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The North Korean police were arguably one of the most important organisations in liberated North Korea. It was instrumental in stabilising the North Korean society and eventually became one of the backbones for both the new North Korean regime and its military force. Scholars of different political orientation have attempted to reconstruct its early history leading to a set of views ranging from the “traditionalist” sovietisation concept to the more contemporary “revisionist” reconstruction that portrayed it as the cooperation of North Korean elites with the Soviet authorities in their bid for the control over the politics and the military, in which the Soviets merely played the supporting role. Drawing from the Soviet archival documents, this paper presents a third perspective, arguing that initially, the Soviet military administration in North Korea did not pursue any clear-cut political goals. On the contrary, the Soviet administration initially viewed North Koreans with distrust, making Soviets constantly conduct direct interventions to prevent North Korean radicals from using the police in their political struggle.
Depression is one of the most common mental health problem and it grows greater every year around the world.
The main aims were to analyze the possibility of using functional and structural neuroimaging methods in diagnosis of different depression types and to find the predictors of pharmacological resistance.
Materials & methods
46 patients with depression syndrome were distributed into 3 groups: 1) Neurotic Depression (Diagnosis: Adjustment disorders) - ND group; 2) Endogenous Depression (Diagnosis: Recurrent Depression, Bipolar Affective Disorder - current depressive episode, Schizoaffective disorder, depressive type) - PD group, 3) Depression due to organic pathology (Diagnosis: Organic depressive disorder, Organic mixed affective disorder) - OD group. Controls were 18 years old- and gender-matched healthy participants. We used several methods of functional (positron-emission tomography, functional magnetic resonance imaging) and structural (voxel-based morphometry, diffusion-tensor imaging) neuroimaging.
We found several functional and structural abnormalities in limbic structures within all three groups. Some of them were the same, some were different. Also we found several functional and structural predictors of pharmacological resistance.
We found several functional and structural abnormalities in all three depressive groups. Almost all of them were parts of so-called frontal-subcortical circuits, dysfunction of which, according to the present knowledge, could play crucial role in depression pathogenesis.
Summarizing our own results and analyzing the data of our colleagues, we complement a theory of depression pathogenesis and propose an original point of view for neurobiological basis of different types of depressive disorders and its pharmacological resistance.
The neuroleptics, which were invented in the middle of the last century, have changed psychiatry as the clinical discipline, and a problem of the pharmacological resistance insensibly has become the main problem. A radical way to overcome the resistance of the anxious and depressive disorders lies in the field of the modern neurosurgical techniques. However, the verification of the resistance still requires more developed approach.
The main aim of our study was to develop and test an integrated neuropsychiatric approach in order to objectify the resistance and the disease severity for the selection of patients for surgical treatment.
Methods and participants
We used different types of neuroimaging techniques for reviewing clinical and neurophysiological correlations: positron-emission tomography (PET), functional magnetic resonance imaging (fMRI), diffusion-tensor imaging (DTI) and its relations to the electroencephalography (EEG) data.
We examined 110 patients with depressive and anxious-obsessive disorders. 40 of them were examined using fMRI, 35 using PET and 35 using DTI. The patients were divided into groups by the ICD-10 criteria. The average age of the group was 46.3 years, the number of males and females in groups was approximately equal.
It was revealed that the degree of resistance had a significant correlation with the number of functional and structural neuroimaging indicators.
We obtained data which objectifies the concept of resistance. We also represent our understanding of clinical and physiological approach to the selection of target structures for stereotaxic neurosurgical exposure (in particular for deep brain stimulation) in the complex treatment.
Depressed patients demonstrate low frustration tolerance which increases the risk of suicide and causes difficulties in social adaptation. Resting-state neuroimaging studies revealed abnormalities in “default-mode” network in Major Depressive Disorder (MDD). To our knowledge, functional network responsible for frustration has not been investigated in depressed subjects previously.
To investigate functional responses to frustration in MDD subjects and healthy controls (HCs).
