Neurexins play diverse functions as presynaptic organizers in various glutamatergic and GABAergic synapses. However, it remains unknown whether and how neurexins are involved in shaping functional properties of the glycinergic synapses, which mediate prominent inhibition in the brainstem and spinal cord. To address these issues, we examined the role of neurexins in a model glycinergic synapse between the principal neuron in the medial nucleus of the trapezoid body (MNTB) and the principal neuron in the lateral superior olive (LSO) in the auditory brainstem. Combining RNAscope with stereotactic injection of AAV-Cre in the MNTB of neurexin1/2/3 conditional triple knockout mice, we showed that MNTB neurons highly express all isoforms of neurexins although their expression levels vary remarkably. Selective ablation of all neurexins in MNTB neurons not only reduced the amplitude but also altered the kinetics of the glycinergic synaptic transmission at LSO neurons. The synaptic dysfunctions primarily resulted from an impaired Ca2+ sensitivity of release and a loosened coupling between voltage-gated Ca2+ channels and synaptic vesicles. Together, our current findings demonstrate that neurexins are essential in controlling the strength and temporal precision of the glycinergic synapse, which therefore corroborates the role of neurexins as key presynaptic organizers in all major types of fast chemical synapses.

The potato psyllid, Bactericera cockerelli (Šulc) (Hemiptera: Triozidae), transmits the pathogen \"Candidatus liberibacter solanacearum\" (Lso), the putative causal agent of zebra chip disease (ZC). ZC is a disease of potato that reduces yield and quality and has disrupted integrated pest management programs in parts of the Americas and New Zealand. Advances in our understanding of the ecological factors that influence ZC epidemiology have been accelerated by the relatively recent identification of Lso and motivated by the steady increase in ZC distribution and the potential for devastating economic losses on a global scale. Management of ZC remains heavily reliant upon insecticides, which is not sustainable from the standpoint of insecticide resistance, nontarget effects on natural enemies, and regulations that may limit such tools. This review synthesizes the literature on potato psyllids and ZC, outlining recent progress, identifying knowledge gaps, and proposing avenues for further research on this important pathosystem of potatoes.

Objective. Current commercial positron emission tomography (PET) scanners have excellent performance and diagnostic image quality primarily due to improvements in scanner sensitivity and time-of-flight (TOF) resolution. Recent years have seen the development of total-body PET scanners with longer axial field-of-view (AFOV) that increase sensitivity for single organ imaging, and also image more of the patient in a single bed position thereby enabling multi-organ dynamic imaging. While studies have shown significant capabilities of these systems, cost will be a major factor in their widespread adoption in the clinic. Here we evaluate alternative designs that achieve many advantages of long AFOV PET while utilizing cost-effective detector hardware.Approach. We utilize Monte Carlo simulations and clinically relevant lesion detectability metric to study the impact of scintillator type lutetium oxyorthosilicate or bismuth germanate (LSO or BGO), scintillator thickness (10-20 mm), and TOF resolution on resultant image quality in a 72 cm long scanner. Detector TOF resolution was varied based on current scanner performance, as well as expected future performance from detector designs that currently hold most promise for scaling into a scanner.Main results. Results indicate that BGO is competitive with LSO (both 20 mm thick) if we assume that it uses TOF (e.g. Cerenkov timing with 450 ps fwhm and Lorentzian distribution) and the LSO scanner has TOF resolution similar to the latest PMT-based scanners (∼500-650 ps). Alternatively, a system using 10 mm thick LSO with 150 ps TOF resolution can also provide similar performance. Both these alternative systems can provide cost savings (25%-33%) relative to a scanner using 20 mm LSO with ∼50% of effective sensitivity, but still 500%-700% higher than a conventional AFOV scanner.Significance. Our results have relevance to the development of long AFOV PET, where reduced cost of these alternative designs can provide wider accessibility for use in situations requiring imaging of multiple organs simultaneously.

