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A Schematic of trial timeline: Rats learn in an operant chamber outfitted with a touchscreen with three different interaction zones (left, center, and right) and a reward port on the opposite side of the chamber. A white circle is presented in the middle zone for 40 s, during which the rat is required to nosepoke to initiate a trial. Subsequently, two identical stimuli are presented on the left and right sides of the screen for 60 s. The rat is required to nosepoke one of these stimuli, selecting either the left or right side. One of the sides has a higher reward probability than the other. The rat either gets rewarded 1 s after the nosepoke or undergoes a 5-second timeout. There is a 10 s Intertrial Interval (ITI) before a new trial begins. B A session consists of 3 blocks of 75 trials each, with two reversals, with the last block increasing in uncertainty. C Following surgery, recovery, handling, and pretraining to respond to touchscreen stimuli on either the left or the right, different schedules are introduced, with each schedule administered across two days each, and increasing in uncertainty. D Sample performance on Schedule 2, where the rat matches the value of the left side and adapts its behavior following a reversal. E Probabilities of choosing the better option, mean ± SEM (shading). There was a significant difference in accuracy, p(Better), by lens implant area (Supplementary Table ). F – H Performance measures by lens implant region to include latencies for Initiation ( F ) group sizes are: n = 1286, n = 1286, n = 1301, n = 1716, n = 1717, n = 1707 respectively; Choice ( G ) group sizes are: n = 1284, n = 1291, n = 1305, n = 1727, n = 1730, n = 1736 respectively; and Reward ( H ) group sizes are: n = 830, n = 851, n = 668, n = 1149, n = 1172, n = 1023 respectively for M2- and OFC-lens implanted rats across all the schedules. The center of each box plot is the median. I Reconstructions of calcium indicator <t>GCaMP6f</t> and GRIN lens implant in all rats. J Photomicrograph of a lens in OFC. K Photomicrograph of a lens in M2. Coronal sections reprinted from The rat brain in stereotaxic coordinates, 7th edition, Paxinos, G. & Watson, C., 2014, with permission from Elsevier. Source data are provided as a Source Data file .
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A Schematic of trial timeline: Rats learn in an operant chamber outfitted with a touchscreen with three different interaction zones (left, center, and right) and a reward port on the opposite side of the chamber. A white circle is presented in the middle zone for 40 s, during which the rat is required to nosepoke to initiate a trial. Subsequently, two identical stimuli are presented on the left and right sides of the screen for 60 s. The rat is required to nosepoke one of these stimuli, selecting either the left or right side. One of the sides has a higher reward probability than the other. The rat either gets rewarded 1 s after the nosepoke or undergoes a 5-second timeout. There is a 10 s Intertrial Interval (ITI) before a new trial begins. B A session consists of 3 blocks of 75 trials each, with two reversals, with the last block increasing in uncertainty. C Following surgery, recovery, handling, and pretraining to respond to touchscreen stimuli on either the left or the right, different schedules are introduced, with each schedule administered across two days each, and increasing in uncertainty. D Sample performance on Schedule 2, where the rat matches the value of the left side and adapts its behavior following a reversal. E Probabilities of choosing the better option, mean ± SEM (shading). There was a significant difference in accuracy, p(Better), by lens implant area (Supplementary Table ). F – H Performance measures by lens implant region to include latencies for Initiation ( F ) group sizes are: n = 1286, n = 1286, n = 1301, n = 1716, n = 1717, n = 1707 respectively; Choice ( G ) group sizes are: n = 1284, n = 1291, n = 1305, n = 1727, n = 1730, n = 1736 respectively; and Reward ( H ) group sizes are: n = 830, n = 851, n = 668, n = 1149, n = 1172, n = 1023 respectively for M2- and OFC-lens implanted rats across all the schedules. The center of each box plot is the median. I Reconstructions of calcium indicator <t>GCaMP6f</t> and GRIN lens implant in all rats. J Photomicrograph of a lens in OFC. K Photomicrograph of a lens in M2. Coronal sections reprinted from The rat brain in stereotaxic coordinates, 7th edition, Paxinos, G. & Watson, C., 2014, with permission from Elsevier. Source data are provided as a Source Data file .