15 subjects with MDD and 15 HCs underwent 10-min fMRI scanning. We used modified Stroop-test to investigate subjects’ responses to frustration. There were two sessions: during the first one the subject had to determine the color of the text by pressing corresponding button while scanning; the second one was a “frustrative” part when the subject had to respond within a short period of time. We modified this interval so that it was almost impossible to respond correctly and keep within the allotted time. The subject was being informed on its performance during the test. Independent component analysis was used to isolate the frustration network in each subject. Group maps of the response network were compared. A within-group analysis was performed in the MDD group to explore effects of depression scores on functional connectivity.
We revealed differences in limbic functional connectivity patterns during the test perfomance in MDD in comparison to HCs.
The findings suggest that low frustration tolerance in depressed patients can be explained by the impaired function of stress-response brain network and reveal perspectives for future research on depression and suicide risk.
Major depressive disorder (MDD) is associated with low frustration tolerance, which is a risk factor for suicide. Hippocampal structural and functional abnormalities have been documented to play one of the crucial roles in the pathophysiology of depression. Recent studies have revealed functional differentiation of the hippocampus. Thus, activity of the anterior part was shown to be associated with negative affect mediation.
To investigate brain mechanisms of frustration, comparing its impact on anterior hippocampal connectivity in MDD patients and healthy controls (HCs).
14 MDD and 14 HC right-handed subjects were included in the study and underwent comprehensive clinical assessment. MDD was diagnosed during psychiatric interview according to ICD-10 criteria. The Hamilton Depression Rating Scale was additionally used to assess depressive symptoms. The original Stroop test was modified to evoke a state of frustration by administrering impossible task conditions and negative feedback during 10-min functional magnetic resonance scanning session. Psychophysiological interactions were used to analyze left and right anterior hippocampal functional connectivity changes in response to frustration. The resulted Z-maps were adjusted using Z > 2.3 threshold and a (corrected) cluster significance threshold of p = 0.05.
Increased functional connectivity of the left anterior hippocampus in response to frustration was significantly higher in MDD patients compared to HCs in the pars opercularis of the right prefrontal cortex and bilateral posterior cingulate regions.
The results revealed that depressed patients demonstrate abnormally increased anterior hippocampal response to frustration, suggesting that hippocampal-neocortical network impairment may contribute to decreased frustration tolerance associated with MDD
To date 56 reciprocal microdeletion/microduplication syndromes have been described. Due to intensive application of microarray technologies new submicroscopic rearrangements are being published. The reciprocal rearrangements are particularly valuable, since they allow to determine the dosage-sensitive pathogenic genes.
To improve ID diagnostics.
To identify novel candidate loci of ID.
We performed the genome-wide analysis for 79 patients with idiopathic ID using CGH Microarray Kits 4×44K and 8×60K (Agilent Technologies, USA). Pathogenically significant cases were confirmed by qPCR.
We present two patients with microdeletion (369 kb) and microduplication (766 kb) at 3p26.3 containing the only gene - CNTN6. The microduplication was inherited from apparently healthy father. The child with microdeletion was an orphan. Recently, the microduplication in 3p26.3 (containing CNTN6) has been shown to be associated with autism spectrum disorders (ASDs). Contactin 6 is also suggested to play a neuroprotective role in ischemic injury and contribute to granule cell maturation and/or synaptic formation in the developing cerebellum.
Considering the experiments with mice we found myotonic syndrome, late development of sit and walk ability in the anamnesis, current fine motor skills impairment and dysarthria in patient with dup3p26.3. His IQ is 47. Dysarthria was also observed in the patient with del3p26.3 (IQ 55).
Obviously, CNTN6 can be a novel pathogenic gene associated with ASDs, ID, and motor functions impairment. This study was supported by EU Seventh Framework Program, CHERISH project no. 223692 and by Federal Program of Ministry of Education and Science of Russian Federation no. 8727.
Affective disorders are common in patients with temporal lobe epilepsy, especially in cases of left-sided epileptic focus localization (lsTLE).
