Crickets receive auditory information from their environment via ears located on the front legs. Ascending interneurons forward auditory activity to the brain, which houses a pattern recognition ...network for phonotaxis to conspecific calling songs and which controls negative phonotaxis to high-frequency sound pulses. Descending brain neurons, however, which are clearly involved in controlling these behaviors, have not yet been identified. We describe a descending auditory-responsive brain neuron with an arborization pattern that coincides with the ring-like auditory neuropil in the brain formed by the axonal arborizations of ascending and local interneurons, indicating its close link to auditory processing. Spiking activity of this interneuron occurs with a short latency to calling song patterns and the neuron copies the sound pulse pattern. The neuron preferentially responds to short sound pulses, but its activity appears to be independent of the calling song pattern recognition process. It also receives a weaker synaptic input in response to high-frequency pulses, which may contribute to its short latency spiking responses. This interneuron could be a crucial part in the auditory-to-motor transformation of the nervous system and contribute to the motor control of cricket auditory behavior.
Desert locusts, Schistocerca gregaria, show extreme phenotypic plasticity, transforming between a little-seen solitarious phase and the notorious swarming gregarious phase depending on population ...density. An essential tipping point in the process of swarm formation is the initial switch from strong mutual aversion in solitarious locusts to coherent group formation and greater activity in gregarious locusts. We show here that serotonin, an evolutionarily conserved mediator of neuronal plasticity, is responsible for this behavioral transformation, being both necessary if behavioral gregarization is to occur and sufficient to induce it. Our data demonstrate a neurochemical mechanism linking interactions between individuals to large-scale changes in population structure and the onset of mass migration.
While compensatory saccades indicate vestibular loss in the conventional head impulse test paradigm (HIMP), in which the participant fixates an earth-fixed target, we investigated a complementary ...suppression head impulse paradigm (SHIMP), in which the participant is fixating a head-fixed target to elicit anticompensatory saccades as a sign of vestibular function.
HIMP and SHIMP eye movement responses were measured with the horizontal video head impulse test in patients with unilateral vestibular loss, patients with bilateral vestibular loss, and in healthy controls.
Vestibulo-ocular reflex gains showed close correlation (R(2) = 0.97) with slightly lower SHIMP than HIMP gains (mean gain difference 0.06 ± 0.05 SD, p < 0.001). However, the 2 paradigms produced complementary catch-up saccade patterns: HIMP elicited compensatory saccades in patients but rarely in controls, whereas SHIMP elicited large anticompensatory saccades in controls, but smaller or no saccades in bilateral vestibular loss. Unilateral vestibular loss produced covert saccades in HIMP, but later and smaller saccades in SHIMP toward the affected side. Cumulative HIMP and SHIMP saccade amplitude differentiated patients from controls with high sensitivity and specificity.
While compensatory saccades indicate vestibular loss in conventional HIMP, anticompensatory saccades in SHIMP using a head-fixed target indicate vestibular function. SHIMP saccades usually appear later than HIMP saccades, therefore being more salient to the naked eye and facilitating vestibulo-ocular reflex gain measurements. The new paradigm is intuitive and easy to explain to patients, and the SHIMP results complement those from the standard video head impulse test.
This case-control study provides Class III evidence that SHIMP accurately identifies patients with unilateral or bilateral vestibulopathies.
Restricting centriole duplication to once per cell cycle is critical for chromosome segregation and genomic stability, but the mechanisms underlying this block to reduplication are unclear. Genetic ...analyses have suggested an involvement for Skp/Cullin/F box (SCF)-class ubiquitin ligases in this process. In this study, we describe a mechanism to prevent centriole reduplication in Drosophila melanogaster whereby the SCF E3 ubiquitin ligase in complex with the F-box protein Slimb mediates proteolytic degradation of the centrosomal regulatory kinase Plk4. We identified SCFSlimb as a regulator of centriole duplication via an RNA interference (RNAi) screen of Cullin-based ubiquitin ligases. We found that Plk4 binds to Slimb and is an SCFSlimb target. Both Slimb and Plk4 localize to centrioles, with Plk4 levels highest at mitosis and absent during S phase. Using a Plk4 Slimb-binding mutant and Slimb RNAi, we show that Slimb regulates Plk4 localization to centrioles during interphase, thus regulating centriole number and ensuring the block to centriole reduplication.
Thanatosis Rogers, Stephen M.; Simpson, Stephen J.
Current biology,
11/2014, Letnik:
24, Številka:
21
Journal Article
Recenzirano
Odprti dostop
In this quick guide, Rogers and Simpson provide an overview of thanatosis, the fascinating behaviour of feigning death, seen in animals ranging from insects to mammals.
Cytoplasmic microtubules are tubular polymers that can harbor small proteins or filaments inside their lumen. The identities of these objects and mechanisms for their accumulation have not been ...conclusively established. Here, we used cryogenic electron tomography of Drosophila S2 cell protrusions and found filaments inside the microtubule lumen, which resemble those reported recently in human HAP1 cells. The frequency of these filaments increased upon inhibition of the sarco/endoplasmic reticulum Ca
ATPase with the small molecule drug thapsigargin. Subtomogram averaging showed that the luminal filaments adopt a helical structure reminiscent of cofilin-bound actin (cofilactin). Consistent with this, we observed cofilin dephosphorylation, an activating modification, in cells under the same conditions that increased luminal filament occurrence. Furthermore, RNA interference knock-down of cofilin reduced the frequency of luminal filaments with cofilactin morphology. These results suggest that cofilin activation stimulates its accumulation on actin filaments inside the microtubule lumen.
