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Article: Extinction as a deficit of the decision-making circuitry in the posterior parietal cortex.

Christopoulos, Vassilios N / Andersen, Kristen N / Andersen, Richard A

2018 Volume 151, Page(s) 163–182

Abstract: Extinction is a common neurologic deficit that often occurs as one of a constellation of symptoms seen with lesions of the posterior parietal cortex (PPC). Although extinction has typically been considered a deficit in the allocation of attention, new ... ...

Abstract	Extinction is a common neurologic deficit that often occurs as one of a constellation of symptoms seen with lesions of the posterior parietal cortex (PPC). Although extinction has typically been considered a deficit in the allocation of attention, new findings, particularly from nonhuman primate studies, point to one potential and important source of extinction as damage to decision-making circuits for actions within the PPC. This new understanding provides clues to potential therapies for extinction. Also the finding that the PPC is important for action decisions and action planning has led to new neuroprosthetic applications using PPC recordings as control signals to assist paralyzed patients.
MeSH term(s)	Animals ; Decision Making/physiology ; Humans ; Parietal Lobe/physiopathology ; Perceptual Disorders/physiopathology
Language	English
Publishing date	2018-03-08
Publishing country	Netherlands
Document type	Journal Article ; Review
ISSN	0072-9752
ISSN	0072-9752
DOI	10.1016/B978-0-444-63622-5.00008-5
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Article ; Online: Creating site-specific isopeptide linkages between proteins with the traceless Staudinger ligation.

Andersen, Kristen A / Raines, Ronald T

Methods in molecular biology (Clifton, N.J.)

2015 Volume 1248, Page(s) 55–65

Abstract: Site-specific isopeptide linkages between the ε-amino group of a lysine residue in one protein and a carboxyl group in another are central to ubiquitin-mediated protein degradation and other cellular processes. These linkages are inaccessible with common ...

Abstract	Site-specific isopeptide linkages between the ε-amino group of a lysine residue in one protein and a carboxyl group in another are central to ubiquitin-mediated protein degradation and other cellular processes. These linkages are inaccessible with common recombinant DNA techniques. Here, we describe a method to link two proteins by an authentic isopeptide bond. The method unites three techniques at the forefront of molecular biology. An azidonorleucine residue is installed at a desired site in a substrate protein by nonnatural amino acid incorporation, and a phosphinothioester is installed at the C terminus of a pendant protein by expressed protein ligation. Then, the traceless Staudinger ligation is used to link the substrate and pendant proteins via an isopeptide bond. This method facilitates the study of otherwise intractable protein structure-function relationships.
MeSH term(s)	Cross-Linking Reagents/chemistry ; Peptides/chemistry ; Proteins/chemistry
Chemical Substances	Cross-Linking Reagents ; Peptides ; Proteins
Language	English
Publishing date	2015
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-2020-4_4
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Article ; Online: Trifluoroiodomethane as a Precursor to High Global Warming Potential Climate Pollutants: Could the Transformation of Climatically Benign CF

Taddonio, Kristen N / Dreyfus, Gabrielle B / Andersen, Stephen O / Ravishankara, A R

Environmental science & technology

2023 Volume 57, Issue 32, Page(s) 11731–11737

Abstract: The transition away from the production and consumption of high global warming potential (GWP) hydrofluorocarbons (HFCs) under the 2016 Kigali Amendment to the Montreal Protocol on Substances that Deplete the Ozone Layer (Montreal Protocol) has prompted ... ...

Abstract	The transition away from the production and consumption of high global warming potential (GWP) hydrofluorocarbons (HFCs) under the 2016 Kigali Amendment to the Montreal Protocol on Substances that Deplete the Ozone Layer (Montreal Protocol) has prompted air conditioning, refrigeration, and heat pump equipment manufacturers to seek alternative refrigerants with lower direct climate impacts. Additional factors affecting alternative refrigerant choice include safety (i.e., flammability and toxicity), environmental, and thermodynamic constraints. At the same time, manufacturers are incentivized to seek refrigerants with higher energy efficiency, which saves on electricity costs and reduces indirect greenhouse gas emissions from electricity generation. The life cycle climate performance (LCCP) metric is commonly used to assess the combined direct and indirect climate impacts of refrigerant-use equipment. Here, we consider an additional impact on climate performance: the degradation of refrigerant in equipment, i.e., the direct climate impacts of high-GWP byproducts that can form as the result of adding trifluoroiodomethane (CF
MeSH term(s)	Global Warming ; Environmental Pollutants ; Greenhouse Gases ; Air Pollutants/analysis ; Rwanda
Chemical Substances	Environmental Pollutants ; Greenhouse Gases ; trifluoroiodomethane (42A379KB0U) ; Air Pollutants
Language	English
Publishing date	2023-08-03
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1520-5851
ISSN (online)	1520-5851
DOI	10.1021/acs.est.3c01079
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Article ; Online: Gender Moderates Results of a Randomized Clinical Trial for the Khanya Intervention for Substance Use and ART Adherence in HIV Care in South Africa.

