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Article ; Online: Post-colonoscopy cancer: Due to missed pathology or different molecular pathways?

Gupta, A / Metz, A / Macrae, F A

Journal of gastroenterology and hepatology

2023 Volume 38, Issue 9, Page(s) 1663

MeSH term(s)	Humans ; Colonoscopy ; Colorectal Neoplasms/pathology ; Colonic Polyps
Language	English
Publishing date	2023-07-30
Publishing country	Australia
Document type	Letter ; Comment
ZDB-ID	632882-9
ISSN	1440-1746 ; 0815-9319
ISSN (online)	1440-1746
ISSN	0815-9319
DOI	10.1111/jgh.16305
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Article: Genotype-phenotype correlation of BMPR1a disease causing variants in juvenile polyposis syndrome.

Papadopulos, M E / Plazzer, J P / Macrae, F A

Hereditary cancer in clinical practice

2023 Volume 21, Issue 1, Page(s) 12

Abstract: Background: Juvenile Polyposis Syndrome (JPS) is an autosomal dominant condition with hamartomatous polyps in the gastrointestinal tract, associated with an increased risk of gastrointestinal malignancy. Disease causing variants (DCVs) in BMPR1a or ... ...

Abstract	Background: Juvenile Polyposis Syndrome (JPS) is an autosomal dominant condition with hamartomatous polyps in the gastrointestinal tract, associated with an increased risk of gastrointestinal malignancy. Disease causing variants (DCVs) in BMPR1a or SMAD4 account for 45-60% of JPS cases, with BMPR1a DCVs accounting for 17-38% of JPS cases. Within those with either a BMPR1a or SMAD4 DCV, there is phenotypic variability in location of polyps, risk of malignancy and extra-intestinal manifestations with limited published reports of gene-phenotype association or genotype-phenotype correlation. We aimed to identify any gene-phenotype association or genotype-phenotype correlation in BMPR1a to inform surveillance recommendations, and gene-specific modification to the ACMG classification of pathogenicity of DCVs. Methods: A literature search was performed through EMBASE, MEDLINE and PubMed. Studies that were included explored BMPR1a DCV-related JPS or contiguous deletion of PTEN and BMPR1a. Data was also drawn from the BMPR1a specific databases on LOVD and ClinVar. Results: There were 211 DCVs in BMPR1a identified, 82 from patients with JPS in the literature, and 17 from LOVD and 112 from ClinVar classified as pathogenic or likely pathogenic. These included missense, nonsense and frameshift variants and large deletions, occurring across all functional domains of the gene. Unlike in SMAD4 carriers, gastric polyposis and malignancy were not identified in our review in BMPR1a carriers, but colonic polyposis and malignancy occurred in carriers of either BMPR1a or SMAD4 DCVs. Those with contiguous deletion of PTEN and BMPR1a can present with JPS of infancy, with a severe phenotype of GI bleeding, diarrhoea, exudative enteropathy and rectal prolapse. No specific BMPR1a genotype-phenotype correlation could be ascertained including by variant type or functional domain. Conclusion: Phenotypic characteristics cannot be used to inform variant location in BMPR1a. However, the phenotypic characteristics of BMPR1a DCV carriers, being almost exclusively related to the colon and rectum, can assist in pathogenicity assessment of BMPR1a variants. Given these findings, we propose that carriers of BMPR1a DCVs should only require surveillance for colorectal polyps and malignancy, and that surveillance for gastric polyps and malignancy may be unnecessary. However variant location within BMPR1a does not support differential surveillance recommendations.
Language	English
Publishing date	2023-07-03
Publishing country	Poland
Document type	Journal Article ; Review
ZDB-ID	2252512-9
ISSN	1897-4287 ; 1731-2302
ISSN (online)	1897-4287
ISSN	1731-2302
DOI	10.1186/s13053-023-00255-3
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Article ; Online: Cryoneurolysis of the Femoral Nerve for Focal Spasticity in an Ambulatory Patient.

Boissonnault, Ève / MacRae, Fraser / Hashemi, Mahdis / Bursuc, Andrei / Winston, Paul

Archives of rehabilitation research and clinical translation

2024 Volume 6, Issue 1, Page(s) 100319

Abstract: Introduction: Spasticity of the knee extensors is a common presentation among patients with multiple sclerosis. The resulting stiff leg gait can result in increased risk of falls, heightened energy expenditure during gait, lowered gait speed, and ... ...

