Limited digestion with trypsin of both calf thymus H1 histone and the fragment 1 -120 of the H1 molecule has resulted in the isolation of the fragment 35-120. This fragment assumes a globular structure under physiological conditions of pH and ionic strength. The variable N-terminal portion of the molecule, up to residue 34, is not required for the formation of the HI globular structure.Proton nuclear magnetic resonance (NMR) and ultracentrifugation studies show that the H1 histone molecule consists of three distinct structural domains under structuring conditions : a random coil 'nose' consisting of 35 to 40 residues from the N-terminal end; a globular 'head' involving the next approximately 80 residues; and a random-coil 'tail' of the remainder of the molecule.The closely related class of basic eukaryotic chromosomal proteins, generically known as the very-lysine-rich or H1 histones, are quite distinct from the other histones on several counts. They are not, as are the other histones, required for the formation of the nucleosome substructure of the chromosome [l]. It is widely believed that they are involved in higher-order structures in the chromosome [2]. It is noteworthy that even in single tissues there are several subfractions of this protein, and that the relative proportions of the subfractions vary from tissue to tissue of the same species [3,4], implying that they are not functionally identical. Metabolic modification (phosphorylation) of the corresponding proteins in the synchronous slime mould Physarum polycephalum is associated with the initiation of mitotic chromosome condensation [5,6].In early sequence studies Bustin and Cole [7] recognised three distinct regions of the H1 molecule, based on amino acid composition. Firstly a region of about 40 residues starting from the N-terminus which is highly variable in sequence between subfractions. The next 80 residues are highly conserved and include nearly all of the hydrophobic residues in the molecule. The remainder of the molecule (about 95 residues) is highly basic, and contains repetitive sequences rich in lysine, alanine and proline.In a previous paper [8] it has been shown that part of the H1 molecule adopts a globular structure Abbreviations. NMR, proton nuclear magnetic resonance; dansyl, 5-dimethylaminonaphthalene-I-sulphonyl.under physiological conditions of ionic strength and pH. It has also been shown that the basic 'tail' of the molecule is not required for the formation of this structure, and that the C-terminal limit of the minimum globular structure is somewhere between residues 107 and 120 [8,9]. (The sequence numbering is based on alignment with the sequence of RTL3 H1, a subfraction from rabbit thymus gland, which has been published up to residue 107 [lo].) Additional sequence information has been made available to us (H. W. Hsiang and R. D. Cole, private communication). As a result of this numbering system the residue numbers may not be precisely correct for all subfractions owing to the possibility of insertions or deletions in the ...

BackgroundDelirium is a common severe neuropsychiatric condition secondary to physical illness, which predominantly affects older adults in hospital. Prior to this study, the UK point prevalence of delirium was unknown. We set out to ascertain the point prevalence of delirium across UK hospitals and how this relates to adverse outcomes.MethodsWe conducted a prospective observational study across 45 UK acute care hospitals. Older adults aged 65 years and older were screened and assessed for evidence of delirium on World Delirium Awareness Day (14th March 2018). We included patients admitted within the previous 48 h, excluding critical care admissions.ResultsThe point prevalence of Diagnostic and Statistical Manual on Mental Disorders, Fifth Edition (DSM-5) delirium diagnosis was 14.7% (222/1507). Delirium presence was associated with higher Clinical Frailty Scale (CFS): CFS 4–6 (frail) (OR 4.80, CI 2.63–8.74), 7–9 (very frail) (OR 9.33, CI 4.79–18.17), compared to 1–3 (fit). However, higher CFS was associated with reduced delirium recognition (7–9 compared to 1–3; OR 0.16, CI 0.04–0.77). In multivariable analyses, delirium was associated with increased length of stay (+ 3.45 days, CI 1.75–5.07) and increased mortality (OR 2.43, CI 1.44–4.09) at 1 month. Screening for delirium was associated with an increased chance of recognition (OR 5.47, CI 2.67–11.21).ConclusionsDelirium is prevalent in older adults in UK hospitals but remains under-recognised. Frailty is strongly associated with the development of delirium, but delirium is less likely to be recognised in frail patients. The presence of delirium is associated with increased mortality and length of stay at one month. A national programme to increase screening has the potential to improve recognition.

