Rapid Resetting Research Articles

Current-Controllable and Reversible Multi-Resistance-State Based on Domain Wall Number Transition in 2D Ferromagnet Fe3GeTe2.

Controlling the multi-state switching is significantly essential for the extensive utilization of 2D ferromagnet in magnetic racetrack memories, topological devices, and neuromorphic computing devices. The development of all-electric functional nanodevices with multi-state switching and a rapid reset remains challenging. Herein, to imitate the potentiation and depression process of biological synapses, a full-current strategy is unprecedently established by the controllable resistance-state switching originating from the spin configuration rearrangement by domain wall number modulation in Fe3GeTe2. In particular, a strong correlation is uncovered in the reduction of domain wall number with the corresponding resistance decreasing by in-situ Lorentz transmission electron microscopy. Interestingly, the magnetic state is reversed instantly to the multi-domain wall state under a single pulse current with a higher amplitude, attributed to the rapid thermal demagnetization by simulation. Based on the neuromorphic computing system with full-current-driven artificial Fe3GeTe2 synapses with multi-state switching, a high accuracy of ≈91% is achieved in the handwriting image recognition pattern. The results identify 2D ferromagnet as an intriguing candidate for future advanced neuromorphic spintronics.

Germ cell-specific eIF4E1b regulates maternal mRNA translation to ensure zygotic genome activation.

Translation of maternal mRNAs is detected before transcription of zygotic genes and is essential for mammalian embryo development. How certain maternal mRNAs are selected for translation instead of degradation and how this burst of translation affects zygotic genome activation remain unknown. Using gene-edited mice, we document that the oocyte-specific eukaryotic translation initiation factor 4E family member 1b (eIF4E1b) is the regulator of maternal mRNA expression that ensures subsequent reprogramming of the zygotic genome. In oocytes, eIF4E1b binds to transcripts encoding translation machinery proteins, chromatin remodelers, and reprogramming factors to promote their translation in zygotes and protect them from degradation. The protein products are thought to establish an open chromatin landscape in one-cell zygotes to enable transcription of genes required for cleavage stage development. Our results define a program for rapid resetting of the zygotic epigenome that is regulated by maternal mRNA expression and provide new insights into the mammalian maternal-to-zygotic transition.

Rapid and unconditional parametric reset protocol for tunable superconducting qubits

Qubit initialization is a critical task in quantum computation and communication. Extensive efforts have been made to achieve this with high speed, efficiency and scalability. However, previous approaches have either been measurement-based and required fast feedback, suffered from crosstalk or required sophisticated calibration. Here, we report a fast and high-fidelity reset scheme, avoiding the issues above without any additional chip architecture. By modulating the flux through a transmon qubit, we realize a swap between the qubit and its readout resonator that suppresses the excited state population to 0.08% ± 0.08% within 34 ns (284 ns if photon depletion of the resonator is required). Furthermore, our approach (i) can achieve effective second excited state depletion, (ii) has negligible effects on neighboring qubits, and (iii) offers a way to entangle the qubit with an itinerant single photon, useful in quantum communication applications.

Positional Information and Stem Cells Combine to Result in Planarian Regeneration.

The capacity for regeneration is broad in the animal kingdom. Planarians are flatworms that can regenerate any missing body part and their regenerative powers have combined with ease of experimentation to make them a classic regeneration model for more than a century. Pluripotent stem cells called neoblasts generate missing planarian tissues. Fate specification happens in the neoblasts, and this can occur in response to regeneration instructions in the form of positional information. Fate specification can lead to differentiating cells in single steps rather than requiring a long lineage hierarchy. Planarians display constitutive expression of positional information from muscle cells, which is required for patterned maintenance of tissues in tissue turnover. Amputation leads to the rapid resetting of positional information in a process triggered by wound signaling and the resetting of positional information is required for regeneration. These findings suggest a model for planarian regeneration in which adult positional information resets after injury to regulate stem cells to bring about the replacement of missing parts.