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A Schematic of trial timeline: Rats learn in an operant chamber outfitted with a touchscreen with three different interaction zones (left, center, and right) and a reward port on the opposite side of the chamber. A white circle is presented in the middle zone for 40 s, during which the rat is required to nosepoke to initiate a trial. Subsequently, two identical stimuli are presented on the left and right sides of the screen for 60 s. The rat is required to nosepoke one of these stimuli, selecting either the left or right side. One of the sides has a higher reward probability than the other. The rat either gets rewarded 1 s after the nosepoke or undergoes a 5-second timeout. There is a 10 s Intertrial Interval (ITI) before a new trial begins. B A session consists of 3 blocks of 75 trials each, with two reversals, with the last block increasing in uncertainty. C Following surgery, recovery, handling, and pretraining to respond to touchscreen stimuli on either the left or the right, different schedules are introduced, with each schedule administered across two days each, and increasing in uncertainty. D Sample performance on Schedule 2, where the rat matches the value of the left side and adapts its behavior following a reversal. E Probabilities of choosing the better option, mean ± SEM (shading). There was a significant difference in accuracy, p(Better), by lens implant area (Supplementary Table ). F – H Performance measures by lens implant region to include latencies for Initiation ( F ) group sizes are: n = 1286, n = 1286, n = 1301, n = 1716, n = 1717, n = 1707 respectively; Choice ( G ) group sizes are: n = 1284, n = 1291, n = 1305, n = 1727, n = 1730, n = 1736 respectively; and Reward ( H ) group sizes are: n = 830, n = 851, n = 668, n = 1149, n = 1172, n = 1023 respectively for M2- and OFC-lens implanted rats across all the schedules. The center of each box plot is the median. I Reconstructions of calcium indicator <t>GCaMP6f</t> and GRIN lens implant in all rats. J Photomicrograph of a lens in OFC. K Photomicrograph of a lens in M2. Coronal sections reprinted from The rat brain in stereotaxic coordinates, 7th edition, Paxinos, G. & Watson, C., 2014, with permission from Elsevier. Source data are provided as a Source Data file .
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A Schematic of trial timeline: Rats learn in an operant chamber outfitted with a touchscreen with three different interaction zones (left, center, and right) and a reward port on the opposite side of the chamber. A white circle is presented in the middle zone for 40 s, during which the rat is required to nosepoke to initiate a trial. Subsequently, two identical stimuli are presented on the left and right sides of the screen for 60 s. The rat is required to nosepoke one of these stimuli, selecting either the left or right side. One of the sides has a higher reward probability than the other. The rat either gets rewarded 1 s after the nosepoke or undergoes a 5-second timeout. There is a 10 s Intertrial Interval (ITI) before a new trial begins. B A session consists of 3 blocks of 75 trials each, with two reversals, with the last block increasing in uncertainty. C Following surgery, recovery, handling, and pretraining to respond to touchscreen stimuli on either the left or the right, different schedules are introduced, with each schedule administered across two days each, and increasing in uncertainty. D Sample performance on Schedule 2, where the rat matches the value of the left side and adapts its behavior following a reversal. E Probabilities of choosing the better option, mean ± SEM (shading). There was a significant difference in accuracy, p(Better), by lens implant area (Supplementary Table ). F – H Performance measures by lens implant region to include latencies for Initiation ( F ) group sizes are: n = 1286, n = 1286, n = 1301, n = 1716, n = 1717, n = 1707 respectively; Choice ( G ) group sizes are: n = 1284, n = 1291, n = 1305, n = 1727, n = 1730, n = 1736 respectively; and Reward ( H ) group sizes are: n = 830, n = 851, n = 668, n = 1149, n = 1172, n = 1023 respectively for M2- and OFC-lens implanted rats across all the schedules. The center of each box plot is the median. I Reconstructions of calcium indicator <t>GCaMP6f</t> and GRIN lens implant in all rats. J Photomicrograph of a lens in OFC. K Photomicrograph of a lens in M2. Coronal sections reprinted from The rat brain in stereotaxic coordinates, 7th edition, Paxinos, G. & Watson, C., 2014, with permission from Elsevier. Source data are provided as a Source Data file .
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A Schematic of trial timeline: Rats learn in an operant chamber outfitted with a touchscreen with three different interaction zones (left, center, and right) and a reward port on the opposite side of the chamber. A white circle is presented in the middle zone for 40 s, during which the rat is required to nosepoke to initiate a trial. Subsequently, two identical stimuli are presented on the left and right sides of the screen for 60 s. The rat is required to nosepoke one of these stimuli, selecting either the left or right side. One of the sides has a higher reward probability than the other. The rat either gets rewarded 1 s after the nosepoke or undergoes a 5-second timeout. There is a 10 s Intertrial Interval (ITI) before a new trial begins. B A session consists of 3 blocks of 75 trials each, with two reversals, with the last block increasing in uncertainty. C Following surgery, recovery, handling, and pretraining to respond to touchscreen stimuli on either the left or the right, different schedules are introduced, with each