The first Ukrainian translation of J. Thomasius’ work “Nucleus disputationis de plagio literario maxime theoreticus, thesibus paucis & brevibus comprehensus”.

There is a paucity of treatment options for cognitively normal individuals with drug resistant genetic generalized epilepsy. Centromedian nucleus of the thalamus deep brain stimulation may be a viable treatment for GGE. Here, we present the case of a 27-year-old cognitively normal woman with drug resistant GGE, with childhood onset. Seizure semiology are absence seizures and generalized onset tonic clonic seizures. At baseline she had 4–8 GTC seizures per month and weekly absence seizures despite three antiseizure medications and vagus (...) nerve stimulation. A multidisciplinary committee recommended off-label use of CM DBS in this patient. Over 12-months of CM DBS she had two GTC seizure days, which were in the setting of medication withdrawal and illness, and no GTC seizures in the last 6 months. There was no significant change in the burden of absence seizures. Presently, just two studies clearly document CM DBS in cognitively normal individuals with GGE or idiopathic generalized epilepsy [in contrast to studies of cognitively impaired individuals with developmental and epileptic encephalopathies ]. Our results suggest that CM DBS can be an effective treatment for cognitively normal individuals with GGE and underscore the need for prospective studies of CM DBS. (shrink)

Deep Brain Stimulation (DBS) is an effective treatment for advanced Parkinson’s disease. However, identifying stimulation parameters, such as contact and current amplitudes, is time-consuming based on trial and error. Directional leads add more stimulation options and render this process more challenging with a higher workload for neurologists and more discomfort for patients. In this study, a sweet spot-guided algorithm was developed that automatically suggested stimulation parameters. These suggestions were retrospectively compared to clinical monopolar reviews. A cohort of 24 Parkinson’s disease (...) patients underwent bilateral DBS implantation in the subthalamic nucleus at our center. First, the DBS’ leads were reconstructed with the open-source toolbox Lead-DBS. Second, a sweet spot for rigidity reduction was set as the desired stimulation target for programming. This sweet spot and estimations of the volume of tissue activated were used to suggest (i) the best lead level, (ii) the best contact, and (iii) the effect thresholds for full therapeutic effect for each contact. To assess these sweet spot-guided suggestions, the clinical monopolar reviews were considered as ground truth. In addition, the sweet spot-guided suggestions for best lead level and best contact were compared against reconstruction-guided suggestions, which considered the lead location with respect to the subthalamic nucleus. Finally, a graphical user interface was developed as an add-on to Lead-DBS and is publicly available. With the interface, suggestions for all contacts of a lead can be generated in a few seconds. The accuracy for suggesting the best out of four lead levels was 56%. These sweet spot-guided suggestions were not significantly better than reconstruction-guided suggestions (p = 0.3). The accuracy for suggesting the best out of eight contacts was 41%. These sweet spot-guided suggestions were significantly better than reconstruction-guided suggestions (p < 0.001). The sweet spot-guided suggestions of each contact’s effect threshold had a mean error of 1.2 mA. On an individual lead level, the suggestions can vary more with mean errors ranging from 0.3 to 4.8 mA. Further analysis is warranted to improve the sweet spot-guided suggestions and to account for more symptoms and stimulation-induced side effects. (shrink)

Aggressive behavior is instinctively driven behavior that helps animals to survive and reproduce and is closely related to multiple behavioral and physiological processes. The dorsal raphe nucleus (DRN) is an evolutionarily conserved midbrain structure that regulates aggressive behavior by integrating diverse brain inputs. The DRN consists predominantly of serotonergic (5‐HT:5‐hydroxytryptamine) neurons and decreased 5‐HT activity was classically thought to increase aggression. However, recent studies challenge this 5‐HT deficiency model, revealing a more complex role for the DRN 5‐HT system in (...) aggression. Furthermore, emerging evidence has shown that non‐5‐HT populations in the DRN and specific neural circuits contribute to the escalation of aggressive behavior. This review argues that the DRN serves as a multifaceted modulator of aggression, acting not only via 5‐HT but also via other neurotransmitters and neural pathways, as well as different subsets of 5‐HT neurons. In addition, we discuss the contribution of DRN neurons in the behavioral and physiological aspects implicated in aggressive behavior, such as arousal, reward, and impulsivity, to further our understanding of DRN‐mediated aggression modulation. (shrink)

The origin of mitosis and the nuclear envelope were the pivotal processes in the evolutionary origin of the nucleus; they probably occurred in a wall‐less mutant bacterium that evolved a cytoskeleton and phagocytosis about 1500 million years ago. Principles of intracellular coevolution clarify their origin, as well as that of nucleosomes, spliceosomes, and the evolution of genome size.

