[Clinical phenotype and genotype analysis of progressive familial intrahepatic cholestasis type 3 caused by novel ABCB4 gene mutation].

Objective: To investigate the pathogenic mechanism and clinical characteristics of the novel splicing variant of ATP-binding cassette subfamily B member 4 (ABCB4) and provide a basis for subsequent genetic diagnosis. Methods: The clinical data of a 5-year-old child with cholestatic liver disease admitted to the Beijing Children's Hospital of Capital Medical University was retrospectively analyzed. The pathogenic variations were detected by whole exome sequencing and verified by Sanger sequencing, and bioinformatics was used to predict the pathogenicity of the mutation sites. Possible pathogenic variations were verified in vitro by Minigene assay. The clinical outcome was followed after discharge from hospital. Results: The 5-year-old boy had developed cholestasis at the age of 11 months. His physical examination showed obvious enlargement of the liver and spleen. Cholestatic cirrhosis was diagnosed by liver function tests, abdominal ultrasonography, liver biopsy and pathology. The results of genetic analysis showed that the patient was a complex heterozygote of the ABCB4 gene, with a pathogenic mutation c.2860G>A and a novel mutation c.2065-8T>G, derived from the mother and father respectively. The conservative prediction of the c.2065-8T>G site showed that this region was highly conserved and may affect splicing. Minigene assay results confirmed that the c.2065-8T>G mutation resulted in a 7 bp retention of intron 16 in the mature mRNA. In the absence of nonsense-mediated mRNA decay, the amino acid frameshift forms a truncated protein, which is represented by p.Glu689ValfsTer19. The patient was diagnosed as progressive familial intrahepatic cholestasis type 3 (PFIC3) and treated with ursodeoxycholic acid (UDCA). His clinical symptoms improved during 18 months of follow-up. Conclusions: The c.2065-8T>G variant is confirmed to affect the splicing process and exhibits complex heterozygosity with c.2860G>A, which is identified as the cause of the disease. PFIC3 children with this variant showed cholestatic liver disease as the main manifestation with a slow progression and was sensitive to treatment with UDCA.

Effects of the bovine SLICK1 mutation in PRLR on sweat gland area, FOXA1 abundance, and global gene expression in skin.

The SLICK1 mutation in the prolactin receptor (PRLR) results in a short-hair coat and increased ability to regulate body temperature during heat stress. It is unclear whether the mutation affects capacity for sweating. The objective of this observational study was to evaluate whether the SLICK1 mutation in PRLR alters characteristics of skin related to sweat gland abundance or function. Skin biopsies from 31 Holstein heifers, including 14 wild-type (SL-/-) and 17 heterozygous slick (SL+/-), were subjected to histological analysis to determine the percent of the surface area of skin sections that are occupied by sweat glands. We detected no effect of genotype on this variable. Immunohistochemical analysis of the forkhead transcription factor A1 (FOXA1), a protein essential for sweating in mice, from 6 SL-/- and 6 SL+/- heifers indicated twice as much FOXA1 in sweat glandular epithelia of SL+/- heifers as in SL-/- heifers. Results from RNA sequencing of skin biopsies from 5 SL-/- and 7 SL+/- heifers revealed few genes that were differentially expressed and none that have been associated with sweat gland development or function. In conclusion, results do not support the idea that the SLICK1 mutation changes the abundance of sweat glands in skin, but do show that functional properties of sweat glands, as indicated by increased abundance of immunoreactive FOXA1, are modified by inheritance of the mutation in PRLR.

[Clinical features and risk factors for early relapse of pediatric ulcerative colitis].

