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In patients consulting otologists for vertigo a functional source can be expected in 50% of the patients and more frequently among young females than among older male subjects. Functional vertigo is frequently perceived as a turning sensation inside the head, functional dizziness frequently as a rocking sensation of the whole body, while patients with vertigo of somatic origin frequently seem to complain of a spinning sensation outside the head. The duration pattern of functional vertigo is frequently of a fluctuating or continuous type, while in the nonfunctional subjects it is of 2-5 hr. duration. In patients with vertigo of functional origin eye-closure tends to release rather than inhibit nystagmus. [ABSTRACT FROM AUTHOR]

Most measurements and models of forest carbon cycling neglect the carbon flux associated with the turnover of branch biomass, a physiological process quantified for other organs (fine roots, leaves, and stems). Synthesizing data from boreal, temperate, and tropical forests (184,815 trees), we found that including branch turnover increased empirical estimates of aboveground wood production by 16% (equivalent to 1.9 Pg Cy -1 globally), of similar magnitude to the observed global forest carbon sinks. In addition, reallocating carbon to branch turnover in model simulations reduced stem wood biomass, a long-lasting carbon storage, by 7 to 17%. This prevailing neglect of branch turnover suggests widespread biases in carbon flux estimates across global datasets and model simulations. Branch litterfall, sometimes used as a proxy for branch turnover, ignores carbon lost from attached dead branches, underestimating branch C turnover by 38% in a pine forest. Modifications to field measurement protocols and existing models are needed to allow a more realistic partitioning of wood production and forest carbon storage., Competing Interests: Competing interests statement:The authors declare no competing interest.

There are growing doubts about the true role of the common mycorrhizal networks (CMN or wood wide web) connecting the roots of trees in forests. We question the claims of a substantial carbon transfer from 'mother trees' to their offspring and nearby seedlings through the CMN. Recent reviews show that evidence for the 'mother tree concept' is inconclusive or absent. The origin of this concept seems to stem from a desire to humanize plant life but can lead to misunderstandings and false interpretations and may eventually harm rather than help the commendable cause of preserving forests. Two recent books serve as examples: The Hidden Life of Trees and Finding the Mother Tree., Competing Interests: Declaration of interests T. N. declares a conflicting interest as he owns shares in and works part time for the company Arevo AB that develops, produces, and markets organic fertilizers. The other authors have no conflicting interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Seminal scientific papers positing that mycorrhizal fungal networks can distribute carbon (C) among plants have stimulated a popular narrative that overstory trees, or 'mother trees', support the growth of seedlings in this way. This narrative has far-reaching implications for our understanding of forest ecology and has been controversial in the scientific community. We review the current understanding of ectomycorrhizal C metabolism and observations on forest regeneration that make the mother tree narrative debatable. We then re-examine data and conclusions from publications that underlie the mother tree hypothesis. Isotopic labeling methods are uniquely suited for studying element fluxes through ecosystems, but the complexity of mycorrhizal symbiosis, low detection limits, and small carbon discrimination in biological processes can cause researchers to make important inferences based on miniscule shifts in isotopic abundance, which can be misleading. We conclude that evidence of a significant net C transfer via common mycorrhizal networks that benefits the recipients is still lacking. Furthermore, a role for fungi as a C pipeline between trees is difficult to reconcile with any adaptive advantages for the fungi. Finally, the hypothesis is neither supported by boreal forest regeneration patterns nor consistent with the understanding of physiological mechanisms controlling mycorrhizal symbiosis., (© 2023 The Authors. New Phytologist © 2023 New Phytologist Foundation.)