Dr Seuren's study deals with the problem of presenting an adequate model of grammatical description. The model he proposes conforms in its main outlines to the transformational generative grammar established by Chomsky, but differs in important respects. These mainly affect that part of Chomsky's syntactic component known as the 'base', which generates basic or 'deep' structures. In the model of the base proposed here two main constituents are distinguished for every deep structure representation of a sentence, vis-a-vis the operators and (...) the nucleus. The deep structure of a sentence is thus seen to be very similar to the logical structure of a proposition. The arguments given in support of this analysis are based on mainly on considerations of simplicity and semantic adequacy. (shrink)

Aggleton & Brown propose that familiarity-based recognition depends on a perirhinal-medial dorsal thalamic system. However, connections between these structures are sparse or absent. In contrast, the perirhinal cortex is connected to midline/intralaminar nuclei. In a human, a lesion in this thalamic domain, sparing the medial dorsal nucleus, impaired familiarity-based recognition while sparing recollective-based recognition. It is thus more likely that the intralaminar/midline nuclei are involved in recognition.

Deep brain stimulation of the subthalamic nucleus is a clinically effective tool for treating medically refractory Parkinson’s disease, but its neural mechanisms remain debated. Previous work has demonstrated that STN DBS results in evoked potentials in the primary motor cortex, suggesting that modulation of cortical physiology may be involved in its therapeutic effects. Due to technical challenges presented by high-amplitude DBS artifacts, these EPs are often measured in response to low-frequency stimulation, which is generally ineffective at PD symptom management. (...) This study aims to characterize STN-to-cortex EPs seen during clinically relevant high-frequency STN DBS for PD. Intraoperatively, we applied STN DBS to 6 PD patients while recording electrocorticography from an electrode strip over the ipsilateral central sulcus. Using recently published techniques, we removed large stimulation artifacts to enable quantification of STN-to-cortex EPs. Two cortical EPs were observed – one synchronized with DBS onset and persisting during ongoing stimulation, and one immediately following DBS offset, here termed the “start” and the “end” EPs respectively. The start EP is, to our knowledge, the first long-latency cortical EP reported during ongoing high-frequency DBS. The start and end EPs differ in magnitude and latency, and the end, but not the start, EP magnitude has a significant relationship to ongoing high gamma power during the EP. These contrasts may suggest mechanistic or circuit differences in EP production during the two time periods. This represents a potential framework for relating DBS clinical efficacy to the effects of a variety of stimulation parameters on EPs. (shrink)

Mitotic recombination is a repair process which is known to repair double strand breaks and to fill double‐strand gaps by copying a homologous sequence. Meiotic recombination is a process of heteroduplex formation which sometimes generates crossovers. Evidence is presented that the later stages of meiotic recombination have some characteristics of mitotic repair recombination, leading to the conclusion that mismatch repair may be a recombinogenic repair process. The evidence suggests that the recombinational repair process generates hetero‐duplex bubbles which can move. Some (...) bubbles become crossovers. Others cease to exist, perhaps because topoisomerase activity breaks them down. (shrink)