To characterize connectivity patterns of brain default mode network (DMN) in lsTLE patients with and without anxiety and depressive disorders.
Subjects and methods
28 lsTLE patients, divided into two groups: patients with (“affective” group) and without anxiety- depressive symptoms. Beck Depression Inventory (BDI), Hospital Anxiety Depressive Scale (HADS), Hamilton Anxiety Scale (HAM-A) and Montgomery-Asberg Depressive Rating Scale (MADRS) were used to assess affective symptoms. All subjects underwent 9-min resting-state fMRI scanning session. Independent component analysis (ICA) was used to isolate DMN. The resulted maps were compared in groups using two-sample t-test. The results were considered as statistically significant according to threshold of p < 0.005 with a 10-voxel extent that has recently been shown to produce an optimal balance between Types I and II error rates in fMRI studies (Lieberman, 2009). The data were processed and analyzed using SPM8 and “GIFT” toolbox for ICA “GIFT”.
Mild depression and moderate-severe anxiety levels were observed in the "affective" group. Significantly increased functional connectivity was found in “affective” group in the right cerebellum (culmen), right gyrus fusiformis, dorsolateral prefrontal and midcingulate area, and in the left insula.
We found that brain DMN is altered by affective disorders associated with lsTLE. The observed regional pattern of difference can reflect the impaired levels of self-control often present in lsTLE patients with affective symptoms
Depression is common in Alzheimer's disease (AD) with important clinical implications, but the etiology is not known.
30 subjects (15 with depression and 15 non-depressed matched for age, gender and cognitive impairment) with mild probable AD, defined as Mini-Mental State Examination score of 20 or above, diagnosed according to NINCDS-ADRDA criteria were included in the study. Data were collected at geriatric medicine and psychiatry outpatient clinics at three hospitals in Western Norway and all subjects underwent comprehensive clinical assessment. Montgomery-Asberg Depression Rating Scale with a cut-off point of 6/7 was used to evaluate depression. Automatic preprocessing using Freesurfer included steps for white and grey matter surface reconstruction. The resulting cortical thickness measurement was used in the subsequent GLM-based analysis. Correction for multiple comparisons was carried out cluster-wise by method of Monte Carlo.
We found 3 clusters of significantly reduced cortical thickness in the depressed group. The first cluster (p = 0,0014) contained Left Frontal Pole and Lateral Orbitofrontal cortex. The second cluster (p = 0,0131) included Left Anterior Temporal Area; Right Medial Prefrontal, Anterior Cingulate, Subgenual Cingulate and Medial Orbitofrontal cortex were included in the third cluster (p = 0,0032).
Depression in AD is associated with reduced cortical thickness in prefrontal and anterior temporal cortices. These areas have been found to be associated with depression in other age-related disorders as well as in major depression. This convergence of morphological profiles suggests a possible unity of depression brain mechanisms across disorders.
Depression is common in the elderly with a significant impact on the quality of life, and increased risk for developing dementia. However, the underlying structural brain changes are not well established.
To investigate neuroanatomical correlates of depressive symptoms in elderly people with and without mild cognitive impairment (MCI).
621 subjects with (n = 395) and without (n = 226) MCI selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were included in the study. Geriatric Depression Scale (GDS-15) with a cut-off point of 6 was used to evaluate depression. All subjects had T1 3D MRI images acquired at multiple ADNI sites using a standardized MRI protocol. Image post-processing included steps for brain segmentation and cortex reconstruction, and was performed using the software Freesurfer. General linear modeling was used to investigate depression-associated brain differences in patients with and without MCI (using age and gender as nuisance covariates).
No depression-associated differences in cortical thickness were observed in subjects without MCI, whereas MCI subjects with depressive symptoms revealed significant thinning in right parahippocampal, middle temporal, left parahippocampal and entorinal gyri compared to non-depressed MCI patients.
We found that depressive symptoms in elderly patients with MCI are associated with more severe atrophy in medial temporal area, suggesting a possible contribution of Alzheimer's pathology in the pathogenesis of depression in this group.