Objective: To investigate the clinical features of pediatric ulcerative colitis (UC) and analyze the risk factors of disease relapse. Methods: The clinical data of 79 children with UC diagnosed in Beijing Children's Hospital, Capital Medical University from January 2016 to February 2021 were retrospectively analyzed. They were divided into early relapse group and non-early relapse group according to the clinical relapse within 12 months after diagnosis. T-test, rank sum test, χ2 test or Fisher's exact test were used to compare the variables between the 2 groups, including the clinical features, laboratory examination results and treatments. The Logistic regression was used to analyze the risk factors of early relapse. The cumulative relapse rate during follow-up was calculated by Kaplan-Meier method. Results: Among the 79 UC children, 46 were males and 33 were females, and the age of onset was 10.6 (6.4, 12.7) years. The children were mainly characterized by extensive disease (E3) and pancolitis (E4) (51/79, 65%), moderate to severe activity (48/79, 61%) and moderate to severe inflammation of colonic mucosa (71/79, 90%). Thirty-eight (48%) patients had atypical phenotype and 17 (22%) had extraintestinal manifestations. The follow-up period was 43.9 (22.8, 61.3) months, and of the 41 patients rechecked with colonoscopy, 7 (17%) had disease progression. According to Kaplan-Meier analysis, the cumulative relapse rate of the 79 cases at 3 months, 6 months, 1 year and 2 years after diagnosis were 27% (21/79), 47% (37/79), 57% (45/79) and 73% (53/73), respectively. There were 45 children (57%) in early relapse group and 34 (43%) in non-early relapse group. In early relapse group, hemoglobin and mucosal healing rate were both significantly lower (105 (87, 122) vs. 120 (104, 131) g/L, 28% (7/25) vs. 7/9, Z=-2.38, χ²=4.87, both P<0.05). The rate of steroid-dependent, E3 and step-up therapy during the induction period were all significantly higher than those in non-early relapse group (11/19 vs. 1/12, 24% (11/45) vs. 6% (2/34), 29% (13/45) vs. 6% (2/34), χ²=5.67, 4.85, 6.66, all P<0.05). Multivariate Logistic regression analysis showed that extraintestinal manifestations (OR=4.33, 95%CI 1.05-17.83), E3 (OR=8.27, 95%CI 1.47-46.46) and step-up therapy during the induction period (OR=5.58, 95%CI 1.01-30.77) were independent risk factors for early relapse. Conclusions: Pediatric UC is usually extensive and severe, with atypical phenotype, a high rate of relapse and a risk of disease progression. Extraintestinal manifestations, E3 and step-up therapy during the induction period are independent risk factors for early relapse.

[Epidemiological investigation of tinnitus in Sichuan and Chongqing].

Objectives: To investigate the prevalence and associated risk factors of tinnitus in Sichuan and Chongqing. Methods: We designed a tinnitus epidemiological questionnaire. The multi-stage stratified cluster random sampling methods was applied to obtain study subjects in six areas (Nanchong, Jiangjin, Fengdu, Yunyang, Suining and Ya'an), which were selected for epidemiological investigation. Home visit completion of epidemiological questionnaires was conducted. The trained investigators guided the respondents to fill in the tinnitus epidemiological questionnaires, and the epidemiological status of six areas on prevalence and risk factor was investigated. SPSS 22.0 software was used for statistical analysis. Results: Sampling population were 10 289, in which 9 273 were valid questionnaires. There were 4 281 males and 4 992 females, with an average age of 47.3 years, among which 34.83% (3 230/9 273) had tinnitus. 3.99% (370/9 273) were diagnosed with bothersome tinnitus. In a multivariable logistic regression mod, the following factors were associated with onsetting of tinnitus: sleep disorder [Odds Ratio(OR)=3.74] and noise exposure(OR=1.99). The risk of disease was lowest in the age of 30-40 years old, while the risk of disease was higher for people under 30 and over 40. In another multivariable logistic regression mode, the following factors were associated with having bothersome tinnitus: older people were more likely to suffer from tinnitus, sleep disorders (OR=4.68) and noise exposure (OR=1.56). Conclusions: The prevalence of tinnitus in Sichuan and Chongqing is about 34.83%, but most of the tinnitus is short-lived and has low loudness, which will not affect the patients. Only a small number of patients with tinnitus (3.99%) persist and affect their health and need treatment. The occurrence and exacerbation of tinnitus may be related to sleep, age, and noise exposure.

Unusual competition of superconductivity and charge-density-wave state in a compressed topological kagome metal.

