Probing Natural Killer Cell Education by Ly49 Receptor Expression Analysis and Computational Modelling in Single MHC Class I Mice

Murine natural killer (NK) cells express inhibitory Ly49 receptors for MHC class I molecules, which allows for “missing self” recognition of cells that downregulate MHC class I expression. During murine NK cell development, host MHC class I molecules impose an “educating impact” on the NK cell pool. As a result, mice with different MHC class I expression display different frequency distributions of Ly49 receptor combinations on NK cells. Two models have been put forward to explain this impact. The two-step selection model proposes a stochastic Ly49 receptor expression followed by selection for NK cells expressing appropriate receptor combinations. The sequential model, on the other hand, proposes that each NK cell sequentially expresses Ly49 receptors until an interaction of sufficient magnitude with self-class I MHC is reached for the NK cell to mature. With the aim to clarify which one of these models is most likely to reflect the actual biological process, we simulated the two educational schemes by mathematical modelling, and fitted the results to Ly49 expression patterns, which were analyzed in mice expressing single MHC class I molecules. Our results favour the two-step selection model over the sequential model. Furthermore, the MHC class I environment favoured maturation of NK cells expressing one or a few self receptors, suggesting a possible step of positive selection in NK cell education. Based on the predicted Ly49 binding preferences revealed by the model, we also propose, that Ly49 receptors are more promiscuous than previously thought in their interactions with MHC class I molecules, which was supported by functional studies of NK cell subsets expressing individual Ly49 receptors

Oscillatory Instabilities of Standing Waves in One-Dimensional Nonlinear Lattices

In one-dimensional anharmonic lattices, we construct nonlinear standing waves (SWs) reducing to harmonic SWs at small amplitude. For SWs with spatial periodicity incommensurate with the lattice period, a transition by breaking of analyticity versus wave amplitude is observed. As a consequence of the discreteness, oscillatory linear instabilities, persisting for arbitrarily small amplitude in infinite lattices, appear for all wave numbers Q not equal to zero or \pi. Incommensurate analytic SWs with |Q|>\pi/2 may however appear as 'quasi-stable', as their instability growth rate is of higher order.Comment: 4 pages, 6 figures, to appear in Phys. Rev. Let

Pseudomonas sp. strain MF30 suppresses Fusarium wilt of tomato in vivo

In a search of bacterial biological control agents, 50 bacterial isolates collected from roots of wild plants in northern Sweden were tested in vivo for suppression of wilt of tomato caused by Fusarium oxysporum f. sp. lycopersici. Tomato plants were sown in 10-cm-diam. pots and after 21 d 7 ml of bacterial suspension (ca. 2x109 cfu ml-1) was poured into the soil around each plant. Two days later, 10 ml of pathogen suspension was soil-inoculated (106 conidia ml-1) around the same plants. After a further 20 days, disease incidence was measured. One bacterial isolate, MF30, protected plants from Fusarium wilt, even though the fungal pathogen and not MF30 actually colonized the plant. Several mechanisms may have contributed to the suppression of Fusarium wilt, including systemic induced resistance. The MF30 strain is highly similar to members of the RNA group I of the Pseudomonas fluorescens, well known for its capacity to induce systemic resistance

Deep brain stimulation in the subthalamic nuclei alters postural alignment and adaptation in Parkinson’s disease

© 2021 The Authors. Published by PLOS. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1371/journal.pone.0259862Parkinson’s disease (PD) can produce postural abnormalities of the standing body position such as kyphosis. We investigated the effects of PD, deep brain stimulation (DBS) in the subthalamic nucleus (STN), vision and adaptation on body position in a well-defined group of patients with PD in quiet standing and during balance perturbations. Ten patients with PD and 25 young and 17 old control participants were recruited. Body position was measured with 3D motion tracking of the ankle, knee, hip, shoulder and head. By taking the ankle as reference, we mapped the position of the joints during quiet standing and balance perturbations through repeated calf muscle vibration. We did this to explore the effect of PD, DBS in the STN, and vision on the motor learning process of adaptation in response to the repeated stimulus. We found that patients with PD adopt a different body position with DBS ON vs. DBS OFF, to young and old controls, and with eyes open vs. eyes closed. There was an altered body position in PD with greater flexion of the head, shoulder and knee (p≤0.042) and a posterior position of the hip with DBS OFF (p≤0.014). With DBS ON, body position was brought more in line with the position taken by control participants but there was still evidence of greater flexion at the head, shoulder and knee. The amplitude of movement during the vibration period decreased in controls at all measured sites with eyes open and closed (except at the head in old controls with eyes open) showing adaptation which contrasted the weaker adaptive responses in patients with PD. Our findings suggest that alterations of posture and greater forward leaning with repeated calf vibration, are independent from reduced movement amplitude changes. DBS in the STN can significantly improve body position in PD although the effects are not completely reversed. Patients with PD maintain adaptive capabilities by leaning further forward and reducing movement amplitude despite their kyphotic posture.Published onlin

