Biology subjects

Phillips, H.

Publications and source records attributed to Phillips, H..

4 recordsLinked to original sources

bioRxiv2026

Brain Age in Conduct Disorder: A Mega-Analysis of the ENIGMA Antisocial Behavior Working Group

Conduct disorder (CD) is the leading global cause of mental health burden in children and adolescents and has recently been hypothesized to be a neurodevelopmental disorder. Although prior research has identified neuroanatomical differences associated with CD, it remains unclear whether these differences reflect atypical brain development. Here, we investigated the difference between an individuals brain age and chronological age as a proxy for variations in brain maturation. Using a pretrained model, we estimated brain age from structural neuroimaging data obtained from 1,119 youth with CD and 1,183 typically developing controls across 14 international cohorts participating in the ENIGMA-Antisocial Behavior Working Group. Youth with CD exhibited a statistically robust but small acceleration in brain age compared to typically developing youth (around 0.50 years), which was restricted to the adolescence-onset subtype of the disorder. Our large-scale, coordinated analysis provides the first evidence of accelerated neurodevelopment as a potential mechanism underlying CD.

neuroscience↗

bioRxiv2024

Autophagy suppression in DNA damaged cells occurs through a newly identified p53-proteasome-LC3 axis

Macroautophagy is thought to have a critical role in shaping and refining cellular proteostasis in eukaryotic cells recovering from DNA damage. Here, we report a mechanism by which autophagy is suppressed in cells exposed to bacterial toxin-, chemical-, or radiation-mediated sources of genotoxicity. Autophagy suppression is directly linked to cellular responses to DNA damage, and specifically the stabilization of the tumor suppressor p53, which is both required and sufficient for regulating the ubiquitination and proteasome-dependent reduction in cellular pools of microtubule-associated protein 1 light chain 3 (LC3A/B), a key precursor of autophagosome biogenesis and maturation, in both epithelial cells and an ex vivo organoid model. Our data indicate that suppression of autophagy, through a newly identified p53-proteasome-LC3 axis, is a conserved cellular response to multiple sources of genotoxicity. Such a mechanism could potentially be important for realigning proteostasis in cells undergoing DNA damage repair.

cell biology↗

bioRxiv2020

Arterial endoglin does not protect against arteriovenous malformations

Endoglin (ENG) forms a receptor complex with ALK1 in endothelial cells (ECs) to promote BMP9/10 signalling. Loss of function mutations in either ENG or ALK1 genes lead to the inherited vascular disorder Hereditary Haemorrhagic Telangiectasia (HHT), characterised by arteriovenous malformations (AVMs). However, the vessel-specific role of ENG and ALK1 proteins in protecting against AVMs is unclear. For example, AVMs have been described to initiate in arterioles, whereas ENG is predominantly expressed in venous ECs. To investigate whether ENG has any arterial involvement in protecting against AVM formation we specifically depleted the Eng gene in venous and capillary endothelium whilst maintaining arterial expression, and investigated how this affected the incidence and location of AVMs in comparison with pan-endothelial Eng knockdown. MethodsUsing the mouse neonatal retinal model of angiogenesis, we first established the earliest time point at which Apj-Cre-ERT2 activity was present in venous and capillary ECs but absent from arterial ECs. We then compared the incidence of AVMs following pan-endothelial or venous/capillary-specific ENG knockout. ResultsActivation of Apj-Cre-ERT2 with tamoxifen from postnatal day (P) 5 ensured preservation of arterial ENG protein expression. Specific loss of ENG expression in ECs of veins and capillaries led to retinal AVMs at a similar frequency to pan-endothelial loss of ENG. AVMs occurred in the proximal as well as the distal part of the retina consistent with a defect in vascular remodelling during maturation of the vasculature. ConclusionExpression of ENG is not required in arterial ECs to protect against AVM formation.

genetics↗

bioRxiv2019

Yield, nutritional quality, and fatty acid content of organic winter rye (Secale cereale) and winter wheat (Triticum aestivum) forages under cattle (Bos taurus) grazing conditions

The objective of this study was to assess yield, nutritional quality, and fatty acid compositions of winter rye (Secale cereale) and winter wheat (Triticum aestivum) forages for grazing cattle (Bos taurus) in an organic system. The rye and wheat were established on two 4 ha plots in September 2015. Six groups of dairy steers rotationally grazed rye (n = 3) or wheat (n = 3) plots divided into seven paddocks (n = 14) from April to June 2016. Forage samples (n = 96) taken prior to paddock grazing were used to analyze forage characteristics. Mixed models with fixed factors of forage, date, and their interaction, a random subject factor of group nested in paddock, and a repeated effect of date were used for each outcome. The linear effect of date on fatty acids was obtained by substituting date as a continuous variable. The mean forage yield for rye was greater (P < 0.05) than wheat (mean {+/-} standard error; 2840 and 2571 {+/-} 82 kg ha-1, respectively). However, rye yielded less in the latter part of the grazing period. Wheat (19.3 {+/-} 0.30% DM) had greater (P < 0.001) crude protein than rye (17.6 {+/-} 0.30% DM). In general, crude protein, digestibility, and minerals decreased during the grazing period. Wheat (66.3 {+/-} 0.54 g 100g-1) had greater (P < 0.001) alpha-linolenic acid (18:3n-3) concentration than rye (63.3 {+/-} 0.54 g 100g-1). Although both forages decreased (P < 0.05) in alpha-linolenic acid concentration, wheat decreased 2.49 times more (P < 0.001) per d compared to rye forage. Winter rye and winter wheat forages are viable for cattle grazing. Producers should initiate early grazing to maximize protein, digestibility, and alpha-linolenic acid intake while the forages are immature.

plant biology↗