Microtubule severing is a biochemical reaction that generates an internal break in a microtubule and regulation of microtubule severing is critical for cellular processes such as ciliogenesis, ...morphogenesis, and meiosis and mitosis. Katanin is a conserved heterodimeric ATPase that severs and disassembles microtubules, but the molecular determinants for regulation of microtubule severing by katanin remain poorly defined. Here we show that the non-catalytic domains of Drosophila katanin regulate its abundance and activity in living cells. Our data indicate that the microtubule-interacting and trafficking (MIT) domain and adjacent linker region of the Drosophila katanin catalytic subunit Kat60 cooperate to regulate microtubule severing in two distinct ways. First, the MIT domain and linker region of Kat60 decrease its abundance by enhancing its proteasome-dependent degradation. The Drosophila katanin regulatory subunit Kat80, which is required to stabilize Kat60 in cells, conversely reduces the proteasome-dependent degradation of Kat60. Second, the MIT domain and linker region of Kat60 augment its microtubule-disassembly activity by enhancing its association with microtubules. On the basis of our data, we propose that the non-catalytic domains of Drosophila katanin serve as the principal sites of integration of regulatory inputs, thereby controlling its ability to sever and disassemble microtubules.
Hypoxanthine catabolism
is potentially dangerous as it fuels production of urate and, most importantly, hydrogen peroxide. However, it is unclear whether accumulation of intracellular and supernatant ...hypoxanthine in stored red blood cell units is clinically relevant for transfused recipients. Leukoreduced red blood cells from glucose-6-phosphate dehydrogenase-normal or -deficient human volunteers were stored in AS-3 under normoxic, hyperoxic, or hypoxic conditions (with oxygen saturation ranging from <3% to >95%). Red blood cells from healthy human volunteers were also collected at sea level or after 1-7 days at high altitude (>5000 m). Finally, C57BL/6J mouse red blood cells were incubated
with
C
-aspartate or
C
-adenosine under normoxic or hypoxic conditions, with or without deoxycoformycin, a purine deaminase inhibitor. Metabolomics analyses were performed on human and mouse red blood cells stored for up to 42 or 14 days, respectively, and correlated with 24 h post-transfusion red blood cell recovery. Hypoxanthine increased in stored red blood cell units as a function of oxygen levels. Stored red blood cells from human glucose-6-phosphate dehydrogenase-deficient donors had higher levels of deaminated purines. Hypoxia
and
decreased purine oxidation and enhanced purine salvage reactions in human and mouse red blood cells, which was partly explained by decreased adenosine monophosphate deaminase activity. In addition, hypoxanthine levels negatively correlated with post-transfusion red blood cell recovery in mice and - preliminarily albeit significantly - in humans. In conclusion, hypoxanthine is an
metabolic marker of the red blood cell storage lesion that negatively correlates with post-transfusion recovery
Storage-dependent hypoxanthine accumulation is ameliorated by hypoxia-induced decreases in purine deamination reaction rates.
Band 3 (anion exchanger 1; AE1) is the most abundant membrane protein in red blood cells, which in turn are the most abundant cells in the human body. A compelling model posits that, at high oxygen ...saturation, the N-terminal cytosolic domain of AE1 binds to and inhibits glycolytic enzymes, thus diverting metabolic fluxes to the pentose phosphate pathway to generate reducing equivalents. Dysfunction of this mechanism occurs during red blood cell aging or storage under blood bank conditions, suggesting a role for AE1 in the regulation of the quality of stored blood and efficacy of transfusion, a life-saving intervention for millions of recipients worldwide. Here we leveraged two murine models carrying genetic ablations of AE1 to provide mechanistic evidence of the role of this protein in the regulation of erythrocyte metabolism and storage quality. Metabolic observations in mice recapitulated those in a human subject lacking expression of AE11-11 (band 3 Neapolis), while common polymorphisms in the region coding for AE11-56 correlate with increased susceptibility to osmotic hemolysis in healthy blood donors. Through thermal proteome profiling and crosslinking proteomics, we provide a map of the red blood cell interactome, with a focus on AE11-56 and validate recombinant AE1 interactions with glyceraldehyde 3-phosphate dehydrogenase. As a proof-of-principle and to provide further mechanistic evidence of the role of AE1 in the regulation of redox homeo stasis of stored red blood cells, we show that incubation with a cell-penetrating AE11-56 peptide can rescue the metabolic defect in glutathione recycling and boost post-transfusion recovery of stored red blood cells from healthy human donors and genetically ablated mice.
The infective juvenile (J2) stage of endoparasitic plant nematodes uses plant chemical signals, released from roots, to localize and infect hosts. We examined the behaviors of soybean cyst nematode ...(Heterodera glycines) and root-knot nematode (Meloidogyne incognita) J2 in the presence of root signals from marigold (Tagetes patula), soybean (Glycine max), and pepper (Capsicum annuum). Signals were obtained from sources commonly used in phytoparasitic nematode chemotaxis studies: root tips, root exudates, and root extracts. Root tips from each plant species attracted M. incognita but H. glycines was attracted only to soybean. In contrast, root exudates prepared from marigold, pepper, or soybean seedlings were attractive to H. glycines but were repellent to M. incognita. Root extracts had the same effect as exudates. Fractionation of exudates by reversed-phase high-performance liquid chromatography (HPLC) (acetonitrile CH
CN and 0.1% trifluoroacetic acid) revealed highly polar and less polar components affecting behaviors. Fractions eluting at 12% CH
CN from all three plants attracted H. glycines and repelled M. incognita. None of the less polar HPLC fractions (>15% CH
CN) affected H. glycines but those from G. max and T. patula repelled M. incognita. Differences among exudates and effects of fractionation on behavior are discussed.
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