\'Candidatus Liberibacter solanacearum\' (Lso) is the causal agent of zebra chip of potato (Solanum tuberosum), which can significantly reduce potato yield. In this study, a loop-mediated isothermal amplification (LAMP) method for the detection of Lso haplotypes A and B was developed and evaluated. Two sets of LAMP primers named LAMP-A and LAMP-B were designed and tested for specificity and sensitivity. Both LAMP-A and LAMP-B were specific to Lso in in silico analysis using the Primer-Blast tool. The LAMP-A and LAMP-B could only produce positive signals from DNA mixtures of Lso-infected tomato but not from the genomic DNA of 37 nontarget plant pathogens. The sensitivity of LAMP-A and LAMP-B on Lso haplotypes A and B were tested on gBlocks and genomic DNA from Lso-infected tomato. On the genomic DNA for LAMP-A, the lowest amount of template DNA for a positive LAMP reaction was 2 to 20 ng on four haplotype A strains and 20 to 80 ng on four haplotype B strains; for LAMP-B, the lowest amount of template DNA for a positive LAMP reaction was 0.02 to 2 ng on four haplotype B strains and 20 ng to no amplification on four haplotype A strains. On gBlocks for LAMP-A, the lowest number of copies for a positive LAMP reaction was 60 on haplotype A and 600 on haplotype B; for LAMP-B, the lowest number of copies for a positive LAMP reaction was 60 on haplotype B and 600 on haplotype A. Therefore, considering the convenience of the LAMP technique, as well as the high specificity and sensitivity, the LAMP-A and LAMP-B primers can be used together to test the probable Lso-infected plant or psyllid samples to rapidly, accurately, and directly differentiate haplotypes A and B. We highly recommend this LAMP system to plant pathology practitioners and diagnostic labs for routine detection of Lso and confirmation of zebra chip disease on potato or tomato.

Interaural time difference (ITD) sensitivity with cochlear implant stimulation is remarkably similar to envelope ITD sensitivity using conventional acoustic stimulation. This holds true for human perception, as well as for neural response rates recorded in the inferior colliculus of several mammalian species. We hypothesize that robust excitatory-inhibitory (EI) interaction is the dominant mechanism. Therefore, we connected the same single EI-model neuron to either a model of the normal acoustic auditory periphery or to a model of the electrically stimulated auditory nerve. The model captured most features of the experimentally obtained response properties with electric stimulation, such as the shape of rate-ITD functions, the dependence on stimulation level, and the pulse rate or modulation-frequency dependence. Rate-ITD functions with high-rate, amplitude-modulated electric stimuli were very similar to their acoustic counterparts. Responses obtained with unmodulated electric pulse trains most resembled acoustic filtered clicks. The fairly rapid decline of ITD sensitivity at rates above 300 pulses or cycles per second is correctly simulated by the 3.1-ms time constant of the inhibitory post-synaptic conductance. As the model accounts for these basic properties, it is expected to help in understanding and quantifying the binaural hearing abilities with electric stimulation when integrated in bigger simulation frameworks.

In all mammals, the superior olivary complex (SOC) comprises a group of auditory brainstem nuclei that are important for sound localization. Its principal nuclei, the lateral superior olive (LSO) and the medial superior olive (MSO) process interaural time and intensity differences, which are the main cues for sound localization in the horizontal plane. Toothed whales (odontocetes) rely heavily on hearing and echolocation for foraging, orientation, and communication and localize sound with great acuity. The investigation of the SOC in odontocetes provides insight into adaptations to underwater hearing and echolocation. However, quantitative anatomical data for odontocetes are currently lacking. We quantified the volume, total neuron number, and neuron density of the LSO of six common dolphins (Delphinus delphis) using the Cavalieri principle and the unbiased stereology optical fractionator. Our results show that the LSO in D. delphis has a volume of 150 + (SD = 27) mm3 , which is on average 69 (SEM = 19) times larger than the LSO in human, or 37 (SEM = 11) times larger than the human LSO and MSO combined. The LSO of D. delphis contains 20,876 ± (SD = 3300) neurons. In comparison, data reported for the human brainstem indicate the LSO has only about ¼ that number but about the same number for the LSO and MSO combined (21,100). LSO neurons range from 21 to 25 μm (minor axis) and from 44 to 61 μm (major axis) in transverse sections. The LSO neuron packing density is 1080 ± (SD = 204) neurons/mm3 , roughly half of the LSO neuron density in human. SMI-32-immunohistochemistry was used to visualize projection neurons in the LSO and revealed the presence of principal, marginal, and multipolar neurons in transverse sections. The distinct morphology of the LSO likely reflects the common dolphin\'s superb sensitivity to ultra-high frequencies and ability to detect and analyze sounds and their location as part of its underwater spatial localization and echolocation tasks.

