A novel potent metal-binding NDM-1 inhibitor was identified by fragment virtual,SPR and NMR screening

NDM-1 can hydrolyze nearly all available β-lactam antibiotics, including carbapenems. NDM-1 producing bacterial strains are worldwide threats. It is still very challenging to find a potent NDM-1 inhibitor for clinical use. In our study, we used a metal-binding pharmacophore (MBP) enriched virtual fragment library to screen NDM-1 hits. SPR screening helped to verify the MBP virtual hits and identified a new NDM-1 binder and weak inhibitor A1. A solution NMR study of ¹⁵N-labeled NDM-1 showed that A1 disturbed all three residues coordinating the second zinc ion (Zn2) in the active pocket of NDM-1. The perturbation only happened in the presence of zinc ion, indicating that A1 bound to Zn2. Based on the scaffold of A1, we designed and synthesized a series of NDM-1 inhibitors. Several compounds showed synergistic antibacterial activity with meropenem against NDM-1 producing K. pneumoniae.     

Movement patterns and space use of the first giant anteater (Myrmecophaga tridactyla) monitored in São Paulo State,Brazil

This study analyzes a giant anteater’s (Myrmecophaga tridactyla) movement patterns and space use in São Paulo, Brazil. It is the first study to track a giant anteater with Iridium-GPS. The anteater traveled an average distance of 1326 m day^–1 with an average speed of 1.04 m min^–1. Home range by Kernel was 2.46 km² while the core area was 0.75 km², and estimates by Brownian bridge and minimum convex polygon were also provided. The anteater used shrub savanna, open savanna, and water habitats more than expected. Monitoring ended just after 10 days when the female giant anteater’s GPS was found on an illegal trail.     

The structure of 180° supernumerary limbs and a hypothesis of their formation

The results of a detailed analysis of 100 supernumerary limbs generated by 180° ipsilateral rotation (on the same limb stump) of regeneration blastemas is presented. The limbs were analyzed in terms of their position of origin, frequency, cartilage structure by Victoria blue staining, and muscle structure by serial sections. Single, double, or triple supernumeraries can be produced at no unique position of origin, although the posterodorsal quadrant was preferred. Four classes of supernumerary limbs were generated by such operations—normal; double dorsal or double ventral; part normal/part mirror imaged; part normal/part inverted in approximately equal frequencies. After amputation of these supernumeraries the same muscle patterns are faithfully regenerated. A hypothesis to explain the production of these abnormal limbs is proposed based on the observed phenomenon of fusion of supernumerary blastemata, but their regenerative behaviour presents problems for current models of pattern formation. Similar results have been obtained with developing limb buds and the relation between development and regeneration is discussed.     

Convergence of visual,haltere, and prosternai inputs at neck motor neurons of Calliphora erythrocephala

Summary Neck muscles of Calliphora erythrocephala, situated in the anterior prothorax, are innervated on each side by 8 motor neurons arising in the brain (cervical nerve neurons, CN1–8) and at least 13 motor neurons arising in the prothoracic ganglion (anterior dorsal and frontal nerve neurons, ADN1,2 and FN1-11). Three prominent motor neurons (CN6 and FN1,2) are described in detail with special emphasis on their relationships with giant visual interneurons from the lobula plate, haltere interneurons, and primary afferents from the prosternal organs and halteres. These sensory organs detect head movement and body yaw, respectively. Neuronal relationships indicate that head movement is under multimodal sensory control that includes giant motion-sensitive neurons previously supposed to mediate the optomotor response in flying flies. The described pathways provide anatomical substrates for the control of optokinetic and yaw-incurred head movements that behavioural studies have shown must exist.     

Biosynthesis of bacterial glycogen: purification and characterization of ADPglucose pyrophosphorylase with modified regulatory properties from Escherichia coli B mutant CL1136-504

The l-thyroxine binding site in human serum thyroxine-binding globulin was investigated by affinity labeling with N-bromoacetyl-l-thyroxine (BrAcT₄). Competitive binding studies showed that, in the presence of 100 molar excess of BrAcT₄, binding of thyroxine to thyroxine-binding globulin was nearly totally abolished. The reaction of BrAcT₄ to form covalent binding was inhibited in the presence of thyroxine and the affinity-labeled thyroxinebinding globulin lost its ability to bind thyroxine. These results indicate BrAcT₄ and thyroxine competed for the same binding site. Affinity labeling with 2 mol of BrAcT₄/mol of thyroxine-binding globulin resulted in the covalent attachment of 0.7 mol of ligand. By amino acid analysis and high voltage paper electrophoresis, methionine was identified as the major residue labeled (75%). Lysine, tyrosine, and histidine were also found to be labeled to the extent of 8, 8, and 5%, respectively.     