Parkinson´s disease (PD) is a neurodegenerative disorder characterized by motor symptoms following dopaminergic depletion in the substantia nigra. Besides motor impairments however, several non-motor detriments can have the potential to considerably impact subjectively perceived quality of life in patients. Particularly emotion recognition of facial expressions has been shown to be affected in PD, and especially the perception of negative emotions like fear, anger or disgust is impaired. While emotion processing generally refers to automatic implicit as well as conscious explicit processing, (...) the focus of most previous studies in PD was on explicit recognition of emotions only, while largely ignoring implicit processing deficits. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is widely accepted as therapeutic measure in the treatment of PD and has been shown to advantageously influence motor problems. Among various concomitant non-motor effects of STN-DBS, modulation of facial emotion recognition under subthalamic stimulation has been investigated in previous studies with rather heterogeneous results. While there seems to be consensus regarding the processing of disgust which significantly deteriorates under STN stimulation, findings concerning emotions like fear or happiness report heterogeneous data and seem to depend on various experimental settings and measurements. In the present review, we summarized previous investigations focusing on STN-DBS influence on recognition of facial emotional expressions in patients suffering from PD. In a first step, we provide a synopsis of disturbances and problems in facial emotion processing observed in patients with PD. Secondly, we present findings of STN-DBS influence on facial emotion recognition and especially highlight different impacts of stimulation on implicit and explicit emotional processing. (shrink)

The origin of the eukaryotic cell nucleus and the selective forces that drove its evolution remain unknown and are a matter of controversy. Autogenous models state that both the nucleus and endoplasmic reticulum (ER) derived from the invagination of the plasma membrane, but most of them do not advance clear selective forces for this process. Alternative models proposing an endosymbiotic origin of the nucleus fail to provide a pathway fully compatible with our knowledge of cell biology. We (...) propose here an evolutionary scenario that reconciles both an ancestral endosymbiotic origin of the eukaryotic nucleus (endosymbiosis of a methanogenic archaeon within a fermentative myxobacterium) with an autogenous generation of the contemporary nuclear membrane and ER from the bacterial membrane. We specifically state two selective forces that operated sequentially during its evolution: (1) metabolic compartmentation to avoid deleterious co‐existence of anabolic (autotrophic synthesis by the methanogen) and catabolic (fermentation by the myxobacterium) pathways in the cell, and (2) avoidance of aberrant protein synthesis due to intron spreading in the ancient archaeal genome following mitochondrial acquisition and loss of methanogenesis. BioEssays 28: 525–533, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Bosbach and Riečan states on residuated lattices both are generalizations of probability measures on Boolean algebras. Just from the observation that both of them can be defined by using the canonical structure of the standard MV-algebra on the unit interval [0, 1], generalized Riečan states and two types of generalized Bosbach states on residuated lattices were recently introduced by Georgescu and Mureşan through replacing the standard MV-algebra with arbitrary residuated lattices as codomains. In the present paper, the Glivenko theorem is (...) first extended to residuated lattices with a nucleus, which gives several necessary and sufficient conditions for the underlying nucleus to be a residuated lattice homomorphism. Then it is proved that every generalized Bosbach state (of type I, or of type II) compatible with the nucleus on a nucleus-based-Glivenko residuated lattice is uniquely determined by its restriction on the nucleus image of the underlying residuated lattice, and every relatively generalized Riečan state compatible with the double relative negation on an arbitrary residuated lattice is uniquely determined by its restriction on the double relative negation image of the residuated lattice. Our results indicate that many-valued probability theory compatible with nuclei on residuated lattices reduces in essence to probability theory on algebras of fixpoints of the underlying nuclei. (shrink)

BackgroundThe cognitive outcomes induced by subthalamic nucleus deep brain stimulation (STN-DBS) remain unclear, especially in PD patients with mild cognitive impairment (MCI). This study explored the cognitive effects of STN-DBS in PD patients with MCI.MethodsThis was a retrospective cohort study that included 126 PD patients who underwent STN-DBS; all patients completed cognitive and motor assessments before and at least 6 months after surgery. Cognitive changes were mainly evaluated by the Montreal cognitive assessment (MoCA) scale and the seven specific MoCA (...) domains, including visuospatial/executive function, naming, attention, language, abstract, delayed recall, and orientation. Motor improvement was evaluated by the UPDRS-III. Cognitive changes and motor improvements were compared between PD-MCI and normal cognitive (NC) patients. Logistic regression analyses were performed to explore predictors of post-operative cognitive change.ResultsAt the time of surgery, 61.90% of the included PD patients had MCI. Compared with the PD-MCI group, the PD-NC group had a significantly higher proportion of cases with post-operative cognitive decline during follow-up of up to 36 months (mean 17.34 ± 10.61 months), mainly including in global cognitive function, visuospatial/executive function and attention. Covariate-adjusted binary logistic regression analyses showed that pre-operative global cognitive status was an independent variable for post-operative cognitive decline. We also found that pre-operative cognitive specific function could predict its own decline after STN-DBS, except for the naming and orientation domains.ConclusionPD-MCI patients are at a lower risk of cognitive decline after STN-DBS compared with PD-NC patients. (shrink)