Genetic disorders underlie a significant number of cases of mental retardation (MR). However, the traditionally used routine karyotyping is not able to detect small but often clinically relevant aberrations. High-resolution genome-wide microarray technologies may help to increase the detectability of MR etiology.
To improve MR diagnostics.
To identify the novel CNV regions and susceptibility genes in MR patients.
Large chromosomal rearrangements, biochemical defects, and known monogenic syndromes accompanied by MR were ruled out for 71 patients. Further the genome-wide analysis using CGH Microarray Kits 4×44K and 8×60K (Agilent Technologies, USA) was performed.
Eight novel CNVs in 9 patients not described in healthy individuals and not associated with any disease were indentified implicating regions at 11q22.3, 5q33.1, 3p26.3, 15q11.1-q11.2, 15q22.2, 1q25.1-q25.2, 7q21.3, 2q12.3. They include candidate genes DDX10 (putative RNA helicase), IL17B (cytokine, primarily localized to neuronal cell bodies), CNTN6 (may play a role in the formation of axon connections), TLN2 (plays a role in cell adhesion and recycling of synaptic vesicles), TNR (an extracellular matrix protein, expressed primarily in the central nervous system), ASTN1 (a neuronal adhesion molecule), PON1 (detoxifies organophosphate neurotoxicants), and SLC5A7 (choline transporter in the brain and periphery).
Previously unknown CNVs, containing genes responsible for proper central nervous system functioning, were detected in 13% of patients. The novel CNVs and genes identified by aCGH may help discovering new etiological mechanisms of MR. This study was supported by European Community's Seventh Framework Programme, CHERISH (project 223692) and by Federal Program (grant 8727).
Over 20% of patients with developmental delay (DD) has copy number variations (CNV) of unknown significance. Some CNV may be associated with disease in a patient and also present in their apparently healthy parents. According to the two-hit model another CNV may contribute to phenotypic variation of such genomic disorders.
DD diagnostics improvement.
Understanding the pathogenic significance of concomitant 3q13.31 and 22q13.32-q13.33 microdeletions.
Ring chromosome 22 was first detected by conventional cytogenetics. Microdeletions at 3q13.31 and 22q13.32–q13.33 were revealed by agilent technologies 60 K microarray and confirmed by qPCR. Ring chromosome was confirmed by FISH.
We present a four-year-old girl with del22q13.32-q13.33 resulted in a ring chromosome 22 and a single TUSC7 gene microdeletion at 3q13.31. The del22q13.32-q13.33 originated de novo, whereas del3q13.31 was inherited from healthy mother. The 22q13.32-q13.33 locus is associated with Phelan-McDermid syndrome (PHMDS, OMIM 606232). The patient demonstrated features both typical for the syndrome (psychomotor and speech development delay, autistic signs, aggression, sleep alteration, seizures) and atypical – attention deficit-hyperactivity disorder (ADHD), ventriculomegaly, and reduced size of cerebella hemispheres (Dandy-Walker variant). ADHD and ventriculomegaly were previously described in patients with del3q13.31 (OMIM 615433) but Dandy-Walker variant was observed in our patient for the first time. Possibly, atypical for PHMDS features, may result from trans-epistasis of microdeletions.
Multiple CNVs in one patient complicate genotype-phenotype correlations due to possible overlapping phenotypes and/or modifying effect of variants. This study was supported by Russian Science Foundation, grant no. 16-15-10231.
Digenean larvae of hermaphroditic generation – cercariae – are known to be polymorphic at genetic and behavioural levels. Cercariae arise as a result of parthenogenetic reproduction of intramolluscan stages, and represent a clone if a snail was infected with a single miracidium. Here we investigated cercarial clones of Himasthla elongata – namely, the infectivity of cercariae with normal (negative) and deviant (positive) photoreaction. In our study, most H. elongata clones showed intraclonal variance in their response to light. The proportion of photopositive cercariae ranged between 0.2% and 60% in different H. elongata clones. Photopositive larvae demonstrated significantly reduced rates of encystment in Mytilus edulis haemolymph in vitro and in young mussels. We discuss the possible mechanisms behind intraclonal variations, such as non-specific genomic rearrangements.