Scalable hyperfine qubit state detection via electron shelving in the 2D5/2 and 2F7/2 manifolds in 171Yb+

Qubits encoded in hyperfine states of trapped ions are ideal for quantum computation given their long lifetimes and low sensitivity to magnetic fields, yet they suffer from off-resonant scattering during detection, often limiting their measurement fidelity. In ${}^{171}{\text{Yb}}^{+}$ this is exacerbated by a low fluorescence yield, which leads to a need for complex and expensive hardware, a problematic bottleneck especially when scaling up the number of qubits. We demonstrate a detection routine based on electron shelving to address this issue in ${}^{171}{\text{Yb}}^{+}$ and achieve a $5.6\ifmmode\times\else\texttimes\fi{}$ reduction in single-ion detection error on an avalanche photodiode to $1.8(2)\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}3}$ in a 100 $\ensuremath{\mu}\mathrm{s}$ detection period and a $4.3\ifmmode\times\else\texttimes\fi{}$ error reduction on an electron multiplying CCD camera with $7.7(2)\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}3}$ error in 400 $\ensuremath{\mu}\mathrm{s}$. We further improve the characterization of a repump transition at 760 nm to enable a more rapid reset of the auxiliary ${}^{2}{F}_{7/2}$ states populated after shelving. Finally, we examine the detection fidelity limit using the long-lived ${}^{2}{F}_{7/2}$ state, achieving further $300\ifmmode\times\else\texttimes\fi{}$ and $12\ifmmode\times\else\texttimes\fi{}$ reductions in error to $6(7)\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}6}$ and $6.3(3)\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}4}$ in 1 ms on the respective detectors. While shelving-rate limited in our setup, we suggest various techniques to realize this detection method at speeds compatible with quantum information processing, providing a pathway to ultrahigh-fidelity detection in ${}^{171}{\text{Yb}}^{+}$.

The locus coeruleus on stress: Bridging the translational gap

AbstractBackgroundLoss of locus coeruleus (LC) neurons is one of the earliest and most pronounced features of Alzheimer's disease (AD). Stress is one of the most powerful activators of LC activity, and a risk factor for the development of AD. However, the small size of the LC, and its location deep in the brainstem, make systematic investigations of this nucleus extremely challenging. Here, we develop translational tools that can link animal and human research to study how stress impacts the LC, and how this might contribute to the risk of developing AD.MethodsFirst, to study how the LC drives functional changes across brain networks, we developed a new chemo‐connectomic approach that combines DREADD/chemogenetic manipulation of the LC with resting‐state fMRI analyses (rs‐fMRI) in mice. Second, we employ pupillometry – a clinically widespread and readily available tool – together with optogenetic LC stimulation to assess the impact of various, physiologically relevant LC stimulation paradigms on pupil diameter. Third, we leverage novel genetic tools to perform multi‐omic molecular screens in the mouse LC, to analyze sex differences and stress‐induced molecular changes.ResultsChemo‐connectomics shows that strong LC activation triggers a rapid network reset and potently activates saliency networks, thus revealing striking similarities between LC activation in the mouse and stress‐related rs‐fMRI data in humans. Pupillometry shows that optogenetic LC stimulation faithfully triggers pupil dilation, a response that scales with stimulation intensity and frequency. Molecular screening reveals – for the first time – the impact of acute stress on the transcriptional and translational landscape of the locus coeruleus, while sex differences appear to be subtle.ConclusionIn combination, these approaches allow us to dissect LC function from molecules to circuits to brain‐wide networks. While pupillometry provides a simple and clinically available window into LC function, chemo‐connectomics holds the potential to identify noradrenaline‐based network signatures that can identify high‐risk populations (or specific subgroups) of AD patients using rs‐fMRI. Finally, the ability to perform high‐throughput molecular screens in mice allows us to explore stress‐induced changes in LC function, and link these changes to neurodegenerative disease processes.

Rapid Jetlag Resetting of Behavioral, Physiological, and Molecular Rhythms in Proestrous Female Mice.