Retrograde plastid‐to‐nucleus signaling plays a central role in coordinating nuclear and plastid gene expression. The gun (genomes uncoupled) mutants of Arabidopsis have been used to demonstrate that Mg‐protoporphyrin (Mg‐Proto) acts as a plastid signal to repress the transcription of nuclear photosynthesis genes.1 It is unclear how Mg‐Proto triggers repression, but several components of this pathway have been recently identified. These include the products of GUN4 and GUN5. GUN5 is the ChlH subunit of Mg‐chelatase, which produces Mg‐Proto, and GUN4 is (...) a regulator of ChlH activity.2 GUN4 might also play a role in photoprotection and in the trafficking of Mg‐Proto. BioEssays 25:631–636, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

The multistep pathway of eukaryotic gene expression involves a series of highly regulated events in the nucleus and cytoplasm. In the nucleus, genes are transcribed into pre‐messenger RNAs which undergo a series of nuclear processing steps. Mature mRNAs are then transported to the cytoplasm, where they are translated into protein and degraded at a rate dictated by transcript‐ and cell‐type‐specific cues. Until recently, these individual nuclear and cytoplasmic events were thought to be primarily regulated by different RNA‐ and (...) DNA‐binding proteins that are localized either only in the nucleus or only the cytoplasm. Here, we describe multifunctional proteins that control both nuclear and cytoplasmic steps of gene expression. One such class of multifunctional proteins (e.g., Bicoid and Y‐box proteins) regulates both transcription and translation whereas another class (e.g., Sex‐lethal) regulates both nuclear RNA processing and translation. Other events controlled by multifunctional proteins include assembly of spliceosome components, spliceosome recycling, RNA editing, cytoplasmic mRNA localization, and cytoplasmic RNA stability. The existence of multifunctional proteins may explain the paradoxical involvement of the nucleus in an RNA surveillance pathway (nonsense‐mediated decay) that detects cytoplasmic signals (premature termination codons). We speculate that shuttling multifunctional proteins serve to efficiently link RNA metabolism in the cytoplasmic and nuclear compartments. BioEssays 23:775–787, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

During evolution, the genomes of eukaryotic cells have undergone major restructuring to meet the new regulatory challenges associated with compartmentalization of the genetic material in the nucleus and the organelles acquired by endosymbiosis (mitochondria and plastids). Restructuring involved the loss of dispensable or redundant genes and the massive translocation of genes from the ancestral organelles to the nucleus. Genomics and bioinformatic data suggest that the process of DNA transfer from organelles to the nucleus still continues, providing raw (...) material for evolutionary tinkering in the nuclear genome. Recent reconstruction of these events in the laboratory has provided a unique tool to observe genome evolution in real time and to study the molecular mechanisms by which plastid genes are converted into functional nuclear genes. Here, we summarize current knowledge about plastid‐to‐nuclear gene transfer in the context of genome evolution and discuss new insights gained from experiments that recapitulate endosymbiotic gene transfer in the laboratory. BioEssays 30:556–566, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Evidence has recently been obtained suggesting that the accumulation of specific endogenous proteins by the nucleus is due both to facilitated transport across the envelope and intranuclear binding. Using recombinant DNA methodology, polypeptide domains containing the signals required for nuclear accumulation have been identified in several karyophilic proteins.

Nuclear proteins are synthesized in the cytoplasm and must subsequently enter the nucleus. Recent experiments indicate some similarities and some differences between protein localization to the nucleus and localization to other organelles.