Understanding the competition between superconductivity and other ordered states (such as antiferromagnetic or charge-density-wave (CDW) state) is a central issue in condensed matter physics. The recently discovered layered kagome metal AV3Sb5 (A = K, Rb, and Cs) provides us a new playground to study the interplay of superconductivity and CDW state by involving nontrivial topology of band structures. Here, we conduct high-pressure electrical transport and magnetic susceptibility measurements to study CsV3Sb5 with the highest Tc of 2.7 K in AV3Sb5 family. While the CDW transition is monotonically suppressed by pressure, superconductivity is enhanced with increasing pressure up to P1 ≈ 0.7 GPa, then an unexpected suppression on superconductivity happens until pressure around 1.1 GPa, after that, Tc is enhanced with increasing pressure again. The CDW is completely suppressed at a critical pressure P2 ≈ 2 GPa together with a maximum Tc of about 8 K. In contrast to a common dome-like behavior, the pressure-dependent Tc shows an unexpected double-peak behavior. The unusual suppression of Tc at P1 is concomitant with the rapidly damping of quantum oscillations, sudden enhancement of the residual resistivity and rapid decrease of magnetoresistance. Our discoveries indicate an unusual competition between superconductivity and CDW state in pressurized kagome lattice.

Intrinsic Spin Susceptibility and Pseudogaplike Behavior in Infinite-Layer LaNiO_{2}.

The recent discovery of superconductivity in doped infinite-layer nickelates has stimulated intensive interest, especially for similarities and differences compared to that in cuprate superconductors. In contrast to cuprates, although earlier magnetization measurement reveals a Curie-Weiss-like behavior in undoped infinite-layer nickelates, there is no magnetic ordering observed by elastic neutron scattering down to liquid helium temperature. Until now, the nature of the magnetic ground state in undoped infinite-layer nickelates was still elusive. Here, we perform a nuclear magnetic resonance (NMR) experiment through ^{139}La nuclei to study the intrinsic spin susceptibility of infinite-layer LaNiO_{2}. First, the signature for magnetic ordering or freezing is absent in the ^{139}La NMR spectrum down to 0.24 K, which unambiguously confirms a paramagnetic ground state in LaNiO_{2}. Second, a pseudogaplike behavior instead of Curie-Weiss-like behavior is observed in both the temperature-dependent Knight shift and nuclear spin-lattice relaxation rate (1/T_{1}), which is widely observed in both underdoped cuprates and iron-based superconductors. Furthermore, the scaling behavior between the Knight shift and 1/T_{1}T has also been discussed. Finally, the present results imply a considerable exchange interaction in infinite-layer nickelates, which sets a strong constraint for the proposed theoretical models.

[Mutation analysis and prenatal diagnosis of MYO7A gene in a case of Usher syndrome type 1].

Objective: To analyze the clinical characteristics and identify the causative gene of a case with congenital deafness. Methods: Detailed medical history and clinical examination of a 4-year-old male child with congenital deafness were conducted in the First Affiliated Hospital of Army Military Medical University in June 2016. He was diagnosed with sensorineural deafness. The venous blood of the child and his parents was drawn, and genomic DNA was extracted. Proband's DNA was performed with targeted capture of high-throughput sequencing, then Sanger sequencing was used to verify the suspected mutation and segregation in this pedigree. According to the genetic diagnosis of the proband's deafness, ophthalmic examinations were performed. Genetic prenatal diagnosis was performed when the proband's mother was pregnant again. Results: The patient was detected with p.Trp1466Ter/p.Tyr2042Ter compound heterozygous mutations of MYO7A gene with targeted high-throughput sequencing. The mutation of p.Trp1466Ter was a reported mutation, while p.Tyr2042Ter has not been reported. In addition to congenital deafness, retinitis pigmentosa was also found by ophthalmologic examination, and the patient was clinically diagnosed with Usher syndrome type 1. Amniocentesis and fetal DNA sequencing were performed on the repregnancy fetus of this family at 18 weeks of gestation. The heterozygous mutation of MYO7A gene p.Tyr2042Ter was found, and the other allele was the wild type, indicating that the child will not exhibit clinical manifestations of Usher syndrome type 1. Indeed, the second child passed neonatal hearing screening. Conclusions: The clinical features and genetic variants were delineated in this family with Usher syndrome type 1. The results of the current study have enriched the phenotype and genotype data of the disease and provided a basis for genetic counseling.