A gradual adaptation to a shifted light-dark (LD) cycle is a key element of the circadian clock system and believed to be controlled by the central circadian pacemaker, the suprachiasmatic nucleus (SCN). Endocrine factors have a strong influence on the regulation of the circadian clock network and alter acute photic responses of the SCN clock. In females, endocrine function depends on the stage of the ovarian cycle. So far, however, little is known about the effect of the estrous cycle on behavioral and molecular responses to shifts in the LD rhythm. Based on this, we investigated whether estrous state affects the kinetics of phase shift during jetlag in behavior, physiology, and molecular clock rhythms in the SCN and in peripheral tissues. Female mice exposed to an advanced LD phase at proestrous or metestrous showed different phase-shift kinetics, with proestrous females displaying accelerated adaptation in behavior and physiology. Constant darkness release experiments suggest that these fast phase shifts do not reflect resetting of the SCN pacemaker. Explant experiments on SCN, adrenal gland, and uterus confirmed this finding with proestrous females showing significantly faster clock phase shifts in peripheral tissues compared with the SCN. Together, these findings provide strong evidence for an accelerated adaptation of proestrous compared with metestrous females to new LD conditions that is accompanied by rapid behavioral, physiological, and molecular rhythm resetting. Not only do these findings open up a new avenue to understand the effect of estrous cycle on the clock network under changing environmental conditions but also imply a greater susceptibility in proestrous females.

Transcriptome analysis of primary podocytes reveals novel calcium regulated regulatory networks.

Podocytes are pivotal in establishing the selective permeability of the glomerular filtration barrier. Recently, we showed that an increase of the intracellular calcium ion concentration [Ca2+ ] causes a rapid and transient actin reset (CaAR) measurable through live imaging microscopy using lifeact-mCherry as an actin dye in different cell types including the podocyte. This and other studies show the critical role [Ca2+ ] and the actin cytoskeleton play in podocyte homeostasis. To further investigate the role of [Ca2+ ] and the actin cytoskeleton in podocytes, we used a double fluorescent reporter mouse model to establish a primary podocyte culture system. We treated these podocytes temporarily with a Calcium Ionophore and facultatively with Latrunculin A, an inhibitor of actin polymerization. Unbiased genome wide transcriptional analysis identified a transcriptional response in podocytes to elevated [Ca2+ ] levels, affecting mRNA levels of PDGF-BB, RICTOR, and MIR17HG as mediators of Ca2+ -signaling. Comparison of the ex vivo transcriptional response from the primary podocyte culture with glomerular transcripts across a wide spectrum of CKD disease confirmed co-regulation of transcript sets, establishing the disease relevance of the model system. Our findings demonstrate novel [Ca2+ ] regulated gene networks in podocytes deepening our understanding of podocyte biology and disease.

The rapid resetting of the Ca isotopic signatures of calcite at ambient temperature during its congruent dissolution, precipitation, and at equilibrium

This study provides direct experimental evidence of the resetting of the calcium (Ca) isotope signatures of calcite in the presence of an aqueous fluid during its congruent dissolution, precipitation, and at equilibrium at ambient temperatures over week-long timescales. Batch reactor experiments were performed at 25 °C in aqueous NaCl solutions; air or CO2-gas mixtures were bubbled through this fluid to fix pH. During congruent calcite dissolution, the fluid became enriched in isotopically heavy Ca, and the Ca isotope composition continued to become heavier after the fluid attained bulk chemical equilibrium with the mineral; the δ44/42Ca composition of the fluid was up to 0.8‰ higher than the dissolving calcite at the end of the dissolution experiments. Calcite precipitation was provoked by increasing the reactor fluid pH after chemical equilibrium had been attained via dissolution. Rayleigh isotope fractionation effects were observed immediately after the pH was increased and rapid calcite precipitation occurred. However, isotopic exchange continued after the system chemically equilibrated, eradicating this Rayleigh signal. Taken together, these observations 1) confirm dynamic mineral-fluid equilibrium (i.e. dissolution and precipitation occur at equal, non-zero rates at equilibrium), and 2) indicate that isotopic compositions of calcite can readily equilibrate even when this mineral is in bulk chemical equilibrium with its coexisting fluid. This latter observation suggests the preservation of paleo-environmental isotopic signatures in calcite may require a combination of the isolation of the fluid-mineral system from external chemical input and/or the existence of a yet to be defined calcite dissolution/precipitation inhibition mechanism.

The Many Roles of Ubiquitin in NF-κB Signaling.

The nuclear factor κB (NF-κB) signaling pathway ubiquitously controls cell growth and survival in basic conditions as well as rapid resetting of cellular functions following environment changes or pathogenic insults. Moreover, its deregulation is frequently observed during cell transformation, chronic inflammation or autoimmunity. Understanding how it is properly regulated therefore is a prerequisite to managing these adverse situations. Over the last years evidence has accumulated showing that ubiquitination is a key process in NF-κB activation and its resolution. Here, we examine the various functions of ubiquitin in NF-κB signaling and more specifically, how it controls signal transduction at the molecular level and impacts in vivo on NF-κB regulated cellular processes.

