scholarly journals Experimenter sex modulates mouse biobehavioural and pharmacological responses

2022 ◽  
Author(s):  
Polymnia Georgiou ◽  
Panos Zanos ◽  
Ta-Chung M Mou ◽  
Xiaoxian An ◽  
Danielle M Gerhard ◽  
...  
Keyword(s):  
Human Male ◽  
Male Scent ◽  
Hippocampal Area ◽  
Stress Susceptibility ◽  
Necessary And Sufficient ◽  
Crf Neurons ◽  
Quantitative Contributions ◽  
Increased Susceptibility

Differential rodent responses to the sex of human experimenters could have far reaching consequences in preclinical studies. Here, we show that the sex of human experimenters affects mouse behaviours and responses to the rapid-acting antidepressant ketamine and its bioactive metabolite (2R,6R)-hydroxynorketamine. We found that mice manifest aversion to human male odours, preference to female odours, and increased susceptibility to stress when handled by male experimenters. This male induced aversion and stress susceptibility is mediated by the activation of brain corticotropin-releasing factor (CRF) neurons projecting from the entorhinal cortrex to hippocampal area CA1. We further establish that exposure to male scent prior to ketamine administration activates CRF neurons projecting from the entorhinal cortex to hippocampus, and that CRF is necessary and sufficient for the in vivo and in vitro actions of ketamine. Further understanding of the specific and quantitative contributions of the sex of human experimenters to different experimental outcomes in rodents may lead not only to reduced heterogeneity between studies, but also increased capability to uncover novel biological mechanisms.

scholarly journals The ER–Golgi intermediate compartment is a key membrane source for the LC3 lipidation step of autophagosome biogenesis

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Liang Ge ◽  
David Melville ◽  
Min Zhang ◽  
Randy Schekman
Keyword(s):  
Autophagosome Formation ◽  
Functional Studies ◽  
A Cell ◽  
Intermediate Compartment ◽  
Membrane Isolation ◽  
Necessary And Sufficient ◽  
Organelle Membrane ◽  
Catabolic Process

Autophagy is a catabolic process for bulk degradation of cytosolic materials mediated by double-membraned autophagosomes. The membrane determinant to initiate the formation of autophagosomes remains elusive. Here, we establish a cell-free assay based on LC3 lipidation to define the organelle membrane supporting early autophagosome formation. In vitro LC3 lipidation requires energy and is subject to regulation by the pathways modulating autophagy in vivo. We developed a systematic membrane isolation scheme to identify the endoplasmic reticulum–Golgi intermediate compartment (ERGIC) as a primary membrane source both necessary and sufficient to trigger LC3 lipidation in vitro. Functional studies demonstrate that the ERGIC is required for autophagosome biogenesis in vivo. Moreover, we find that the ERGIC acts by recruiting the early autophagosome marker ATG14, a critical step for the generation of preautophagosomal membranes.

scholarly journals Probiotics in Fish Nutrition—Long-Standing Household Remedy or Native Nutraceuticals?

Water ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1348
Author(s):  
Sven Wuertz ◽  
Arne Schroeder ◽  
Konrad M. Wanka
Keyword(s):  
Disease Resistance ◽  
Fish Host ◽  
In Vitro Assays ◽  
Fish Nutrition ◽  
Human Consumption ◽  
Feed Conversion ◽  
Resistance Decrease ◽  
Stress Susceptibility

Over the last decades, aquaculture production increased rapidly. The future development of the industry highly relies on the sustainable utilization of natural resources. The need for improving disease resistance, growth performance, food conversion, and product safety for human consumption has stimulated the application of probiotics in aquaculture. Probiotics increase growth and feed conversion, improve health status, raise disease resistance, decrease stress susceptibility, and improve general vigor. Currently, most probiotics still originate from terrestrial sources rather than fish. However, host-associated (autochthonous) probiotics are likely more persistent in the gastrointestinal tract of fish and may, therefore, exhibit longer-lasting effects on the host. Probiotic candidates are commonly screened in in vitro assays, but the transfer to in vivo assessment is often problematic. In conclusion, modulation of the host-associated microbiome by the use of complex probiotics is promising, but a solid understanding of the interactions involved is only in its infancy and requires further research. Probiotics could be used to explore novel ingredients such as chitin-rich insect meal, which cannot be digested by the fish host alone. Most importantly, probiotics offer the opportunity to improve stress and disease resistance, which is among the most pressing problems in aquaculture.