Stochastic roughness is a widespread feature of natural surfaces and is an inherent byproduct of most fabrication techniques. In view of the rapid development of microfluidics, the important question is how this inevitable problem affects the low-Reynolds-number flows that are common for micro-devices. Moreover, one could potentially turn the flaw into a virtue and control the flow properties by means of specially ‘tuned’ random roughness. In this paper we investigate theoretically the statistics of fluctuations in fluid velocity produced by the waviness irregularities at the surface of a no-slip wall. Particular emphasis is laid on the issue of the universality of our findings.
This paper describes a model of electron energization and cyclotron-maser emission applicable to astrophysical magnetized collisionless shocks. It is motivated by the work of Begelman, Ergun and Rees [Astrophys. J. 625, 51 (2005)] who argued that the cyclotron-maser instability occurs in localized magnetized collisionless shocks such as those expected in blazar jets. We report on recent research carried out to investigate electron acceleration at collisionless shocks and maser radiation associated with the accelerated electrons. We describe how electrons accelerated by lower-hybrid waves at collisionless shocks generate cyclotron-maser radiation when the accelerated electrons move into regions of stronger magnetic fields. The electrons are accelerated along the magnetic field and magnetically compressed leading to the formation of an electron velocity distribution having a horseshoe shape due to conservation of the electron magnetic moment. Under certain conditions the horseshoe electron velocity distribution function is unstable to the cyclotron-maser instability [Bingham and Cairns, Phys. Plasmas 7, 3089 (2000); Melrose, Rev. Mod. Plasma Phys. 1, 5 (2017)].
We investigate theoretically the near-wall region in elastic turbulence of a dilute polymer solution in the limit of large Weissenberg number. As has been established experimentally, elastic turbulence possesses a boundary layer where the fluid velocity field can be approximated by a steady shear flow with relatively small fluctuations on the top of it. Assuming that at the bottom of the boundary layer the dissolved polymers can be considered as passive objects, we examine analytically and numerically the statistics of the polymer conformation, which is highly non-uniform in the wall-normal direction. Next, imposing the condition that the passive regime terminates at the border of the boundary layer, we obtain an estimate for the ratio of the mean flow to the magnitude of the flow fluctuations. This ratio is determined by the polymer concentration, the radius of gyration of polymers and their length in the fully extended state. The results of our asymptotic analysis reproduce the qualitative features of elastic turbulence at finite Weissenberg numbers.
Each piece of data is valuable for unearthing the earliest history of tetrapod origin. Despite frequently incomplete preservation, each skeletal element provides important information on the morphology, phylogeny and faunistic diversity of early tetrapodomorphs. We describe here new and earlier collected material from the fossil vertebrate site Yam-Tesovo on the Oredezh River (Leningrad Region, northwestern Russia) in the deposits of the Yam-Tesovo Formation within the Amata Regional Stage (?lowermost Frasnian, Upper Devonian). Upon similarity of their dermal ornamentation, two mandibular fragments are suggested to belong to the new tetrapodomorph taxon Rubrognathuskuleshovi n. gen. et sp. This species demonstrates a general ‘elpistostegalian' morphological pattern with some early tetrapod characters. The new taxon is characterised by an almost closed intercoronoid fossa, a prearticular that is strongly convex in section and bearing small teeth along its dorsal margin, low vertical coronoid laminae and coronoid fangs that enter the coronoid tooth row. The mandibular canal runs partly in open groove or opens to the surface by a row of large pores. The dermal ornament consists of a network of small ridges forming tubercles in the nodes. The postfrontal assigned to Tetrapodomorpha shows a ‘tetrapod-like' pits-and-ridges sculpturing and a supraorbital ridge characteristic of early tetrapods as well as ‘elpistostegalians'. Its long posterolateral bone margin demonstrates a lateral projection similar to that in Tiktaalik and unknown in other ‘elpistostegalians' and early tetrapods. An unusually flattened vomer is doubtfully related to the tetrapodomorph genus Livoniana Ahlberg, Lukševičs & Mark-Kurik, 2000, based upon characteristic multiple tooth rows. Teeth in rows decrease labially and show no clearly enlarged fang pairs. New finds of the last two decades present the earliest records of some tetrapod characters in non-limbed tetrapodomorphs. This challenges previous hypotheses on the origin of tetrapods.