schedule administered across two days each, and increasing in uncertainty. D Sample performance on Schedule 2, where the rat matches the value of the left side and adapts its behavior following a reversal. E Probabilities of choosing the better option, mean ± SEM (shading). There was a significant difference in accuracy, p(Better), by lens implant area (Supplementary Table ). F – H Performance measures by lens implant region to include latencies for Initiation ( F ) group sizes are: n = 1286, n = 1286, n = 1301, n = 1716, n = 1717, n = 1707 respectively; Choice ( G ) group sizes are: n = 1284, n = 1291, n = 1305, n = 1727, n = 1730, n = 1736 respectively; and Reward ( H ) group sizes are: n = 830, n = 851, n = 668, n = 1149, n = 1172, n = 1023 respectively for M2- and OFC-lens implanted rats across all the schedules. The center of each box plot is the median. I Reconstructions of calcium indicator <t>GCaMP6f</t> and GRIN lens implant in all rats. J Photomicrograph of a lens in OFC. K Photomicrograph of a lens in M2. Coronal sections reprinted from The rat brain in stereotaxic coordinates, 7th edition, Paxinos, G. & Watson, C., 2014, with permission from Elsevier. Source data are provided as a Source Data file .
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A Schematic of trial timeline: Rats learn in an operant chamber outfitted with a touchscreen with three different interaction zones (left, center, and right) and a reward port on the opposite side of the chamber. A white circle is presented in the middle zone for 40 s, during which the rat is required to nosepoke to initiate a trial. Subsequently, two identical stimuli are presented on the left and right sides of the screen for 60 s. The rat is required to nosepoke one of these stimuli, selecting either the left or right side. One of the sides has a higher reward probability than the other. The rat either gets rewarded 1 s after the nosepoke or undergoes a 5-second timeout. There is a 10 s Intertrial Interval (ITI) before a new trial begins. B A session consists of 3 blocks of 75 trials each, with two reversals, with the last block increasing in uncertainty. C Following surgery, recovery, handling, and pretraining to respond to touchscreen stimuli on either the left or the right, different schedules are introduced, with each schedule administered across two days each, and increasing in uncertainty. D Sample performance on Schedule 2, where the rat matches the value of the left side and adapts its behavior following a reversal. E Probabilities of choosing the better option, mean ± SEM (shading). There was a significant difference in accuracy, p(Better), by lens implant area (Supplementary Table ). F – H Performance measures by lens implant region to include latencies for Initiation ( F ) group sizes are: n = 1286, n = 1286, n = 1301, n = 1716, n = 1717, n = 1707 respectively; Choice ( G ) group sizes are: n = 1284, n = 1291, n = 1305, n = 1727, n = 1730, n = 1736 respectively; and Reward ( H ) group sizes are: n = 830, n = 851, n = 668, n = 1149, n = 1172, n = 1023 respectively for M2- and OFC-lens implanted rats across all the schedules. The center of each box plot is the median. I Reconstructions of calcium indicator <t>GCaMP6f</t> and GRIN lens implant in all rats. J Photomicrograph of a lens in OFC. K Photomicrograph of a lens in M2. Coronal sections reprinted from The rat brain in stereotaxic coordinates, 7th edition, Paxinos, G. & Watson, C., 2014, with permission from Elsevier. Source data are provided as a Source Data file .
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A Schematic of trial timeline: Rats learn in an operant chamber outfitted with a touchscreen with three different interaction zones (left, center, and right) and a reward port on the opposite side of the chamber. A white circle is presented in the middle zone for 40 s, during which the rat is required to nosepoke to initiate a trial. Subsequently, two identical stimuli are presented on the left and right sides of the screen for 60 s. The rat is required to nosepoke one of these stimuli, selecting either the left or right side. One of the sides has a higher reward probability than the other. The rat either gets rewarded 1 s after the nosepoke or undergoes a 5-second timeout. There is a 10 s Intertrial Interval (ITI) before a new trial begins. B A session consists of 3 blocks of 75 trials each, with two reversals, with the last block increasing in uncertainty. C Following surgery, recovery, handling, and pretraining to respond to touchscreen stimuli on either the left or the right, different schedules are introduced, with each schedule administered across two days each, and increasing in uncertainty. D Sample performance on Schedule 2, where the rat matches the value of the left side and adapts its behavior following a reversal. E Probabilities of choosing the better option, mean ± SEM (shading). There was a significant difference in accuracy, p(Better), by lens implant area (Supplementary Table ). F – H Performance measures by lens implant region to include latencies for Initiation ( F ) group sizes are: n = 1286, n = 1286, n = 1301, n = 1716, n = 1717, n = 1707 respectively; Choice ( G ) group sizes are: n = 1284, n = 1291, n = 1305, n = 1727, n = 1730, n = 1736 respectively; and Reward ( H ) group sizes are: n = 830, n = 851, n = 668, n = 1149, n = 1172, n = 1023 respectively for M2- and OFC-lens implanted rats across all the schedules. The center of each box plot is the median. I Reconstructions of calcium indicator <t>GCaMP6f</t> and GRIN lens implant in all rats. J Photomicrograph of a lens in OFC. K Photomicrograph of a lens in M2. Coronal sections reprinted from The rat brain in stereotaxic coordinates, 7th edition, Paxinos, G. & Watson, C., 2014, with permission from Elsevier. Source data are provided as a Source Data file .