Treatment of chicken erythrocyte histone H5 with trypsin in a high-ionic-strength medium results in very rapid initial digestion and the formation of a 'limiting' resistant product peptide. Under these solution conditions the H5 molecule is maximally folded by spectroscopic criteria and it is concluded that the resistant peptide, GH5, represents a globular folded region of the molecule whilst the rapidly digested parts are disordered. The peptide GH5 is shown to comprise the sequence 22-100. In support of this conclusion it is shown that whilst intact histone H5 is hydrodynamically far from being a compact globular shape, peptide GH5 is approximately spherical by hydrodynamic and scattering criteria. Further more, peptide GH5 retains all the whelical structure of intact H5 (circular dichroism) and appears to also maintain all the tertiary structure (nuclear magnetic resonance). It follows that in solution at high ionic strength, histone H5 consists of three domains: an N-terminal disordered region 1-21, a compact globular central domain 22-100 and a long disordered C-terminal chain 101 -185. Structural parallels are drawn with the three-domain structure of the histone H1 moleculeThe nucleated erythrocytes of birds, reptiles, amphibians and fish contain a basic histone H5 that partially, but not completely replaces histone HI in the mature erythrocyte 11 -51. These two histones have a similar molecular weight (HI : 217 residues [6], H5: 185 residues [7]) and amino acid composition. The main distinction is that histone H5 contains substantially more arginine and serine than histone H I . Studies in this laboratory have demonstrated that histone H1 contains three distinct conformational domains : the N-terminal sequence of 35 residues and the C-terminal 95 residues are disordered in solution, whilst the central region of about 88 residues is compact and approximately spherical [8]. In two similar studies on histone H5 [7,9] the conclusion was reached that in free solution there is a compact folded conformation in the N-terminal half of the molecule which does not extend far beyond residue 99 and inay extend right up to the N-terminus. In the present study histone H5 has been digested with trypsin to give a limiting product peptide, and this peptide has been isolated and identified. It is then shown that although the intact H5 molecule is far from fully compact, the tryptic peptide appears to be fully compact and approximately spherical by hydrodynamic and scattering criteria. Circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy are Ahbrrviatiom. NM R, nuclear magnctic resonance; CD, circularused to demonstrate that the peptide retains all the helicity and the features of tertiary folding that are observed in intact H5. MATERIALS AND METHODS Preprution of Histone H5Chicken erythrocyte histone H5 was prepared by the acid extraction method of Murray et al. [lo] and purified by chromatography on a Biogel P-60 column, eluting with 20 mM HCI, 50 mM NaCI. Gel ElectrophoresisA modified Laemmli sodium ...

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Proton magnetic resonance, circular dichroism and other studies of whole and cleaved calf thymus histone H1 (formerly F1) reveal the presence of specific folded structures in the region approximately from residue 40-115. Ionic, hydrogen-bond and hydrophobic interactions all appear to contribute to the stability of the structure, which is predicted to contain a-helices in regions 42-55 and 58-75. No evidence was found for 8-structures, either inter or intramolecular, or for any structure formation outside the region 40-115. At 18 "C and a protein concentration of 2 mM the first-order exchange rate between random-coil and structured forms is slower than 80 s-'; at 40 "C the exchange rate is faster than 330 s-The very-lysine-rich histone H 1 (formerly called F1 or I; the nomenclature used in this paper is taken from [I]), exhibits several features which distinguish it from the other histone fractions found in eukaryote chromatin. It has the highest molecular weight (approx. 23000) and has a very high lysine : arginine ratio of over 15 : 1, varying up to 21 : 1 for some subfractions.Over 25 % of the molecule consists of lysine residues, but despite this very basic nature histone H1 is the fraction most easily removed from chromatin on increasing the ionic strength of the solution. Histone H1 has been implicated in the condensation of chromatin in two ways : increase in ionic strength of a chromatin gel in the region below that required to remove histone H1 (0.1-0.3 M NaC1) causes a ten-fold physical contraction of the gel which is dependent on the Abbreviations. NMR, nuclear magnetic resonance; CD, circular dichroism. presence of histone H1 [2]; and in the true slime mould P. polycephalum the very-lysine-rich histone H1 undergoes a peak of phosphorylation late in G2 phase at a point in the cell cycle which corresponds to chromosome condensation [3]. This latter observation has led to the proposal that phosphorylation of histone H1 may be part of a mitotic trigger mechanism [4,5]. Furthermore, a histone Hl/DNA reconstituted complex also exhibits physical condensation at the same ionic strengths as those required for chromatin. This effect and that of histone H1 in chromatin gel will be described in the succeeding paper of this series.Mammalian histone H1 has been subjected to several sequence determinations, which reveal some sequence microheterogeneity which is both species and tissue specific [7,8]. The experiments described in this paper were carried out using unfractionated calf thyEur. J. Biochem. 52 (1975)