Understanding how plant water uptake interacts with acquisition of soil nitrogen (N) and other nutrients is fundamental for predicting plant responses to a changing environment, but it is an area where models disagree. We present a novel isotopic labelling approach which reveals spatial patterns of water and N uptake, and their interaction, by trees. The stable isotopes 15 N and 2 H were applied to a small area of the forest floor in stands with high and low soil N availability. Uptake by surrounding trees was measured. The sensitivity of N acquisition to water uptake was quantified by statistical modelling. Trees in the high-N stand acquired twice as much 15 N as in the low-N stand and around half of their N uptake was dependent on water uptake ( 2 H enrichment). By contrast, in the low-N stand there was no positive effect of water uptake on N uptake. We conclude that tree N acquisition was only marginally dependent on water flux toward the root surface under low-N conditions whereas under high-N conditions, the water-associated N uptake was substantial. The results suggest a fundamental shift in N acquisition strategy under high-N conditions., (© 2021 The Authors. New Phytologist © 2021 New Phytologist Foundation.)

Cellular respiration via the alternative oxidase pathway (AOP) leads to a considerable loss in efficiency. Compared to the cytochrome pathway (COP), AOP produces 0-50% as much ATP per carbon (C) respired. Relative partitioning between the pathways can be measured in vivo based on their differing isotopic discriminations against 18 O in O 2 . Starting from published methods, we have refined and tested a new protocol to improve measurement precision and efficiency. The refinements detect an effect of tissue water content (P < 0.0001), which we have removed, and yield precise discrimination endpoints in the presence of pathway-specific respiratory inhibitors [CN - and salicylhydroxamic acid (SHAM)], which improves estimates of AOP/COP partitioning. Fresh roots of Pinus sylvestris were sealed in vials with a CO 2 trap. The air was replaced to ensure identical starting conditions. Headspace air was repeatedly sampled and isotopically analyzed using isotope-ratio mass spectrometry. The method allows high-precision measurement of the discrimination against 18 O in O 2 because of repeated measurements of the same incubation vial. COP and AOP respiration discriminated against 18 O by 15.1 ± 0.3‰ and 23.8 ± 0.4‰, respectively. AOP contributed to root respiration by 23 ± 0.2% of the total in an unfertilized stand. In a second, nitrogen-fertilized, stand AOP contribution was only 14 ± 0.2% of the total. These results suggest the improved method can be used to assess the relative importance of COP and AOP activities in ecosystems, potentially yielding information on the role of each pathway for the carbon use efficiency of organisms., (© 2018 Scandinavian Plant Physiology Society.)

Stem compression reduces or terminates the phloem-mediated transport of carbohydrates and other solutes in tree stems, without causing permanent damage to phloem functioning (Henriksson et al. Tree Physiol. 35:1075-1085, 2015). This has been tested on two species of pine trees, with diameters ranging from 3 to 26 cm in a forest in northern Sweden (Henriksson et al. Tree Physiol. 35:1075-1085, 2015) and in Harvard Forest, USA. Halting the phloem transport of trees in a forest is useful for studying tree physiological processes related to, or dependent on, phloem-transported compounds as well as downstream processes, in particular interactions with soil microbes. Phloem compression can be deployed in the lab and field on single trees, subsets, or over larger areas, depending on what is relevant for a particular research question.

