Functional analysis of secreted and transmembrane proteins critical to mouse development

ABSTRACT Mice homozygous for the s1Acrg deletion at the Ednrb locus arrest at embryonic day 8.5. To determine the molecular basis of this defect, we initiated positional cloning of the s1Acrg minimal region. The mouseUch-L3 (ubiquitin C-terminal hydrolase L3) gene was mapped within the s1Acrg minimal region. BecauseUch-L3 transcripts were present in embryonic structures relevant to the s1Acrg phenotype, we created a targeted mutation in Uch-L3 to address its role during development and its possible contribution to thes1Acrg phenotype. Mice homozygous for the mutation Uch-L3Δ3-7 were viable, with no obvious developmental or histological abnormalities. Although high levels of Uch-L3 RNA were detected in testes and thymus,Uch-L3Δ3-7 homozygotes were fertile, and no defect in intrathymic T-cell differentiation was detected. We conclude that the s1Acrg phenotype is either complex and multigenic or due to the loss of another gene within the region. We propose that Uch-L3 may be functionally redundant with its homologue Uch-L1.

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Systems evaluation reveals novel transporter YohJK renders 3-hydroxypropionate tolerance in Escherichia coli

Scientific Reports ◽

10.1038/s41598-020-76120-3 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Thuan Phu Nguyen-Vo ◽

Seyoung Ko ◽

Huichang Ryu ◽

Jung Rae Kim ◽

Donghyuk Kim ◽

...

Keyword(s):

Escherichia Coli ◽

Functional Analysis ◽

Transcription Factor ◽

Binding Sites ◽

Deletion Mutant ◽

Transmembrane Proteins ◽

Rna Seq ◽

Wild Type ◽

Drastic Reduction ◽

Functional Studies

Abstract Previously, we have reported that 3-hydroxypropionate (3-HP) tolerance in Escherichia coli W is improved by deletion of yieP, a less-studied transcription factor. Here, through systems analyses along with physiological and functional studies, we suggest that the yieP deletion improves 3-HP tolerance by upregulation of yohJK, encoding putative 3-HP transporter(s). The tolerance improvement by yieP deletion was highly specific to 3-HP, among various C2–C4 organic acids. Mapping of YieP binding sites (ChIP-exo) coupled with transcriptomic profiling (RNA-seq) advocated seven potential genes/operons for further functional analysis. Among them, the yohJK operon, encoding for novel transmembrane proteins, was the most responsible for the improved 3-HP tolerance; deletion of yohJK reduced 3-HP tolerance regardless of yieP deletion, and their subsequent complementation fully restored the tolerance in both the wild-type and yieP deletion mutant. When determined by 3-HP-responsive biosensor, a drastic reduction of intracellular 3-HP was observed upon yieP deletion or yohJK overexpression, suggesting that yohJK encodes for novel 3-HP exporter(s).

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Clinical Issues: What’s in a Word? A Functional Analysis of Word Learning

Perspectives on Language Learning and Education ◽

10.1044/lle12.3.4 ◽

2005 ◽

Vol 12 (3) ◽

pp. 4-8 ◽

Cited By ~ 7

Author(s):

Prahlad Gupta

Keyword(s):

Functional Analysis ◽

Word Learning ◽

Clinical Issues

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Review for "High‐throughput single‐cell sequencing of paired TCRα and TCRβ genes for the direct expression‐cloning and functional analysis of murine T cell receptors"

10.1002/eji.201848030/v1/review1 ◽

2019 ◽

Keyword(s):

Functional Analysis ◽

T Cell ◽

Single Cell ◽

High Throughput ◽

T Cell Receptors ◽

Expression Cloning ◽

Cell Receptors ◽

Single Cell Sequencing

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Case Formulation and Design of Behavioral Treatment Programs

European Journal of Psychological Assessment ◽

10.1027//1015-5759.19.3.164 ◽

2003 ◽

Vol 19 (3) ◽

pp. 164-174 ◽

Cited By ~ 27

Author(s):

Stephen N. Haynes ◽

Andrew E. Williams

Keyword(s):

Functional Analysis ◽

Behavior Problems ◽

Behavioral Treatment ◽

Clinical Case ◽

Relative Magnitude ◽

Mechanisms Of Action ◽

Treatment Programs ◽

Case Formulation ◽

Functional Relations ◽

Causal Variables

Summary: We review the rationale for behavioral clinical case formulations and emphasize the role of the functional analysis in the design of individualized treatments. Standardized treatments may not be optimally effective for clients who have multiple behavior problems. These problems can affect each other in complex ways and each behavior problem can be influenced by multiple, interacting causal variables. The mechanisms of action of standardized treatments may not always address the most important causal variables for a client's behavior problems. The functional analysis integrates judgments about the client's behavior problems, important causal variables, and functional relations among variables. The functional analysis aids treatment decisions by helping the clinician estimate the relative magnitude of effect of each causal variable on the client's behavior problems, so that the most effective treatments can be selected. The parameters of, and issues associated with, a functional analysis and Functional Analytic Clinical Case Models (FACCM) are illustrated with a clinical case. The task of selecting the best treatment for a client is complicated because treatments differ in their level of specificity and have unequally weighted mechanisms of action. Further, a treatment's mechanism of action is often unknown.

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