Changes in the shape and structural organization of the cell nucleus occur during many fundamental processes including development, differentiation and aging. In many of these processes, the cell responds to physical forces by altering gene expression within the nucleus. How the nucleus itself senses and responds to such mechanical cues is not well understood. In addition to these external forces, epigenetic modifications of chromatin structure inside the nucleus could also alter its physical properties. To achieve a (...) better understanding, we need to elucidate the relationship between nuclear structure and material properties. Recently, new approaches have been developed to systematically investigate nuclear mechanical properties. These experiments provide important new insights into the disease mechanism of a growing class of tissue‐specific disorders termed ‘nuclear envelopathies’. Here we review our current understanding of what determines the shape and mechanical properties of the cell nucleus. BioEssays 30:226–236, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

High-spin states in the odd-odd N = Z nucleus Co-54 have been investigated by the fusion-evaporation reaction Si-28(S-32,1 alpha 1p1n)Co-54. Gamma-ray information gathered with the Ge detector array Gammasphere was correlated with evaporated particles detected in the charged particle detector system Microball and a 1 pi neutron detector array. A significantly extended excitation scheme of Co-54 is presented, which includes a candidate for the isospin T = 1, 6(+) state of the 1f(7/2)(-2) multiplet. The results are compared to large-scale (...) shell-model calculations in the fp shell. Effective interactions with and without isospin-breaking terms have been used to probe isospin symmetry and isospin mixing. A quest for deformed high-spin rotational cascades proved negative. This feature is discussed by means of cranking calculations. (shrink)

Two rotational bands have been identified and characterized in the proton-magic N = Z + 1 nucleus Ni-57. These bands complete the systematics of well-and superdeformed rotational bands in the light nickel isotopes starting from doubly magic Ni-56 to Ni-60. High-spin states in Ni-57 have been produced in the fusion-evaporation reaction Si-28(S-32, 2p1n)Ni-57 and studied with the gamma-ray detection array GAMMASPHERE operated in conjunction with detectors for evaporated light charged particles and neutrons. The features of the rotational bands in (...) Ni-57 are compared to those of neighbouring isotopes and interpreted by means of configuration-dependent cranked Nilsson-Strutinsky calculations. The two observed high-spin bands are considered signature partners and assigned to configurations with one 1g(9/2) proton and one 1g(9/2) neutron, resulting in an unambiguous understanding of the energetically favoured signature alpha = -1/2 band but a somewhat less satisfactory description of the signature alpha = +1/2 band. (shrink)

We considered peculiarities of the evolution of a region with sharp boundaries that is filled with a partially ionized plasma and is a part of the volume of a condensed target. The creation of such a region in the near-surface layer of the target can be related to the action of an external impulse symmetric ionizator or to the action of an intense small-extension shock wave on the target surface. We defined the conditions such that their fulfilment during the establishment (...) of the equilibrium between the Coulomb attraction of electrons and ions with atom ionization multiplicity Z* 1 and the kinetic pressure of electrons causes both the compression of this region and its ionization to the state with Z* 2 > Z* 1. The last leads to a further additional compression and ionization. Under these conditions, the spontaneous avalanche-like ionization of atoms of the target to the state of ‘‘bare’’ nuclei occurs synchronously with the avalanche-like metallization and the self-compression of the target. We showed that the avalanche-like ionization and the self-compression of the target happen in the case where the gas of degenerate electrons has drift momentum. If the region with initial ionization has the form of thin spherical layer, the process of avalanche-like ionization and self-compression of the target in this region is accompanied by the accelerated movement of the plasma layer to the target center. One of the reasons for the accelerated movement is the surface tension in a bounded domain of the nonequilibrium plasma layer neutralized by ions of the target. With increase in the velocity of movement of this layer to the target center, the additional self-compression of the system of electrons and nuclei to the state of degenerate electron gas occurs. At the leading edge of the running layer with extremely high electron density which is neutralized by nuclei of the target, the formation of a collapse of the electron--nucleus system proceeds, and the binding energy maximum for the electron--nucleus system shifts from A≈60 to A ≫ 60. This result makes possible the fast synthesis of superheavy nuclei. The decay of the collapse state, a partial restoration of the target structure, its rapid cooling, and the condensation of a part of the products of nuclear reactions happen in the target volume at the trailing edge of the moving plasma layer. Upon such a scanning propagation of the wave with high electron density, all the target substance is involved, step-by-step, to the process of nuclear transformations. At the target center, the moving plasma layer is squeezed with the formation of the state of quasistationary collapse under inertial confinement. Then the collapse state decays irreversibly. (shrink)

