Rhein alleviates MPTP-induced Parkinson's disease by suppressing neuroinflammation via MAPK/IκB pathway.

Background: Parkinson's disease (PD) is a common neurodegenerative disease with a rapid increase in incidence in recent years. Existing treatments cannot slow or stop the progression of PD. It was proposed that neuroinflammation leads to neuronal death, making targeting neuroinflammation a promising therapeutic strategy. Our previous studies have demonstrated that rhein protects neurons in vitro by inhibiting neuroinflammation, and it has been found to exhibit neuroprotective effects in Alzheimer's disease and epilepsy, but its neuroprotective mechanisms and effects on PD are still unclear. Methods: PD animal model was induced by 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP). ELISA, RT-qPCR, western blot and Immunofluorescence were used to detect the levels of inflammatory cytokines and M1 polarization markers. The protein expression levels of signaling pathways were measured by western blot. Hematoxylin-eosin (HE) staining showed that rhein did not damage the liver and kidney. Two behavioral tests, pole test and rotarod test, were used to evaluate the improvement effect of rhein on movement disorders. The number of neurons in the substantia nigra was evaluated by Nissl staining. Immunohistochemistry and western blot were used to detect tyrosine hydroxylase (TH) and α-synuclein. Results: Rhein inhibited the activation of MAPK/IκB signaling pathway and reduced the levels of pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α) and M1 polarization markers of microglia in vivo. In a mouse model of PD, rhein ameliorated movement disorders, reduced dopaminergic neuron damage and α-synuclein deposition. Conclusion: Rhein inhibits neuroinflammation through MAPK/IκB signaling pathway, thereby reducing neurodegeneration, α-synuclein deposition, and improving movement disorders in Parkinson's disease.

A novel SEMA6B variant causes adult-onset progressive myoclonic epilepsy-11 in a Chinese family: A case report and literature review.

This study describes a patient with progressive myoclonic epilepsy-11 (EPM-11), which follows autosomal dominant inheritance caused by a novel SEMA6B variant. Most patients develop this disease during infancy or adolescence with action myoclonus, generalized tonic-clonic seizures (GTCS), and progressive neurological deterioration. No cases of adult-onset EPM-11 have been reported yet. Here, we present one case of adult-onset EPM-11 who experienced gait instability, seizures, and cognitive impairment, and harbored a novel missense variant, c.432C>G (p.C144W). Our findings provide a foundation for a better understanding of the phenotypic and genotypic profiles of EPM-11. Further functional studies are recommended to elucidate the pathogenesis of this disease.

The Genetic Echo of the Tarim Mummies in Modern Central Asians.

The diversity of Central Asians has been shaped by multiple migrations and cultural diffusion. Although ancient DNA studies have revealed the demographic changes of the Central Asian since the Bronze Age, the contribution of the ancient populations to the modern Central Asian remains opaque. Herein, we performed high-coverage sequencing of 131 whole genomes of Indo-European-speaking Tajik and Turkic-speaking Kyrgyz populations to explore their genomic diversity and admixture history. By integrating the ancient DNA data, we revealed more details of the origins and admixture history of Central Asians. We found that the major ancestry of present-day Tajik populations can be traced back to the admixture of the Bronze Age Bactria-Margiana Archaeological Complex and Andronovo-related populations. Highland Tajik populations further received additional gene flow from the Tarim mummies, an isolated ancient North Eurasian-related population. The West Eurasian ancestry of Kyrgyz is mainly derived from Historical Era populations in Xinjiang of China. Furthermore, the recent admixture signals detected in both Tajik and Kyrgyz are ascribed to the expansions of Eastern Steppe nomadic pastoralists during the Historical Era.

Tracing the Genetic Legacy of the Tibetan Empire in the Balti.

