin M. / Chimeddorj, Buyanaa / Dalannast, Munkhnast / Fagan, William F. / Leimgruber, Peter / Müller, Thomas

Biological Conservation. 2023 Oct., v. 286 p.110271-

2023

Abstract: Increasing habitat fragmentation and disturbance threaten long-distance movements of ungulates. While the effects of impermeable barriers on ungulate migrations have been well researched, quantitative evidence for gradual, long-term changes of mobility ... ...

Abstract	Increasing habitat fragmentation and disturbance threaten long-distance movements of ungulates. While the effects of impermeable barriers on ungulate migrations have been well researched, quantitative evidence for gradual, long-term changes of mobility remains rare. We investigated changes in movement behavior of Mongolian gazelle Procapra gutturosa using GPS tracking data collected from 62 gazelle individuals between 2007 and 2021. We quantified 16-day displacement distances as a metric for long-distance movements before using linear mixed models, generalized additive models and quantile regressions to assess how anthropogenic and environmental factors affected gazelle movement behavior. Long-distance 16-day movements decreased by 36 %, from 142 km in 2007 to 92 km in 2021. Changes in mobility were affected by increasing vehicle numbers in Mongolia, but could not be explained by concurrent changes in other environmental factors like temperature, precipitation or vegetation greenness. Gazelle movement decreased close to roads, and gazelles stayed further away from roads during the snow-free season, when traffic likely is most intense. Conserving landscape permeability is essential for maintaining populations of highly mobile species. Our study provides evidence for a gradual decline in gazelle mobility over fifteen years as a response to increasing anthropogenic impact. The transportation infrastructure permeating the Eastern Steppe does not pose physical barriers, yet our findings suggest that increasing traffic volume may create semipermeable barriers to gazelle movement. As human activity is increasing, interactions between ungulates and vehicle traffic need to be closely monitored to identify and mitigate semipermeable barrier effects before landscape permeability is severely altered.
Keywords	Procapra ; anthropogenic activities ; gazelles ; habitat fragmentation ; humans ; infrastructure ; landscapes ; permeability ; steppes ; temperature ; traffic ; Mongolia ; Animal movement ; Connectivity ; GPS tracking ; Semipermeable barriers ; Ungulate migration
Language	English
Dates of publication	2023-10
Publishing place	Elsevier Ltd
Document type	Article ; Online
ISSN	0006-3207
DOI	10.1016/j.biocon.2023.110271
Database	NAL-Catalogue (AGRICOLA)

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Article: SYGNALing a Red Light for Glioblastoma.

Brooks, Aaron N / Mueller, William F / Steinmetz, Lars M

Cell systems

2016 Volume 3, Issue 2, Page(s) 118–120

Abstract: A new multiomic network inference pipeline, SYGNAL, integrates patient data with mechanistically accurate transcriptional regulatory networks to predict drug combinations with synergistic anti-proliferative effects on glioblastoma multiforme. ...

Abstract	A new multiomic network inference pipeline, SYGNAL, integrates patient data with mechanistically accurate transcriptional regulatory networks to predict drug combinations with synergistic anti-proliferative effects on glioblastoma multiforme.
MeSH term(s)	Brain Neoplasms/genetics ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Glioblastoma/genetics ; Humans
Language	English
Publishing date	2016-08-30
Publishing country	United States
Document type	Journal Article ; Comment
ISSN	2405-4712
ISSN	2405-4712
DOI	10.1016/j.cels.2016.08.002
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