Design and chemical synthesis of a homogeneous polymer-modified erythropoiesis protein

We report the design and total chemical synthesis of "synthetic erythropoiesis protein" (SEP), a 51-kilodalton protein-polymer construct consisting of a 166-amino-acid polypeptide chain and two covalently attached, branched, and monodisperse polymer moieties that are negatively charged. The ability to control the chemistry allowed us to synthesize a macromolecule of precisely defined covalent structure. SEP was homogeneous as shown by high-resolution analytical techniques, with a mass of 50,825 +/-10 daltons by electrospray mass spectrometry, and with a pI of 5.0. In cell and animal assays for erythropoiesis, SEP displayed potent biological activity and had significantly prolonged duration of action in vivo. These chemical methods are a powerful tool in the rational design of protein constructs with potential therapeutic applications.     

A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA

Fluoroquinolones are gaining increasing importance in the treatment of tuberculosis. The expression of MfpA, a member of the pentapeptide repeat family of proteins from Mycobacterium tuberculosis, causes resistance to ciprofloxacin and sparfloxacin. This protein binds to DNA gyrase and inhibits its activity. Its three-dimensional structure reveals a fold, which we have named the right-handed quadrilateral beta helix, that exhibits size, shape, and electrostatic similarity to B-form DNA. This represents a form of DNA mimicry and explains both its inhibitory effect on DNA gyrase and fluoroquinolone resistance resulting from the protein's expression in vivo.     

A process for controlling intracellular bacterial infections induced by membrane injury

Strategies for inhibiting phagolysosome fusion are essential for the intracellular survival and replication of many pathogens. We found that the lysosomal synaptotagmin Syt VII is required for a mechanism that promotes phagolysosomal fusion and limits the intracellular growth of pathogenic bacteria. Syt VII was required for a form of Ca2+-dependent phagolysosome fusion that is analogous to Ca2+-regulated exocytosis of lysosomes, which can be triggered by membrane injury. Bacterial type III secretion systems, which permeabilize membranes and cause Ca2+ influx in mammalian cells, promote lysosomal exocytosis and inhibit intracellular survival in Syt VII +/+ but not -/- cells. Thus, the lysosomal repair response can also protect cells against pathogens that trigger membrane permeabilization.     

Species coextinctions and the biodiversity crisis

To assess the coextinction of species (the loss of a species upon the loss of another), we present a probabilistic model, scaled with empirical data. The model examines the relationship between coextinction levels (proportion of species extinct) of affiliates and their hosts across a wide range of coevolved interspecific systems: pollinating Ficus wasps and Ficus, parasites and their hosts, butterflies and their larval host plants, and ant butterflies and their host ants. Applying a nomographic method based on mean host specificity (number of host species per affiliate species), we estimate that 6300 affiliate species are "coendangered" with host species currently listed as endangered. Current extinction estimates need to be recalibrated by taking species coextinctions into account.     

On the origin of interictal activity in human temporal lobe epilepsy in vitro

The origin and mechanisms of human interictal epileptic discharges remain unclear. Here, we describe a spontaneous, rhythmic activity initiated in the subiculum of slices from patients with temporal lobe epilepsy. Synchronous events were similar to interictal discharges of patient electroencephalograms. They were suppressed by antagonists of either glutamatergic or gamma-aminobutyric acid (GABA)-ergic signaling. The network of neurons discharging during population events comprises both subicular interneurons and a subgroup of pyramidal cells. In these pyramidal cells, GABAergic synaptic events reversed at depolarized potentials. Depolarizing GABAergic responses in neurons downstream to the sclerotic CA1 region contribute to human interictal activity.     

Thermal contrast in the atmosphere of venus: initial appraisal from pioneer venus probe data

The altitude profiles of temperature and pressure measured during the descent of the four Pioneer Venus probes show small contrast below the clouds but significant differences within the clouds at altitudes from 45 to 61 kilometers. At 60 kilometers, the probe which entered at 59.3 degrees north latitude sensed temperatures 25 K below those of the lower latitude probes, and a sizable difference persisted down to and slightly below the cloud base. It also sensed pressure below those of the other probes by as much as 49 millibars at a mean pressure of 200 millibars. The measured pressure differences are consistent with cyclostrophic balance of zonal winds ranging from 130 +/- 20 meters per second at 60 kilometers to 60 +/- 17 meters per second at 40 kilometers, with evidence in addition of a nonaxisymmetric component of the winds. The clouds were found to be 10 to 20 K warmer than the extended profiles of the lower atmosphere, and the middle cloud is convectively unstable. Both phenomena are attributed to the absorption of thermal radiation from below. Above the clouds, in the lower stratosphere, the lapse rate decreases abruptly to 3.5 K per kilometer, and a superimposed wave is evident. At 100 kilometers, the temperature is minimum, with a mean value of about 170 K.     

Long-term trends in the abundance of Mediterranean wetland vertebrates: From global recovery to localized declines

Biodiversity loss is unevenly distributed in space and time. Species have reached critically low population sizes in some areas, and remain abundant in others. Similarly, some species may benefit from successful conservation plans, while others still experience severe population depletions driven by negative impacts of human activities. Although several indicators have been proposed to measure the fate of biodiversity, they are generally only implemented globally so their relevance for regional assessment is still unclear. Here, we calculated the first regional trend in the Living Planet Index for the Mediterranean wetlands (Med LPI), an indicator that summarizes the fate of global biological diversity based on the temporal trends in abundance of vertebrate populations. The Med LPI was based on 1641 vertebrate populations of 311 species recorded in Mediterranean wetlands from 1970–2008, in 27 different countries. We investigated whether trends in the Med LPI differed between eastern and western Mediterranean countries, which have different socio-economic contexts. Finally, we assessed whether and how the trend in the Med LPI was robust to changes in the number and identity of species considered. We found that, at the Mediterranean scale, the Med LPI increased steeply, which could be taken at first sight, as a general recovery of wetland biodiversity in this biogeographical region. However, we found highly contrasting spatial trends within the Mediterranean region: the average trend was positive for western and negative for eastern countries. Moreover, we showed that depending on the method used to estimate the trend in Med LPI, it can be sensitive to the number and identity of the species considered. We suggest that understanding the regional discrepancies of the trend in biodiversity indicators as well as their robustness to the species represented in the index will enhance progress assessment towards global and regional conservation strategies.