The rise and expansion of Tibetan Empire in the 7th to 9th centuries AD affected the course of history across East Eurasia, but the genetic impact of Tibetans on surrounding populations remains undefined. We sequenced 60 genomes for four populations from Pakistan and Tajikistan to explore their demographic history. We showed that the genomes of Balti people from Baltistan comprised 22.6-26% Tibetan ancestry. We inferred a single admixture event and dated it to about 39-21 generations ago, a period that postdated the conquest of Baltistan by the ancient Tibetan Empire. The analyses of mitochondrial DNA, Y, and X chromosome data indicated that both ancient Tibetan males and females were involved in the male-biased dispersal. Given the fact that the Balti people adopted Tibetan language and culture in history, our study suggested the impact of Tibetan Empire on Baltistan involved dominant cultural and minor demic diffusion.

Author Correction: 863 genomes reveal the origin and domestication of chicken.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

863 genomes reveal the origin and domestication of chicken.

Despite the substantial role that chickens have played in human societies across the world, both the geographic and temporal origins of their domestication remain controversial. To address this issue, we analyzed 863 genomes from a worldwide sampling of chickens and representatives of all four species of wild jungle fowl and each of the five subspecies of red jungle fowl (RJF). Our study suggests that domestic chickens were initially derived from the RJF subspecies Gallus gallus spadiceus whose present-day distribution is predominantly in southwestern China, northern Thailand and Myanmar. Following their domestication, chickens were translocated across Southeast and South Asia where they interbred locally with both RJF subspecies and other jungle fowl species. In addition, our results show that the White Leghorn chicken breed possesses a mosaic of divergent ancestries inherited from other subspecies of RJF. Despite the strong episodic gene flow from geographically divergent lineages of jungle fowls, our analyses show that domestic chickens undergo genetic adaptations that underlie their unique behavioral, morphological and reproductive traits. Our study provides novel insights into the evolutionary history of domestic chickens and a valuable resource to facilitate ongoing genetic and functional investigations of the world's most numerous domestic animal.

Lymphocyte To High-Density Lipoprotein Ratio As A New Indicator Of Inflammation And Metabolic Syndrome.

PURPOSE: Metabolic syndrome (MetS), which is a global public health problem, is a state of chronic low-grade inflammation. This study looked at the changes in hematological parameters and the predictive value of the lymphocyte to high-density lipoprotein cholesterol (HDL-C) ratio (LHR) as a new index in subjects with and without MetS in coastal cities in southern China. PATIENTS AND METHODS: In this cross-sectional study, there were 852 participants (n = 598 with MetS and n = 254 without MetS). MetS was defined in accordance with the National Cholesterol Education Program, Adult Treatment Panel III (NCEP-ATP III) criteria. RESULTS: MetS was positively correlated with white blood cell count, total lymphocyte count, neutrophil count, red blood cell count, hematocrit, hemoglobin, and high-sensitivity C-reactive protein levels (p<0.05). In addition, there was a positive correlation between LHR and the number of metabolic risk factors for MetS. In a logistic regression analysis, LHR (odds ratio: 4.117; 95% CI: 2.766-6.309; p<0.001) was an independent predictor of MetS. When a receiver operating characteristic (ROC) curve analysis was used to assess the value of LHR for predicting MetS, the area under the curve yielded a cut-off value of 1.657, with a sensitivity of 65% and a specificity of 64% (p<0.0001). CONCLUSION: In summary, MetS can involve changes in blood parameters, and LHR may be a useful marker of inflammation to assess the presence and severity of MetS.

Correction to: The evolutionary genetics of lactase persistence in seven ethnic groups across the Iranian plateau.

AbstractIn the original publication of this article [1], the colors of the Fig. 1 are wrong, and are revised in the updated figure below.

The evolutionary genetics of lactase persistence in seven ethnic groups across the Iranian plateau.