We analyse velocity fluctuations inside coherent vortices generated as a result of the inverse cascade in the two-dimensional (2-D) turbulence in a finite box. As we demonstrated in Kolokolov & Lebedev (Phys. Rev. E, vol. 93, 2016, 033104), the universal velocity profile, established in Laurie et al. (Phys. Rev. Lett., vol. 113, 2014, 254503), corresponds to the passive regime of the flow fluctuations. This property enables one to calculate correlation functions of the velocity fluctuations in the universal region. We present the results of the calculations that demonstrate a non-trivial scaling of the structure function. In addition the calculations reveal strong anisotropy of the structure function.
This study aimed to assess the results of endomyocardial biopsy from the right ventricle to establish the possible cause for drug-refractory arrhythmias in children.
Materials and methods
We enrolled 19 consecutive young patients with drug-refractory arrhythmia, from 2010 to 2013, who underwent endomyocardial biopsy. Inclusion criteria were as follows: age <18 years with a structurally normal heart or mild changes in a structure of the heart initially diagnosed as arrhythmia-induced cardiomyopathy. Overall, 86 biopsies were performed in 19 patients. Histopathological analysis, immunohistochemistry, and polymerase chain reaction were used for the interpretation of the endomyocardial biopsy.
The mean age of the patient population was 14.1±2.9 year (range from 7 to 17 years). All these patients had a history of drug-refractory arrhythmia for >5 months (mean 30 months). Patients underwent a complete history investigation, physical examination, laboratory studies, echocardiography, electrocardiography, treadmill test, and Holter monitoring before endomyocardial biopsy; two patients with arrhythmogenic right ventricular dysplasia had implantable cardioverter defibrillator implantation and further appropriate successful device shocks. Myocarditis was diagnosed based on histopathological and immunohistological analyses in nine (47.4%) patients. Polymerase chain reaction was positive for viral genome in four of them; five patients had active myocarditis. Radiofrequency ablation was performed in 17 patients; five out of six (83%) endomyocardial biopsy-proved myocarditis patients had successful radiofrequency ablation. No significant complication was reported during ablation and endomyocardial biopsy.
Approximately half of the children with drug-refractory arrhythmia had unsuspected myocarditis according to the results of the endomyocardial biopsy.
An incomplete carcass of an extinct bison, Bison ex gr. priscus, was discovered in 2012 in the mouth of the Rauchua River (69°30′N, 166°49′E), Chukotka. The carcass included the rump with two hind limbs, ribs, and large flap of hide from the abdomen and sides, several vertebrae, bones of the forelimbs and anterior autopodia, stomach with its contents, and wool. The limb bones are relatively gracile, which is unusual in bison, and a SEM study of the hair microstructure suggests higher insulating capacity than in extant members of the genus. Additionally, mitochondrial DNA analyses indicate that the Rauchua bison belonged to a distinct and previously unidentified lineage of steppe bison. Two radiocarbon dates suggest a Holocene age for the bison: a traditional 14C date provided an estimate of 8030 ± 70 14C yr ВР (SPb-743) and an AMS radiocarbon date provided an age of 9497 ± 92 14C yr BP (AA101271). These dates make this the youngest known bison from Chukotka. Analysis of stomach contents revealed a diet of herbaceous plants (meadow grasses and sedges) and shrubs, suggesting that the early Holocene vegetation near the mouth of the Rauchua River was similar to that of the present day: tundra-associated vegetation with undersized plants.