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Figure 7. SPP1+ profibrotic macrophages expand in human CKD and heart failure (A) UMAP embedding of 4,404 mononuclear phagocytes sub-clustered from CD10 single cells from 15 human kidneys by Kuppe et al.6 Labels refer to clusters. cDC, conventional dendritic cells; Mono, monocytes; Res-like Mac, resident-like macrophages; SPP1 Mac, SPP1+ macrophages. (B) Bar plot of cluster cell numbers in CKD versus healthy kidneys after normalization via Log2 transformation. Log2FC, log 2-Fold Change. (C) RNA-ISH for SPP1 and COL1A1 combined with immunofluorescent CD68 staining in human kidney <t>nephrectomies.</t> SPP1+CD68+ macrophages are circled in white. Scale bar = 30 mm. (D) Pearson correlation of the number of COL1A1+ fibroblasts with SPP1+CD68+ macrophages in human kidney nephrectomies (n = 41). (E) UMAP embedding of 20,892 mononuclear phagocytes sub-clustered from CD45+ single cells from six human heart samples from Rao et al.50 Labels refer to clusters. Inflam. Mac, inflammatory macrophages. (F) Bar plot of cluster cell numbers in heart failure versus healthy hearts after normalization via Log2 transformation. Log2FC, log 2-Fold Change. (G) Cardiac ECM regulator score stratified by immune cell type. For (B) and (F), Fisher’s exact test was computed using false discovery rate correction for multiple testing. For (G), a two-tailed unpaired t test was performed. ***p < 0.001, ****p < 0.0001. See also Figure S7.
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Figure 7. SPP1+ profibrotic macrophages expand in human CKD and heart failure (A) UMAP embedding of 4,404 mononuclear phagocytes sub-clustered from CD10 single cells from 15 human kidneys by Kuppe et al.6 Labels refer to clusters. cDC, conventional dendritic cells; Mono, monocytes; Res-like Mac, resident-like macrophages; SPP1 Mac, SPP1+ macrophages. (B) Bar plot of cluster cell numbers in CKD versus healthy kidneys after normalization via Log2 transformation. Log2FC, log 2-Fold Change. (C) RNA-ISH for SPP1 and COL1A1 combined with immunofluorescent CD68 staining in human kidney <t>nephrectomies.</t> SPP1+CD68+ macrophages are circled in white. Scale bar = 30 mm. (D) Pearson correlation of the number of COL1A1+ fibroblasts with SPP1+CD68+ macrophages in human kidney nephrectomies (n = 41). (E) UMAP embedding of 20,892 mononuclear phagocytes sub-clustered from CD45+ single cells from six human heart samples from Rao et al.50 Labels refer to clusters. Inflam. Mac, inflammatory macrophages. (F) Bar plot of cluster cell numbers in heart failure versus healthy hearts after normalization via Log2 transformation. Log2FC, log 2-Fold Change. (G) Cardiac ECM regulator score stratified by immune cell type. For (B) and (F), Fisher’s exact test was computed using false discovery rate correction for multiple testing. For (G), a two-tailed unpaired t test was performed. ***p < 0.001, ****p < 0.0001. See also Figure S7.
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Figure 7. SPP1+ profibrotic macrophages expand in human CKD and heart failure (A) UMAP embedding of 4,404 mononuclear phagocytes sub-clustered from CD10 single cells from 15 human kidneys by Kuppe et al.6 Labels refer to clusters. cDC, conventional dendritic cells; Mono, monocytes; Res-like Mac, resident-like macrophages; SPP1 Mac, SPP1+ macrophages. (B) Bar plot of cluster cell numbers in CKD versus healthy kidneys after normalization via Log2 transformation. Log2FC, log 2-Fold Change. (C) RNA-ISH for SPP1 and COL1A1 combined with immunofluorescent CD68 staining in human kidney <t>nephrectomies.</t> SPP1+CD68+ macrophages are circled in white. Scale bar = 30 mm. (D) Pearson correlation of the number of COL1A1+ fibroblasts with SPP1+CD68+ macrophages in human kidney nephrectomies (n = 41). (E) UMAP embedding of 20,892 mononuclear phagocytes sub-clustered from CD45+ single cells from six human heart samples from Rao et al.50 Labels refer to clusters. Inflam. Mac, inflammatory macrophages. (F) Bar plot of cluster cell numbers in heart failure versus healthy hearts after normalization via Log2 transformation. Log2FC, log 2-Fold Change. (G) Cardiac ECM regulator score stratified by immune cell type. For (B) and (F), Fisher’s exact test was computed using false discovery rate correction for multiple testing. For (G), a two-tailed unpaired t test was performed. ***p < 0.001, ****p < 0.0001. See also Figure S7.
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Image Search Results