Belus, Jennifer M / Joska, John A / Bronsteyn, Yosef / Rose, Alexandra L / Andersen, Lena S / Regenauer, Kristen S / Myers, Bronwyn / Hahn, Judith A / Orrell, Catherine / Safren, Steve A / Magidson, Jessica F

AIDS and behavior

2022 Volume 26, Issue 11, Page(s) 3630–3641

Abstract: Little is known about gender effects of alcohol and drug use (AOD) among people living with HIV (PLWH) in resource-limited settings. Using multilevel models, we tested whether gender moderated the effect of Khanya, a cognitive-behavioral therapy-based ... ...

Abstract	Little is known about gender effects of alcohol and drug use (AOD) among people living with HIV (PLWH) in resource-limited settings. Using multilevel models, we tested whether gender moderated the effect of Khanya, a cognitive-behavioral therapy-based intervention addressing antiretroviral (ART) adherence and AOD reduction. We enrolled 61 participants from HIV care and examined outcomes at 3- and 6-months compared to enhanced treatment as usual (ETAU). Gender significantly moderated the effect of Khanya on ART adherence (measured using electronically-monitored and biomarker-confirmed adherence), such that women in Khanya had significantly lower ART adherence compared to men in Khanya; no gender differences were found for AOD outcomes. Exploratory trajectory analyses showed men in Khanya and both genders in ETAU had significant reductions in at least one AOD outcome; women in Khanya did not. More research is needed to understand whether a gender lens can support behavioral interventions for PLWH with AOD.Trial registry ClinicalTrials.gov identifier: NCT03529409. Trial registered on May 18, 2018.
MeSH term(s)	Anti-Retroviral Agents/therapeutic use ; Female ; HIV Infections/drug therapy ; HIV Infections/epidemiology ; Humans ; Male ; Medication Adherence ; South Africa/epidemiology ; Substance-Related Disorders/complications ; Substance-Related Disorders/epidemiology
Chemical Substances	Anti-Retroviral Agents
Language	English
Publishing date	2022-07-27
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	1339885-4
ISSN	1573-3254 ; 1090-7165
ISSN (online)	1573-3254
ISSN	1090-7165
DOI	10.1007/s10461-022-03765-8
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Article ; Online: Interventions for Pancreatitis-New Approaches, Knowledge Gaps, and Research Opportunities: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop.

Phillips, Anna Evans / Hughes, Steven J / Andersen, Dana K / Bell, Adam / Brand, Randall / Coté, Gregory A / Cowdin, Adriana / Diazgranados, Nancy / Dudeja, Vikas / Duggan, Sinead N / Fogel, Evan / Forsmark, Chris E / Freeman, A Jay / Gittes, George / Hart, Phil A / Jeon, Christie / Nealon, William / Neoptolemos, John / Palermo, Tonya M /

Pandol, Stephen / Roberts, Kristen M / Rosenthal, Martin / Singh, Vikesh K / Yadav, Dhiraj / Whitcomb, David C / Zyromski, Nicholas

Pancreas

2024 Volume 53, Issue 4, Page(s) e368–e377

Abstract: Abstract: There exists no cure for acute, recurrent acute or chronic pancreatitis and treatments to date have been focused on managing symptoms. A recent workshop held by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) ... ...