For amplitude-modulated sound, the envelope interaural time difference (ITDENV) is a potential cue for sound-source location. ITDENV is encoded in the lateral superior olive (LSO) of the auditory brainstem, by excitatory-inhibitory (EI) neurons receiving ipsilateral excitation and contralateral inhibition. Between human listeners, sensitivity to ITDENV varies considerably, but ultimately decreases with increasing stimulus carrier frequency, and decreases more strongly with increasing modulation rate. Mechanisms underlying the variation in behavioral sensitivity remain unclear. Here, with increasing carrier frequency (4-10 kHz), as we phenomenologically model the associated decrease in ITDENV sensitivity using arbitrarily fewer neurons consistent across populations, we computationally model the variable sensitivity across human listeners and modulation rates (32-800 Hz) as the decreasing range of membrane frequency responses in LSO neurons. Transposed tones stimulate a bilateral auditory-periphery model, driving model EI neurons where electrical membrane impedance filters the frequency content of inputs driven by amplitude-modulated sound, evoking modulation filtering. Calculated from Fisher information in spike-rate functions of ITDENV, for model EI neuronal populations distinctly reflecting the LSO range in membrane frequency responses, just-noticeable differences in ITDENV collectively reproduce the largest variation in ITDENV sensitivity across human listeners. These slow to fast model populations each generally match the best human ITDENV sensitivity at a progressively higher modulation rate, by membrane-filtering and spike-generation properties producing realistically less than Poisson variance. Non-resonant model EI neurons are also sensitive to interaural intensity differences. With peripheral filters centered between carrier frequency and modulation sideband, fast resonant model EI neurons extend ITDENV sensitivity above 500-Hz modulation.

Comprehensive information on the characteristics of surgical heart valves (SHVs) is essential for optimal valve selection. Such information is also important in assessing SHV function after valve replacement. Despite the existing regulatory framework for SHV sizing and labelling, this information is challenging to obtain in a uniform manner for various SHVs. To ensure that clinicians are adequately informed, the European Association for Cardio-Thoracic Surgery (EACTS), The Society of Thoracic Surgeons (STS) and American Association for Thoracic Surgery (AATS) set up a Task Force comprised of cardiac surgeons, cardiologists, engineers, regulatory bodies, representatives of the International Organization for Standardization and major valve manufacturers. Previously, the EACTS-STS-AATS Valve Labelling Task Force identified the most important problems around SHV sizing and labelling. This Expert Consensus Document formulates recommendations for providing SHV physical dimensions, intended implant position and haemodynamic performance in a transparent, uniform manner. Furthermore, the Task Force advocates for the introduction and use of a standardized chart to assess the probability of prosthesis-patient mismatch and calls valve manufacturers to provide essential information required for SHV choice on standardized Valve Charts, uniformly for all SHV models.

Zebra chip (ZC) disease of potato (Solanum tuberosum) is associated with infection by \'Candidatus Liberibacter solanacearum\' (Lso). Two haplotypes of Lso-A and B-occur in the United States. Lso haplotype B is more virulent than haplotype A, causing greater disease incidence in tubers, more severe symptoms, and greater loss in tuber yield. This study assessed whether tubers from infected plants generate new infected plants the following year. The effects of both Lso haplotypes A and B on tuber resprout were examined on five potato cultivars. When compared with noninfected tubers, overall plant emergence rate from Lso A- or B-infected tubers was lower, plants emerged slower, and plants generated lower daughter tuber yields in weight and quantity. Plants generally emerged poorly from Lso B-infected tubers and produced lower daughter tuber yields than Lso A-infected tubers. Regardless of Lso treatment, all daughter tubers were asymptomatic, and only 0.3% tested positive for Lso in experiments conducted over 2 years. This suggests that plants generated from Lso A- and Lso B-infected seed potatoes with severe ZC symptoms are likely not a significant source of Lso in potato fields.

Anisotropy of tracer-coupled networks is a hallmark in many brain regions. In the past, the topography of these networks was analyzed using various approaches, which focused on different aspects, e.g., position, tracer signal, or direction of coupled cells. Here, we developed a vector-based method to analyze the extent and preferential direction of tracer spreading. As a model region, we chose the lateral superior olive-a nucleus that exhibits specialized network topography. In acute slices, sulforhodamine 101-positive astrocytes were patch-clamped and dialyzed with the GJ-permeable tracer neurobiotin, which was subsequently labeled with avidin alexa fluor 488. A predetermined threshold was used to differentiate between tracer-coupled and tracer-uncoupled cells. Tracer extent was calculated from the vector means of tracer-coupled cells in four 90° sectors. We then computed the preferential direction using a rotating coordinate system and post hoc fitting of these results with a sinusoidal function. The new method allows for an objective analysis of tracer spreading that provides information about shape and orientation of GJ networks. We expect this approach to become a vital tool for the analysis of coupling anisotropy in many brain regions.