Cortico-striatal gamma oscillations are modulated by dopamine D3 receptors in dyskinetic rats

Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Currently,studies have reported increased oscillation power in cases of levodopa-induced dyskinesia.However,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia.Furthermore,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is unclear.We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease.Furthermore,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma flow.Administration of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum flow.However,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum direction.These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.

Origin of Magnetic Fields of Stellar Objects in the Universe Based on the 5D Projection Theory

Beginning with a 5D homogeneous universe [1], we have provided a plausible explanation of the self-rotation phenomenon of stellar objects previously with illustration of large number of star samples [2], via a 5D-4D projection. The origin of such rotation is the balance of the angular momenta of stars and that of positive and negative charged e-trino pairs, within a 3D ⊗1D?void of the stellar object, the existence of which is based on conservation/parity laws in physics if one starts with homogeneous 5D universe. While the in-phase e-trino pairs are proposed to be responsible for the generation of angular momentum, the anti-phase but oppositely charge pairs necessarily produce currents. In the 5D to 4D projection, one space variable in the 5D manifold was compacted to zero in most other 5D theories (including theories of Kaluza-Klein and Einstein [3] [4]). We have demonstrated, using the Fermat’s Last Theorem [5], that for validity of gauge invariance at the 4D-5D boundary, the 4th space variable in the 5D manifold is mapped into two current rings at both magnetic poles as required by Perelman entropy mapping;these loops are the origin of the dipolar magnetic field. One conclusion we draw is that there is no gravitational singularity, and hence no black holes in the universe, a result strongly supported by the recent discovery of many stars with masses well greater than 100 solar mass [6] [7] [8], without trace of phenomena observed (such as strong gamma and X ray emissions), which are supposed to be associated with black holes. We analyze the properties of such loop currents on the 4D-5D boundary, where Maxwell equations are valid. We derive explicit expressions for the dipolar fields over the whole temperature range. We then compare our prediction with measured surface magnetic fields of many stars. Since there is coupling in distribution between the in-phase and anti-phase pairs of e-trinos, the generated mag-netic field is directly related to the angular momentum, leading to the result that the magnetic field can be expressible in terms of only the mechanical variables (mass M, radius R, rotation period P)of a star, as if Maxwell equations are “hidden”. An explanation for the occurrence of this “un-expected result” is provided in Section (7.6). Therefore we provide satisfactory answers to a number of “mysteries” of magnetism in astrophysics such as the “Magnetic Bode’s Relation/Law” [9] and the experimental finding that B-P graph in the log-log plot is linear. Moreover, we have developed a new method for studying the relations among the data (M, R, P) during stellar evolution. Ten groups of stellar objects, effectively over 2000 samples are used in various parts of the analysis. We also explain the emergence of huge magnetic field in very old stars like White Dwarfs in terms of formation of 2D Semion state on stellar surface and release of magnetic flux as magnetic storms upon changing the 2D state back to 3D structure. Moreover, we provide an explanation, on the ground of the 5D theory, for the detection of extremely weak fields in Venus and Mars and the asymmetric distribution of magnetic field on the Martian surface. We predict the equatorial fields B of the newly discovered Trappist-1 star and the 6 nearest planets. The log B?−?log P graph for the 6 planets is linear and they satisfy the Magnetic Bode’s relation. Based on the above analysis, we have discovered several new laws of stellar magnetism, which are summarized in Section (7.6).

Effect of cis-9,trans-11-conjugated linoleic acid on cell cycle of gastric adenocarcinoma cell line(SGC-7901)

AIM: To determine the effect of cis -9, trans -11-conjugated linoleic acid (c9, t11-CLA) on the cell cycle of gastric cancer cells (SGC-7901) and its possible mechanism in inhibition cancer growth. METHODS: Using cell culture and immunocytochemical techniques, we examined the cell growth, DNA synthesis, expression of PCNA, cyclin A, B(1), D(1), p16(ink4a) and p21(cip/waf1) of SGC-7901 cells which were treated with various c9, t11-CLA concentrations (25, 50, 100 and 200 micromol.L(-1))of c 9, t 11-CLA for 24 and 48h, with a negative control (0.1% ethane). RESULTS: The cell growth and DNA synthesis of SGC-7901 cells were inhibited by c9, t11-CLA.SGC-7901 cells. Eight day after treatment with various concentrations of c9, t11-CLA mentioned above, the inhibition rates were 5.92%, 20.15%, 75.61% and 82.44%, respectively and inhibitory effect of c9, t11-CLA on DNA synthesis (except for 25 micromol.L, 24h) showed significantly less (3)H-TdR incorporation than that in the negative controls (P【0.05 and P【0.01). Immunocytochemical staining demonstrated that SGC-7901 cells preincubated in media supplemented with different c9, t11-CLA concentrations at various times significantly decreased the expressions of PCNA (the expression rates were 7.2-3.0%, 24h and 9.1-0.9% at 48h, respectively), Cyclin A (11.0-2.3%, 24h and 8.5-0.5%,48h), B(1) (4.8-1.8% at 24h and 5.5-0.6% at 48h)and D(1) (3.6-1.4% at 24h and 3.7%-0 at 48h) as compared with those in the negative controls(the expressions of PCNA, Cyclin A, B(1) and D(1) were 6.5% at 24h and 9.0% at 48h, 4.2% at 24h and 5.1% at 48h, 9.5% at 24h and 6.0% at 48h,respectively)(P【0.01), whereas the expressions of P16(ink4a) and P21(cip/waf1), cyclin-dependent kinases inhibitors(CDKI), were increased. CONCLUSION: The cell growth and proliferation of SGC-7901 cell is inhibited by c9, t11-CLA via blocking the cell cycle, with reduced expressions of cyclin A,B(1) and D(1) and enhanced expressions of CDKI(P16(ink4a) and p21(cip/waf1)).

Transretinoic acid inhibits rats gastric epithelial dysplasia induced by N-methyi-N-nitro-N-nitrosoguanidine:influences on cell apoptosis and expression of its regulatory genes

INTRODUCTIONGastric epithelial dysplasia (GED) hypothetically is a straight-forward concept: dysplastic epithelium replacing the normal gastric epithelium of the stomach [1].In the stomach ,like any other segment of the gut ,it is defined as an unequivocal non-invasive epithelial change[2,3].The observation of gastric dysplasia as a cancerous lesion was recognized over a century ago ,but it is only after the advent of gastroscopy that its clinical significance has been stressed[4-7].

An Improved Coupled Level Set and Continuous Moment-of-Fluid Method for Simulating Multiphase Flows with Phase Change

An improved algorithm for computing multiphase flows is presented in which the multimaterial Moment-of-Fluid(MOF)algorithm for multiphase flows,initially described by Li et al.(2015),is enhanced addressing existing MOF difficulties in computing solutions to problems in which surface tension forces are crucial for understanding salient flow mechanisms.The Continuous MOF(CMOF)method is motivated in this article.The CMOF reconstruction method inherently removes the"checkerboard instability"that persists when using the MOF method on surface tension driven multiphase(multimaterial)flows.The CMOF reconstruction algorithm is accelerated by coupling the CMOF method to the level set method and coupling the CMOF method to a decision tree machine learning(ML)algorithm.Multiphase flow examples are shown in the two-dimensional(2D),three-dimensional(3D)axisymmetric"RZ",and 3D coordinate systems.Examples include two material and three material multiphase flows:bubble formation,the impingement of a liquid jet on a gas bubble in a cryogenic fuel tank,freezing,and liquid lens dynamics.

Measurement of two new indicators of cardiac reserve in humans, rats, rabbits, and dogs

Background: It is difficult to observe the phenomena of cardiac fatigue under a low or moderate workload test, and little was reported about cardiac fatigue under a heavy workload test because of the potential risk (sudden death) of prolonged strenuous exercise. Animal experiments would be helpful to resolve this problem. The objective of this study was to obtain baseline data of two new indicators of cardiac reserve in rats, rabbits, and dogs. Methods: Ten New Zealand White rabbits (1. 5 to 2 kg, 4 females), 10 male Wistar rats (2 months old), and 10 Golden Retriever dogs (40 days old, 5 females) were included in this study. Phonocardiogram of each animal was recorded. The basic points concerning heart sound quantitative analysis were: 1) measuring the duration and the amplitude of relevant heart sound components;2) calculating and analyzing relevant indicators based on the data obtained from the above measurements, including the ratio of diastolic to systolic duration (D/S) and the ratio of the amplitude of the first heart sound to the amplitude of the second heart sound (S1/S2). Results: The baseline data of D/S ratio and S1/S2 ratio in rats, rabbits, and dogs were obtained. The swimming time to exhaustion for rabbits was several to a dozen minutes, and for rats, several hours. Conclusion: D/S ratio has an important biological implication, which is a safe and easy indicator for evaluating the cardiac health status of both animals and humans.

Determination of 13 Trace Elements in Anshun Thorn Pear (Rosa roxburghii) and Golden Thorn Pear (Rosa sterilis S.D.Shi) by ICP-MS

[Objectives] This study was conducted to establish an analytical method for the establishment of 13 trace elements in Anshun thorn pear(Rosa roxburghii) and golden thorn pear(Rosa sterilis S. D. Shi). [Methods] Nitric acid was used as the digestion system for microwave digestion. Inductively coupled plasma mass spectrometry(ICP-MS) was used to determine the trace elements in thorn pear and golden thorn pear. [Results] Be, Ti, V, Cr, Mn, Co, Ni, As, Sr, Mo, Cd, Sb and Hg were determined by ICP-MS method in thorn pear and golden thorn pear. The correlation coefficients of the regression equations of the elements were higher than 0.996; the precision RSD was lower than 2.87%; and the recovery ranged from 94.3% to 109.8%. [Conclusions] The method has the advantages of high sensitivity, good accuracy and simultaneous detection of multiple elements, and provides a reference method and theoretical basis for determining trace elements in thorn pear and golden thorn pear and other fruits.

Vitamin D and selenium for type 2 diabetes mellitus with Hashimoto’s thyroiditis:Dosage and duration insights

This letter discusses the publication by Feng et al.Iodine,selenium,and vitamin D are closely associated with thyroid hormone production in humans;however,the efficacy of selenium and vitamin D supplementation for type 2 diabetes mellitus(T2DM)patients with Hashimoto’s thyroiditis(HT)remains controversial.In the retrospective study we discuss herein,the authors highlighted significant improvements in thyroid function,thyroid antibodies,blood glucose,and blood lipid in T2DM patients with HT following addition of vitamin D and selenium to their antidiabetic regimens,underscoring the value of these supplements.Our team is currently engaged in research exploring the relationship between micronutrients and HT,and we have obtained invaluable insights from the aforementioned study.Based on this research and current literature,we recommend a regimen of 4000 IU/day of vitamin D and 100-200μg/day of selenium for over three months to six months for patients with HT,particularly for those with concurrent T2DM.

A New Approach with Three Dimension Figure and ANSI/IEEE C57.104 Standard Rule Diagnoses Transformer’s Insulating Oil

The dissolved gas analysis (DGA) is an effective method for detecting incipient faults in immersed oil power transformers. In this paper, we investigate the DGA methods and employ the ANSI/IEEE C57.104 standards (guidelines for the interpretation of gases generated in oil-immersed transformers) and IEC Basic Gas Ratio method to design a heuristic power transformer fault diagnosis tool in practice. The proposed tool is implemented by a MATLAB program and it can provide users a transformer diagnosis result. The user keys in the data of H2, CH4, C2H2, C2H4, and C2H6 gases dissolved from the immersed oil transformer’s insulating oil measured by ASTM D3612. The analyzed results will be represented in texts and figures. The real measured data of the transformer oil were taken from Taiwan Power Company substations to verify the validation and accuracy of the developed diagnosis tool.

Dementia and osteoporosis in a geriatric population: Is there a common link?

AIM To determine the existence of a common pathological link between dementia and osteoporosis through reviewing the current evidence base. METHODS This paper reviews the current literature on osteoporosis and dementia in order to ascertain evidence of a common predisposing aetiology. A literature search of Ovid MEDLINE(1950 to June 2016) was conducted. The keywords "osteoporosis", "osteoporotic fracture", "dementia" and "Alzheimer's disease"(AD) were used to determine the theoretical links with the most significant evidence base behind them. The key links were found to be vitamins D and K, calcium, thyroid disease, statins, alcohol and sex steroids. These subjects were then searched in combination with the previous terms and the resulting papers manually examined. Theoretical, in vitro and in vivo research were all used to inform this review which focuses on the most well developed theoretical common causes for dementia(predominantly Alzheimer's type) and osteoporosis.RESULTS Dementia and osteoporosis are multifaceted disease processes with similar epidemiology and a marked increase in prevalence in elderly populations. The existence of a common link between the two has been suggested despite a lack of clear pathological overlap in our current understanding. Research to date has tended to be fragmented and relatively weak in nature with multiple confounding factors reflecting the difficulties of in vivo experimentation in the population of interest. Despite exploration of various possible mechanisms in search for a link between the two pathologies, this paper found that it is possible that these associations are coincidental due to the nature of the evidence available. One finding in this review is that prior investigation into common aetiologies has found raised amyloid beta peptide levels in osteoporotic bone tissue, with a hypothesis that amyloid beta disorders are systemic disorders resulting in differing tissue manifestations. However, our findings were that the most compelling evidence of a common yet independent aetiology lies in the APOE4 allele, which is a well-established risk for AD but also carries an independent association with fracture risk. The mechanism behind this is thought to be the reduced plasma vitamin K levels in individuals exhibiting the APOE4 allele which may be amplified by the nutritional deficiencies associated with dementia, which are known to include vitamins K and D. The vitamin theory postulates that malnutrition and reduced exposure to sunlight in patients with AD leads to vitamin deficiencies. CONCLUSION Robust evidence remains to be produced regarding potential links and regarding the exact aetiology of these diseases and remains relevant given the burden of dementia and osteoporosis in our ageing population. Future research into amyloid beta, APOE4 and vitamins K and D as the most promising aetiological links should be welcomed.

Choice of an Advanced Rheological Model for Modeling the Viscoelastic Behavior of Hot Mixtures Asphalt (HMA) from Sénégal (West Africa)

The main purpose of this article is to choose among advanced rheological models used in the French rational design, one that best represents the viscoelastic behavior of asphalt mixtures mixed with aggregates of Senegal. The model chosen will be the basis for the development of computational tools for stress and strain for Senegal. However, the calibration of these models needs complex modulus test results. In opposition to mechanical models the complex modulus can directly characterize the viscoelastic behavior of bituminous materials. Here determination is performed in the laboratory by using several types of tests divided into two groups: homogeneous tests and non-homogeneous tests. The choice of model will be carried out by statistical analysis through the least squares method. To this end, a study was carried out to “Laboratory of Pavement and Bituminous Materials” (LCMB) with asphalt concrete mixed with aggregate from Senegal named basalt of Diack and quartzite of Bakel. In this study, the test used to measure the complex modulus is the Canadian test method LC 26-700 (Determination of the complex modulus by tension-compression). There mainly exist two viewing complex modulus planes for laboratory test results: the Cole and Cole plane and the Black space. The uniqueness of the data points in these two areas means that studied asphalt concretes are thermorheologically simple and that the principle of time-temperature superposition can be applied. This means that the master curve may be drawn and that the same modulus value can be obtained for different pairs (frequency-temperature). These master curves are fitted during the calibration process by the advanced rheological models. One of the most used software in the French rational design for the visualization of complex modulus test results and calibration of rheological models developed tools is named Visco-analysis. In this study, its use in interpreting the complex modulus test results and calibration models shows that, the studied asphalt concretes are thermorheologically simple, because they present good uniqueness of their Black and Cole and Cole and Black diagrams. They allow a good application of the principle of time temperature superposition. The statistical analysis of calibration models by the least squares method has shown that the three studied models are suitable for modeling the linear viscoelastic behavior of asphalt mixtures formulated with the basalt of Diack and the quartzite of Bakel. Indeed their calibration has very similar precision values of “Sum of Squared Deviation” (SSD) about 0.185. However, the lower precision value (0.169) is obtained with the 2S2P1D model.

Effect of Perturbations in Coriolis and Centrifugal Forces on the Non-Linear Stability of <i>L</i>₄in the Photogravitational Restricted Three Body Problem

Effect of perturbations in Coriolis and centrifugal forces on the non-linear stability of the libration point L4 in the restricted three body problem is studied when both the primaries are axis symmetric bodies (triaxial rigid bodies) and the bigger primary is a source of radiation. Moser’s conditions are utilized in this study by employing the iterative scheme of Henrard for transforming the Hamiltonian to the Birkhoff’s normal form with the help of double D’Alembert’s series. It is found that L4 is stable for all mass ratios in the range of linear stability except for the three mass ratios μc1, μc2 and μc3, which depend upon the perturbations ε1 and ε1 in the Coriolis and centrifugal forces respectively and the parameters A1,A2,A3 and A4 which depend upon the semi-axes a1,b1,c1;a2,b2,c2 of the triaxial rigid bodies and p, the radiation parameter.

Spatial analysis of tuberculosis in four main ethnic communities in Taiwan during 2005 to 2009

The aim of the present study was to assess spatial features of tuberculosis prevalence and their relationships with four main ethnic communities in Taiwan. Methods of spatial analysis were clustering pattern determination (such as global version of Moran’s test and local version of Gi*(d) statistic), using logistic regression calculations to identify spatial distributions over a contiguous five years and identify significant similarities, discriminant analysis to classify variables, and geographically weighted regression (GWR) to determine the strength of relationships between tuberculosis prevalence and ethnic variables in spatial features. Tuberculosis demonstrated decreasing trends in prevalence in both genders during 2005 to 2009. All results of the global Moran’s tests indicated spatial heterogeneity and clusters in the plain and mountainous Aboriginal townships. The Gi*(d) statistic calculated z-score outcomes, categorized as clusters or non-clusters, at at 5% significance level. According to the stepwise Wilks’ lambda discriminant analysis, in the Aborigines and Hoklo communities townships with clusters of tuberculosis cases differentiated from townships without cluster cases, to a greater extent than in the other communities. In the GWR models, the explanatory variables demonstrated significant and positive signs of parameter estimates in clusters occurring in plain and mountainous aboriginal townships. The explanatory variables of both the Hoklo and Hakka communities demonstrated significant, but negative, signs of parameter estimates. The Mainlander community did not significantly associate with cluster patterns of tuberculosis in Taiwan. Results indicated that locations of high tuberculosis prevalence closely related to areas containing higher proportions of the Aboriginal community in Taiwan. This information is relevant for assessment of spatial risk factors, which, in turn, can facilitate the planning of the most advantageous types of health care policies, and implementation of effective health care services.

Three new alternative splicing variants of human cytochrome P450 2D6 mRNA in human extratumoral liver tissue

AIM: To identify the new alternative splicing variants of human CYP2D6 in human extratumoral liver tissue with RT-PCR and sequencing. METHODS: Full length of human CYP2D6 cDNAs was amplificated by reverse transcription-polymerase chain reaction (RT-PCR) from a human extratumoral liver tissue and cloned into pGEM-T vector. The cDNA was sequenced. Exons from 1 to 4 of human CYP2D6 cDNAs were also amplificated by RT-PCR from extratumoral liver tissues of 17 human hepatocellular carcinomas. Some RT-PCR products were sequenced. Exons 1 to 4 of CYP2D6 gene were amplified by PCR from extratumoral liver tissue DNA. Two PCR products from extratumoral liver tissues expressing skipped mRNA were partially sequenced. RESULTS: One of the CYP2D6 cDNAs had 470 nucleotides from 79 to 548 (3' portion of exons 1 to 5' portion of exon 4), and was skipped. Exons 1 to 4 of CYP2D6 cDNA were assayed with RT-PCR in 17 extratumoral liver tissues. Both wild type and skipped mRNAs were expressed in 4 samples, only wild type mRNA was expressed in 5 samples, and only skipped mRNA was expressed in 8 samples. Two more variants were identified by sequencing the RT-PCR products of exons 1 to 4 of CYP2D6 cDNA. The second variant skipped 411 nucleotides from 175 to 585. This variant was identified in 4 different liver tissues by sequencing the RT-PCR products. We sequenced partially 2 of the PCR products amplified of CYP2D6 exon 1 to exon 4 from extratumoral liver tissue genomic DNA that only expressed skipped mRNA by RT-PCR. No point mutations around exon 1, intron 1, and exon 4, and no deletion in CYP2D6 gene were detected. The third variant was the skipped exon 3, and 153 bp was lost. CONCLUSION: Three new alternative splicing variants of CYP2D6 mRNA have been identified. They may not be caused by gene mutation and may lose CYP2D6 activity and act as a down-regulator of CYP2D6.

Multi-center pragmatic studies evaluating the time indicator of cardiac perfusion reserve

Background: Since the greater part of coronary blood flow takes place during the diastolic phase of each cardiac cycle, a time indicator of myocardial perfusion reserve, the ratio of diastolic to systolic duration (D/S ratio), was presented. The objective of this study was to evaluate the accuracy and precision, the biological implication, and the applications of D/S ratio. Methods: Multi-center pragmatic studies evaluating the time indicator of cardiac perfusion reserve were performed. Related experiments, clinical trials, and surveys were conducted at 5 centers. Results: The results showed that the measurement of D/S ratio is both accurate and precise;the mean values of D/S of all of the 3 species studied (human, rabbit, and rat) were greater than 1. These application studies on D/S ratio showed that a close negative correlation existed between D/S ratio and New York Heart Association Functional Classification (NYHA FC) (r = –0.659, p pregnant women with pre-eclampsia and either normal pregnant women or non-pregnant women were significant (p Conclusions: D/S ratio has important biological implication, which is a safe, easy, reliable, and effective indicator, can be used to evaluate fitness levels, served as a pathophysiological marker for screening of cardiovascular disease (CVD), for predicting risk of cardiac events, and for evaluating the severity and prognosis of CVD.

Dopamine: an immune transmitter

The dopaminergic system controls several vital central nervous system functions, including the control of movement, reward behaviors and cognition. Alterations of dopaminergic signaling are involved in the pathogenesis of neurodegenerative and psychiatric disorders, in particular Parkinson’s disease, which are associated with a subtle and chronic inflammatory response. A substantial body of evidence has demonstrated the non-neuronal expression of dopamine, its receptors and of the machinery that governs synthesis, secretion and storage of dopamine across several immune cell types. This review aims to summarize current knowledge on the role and expression of dopamine in immune cells. One of the goals is to decipher the complex mechanisms through which these cell types respond to dopamine, in order to address the impact this has on neurodegenerative and psychiatric pathologies such as Parkinson’s disease. A further aim is to illustrate the gaps in our understanding of the physiological roles of dopamine to encourage more targeted research focused on understanding the consequences of aberrant dopamine production on immune regulation. These highlights may prompt scientists in the field to consider alternative functions of this important neurotransmitter when targeting neuroinflammatory/neurodegenerative pathologies.

广东汉族人群D22S1045、D1S1656、D2S441和D10S1248基因座的遗传多态性分析

目的调查广东汉族人群D22S1045、D1S1656、D2S441和D10S1248等4个短串联重复序列(STR)基因座的遗传多态性。方法采用德国Qiagen公司的Hexaplex ESS试剂盒复合扩增169个广东汉族个体的4个STR基因座。扩增产物经美国ABI公司的3100遗传分析仪电泳分析其基因型,在各基因座均符合Hardy-Weinberg平衡的基础上计算其遗传学参数:基因频率、杂合度(H)、多态信息含量(P1C)、个体识别能力(PD)和非父排除率(PE)。结果169名无关个体4个STR基因座中共检出40个等位基因,4个基因座的基因型分布均符合Hardy-Weinberg平衡(P】0.05),

Taking out the garbage:cathepsin D and calcineurin in neurodegeneration

Cellular homeostasis requires a tightly controlled balance between protein synthesis, folding and degradation. Especially long-lived, post-mitotic cells such as neurons depend on an efficient proteostasis system to maintain cellular health over decades. Thus, a functional decline of processes contributing to protein degradation such as autophagy and general lysosomal proteolytic capacity is connected to several age-associated neurodegenerative disorders, including Parkinson＇s, Alzheimer＇s and Huntington＇s diseases. These so called proteinopathies are characterized by the accumulation and misfolding of distinct proteins, subsequently driving cellular demise. We recently linked efficient lysosomal protein breakdown via the protease cathep- sin D to the Ca2＋/calmodulin-dependent phosphatase calcineurin. In a yeast model for Parkinson＇s disease, functional calcineurin was required for proper trafficking of cathepsin D to the lysosome and for recycling of its endosomal sorting receptor to allow further rounds of shuttling. Here, we discuss these findings in relation to present knowledge about the involvement of cathepsin D in proteinopathies in general and a possible connection between this protease, calcineurin signalling and endosomal sorting in particular. As dysregulation of Ca2＋ homeostasis as well as lysosomal impairment is connected to a plethora of neurode- generative disorders, this novel interplay might very well impact pathologies beyond Parkinson＇s disease.

Vitamin D, selenium in type 2 diabetes and Hashimoto's thyroiditis: Is it effective?

The study by Feng et al,explores treatment approaches for these coexisting conditions.It emphasizes the potential advantages of selenium and vitamin D supplementation but also raises methodological and patient selection concerns.Findings indicate a complex interplay between interventions and disease markers,prompting the need for further research.Despite limitations,the study offers valuable insights into managing the intricate relationship between type 2 diabetes mellitus and Hashimoto's thyroiditis.The authors'contributions shed light on potential treatment avenues,although careful consideration of study design and patient characteristics is warranted for future investigations in this domain.

A Creation Model from the Gell-Mann Standard Model to the Creation of Bio Cells: Based on the Assumption of Homogeneous 5D Space-Time Universe

In this paper, we briefly go over the homogeneous 5D model field theory: from the 5D space-time inception, to its quantum field solutions given in terms of Higgs vacuum, filled with magnetic monopole bose fields of all energies. Then through the space dimension reduction projections, the Gell-Mann standard model was obtained as well as a quantum to Classical connection was made via introducing Bose distribution to the monopoles to obtain the Perelman entropy and Ricci Flow mappings. This provided us a picture to the creation of Astronomical objects, from galaxies to stars and planets. This method of splitting the monopole energy into ranges is extended to show that below the basic rest mass range of the electron and Quark, it still can be applied to explaining for the creation of the chemical elements periodic table. But perhaps the most interesting is in the lowest hundreds of Hz energy range, obtained from yet another 3 fold space symmetry breaking, into 2D × 1D, producing bio nitrogenous bases composed of 3 Carbon 12 in hexagon structures, due to preservation of the 1D monopole standing waves of this low frequencies. From that by imposing gauge changes the monopole states into DNA spectra. Since such spectra states retain the DLRO, it induces formation of charge carriers periodicity in a spherical bio cell.. It was then argued that due to cell’s surface proteins, the structure must contain partial filled VB, with “p” state hole density, and empty CB, separated from VB by a positive band gap. Such band structures resemble known HTC Cuprate ceramics. Since the HTC goes through a Superconductivity transition via the simultaneous bose exciton condensation, providing a Coulomb pressure, which reduces the band gap substantially, and induces the ODLRO transition of the hole density. The same obviously applies to the bio cells. Because of the near continuous exciton levels generated, a matching to the DNA spectra then can always occur by selective choices of proteins on the cell surface. Judging from a numerical study, we did years ago on YBCO, with doping. We found with a large enough VB hole density, the exciton induced superconducting gap can easily lead to Tc in the room temperature range. In fact by EMF excitation can increase the exciton pressure and trigger the ODLRO transition Tc upward. In fact, numerical results then suggest there do exist coherent EMF spectra from three key elements: Water, Carbon and Hydrogen, together with Oxygen, as studied over the years by numerous people, starting from Schrödinger to most recently Geesink.