Abstract	Abstract: There exists no cure for acute, recurrent acute or chronic pancreatitis and treatments to date have been focused on managing symptoms. A recent workshop held by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) focused on interventions that might disrupt or perhaps even reverse the natural course of this heterogenous disease, aiming to identify knowledge gaps and research opportunities that might inform future funding initiatives for NIDDK. The breadth and variety of identified active or planned clinical trials traverses the spectrum of the disease and was conceptually grouped for the workshop into behavioral, nutritional, pharmacologic and biologic, and mechanical interventions. Cognitive and other behavioral therapies are proven interventions for pain and addiction, but barriers exist to their use. Whilst a disease specific instrument quantifying pain is now validated, an equivalent is lacking for nutrition - and both face challenges in ease and frequency of administration. Multiple pharmacologic agents hold promise. Ongoing development of Patient Reported Outcome (PRO) measurements can satisfy Investigative New Drug (IND) regulatory assessments. Despite multiple randomized clinical trials demonstrating benefit, great uncertainty remains regarding patient selection, timing of intervention, and type of mechanical intervention (endoscopic versus surgery). Challenges and opportunities to establish beneficial interventions for patients were identified.
MeSH term(s)	Humans ; Diabetes Mellitus/diagnosis ; Diabetes Mellitus/therapy ; National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) ; Pain ; Pancreatitis, Chronic/therapy ; Pancreatitis, Chronic/drug therapy ; United States
Language	English
Publishing date	2024-03-13
Publishing country	United States
Document type	Congress
ZDB-ID	632831-3
ISSN	1536-4828 ; 0885-3177
ISSN (online)	1536-4828
ISSN	0885-3177
DOI	10.1097/MPA.0000000000002333
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Zs.A 2160: Show issues

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Article ; Online: Optic ataxia: from Balint's syndrome to the parietal reach region.

Andersen, Richard A / Andersen, Kristen N / Hwang, Eun Jung / Hauschild, Markus

Neuron

2014 Volume 81, Issue 5, Page(s) 967–983

Abstract: Optic ataxia is a high-order deficit in reaching to visual goals that occurs with posterior parietal cortex (PPC) lesions. It is a component of Balint's syndrome that also includes attentional and gaze disorders. Aspects of optic ataxia are misreaching ... ...

Abstract	Optic ataxia is a high-order deficit in reaching to visual goals that occurs with posterior parietal cortex (PPC) lesions. It is a component of Balint's syndrome that also includes attentional and gaze disorders. Aspects of optic ataxia are misreaching in the contralesional visual field, difficulty preshaping the hand for grasping, and an inability to correct reaches online. Recent research in nonhuman primates (NHPs) suggests that many aspects of Balint's syndrome and optic ataxia are a result of damage to specific functional modules for reaching, saccades, grasp, attention, and state estimation. The deficits from large lesions in humans are probably composite effects from damage to combinations of these functional modules. Interactions between these modules, either within posterior parietal cortex or downstream within frontal cortex, may account for more complex behaviors such as hand-eye coordination and reach-to-grasp.
MeSH term(s)	Agnosia/physiopathology ; Animals ; Ataxia/physiopathology ; Attention/physiology ; Humans ; Parietal Lobe/physiopathology ; Psychomotor Performance/physiology
Language	English
Publishing date	2014-03-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	808167-0
ISSN	1097-4199 ; 0896-6273
ISSN (online)	1097-4199
ISSN	0896-6273
DOI	10.1016/j.neuron.2014.02.025
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Zs.A 2496: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 92: Show issues

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Article ; Online: Serum Biomarkers of Nociceptive and Neuropathic Pain in Chronic Pancreatitis.

The journal of pain

2023 Volume 24, Issue 12, Page(s) 2199–2210

Abstract: Debilitating abdominal pain is a common symptom affecting most patients with chronic pancreatitis (CP). There are multiple underlying mechanisms that contribute to CP-related pain, which makes successful treatment difficult. The identification of ... ...