Manipulating tree belowground carbon (C) transport enables investigation of the ecological and physiological roles of tree roots and their associated mycorrhizal fungi, as well as a range of other soil organisms and processes. Girdling remains the most reliable method for manipulating this flux and it has been used in numerous studies. However, girdling is destructive and irreversible. Belowground C transport is mediated by phloem tissue, pressurized through the high osmotic potential resulting from its high content of soluble sugars. We speculated that phloem transport may be reversibly blocked through the application of an external pressure on tree stems. Thus, we here introduce a technique based on compression of the phloem, which interrupts belowground flow of assimilates, but allows trees to recover when the external pressure is removed. Metal clamps were wrapped around the stems and tightened to achieve a pressure theoretically sufficient to collapse the phloem tissue, thereby aiming to block transport. The compression's performance was tested in two field experiments: a (13)C canopy labelling study conducted on small Scots pine (Pinus sylvestris L.) trees [2-3 m tall, 3-7 cm diameter at breast height (DBH)] and a larger study involving mature pines (∼15 m tall, 15-25 cm DBH) where stem respiration, phloem and root carbohydrate contents, and soil CO2 efflux were measured. The compression's effectiveness was demonstrated by the successful blockage of (13)C transport. Stem compression doubled stem respiration above treatment, reduced soil CO2 efflux by 34% and reduced phloem sucrose content by 50% compared with control trees. Stem respiration and soil CO2 efflux returned to normal within 3 weeks after pressure release, and (13)C labelling revealed recovery of phloem function the following year. Thus, we show that belowground phloem C transport can be reduced by compression, and we also demonstrate that trees recover after treatment, resuming C transport in the phloem., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Genomic characterization of pediatric acute lymphoblastic leukemia (ALL) has identified distinct patterns of genes and pathways altered in patients with well-defined genetic aberrations. To extend the spectrum of known somatic variants in ALL, we performed whole genome and transcriptome sequencing of three B-cell precursor patients, of which one carried the t(12;21)ETV6-RUNX1 translocation and two lacked a known primary genetic aberration, and one T-ALL patient. We found that each patient had a unique genome, with a combination of well-known and previously undetected genomic aberrations. By targeted sequencing in 168 patients, we identified KMT2D and KIF1B as novel putative driver genes. We also identified a putative regulatory non-coding variant that coincided with overexpression of the growth factor MDK. Our results contribute to an increased understanding of the biological mechanisms that lead to ALL and suggest that regulatory variants may be more important for cancer development than recognized to date. The heterogeneity of the genetic aberrations in ALL renders whole genome sequencing particularly well suited for analysis of somatic variants in both research and diagnostic applications., (© 2014 WILEY PERIODICALS, INC.)

Background: Target enrichment and resequencing is a widely used approach for identification of cancer genes and genetic variants associated with diseases. Although cost effective compared to whole genome sequencing, analysis of many samples constitutes a significant cost, which could be reduced by pooling samples before capture. Another limitation to the number of cancer samples that can be analyzed is often the amount of available tumor DNA. We evaluated the performance of whole genome amplified DNA and the power to detect subclonal somatic single nucleotide variants in non-indexed pools of cancer samples using the HaloPlex technology for target enrichment and next generation sequencing., Results: We captured a set of 1528 putative somatic single nucleotide variants and germline SNPs, which were identified by whole genome sequencing, with the HaloPlex technology and sequenced to a depth of 792-1752. We found that the allele fractions of the analyzed variants are well preserved during whole genome amplification and that capture specificity or variant calling is not affected. We detected a large majority of the known single nucleotide variants present uniquely in one sample with allele fractions as low as 0.1 in non-indexed pools of up to ten samples. We also identified and experimentally validated six novel variants in the samples included in the pools., Conclusion: Our work demonstrates that whole genome amplified DNA can be used for target enrichment equally well as genomic DNA and that accurate variant detection is possible in non-indexed pools of cancer samples. These findings show that analysis of a large number of samples is feasible at low cost, even when only small amounts of DNA is available, and thereby significantly increases the chances of indentifying recurrent mutations in cancer samples.

Deadenylation of eukaryotic mRNA is a mechanism critical for mRNA function by influencing mRNA turnover and efficiency of protein synthesis. Here, we review poly(A)-specific ribonuclease (PARN), which is one of the biochemically best characterized deadenylases. PARN is unique among the currently known eukaryotic poly(A) degrading nucleases, being the only deadenylase that has the capacity to directly interact during poly(A) hydrolysis with both the m(7)G-cap structure and the poly(A) tail of the mRNA. In short, PARN is a divalent metal-ion dependent poly(A)-specific, processive and cap-interacting 3'-5' exoribonuclease that efficiently degrades poly(A) tails of eukaryotic mRNAs. We discuss in detail the mechanisms of its substrate recognition, catalysis, allostery and processive mode of action. On the basis of biochemical and structural evidence, we present and discuss a working model for PARN action. Models of regulation of PARN activity by trans-acting factors are discussed as well as the physiological relevance of PARN.