Deep brain stimulation of the subthalamic nucleus is an effective treatment for the motor symptoms of movement disorders including Parkinson's Disease. Despite its therapeutic benefits, STN-DBS has been associated with adverse effects on mood and cognition. Specifically, apathy, which is defined as a loss of motivation, has been reported to emerge or to worsen following STN-DBS. However, it is often challenging to disentangle the effects of STN-DBSper sefrom concurrent reduction of dopamine replacement therapy, from underlying PD pathology or from (...) disease progression. To this end, pre-clinical models allow for the dissociation of each of these factors, and to establish neural substrates underlying the emergence of motivational symptoms following STN-DBS. Here, we performed a systematic analysis of rodent studies assessing the effects of STN-DBS on reward seeking, reward motivation and reward consumption across a variety of behavioral paradigms. We find that STN-DBS decreases reward seeking in the majority of experiments, and we outline how design of the behavioral task and DBS parameters can influence experimental outcomes. While an early hypothesis posited that DBS acts as a “functional lesion,” an analysis of lesions and inhibition of the STN revealed no consistent pattern on reward-related behavior. Thus, we discuss alternative mechanisms that could contribute to the amotivational effects of STN-DBS. We also argue that optogenetic-assisted circuit dissection could yield important insight into the effects of the STN on motivated behavior in health and disease. Understanding the mechanisms underlying the effects of STN-DBS on motivated behavior-will be critical for optimizing the clinical application of STN-DBS. (shrink)

Our current work examined the interface between thinking style and emotional experience at both the behavioral and neuropsychological levels. Thirty-nine Chinese participants completed the triad task, and we calculated the rate of individually selected relationship pairings to overall selections to represent their holistic thinking tendencies. In addition, participants in the top one-third of the ratio score were classified into the high holistic thinking group, while those in the bottom one-third of the ratio score were classified into the low holistic thinking (...) group. We used the sensitivity to punishment and sensitivity to reward questionnaire to examine how people elicit positive and negative affective behaviors. Additionally, we examined the volume of the amygdala and nucleus accumbens and their functional connectivity in the resting-state. We found that high holistic thinkers were much less sensitive to rewards than low holistic thinkers. In other words, individuals with high holistic thinking are less likely to pursue behaviors that have positive emotional outcomes. Furthermore, their bilateral nucleus accumbens and right amygdala volumes were smaller than those of low holistic thinkers. Hierarchical regression analysis showed that holistic thinking tendency can negatively predict the volume of the left nucleus accumbens and right amygdala. Finally, resting-state functional connectivity results showed increased functional connectivity FC between left nucleus accumbens and bilateral amygdala in high holistic thinkers. These findings provide emotion-related manifestations of thinking styles at the behavioral and neural levels. (shrink)

The nucleolus is a region of the nucleus with high protein density and it acts as a ribosome factory. The nucleolus contains a distinct region of the genome, the ribosomal RNA gene repeats (rDNA) that supply ribosomal RNA (rRNA) molecules. The rDNA is the most‐abundant gene and occupies a large part of the genome, for example, there are thousands of rDNA copies in the genomes of plant cells. Therefore, it is natural to suppose that the condition of the rDNA, (...) such as its stability, might affect cellular functions. Here I would like to propose a new model regarding the roles of the rDNA and nucleolus. The key point of this model is that they act to preserve genome stability and trigger aging. BioEssays 30:267–272, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Lewis emphasizes the role of theta oscillations in emergent coupling among neural subsystems during emotionally relevant tasks or situations. Here I present some recent data on the relationship of rhythmic neuronal discharge in the supramammillary nucleus and the large-scale theta oscillations in the limbic system which provide support to many of his ideas regarding vertical integration in dynamic systems.

