α-Synucleinopathies are characterized by autonomic dysfunction and motor impairments. In the pure autonomic failure (PAF), α-synuclein (α-Syn) pathology is confined within the autonomic nervous ...system with no motor features, but mouse models recapitulating PAF without motor dysfunction are lacking. Here, we show that in TgM83
mice, inoculation of α-Syn preformed fibrils (PFFs) into the stellate and celiac ganglia induces spreading of α-Syn pathology only through the autonomic pathway to both the central nervous system (CNS) and the autonomic innervation of peripheral organs bidirectionally. In parallel, the mice develop autonomic dysfunction, featured by orthostatic hypotension, constipation, hypohidrosis and hyposmia, without motor dysfunction. Thus, we have generated a mouse model of pure autonomic dysfunction caused by α-Syn pathology. This model may help define the mechanistic link between transmission of pathological α-Syn and the cardinal features of autonomic dysfunction in α-synucleinopathy.
Chlorophyll (Chl) content, especially Chl b content, and stomatal conductance (Gs) are the key factors affecting the net photosynthetic rate (Pn). Setaria italica, a diploid C4 panicoid species with ...a simple genome and high transformation efficiency, has been widely accepted as a model in photosynthesis and drought-tolerance research. The current study characterized Chl content, Gs, and Pn of 48 Setaria mutants induced by ethyl methanesulfonate. A total of 24, 34, and 35 mutants had significant variations in Chl content, Gs, and Pn, respectively. Correlation analysis showed a positive correlation between increased Gs and increased Pn, and a weak correlation between decreased Chl b content and decreased Pn was also found. Remarkably, two mutants behaved with significantly decreased Chl b content but increased Pn compared to Yugu 1. Seven mutants behaved with significantly decreased Gs but did not decrease Pn compared to Yugu 1. The current study thus identified various genetic lines, further exploration of which would be beneficial to elucidate the relationship between Chl content, Gs, and Pn and the mechanism underlying why C4 species are efficient at photosynthesis and water saving.
Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by expanded CAG trinucleotide repeats (>36) in exon 1 of
gene that encodes huntingtin protein. ...Although HD is characterized by a predominant loss of neurons in the striatum and cortex, previous studies point to a critical role of aberrant accumulation of mutant huntingtin in microglia that contributes to the progressive neurodegeneration in HD, through both cell-autonomous and non-cell-autonomous mechanisms. Microglia are resident immune cells in the central nervous system (CNS), which function to surveil the microenvironment at a quiescent state. In response to various pro-inflammatory stimuli, microglia become activated and undergo two separate phases (M1 and M2 phenotype), which release pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), anti-inflammatory cytokines, and growth factors (TGF-β, CD206, and Arg1), respectively. Immunoregulation by microglial activation could be either neurotoxic or neuroprotective. In this review, we summarized current understanding about microglial activation in the pathogenesis and progression of HD, with a primary focus of M1 and M2 phenotype of activated microglia and their corresponding signaling pathways.
Objective
To evaluate the effects of body mass index (BMI) in patients with polycystic ovary syndrome (PCOS) undergoing controlled ovarian stimulation (COS) with intrauterine insemination (IUI).
...Methods
This retrospective study evaluated couples with PCOS undergoing COS and IUI. The relationship between cumulative IUI pregnancy outcomes and BMI, treatment cycles, treatment schemes, number of dominant follicles, endometrial thickness, infertility duration and type of infertility was analysed.
Results
The study evaluated 831 IUI cycles in 451 couples with PCOS. Compared with normoweight women, overweight and obese women required more human menopausal gonadotropin (hMG) doses and more days of COS. Gestational diabetes mellitus occurred more frequently in the obese group than in the other BMI groups. The clinical pregnancy and live birth rates in the hMG, clomiphene citrate (CC) + hMG and letrozole (LE) + hMG groups were significantly higher than those in the CC and LE groups. The clinical pregnancy rate was higher in the secondary infertility group compared with the primary infertility group.
