Surface-to-space atmospheric waves from Hunga Tonga-Hunga Ha'apai eruption.

The January 2022 Hunga Tonga-Hunga Ha'apai eruption was one of the most explosive volcanic events of the modern era1,2, producing a vertical plume that peaked more than 50 km above the Earth3. The initial explosion and subsequent plume triggered atmospheric waves that propagated around the world multiple times4. A global-scale wave response of this magnitude from a single source has not previously been observed. Here we show the details of this response, using a comprehensive set of satellite and ground-based observations to quantify it from surface to ionosphere. A broad spectrum of waves was triggered by the initial explosion, including Lamb waves5,6 propagating at phase speeds of 318.2 ± 6 m s-1 at surface level and between 308 ± 5 to 319 ± 4 m s-1 in the stratosphere, and gravity waves7 propagating at 238 ± 3 to 269 ± 3 m s-1 in the stratosphere. Gravity waves at sub-ionospheric heights have not previously been observed propagating at this speed or over the whole Earth from a single source8,9. Latent heat release from the plume remained the most significant individual gravity wave source worldwide for more than 12 h, producing circular wavefronts visible across the Pacific basin in satellite observations. A single source dominating such a large region is also unique in the observational record. The Hunga Tonga eruption represents a key natural experiment in how the atmosphere responds to a sudden point-source-driven state change, which will be of use for improving weather and climate models.

An Arabidopsis gene regulatory network for secondary cell wall synthesis.

The plant cell wall is an important factor for determining cell shape, function and response to the environment. Secondary cell walls, such as those found in xylem, are composed of cellulose, hemicelluloses and lignin and account for the bulk of plant biomass. The coordination between transcriptional regulation of synthesis for each polymer is complex and vital to cell function. A regulatory hierarchy of developmental switches has been proposed, although the full complement of regulators remains unknown. Here we present a protein-DNA network between Arabidopsis thaliana transcription factors and secondary cell wall metabolic genes with gene expression regulated by a series of feed-forward loops. This model allowed us to develop and validate new hypotheses about secondary wall gene regulation under abiotic stress. Distinct stresses are able to perturb targeted genes to potentially promote functional adaptation. These interactions will serve as a foundation for understanding the regulation of a complex, integral plant component.

Using sub-limb observations to measure gravity waves excited by convection.

Convective gravity waves are a major driver of atmospheric circulation, including the stratospheric and mesospheric quasi-biennial oscillation (QBO) and the Brewer-Dobson circulation. Previous work shows clear evidence that these waves can be excited by both single convective cells and by mesoscale convective complexes acting as a single unit. However, the partitioning of the generated waves and, crucially for atmospheric model development, the flux of momentum they transport between these two types of excitation process remains highly uncertain due to a fundamental lack of suitable observations at the global scale. Here, we use both theoretical calculations and sampled output from a high-resolution weather model to demonstrate that a satellite instrument using a sub-limb geometry would be well suited to characterising the short-vertical short-horizontal gravity waves these systems produce, and hence to provide the scientific knowledge needed to identify the relative wave-driving contribution of these two types of convective wave excitation.

Regeneration of sensory hair cells after acoustic trauma.

Any loss of cochlear hair cells has been presumed to result in a permanent hearing deficit because the production of these cells normally ceases before birth. However, after acoustic trauma, injured sensory cells in the mature cochlea of the chicken are replaced. New cells appear to be produced by mitosis of supporting cells that survive at the lesion site and do not divide in the absence of trauma. This trauma-induced division of normally postmitotic cells may lead to recovery from profound hearing loss.

Ultrastructural evidence for hair cell regeneration in the mammalian inner ear.

It has long been thought that hair cell loss from the inner ears of mammals is irreversible. This report presents scanning electron micrographs and thin sections of the utricles from the inner ears of guinea pigs that show that, after hair cell loss caused by treatment with the aminoglycoside gentamicin, hair cells reappeared. Four weeks after the end of treatment, a large number of cells with immature hair bundles in multiple stages of development could be identified in the utricle. Thin sections showed that lost type 1 hair cells were replaced by cells with a morphology similar to that of type 2 hair cells. These results indicate an unexpected capacity for hair cell regeneration in vivo in the mature mammalian inner ear.