Poly(A)-specific ribonuclease (PARN) is a mammalian 3'-exoribonuclease that degrades poly(A) with high specificity. To reveal mechanisms by which poly(A) is recognized by the active site of PARN, we have performed a kinetic analysis using a large repertoire of trinucleotide substrates. Our analysis demonstrated that PARN harbors specificity for adenosine recognition in its active site and that the nucleotides surrounding the scissile bond are critical for adenosine recognition. We propose that two binding pockets, which interact with the nucleotides surrounding the scissile bond, play a pivotal role in providing specificity for the recognition of adenosine residues by the active site of PARN. In addition, we show that PARN, besides poly(A), also quite efficiently degrades poly(U), approximately 10-fold less efficiently than poly(A). The poly(U)-degrading property of PARN could be of biological significance as oligo(U) tails recently have been proposed to play a role in RNA stabilization and destabilization.

Poly(A)-specific ribonuclease (PARN) is a homodimeric, processive, and cap-interacting 3' exoribonuclease that efficiently degrades eukaryotic mRNA poly(A) tails. The crystal structure of a C-terminally truncated PARN in complex with m(7)GpppG reveals that, in one subunit, m(7)GpppG binds to a cavity formed by the RRM domain and the nuclease domain, whereas in the other subunit, it binds almost exclusively to the RRM domain. Importantly, our structural and competition data show that the cap-binding site overlaps with the active site in the nuclease domain. Mutational analysis demonstrates that residues involved in m(7)G recognition are crucial for cap-stimulated deadenylation activity, and those involved in both cap and poly(A) binding are important for catalysis. A modeled PARN, which shows that the RRM domain from one subunit and the R3H domain from the other subunit enclose the active site, provides a structural foundation for further studies to elucidate the mechanism of PARN-mediated deadenylation.

Poly(A)-specific ribonuclease (PARN) is an oligomeric, processive and cap-interacting 3' exoribonuclease that efficiently degrades mRNA poly(A) tails. Here we show that the RNA recognition motif (RRM) of PARN harbors both poly(A) and cap binding properties, suggesting that the RRM plays an important role for the two critical and unique properties that are tightly associated with PARN activity, i.e. recognition and dependence on both the cap structure and poly(A) tail during poly(A) hydrolysis. We show that PARN and its RRM have micromolar affinity to the cap structure by using fluorescence spectroscopy and nanomolar affinity for poly(A) by using filter binding assay. We have identified one tryptophan residue within the RRM that is essential for cap binding but not required for poly(A) binding, suggesting that the cap- and poly(A)-binding sites associated with the RRM are both structurally and functionally separate from each other. RRM is one of the most commonly occurring RNA-binding domains identified so far, suggesting that other RRMs may have both cap and RNA binding properties just as the RRM of PARN.

Peak velocities of voluntary saccades and fast phases of different qualities of nystagmus were studied in 20 normal subjects, 5 patients with pontine lesions and 5 patients with lesions in the frontal cortex. The peak velocity of saccades was related to the amplitude of the eye movement, the alertness of the subject and whether the subject could see the target or not. The effect of the age was not significant. The quick phases of caloric, optokinetic and angular acceleration induced nystagmus were equally rapid but somewhat slower than that of vestibular nystagmus recorded in standardized visual surrounding. In the same visual condition saccades were always faster than quick phases of nystagmus. Patients with cortical lesions had normal velocities in saccades and quick phases of nystagmus. Patients with pontine disorders had significantly reduced saccadic and quick phase velocity, and some of the patients exhibited dissociations between velocity mechanisms while the somewhat higher velocity in quick phase of vestibular nystagmus recorded in light is probably related to higher attention evoked by vestibular-visual interaction.

A vertigo perceived as a spinning sensation outside the head indicates a somatic vestibular disturbance including a Ménièr's disease. A turning sensation inside the head indicates a functional or vascular disorder while a sensation of unsteadiness often as if being slowly rocked indicates a functional disorder.

The maximum velocity gain of smooth pursuit and optokinetic, vestibular, and optovestibular slow phases was examined in 15 patients with pontine, 10 with medullary, 10 with cerebellar, and 5 with combined cerebello-brain stem disorders. Marked dissociations were observed between smooth pursuit and optokinetic slow phases, especially in medullary disease. A cerebellar deficit enhanced slow phase velocity gain during rotation in darkness, whereas the corresponding gain during rotation in light was normal.

