Soviet psychiatric abuse: allegations met by red tape

Responding to accusations by human rights groups concerning the confinement of dissidents in mental hospitals, the Soviet All-Union Society of Psychiatrists (AUSP) has supplied the World Psychiatric Association (WPA) with data on two alleged cases of abuse and promised information on four more. Some member societies are suspicious that the move is simply a delaying tactic to forestall possible ouster of the AUSP from the WPA. Some members are also concerned that the WPA executive council's "overscrupulous" stance on confidentiality has hindered investigation of complaints of psychiatric abuse.     

The short song of Brewer's Sparrow: individual and geographic variation in southern Idaho

Brewer's Sparrows ( Spizella breweri ) have two song types--a ""short"" song that has 1 to 3 trill types and a ""long"" song that has 5 to 10 or more trill types. I describe the short song and examine patterns of individual and geographic song variation from 15 sites on the Snake River Plain in southern Idaho. Territorial males sang the short song regularly during the breeding season. Two-trill song types comprised 72.9% of all song types, with 3-trill types (18.8%) and 1-trill types (8.2%) less frequent. Over 90% of the males sang their song type(s) essentially without variation. Many trill types appeared most often in only 1 of 3 possible song positions, i.e., 1st, 2nd, or 3rd trill. Trill types that occurred in different song positions differed in syllables per second, trill and syllable duration, and frequency variables. First trill types were more variable than 2nd or 3rd trill types. There was no evidence that birds at sites closer together shared more trill types or pairs of trill types than those farther apart. There was no tendency for territorial neighbors to sing similar song types. Brewer's Sparrows' small territories, dense populations, and apparently high rate of annual turnover may mediate against the evolution of song sharing or vocal dialects.     

A Comparison of SuperDARN-Derived Plasma Convection and DMSP Ion Drift Measurements

Recently several studies indicated possible deterioration of accuracy in the SuperDARN convection measurements at large distances （〉2 500 km）. In this study, the SuperDARN-derived convection was compared with ion drift measurements given by the DMSP satellites, focused on SuperDARN far-range measurements, to investigate the above-mentioned problem. Two different procedures of SuperDARN convection estimation were applied. An overall reasonable agreement between two observation systems were found though individual points in some passes show significant differences. Besides, a tendency is also clear that the SuperDARN-derived velocities were slightly smaller than those of DMSP ion drift measurements. Potential factors contributing to the velocity differences were explained.     

A tidally distorted dwarf galaxy near NGC 4449

NGC 4449 is a nearby Magellanic irregular starburst galaxy with a B-band absolute magnitude of -18 and a prominent, massive, intermediate-age nucleus at a distance from Earth of 3.8?megaparsecs (ref. 3). It is wreathed in an extraordinary neutral hydrogen (H?I) complex, which includes rings, shells and a counter-rotating core, spanning ～90?kiloparsecs (kpc; refs 1, 4). NGC 4449 is relatively isolated, although an interaction with its nearest known companion--the galaxy DDO 125, some 40?kpc to the south--has been proposed as being responsible for the complexity of its H?I structure. Here we report the presence of a dwarf galaxy companion to NGC 4449, namely NGC 4449B. This companion has a V-band absolute magnitude of -13.4 and a half-light radius of 2.7?kpc, with a full extent of around 8?kpc. It is in a transient stage of tidal disruption, similar to that of the Sagittarius dwarf near the Milky Way. NGC 4449B exhibits a striking S-shaped morphology that has been predicted for disrupting galaxies but has hitherto been seen only in a dissolving globular cluster. We also detect an additional arc or disk ripple embedded in a two-component stellar halo, including a component extending twice as far as previously known, to about 20?kpc from the galaxy's centre.     

Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanism

Insulin-degrading enzyme (IDE), a Zn2+-metalloprotease, is involved in the clearance of insulin and amyloid-beta (refs 1-3). Loss-of-function mutations of IDE in rodents cause glucose intolerance and cerebral accumulation of amyloid-beta, whereas enhanced IDE activity effectively reduces brain amyloid-beta (refs 4-7). Here we report structures of human IDE in complex with four substrates (insulin B chain, amyloid-beta peptide (1-40), amylin and glucagon). The amino- and carboxy-terminal domains of IDE (IDE-N and IDE-C, respectively) form an enclosed cage just large enough to encapsulate insulin. Extensive contacts between IDE-N and IDE-C keep the degradation chamber of IDE inaccessible to substrates. Repositioning of the IDE domains enables substrate access to the catalytic cavity. IDE uses size and charge distribution of the substrate-binding cavity selectively to entrap structurally diverse polypeptides. The enclosed substrate undergoes conformational changes to form beta-sheets with two discrete regions of IDE for its degradation. Consistent with this model, mutations disrupting the contacts between IDE-N and IDE-C increase IDE catalytic activity 40-fold. The molecular basis for substrate recognition and allosteric regulation of IDE could aid in designing IDE-based therapies to control cerebral amyloid-beta and blood sugar concentrations.     

Novel renin inhibitors containing the amino acid statine

The proteolytic enzyme renin (EC3.4.99.19) cleaves the protein substrate angiotensinogen to yield angiotensin I, the decapeptide substrate transformed by converting enzyme into the pressor substance angiotensin II. Although the contribution of this pathway to the maintenance of normal blood pressure is unclear, it seems to be a major factor in various hypertensive states. Important progress in the control of hypertension has been achieved by development of the potent inhibitors SQ-14,225 (captopril) and MK-421 (enalapril maleate), which block the generation of angiotensin II by the inhibition of angiotensin converting enzyme. An attractive alternative to the inhibition of converting enzyme would be the blockade of the preceding step in the cascade, the renin reaction. We report here new highly potent (IC50 = 10(-9)-10(-8) M) competitive inhibitors of renin in which statine, (3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid, is incorporated into analogues of the pig renin substrate (Fig. 1).     

Structural basis for modulation and agonist specificity of HCN pacemaker channels

The family of hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channels are crucial for a range of electrical signalling, including cardiac and neuronal pacemaker activity, setting resting membrane electrical properties and dendritic integration. These nonselective cation channels, underlying the I(f), I(h) and I(q) currents of heart and nerve cells, are activated by membrane hyperpolarization and modulated by the binding of cyclic nucleotides such as cAMP and cGMP. The cAMP-mediated enhancement of channel activity is largely responsible for the increase in heart rate caused by beta-adrenergic agonists. Here we have investigated the mechanism underlying this modulation by studying a carboxy-terminal fragment of HCN2 containing the cyclic nucleotide-binding domain (CNBD) and the C-linker region that connects the CNBD to the pore. X-ray crystallographic structures of this C-terminal fragment bound to cAMP or cGMP, together with equilibrium sedimentation analysis, identify a tetramerization domain and the mechanism for cyclic nucleotide specificity, and suggest a model for ligand-dependent channel modulation. On the basis of amino acid sequence similarity to HCN channels, the cyclic nucleotide-gated, and eag- and KAT1-related families of channels are probably related to HCN channels in structure and mechanism.