BACKGROUND: The ability to digest dietary lactose is associated with lactase persistence (LP) in the intestinal lumen in human. The genetic basis of LP has been investigated in many populations in the world. Iran has a long history of pastoralism and the daily consumption of dairy products; thus, we aim to assess how LP has evolved in the Iranian population. We recruited 400 adult individuals from seven Iranian ethnic groups, from whom we investigated their lactose tolerance and screened the genetic variants in their lactase gene locus. RESULTS: The LP frequency distribution ranged from 0 to 29.9% in the seven Iranian ethnic groups with an average value of 9.8%. The variants, - 13910*T and - 22018*A, were significantly associated with LP phenotype in Iranians. We found no evidence of hard selective sweep for - 13910*T and - 22018*A in Persians, the largest ethnic group of Iran. The extremely low frequency of - 13915*G in the Iranian population challenged the view that LP distribution in Iran resulted from the demic diffusion, especially mediated by the spread of Islam, from the Arabian Peninsula. CONCLUSIONS: Our results indicate the distribution of LP in seven ethnic groups across the Iranian plateau. Soft selective sweep rather than hard selective sweep played a substantial role in the evolution of LP in Iranian populations.

Expression and significance of Sirt1 in renal allografts at the early stage of chronic renal allograft dysfunction.

OBJECTIVE: To investigate the expression and significance of Sirt1 in renal allografts at the early stage of chronic renal allograft dysfunction (CRAD). METHODS: CRAD rat models were established using classical orthotopic F344-Lewis kidney transplantation. F344 and Lewis uninephrectomized rats were used as controls. Twelve weeks after the operation, the rats were sacrificed for renal function, histological, immunohistochemistry and molecular biological analyses. RESULTS: The 24-h urinary protein excretion and serum creatinine levels, urine microalbumin/creatinine ratios, and Banff score sums were significantly increased in the CRAD group compared with those in the F344 and Lewis control groups. The degree of mononuclear cell infiltration and interstitial fibrosis (IF) was higher in the CRAD group than in the control groups. Sirt1, TGF-ß1, MCP-1, ICAM-1 expression was up-regulated in CRAD. Furthermore, Sirt1 expression was negatively correlated with the 24-h urinary protein excretion and serum creatinine levels, Banff score sums, mononuclear cell infiltration and IF severity, and TGF-ß1, MCP-1 and ICAM-1 expression levels. CONCLUSION: Sirt1 might be involved in the pathogenic process of IF and inflammation at the early stage of CRAD. Thus, Sirt1 represents a novel therapeutic strategy and target for the early prevention and treatment of CRAD.

Mitochondrial genomes uncover the maternal history of the Pamir populations.

The Pamirs, among the world's highest mountains in Central Asia, are one of homelands with the most extreme high altitude for several ethnic groups. The settlement history of modern humans on the Pamirs remains still opaque. Herein, we have sequenced the mitochondrial DNA (mtDNA) genomes of 382 individuals belonging to eight populations from the Pamirs and the surrounding lowlands in Central Asia. We construct the Central Asian (including both highlanders and lowlanders) mtDNA haplogroup tree at the highest resolution. All the matrilineal components are assigned into the defined mtDNA haplogroups in East and West Eurasians. No basal lineages that directly emanate from the Eurasian founder macrohaplogroups M, N, and R are found. Our data support the origin of Central Asian being the result of East-West Eurasian admixture. The coalescence ages for more than 93% mtDNA lineages in Central Asians are dated after the last glacial maximum (LGM). The post-LGM and/or later dispersals/admixtures play dominant roles in shaping the maternal gene pool of Central Asians. More importantly, our analyses reveal the mtDNA heterogeneity in the Pamir highlanders, not only between the Turkic Kyrgyz and the Indo-European Tajik groups, but also among three highland Tajiks. No evidence supports positive selection or relaxation of selective constraints in the mtDNAs of highlanders as compared to that of lowlanders. Our results suggest a complex history for the peopling of Pamirs by multiple waves of migrations from various genetic resources during different time scales.