Phylogenetic diversity is a better predictor of wetland community resistance to Alternanthera philoxeroides invasion than species richness.

Highly biodiversity communities have been shown to better resist plant invasions through complementarity effects. Species richness (SR) is a widely used biodiversity metric but lacks explanatory power when there are only a few species. Communities with low SR can have a wide variety of phylogenetic diversities (PD), which might allow for a better prediction of invasibility. We assessed the effect of diversity reduction of a wetland community assemblage typical of the Beijing area on biotic resistance to invasion of the exotic weed Alternanthera philoxeroides and compared the reduction in SR and PD in predicting community invasibility. The eight studied resident species performed similarly when grown alone and when grown in eight-species communities together with the invasive A. philoxeroides. Variation partitioning showed that PD contributed more to variation in both A. philoxeroides traits and community indicators than SR. All A. philoxeroides traits and community indicators, except for evenness index, showed a linear relationship with PD. However, only stem length of A. philoxeroides differed between the one- and two-species treatments, and the diversity index of the communities differed between the one- and two-species treatments and between the one- and four-species treatments. Our results showed that in natural or semi-natural wetlands with relatively low SR, PD may be a better predictor of invasibility than SR. When designing management strategies for mitigating A. philoxeroides invasion, deliberately raising PD is expected to be more efficient than simply increasing species number.

Effects of parental light environment on growth and morphological responses of clonal offspring.

Environments experienced by parent ramets of clonal plants can potentially influence fitness of clonal offspring ramets. Such clonal parental effects may result from heritable epigenetic changes, such as DNA methylation, which can be removed by application of DNA de-methylation agents such as 5-azacytidine. To test whether parental shading effects occur via clonal generation and whether DNA methylation plays a role in such effects, parent plants of the clonal herb Alternanthera philoxeroides were first subjected to two levels of light intensity (high versus low) crossed with two levels of DNA de-methylation (no or with de-methylation by application of 5-azacytidine), and then clonal offspring taken from each of these four types of parent plant were subjected to the same two light levels. Parental shading effects transmitted via clonal generation decreased growth and modified morphology of clonal offspring. Offspring responses were also influenced by DNA methylation level of parent plants. For clonal offspring growing under low light, parental shading effects on growth and morphology were always negative, irrespective of the parental de-methylation treatment. For clonal offspring growing under high light, parental shading effects on offspring growth and morphology were negative when the parents were not treated with 5-azacytidine, but neutral when they were treated with 5-azacytidine. Overall, parental shading effects on clonal offspring performance of A. philoxeroides were found, and DNA methylation is likely to be involved in such effects. However, parental shading effects contributed little to the tolerance of clonal offspring to shading.

[Clinical analysis of eosinophilic gastroenteritis in 71 children].