Conclusion
Obese women might require more hMG doses and more days of COS to overcome the effects of weight. As BMI increases, the incidence of gestational diabetes might also increase. The number of cycles and type of infertility may have a predictive value for pregnancy outcomes.
The extragynoecial compitum formed by the incomplete fusion of carpel margins, while allowing intercarpellary growth of pollen tubes in apocarpous angiosperms, may also increase the risk of ...reproductive interference caused by heterospecific pollen (HP) deposition. In
Sagittaria
, congeneric HP tubes grow via different paths and enter the ovules later than conspecific pollen (CP) tubes. However, it is unclear how the growth advantage of the CP tube helps ensure reproductive success when HP is deposited on the stigmas. We performed molecular characterization of interspecies-pollinated seeds to examine the consequences of interspecific pollen deposition between
Sagittaria pygmaea
and
S. trifolia
. We also conducted CP–HP (1:1) mixed pollination and delayed CP pollination treatments to explore the seed-siring abilities of CP and HP. Our results showed that although HP could trigger the development of fruits, the interspecies-pollinated seeds contained partially developed embryos and could not germinate. More than 70% of the embryos in these seeds were molecularly identified as hybrids of both species, suggesting that HP tubes could enter the ovules and fertilize the egg cells. Moreover, CP could sire more offspring (≥70%) after the CP–HP (1:1) mixed pollination treatment, even when HP reached the stigma 0.5–1 h earlier than CP (≥50%). Following adequate CP vs. HP (1:1) pollination on carpels on two sides of the apocarpous gynoecium, both species produced > 70% conspecific seeds, indicating that the CP tubes could occupy ovules that should be occupied by HP via the extragynoecial compitum. Our results reveal that in
Sagittaria
, pollen deposition from co-existing congeneric heterospecies leads to interspecific seed discounting. However, the CP advantage mediated by the extragynoecial compitum is an effective strategy to mitigate the effects of interspecific pollen deposition. This study improves our understanding of how apocarpous angiosperms with an extragynoecial compitum can maintain species stability and mitigate the negative reproductive interference effect from sympatrically distributed related species.
The locus for familial cortical myoclonic tremor with epilepsy (FCMTE) has long been mapped to 8q24 in linkage studies, but the causative mutations remain unclear. Recently, expansions of intronic ...TTTCA and TTTTA repeat motifs within
were found to be involved in the pathogenesis of FCMTE in Japanese pedigrees. We aim to identify the causative mutations of FCMTE in Chinese pedigrees.
We performed genetic linkage analysis by microsatellite markers in a five-generation Chinese pedigree with 55 members. We also used array-comparative genomic hybridisation (CGH) and next-generation sequencing (NGS) technologies (whole-exome sequencing, capture region deep sequencing and whole-genome sequencing) to identify the causative mutations in the disease locus. Recently, we used low-coverage (~10×) long-read genome sequencing (LRS) on the PacBio Sequel and Oxford Nanopore platforms to identify the causative mutations, and used repeat-primed PCR for validation of the repeat expansions.
Linkage analysis mapped the disease locus to 8q23.3-24.23. Array-CGH and NGS failed to identify causative mutations in this locus. LRS identified the intronic TTTCA and TTTTA repeat expansions in
as the causative mutations, thus corroborating the recently published results in Japanese pedigrees.
We identified the pentanucleotide repeat expansion in
as the causative mutation in Chinese FCMTE pedigrees. Our study also suggested that LRS is an effective tool for molecular diagnosis of genetic disorders, especially for neurological diseases that cannot be positively diagnosed by conventional clinical microarray and NGS technologies.