A Schematic of trial timeline: Rats learn in an operant chamber outfitted with a touchscreen with three different interaction zones (left, center, and right) and a reward port on the opposite side of the chamber. A white circle is presented in the middle zone for 40 s, during which the rat is required to nosepoke to initiate a trial. Subsequently, two identical stimuli are presented on the left and right sides of the screen for 60 s. The rat is required to nosepoke one of these stimuli, selecting either the left or right side. One of the sides has a higher reward probability than the other. The rat either gets rewarded 1 s after the nosepoke or undergoes a 5-second timeout. There is a 10 s Intertrial Interval (ITI) before a new trial begins. B A session consists of 3 blocks of 75 trials each, with two reversals, with the last block increasing in uncertainty. C Following surgery, recovery, handling, and pretraining to respond to touchscreen stimuli on either the left or the right, different schedules are introduced, with each schedule administered across two days each, and increasing in uncertainty. D Sample performance on Schedule 2, where the rat matches the value of the left side and adapts its behavior following a reversal. E Probabilities of choosing the better option, mean ± SEM (shading). There was a significant difference in accuracy, p(Better), by lens implant area (Supplementary Table ). F – H Performance measures by lens implant region to include latencies for Initiation ( F ) group sizes are: n = 1286, n = 1286, n = 1301, n = 1716, n = 1717, n = 1707 respectively; Choice ( G ) group sizes are: n = 1284, n = 1291, n = 1305, n = 1727, n = 1730, n = 1736 respectively; and Reward ( H ) group sizes are: n = 830, n = 851, n = 668, n = 1149, n = 1172, n = 1023 respectively for M2- and OFC-lens implanted rats across all the schedules. The center of each box plot is the median. I Reconstructions of calcium indicator GCaMP6f and GRIN lens implant in all rats. J Photomicrograph of a lens in OFC. K Photomicrograph of a lens in M2. Coronal sections reprinted from The rat brain in stereotaxic coordinates, 7th edition, Paxinos, G. & Watson, C., 2014, with permission from Elsevier. Source data are provided as a Source Data file .