Objective: To summarize the clinical data including manifestations, diagnosis, treatment and prognosis of eosinophilic gastroenteritis (EGE) in children. Methods: A retrospective analysis was performed in 71 patients with pathologically proven EGE at Beijing Children's Hospital Affiliated to Capital Medical University from January 2008 to January 2017. Their clinical manifestations, laboratory and imaging examinations, endoscopic findings, histopathological examinations, and treatment were collected and analyzed. Results: Among 71 EGE cases, 47 (66%) cases were male and 24 (34%) cases were female, and the median age was 9.2 (0.2-16.5) years old. The main clinical manifestations included abdominal pain (76%, 54/71), vomiting (68%, 48/71), anorexia (54%, 38/71), weight loss (38%, 27/71), and diarrhea (37%, 26/71). There were 27 cases (38%) with a history of allergic diseases or family history. The median absolute value of eosinophil in peripheral blood of the 71 patients was 0.4 (0-36.8)×10(9)/L, and 27 cases (38%) showed an increase in eosinophil counts. Serum IgE was measured in 52 patients (104.3 (3.4- 3 000.0)×10(3) U/L), and 30 patients (58%) showed an increase in serum IgE. A large number of eosinophils ((41.0±8.5)/HP) were found in 3 patients' ascites. The endoscopic examination of upper gastrointestinal tract revealed hyperemic edema in 62 cases (87%), plaque in 44 cases (62%), erosion in 17 cases (24%) and ulceration in 16 cases (23%). Histopathologically, in 8 cases (11%) the disease involved both stomach and duodeneum, in 21 cases (30%) involved stomach only, and in 37 cases (52%) involved duodeneum only. In addition, in 6 cases (8%) the disease involved esophagus and in 10 cases (14%) involved colorectum. Microscopically, eosinophil counts averaged 67/HP, 33/HP, 40/HP and 38/HP in esophageal, gastric, duodenal and colorectal mucosa respectively. A total of 34 cases were treated with glucocorticoid, and all these patients had alleviation of symptoms, which occurred within 14.9 days on average, but EGE recurred in 11 cases (32%). Conclusions: The clinical symptoms and endoscopic findings of EGE are diverse and nonspecific. Histopathological examination of gastrointestinal mucosa is particularly important for the diagnosis. Glucocorticoid treatment is effective, but the patients with EGE are prone to relapse.

[Clinical analysis of intestinal lymphangiectasia in 47 children].

Objective: To analyze the clinical manifestations, diagnosis, treatment and prognosis of intestinal lymphangiectasia (IL) in children in order to improve the skills of diagnosis and treatment of IL. Method: Clinical manifestations, laboratory findings, gastroscopic findings, histopathological examinations and lymphatic radionuclide imaging assessments were analyzed retrospectively among 47 IL patients who were hospitalized in the Gastroenterology Department of Beijing Children's Hospital Affiliated to Capital Medical University from June 2007 to December 2015. All patients were followed up by telephone. According to the various causes, the patients were divided into the primary intestinal lymphangiectasia (PIL) group and secondary IL group, and their clinical manifestations were compared by t test, Rank sum test or Chi-square test. Result: In 47 IL patients, there were 38 children (81%) younger than 3 years old. There were 43 PIL patients (91%) and 4 secondary IL patients (9%). Between PIL and secondary IL, there were statistical differences in serum albumin (t=-3.950, P<0.005) , globulin(t=-2.850, P=0.007), age of onset(U=27.000, P=0.024), age at diagnosis(U=29.000, P=0.030) and course of disease(U=26.500, P=0.023), whereas there were no statistical differences in lymphocyte count, IgG, lymphatic radionuclide imaging, histopathology and gender(all P>0.05). Edema (44 cases, 94%), diarrhea (42 cases, 89%), accompanied with infection (35 cases, 74%) and ascites (30 cases, 64%) were the main clinical manifestations. In 47 IL patients, 45 patients were done gastroscopy and histopathological examinations, and there were 31 patients' histopathological examinations(69%) were positive. Forty patients were done lymphatic radionuclide imaging, and there was evidence of protein losing from gut via lymphatic radionuclide imaging in 39 patients(98%). Among 47 patients, 35 patients (74%) were followed up, 32 patients had good prognosis, 2 patient failed to show evidence of improvement, 1 patient died and no patient experienced a relapse till the end of the follow-up. In 35 patients, 28 patients were treated with medium chain triglycerides (MCT) dietary therapy, 26 patients showed improvement in symptoms, and 2 patients had no improvement. Among 35 patients with follow-up, there were 6 patients received surgical treatment, and their symptoms were improved. Conclusion: PIL are the majority of IL in children younger than 3 years old. The main clinical manifestations are edema, diarrhea, accompanied with infection and ascites. For the patients without the evidence of lymphangiectasia from duodenum histopathological examination, further consideration of lymphatic radionuclide imaging, clinical manifestations, and laboratory studies are needed to make a final diagnosis. MCT dietary therapy is the cornerstone of IL medical management.

Clonal integration facilitates spread of Paspalum paspaloides from terrestrial to cadmium-contaminated aquatic habitats.

Cadmium (Cd) is a hazardous environmental pollutant with high toxicity to plants, which has been detected in many wetlands. Clonal integration (resource translocation) between connected ramets of clonal plants can increase their tolerance to stress. We hypothesised that clonal integration facilitates spread of amphibious clonal plants from terrestrial to Cd-contaminated aquatic habitats. The spread of an amphibious grass Paspalum paspaloides was simulated by growing basal older ramets in uncontaminated soil connected (allowing integration) or not connected (preventing integration) to apical younger ramets of the same fragments in Cd-contaminated water. Cd contamination of apical ramets of P. paspaloides markedly decreased growth and photosynthetic capacity of the apical ramets without connection to the basal ramets, but did not decrease these properties with connection. Cd contamination did not affect growth of the basal ramets without connection to the apical ramets, but Cd contamination of 4 and 12 mg·l-1 significantly increased growth with connection. Consequently, clonal integration increased growth of the apical ramets, basal ramets and whole clones when the apical ramets were grown in Cd-contaminated water of 4 and 12 mg·l-1 . Cd was detected in the basal ramets with connection to the apical ramets, suggesting Cd could be translocated due to clonal integration. Clonal integration, most likely through translocation of photosynthates, can support P. paspaloides to spread from terrestrial to Cd-contaminated aquatic habitats. Amphibious clonal plants with a high ability for clonal integration are particularly useful for re-vegetation of degraded aquatic habitats caused by Cd contamination.

[Single center retrospective study of 184 children with inflammatory bowel disease seen from 2000-2014].

Objective: To investigate the clinical data of children with inflammatory bowel disease (IBD) retrospectively, including Crohn's disease (CD) and ulcerative colitis (UC) and identify the clinical characteristics and trends of change. Method: Clinical data of hospitalized patients diagnosed as IBD in Beijing Children's Hospital from January 2000 to December 2014 were collected and retrospectively analyzed. Patients were divided into six groups based on type of disease and year of admission: Group A1(CD, 2000-2004) included 12 patients, Group B1(CD, 2005-2009) included 11, Group C1(CD, 2010-2014) included 51; Group A2(UC, 2000-2004) included 17, Group B2(UC, 2005-2009) included 25, Group C2(UC, 2010-2014) included 68. Result: A total of 184 IBD patients were included in the study, 74 had CD and 110 had UC. The hospitalization constituent ratio of CD increased from 0.6/10 000 in Year 2000 to 2.9/10 000 in Year 2014. The hospitalization constituent ratio of UC increased from 0.5/10 000 in Year 2001 to 3.9/10 000 in Year 2014. The hospitalization constituent ratios of CD and UC both increased gradually(P<0.05). Up to 61.4%(113/184) of IBD patients belong to early onset IBD, furthermore the very early onset IBD and infantile IBD accounted for 41.8%(77/184) and 26.6%(49/184) respectively. For CD, ileocolonic type(47.3%, 35/74) and non-structuring, non-penetrating type (67.6%, 50/74) were more common. Perianal disease occured in 31.1%(23/74) of CD patients; 81.1%(60/74) of CD patients had moderate/severe activity. For UC, pancolitis type(59.1%, 65/110) was more common. There were no significant changes for location of pathological change, disease behavior, activity degree of CD, extent of UC lesion and incidence of surgery, intestinal perforation and hemorrhage of gastrointestinal tract for IBD in the past 15 years(P>0.05). Severe UC(S3) was more common in Group A2(64.7%, 11/17), but moderate UC(S2) was more common in Group C2(48.5%, 33/68), the difference was statistically significant (P=0.001 7). Conclusion: During the past 15 years, the hospitalization constituent ratio for IBD in our hospital showed a growing trend. The ratio of infantile IBD and very early onset IBD was high. For CD, perianal disease was commonly seen and most patients had moderate/severe activity. The surgery rate and incidence of intestinal obstruction and perforation were higher in the CD patients than UC patients. For UC, the lesions were more extensively combined with higher disease activity.

