46 research outputs found
Coatomer and dimeric ADP ribosylation factor 1 promote distinct steps in membrane scission
During membrane budding, coatomer drives initial curvature of the bud, whereas dimeric Arf1 is necessary for membrane scission
Membrane curvature in cell biology: An integration of molecular mechanisms.
Curving biological membranes establishes the complex architecture of the cell and mediates membrane traffic to control flux through subcellular compartments. Common molecular mechanisms for bending membranes are evident in different cell biological contexts across eukaryotic phyla. These mechanisms can be intrinsic to the membrane bilayer (either the lipid or protein components) or can be brought about by extrinsic factors, including the cytoskeleton. Here, we review examples of membrane curvature generation in animals, fungi, and plants. We showcase the molecular mechanisms involved and how they collaborate and go on to highlight contexts of curvature that are exciting areas of future research. Lessons from how membranes are bent in yeast and mammals give hints as to the molecular mechanisms we expect to see used by plants and protists
Premature ovarian failure and ovarian autoimmunity
Premature ovarian failure (POF) is defined as a syndrome characterized by
menopause before the age of 40 yr. The patients suffer from anovulation
and hypoestrogenism. Approximately 1% of women will experience menopause
before the age of 40 yr. POF is a heterogeneous disorder with a
multicausal pathogenesis involving chromosomal, genetic, enzymatic,
infectious, and iatrogenic causes. There remains, however, a group of POF
patients without a known etiology, the so-called "idiopathic" form. An
autoimmune etiology is hypothesized for the POF cases with a concomitant
Addison's disease and/or oophoritis. It is concluded in this review that
POF in association with adrenal autoimmunity and/or Addison's disease
(2-10% of the idiopathic POF patients) is indeed an autoimmune disease.
The following evidence warrants this view: 1) The presence of
autoantibodies to steroid-producing cells in these patients; 2) The
characterization of shared autoantigens between adrenal and ovarian
steroid-producing cells; 3) The histological picture of the ovaries of
such cases (lymphoplasmacellular infiltrate around steroid-producing
cells); 4) The existence of various autoimmune animal models for this
syndrome, which underlines the autoimmune nature of the disease. There is
some circumstantial evidence for an autoimmune pathogenesis in idiopathic
POF patients in the absence of adrenal autoimmunity or Addison's disease.
Arguments in support of this are: 1) The presence of cellular immune
abnormalities in this POF patient group reminiscent of endocrine
autoimmune diseases such as IDDM, Graves' disease, and Addison's disease;
2) The more than normal association with IDDM and myasthenia gravis. Data
on the presence of various ovarian autoantibodies and anti-receptor
antibodies in these patients are, however, inconclusive and need further
evaluation. A strong argument against an autoimmune pathogenesis of POF in
these patients is the nearly absent histological confirmation (the
presence of an oophoritis) in these cases (< 3%). However, in animal
models using ZP immunization, similar follicular depletion and fibrosis
(as in the POF women) can be detected. Accepting the concept that POF is a
heterogenous disorder in which some of the idiopathic forms are based on
an abnormal self-recognition by th
Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
The production of peroxide and superoxide is an inevitable consequence of
aerobic metabolism, and while these particular "reactive oxygen species" (ROSs)
can exhibit a number of biological effects, they are not of themselves
excessively reactive and thus they are not especially damaging at physiological
concentrations. However, their reactions with poorly liganded iron species can
lead to the catalytic production of the very reactive and dangerous hydroxyl
radical, which is exceptionally damaging, and a major cause of chronic
inflammation. We review the considerable and wide-ranging evidence for the
involvement of this combination of (su)peroxide and poorly liganded iron in a
large number of physiological and indeed pathological processes and
inflammatory disorders, especially those involving the progressive degradation
of cellular and organismal performance. These diseases share a great many
similarities and thus might be considered to have a common cause (i.e.
iron-catalysed free radical and especially hydroxyl radical generation). The
studies reviewed include those focused on a series of cardiovascular, metabolic
and neurological diseases, where iron can be found at the sites of plaques and
lesions, as well as studies showing the significance of iron to aging and
longevity. The effective chelation of iron by natural or synthetic ligands is
thus of major physiological (and potentially therapeutic) importance. As
systems properties, we need to recognise that physiological observables have
multiple molecular causes, and studying them in isolation leads to inconsistent
patterns of apparent causality when it is the simultaneous combination of
multiple factors that is responsible. This explains, for instance, the
decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference