Hemopoietic tissue volume is a heritable trait in the schistosome-transmitting snailBiomphalaria glabrata

2016 ◽  
Vol 135 (2) ◽  
pp. 108-116 ◽  
Author(s):  
John T. Sullivan ◽  
Roxxana V. Beltran ◽  
Brandon C. Cruz ◽  
Rhea A. Manuel ◽  
John K. White
2020 ◽  
Vol 32 (4) ◽  
pp. 1190-1205
Author(s):  
Natasha Marrus ◽  
Julia D. Grant ◽  
Brooke Harris-Olenak ◽  
Jordan Albright ◽  
Drew Bolster ◽  
...  

AbstractImpairment in reciprocal social behavior (RSB), an essential component of early social competence, clinically defines autism spectrum disorder (ASD). However, the behavioral and genetic architecture of RSB in toddlerhood, when ASD first emerges, has not been fully characterized. We analyzed data from a quantitative video-referenced rating of RSB (vrRSB) in two toddler samples: a community-based volunteer research registry (n = 1,563) and an ethnically diverse, longitudinal twin sample ascertained from two state birth registries (n = 714). Variation in RSB was continuously distributed, temporally stable, significantly associated with ASD risk at age 18 months, and only modestly explained by sociodemographic and medical factors (r2 = 9.4%). Five latent RSB factors were identified and corresponded to aspects of social communication or restricted repetitive behaviors, the two core ASD symptom domains. Quantitative genetic analyses indicated substantial heritability for all factors at age 24 months (h2 ≥ .61). Genetic influences strongly overlapped across all factors, with a social motivation factor showing evidence of newly-emerging genetic influences between the ages of 18 and 24 months. RSB constitutes a heritable, trait-like competency whose factorial and genetic structure is generalized across diverse populations, demonstrating its role as an early, enduring dimension of inherited variation in human social behavior. Substantially overlapping RSB domains, measurable when core ASD features arise and consolidate, may serve as markers of specific pathways to autism and anchors to inform determinants of autism's heterogeneity.


1998 ◽  
Vol 7 (5) ◽  
pp. 469-478 ◽  
Author(s):  
Jan P. Stegemann ◽  
John J. O'Neil ◽  
Don T. Nicholson ◽  
Claudy J.-P. Mullon

Accurate and consistent measurement of tissue volume is critical to performing many types of islet research; however, conventional visual determination of isolated islet yields through a microscope is heavily operator dependent. An improved method of islet volume determination using digital image analysis (DIA) was developed to remove operator bias and automate the islet counting process. A series of 140 porcine islet isolations were used to evaluate the DIA method in three separate stages. In Stage 1 ( n = 29 isolations), the conventional and DIA methods were correlated with two other independent islet quantitation methods: insulin extraction, and DNA extraction. It was found that volumes determined by DIA correlated more closely with insulin content and DNA content than did conventionally determined volumes. In Stages 2 and 3 ( n = 54 and 57 isolations, respectively), it was shown that an increase in the number of fields analyzed by DIA did not significantly improve the quality of the correlations. Inclusion of very small tissue (<50 fun in diameter), which is ignored in the conventional protocol affected yields by less than 10% and did not significantly improve the correlation with insulin or DNA content. Quantitation of isolated islet tissue volume using DIA has been shown to be rapid, consistent, and objective. In the laboratory, use of this method as the standard for islet volume measurement will allow more meaningful comparison of experimental results between centers. In the clinic, its use will allow more accurate dosing of transplanted tissue. © 1998 Elsevier Science Inc.


2019 ◽  
Vol 81 (5) ◽  
pp. 3056-3064 ◽  
Author(s):  
Thomas A. Perry ◽  
Andrew Gait ◽  
Terence W. O’Neill ◽  
Matthew J. Parkes ◽  
Richard Hodgson ◽  
...  

Author(s):  
M. Luu ◽  
P. Vabres ◽  
H. Devilliers ◽  
R. Loffroy ◽  
A. Phan ◽  
...  

ABSTRACT Purpose PIK3CA pathogenic variants in the PIK3CA-related overgrowth spectrum (PROS) activate phosphoinositide 3-kinase signaling, providing a rationale for targeted therapy, but no drug has proven efficacy and safety in this population. Our aim was to establish the six-month tolerability and efficacy of low-dose taselisib, a selective class I PI3K inhibitor, in PROS patients. Methods Patients over 16 years with PROS and PIK3CA pathogenic variants were included in a phase IB/IIA multicenter, open-label single-arm trial (six patients at 1 mg/day of taselisib, then 24 at 2 mg/day). The primary outcome was the occurrence of dose limiting toxicity (DLT). Efficacy outcomes were the relative changes after treatment of (1) tissue volume at affected and unaffected sites, both clinically and on imaging; (2) cutaneous vascular outcomes when relevant; (3) biologic parameters; (4) quality of life; and (5) patient-reported outcomes. Results Among 19 enrolled patients, 2 experienced a DLT (enteritis and pachymeningitis) leading to early trial termination (17 treated, 10 completed the study). No serious adverse reaction occurred in the 1 mg cohort (n = 6). No significant reduction in affected tissue volume was observed (mean −4.2%; p = 0.81; SD 14.01). Thirteen (76.4%) participants reported clinical improvement (pain reduction, chronic bleeding resolution, functional improvement). Conclusion Despite functional improvement, the safety profile of low-dose taselisib precludes its long-term use.


2007 ◽  
Vol 29 (2) ◽  
pp. 210-214 ◽  
Author(s):  
W. P. Martins ◽  
R. A. Ferriani ◽  
D. A. Barra ◽  
R. M. dos Reis ◽  
M. A. V. Bortolieiro ◽  
...  

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