Abstract	Debilitating abdominal pain is a common symptom affecting most patients with chronic pancreatitis (CP). There are multiple underlying mechanisms that contribute to CP-related pain, which makes successful treatment difficult. The identification of biomarkers for subtypes of pain could provide viable targets for nonopioid interventions and the development of mechanistic approaches to pain management in CP. Nineteen inflammation- and nociception-associated proteins were measured in serum collected from 358 subjects with definite CP enrolled in PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, a prospective observational study of pancreatitis in US adult subjects. First, serum levels of putative biomarkers were compared between CP subjects with and without pain. Only platelet-derived growth factor B (PDGF-B) stood out, with levels significantly higher in the CP pain group as compared to subjects with no pain. Subjects with pain were then stratified into 4 pain subtypes (Neuropathic, Nociceptive, Mixed, and Unclassified). A comparison of putative biomarker concentration among 5 groups (no pain and 4 pain subtypes) identified unique proteins that were correlated with pain subtypes. Serum transforming growth factor beta 1 (TGFβ1) level was significantly higher in the Nociceptive pain group compared to the No pain group, suggesting that TGFβ1 may be a biomarker for nociceptive pain. The Neuropathic pain only group was too small to detect statistical differences. However, glycoprotein 130 (GP130), a coreceptor for interleukin 6, was significantly higher in the Mixed pain group compared to the groups lacking a neuropathic pain component. These data suggest that GP130 may be a biomarker for neuropathic pain in CP. PERSPECTIVE: Serum TGFβ1 and GP130 may be biomarkers for nociceptive and neuropathic CP pain, respectively. Preclinical data suggest inhibiting TGFβ1 or GP130 reduces CP pain in rodent models, indicating that additional translational and clinical studies may be warranted to develop a precision medicine approach to the management of pain in CP.
MeSH term(s)	Adult ; Humans ; Biomarkers ; Chronic Pain ; Cytokine Receptor gp130 ; Neuralgia/diagnosis ; Neuralgia/etiology ; Neuralgia/drug therapy ; Nociception ; Nociceptive Pain ; Pancreatitis, Chronic/complications ; Pancreatitis, Chronic/diagnosis
Chemical Substances	Biomarkers ; Cytokine Receptor gp130 (133483-10-0)
Language	English
Publishing date	2023-07-13
Publishing country	United States
Document type	Observational Study ; Journal Article
ZDB-ID	2018789-0
ISSN	1528-8447 ; 1526-5900
ISSN (online)	1528-8447
ISSN	1526-5900
DOI	10.1016/j.jpain.2023.07.006
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Zs.A 5237: Show issues

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Article ; Online: Intrinsic site-selectivity of ubiquitin dimer formation.

Andersen, Kristen A / Martin, Langdon J / Prince, Joel M / Raines, Ronald T

Protein science : a publication of the Protein Society

2015 Volume 24, Issue 2, Page(s) 182–189

Abstract: The post-translational modification of proteins with ubiquitin can take on many forms, including the decoration of substrates with polymeric ubiquitin chains. These chains are linked through one of the seven lysine residues in ubiquitin, with the ... ...

Abstract	The post-translational modification of proteins with ubiquitin can take on many forms, including the decoration of substrates with polymeric ubiquitin chains. These chains are linked through one of the seven lysine residues in ubiquitin, with the potential to form a panoply of linkage combinations as the chain length increases. The ensuing structural diversity of modifications serves a variety of signaling functions. Still, some linkages are present at a much higher level than others in cellulo. Although ubiquitination is an enzyme-catalyzed process, the large disparity of abundancies led us to the hypothesis that some linkages might be intrinsically faster to form than others, perhaps directing the course of enzyme evolution. Herein, we assess the kinetics of ubiquitin dimer formation in an enzyme-free system by measuring the rate constants for thiol-disulfide interchange between appropriate ubiquitin variants. Remarkably, we find that the kinetically expedient linkages correlate with those that are most abundant in cellulo. As the abundant linkages also appear to function more broadly in cellulo, this correlation suggests that the more accessible chains were selected for global roles.
MeSH term(s)	Disulfides/chemistry ; Humans ; Models, Molecular ; Protein Multimerization ; Ubiquitin/chemistry ; Ubiquitination
Chemical Substances	Disulfides ; Ubiquitin
Language	English
Publishing date	2015-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1106283-6
ISSN	1469-896X ; 0961-8368
ISSN (online)	1469-896X
ISSN	0961-8368
DOI	10.1002/pro.2603
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Zs.A 3407: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Boronic Acid for the Traceless Delivery of Proteins into Cells.

Andersen, Kristen A / Smith, Thomas P / Lomax, Jo E / Raines, Ronald T

ACS chemical biology

2015 Volume 11, Issue 2, Page(s) 319–323

Abstract: The use of exogenous proteins as intracellular probes and therapeutic agents is in its infancy. A major hurdle has been the delivery of native proteins to an intracellular site of action. Herein, we report on a compact delivery vehicle that employs the ... ...

