Hydrodynamic reception in the Australian water rat, Hydromys chrysogaster.

The Australian water rat, Hydromys chrysogaster, preys on a wide variety of aquatic and semiaquatic arthropods and vertebrates, including fish. A frequently observed predatory strategy of Hydromys is sitting in wait at the water's edge with parts of its vibrissae submersed. Here we show that Hydromys can detect water motions with its whiskers. Behavioural thresholds range from 1.0 to 9.4 mm s-1 water velocity, based on maximal horizontal water velocity in the area covered by the whiskers. This high sensitivity to water motions would enable Hydromys to detect fishes passing by. No responses to surface waves generated by a vibrating rod and resembling the surface waves caused by struggling insects were found.

Prerequisites of Isopeptide Bond Formation in Microcystin Biosynthesis.

The biosynthesis of the potent cyanobacterial hepatotoxin microcystin involves isopeptide bond formation through the carboxylic acid side chains of d-glutamate and ß-methyl d-aspartate. Analysis of the in vitro activation profiles of the two corresponding adenylation domains, McyE-A and McyB-A2 , either in a didomain or a tridomain context with the cognate thiolation domain and the upstream condensation domain revealed that substrate activation of both domains strictly depended on the presence of the condensation domains. We further identified two key amino acids in the binding pockets of both adenylation domains that could serve as a bioinformatic signature of isopeptide bond-forming modules incorporating d-glutamate or d-aspartate. Our findings further contribute to the understanding of the multifaceted role of condensation domains in nonribosomal peptide synthetase assembly lines.

From the observation of atypical cells on blood smear to the diagnosis of mast cell leukemia: a case report in a 79 year old woman consulting for anemia.

Mast cell leukemia is an extremely rare disease, which belongs to the systemic mastocytosis group (WHO 2016). We are reporting the case of a 79-year-old woman, without any hematological particular history consulting for hyperthermia, repeated malaise and subacute anemia. Her clinical examination was normal. Unusual cells were seen on blood and bone marrow smears. They represent more than 10% of blood nucleated cells end more than 20% of the bone marrow nucleated cells. Bone marrow immunophenotyping was performed to characterize these cells. It revealed a cell subset expressing the surface antigens CD117, CD2 and CD25. This immunophenotypic profile is the hallmark of malignant mast cells. Then mast cell leukemia diagnosis could have been made and KIT gene sequencing highlighted the N822Y mutation in exon 17. The patient was initially treated with midostaurin, a tyrosine kinase inhibitor. Lack of therapeutic response and absence of the KIT D816V mutation led to switch to imatinib, following the latest scientific recommendations.

Biomechanical testing of a PEEK-based dynamic instrumentation device in a lumbar spine model.

BACKGROUND: The purpose of this study was to investigate the range-of-motion after posterior polyetheretherketone-based rod stabilisation combined with a dynamic silicone hinge in order to compare it with titanium rigid stabilisation. METHODS: Five human cadaveric lumbar spines with four vertebra each (L2 to L5) were tested in a temperature adjustable spine-testing set-up in four trials: (1) native measurement; (2) kinematics after rigid monosegmental titanium rod instrumentation with anterior intervertebral bracing of the segment L4/5; (3) kinematics after hybrid posterior polyetheretherketone rod instrumentation combined with a silicone hinge within the adjacent level (L3/4) and (4) kinematics after additional decompression with laminectomy of L4 and bilateral resection of the inferior articular processes (L3). During all steps, the specimens were loaded quasi-statically with 1°/s with pure moment up to 7.5Nm in flexion/extension, lateral bending and axial rotation. FINDINGS: In comparison to the native cadaveric spine, both the titanium device and polyetheretherketone-based device reduce the range-of-motion within the level L4/5 significantly (flexion/extension: reduction of 77%, p<0.001; lateral bending: reduction of 62%, p<0.001; axial rotation: reduction of 71%, p<0.001). There was a clear stabilisation effect after hybrid-instrumentation within the level L3/4, especially in flexion/extension (64%, p<0.001) and lateral bending (62%, p<0.001) but without any effect on the axial rotation. Any temperature dependency has not been observed. INTERPRETATION: Surprisingly, the hybrid device compensates for laminectomy L4 and destabilising procedure within the level L3/4 in comparison to other implants. Further studies must be performed to show its effectiveness regarding the adjacent segment instability.

Biochemical Dissection of the Natural Diversification of Microcystin Provides Lessons for Synthetic Biology of NRPS.

The cyanobacterial hepatotoxin microcystin is assembled at a non-ribosomal peptide synthetase (NRPS) complex. The enormous structural diversity of this peptide, which is also found in closely related strains, is the result of frequent recombination events and point mutations. Here, we have compared the in vitro activation profiles of related monospecific and multispecific modules that either strictly incorporate leucine or arginine or incorporate chemically diverse amino acids in parallel into microcystin. By analyzing di- and tri-domain proteins we have dissected the role of adenylation and condensation domains for substrate specificity. We have further analyzed the role of subdomains and provide evidence for an extended gatekeeping function for the condensation domains of multispecific modules. By reproducing natural point mutations, we could convert a monospecific module into a multispecific module. Our findings may inspire novel synthetic biology approaches and demonstrate how recombination platforms of NRPSs have developed in nature.

Harnessing the evolvability of tricyclic microviridins to dissect protease-inhibitor interactions.

Understanding and controlling proteolysis is an important goal in therapeutic chemistry. Among the natural products specifically inhibiting proteases microviridins are particularly noteworthy. Microviridins are ribosomally produced and posttranslationally modified peptides that are processed into a unique, cagelike architecture. Here, we report a combined rational and random mutagenesis approach that provides fundamental insights into selectivity-conferring moieties of microviridins. The potent variant microviridin J was co-crystallized with trypsin, and for the first time the three-dimensional structure of microviridins was determined and the mode of inhibition revealed.

Photopheresis in pediatric patients with low-body weight using the UVAR XTS system.

BACKGROUND: Photopheresis (ECP) with the UVAR XTS system has been limited to patients with a body weight > 40 kg, because extracorporeal blood volumes (ECV) may exceed 15% of the total blood volumes in low-body-weight patients. Because of these instrument characteristics, the use of ECP is limited in pediatric patients. PATIENTS AND METHODS: In 5 patients (age 4 to 15 years) with graft-versus-host disease and with a body weight between 13 and 34 kilograms, photopheresis was performed using the UVAR XTS system. In 3 patients ECP could be performed by balancing the ECV with saline infusions. In 2 patients the system was modified in that the instrument was primed with packed red cells. During the treatment, fluid balance was guaranteed by a reservoir from a transfusion bag connected in parallel. RESULTS: Together 223 procedures were performed, among them 28 with the modification of the system. The treatments were well tolerated, and no episodes of hypotension were observed. CONCLUSIONS: It is possible to run ECP in low-body weight patients with the UVAR XTS system.