[Clinical analysis of 11 children with pancreatic cystic fibrosis].

Objective: To increase the recognition of pancreatic cystic fibrosis (PCF) in children and facilitate diagnosing and treatment of this rare entity. Method: This is a retrospective analysis of children who presented to Beijing Children's Hospital affiliated to Capital Medical University from January 2010 to December 2015. We describe their clinical features, laboratory testing and management. Result: Eleven children were diagnosed with PCF by genetic testing or sweat chloride test during these 5 years, including 4 boys and 7 girls. Their age ranged from 0.5-14.3 (mean 9.0±3.9) years. Family history was positive in 3 children. Significant clinical findings on presentation were: malnutrition 6, including 2 cases of mild, moderate and severe malnutrition each; diarrhea 4 (yellow mushy or watery stool with frequency ranging from 2-5 times a day), including 1 case of acute diarrhea and 3 of chronic diarrhea, 3 of them had steatorrhea; abdominal pain 3. All of them had pancreatic lesions shown by abdominal ultrasound. Blood tests showed 6 cases had elevated serum amylase and lipase. The main treatment was pancreatic replacement therapy and nutritional support. Conclusion: PCF is rare in children. Malnutrition, diarrhea and abdominal pain are the main clinical manifestations. Treatment is mostly pancreatic enzymes replacement and supportive care.

Effects of clonal fragmentation on intraspecific competition of a stoloniferous floating plant.

Disturbance is common and can fragment clones of plants. Clonal fragmentation may affect the density and growth of ramets so that it could alter intraspecific competition. To test this hypothesis, we grew one (low density), five (medium density) or nine (high density) parent ramets of the floating invasive plant Pistia stratiotes in buckets, and newly produced offspring ramets were either severed (with fragmentation) or remained connected to parent ramets (no fragmentation). Increasing density reduced biomass of the whole clone (i.e. parent ramet plus its offspring ramets), showing intense intraspecific competition. Fragmentation decreased biomass of offspring ramets, but increased biomass of parent ramets and the whole clone, suggesting significant resource translocation from parent to offspring ramets when clones were not fragmented. There was no interaction effect of density x fragmentation on biomass of the whole clone, and fragmentation did not affect competition intensity index. We conclude that clonal fragmentation does not alter intraspecific competition between clones of P. stratiotes, but increases biomass production of the whole clone. Thus, fragmentation may contribute to its interspecific competitive ability and invasiveness, and intentional fragmentation should not be recommended as a measure to stop the rapid growth of this invasive species.

Autophagy prevents irradiation injury and maintains stemness through decreasing ROS generation in mesenchymal stem cells.

Stem cells were characterized by their stemness: self-renewal and pluripotency. Mesenchymal stem cells (MSCs) are a unique type of adult stem cells that have been proven to be involved in tissue repair, immunoloregulation and tumorigenesis. Irradiation is a well-known factor that leads to functional obstacle in stem cells. However, the mechanism of stemness maintenance in human MSCs exposed to irradiation remains unknown. We demonstrated that irradiation could induce reactive oxygen species (ROS) accumulation that resulted in DNA damage and stemness injury in MSCs. Autophagy induced by starvation or rapamycin can reduce ROS accumulation-associated DNA damage and maintain stemness in MSCs. Further, inhibition of autophagy leads to augment of ROS accumulation and DNA damage, which results in the loss of stemness in MSCs. Our results indicate that autophagy may have an important role in protecting stemness of MSCs from irradiation injury.

Interactive effects of mechanical stress, sand burial and defoliation on growth and mechanical properties in Cynanchum komarovii.