Abstract	Introduction: Spasticity of the knee extensors is a common presentation among patients with multiple sclerosis. The resulting stiff leg gait can result in increased risk of falls, heightened energy expenditure during gait, lowered gait speed, and compensatory gait mechanisms that increase wear on the hips. Cryoneurolysis is a novel percutaneous, minimally invasive treatment for focal spasticity. Methods: A single patient with multiple sclerosis was treated with cryoneurolysis of the femoral nerve branch to rectus femoris. The patient was followed for 15 months. Spasticity severity, gait speed, and patient reported outcomes were collected at each follow-up. Results: Spasticity severity as per the Modified Ashworth Scale was reduced at 1 month, with change persisting up to 15 months post-procedure. Range of motion as per the Modified Tardieu Scale showed gradual improvement over the 15-month period. Gait speed increased after the procedure from 21.15 seconds to 12.49 seconds for the 10 m walk test 1 month post-procedure, then slowed to baseline after 15 months. The patient's confidence in their gait improved and their independence was maintained throughout the follow-up period. Because of the regression in the 10 m walk test, the patient elected to have the procedure repeated after 15 months. Immediately after the procedure, the 10 m test time improved to 16.20 seconds. Conclusion: Cryoneurolysis of the femoral nerve may be an effective, long-lasting treatment for spasticity causing stiff knee gait in patients with multiple sclerosis.
Language	English
Publishing date	2024-01-05
Publishing country	United States
Document type	Case Reports
ISSN	2590-1095
ISSN (online)	2590-1095
DOI	10.1016/j.arrct.2024.100319
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Article ; Online: The feeding of heather (Calluna vulgaris) to Teladorsagia circumcincta infected lambs reduces parasitism but can detrimentally impact performance.

Shepherd, F / Houdijk, J G M / Chylinski, C / Hutchings, M R / Kelly, R F / Macrae, A / Maurer, V / Salminen, J-P / Engström, M T / Athanasiadou, S

Veterinary journal (London, England : 1997)

2024 Volume 303, Page(s) 106066

Abstract: Gastrointestinal nematode (GIN) infections impact small ruminant health, welfare, and production across farming systems. Rising anthelmintic resistance and regulation of synthetic drug use in organic farming is driving research and development of ... ...

Abstract	Gastrointestinal nematode (GIN) infections impact small ruminant health, welfare, and production across farming systems. Rising anthelmintic resistance and regulation of synthetic drug use in organic farming is driving research and development of sustainable alternatives for GIN control. One alternative is the feeding of plants that contain secondary metabolites (PSMs) e.g., proanthocyanidins (PA, syn. condensed tannins) that have shown anthelmintic potential. However, PSMs can potentially impair performance, arising from reduced palatability and thus intake, digestibility or even toxicity effects. In this study, we tested the trade-off between the antiparasitic and anti-nutritional effects of heather consumption by lambs. The impact of additional feeding of a nematophagous fungus (Duddingtonia flagrans) on larval development was also explored. Lambs infected with Teladorsagia circumcincta or uninfected controls, were offered ad libitum heather, or a control chopped hay for 22 days during the infection patent period. Eight days into the patent period, parasitised lambs were supplemented (or remained unsupplemented) with D. flagrans for a 5-day period. Performance and infection metrics were recorded, and polyphenol levels in the heather and control hay were measured to investigate their association with activity. The lambs consumed heather at approximately 20% of their dry matter intake, which was sufficient to exhibit significant anthelmintic effects via a reduction in total egg output (P = 0.007), compared to hay-fed lambs; the magnitude of the reduction over time in heather fed lambs was almost 10-fold compared to control lambs. Negative effects on production were shown, as heather-fed lambs weighed 6% less than hay-fed lambs (P < 0.001), even though dry matter intake (DMI) of heather increased over time. D. flagrans supplementation lowered larval recovery in the faeces of infected lambs by 31.8% (P = 0.003), although no interactions between feeding heather and D. flagrans were observed (P = 0.337). There was no significant correlation between PA, or other polyphenol subgroups in the diet and egg output, which suggests that any association between heather feeding and anthelmintic effect is not simply and directly attributable to the measured polyphenols. The level of heather intake in this study showed no antagonistic effects on D. flagrans, demonstrating the methods can be used in combination, but provide no additive effect on overall anthelmintic efficacies. In conclusion, heather feeding can assist to reduce egg outputs in infected sheep, but at 20% of DMI negative effects on lamb performance can be expected which may outweigh any antiparasitic benefits.
MeSH term(s)	Animals ; Sheep ; Calluna ; Nematoda ; Nematode Infections/prevention & control ; Nematode Infections/veterinary ; Nematode Infections/parasitology ; Feces/parasitology ; Gastrointestinal Diseases/veterinary ; Polyphenols/therapeutic use ; Anthelmintics/pharmacology ; Anthelmintics/therapeutic use ; Antiparasitic Agents/therapeutic use ; Sheep Diseases/drug therapy ; Sheep Diseases/prevention & control ; Sheep Diseases/parasitology ; Parasite Egg Count/veterinary
Chemical Substances	Polyphenols ; Anthelmintics ; Antiparasitic Agents
Language	English
Publishing date	2024-01-18
Publishing country	England
Document type	Journal Article
ZDB-ID	428614-5
ISSN	1532-2971 ; 0372-5545 ; 1090-0233
ISSN (online)	1532-2971
ISSN	0372-5545 ; 1090-0233
DOI	10.1016/j.tvjl.2024.106066
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Article ; Online: A Case Report of Cryoneurolysis for Dorsal Foot Pain and Toe Clawing in a Patient With Multiple Sclerosis.