Transport of macromolecules from the nucleus to the cytoplasm is essential for nearly all cellular and developmental events, and when mis‐regulated, is associated with diseases, tumor formation/growth, and cancer progression. Nuclear Envelope (NE)‐budding is a newly appreciated nuclear export pathway for large macromolecular machineries, including those assembled to allow co‐regulation of functionally related components, that bypasses canonical nuclear export through nuclear pores. In this pathway, large macromolecular complexes are enveloped by the inner nuclear membrane, transverse the perinuclear space, and (...) then exit through the outer nuclear membrane to release its contents into the cytoplasm. NE‐budding is a conserved process and shares many features with nuclear egress mechanisms used by herpesviruses. Despite its biological importance and clinical relevance, little is yet known about the regulatory and structural machineries that allow NE‐budding to occur in any system. Here we summarize what is currently known or proposed for this intriguing nuclear export process. (shrink)

In agreement with Behrendt & Young (B&Y), we considered the role of perception disturbances in schizophrenia in our first clinical approaches, using the Bender test with schizophrenic patients. Following this, we reproduced nuclear symptoms of schizophrenia in animal models, showing that perceptual disturbances, acquisition disturbances, and decrease in affective levels can be induced by glutamatergic blockade within the nucleus accumbens septi. Our results link the proposed corticostriatal dysfunction with the thalamocortical disturbances underlying perceptual problems reviewed by B&Y.

Mitochondria are increasingly being recognized as information hubs that sense cellular changes and transmit messages to other cellular components, such as the nucleus, the endoplasmic reticulum (ER), the Golgi apparatus, and lysosomes. Nonetheless, the interaction between mitochondria and the nucleus is of special interest because they both host part of the cellular genome. Thus, the communication between genome‐bearing organelles would likely include gene expression regulation. Multiple nuclear‐encoded proteins have been known to regulate mitochondrial gene expression. On the contrary, (...) no mitochondrial‐encoded factors are known to actively regulate nuclear gene expression. MOTS‐c (mitochondrial open reading frame of the 12S ribosomal RNA type‐c) is a recently identified peptide encoded within the mitochondrial 12S ribosomal RNA gene that has metabolic functions. Notably, MOTS‐c can translocate to the nucleus upon metabolic stress (e.g., glucose restriction and oxidative stress) and directly regulate adaptive nuclear gene expression to promote cellular homeostasis. It is hypothesized that cellular fitness requires the coevolved mitonuclear genomes to coordinate adaptive responses using gene‐encoded factors that cross‐regulate the opposite genome. This suggests that cellular gene expression requires the bipartite split genomes to operate as a unified system, rather than the nucleus being the sole master regulator. (shrink)

From cytological examination, the size and form of the chromosomes in the eukaryotic nucleus are invariant across generations, leading to the expectation that constancy of inheritance likely depends on constancy of the chromosomal DNA molecule conveying the constant phenotype. Indeed, except for rare mutations, major phenotypic traits appear largely without change from generation to generation. Thus, when it was discovered that the inheritance of traits for bacteria, mitochondria and chloroplasts was also constant, it was assumed that chromosomes in those (...) locations were also constant. Such has not turned out to be the case, however; those chromosomes are highly variable in structure. I propose, therefore, that only for the nucleus is there a requirement that a chromosome be “finished” (contain only fully replicated genomes) before it may segregate to daughter cells. This requirement does not apply to the variable chromosomes among chloroplasts, mitochondria and bacteria. BioEssays 29:474–483, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Patients with advanced Alzheimer's disease experience cognitive impairment and physical disabilities in daily life. Currently, there are no treatments available to slow down the course of the disease, and limited treatments exist only to treat symptoms. However, deep brain stimulation of the nucleus basalis of Meynert has been reported to improve cognitive function in individuals with AD. Here, we report the effects of NBM-DBS on cognitive function in a subject with severe AD. An 80-year-old male with severe AD underwent (...) surgery for bilateral NBM-DBS electrode placement. After 10 weeks of stimulation, Mini-Mental State Examination assessment improved from a score of 5 to 9 points, and assessment using the Alzheimer's Disease Assessment Scale–Cognitive Subscale showed a marked reduction in total score from 43 to 33 points, suggesting cognitive benefits from NBM-DBS. The patient's postoperative course was complicated by a subdural effusion that occurred several days after surgery, with complete recovery. Interestingly, the subject also displayed abnormal thermoregulation with stimulation initiation and stimulation parameter modifications. NBM-DBS may serve as a potential therapy for severe AD patients.Clinical Trial Registration: ChiCTR1900022324. (shrink)