Multistability in recurrent neural loops arising from delay

The dynamics of a recurrent inhibitory neural loop composed of a periodically spiking Aplysia motoneuron reciprocally connected to a computer are investigated as a function of the time delay, tau, for propagation around the loop. It is shown that for certain choices of tau, multiple qualitatively different neural spike trains co-exist. A mathematical model is constructed for the dynamics of this pulsed-coupled recurrent loop in which all parameters are readily measured experimentally: the phase resetting curve of the neuron for a given simulated postsynaptic current and tau. For choices of the parameters for which multiple spiking patterns co-exist in the experimental paradigm, the model exhibits multistability. Numerical simulations suggest that qualitatively similar results will occur if the motoneuron is replaced by several other types of neurons and that once tau becomes sufficiently long, multistability will be the dominant form of dynamical behavior. These observations suggest that great care must be taken in determining the etiology of qualitative changes in neural spiking patterns, particularly when propagation times around polysynaptic loops are long.     

Functional morphology of the submaxillary salivary glands during age involution in albino rats

A quantitative study was made of the morphological and functional characteristics of different parts of the submaxillary salivary glands of albino rats in different stages of involution of the neuroendocrine system. During aging the salivary gland function of rats is preserved, and just as in young animals, clear cyclic fluctuations are observed depending on the phases of the estrous cycle, although the basal level of proteins and mucopolysaccharides is reduced, to correspond on average to the minimal found in young animals. Meanwhile activation of the enzymes responsible for energy and transport processes in the cell is observed and relations between the enzymes are altered. The results prove that the salivary glands are connected with the endocrine system and they confirm the view that in early age involution what occurs is not so much a change of function as a disturbance of relations between the different indices of functional activity of the organ.Department of Pathological Anatomy, I. P. Pavlov First Leningrad Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. K. Kulagin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 12, pp. 736–739, December, 1979.     

不同辐射抗拒鼻咽癌细胞微小RNA差异表达的研究

目的: 在验证鼻咽癌（nasopharygycarcinoma, NPC）细胞CNE-1和CNE-2不同辐射抗拒性的基础上，探索微小RNA(miRNA)在CNE-1和CNE-2中的表达差异。方法: 通过观察X线照射对CNE-1和 CNE-2 细胞克隆形成数目的影响，利用SigmaPlot 软件进行分析及线性二次模型拟合存活曲线, 比较CNE-1和CNE-2 细胞剂量存活曲线及其生物学参数；采用Paraflo microfluidic microRNA芯片检测，用激光扫描器收集杂交的图像，经LOWESS 滤器规范信号后分析数据差异,根据Targetscan3.1数据库资料 (http:∥www.targetscan.org)，预测CNE-1和CNE-2细胞microRNA差异表达与NPC放射敏感性差异的关系。结果: 发现在CNE-1和CNE-2细胞中miRNA的差异表达，即与CNE-2细胞比，在检测的326个microRNA中，CNE-1细胞中有20个miRNA上调，13个miRNA下调，其中检测量的绝对值在2 000以上且两者相差在3倍以上的miRNA有hsa-miR-152、hsa-miR-7、hsa-miR-205和hsa-miR-572；分析结果提示明显差异表达的miRNA与放疗敏感性密切相关。结论: 不同辐射抗拒NPC细胞株CNE-1和CNE-2细胞的microRNA的表达有差异；差异表达的miRNA与放疗敏感有关。     

Development of neural stem cells at different sites of fetus brain of different gestational age

Objective: This study aimed to investigate the development of neural stem cells (NSCs) in fetal brain, which may provide experimental evidence for the clinical treatment of brain injury in children. Methods: A total of 60 fetuses were collected after labor induction and divided into 6 groups according to the gestational age (16 w, 20 w, 24 w, 28 w, 32 w and 36 w; n=10 per group). The hippocampus, striatum, subventricular zone, frontal lobe, temporal lobe, occipital lobe and parietal lobe were harvested. In situ hybridization, immunohistochemistry and light microscopy were done to determine the morphology and quantity of NSCs. Results: NSCs were identified in the brain of fetuses with different gestational age. NSCs were round, oval, spindle-shaped, starlike, triangular or polygonal. NSC colony was also observed with symmetrical or asymmetrical division. Single NSC, group-like NSCs and cluster-like NSCs were found in the different sites of fetal brain, and NCSs interacted with each other via synapses. However, the distribution, morphology, growth and quantity of NSCs were different in the brain of fetuses with different gestational age. The number of NSCs reduced with the increase in gestational age, but they were always observed. Conclusion: The morphology of NSCs in fetal brain is variable and they are widely distributed in the hippocampus, subventricular zone, striatum and cortex. The number of NSCs reduced with the increase of gestational age.     

The possible impairment of respiratory-related neural loops may be associated with the silent pneumonia induced by SARS-CoV-2

As compared to many other viral pulmonary infections, there existed several peculiar manifestations in the COVID-19 patients, including the “silence” of pneumonia in both mild and severe cases and a long intensive care unit stay for those requiring invasive mechanical ventilation. Similar silent pneumonia has been documented in the infectioninduced by H5N1 influenza virus HK483 and was found to result from the direct attack of the virus on the bronchopulmonary C-fibers at the early stage and the final infection in the brainstem at the late stage. The long stay of critical patients in the intensive care unit is possibly due to the depression of central respiratory drive, which resulted in the failure to wean from the mechanic ventilation. Carotid and aortic bodies and bronchopulmonary C-fibers are two key peripheral components responsible for the chemosensitive responses in the respiratory system, while triggering respiratory reflexes depends predominantly on the putative chemosensitive neurons located in the pontomedullary nuclei. In view of the findings for the H5N1 influenza virus, the silence of pneumonia induced by SARS-CoV-2 may be due to the possible impairment of peripheral chemosensitive reflexes as well as the damage to the respiratory-related central neurons.     

Lymphoid follicles of different phenotype appear in ileum during involution of the sheep ileal Peyer's patch

The ileal Peyer's patch (IPP) of young sheep is a site of diversification of the primary antibody repertoire and where involution takes place at young age. Tissue samples from the ileum were collected in 134 animals aged from 1 month to 6 years, and IPP follicle phenotypes were characterised. We describe a new type of ileal lymphoid follicles that became relatively more frequent during involution, and had numerous intrafollicular T-cells and BAQ44A+ B-cells and large interfollicular T-cell areas. As opposed to classical IPP follicles in which the BAQ44A+ cells were confined to the narrow follicle-neck region, the novel atypical ileal lymphoid follicle had these cells distributed throughout the follicle. The relative distribution of cell types in the typical IPP follicle remained fairly constant during involution. Many animals older than 9 months (64/92) still had had typical IPP follicles and even sheep 4 years and older (5/9) had IPP-type follicles.     

Three different ABCA4 mutations in the same large family with several consanguineous loops affected with autosomal recessive cone-rod dystrophy

A large multiplex family presumably affected with autosomal recessive cone-rod dystrophy (CRD) was ascertained from Israel. In this family of Christian Arab ancestry with six consanguineous loops, linkage analysis failed to identify homozygosity in all six nuclear families at any of the three arCORD loci hitherto reported. However, homozygosity was found at the CORD3 locus for two nuclear families and the segregation of three distinct haplotypes at this locus in the whole pedigree suggested the alteration of the ABCA4 gene. This hypothesis was confirmed by the identification of three distinct mutations. Subsequently, with regard to the wide spectrum of autosomal recessive retinal dystrophies related to ABCA4 mutations, the natural history of the disease was revisited in all patients. Although the diagnosis of CRD was confirmed in 8/9 patients, the last one, aged of 34, displayed typical signs of Stargardt disease without extension to the peripheral retina. The results of this study emphasize the pitfalls of homozygosity mapping in highly inbred families when the heterozygote carrier frequency is particularly high in the general population.     

Hypothesis: involution of the thymus with aging--programmed and beneficial

This is an attempt to find a teleological rationale for the involution of the thymus with aging. The thymus is the first organ in the body to age, which seems incongruent considering its cardinal role in the immune system. An analogical incongruency can be seen in the fact that acute stress is generally accompanied by a reversible involution of the thymus. We hypothesized earlier, that this reversible involution might protect the organism from the danger of autoimmune diseases. It stands to reason that, in nature, conditions leading to stress frequently entail massive tissue destruction. This may cause the appearance of "altered self" components, leading to the formation of autoantibodies. Hence, the temporary shut-off of thymic activity would be beneficial. A similar argument holds in the case of aging and will be elaborated as follows: 1) Formation of antibodies per se entails the danger of autoimmune mechanisms, hence the process is controlled at various levels; 2) The aging process is characterized by the increasing appearance of non-self components as a result of DNA errors and post-translational changes due to free radicals and other high energy oxygen derivatives; 3) Early involution serves, in our opinion, to reduce the risk of autoimmune diseases which increases with aging, and should therefore be regarded as an adaptation of the organism to aging; 4) If this notion proves to be correct the desirability of restoring full thymic activity in old people becomes questionable.     

Thymus involution in the acquired immunodeficiency syndrome

Acquired immunodeficiency syndrome (AIDS) is a severe disorder of unknown etiology and pathogenesis, predominantly affecting homosexual males and other high-risk groups and characterized by profound alterations in T-lymphocyte function. The authors have examined thymus tissue from 14 patients who died of AIDS and compared the results with findings in five control groups: healthy age-matched controls, elderly individuals, patients with chronic or debilitating illnesses other than AIDS, infants with conditions causing "stress atrophy," and patients with myasthenia gravis. The AIDS group included 11 homosexual males, 1 Haitian, 1 homosexual who was also a drug abuser, and a 10-month-old infant believed to have contracted AIDS following blood transfusion. All the AIDS cases showed marked thymus involution with severe depletion of both lymphocytes and epithelial elements. The latter component consisted primarily of thin cords and nests of primitive-appearing epithelial cells that could be defined by positive immunohistochemical staining for keratin. Many cases showed a variable plasma cell infiltration, and the majority exhibited distinct vascular changes in the form of hyalinization and/or onion-skin patterns, primarily in the adventitia. Most striking of all was the marked paucity of Hassall's corpuscles; four patients had none at all, while in the other ten patients all the Hassall's corpuscles were calcified. These changes were far more extensive than those seen in any of the control groups, which retained most of their complement of Hassall's corpuscles even in the face of marked overall involution. The physiologic function of Hassall's corpuscles is not known, but recent immunohistochemical studies have implicated them in the synthesis of "facteur thymique serique" (FTS, thymulin) and other thymic hormones known to play a role in regulating T-helper and suppressor cell activity. It is conceivable that the extensive destruction of Hassall's corpuscles observed in AIDS may be a crucial element in the pathogenesis of this syndrome.     

Increasing skeletal involution in the elderly?

Studies of bone mineral content (MC) of the limbs in normal populations have shown there is an increase of MC during adolescence, a maximum MC for both sexes between 30 and 40 years of age and a subsequent decrease which is at least twice as great in females than in males. There are different findings in the literature on the course of these MC changes with aging. The present cross-sectional study of 180 subjects over age 70 showed a slight increase in the annual decrease of radius MC in females and a distinct acceleration of the MC decrease in males after about 80 years. This occurred for both a pure cortical measuring site of the radius (1/3-site) and for a mixed cancellous/compact site of the distal radius (1/10-site). These findings differ from those in other populations.     

Autoantibodies in healthy subjects of different age groups

Autoantibody determinations in 1284 healthy Caucasian subjects of various age groups were made by indirect immunofluorescence for anti-nuclear, anti-gastric, and anti-thyroglobulin antibodies. A sex-dependent relationship between age and prevalence of anti-gastric and anti-thyroglobulin antibodies was found. No association was found between age and anti-nuclear antibodies.     

不同年龄及性别健康成人血浆同型半胱氨酸的水平研究

目的: 分析不同性别及年龄健康成人的血浆同型半胱氨酸(Hcy)水平,明确健康人群Hcy的标准,为高Hcy血症的防治提供指导和依据。方法: 剔除高血压、脑卒中、冠心病等常见致血Hcy升高因素的健康体检人群,共738人,按不同年龄分为青(≤35岁)、中(≥36,<60岁)、老(≥60岁)3组,并按性别分为男女亚组,以循环酶法分别测定其血浆Hcy水平,进行比较。结果: 各年龄组男性均高于女性(P<0.01);同时男女各组Hcy均随年龄增加而升高,青、中、老组比均有显著差异(P<0.01);男性均数为13.26 μmol/L,女性为9.68 μmol/L,差异显著(P<0.01); 多数男性(73.21%)血Hcy水平在10.01-15.00 μmol/L间,多数女性(84.06%)小于10.00 μmol/L。 结论: (1) 健康成人血浆Hcy水平存在性别和年龄的差异,男性高于女性,并随年龄增加而逐渐升高。(2) 正常健康成人血浆Hcy水平高限的确定,应考虑性别及年龄因素。     

Regional specificity of age effects on the neural correlates of episodic retrieval

We investigated age-related differences in episodic retrieval using a source memory procedure. Age-related differences in retrieval-related activity were analyzed in conditions where source recollection performance was statistically equivalent in young and older subjects. Analyses of BOLD activity revealed a network of regions where recollection effects were equivalent in magnitude in the two age groups. There were no regions where these effects were of greater magnitude in young than in older subjects. In some regions, however, there was a crossover interaction, such that retrieval-related effects reversed in direction between the two age groups. Further analyses of these interactions revealed a dissociation between a posterior hippocampal region where recollection-related activity was confined to the older group, and right fusiform and occipital regions where, in the young group only, activity elicited by studied items was of lower magnitude than activity to new items. We interpret the first of these age-related effects as an example of ‘over-recruitment’ in response to decline in neural efficiency, and discuss whether the second effect indexes an age-related decline in repetition priming.     

不同年龄组基孔肯雅热患者的临床表现比较

目的分析不同年龄组基孔肯雅热患者的临床表现。方法 130例基孔肯雅热患者,按年龄分为三组：〈30岁、30～岁、≥60岁组,分析其临床症状的差异。结果三组患者均出现发热,皮疹的发生率分别为86.8%、91.4%、90.9%,关节痛的比例分别为86.8%、91.4%、95.5%,关节痛持续时间超过14d的比例分别为2.6%、30.0%、36.4%;与〈30岁组比较,30～岁和≥60岁组患者出现关节痛持续时间超过14d以及累及3个或以上关节的比例高,差异均有统计学意义（χ2=13.026,P=0.001;χ2=6.792,P=0.034）。结论基孔肯雅热主要表现为发热、皮疹、关节痛,中、老年组患者出现关节疼痛持续时间较长,累及的关节多。     

Incidence of rotavirus infection in different age groups of pediatric patients with gastroenteritis.

An enzyme immunoassay was used to detect rotavirus in the stools of 176 pediatric patients presenting with gastroenteritis. The highest incidence of rotavirus infection was found among patients less than 1 year of age. In contrast to previously reported studies, 23% of neonates with gastroenteritis had rotavirus in their stools. This relatively easy and rapid method was helpful in the management of pediatric patients with gastroenteritis.