MacRae, Fraser / Speirs, Abby / Bursuc, Andrei / Hashemi, Mahdis / Winston, Paul

Archives of rehabilitation research and clinical translation

2023 Volume 5, Issue 3, Page(s) 100286

Abstract: Toe clawing in patients with upper motor neuron disorders is often attributed to the flexor digitorum longus (FDL) and is a common presentation among patients with multiple sclerosis (MS). This movement may be painful because of the altered pressure ... ...

Abstract	Toe clawing in patients with upper motor neuron disorders is often attributed to the flexor digitorum longus (FDL) and is a common presentation among patients with multiple sclerosis (MS). This movement may be painful because of the altered pressure distribution and may increase the risk of falls, heighten energy expenditure during gait, and lower gait speed. Cryoneurolysis is a minimally invasive treatment that may be beneficial for pain and focal muscle hypertonicity. An ambulatory patient with MS was treated bilaterally with cryoneurolysis to the superficial fibular nerves for pain on the dorsum of the foot, and to the intramuscular tibial nerve motor branch to FDL for toe clawing. The patient felt that toe clawing was immediately reduced during gait and noted the ability to voluntarily spread their toes. The patient stated that the neuropathic pain on the dorsum of the foot was fully eliminated immediately post procedure. The patient reported improved confidence in their gait, maintained independence, and reduced toe clawing during a structured interview 12 weeks after treatment. The effects lasted for 5.5 months before symptoms returned. Retreatment at 6 months reproduced the benefits
Language	English
Publishing date	2023-07-28
Publishing country	United States
Document type	Case Reports
ISSN	2590-1095
ISSN (online)	2590-1095
DOI	10.1016/j.arrct.2023.100286
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Article ; Online: Microfluidic Enrichment and Computational Analysis of Rare Sequences from Mixed Genomic Samples for Metagenomic Mining.

Cui, Naiwen / Faure, Guihem / Singh, Ankita / Macrae, Rhiannon / Zhang, Feng

The CRISPR journal

2022 Volume 5, Issue 5, Page(s) 677–684

Abstract: Many powerful molecular biology tools have their origins in natural systems, including restriction modification enzymes and the CRISPR effectors, Cas9, Cas12, and Cas13. Heightened interest in these systems has led to mining of genomic and metagenomic ... ...

Abstract	Many powerful molecular biology tools have their origins in natural systems, including restriction modification enzymes and the CRISPR effectors, Cas9, Cas12, and Cas13. Heightened interest in these systems has led to mining of genomic and metagenomic data to identify new orthologs of these proteins, new types of CRISPR systems, and uncharacterized natural systems with novel mechanisms. To accelerate metagenomic mining, we developed a high-throughput, low-cost droplet microfluidic-based method for enrichment of rare sequences in a mixed starting population. Using a computational pipeline, we then searched in the enriched data for the presence of CRISPR-Cas systems, identifying a previously unknown CRISPR-Cas system. Our approach enables researchers to efficiently mine metagenomic samples for sequences of interest, greatly accelerating the search for nature's treasures.
MeSH term(s)	CRISPR-Cas Systems/genetics ; Gene Editing/methods ; Microfluidics ; Metagenome/genetics ; Genomics
Language	English
Publishing date	2022-10-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3017891-5
ISSN	2573-1602 ; 2573-1599
ISSN (online)	2573-1602
ISSN	2573-1599
DOI	10.1089/crispr.2022.0054
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Zs.MG 119: Show issues

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Article ; Online: Cryoneurolysis of Anterior and Posterior Divisions of the Obturator Nerve.