Regenerative proliferation in inner ear sensory epithelia from adult guinea pigs and humans.

Supporting cells in the vestibular sensory epithelia from the ears of mature guinea pigs and adult humans proliferate in vitro after treatments with aminoglycoside antibiotics that cause sensory hair cells to die. After 4 weeks in culture, the epithelia contained new cells with some characteristics of immature hair cells. These findings are in contrast to expectations based on previous studies, which had suggested that hair cell loss is irreversible in mammals. The loss of hair cells is responsible for hearing and balance deficits that affect millions of people.

Noradrenergic antagonists mitigate amphetamine-induced recovery.

Brain injury, including that due to stroke, leaves individuals with cognitive deficits that can disrupt daily aspect of living. As of now there are few treatments that shown limited amounts of success in improving functional outcome. The use of stimulants such as amphetamine have shown some success in improving outcome following brain injury. While the pharmacological mechanisms for amphetamine are known; the specific processes responsible for improving behavioral outcome following injury remain unknown. Understanding these mechanisms can help to refine the use of amphetamine as a potential treatment or lead to the use of other methods that share the same pharmacological properties. One proposed mechanism is amphetamine's impact upon noradrenaline (NA). In the current, study noradrenergic antagonists were administered prior to amphetamine to pharmacologically block α- and ß-adrenergic receptors. The results demonstrated that the blockade of these receptors disrupted amphetamines ability to induce recovery from hemispatial neglect using an established aspiration lesion model. This suggests that amphetamine's ability to ameliorate neglect deficits may be due in part to noradrenaline. These results further support the role of noradrenaline in functional recovery. Finally, the development of polytherapies and combined therapeutics, while promising, may need to consider the possibility that drug interactions can negate the effectiveness of treatment.

Hair cell development.

Neurobiologists have been challenged by the desire to understand how the highly specialized ultrastructure of the sensory hair cells of the ear develops, how patterns of phenotypically distinct hair cells are formed and regenerate, and how their specific neural connections are formed. Recent research has addressed some of these challenges at the level of cell and molecular biology, focusing on cell proliferation in hair cell epithelia, the mechanisms that control hair cell differentiation, and the developmental interdependencies between hair cells and neurons. The initial identification of some of the homeobox genes and growth factors that are involved in hair cell development has occurred during the past year.

Brief treatments with forskolin enhance s-phase entry in balance epithelia from the ears of rats.

In the ears of mammals, hair cell loss results in permanent hearing and balance deficits, whereas in fish, amphibians, and birds, the production of replacement hair cells can restore those modalities. In avian ears, continuous exposures to forskolin trigger cell proliferation and the regeneration of hair cells, so we investigated the effect of forskolin on sensory epithelia cultured from the ears of mammals. Continuous 72 hr exposures to forskolin failed to induce proliferation in neonatal rat utricles, but brief (

Intracellular signals that control cell proliferation in mammalian balance epithelia: key roles for phosphatidylinositol-3 kinase, mammalian target of rapamycin, and S6 kinases in preference to calcium, protein kinase C, and mitogen-activated protein kinase.

In fish, amphibians, and birds, the loss of hair cells can evoke S-phase entry in supporting cells and the production of new cells that differentiate as replacement hair cells and supporting cells. Recent investigations have shown that supporting cells from mammalian vestibular epithelia will proliferate in limited numbers after hair cells have been killed. Exogenous growth factors such as glial growth factor 2 enhance this proliferation most potently when tested on vestibular epithelia from neonates. In this study, the intracellular signaling pathways that underlie the S-phase entry were surveyed by culturing epithelia in the presence of pharmacological inhibitors and activators. The results demonstrate that phosphatidylinositol 3-kinase is a key element in the signaling cascades that lead to the proliferation of cells in mammalian balance epithelia in vitro. Protein kinase C, mammalian target of rapamycin, mitogen-activated protein kinase, and calcium were also identified as elements in the signaling pathways that trigger supporting cell proliferation.