scholarly journals An amphipathic helix enables septins to sense micrometer-scale membrane curvature

2019 ◽  
Vol 218 (4) ◽  
pp. 1128-1137 ◽  
Author(s):  
Kevin S. Cannon ◽  
Benjamin L. Woods ◽  
John M. Crutchley ◽  
Amy S. Gladfelter
Keyword(s):  
Membrane Curvature ◽  
Amphipathic Helix ◽  
Curvature Sensing ◽  
C Terminus ◽  
Number Of Binding Sites ◽  
Curved Membranes ◽  
Necessary And Sufficient ◽  
Micrometer Scale

Cell shape is well described by membrane curvature. Septins are filament-forming, GTP-binding proteins that assemble on positive, micrometer-scale curvatures. Here, we examine the molecular basis of curvature sensing by septins. We show that differences in affinity and the number of binding sites drive curvature-specific adsorption of septins. Moreover, we find septin assembly onto curved membranes is cooperative and show that geometry influences higher-order arrangement of septin filaments. Although septins must form polymers to stay associated with membranes, septin filaments do not have to span micrometers in length to sense curvature, as we find that single-septin complexes have curvature-dependent association rates. We trace this ability to an amphipathic helix (AH) located on the C-terminus of Cdc12. The AH domain is necessary and sufficient for curvature sensing both in vitro and in vivo. These data show that curvature sensing by septins operates at much smaller length scales than the micrometer curvatures being detected.

Rapid Differentiation of a Rare Subset of Adult Human Lin−CD34−CD38− Cells Stimulated by Multiple Growth Factors In Vitro

Blood ◽  
1999 ◽  
Vol 94 (6) ◽  
pp. 1926-1932 ◽  
Author(s):  
Tomoaki Fujisaki ◽  
Marc G. Berger ◽  
Stefan Rose-John ◽  
Connie J. Eaves
Keyword(s):  
Growth Factors ◽  
Fold Increase ◽  
Semisolid Medium ◽  
Response Characteristics ◽  
Adult Human ◽  
Liquid Suspension ◽  
Normal Duration ◽  
Necessary And Sufficient

Abstract Recently, several reports of lineage-negative (lin−) CD34− cells with in vivo hematopoietic activity have focused interest on the properties and growth factor response characteristics of these cells. We have now identified a combination of 5 growth factors that are necessary and sufficient to stimulate a marked mitogenic and differentiation response by a subset of human lin−CD34−CD38− cells present in normal adult human marrow and granulocyte colony-stimulating factor (G-CSF)–mobilized blood. Less than 0.1% of the cells in highly purified (including doubly sorted) lin−CD34−CD38− cells from these 2 sources formed colonies directly in semisolid medium or generated such cells after 6 weeks in long-term culture. Nevertheless, approximately 1% of the same lin−CD34−CD38− cells were able to proliferate rapidly in serum-free liquid suspension cultures containing human flt-3 ligand, Steel factor, thrombopoietin, interleukin-3 (IL-3), and hyper–IL-6 to produce a net 28- ± 8-fold increase in total cells within 10 days. Of the cells present in these 10-day cultures, 5% ± 2% were CD34+ and 2.5% ± 0.9% were erythroid, granulopoietic, megakaryocytopoietic, or multilineage colony-forming cells (CFC) (13 ± 7 CFC per lin−CD34−CD38− pre-CFC). In contrast to lin−CD34+CD38−cells, this response of lin−CD34−CD38− cells required exposure to all of the 5 growth factors used. Up to 1.7 × 105 lin−CD34− adult marrow cells failed to engraft sublethally irradiated NOD/SCID-β2M−/− mice. These studies demonstrate unique properties of a rare subset of lin−CD34−CD38− cells present in both adult human marrow and mobilized blood samples that allow their rapid proliferation and differentiation in vitro within an overall period of 3 to 4 weeks. The rapidity of this response challenges current concepts about the normal duration and coordinated control of these processes in adults.