MacRae, Fraser / Brar, Arman / Boissonnault, Eve / Winston, Paul

American journal of physical medicine & rehabilitation

2022 Volume 102, Issue 1, Page(s) e1–e2

MeSH term(s)	Humans ; Obturator Nerve/anatomy & histology ; Cadaver
Language	English
Publishing date	2022-09-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	219390-5
ISSN	1537-7385 ; 0002-9491 ; 0894-9115
ISSN (online)	1537-7385
ISSN	0002-9491 ; 0894-9115
DOI	10.1097/PHM.0000000000002102
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Article: [Rezension von: Advances in economic theory, ed. by Truman F. Bewley]

MacRae, Larry T

Southern economic journal 55 ,1, S. 241-242

1988

Author's details	L. T. McRae
Keywords	40;49
Language	English
Publisher	Wiley Subscription Services, Inc
Publishing place	Hoboken, NJ
Document type	Article
ZDB-ID	219272x ; 2067038-2
ISSN	2325-8012 ; 0038-4038
ISSN (online)	2325-8012
ISSN	0038-4038
Database	ECONomics Information System

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Article: Redirecting the pioneering function of FOXA1 with covalent small molecules.

Won, Sang Joon / Zhang, Yuxiang / Reinhardt, Christopher J / MacRae, Nicole S / DeMeester, Kristen E / Njomen, Evert / Hargis, Lauren M / Remsberg, Jarrett R / Melillo, Bruno / Cravatt, Benjamin F / Erb, Michael A

bioRxiv : the preprint server for biology

2024

Abstract: Pioneer transcription factors (TFs) exhibit a specialized ability to bind to and open closed chromatin, facilitating engagement by other regulatory factors involved in gene activation or repression. Chemical probes are lacking for pioneer TFs, which has ... ...

Abstract	Pioneer transcription factors (TFs) exhibit a specialized ability to bind to and open closed chromatin, facilitating engagement by other regulatory factors involved in gene activation or repression. Chemical probes are lacking for pioneer TFs, which has hindered their mechanistic investigation in cells. Here, we report the chemical proteomic discovery of electrophilic small molecules that stereoselectively and site-specifically bind the pioneer TF, FOXA1, at a cysteine (C258) within the forkhead DNA-binding domain. We show that these covalent ligands react with FOXA1 in a DNA-dependent manner and rapidly remodel its pioneer activity in prostate cancer cells reflected in redistribution of FOXA1 binding across the genome and directionally correlated changes in chromatin accessibility. Motif analysis supports a mechanism where the covalent ligands relax the canonical DNA binding preference of FOXA1 by strengthening interactions with suboptimal ancillary sequences in predicted proximity to C258. Our findings reveal a striking plasticity underpinning the pioneering function of FOXA1 that can be controlled by small molecules.
Language	English
Publishing date	2024-03-21
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.03.21.586158
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Article: Assembly of the Bacterial Ribosome with Circularly Permuted rRNA.

Dong, Xiyu / Sheng, Kai / Gebert, Luca F R / Aiyer, Sriram / MacRae, Ian J / Lyumkis, Dmitry / Williamson, James R

bioRxiv : the preprint server for biology

2024

Abstract: Co-transcriptional assembly is an integral feature of the formation of RNA-protein complexes that mediate translation. For ribosome synthesis, prior studies have indicated that the strict order of transcription of rRNA domains may not be obligatory ... ...

Abstract	Co-transcriptional assembly is an integral feature of the formation of RNA-protein complexes that mediate translation. For ribosome synthesis, prior studies have indicated that the strict order of transcription of rRNA domains may not be obligatory during bacterial ribosome biogenesis, since a series of circularly permuted rRNAs are viable. In this work, we report the insights into assembly of the bacterial ribosome large subunit (LSU) based on cryo-EM density maps of intermediates that accumulate during
Language	English
Publishing date	2024-04-10
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.04.10.588894
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