Strategic alterations of posture are delayed in Parkinson’s disease patients during deep brain stimulation

© 2021 The Authors. Published by Springer. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1038/s41598-021-02813-yParkinson’s disease (PD) is characterized by rigidity, akinesia, postural instability and tremor. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces tremor but the effects on postural instability are inconsistent. Another component of postural control is the postural strategy, traditionally referred to as the ankle or hip strategy, which is determined by the coupling between the joint motions of the body. We aimed to determine whether DBS STN and vision (eyes open vs. eyes closed) affect the postural strategy in PD in quiet stance or during balance perturbations. Linear motion was recorded from the knee, hip, shoulder and head in 10 patients with idiopathic PD with DBS STN (after withdrawal of other anti-PD medication), 25 younger adult controls and 17 older adult controls. Correlation analyses were performed on anterior–posterior linear motion data to determine the coupling between the four positions measured. All participants were asked to stand for a 30 s period of quiet stance and a 200 s period of calf vibration. The 200 s vibration period was subdivided into four 50 s periods to study adaptation between the first vibration period (30–80 s) and the last vibration period (180–230 s). Movement was recorded in patients with PD with DBS ON and DBS OFF, and all participants were investigated with eyes closed and eyes open. DBS settings were randomized and double-blindly programmed. Patients with PD had greater coupling of the body compared to old and young controls during balance perturbations (p ≤ 0.046). Controls adopted a strategy with greater flexibility, particularly using the knee as a point of pivot, whereas patients with PD adopted an ankle strategy, i.e., they used the ankle as the point of pivot. There was higher flexibility in patients with PD with DBS ON and eyes open compared to DBS OFF and eyes closed (p ≤ 0.011). During balance perturbations, controls quickly adopted a new strategy that they retained throughout the test, but patients with PD were slower to adapt. Patients with PD further increased the coupling between segmental movement during balance perturbations with DBS ON but retained a high level of coupling with DBS OFF throughout balance perturbations. The ankle strategy during balance perturbations in patients with PD was most evident with DBS OFF and eyes closed. The increased coupling with balance perturbations implies a mechanism to reduce complexity at a cost of exerting more energy. Strategic alterations of posture were altered by DBS in patients with PD and were delayed. Our findings therefore show that DBS does not fully compensate for disease-related effects on posture.The authors’ wish to acknowledge the financial supported from the Swedish Medical Research Council (grant nr. 17x-05693).Published versio

Spectral analysis of body movement during deep brain stimulation in Parkinson’s disease

This is an accepted manuscript of an article published by Elsevier in Gait and Posture, available online: https://doi.org/10.1016/j.gaitpost.2021.03.023 The accepted version of the publication may differ from the final published version.Background The characteristics of Parkinson’s disease (PD) include postural instability and resting tremor. However, reductions of tremor amplitude do not always improve postural stability. Research question What is the effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on spectral analysis of body movement in patients with PD when tested without anti-PD medication? The effect of visual cues was also studied. Methods Ten patients with PD (mean age 64.3 years, range 59−69 years) and 17 control participants (mean age 71.2 years, range 65–79 years) were recruited. Spectral power following a period of quiet stance (35 s) was analysed in three different spectral power bands (0−4 Hz, 4−7 Hz and 7−25 Hz). Motion markers were secured to the head, shoulder, hip, and knee, which recorded movements in two directions, the anteroposterior and lateral. Results DBS STN significantly changed the spectral distribution pattern across the body in the anteroposterior (p = 0.029) and lateral directions (p ≤ 0.003). DBS predominantly reduced spectral power at the head (p ≤ 0.037) and shoulder (p ≤ 0.031) in the lateral direction. The spectral power of the lower and upper body in patients with PD, with DBS ON, were more similar to the control group, than to DBS OFF. Visual cues mainly reduced spectral power in the anteroposterior direction at the shoulder (p ≤ 0.041) in controls and in patients with PD with DBS ON. Significance There is an altered postural strategy in patients with PD with DBS ON as shown by an altered spectral power distribution pattern across body segments and a reduction of spectral power in the lateral direction at the head and shoulder. A reduction of spectral power in controls and in patients with PD with DBS ON suggests that visual cues are able to reduce spectral power to some extent, but not with DBS OFF where postural sway and power are larger.Published versio

