Import of an incompletely folded precursor protein into isolated mitochondria requires an energized inner membrane, but no added ATP.

We have studied the post-translational import of incomplete precursor chains into isolated yeast mitochondria. The precursor was a fusion protein containing a mitochondrial presequence attached to mouse dihydrofolate reductase. In vitro-synthesis of the precursor was interrupted by the elongation inhibitor cycloheximide and the arrested nascent chains cosedimenting with ribosomes were released by EDTA. These incomplete chains were efficiently imported by isolated yeast mitochondria; their import resembled that of the complete precursor in requiring an energized inner membrane and a mitochondrial presequence. It differed from that of the completed precursor in its resistance to methotrexate (which only binds to correctly folded dihydrofolate reductase) and its independence of added ATP. The incomplete chains were also more sensitive to proteinase K than the completed precursor. We conclude that the incomplete chains were incompletely folded and suggest that the lack of tight folding caused import into mitochondria to become independent of added ATP. This implies that ATP may participate, directly or indirectly, in the unfolding of the precursor for its transport into mitochondria.     

Orientation of Dunnocks (Prunella modularis) at Sunset

To find out the relative importance of the geomagnetic and solar cues for the orientation at the time of sunset, dunnocks were tested outdoors during the spring migration periods of 1982 and 1983. Experimental magnetic fields were produced by Helmholtz coils. In the various magnetic conditions, the following results were obtained:

• 1 In the local geomagnetic field, the dunnocks oriented in a seasonally appropriate northerly direction.
• 2 In a magnetic field the north of which was shifted 120° clock-wise to ESE, the birds showed a corresponding shift in their orientation.
• 3 In a vertical magnetic field without meaningful directional information, birds previously tested in either the local geomagnetic field or the shifted magnetic field now displayed axially bimodal orientation, with the axes of the two groups differing.

These findings indicate that for migratory dunnocks, the magnetic field plays a dominant role in determining their orientation at the time of sunset, and that magnetic information may affect the dunnocks' response to other directional, presumably solar cues as well.     

Transport of proteins into yeast mitochondria

The amino-terminal sequences of several imported mitochondrial precursor proteins have been shown to contain all the information required for transport to and sorting within mitochondria. Proteins transported into the matrix contain a matrix-targeting sequence. Proteins destined for other submitochondrial compartments contain, in addition, an intramitochondrial sorting sequence. The sorting sequence in the cytochrome c1 presequence is a stop-transport sequence for the inner mitochondrial membrane. Proteins containing cleavable presequences can reach the intermembrane space by either of two pathways: (1) Part of the presequence is transported into the matrix; the attached protein, however, is transported across the outer but not the inner membrane (eg, the cytochrome c1 presequence). (2) The precursor is first transported into the matrix; part of the presequence is then removed, and the protein is reexported across the inner membrane (eg, the precursor of the iron-sulphur protein of the cytochrome bc1 complex). Matrix-targeting sequences lack primary amino acid sequence homology, but they share structural characteristics. Many DNA sequences in a genome can potentially encode a matrix-targeting sequence. These sequences become active if positioned upstream of a protein coding sequence. Artificial matrix-targeting sequences include synthetic presequences consisting of only a few different amino acids, a known amphiphilic helix found inside a cytosolic protein, and the presequence of an imported chloroplast protein. Transport of proteins across mitochrondrial membranes requires a membrane potential, ATP, and a 45-kd protein of the mitochondrial outer membrane. The ATP requirement for import is correlated with a stable structure in the imported precursor molecule. We suggest that transmembrane transport of a stably folded precursor requires an ATP-dependent unfolding of the precursor protein.     