Abstract	The use of exogenous proteins as intracellular probes and therapeutic agents is in its infancy. A major hurdle has been the delivery of native proteins to an intracellular site of action. Herein, we report on a compact delivery vehicle that employs the intrinsic affinity of boronic acids for the carbohydrates that coat the surface of mammalian cells. In the vehicle, benzoxaborole is linked to protein amino groups via a "trimethyl lock." Immolation of this linker is triggered by cellular esterases, releasing native protein. Efficacy is demonstrated by enhanced delivery of green fluorescent protein and a cytotoxic ribonuclease into mammalian cells. This versatile strategy provides new opportunities in chemical biology and pharmacology.
MeSH term(s)	Animals ; Boronic Acids/chemistry ; Boronic Acids/metabolism ; CHO Cells ; Cell Line, Tumor ; Cell Membrane Permeability ; Cricetulus ; Drug Carriers/chemistry ; Drug Carriers/metabolism ; Green Fluorescent Proteins/administration & dosage ; Green Fluorescent Proteins/chemistry ; Green Fluorescent Proteins/pharmacokinetics ; Humans ; Models, Molecular ; Ribonucleases/administration & dosage ; Ribonucleases/chemistry ; Ribonucleases/pharmacokinetics
Chemical Substances	Boronic Acids ; Drug Carriers ; Green Fluorescent Proteins (147336-22-9) ; Ribonucleases (EC 3.1.-)
Language	English
Publishing date	2015-12-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	1554-8937
ISSN (online)	1554-8937
DOI	10.1021/acschembio.5b00966
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Article ; Online: Low frequency power in cerebral blood flow is a biomarker of neurologic injury in the acute period after cardiac arrest.

Resuscitation

2022 Volume 178, Page(s) 12–18

Abstract: Aim: Cardiac arrest often results in severe neurologic injury. Improving care for these patients is difficult as few noninvasive biomarkers exist that allow physicians to monitor neurologic health. The amount of low-frequency power (LFP, 0.01-0.1 Hz) in ...

Abstract	Aim: Cardiac arrest often results in severe neurologic injury. Improving care for these patients is difficult as few noninvasive biomarkers exist that allow physicians to monitor neurologic health. The amount of low-frequency power (LFP, 0.01-0.1 Hz) in cerebral haemodynamics has been used in functional magnetic resonance imaging as a marker of neuronal activity. Our hypothesis was that increased LFP in cerebral blood flow (CBF) would be correlated with improvements in invasive measures of neurologic health. Methods: We adapted the use of LFP for to monitoring of CBF with diffuse correlation spectroscopy. We asked whether LFP (or other optical biomarkers) correlated with invasive microdialysis biomarkers (lactate-pyruvate ratio - LPR - and glycerol concentration) of neuronal injury in the 4 h after return of spontaneous circulation in a swine model of paediatric cardiac arrest (Sus scrofa domestica, 8-11 kg, 51% female). Associations were tested using a mixed linear effects model. Results: We found that higher LFP was associated with higher LPR and higher glycerol concentration. No other biomarkers were associated with LPR; cerebral haemoglobin concentration, oxygen extraction fraction, and one EEG metric were associated with glycerol concentration. Conclusion: Contrary to expectations, higher LFP in CBF was correlated with worse invasive biomarkers. Higher LFP may represent higher neurologic activity, or disruptions in neurovascular coupling. Either effect may be harmful in the acute period after cardiac arrest. Thus, these results suggest our methodology holds promise for development of new, clinically relevant biomarkers than can guide resuscitation and post-resuscitation care. Institutional protocol number: 19-001327.
MeSH term(s)	Biomarkers ; Cerebrovascular Circulation/physiology ; Female ; Glycerol ; Heart Arrest/complications ; Humans ; Male ; Resuscitation
Chemical Substances	Biomarkers ; Glycerol (PDC6A3C0OX)
Language	English
Publishing date	2022-07-08
Publishing country	Ireland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	189901-6
ISSN	1873-1570 ; 0300-9572
ISSN (online)	1873-1570
ISSN	0300-9572
DOI	10.1016/j.resuscitation.2022.07.004
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