Journal: Nature Communications

Article Title: Neural coding of choice and outcome are modulated by uncertainty in orbitofrontal but not secondary motor cortex

doi: 10.1038/s41467-025-63866-5

Figure Lengend Snippet: A Schematic of trial timeline: Rats learn in an operant chamber outfitted with a touchscreen with three different interaction zones (left, center, and right) and a reward port on the opposite side of the chamber. A white circle is presented in the middle zone for 40 s, during which the rat is required to nosepoke to initiate a trial. Subsequently, two identical stimuli are presented on the left and right sides of the screen for 60 s. The rat is required to nosepoke one of these stimuli, selecting either the left or right side. One of the sides has a higher reward probability than the other. The rat either gets rewarded 1 s after the nosepoke or undergoes a 5-second timeout. There is a 10 s Intertrial Interval (ITI) before a new trial begins. B A session consists of 3 blocks of 75 trials each, with two reversals, with the last block increasing in uncertainty. C Following surgery, recovery, handling, and pretraining to respond to touchscreen stimuli on either the left or the right, different schedules are introduced, with each schedule administered across two days each, and increasing in uncertainty. D Sample performance on Schedule 2, where the rat matches the value of the left side and adapts its behavior following a reversal. E Probabilities of choosing the better option, mean ± SEM (shading). There was a significant difference in accuracy, p(Better), by lens implant area (Supplementary Table ). F – H Performance measures by lens implant region to include latencies for Initiation ( F ) group sizes are: n = 1286, n = 1286, n = 1301, n = 1716, n = 1717, n = 1707 respectively; Choice ( G ) group sizes are: n = 1284, n = 1291, n = 1305, n = 1727, n = 1730, n = 1736 respectively; and Reward ( H ) group sizes are: n = 830, n = 851, n = 668, n = 1149, n = 1172, n = 1023 respectively for M2- and OFC-lens implanted rats across all the schedules. The center of each box plot is the median. I Reconstructions of calcium indicator GCaMP6f and GRIN lens implant in all rats. J Photomicrograph of a lens in OFC. K Photomicrograph of a lens in M2. Coronal sections reprinted from The rat brain in stereotaxic coordinates, 7th edition, Paxinos, G. & Watson, C., 2014, with permission from Elsevier. Source data are provided as a Source Data file .

Article Snippet: A 1 μL Hamilton syringe and pump delivered GCaMP6f (AVV9-CamKII-GCaMP6f-WPRE-SV40, Addgene, # 100834) through cannulae and injectors in either OFC or M2.

Techniques: Blocking Assay

Figure 7. SPP1+ profibrotic macrophages expand in human CKD and heart failure (A) UMAP embedding of 4,404 mononuclear phagocytes sub-clustered from CD10 single cells from 15 human kidneys by Kuppe et al.6 Labels refer to clusters. cDC, conventional dendritic cells; Mono, monocytes; Res-like Mac, resident-like macrophages; SPP1 Mac, SPP1+ macrophages. (B) Bar plot of cluster cell numbers in CKD versus healthy kidneys after normalization via Log2 transformation. Log2FC, log 2-Fold Change. (C) RNA-ISH for SPP1 and COL1A1 combined with immunofluorescent CD68 staining in human kidney nephrectomies. SPP1+CD68+ macrophages are circled in white. Scale bar = 30 mm. (D) Pearson correlation of the number of COL1A1+ fibroblasts with SPP1+CD68+ macrophages in human kidney nephrectomies (n = 41). (E) UMAP embedding of 20,892 mononuclear phagocytes sub-clustered from CD45+ single cells from six human heart samples from Rao et al.50 Labels refer to clusters. Inflam. Mac, inflammatory macrophages. (F) Bar plot of cluster cell numbers in heart failure versus healthy hearts after normalization via Log2 transformation. Log2FC, log 2-Fold Change. (G) Cardiac ECM regulator score stratified by immune cell type. For (B) and (F), Fisher’s exact test was computed using false discovery rate correction for multiple testing. For (G), a two-tailed unpaired t test was performed. ***p < 0.001, ****p < 0.0001. See also Figure S7.