Prolongation of survival for high-grade malignant gliomas with adjuvant high-dose BCNU and autologous bone marrow transplantation.

Employment of postoperative brain irradiation in the initial management of high-grade malignant glial tumors has now become standard. The addition of conventional chemotherapy to irradiation has not significantly improved median survival beyond 1 year. We treated 25 consecutive patients (13 pilot patients and 12 protocol patients) with histologically confirmed unresectable grade 3 or 4 malignant gliomas with high-dose BCNU (carmustine) followed by autologous bone marrow transplantation and whole brain irradiation. Within 3 weeks of initial surgery, each patient had autologous bone marrow stored (median 2 X 10(8) nucleated cells/kg), and then received BCNU 1,050 mg/m2 intravenously (IV). Peripheral granulocytes recovered (greater than 500/microL) at a median of 19 days (range, 10 to 37 days), and platelets recovered (greater than 20,000/microL) at a median of 18 days (range, 13 to 40 days), following bone marrow infusion. Patients received 60 Gy whole brain irradiation when granulocytes were greater than 1,500/microL. Toxicity was well tolerated. Nausea occurred in 19 patients (76%); however, only eight patients (32%) experienced vomiting (mild in three, moderate in five). Eleven patients (44%) did not require empiric antibiotics, six of whom never developed an absolute granulocyte count less than 500/microL. Three patients with a poor performance status died early (one seizure with vomiting and asphyxiation; one, klebsiella urinary tract infection (UTI) with bacteremia; one, candidal pneumonia), and one additional patient who was performing well died of pulmonary hemorrhage. The 13 pilot patients have now been followed for a median of 23 months, with a significant survival advantage compared with the 52 consecutive historical control patients who received similar surgery and radiotherapy without high-dose BCNU (P = .037). The overall study group of 25 patients also has a significant survival advantage when compared with the same historical control group, with a projected median survival of 26 months (P = .007). This new approach using early postoperative intensive therapy consisting of high-dose BCNU, autologous bone marrow transplantation, and whole brain irradiation appears to significantly improve survival.

Overlap and interdigitation of cortical and thalamic afferents to dorsocentral striatum in the rat.

Dorsocentral striatum (DCS) is an associative region necessary for directed attention in rats. DCS is defined as the main region in which axons from ipsilateral medial agranular cortex (AGm) terminate within the striatum. In this double-labeling study, we placed a green axonal tracer in area AGm and a red one in an additional brain region. We examined the spatial relationship between terminals from area AGm and other portions of the cortical-basal ganglia-thalamic-cortical network involved in directed attention and its dysfunction, hemispatial neglect, in the rat. These include lateral agranular cortex (AGl), posterior parietal cortex (PPC), ventrolateral orbital cortex (VLO), and secondary visual cortex (Oc2M). One important finding is the presence of a dense focus of labeled axons within DCS after injections in cortical area PPC or Oc2M. In these foci, axons from PPC or Oc2M extensively overlap and interdigitate with axons from cortical area AGm. Additionally, retrograde labeling of striatal neurons, along with double anterograde labeling, suggests that axons from cortical area AGm and AGl cross and possibly make contact with the dendritic processes of single medium spiny neurons. Axons from thalamic nucleus LP were observed to form a dense band dorsal to DCS which is similar to that seen following PPC injections, and a significant number of LP axons were also observed within DCS. Projections from thalamic nucleus VL are present in the dense dorsolateral AGm band that abuts the external capsule, are densest in the dorsolateral striatum, and were not observed in DCS. These results extend previous findings that DCS receives input from diverse cortical areas and thalamic nuclei which are themselves interconnected.

Life-sustaining interventions in frail elderly persons. Talking about choices.