Structure of the sugar-phosphate moiety of lipid A from lipooligosaccharide of Neisseria meningitidis group B,strain BC5S No. 125

On the basis of chemical and NMR data the partial structure of lipid A from lipooligosaccharide (LOS) of Neisseria meningitidis group B, strain BC₅S No 125 was established. Lipid A consisted of disaccharide 2-deoxy-6-O-[2-deoxy-2-(3-hydroxytetradecanoylamino)--gluco-pyranosyl]-2-(3-hydroxytetradecanoylamino)--glucopyranose carrying the -(2-aminoethyl)pyrophosphate residue at 0–4 and the pyrophosphate or phosphate residue at 0–1. On hydrolysis of the acidic form of LOS with 1% acetic acid the substituent at 0–1 was practically completely removed whereas that at 0–4 was stable. The analogous hydrolysis of the Mg-salt of LOS was accompanied by splitting off the pyrophosphate linkage in the substituent at 0–4. Hydrolysis of LOS at pH 4.5 in the presence of SDS led mainly to a lipid A preparation retaining both pyrophosphate residues.Abbreviations KDO 2-keto-3-deoxyoctulosonic acid - LA-I, LA-II preparations of lipid A - LOS lipooligosaccharide - LOS-H⁺ the acidic form of LOS - OS oligosaccharide - TLC thin-layer chromatography - GLC-MS gas-liquid chromatography/mass spectrometry     

First reliable record of a fossil species of Anthomyiidae (Diptera), with comments on the definition of recent and fossil clades in phylogenetic classification

All previous records of fossil Anthomyiidae are shown to be unsubstantiated. A female anthomyiid of a new genus and species is hereby described from a piece of Dominican amber (Upper Eocene-Oligocene). Character analysis suggests that the fossil, Coenosopsites poinari gen. & sp. nov. , belongs to a Neotropical clade with two recent genera, Phaonantho Albuquerque and Coenosopsia Malloch. Evidence for a sister-group relationship between Coenosopsites poinari and the genus Coenosopsia is provided. Clades are the only acceptable units of phylogenetic classification. Combining fossil and recent clades in phylogenetic classification requires them to be temporally delimited. Proper application of phylogenetic definitions is essential for this purpose. It is proposed that the units of phylogenetic classification should be taxa for recent clades and plesia for fossil clades. A taxon is defined as node-based with reference to its recent species, while a plesion is defined as apomorphy-based. The term lineage is proposed for a recent clade defined as stem-based with reference to its recent sister group. Individual recent species represent clades that can be incorporated into phylogenetic classification as minimal taxon units. Individual fossil species may not represent clades and thus do not count as proper units of phylogenetic classification. However, the names of fossil species are readily construed also to signify plesia with the fossil species as their only known component. As such, they are proper units of phylogenetic classification.     

Influence of motor unit firing statistics on the median frequency of the EMG power spectrum

Changes in the EMG power spectrum during static fatiguing contractions are often attributed to changes in muscle fibre action potential conduction velocity. Mathematical models of the EMG power spectrum, which have been empirically confirmed, predict that under certain conditions a distinct maximum occurs in the low-frequency part of the spectrum, indicating the dominant firing rate of the motor units. The present study investigated the influence of this firing rate peak on the spectral changes during a static fatiguing contraction at 50% of maximum EMG amplitude in the frontalis and corrugator supercilii muscles. An exponential decrease of the median frequency (MF) of the EMG power spectrum was observed when the firing rate peak was absent. When the firing rate peak was present, an exaggerated decrease of MF in the beginning of the contraction was found, which was associated with an increase in firing rate peak magnitude. In later stages of the contraction, a partial recovery of MF occurred, concomitant with a decrease in firing rate peak magnitude. The influence of the firing rate peak on MF was also investigated during nonfatiguing contractions of the frontalis muscle at 20, 40, 60, and 80% of maximum EMG amplitude. A curvilinear relationship between MF and contraction strength was found, whether firing rate peaks were present or absent. The presence of firing rate peaks, however, was associated with a decrease in MF which was inversely related to contraction strength, due to the inverse relationship between firing rate peak magnitude and contraction strength.     