Journal: Cell reports

Article Title: Platelet-instructed SPP1 + macrophages drive myofibroblast activation in fibrosis in a CXCL4-dependent manner.

doi: 10.1016/j.celrep.2023.112131

Figure Lengend Snippet: Figure 7. SPP1+ profibrotic macrophages expand in human CKD and heart failure (A) UMAP embedding of 4,404 mononuclear phagocytes sub-clustered from CD10 single cells from 15 human kidneys by Kuppe et al.6 Labels refer to clusters. cDC, conventional dendritic cells; Mono, monocytes; Res-like Mac, resident-like macrophages; SPP1 Mac, SPP1+ macrophages. (B) Bar plot of cluster cell numbers in CKD versus healthy kidneys after normalization via Log2 transformation. Log2FC, log 2-Fold Change. (C) RNA-ISH for SPP1 and COL1A1 combined with immunofluorescent CD68 staining in human kidney nephrectomies. SPP1+CD68+ macrophages are circled in white. Scale bar = 30 mm. (D) Pearson correlation of the number of COL1A1+ fibroblasts with SPP1+CD68+ macrophages in human kidney nephrectomies (n = 41). (E) UMAP embedding of 20,892 mononuclear phagocytes sub-clustered from CD45+ single cells from six human heart samples from Rao et al.50 Labels refer to clusters. Inflam. Mac, inflammatory macrophages. (F) Bar plot of cluster cell numbers in heart failure versus healthy hearts after normalization via Log2 transformation. Log2FC, log 2-Fold Change. (G) Cardiac ECM regulator score stratified by immune cell type. For (B) and (F), Fisher’s exact test was computed using false discovery rate correction for multiple testing. For (G), a two-tailed unpaired t test was performed. ***p < 0.001, ****p < 0.0001. See also Figure S7.

Article Snippet: REAGENT or RESOURCE SOURCE IDENTIFIER Antibodies Anti-mouse CD11b (APC) eBioscience Cat# 17-0112-83; RRID: AB_469344 Anti-mouse mCD25 (PE-Cy7) Biolegend Cat# 102016; RRID: AB_312865 Anti-mouse CD4 (PB) Biolegend Cat# 100428; RRID: AB_493647 Anti-human CD68 Agilent Cat# M0876; RRID: AB_2074844 Anti-mouse-Fc (AF488) Jackson ImmunoResearch Cat# 715-545-151; RRID: AB_2341099 mUromoduline abcam Cat# ab207170; RRID: AB_2889163 mPDGFRa R&D Systems Cat# AF1062; RRID: AB_2236897 LTL-Fitc Vector Labs Cat# FL1321; RRID: AB_2336559 mKIM1 R&D Systems Cat#: AF1817; RRID: AB_2116446 mCD68 abcam Cat# ab53444; RRID: AB_869007 Anti-rabbit-Fc (AF647) Dianova Cat# 111-605-008; RRID: AB_2338074 Anti-goat-Fc (Cy3) Dianova Cat# 705-165-147; RRID: AB_2307351 Anti-goat-Fc (AF647) Dianova Cat# 705-605-147; RRID: AB_2340437 Anti-rat-Fc (AF647) Dianova Cat# 712-605-153; RRID: AB_2340694 Bacterial and virus strains pBABE-puro SV40 LT vector Addgene #13970 Biological samples Human nephrectomy tissue samples (healthy and CKD) This paper N/A Chemicals, peptides, and recombinant proteins LPS Sigma-Aldrich L4391-1MG Thrombine Molecular-Innovations MTHROM-0.05MG Critical commercial assays RNA-ScopeTM Multiplex Fluorescent V2 Assay ACD 323100 10x genomics single nuclear RNA-seq kit 10x genomics 1000077 Pikro Siriusred staining kit Morphisto 13422 Cell Tracker CMFDA Dye Thermo Fisher C2925 Cell Tracker CMTPX Dye Thermo Fisher C34552 CD11b-Microbeads Miltenyi Biotech 130-049-601 CD117-Microbeads Miltenyi Biotech 130-091-224 High-Capacity cDNA Reverse Transcription Kit Thermo Fisher 43-688-13 iTaq Univer SYBR Green Supermix Biorad 1725125 Deposited data Data scRNAseq MI hearts (murine) Forte et al.23 E-MTAB-7895 Data of human healthy and CKD kidney Kuppe et al.6 10.5281/zenodo.4059315 Data of human heart samples Rao et al.50 GSE145154 Reference mapping onto Dataset of Sanin et al. Sanin et al.38 GSE171328, GSE157313 Reference mapping of snRNASeq Data of IRI kidney onto murine IRI-snRNASeq dataset Kirita et al.41 GSE139107 (Continued on next page) Cell Reports 42, 112131, February 28, 2023 17

Techniques: Transformation Assay, Staining, Two Tailed Test