BACKGROUND: Engaging older persons in consideration of use of life-sustaining measures, such as cardiopulmonary resuscitation, tube feeding, and urgent intubation, is widely recommended, yet uncommon. METHODS: We studied the short-term impact of a physician-initiated discussion, geared toward guiding informed decision-making, with 20 frail elderly homebound patients. A battery of psychologic rating scales was administered in a pre-post design. Eighteen subjects completed the protocol. Fifteen of the mentally capable surviving subjects were reinterviewed 18 months following the initial discussion to evaluate durability of their decisions. RESULTS: Most welcomed the discussion and clear choices regarding future care usually emerged. Depression rating scales decreased slightly for the entire sample. For the subgroup having relatively internal locus of control, there was an increase in life satisfaction scores. No patient demonstrated signs of emotional trauma consequent to the discussion. On follow-up, several patients were indecisive about their choices. CONCLUSION: Involvement of these patients in decision-making appeared to have no adverse effects, and, for some, it was therapeutic, possibly through enhancement of personal control. Durability of their decisions was not a consistent finding, however.

Early pharmacokinetics and clinical effects of oral D-amphetamine in normal subjects.

Seven normal subjects received 0.25 mg/kg D-amphetamine orally, both after an overnight fast and again after a standard breakfast. Plasma levels, subjective and cardiovascular effects, and observer-rated activation were assessed hourly for 5 hr. Food did not affect amphetamine levels. Plasma levels peaked at 2-3 hr. Maximum cardiovascular effects generally occurred at 1 hr, whereas maximum behavioral and subjective effects occurred at 2 hr. Subjective and behavioral effects declined thereafter, in spite of substantial amphetamine levels. A separate group of 8 subjects received 0.5 mg/kg D-amphetamine orally. Plasma levels, subjective and cardiovascular effects, and activation ratings were assessed hourly for 4 hr. Maximum plasma levels were approximately twice those seen in the first group. In this case, plasma levels peaked at 3-4 hr; blood pressure and subjective and behavioral effects were all maximal at 2-3 hr and were declining by 4 hr, in spite of stable or rising plasma levels.

Disorders of decision in affective disease: an effect of beta-adrenergic dysfunction?

We investigated response bias (defined as the decision rule subjects adopt when uncertain) in two experiments using a variant of Signal Detection Theory (SDT) with the discrimination measure d'L and the bias measure CL, under which it is possible to independently evaluate discrimination and response bias. In the first experiment, manics, depressed subjects, and matched psychiatrically normal controls were tested with a recognition memory task with easier and more difficult components before and after 1 month of appropriate pharmacological treatment. This experiment showed that abnormally conservative bias was characteristic of depression and liberal (yea-saying) bias was found in mania regardless of severity of illness; discrimination deficits were found only when symptoms were severe. After treatment, aspects of discrimination worsened in both hypomanic and depressed nonresponders whereas response bias remained unchanged in these patients. In both groups of responders, improvements in response bias were more dramatic than improvements in discrimination. In the second experiment, psychiatrically normal hypertensives were tested with a Sternberg short-term memory scanning task on and off treatment with the centrally active beta-blocker propranolol. This experiment showed that treatment with propranolol modeled the bias deficit of depression; that is, bias became more conservative. Both sets of results suggest that disorders of decision may be modulated by beta-adrenergic function.

Serial lesion effect in rat medial frontal cortex as a function of age.

This experiment examined the potential for behavioral recovery in juvenile, adult, and senescent rats following serial lesions of medial frontal cortex. The subjects were trained on spatial delayed alternation in a T-maze under conditions designed to enhance the probability of a serial lesion effect. All subjects were given extensive handling and adaptation to the maze, interoperative training, and long interoperative and postoperative intervals. There were several major behavioral findings: (a) the aged intact subjects were not impaired in their ability to learn spatial delayed alternation, (b) one-stage bilateral lesions of frontal cortex produced equivalent deficits on spatial delayed alternation at all ages, (c) subjects in all of the age categories demonstrated a serial lesion effect, but (d) the 150 day and 570 day serial lesions groups demonstrated significantly better performances than the 35 day serial lesions group on several measures of performance.