Identity-by-descent refines mapping of candidate regions for preaxial polydactyly II /III in a large Chinese pedigree.

Preaxial polydactyly (PPD) is congenital hand malformation characterized by the duplication of digit. Herein, we scan the genome-wide SNPs for a large Chinese family with PPD-II/III. We employ the refined IBD algorithm to identify the identity-by-decent (IBD) segments and compare the frequency among the patients and normal relatives. A total of 72 markers of 0.01 percentile of the permutation are identified as the peak signals. Among of them, 57markers locate on chromosome 7q36 which is associated with PPD. Further analyses refine the mapping of candidate region in chromosome 7q36 into two 380 Kb fragments within LMBR1 and SHH respectively. IBD approach is a suitable method for mapping causal gene of human disease. Target-enrichment sequencing as well as functional experiments are required to illustrate the pathogenic mechanisms for PPD in the future.

[Association of waist-to-hip ratio with insulin resistance in non-diabetic normal-weight individuals: a cross-sectional study].

OBJECTIVE: To explore the relationship between waist-to-hip ratio (WHR) and insulin resistance(IR) in non-diabetic normal-weight individuals and investigate how this association differs between male and femalesubjects. METHODS: From June to October, 2012, we performed a cross-sectional survey among 2142 community-based non-diabetic Chinese participants, who were divided into 4 groups according to the gender-specific quartiles of WHR. Homeostatic model assessment of insulin resistance (HOMA-IR), calculated as the product of fasting plasma glucose (mmol/L) and fasting insulin (mU/L) divided by 22.5, was used as the indicator of insulin resistance. Logistic regression models were used to explore the association of WHR with IR in these subjects. RESULTS: In the unadjusted model, WHR was significantly associated with IR in women (OR=6.60, 95%CI: 2.86-15.26, P<0.001); the association was still significant (OR=3.28, 95%CI: 1.34-8.04, P=0.009) after adjustment for the potential confounders including the history of hypertension, coronary heartdisease, current smoker, physical inactivity, and body mass index. CONCLUSION: WHR is independently associated with IR in non-diabetic Chinese women with normal body weight.

Modulation of Root Skewing in Arabidopsis by Apyrases and Extracellular ATP.

When plant primary roots grow along a tilted surface that is impenetrable, they can undergo a slanted deviation from the direction of gravity called skewing. Skewing is induced by touch stimuli which the roots experience as they grow along the surface. Touch stimuli also induce the release of extracellular ATP (eATP) into the plant's extracellular matrix, and two apyrases (NTPDases) in Arabidopsis, APY1 and APY2, can help regulate the concentration of eATP. The primary roots of seedlings overexpressing APY1 show less skewing than wild-type plants. Plants suppressed in their expression of APY1 show more skewing than wild-type plants. Correspondingly, chemical inhibition of apyrase activity increased skewing in mutants and wild-type roots. Exogenous application of ATP or ATPγS also increased skewing in wild-type roots, which could be blocked by co-incubation with a purinergic receptor antagonist. These results suggest a model in which gradients of eATP set up by differential touch stimuli along roots help direct skewing in roots growing along an impenetrable surface.

Actin filaments and microtubules of Arabidopsis suspension cells show different responses to changing turgor pressure.

Past decades have brought great advances in understanding the relationship between turgor pressure and plant cell growth. New studies have provided evidence that turgor pressure acts as a stimulus for cell growth, and is also a developmental cue for post-embryonic organogenesis. However, the subcellular mechanisms underlying plant cell turgor pressure sensing remain unclear. Here, using the relatively simple undifferentiated cells from suspension cultures, we report real-time in vivo observations of the reorganization of microtubules and actin microfilaments induced by turgor pressure changes. We found that these two cytoskeletal elements differed in their reorganization patterns. Our results will be useful in the understanding of the relationship between the cytoskeleton, turgor pressure, and stress in plant cell morphogenesis.