Publications by authors named "Conor Fitzpatrick"

The objective of this study was to establish the impact of β-casein A1/A1, A1/A2 and A2/A2 phenotypes on the cheese-making process, cheese structure and on the subsequent in vitro gastric digestion properties of the cheese samples. The time required for curd cutting in cheese milk containing β-casein A2/A2 was significantly delayed, compared to milks containing β-caseins A1/A1 and A1/A2. After 180 days of ripening no differences were observed in the level of soluble nitrogen at pH 4.

View Article and Find Full Text PDF

Bovine milk proteins account for 10% of the global protein supply, which justifies the importance of thoroughly understanding their digestive processes. Extensive research on digestion is being conducted both and . However, interpretations and comparisons across different studies require a thorough understanding of the methodologies used.

View Article and Find Full Text PDF

Biological sex is an important risk factor in cancer, but the underlying cell types and mechanisms remain obscure. Since tumor development is regulated by the immune system, we hypothesize that sex-biased immune interactions underpin sex differences in cancer. The male-biased glioblastoma multiforme (GBM) is an aggressive and treatment-refractory tumor in urgent need of more innovative approaches, such as considering sex differences, to improve outcomes.

View Article and Find Full Text PDF

Single-cell analyses parse the brain's billions of neurons into thousands of 'cell-type' clusters residing in different brain structures. Many cell types mediate their functions through targeted long-distance projections allowing interactions between specific cell types. Here we used epi-retro-seq to link single-cell epigenomes and cell types to long-distance projections for 33,034 neurons dissected from 32 different regions projecting to 24 different targets (225 source-to-target combinations) across the whole mouse brain.

View Article and Find Full Text PDF

Neuronal cell types are classically defined by their molecular properties, anatomy and functions. Although recent advances in single-cell genomics have led to high-resolution molecular characterization of cell type diversity in the brain, neuronal cell types are often studied out of the context of their anatomical properties. To improve our understanding of the relationship between molecular and anatomical features that define cortical neurons, here we combined retrograde labelling with single-nucleus DNA methylation sequencing to link neural epigenomic properties to projections.

View Article and Find Full Text PDF

Mammalian brain cells show remarkable diversity in gene expression, anatomy and function, yet the regulatory DNA landscape underlying this extensive heterogeneity is poorly understood. Here we carry out a comprehensive assessment of the epigenomes of mouse brain cell types by applying single-nucleus DNA methylation sequencing to profile 103,982 nuclei (including 95,815 neurons and 8,167 non-neuronal cells) from 45 regions of the mouse cortex, hippocampus, striatum, pallidum and olfactory areas. We identified 161 cell clusters with distinct spatial locations and projection targets.

View Article and Find Full Text PDF

Dynamic three-dimensional chromatin conformation is a critical mechanism for gene regulation during development and disease. Despite this, profiling of three-dimensional genome structure from complex tissues with cell-type specific resolution remains challenging. Recent efforts have demonstrated that cell-type specific epigenomic features can be resolved in complex tissues using single-cell assays.

View Article and Find Full Text PDF

Single-cell DNA methylome profiling has enabled the study of epigenomic heterogeneity in complex tissues and during cellular reprogramming. However, broader applications of the method have been impeded by the modest quality of sequencing libraries. Here we report snmC-seq2, which provides improved read mapping, reduced artifactual reads, enhanced throughput, as well as increased library complexity and coverage uniformity compared to snmC-seq.

View Article and Find Full Text PDF

Activity-induced remodeling of neuronal circuits is critical for memory formation. This process relies in part on transcription, but neither the rate of activity nor baseline transcription is equal across neuronal cell types. In this study, we isolated mouse hippocampal populations with different activity levels and used single nucleus RNA-seq to compare their transcriptional responses to activation.

View Article and Find Full Text PDF

Astrocyte dysfunction and neuroinflammation are detrimental features in multiple pathologies of the CNS. Therefore, the development of methods that produce functional human astrocytes represents an advance in the study of neurological diseases. Here we report an efficient method for inflammation-responsive astrocyte generation from induced pluripotent stem cells (iPSCs) and embryonic stem cells.

View Article and Find Full Text PDF

Microglia play essential roles in central nervous system (CNS) homeostasis and influence diverse aspects of neuronal function. However, the transcriptional mechanisms that specify human microglia phenotypes are largely unknown. We examined the transcriptomes and epigenetic landscapes of human microglia isolated from surgically resected brain tissue ex vivo and after transition to an in vitro environment.

View Article and Find Full Text PDF
Article Synopsis
  • Single-cell sequencing methods are valuable for identifying different cell types in specific brain regions and understanding how activated neurons respond to experiences.
  • The study demonstrates that single-nuclei RNA-sequencing (snRNA-seq) effectively captures the changes in gene expression associated with neuronal activity, including the induction of immediate early genes like Fos, Arc, and Egr1.
  • Analysis of mouse dentate granule cells shows significant transcriptional changes after exposure to a new environment, revealing distinct activation states and providing insights into neuronal activation patterns beyond just immediate early genes.
View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_sessionnihorfbi21eptugj478cu5ho7n55osoq): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once