Effects of deep brain stimulation on postural control in Parkinson's disease

This is an accepted manuscript of an article published by Elsevier in Computers in Biology and Medicine on 29/05/2020, available online: https://doi.org/10.1016/j.compbiomed.2020.103828 The accepted version of the publication may differ from the final published version.The standard approach to the evaluation of tremor and stability control in medical practice is subjective scoring. The objective of this study was to show that signal processing of physiological data, that are known to be altered by tremor and other cardinal symptoms in Parkinson's disease (PD), can quantify the postural dynamics of this disease and the effects of DBS technology. We measured postural control and its capacity to adapt to balance perturbations with a force platform and perturbed balance by altering visual feedback and using pseudo-random binary sequence perturbations (PRBS) of different durations. Our signal processing involved converting the postural control data into spectral power with Fast-Fourier Transformation across a wide bandwidth and then subdividing this into three bands (0–4 Hz, 4–7 Hz and 7–25 Hz). We quantified the amount of power in each bandwidth. From 25 eligible participants, 10 PD participants (9 males, mean age 63.8 years) fulfilled the inclusion criteria; idiopathic PD responsive to l-Dopa; >1 year use of bilateral STN stimulation. Seventeen controls (9 males, mean age 71.2 years) were studied for comparison. Participants with PD were assessed after overnight withdrawal of anti-PD medications. Postural control was measured with a force platform during quiet stance (35 s) and during PRBS calf muscle vibration that perturbed stance (200 s). Tests were performed with eyes open and eyes closed and with DBS ON and DBS OFF. The balance perturbation period was divided into five sequential 35-s periods to assess the subject's ability to address postural imbalance using adaptation. The signal processing analyses revealed that activating the DBS device did not significantly change the dynamics of postural control in the 0–4 Hz spectral power but the device reduced the use of spectral power >4 Hz; a finding that was present in both anteroposterior and lateral directions, during vibration, and more so in eyes open tests. Visual feedback, which usually improves postural stability, was less effective in participants with PD with DBS OFF across all postural sway frequencies during quiet stance and during balance perturbations. The expected adaptation of postural control was found in healthy participants between the first and last balance perturbation period. However, adaptation was almost abolished across all spectral frequencies in both the anteroposterior and lateral directions, with both eyes open and eyes closed and DBS ON and OFF in participants with PD. To conclude, this study revealed that the DBS technology altered the spectral frequency dynamics of postural control in participants through a reduction of the power used >4 Hz. Moreover, the DBS device tended to increase the stabilizing effect of vision across all spectral bands. However, the signal processing analyses also revealed that DBS was not able to restore the adaptive motor control abilities in PD

New records of the rare deep-water alga Sebdenia monnardiana (Rhodophyta) and the alien Dictyota cyanoloma (Phaeophyceae ) and the unresolved case of deep-water kelp in the Ionian and Aegean Seas (Greece)

Parts of the macroalgal flora of the eastern Mediterranean remain incompletely known. This applies in particular to the circalittoral communities. This study, based upon 2 cruises in the Ionian and Aegean Seas, surveyed benthic communities from 40 to 150 m depth by remotely-operated vehicle (ROV) with a special focus on detecting communities of the Mediterranean deep-water kelp Laminaria rodriguezii. These were complemented by shallow-water surveys on adjacent coastlines by snorkelling and scuba diving. While no kelp could be detected at any of the sites surveyed, ROV surveys of northern Euboia Island revealed the first east Mediterranean record of Sebdenia monnardiana (Sebdeniales, Rhodophyta). Snorkelling surveys on the coast of southeast Kefalonia yielded the first record of the alien alga Dictyota cyanoloma in Greece. This paper reports rbcL and SSU sequences for Sebdenia monnardiana, and COI for Dictyota cyanoloma.Peer reviewe