Rapid resetting of human peripheral clocks by phototherapy during simulated night shift work

A majority of night shift workers have their circadian rhythms misaligned to their atypical schedule. While bright light exposure at night is known to reset the human central circadian clock, the behavior of peripheral clocks under conditions of shift work is more elusive. The aim of the present study was to quantify the resetting effects of bright light exposure on both central (plasma cortisol and melatonin) and peripheral clocks markers (clock gene expression in peripheral blood mononuclear cells, PBMCs) in subjects living at night. Eighteen healthy subjects were enrolled to either a control (dim light) or a bright light group. Blood was sampled at baseline and on the 4th day of simulated night shift. In response to a night-oriented schedule, the phase of PER1 and BMAL1 rhythms in PBMCs was delayed by ~2.5–3 h (P < 0.05), while no shift was observed for the other clock genes and the central markers. Three cycles of 8-h bright light induced significant phase delays (P < 0.05) of ~7–9 h for central and peripheral markers, except BMAL1 (advanced by +5h29; P < 0.05). Here, we demonstrate in humans a lack of peripheral clock adaptation under a night-oriented schedule and a rapid resetting effect of nocturnal bright light exposure on peripheral clocks.

Rapid Recovery Gene Downregulation during Excess-Light Stress and Recovery in Arabidopsis.

Stress recovery may prove to be a promising approach to increase plant performance and, theoretically, mRNA instability may facilitate faster recovery. Transcriptome (RNA-seq, qPCR, sRNA-seq, and PARE) and methylome profiling during repeated excess-light stress and recovery was performed at intervals as short as 3 min. We demonstrate that 87% of the stress-upregulated mRNAs analyzed exhibit very rapid recovery. For instance, HSP101 abundance declined 2-fold every 5.1 min. We term this phenomenon rapid recovery gene downregulation (RRGD), whereby mRNA abundance rapidly decreases promoting transcriptome resetting. Decay constants (k) were modeled using two strategies, linear and nonlinear least squares regressions, with the latter accounting for both transcription and degradation. This revealed extremely short half-lives ranging from 2.7 to 60.0 min for 222 genes. Ribosome footprinting using degradome data demonstrated RRGD loci undergo cotranslational decay and identified changes in the ribosome stalling index during stress and recovery. However, small RNAs and 5'-3' RNA decay were not essential for recovery of the transcripts examined, nor were any of the six excess light-associated methylome changes. We observed recovery-specific gene expression networks upon return to favorable conditions and six transcriptional memory types. In summary, rapid transcriptome resetting is reported in the context of active recovery and cellular memory.

Calcium-mediated actin reset (CaAR) mediates acute cell adaptations.

Actin has well established functions in cellular morphogenesis. However, it is not well understood how the various actin assemblies in a cell are kept in a dynamic equilibrium, in particular when cells have to respond to acute signals. Here, we characterize a rapid and transient actin reset in response to increased intracellular calcium levels. Within seconds of calcium influx, the formin INF2 stimulates filament polymerization at the endoplasmic reticulum (ER), while cortical actin is disassembled. The reaction is then reversed within a few minutes. This Calcium-mediated actin reset (CaAR) occurs in a wide range of mammalian cell types and in response to many physiological cues. CaAR leads to transient immobilization of organelles, drives reorganization of actin during cell cortex repair, cell spreading and wound healing, and induces long-lasting changes in gene expression. Our findings suggest that CaAR acts as fundamental facilitator of cellular adaptations in response to acute signals and stress.

The effect of L-carnosine on the circadian resetting of clock genes in the heart of rats.

