Use of M13mp phages to study gene regulation, structure and function: cloning and recombinational analysis of genes of the Salmonella typhimurium histidine operon

Gene ◽  
1983 ◽  
Vol 26 (2-3) ◽  
pp. 147-158 ◽  
Author(s):  
Stanley Artz ◽  
Donald Holzschu ◽  
Paul Blum ◽  
Richard Shand
Author(s):  
Steven E. Hyman ◽  
Doug McConnell

‘Mental illness: the collision of meaning with mechanism’ is based on the views of psychiatry that Steven Hyman articulated in his Loebel Lectures—mental illness results from the disordered functioning of the human brain and effective treatment repairs or mitigates those malfunctions. This view is not intended as reductionist as causes of mental illness and contributions to their repair may come from any source that affects the structure and function of the brain. These might include social interactions and other sources of lived experience, ideas (such as those learned in cognitive therapy), gene sequences and gene regulation, metabolic factors, drugs, electrodes, and so on. This, however, is not the whole story for psychiatry on Hyman’s view; interpersonal interactions between clinicians and patients, intuitively understood in such folk psychological terms as selfhood, intention, and agency are also critical for successful practice. As human beings who are suffering, patients seek to make sense of their lives and benefit from the empathy, respect, and a sense of being understood not only as the objects of a clinical encounter, but also as subjects. Hyman’s argument, however, is that the mechanisms by which human brains function and malfunction to produce the symptoms and impairments of mental illness are opaque to introspection and that the mechanistic understandings necessary for diagnosis and treatment are incommensurate with intuitive (folk psychological) human self-understanding. Thus, psychiatry does best when skillful clinicians switch between an objectifying medical and neurobiological stance and the interpersonal stance in which the clinician engages the patients as a subject. Attempts to integrate these incommensurate views of patients and their predicaments have historically produced incoherent explanations of psychopathology and have often led treatment astray. For example, privileging of folk psychological testimony, even when filtered through sophisticated theories has historically led psychiatry into intellectually blind and clinically ineffective cul-de-sacs such as psychoanalysis.


1990 ◽  
Vol 216 (4) ◽  
pp. 883-895 ◽  
Author(s):  
S. Brewer ◽  
M. Tolley ◽  
I.P. Trayer ◽  
G.C. Barr ◽  
C.J. Dorman ◽  
...  

2021 ◽  
Author(s):  
Li-Hsin Chang ◽  
Sourav Ghosh ◽  
Andrea Papale ◽  
Mélanie Miranda ◽  
Vincent Piras ◽  
...  

Topologically Associating Domains (TADs) compartmentalize vertebrate genomes into sub-Megabase functional neighbourhoods for gene regulation, DNA replication, recombination and repair. TADs are formed by Cohesin-mediated loop extrusion, which compacts the DNA within the domain, followed by blocking of loop extrusion by the CTCF insulator protein at their boundaries. CTCF blocks loop extrusion in an orientation dependent manner, with both experimental and in-silico studies assuming that a single site of static CTCF binding is sufficient to create a stable TAD boundary. Here, we report that most TAD boundaries in mouse cells are modular entities where CTCF binding clusters within extended genomic intervals. Optimized ChIP-seq analysis reveals that this clustering of CTCF binding does not only occur among peaks but also frequently within those peaks. Using a newly developed multi-contact Nano-C assay, we confirm that individual CTCF binding sites additively contribute to TAD separation. This clustering of CTCF binding may counter against the dynamic DNA-binding kinetics of CTCF, which urges a re-evaluation of current models for the blocking of loop extrusion. Our work thus reveals an unanticipatedly complex code of CTCF binding at TAD boundaries that expands the regulatory potential for TAD structure and function and can help to explain how distant non-coding structural variation influences gene regulation, DNA replication, recombination and repair.


1988 ◽  
Vol 203 (3) ◽  
pp. 585-606 ◽  
Author(s):  
Maria Stella Carlomagno ◽  
Lorenzo Chiariotti ◽  
Pietro Alifano ◽  
Anna Giulia Nappo ◽  
Carmelo B. Bruni

Biochemistry ◽  
1995 ◽  
Vol 34 (34) ◽  
pp. 10764-10770 ◽  
Author(s):  
Derya H. Ozturk ◽  
Ryan H. Dorfman ◽  
Giovanna Scapin ◽  
James C. Sacchettini ◽  
Charles Grubmeyer

Author(s):  
Peter Sterling

The synaptic connections in cat retina that link photoreceptors to ganglion cells have been analyzed quantitatively. Our approach has been to prepare serial, ultrathin sections and photograph en montage at low magnification (˜2000X) in the electron microscope. Six series, 100-300 sections long, have been prepared over the last decade. They derive from different cats but always from the same region of retina, about one degree from the center of the visual axis. The material has been analyzed by reconstructing adjacent neurons in each array and then identifying systematically the synaptic connections between arrays. Most reconstructions were done manually by tracing the outlines of processes in successive sections onto acetate sheets aligned on a cartoonist's jig. The tracings were then digitized, stacked by computer, and printed with the hidden lines removed. The results have provided rather than the usual one-dimensional account of pathways, a three-dimensional account of circuits. From this has emerged insight into the functional architecture.


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