Harassment of Mature Female Chimpanzees by Young Males in the Mahale Mountains

Juvenile and adolescent male chimpanzees sometimes threaten older, apparently stronger individuals such as mature females. I label the behavior harassment. Harassment comprises 25 behaviors, 14 of which are accompanied by the use of objects such as branches: Clubbing, flailing and throwing are the most common. Females respond to harassment with 10 behaviors, including scream, avoid, ignore, and retaliate. Females tend to respond to harassment by juvenile males by ignoring them. However, they are more likely to retaliate, scream or avoid in response to harassment by adolescent males. I propose the rank improvement hypothesis that harassment initiates the process of male domination of females, and compare the predictions derived from it with those of the exploratory aggression hypothesis. Males stopped harassing females significantly earlier when females ignored them versus when they did not ignore them. This is not consistent with the exploratory aggression hypothesis. Males harassed adult females significantly longer when females retaliated than when they did not, which is consistent with the rank improvement hypothesis. Although the observations are congruent with my hypothesis, we need more data to test it.     

Dynamics of Newly Established Elk Populations

Abstract: The dynamics of newly established elk (Cervus elaphus) populations can provide insights about maximum sustainable rates of reproduction, survival, and increase. However, data used to estimate rates of increase typically have been limited to counts and rarely have included complementary estimates of vital rates. Complexities of population dynamics cannot be understood without considering population processes as well as population states. We estimated pregnancy rates, survival rates, age ratios, and sex ratios for reintroduced elk at Theodore Roosevelt National Park, North Dakota, USA; combined vital rates in a population projection model; and compared model projections with observed elk numbers and population ratios. Pregnancy rates in January (early in the second trimester of pregnancy) averaged 54.1% (SE = 5.4%) for subadults and 91.0% (SE = 1.7%) for adults, and 91.6% of pregnancies resulted in recruitment at 8 months. Annual survival rates of adult females averaged 0.96 (95% CI = 0.94-0.98) with hunting included and 0.99 (95% CI = 0.97-0.99) with hunting excluded from calculations. Our fitted model explained 99.8% of past variation in population estimates and represents a useful new tool for short-term management planning. Although we found no evidence of temporal variation in vital rates, variation in population composition caused substantial variation in projected rates of increase (Λ = 1.20-1.36). Restoring documented hunter harvests and removals of elk by the National Park Service led to a potential rate of Λ = 1.26. Greater rates of increase substantiated elsewhere were within the expected range of chance variation, given our model and estimates of vital rates. Rates of increase realized by small elk populations are too variable to support inferences about habitat quality or density dependence.     

Zur Feinstruktur des dorsalen Riesenfasersystems im Bauchmark des Regenwurms

Zusammenfassung Die proximalen Kollateralen der dorsalen Riesenfasern des Regenwurms wurden in Serienschnitten vom Soma bis zum Eintritt in die Riesenfaser verfolgt und im Hinblick auf ihre Feinstruktur und ihre synaptischen Kontakte Untersucht. Es finden sich sowohl chemische als auch elektrische Synapsen. Ihre Feinstruktur wird mit der bekannter Synapsen anderer Wirbellosen und Wirbeltiere verglichen. In beiden Riesenfasersystemen kommen efferente chemische Synapsen mit feinen postsynaptischen Verzweigungen vor, die anscheinend von Bauchmark-Motoneuronen stammen. Das Axon der medianen Riesenfaser weist darüber hinaus nur noch eine elektrische Synapse mit den Rieseninterneuronen auf. Demgegenüber erhalten die Kollateralen der lateralen Riesenfasern zahlreiche Afferenzen, die zum Teil als sensorische Fasern der Epidermis, multisegmentale Fasern der Hauptfaserzüge und Rieseninterneurone identifiziert werden konnten. Weitere Afferenzen stammen vermutlich von unisegmentalen Interneuronen her. Beide lateralen Riesenzellaxone bilden außerdem miteinander eine elektrische Chiasma-Synapse mit besonderen Membraneinfaltungen.

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Ultrastructure of the dorsal giant fibre system in the ventral nerve cord of the earthwormII. Synaptic connections of the proximal collaterals of the giant fibres

Summary The proximal collaterals of the dorsal giant fibres of the earthworm were traced through serial sections from the cell bodies to the giant axons. Their structure and synaptic connections were examined. There are chemical as well as electrical synapses. Their fine structure is compared to that of other known invertebrate and vertebrate synapses. Both giant fibre systems have efferent chemical connections with thin postsynaptic arborizations which probably belong to ventral cord motoneurons. Moreover the median giant axon is connected by an electrical synapse with the giant interneurons. The lateral giant collaterals on the contrary receive many afferences through chemical synapses which were partly identified as sensory fibers from the epidermis, multisegmental axons from the main fibre bundles or giant interneurones. Other afferences probably come from unisegmental interneurones. In addition both lateral giant axons form an electrical chiasma synapse with special membrane folds.

Mit Unterstützung durch die Deutsche Forschungsgemeinschaft Gu 117/1.