It is reported that the circadian timing system may be included in the mechanism by which L-carnosine (Car) affects multiple physiological alterations including blood glucose, cardiovascular functions etc. However, it is not clear whether Car would affect the circadian rhythm of clock genes in the heart and what is the possible mechanism underlying. To clarify these issues, we compared the effects of Car on the expression of circadian genes in the heart of normal and vagotomized rats under control and jet lag conditions. The normal and vagotomized (va) male Wistar rats were divided into three groups respectively. The control and va-Control groups (fed with regular chow) were sampled before the reversal of LD cycle and feeding schedule (day 0). The normal and va-Normal resetting groups (fed with regular chow) as well as the Car and va-Car resetting groups (fed with Car-containing diet) were sampled on day 3 and day 5 after the experimental jet lag. Car-feeding obviously enhanced the resetting rates of clock genes (Bmal1, Dec1, Cry1) in the heart of normal rats after the experimental jet lag. The unilateral surgical vagotomy didn't alter the diurnal expression patterns and resetting rates of the examined clock genes in normal diet feeding rats. In contrast, it abolished the Car-induced rapid resetting of the clock genes in the heart. Therefore, Car feeding plays a positive role in the circadian resynchronization of the heart clock, which is underlied by the autonomic nervous system.

Fast measurement of binding kinetics with dual slope SPR microchips

We demonstrate a new dual slope SPR technique that is ten-fold faster than the conventional step-response method. The new scheme utilizes rapid slope-based measurements followed by rapid reset, and it separates association and dissociation half reaction measurements at two separate sites inside a dual-chamber PDMS microfluidic chip. For a model CAII-ABS test system, the association and dissociation slopes were measured in 30 seconds compared to 5 minutes for step-response. The values of k(a) and k(d) calculated from the slope method are 3.66 ± 0.19 × 10(3) M(-1) s(-1) and 4.83 ± 0.17 × 10(-2) s(-1), respectively, matching well with step-response values while facilitating ~10 to 15 fold faster detection and quantification.

Experimental Jetlag Disrupts Circadian Clock Genes But Improves Performance in Racehorses After Light-Dependent Rapid Resetting of Neuroendocrine Systems and the Rest-Activity Cycle

Abrupt alterations in the 24-h light : dark cycle, such as those resulting from transmeridian air travel, disrupt circadian biological rhythms in humans with detrimental consequences on cognitive and physical performance. In the present study, a jetlag-simulated phase shift in photoperiod temporally impaired circadian peaks of peripheral clock gene expression in racehorses but acutely enhanced athletic performance without causing stress. Indices of aerobic and anaerobic capacities were significantly increased by a phase-advance, enabling prolonged physical activity before fatigue occurred. This was accompanied by rapid re-entrainment of the molecular clockwork and the circadian pattern of melatonin, with no disturbance of the adrenal cortical axis, but a timely rise in prolactin, which is a hormone known to target organs critical for physical performance. Subsequent studies showed that, unlike the circadian pattern of melatonin, and in contrast to other species, the daily rhythm of locomotor activity was completely eliminated under constant darkness, but it was restored immediately upon the reintroduction of a light : dark cycle. Resetting of the rhythm of locomotion was remarkably fast, revealing a rapid mechanism of adaptation and a species dependency on light exposure for the expression of daily diurnal activity. These results show that horses are exquisitely sensitive to sudden changes in photoperiod and that, unlike humans, can benefit from them; this appears to arise from powerful effects of light underlying a fast and advantageous process of adjustment to the phase shift.

Expression pattern of clock under acute phase-delay of the light/dark cycle in the chicken pineal model

Shift workers have a higher risk of metabolic syndrome, a condition that also develops in mice carrying mutation in their circadian clock gene clock. To collect more data on the transcriptional changes of clock under phase-shifted light/dark LD conditions, we examined the 24 h patterns of clock mRNA expression in vivo and in vitro in chickens exposed acutely to a reversed LD (DL) cycle. Under controlled LD conditions (lights on at 6:00, lights off at 20:00), clock mRNA expression peaked in vivo at 2:00 (Zeitgeber Time 20, ZT20) and in vitro at 22:00 (ZT16). Even higher mRNA contents were measured in the first cycle of in vivo DL conditions between 22:00 and 6:00 (lights at night), but in the second cycle by 2:00, lower mRNA contents were detected than the control peak values seen at this time point. Furthermore, no alterations were found in vitro in clock mRNA content during the first 12 h of DL conditions (lights at night). The differences seen between the first and the second DL cycles in vivo and between the in vivo and in vitro data for the first DL cycle support the idea that neurohumoral signals perturbed by a phase-delayed light–dark cycle may also play a role in the in vivo rapid transcriptional resetting of the circadian clock in the chicken pineal model.