This study aimed to evaluate the changes in the left ventricular (LV) myocardial work (MW) in breast cancer patients following chemotherapy by left ventricular pressure-strain loop (LVPSL).A total of ...50 patients with newly breast cancer undergoing postoperative adjuvant chemotherapy containing anthracycline were selected. Echocardiography was performed before the treatment (T0), the second (T2) and fourth (T4) cycles of chemotherapy, and 3 (P3 m) and 6 (P6 m) months after the end of chemotherapy. The standard dynamic images of the required sections were collected. After off-line analysis, the routine, global myocardial strain, and global MW parameters were obtained, and the average regional MW index (RMWI) and regional MW efficiency (RMWE) at three levels of LV were calculated.Compared with those at T0 and T2, the global work index (GWI), global constructive work (GCW), global work efficiency (GWE), and global longitudinal strain (GLS) gradually decreased and global wasted work (GWW) gradually increased at T4, P0, and P6 m. The mean RMWI and RMWE of the three levels of LV exhibited a gradually decreasing trend at T4, P0, and P6 m compared with those at T0 and T2. The GWI, GCW, GWE, mean RMWI, and RMWE (basal, medial, and apical) were negatively correlated with the GLS (r = −0.76, −0.66, −0.67, −0.76, −0.77, −0.66, −0.67, −0.59, and −0.61, respectively), whereas the GWW was positively correlated with the GLS (r = 0.55).The mean RMWI and RMWE are effective parameters to reflect the cardiotoxicity of LV, and LVPSL has certain value in the evaluation of the left ventricular myocardial work (LVMW) during anthracycline treatment and follow-up in breast cancer patients.
We initiate the Westlake BioBank for Chinese (WBBC) pilot project with 4,535 whole-genome sequencing (WGS) individuals and 5,841 high-density genotyping individuals, and identify 81.5 million SNPs ...and INDELs, of which 38.5% are absent in dbSNP Build 151. We provide a population-specific reference panel and an online imputation server ( https://wbbc.westlake.edu.cn/ ) which could yield substantial improvement of imputation performance in Chinese population, especially for low-frequency and rare variants. By analyzing the singleton density of the WGS data, we find selection signatures in SNX29, DNAH1 and WDR1 genes, and the derived alleles of the alcohol metabolism genes (ADH1A and ADH1B) emerge around 7,000 years ago and tend to be more common from 4,000 years ago in East Asia. Genetic evidence supports the corresponding geographical boundaries of the Qinling-Huaihe Line and Nanling Mountains, which separate the Han Chinese into subgroups, and we reveal that North Han was more homogeneous than South Han.
Chitosan/carbonated hydroxyapatite composite coatings (CCHCs) were fabricated according to the following steps: (i) preparation of calcium carbonate coatings (CCCs) on Ti6Al4V substrates by ...electrophoretic deposition; (ii) transformation of CCCs into carbonated hydroxyapatite coatings (CHACs) in a phosphate buffer solution (PBS); and (iii) formation of CCHCs by modification of CHACs with chitosan. Inorganic constituents in CCHCs are plate-like carbonated hydroxyapatite particles with a low crystallinity. Interestingly, macropores with a pore size of 0.5–2μm still remain among the carbonated hydroxyapatite plates even after the chitosan deposits homogeneously on the coatings. Moreover, CCHCs have moderately hydrophilic surfaces with a contact angle of 29.4° due to the presence of the chitosan. Biocompatibility tests have been carried out by using human bone mesenchymal stem cells (hBMSCs) as cell models. The hBMSCs show better cell morphology, adhesion, spreading and proliferation on CCHCs than on CHACs. The excellent biocompatibility of CCHCs is mainly attributed to the organic/inorganic compositions, macroporous structure and moderately hydrophilic surfaces. Hence, CCHCs have great potentials for bone implants.
•We have fabricated chitosan/carbonated hydroxyapatite composite coatings.•Composite coatings possess uniform surfaces due to the presence of chitosan.•Chitosan makes the coatings possess moderately hydrophilic surfaces.•Composite coatings exhibit better biocompatibility than apatite coatings.
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