Wind drift,compensation, and the use of landmarks by nocturnal bird migrants

In this paper we describe fall nocturnal migration at three localities in eastern New York, one adjacent to the Hudson River, the other two 30 km to the west in a topographically more uniform area. Migrants at both study areas moved southwest in winds not out of the west and were, therefore, seemingly unaffected by the river. In west winds, however, birds away from the river moved south-southeast whereas those in the vicinity of the river flew a track west of south paralleling the river. In addition, a relative increase in the number of migrants along the river compared to away was observed in west winds as birds presumably became concentrated near the river. We conclude that on most autumn nights migrants passing through this area have a preferred track direction toward the southwest and in strong winds from the west and northwest they are drifted. Upon reaching the vicinity of the Hudson River, some birds alter their headings yielding a track direction that closely parallels the river resulting in at least a partial compensation for wind drift. No alternative hypothesis is consistent with all the data.     

The Effects of Zinc Sulphate Anosmia on Homing Pigeons,Columba livia,in a Homing and a Non-homing Experiment

There is debate over whether homing pigeons, Columba livia, use olfactory information as part of their navigational map. Antagonists of the theory argue that homing deficits noted in anosmic pigeons may be due to a non-specific impairment in general information processing. In Experiment I, we present data from a modest investigation describing the typical navigational deficits that occur following zinc sulphate-mediated anosmia. Our results are consistent with previous experiments that noted impairments in homing performance from unfamiliar locations of anosmic pigeons. Experiment II is a critical experiment that involved a spatial working memory paradigm; this paradigm consisted of testing zinc sulphate-treated birds in a forced-choice alternation task in a T-maze. This experiment allowed us to determine whether anosmic pigeons were impaired in memory performance, a robust measure of general information processing. There were no differences between the last day of training and a subsequent-test day when pigeons received an intranasal injection of zinc sulphate. This experiment suggests that zinc sulphate anosmia does not impair general information processing, supporting the hypothesis that homing pigeons use olfactory cues when homing from unfamiliar locations.     

Life Expectancies of South African Adults Starting Antiretroviral Treatment: Collaborative Analysis of Cohort Studies

Background

Few estimates exist of the life expectancy of HIV-positive adults receiving antiretroviral treatment (ART) in low- and middle-income countries. We aimed to estimate the life expectancy of patients starting ART in South Africa and compare it with that of HIV-negative adults.

Methods and Findings

Data were collected from six South African ART cohorts. Analysis was restricted to 37,740 HIV-positive adults starting ART for the first time. Estimates of mortality were obtained by linking patient records to the national population register. Relative survival models were used to estimate the excess mortality attributable to HIV by age, for different baseline CD4 categories and different durations. Non-HIV mortality was estimated using a South African demographic model. The average life expectancy of men starting ART varied between 27.6 y (95% CI: 25.2–30.2) at age 20 y and 10.1 y (95% CI: 9.3–10.8) at age 60 y, while estimates for women at the same ages were substantially higher, at 36.8 y (95% CI: 34.0–39.7) and 14.4 y (95% CI: 13.3–15.3), respectively. The life expectancy of a 20-y-old woman was 43.1 y (95% CI: 40.1–46.0) if her baseline CD4 count was ≥200 cells/µl, compared to 29.5 y (95% CI: 26.2–33.0) if her baseline CD4 count was <50 cells/µl. Life expectancies of patients with baseline CD4 counts ≥200 cells/µl were between 70% and 86% of those in HIV-negative adults of the same age and sex, and life expectancies were increased by 15%–20% in patients who had survived 2 y after starting ART. However, the analysis was limited by a lack of mortality data at longer durations.

Conclusions

South African HIV-positive adults can have a near-normal life expectancy, provided that they start ART before their CD4 count drops below 200 cells/µl. These findings demonstrate that the near-normal life expectancies of HIV-positive individuals receiving ART in high-income countries can apply to low- and middle-income countries as well. Please see later in the article for the Editors'' Summary