Towards practices favourable to plant diversity in hybrid poplar plantations

Much research effort is being devoted to developing forest management practices with limited impacts on biodiversity. While the impact of poplar Populus sp. plantations on biodiversity is relatively well-known at the landscape scale, the impact of alternative management practices at the plantation scale has received much less attention. Yet biodiversity is likely to be impacted by the choice of the poplar clone, stem density at plantation, type and duration of the understory control, and age at which the poplars are harvested. In this study, we investigated the impact of these factors on herbaceous plant communities with data from plant surveys conducted in 85 young (2–5 years) and 96 mature (11–17 years) hybrid poplar high-forest plantations in northern France. On average, ruderal or generalist plants contributed to 40.5% of the plot species richness; tall herbs (60.2%), forest (26%) and meadow plants (13.8%) contributed to the remaining 59.5% more specialised species. Soil moisture and soil nitrogen were major determinants of plant communities: wet soils were favourable to tall herbs, while meadow and forest species preferred moist soils; a significantly lower diversity of the three species groups was reported in the nutrient richer soils (in mature plantations only for forest plants). Mean species richness decreased with plantation age except for forest species. Plant communities in young plantations showed little differences in composition according to the type of understory control (chemical, mechanical or both). The development of a shrubby layer in mature plantations was restricted to the drier soils and was detrimental to both meadow plants and tall herb species. Effects of previous land use on forest and tall herb species were found only in young plantations, suggesting a rapid reset of plant communities for these two groups. This may not be the case for meadow species as the influence of previous land use was significant in mature plantations only. Finally, clone type and stem density at plantation had no significant impact on plant communities. Adjusting age at which the poplars are harvested seems the only effective way to drive plant communities in high-forest poplar plantations: delaying poplar harvest (probably beyond 15–20 years) would benefit forest plants, while advancing poplar harvest (about 10 years) would benefit tall herbs, especially in wet soil conditions.

The FEAR network

Mitosis is governed by the oscillation of cyclin dependent kinase (CDK) activity and ubiquitin-dependent proteolysis. Entry into mitosis is initiated by mitotic cyclin-CDK activation. Anaphase onset occurs upon activation of the Anaphase Promoting Complex/Cyclosome (APC/C), a ubiquitin ligase that promotes the destruction of the anaphase inhibitor Securin. Destruction of Securin initiates chromosome segregation by activation of the protease Separase, allowing it to cleave a subunit of the cohesin complexes that hold the duplicated sister chromatids together. Upon completion of nuclear division cells exit from mitosis, a process defined by the inactivation of CDKs, disassembly of the mitotic spindle, and cytokinesis. In the budding yeast S. cerevisiae, a signaling network known as the FEAR network is critical to ensure accurate anaphase chromosome segregation and the integration of this process with other anaphase events. Here, we summarize what is known about the regulation and function of the FEAR network in budding yeast and discuss the potential for conserved FEAR network functions in other eukaryotes.

An investigation of vitamin B12 deficiency in elderly inpatients in neurology department

To investigate the status of vitamin B12 deficiency in elderly inpatients in the department of neurology. A total number of 827 patients in the department of neurology of Shanghai Punan hospital, from March 2007 to July 2008, were employed in the present study. They were 60 years or older, and the average age was 77.1+/-7.5 years old. All the patients were diagnosed with no severe hepatic or renal dysfunction, without any usage of vitamin B12 during the previous 3 months before the detection. The levels of serum vitamin B12, folate and homocysteine (Hcy) were evaluated. The patients with vitamin B12 deficiency were screened. The resulting symptoms, positive signs of neurological examination, and the neuroelectricphysiological results were compared between patients with or without vitamin B12 deficiency. Vitamin B12 deficiency was found in 163 patients (19.71% of the total patients), and was more prevalent in female than in male patients, also with increased incidences with aging. Patients with low levels of serum vitamin B12 exhibited higher rate of gastrointestinal diseases, while only 9.82% of the vitamin B12 deficient patients had megaloblastic anemia. Symptoms of vitamin B12 deficiency included unsteadily walking in the darkness and hypopallesthesia, and some chronic diseases such as cerebral ischemia, hypertension, Parkinson's disease (Parkinsonism), diabetes mellitus and coronary heart disease. Most of the vitamin B12 deficient patients had neuroelectricphysiological abnormalities. Vitamin B12 deficiency is remarkably common in elderly patients in neurology department, with various and atypical clinical manifestations, and the neurological symptoms are more common than megaloblastic anemia symptoms.