scholarly journals The Pax6 master control gene initiates spontaneous retinal development via a self-organising Turing network

Development ◽  
2020 ◽  
Vol 147 (24) ◽  
pp. dev185827
Author(s):  
Timothy Grocott ◽  
Estefania Lozano-Velasco ◽  
Gi Fay Mok ◽  
Andrea E. Münsterberg
Keyword(s):  
Model Organism ◽  
Control Gene ◽  
Tissue Interactions ◽  
Organ Systems ◽  
Necessary And Sufficient ◽  
Regenerative Therapies ◽  
Further Development ◽  
Master Control

ABSTRACTUnderstanding how complex organ systems are assembled from simple embryonic tissues is a major challenge. Across the animal kingdom a great diversity of visual organs are initiated by a ‘master control gene’ called Pax6, which is both necessary and sufficient for eye development. Yet precisely how Pax6 achieves this deeply homologous function is poorly understood. Using the chick as a model organism, we show that vertebrate Pax6 interacts with a pair of morphogen-coding genes, Tgfb2 and Fst, to form a putative Turing network, which we have computationally modelled. Computer simulations suggest that this gene network is sufficient to spontaneously polarise the developing retina, establishing the first organisational axis of the eye and prefiguring its further development. Our findings reveal how retinal self-organisation may be initiated independently of the highly ordered tissue interactions that help to assemble the eye in vivo. These results help to explain how stem cell aggregates spontaneously self-organise into functional eye-cups in vitro. We anticipate these findings will help to underpin retinal organoid technology, which holds much promise as a platform for disease modelling, drug development and regenerative therapies.

Diadermatic Dose Forms Of Testosterone: In-Vitro Release Studies and in-Vivo Absorption In A Human Male

1989 ◽  
Vol 15 (9) ◽  
pp. 1405-1422
Author(s):  
A. Babar ◽  
R. A. Khaleque ◽  
A. J. Cutie ◽  
F. M. Plakogiannis
Keyword(s):  
In Vitro Release ◽  
Human Male ◽  
Release Studies ◽  
In Vivo Absorption ◽  
Vitro Release

scholarly journals A single domain of yeast poly(A)-binding protein is necessary and sufficient for RNA binding and cell viability.

1987 ◽  
Vol 7 (9) ◽  
pp. 3268-3276 ◽  
Author(s):  
A B Sachs ◽  
R W Davis ◽  
R D Kornberg
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Association Constant ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
High Affinity ◽  
Terminal Domain ◽  
Necessary And Sufficient

The poly(A)-binding protein (PAB) gene of Saccharomyces cerevisiae is essential for cell growth. A 66-amino acid polypeptide containing half of a repeated N-terminal domain can replace the entire protein in vivo. Neither an octapeptide sequence conserved among eucaryotic RNA-binding proteins nor the C-terminal domain of PAB is required for function in vivo. A single N-terminal domain is nearly identical to the entire protein in the number of high-affinity sites for poly(A) binding in vitro (one site with an association constant of approximately 2 X 10(7) M-1) and in the size of the binding site (12 A residues). Multiple N-terminal domains afford a mechanism of PAB transfer between poly(A) strands.

scholarly journals Cytoplasmic Dynein Nucleates Microtubules to Organize Them into Radial Arrays In Vivo

2004 ◽  
Vol 15 (6) ◽  
pp. 2742-2749 ◽  
Author(s):  
Viacheslav Malikov ◽  
Anna Kashina ◽  
Vladimir Rodionov
Keyword(s):  
Cytoplasmic Dynein ◽  
Exact Function ◽  
Necessary And Sufficient ◽  
Stimulation Of ◽  
In Cells