CSF somatostatin in Alzheimer's disease.

Studies have previously demonstrated low somatostatin levels in autopsy cortical tissue from Alzheimer's disease (AD) patients and low somatostatin levels in CSF obtained from subjects with dementia. We evaluated levels of this peptide in 21 non-depressed subjects, 10 with AD, 2 with Parkinson's disease (PD), and 9 with other neurological conditions. The AD patients had significantly lower mean CSF somatostatin than the "other" neurological patients (14.6 +/- 1.5 S.E.M. versus 26.7 +/- 3.2 pg/ml, p less than 0.005). A demented PD subject had a level in the range of the AD group, while the non-demented PD patient had a value above this range. Thus, all 11 patients with AD or PD dementia, analogous disorders, had levels below 21.8 mg/ml, while 7 of the 10 remaining patients had values above 21.8 pg/ml. Age did not explain this finding.

Behavioral effects of phosphatidylserine in the aged Fischer 344 rat: amelioration of passive avoidance deficits without changes in psychomotor task performance.

A series of studies was conducted to evaluate the effects of phosphatidylserine (PS) in aged Fischer 344 rats. No effects were observed in any of four psychomotor tasks in which aged rats normally show deficits, nor on measures of shock sensitivity. However, significant dose-related effects on retention of passive avoidance were observed when PS was given both 30 min prior to training and retention. Further, in a second experiment similar positive effects were observed when PS was given only 30 min prior to training, as well as only 5 min following training. These results suggest that one effect of PS may include an ability to enhance neural events involved in the encoding or consolidation of new information into memory.

Postembryonic growth of the macula neglecta auditory detector in the ray, Raja clavata: continual increases in hair cell number, neural convergence, and physiological sensitivity.

Quantitative scanning electron microscopy in an age series demonstrated that the macula neglecta auditory epithelium of the ray, Raja clavata, produces and accumulates sensory cells perpetually at 1-3 cells/day, so that the total increases from approximately 500 cells at birth to 6,000 at 7 years of age. The shape of the macula also changes with growth, and changes in the marginal zones of small and intermediate size hair cells are consistent with this differential growth and their proposed role as hair cell production sites. The neurons contacting the epithelium do not increase in number as animals age; instead they hypertrophy, increasing axon diameter and terminal field size. A hypothetical double-gradient interaction between the growing nerves and new hair cells is proposed to explain the development of synaptic connections and the continual production of individually oriented, functional hair cells. Electrophysiological recordings from the neurons demonstrated best sensitivities between 40 Hz and 200 Hz, directional receptive fields, and little or no effect of changes in the ear's position relative to gravity. The convergence ratio from sensory cells to neurons increases because of their unequal patterns of growth, and physiological sensitivity improves 500-fold and more as these animals age. These results contrast with current information on mammalian ears, where it appears that sensory cells are not produced at any time after birth.

Auditory neurons expand their terminal arbors throughout life and orient toward the site of postembryonic hair cell production in the macula neglecta in elasmobranchs.

The population of sensory hair cells in the macula neglecta auditory epithelium in skates increases from 500 to more than 3,000 postembryonically, but during the same time period the number of neurons innervating the epithelium changes by a much smaller amount, if at all. Morphometric analyses of the peripheral terminal arbors of these neurons demonstrate that the arbors expand in area through intussusceptive growth, so that each neuron contacts more hair cells as the epithelium grows by appositional addition of new hair cells at its outer edge. The synaptic contacts that these neurons make with hair cells may not be permanent. Many of the neurons that innervate the growing macula appear to shift their terminal arbors, breaking synaptic contacts with older hair cells in the center of the sensory epithelium as they branch to form new contacts with younger hair cells that are located in the periphery of the epithelium. Over 80% of the terminal branches of these auditory neurons are directed toward the outer edge of the macula, the site where new hair cells are produced. This suggests that the growth cones of these continually growing neurons are guided to newly produced hair cells by an active attraction mechanism.