Peak velocity of saccade, maximum velocity of smooth pursuit, and peak velocity of slow phase of vestibular and optovestibular nystagmus were measured three times daily on three separate days in 6 healthy subjects in order to estimate the intra-individual variation of the results of oculomotor tests. Analysis of variance revealed that the oculomotor performance of the individual subjects varied systematically, depending on whether the tests were performed in the morning, at noon, or late in the afternoon. In particular, the velocity of saccade displayed lowest values in the afternoon. The present results indicate that oculomotor performance may depend on the individual biological rhythm of fatigue; however, it is also possible that eye motor behaviour is coupled to an independent rhythm of motor activity. Circadian rhythmicity of oculomotor performance should be considered in follow-up studies and in examination of patients with reduced vigilance.

A conception of the mechanism for initiating symptoms in Ménière's disease has been forwarded. According to this conception production of endolymph may vary also in normals. The hydrops in Ménière cases is brought about by a relative insufficiency in endolymphatic draining routes and the hydrops presents itself only at peak endolymph production periods. The attacks of vertigo are brought about at the distension of the sacs as well as of the regaining of normal shape of the sacs. The mechanism causing the vertigo could be an effect of mechanical push-and-pull effect on the sensory epithelium of the cristae. The early low-tone hearing loss and the persistant normal caloric reactivity also in advanced Méière cases may be due to simple physical laws : distensions of sacs with equal walls will more easily be brought about in wider than narrow compartments.

Eye movements in 30 patients with brain-stem lesions were evaluated with electro-oculography, and the findings were analyzed with regard to the site of the lesion in the brain stem. Eye velocities generally were reduced more severely in pontine than in medullary lesions. In medullary lesions, there even was a slight enhancement of the velocities in the fast component of optokinetic and postrotatory nystagmus. In contrast to the slow-phase velocity of OKN, which often was preserved in medullary lesions, the smooth-pursuit velocity was reduced in lesions at all levels in the brian stem. This indicates that these two types of visually induced eye movements use different mechanisms.

Optokinetic nystagmus (OKN) was studied in ten patients with vestibular neuritis, and in seventeen patients with unilateral and thirteen patients with bilateral infratentorial lesions and compared with OKN in fifty healthy subjects. Mean and maximum slow phase velocity of OKN was calculated as well as the asymmetry of responses. The efficiency of the different variables in OKN, in discriminating between different lesion sites, was tested in a linear discriminant function analysis. Slow phase velocity of OKN could satisfactorily separate patients with infratentorial lesions from healthy subjects or subjects with vestibular neuritis. Asymmetry of OKN did not contribute further to the correct diagnosis.

During recent decades a vast amount of literature concerning horizontal optokinetic nystagmus has emerged, regarding which--and especially as regards our own work--this report is intended to consider the clinical value of optokinetic nystagmus.

The effects of TTS-scopolamine, dimenhydrinate, lidocaine, and tocainide on motion sickness and vertigo and on caloric and postrotatory nystagmus were evaluated in healthy volunteers. TTS-scopolamine was administered transdermally (delivering approximately 10 micrograms X h-1 scopolamine base) and 100 mg dimenhydrinate orally. Lidocaine and tocainide were administered intravenously (average plasma concentration of lidocaine 6 mol X L-1 and of tocainide 20 mol X L-1). TTS-scopolamine and dimenhydrinate significantly reduced vertigo induced by calorization of the ears, nausea provoked with Coriolis maneuvre, and nystagmus in caloric and rotatory tests. During treatment with lidocaine and tocainide no alleviation of vertigo and nausea was observed. Caloric nystagmus was reduced but rotation induced nystagmus was virtually unchanged. Presumably the motion sickness drugs act at the brain stem where TTS-scopolamine and dimenhydrinate have their target cells in the vestibular nuclei. Furthermore, the alleviation of motion sickness was linked to a decline of nystagmus. Lidocaine and tocainide, the action of which in vertigo and nausea in patients is proposed to be on the vestibular end organs and the supratentorial brain structures, consistently failed to alleviate motion sickness.