Numerous evidence demonstrates that dynein is crucial for organization of microtubules (MTs) into radial arrays, but its exact function in this process is unclear. Here, we studied the role of cytoplasmic dynein in MT radial array formation in the absence of the centrosome. We found that dynein is a potent MT nucleator in vitro and that stimulation of dynein activity in cytoplasmic fragments of melanophores induces nucleation-dependent formation of MT radial array in the absence of the centrosome. This new property of dynein, in combination with its known role as an MT motor that is essential for MT array organization in the absence and presence of the centrosome, makes it a unique molecule whose activity is necessary and sufficient for the formation and maintenance of MT radial arrays in cells.

scholarly journals The eutT Gene of Salmonella enterica Encodes an Oxygen-Labile, Metal-Containing ATP:Corrinoid Adenosyltransferase Enzyme

2004 ◽  
Vol 186 (17) ◽  
pp. 5708-5714 ◽  
Author(s):  
Nicole R. Buan ◽  
Sang-Jin Suh ◽  
Jorge C. Escalante-Semerena
Keyword(s):  
Nitrogen Source ◽  
Salmonella Enterica ◽  
Metal Ion ◽  
Complete Loss ◽  
Cell Extracts ◽  
Mutant Strains ◽  
Catalytic Role ◽  
Necessary And Sufficient

ABSTRACT The eutT gene of Salmonella enterica was cloned and overexpressed, and the function of its product was established in vivo and in vitro. The EutT protein has an oxygen-labile, metal-containing ATP:co(I)rrinoid adenosyltransferase activity associated with it. Functional redundancy between EutT and the housekeeping ATP:co(I)rrinoid adenosyltransferase CobA enzyme was demonstrated through phenotypic analyses of mutant strains. Lack of CobA and EutT blocked ethanolamine utilization. EutT was necessary and sufficient for growth of an S. enterica cobA eutT strain on ethanolamine as a carbon and energy or nitrogen source. A eutT+ gene provided in trans corrected the adenosylcobalamin-dependent transcription of a eut-lacZ operon fusion in a cobA strain. Cell extracts enriched for EutT protein contained strong, readily detectable ATP:co(I)rrinoid adenosyltransferase activity. The activity was only detected in extracts maintained under anoxic conditions, with complete loss of activity upon exposure to air or treatment with the Fe2+ ion chelator bathophenanthroline. While the involvement of another metal ion cannot be ruled out, the observed sensitivity to air and bathophenanthroline suggests involvement of Fe2+. We propose that the EutT protein is a unique metal-containing ATP:co(I)rrinoid adenosyltransferase. It is unclear whether the metal ion plays a structural or catalytic role.

scholarly journals Direct regulation of nacre, a zebrafish MITF homolog required for pigment cell formation, by the Wnt pathway

2000 ◽  
Vol 14 (2) ◽  
pp. 158-162 ◽  
Author(s):  
Richard I. Dorsky ◽  
David W. Raible ◽  
Randall T. Moon
Keyword(s):  
Cell Differentiation ◽  
Binding Sites ◽  
Pigment Cell ◽  
Cell Formation ◽  
Dominant Negative ◽  
Reporter Construct ◽  
Cell Fates ◽  
Necessary And Sufficient

We have shown that Wnt signals are necessary and sufficient for neural crest cells to adopt pigment cell fates. nacre, a zebrafish homolog of MITF, is required for pigment cell differentiation. We isolated a promoter region of nacre that contains Tcf/Lef binding sites, which can mediate Wnt responsiveness. This promoter binds to zebrafish Lef1 protein in vitro, and a nacre reporter construct is strongly repressed by dominant-negative Tcf in melanoma cells. Mutation of Tcf/Lef sites abolishes Lef1 binding and reporter function in vivo. Wnt signaling therefore directly activatesnacre, which in turn leads to pigment cell differentiation.

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