In drylands, wind, sand burial and grazing are three important factors affecting growth and mechanical properties of plants, but their interactive effects have not yet been investigated. Plants of the semi-shrub Cynanchum komarovii, common in semi-arid parts of NE Asia, were subjected to brushing, burial and defoliation. We measured biomass allocation and relative increment rates of dry mass (RGR(m)), height (RGR(h)) and basal diameter (RGR(d)). We also measured the stem mechanical properties, Young's modulus (E), second moment of area (I), flexural stiffness (EI) and breaking stress (σ(b)), and scaled these traits to the whole-plant level to determine the maximum lateral force (F(lateral)) and the buckling safety factor (BSF). Brushing increased RGR(m); neither burial nor defoliation independently affected RGR(m), but together they reduced it. Among buried plants, brushing positively affected stem rigidity and strength through increasing RGR(d), E, I and EI, and at whole plant level this resulted in a larger BSF and F(lateral). However, among unburied plants this pattern was not observed. Our results thus show that effects of mechanical stress and grazing on plants can be strongly modified by burial, and these interactions should be taken into account when considering adaptive significance of plant mechanical traits in drylands.

Brushing effects on the growth and mechanical properties of Corispermum mongolicum vary with water regime.

High water availability and mechanical stress can induce opposite responses in plants. In arid areas of Northern China the occurrence of high wind and high water availability tend to be negatively correlated. Since turgor pressure is a determinant of the mechanical stability of annuals, it is hypothesised that the effects of mechanical perturbation (MP) on annuals may depend on soil water availability. To test this proposal, we conducted an experiment in which a pioneering annual Corispermum mongolicum was subjected to two levels of MP and water supply, and then determined its growth and mechanical traits. Brushing had no effect on plant height and total biomass, but stimulated leaf and branch production. Water supply affected plant height, basal diameter, total biomass and stem rigidity, but not leaf and branch number, root/shoot ratio or flexibility. With high water availability, brushing stimulated the production of stiffer stems (thicker and with a higher Young's modulus) and more roots relative to shoot mass, but with low water availability MP induced the opposite response. This shows that both the degree and direction of plant responses to MP depend on the presence of other factors. We discuss how the interactive effects of MP and water availability on growth and mechanical properties may help C. mongolicum to establish in windy and arid environments.

Clonal integration supports the expansion from terrestrial to aquatic environments of the amphibious stoloniferous herb Alternanthera philoxeroides.

Effects of clonal integration on land plants have been extensively studied, but little is known about the role in amphibious plants that expand from terrestrial to aquatic conditions. We simulated expansion from terrestrial to aquatic habitats in the amphibious stoloniferous alien invasive alligator weed (Alternanthera philoxeroides) by growing basal ramets of clonal fragments in soils connected (allowing integration) or disconnected (preventing integration) to the apical ramets of the same fragments submerged in water to a depth of 0, 5, 10 or 15 cm. Clonal integration significantly increased growth and clonal reproduction of the apical ramets, but decreased both of these characteristics in basal ramets. Consequently, integration did not affect the performance of whole clonal fragments. We propose that alligator weed possesses a double-edged mechanism during population expansion: apical ramets in aquatic habitats can increase growth through connected basal parts in terrestrial habitats; however, once stolon connections with apical ramets are lost by external disturbance, the basal ramets in terrestrial habitats increase stolon and ramet production for rapid spreading. This may contribute greatly to the invasiveness of alligator weed and also make it very adaptable to habitats with heavy disturbance and/or highly heterogeneous resource supply.

Role of the C-terminal domain in inactivation of brain and cardiac sodium channels.

Inactivation is a fundamental characteristic of Na(+) channels, and small changes cause skeletal muscle paralysis and myotonia, epilepsy, and cardiac arrhythmia. Brain Na(v)1.2a channels have faster inactivation than cardiac Na(v)1.5 channels, but minor differences in inactivation gate structure are not responsible. We constructed chimeras in which the C termini beyond the fourth homologous domains of Na(v)1.2a and Na(v)1.5 were exchanged. Replacing the C-terminal domain (CT) of Na(v)1.2a with that of Na(v)1.5 (Na(v)1.2/1.5CT) slowed inactivation at +40 mV approximately 2-fold, making it similar to Na(v)1.5. Conversely, replacing the CT of Na(v)1.5 with that of Na(v)1.2a (Nav1.5/1.2CT) accelerated inactivation, making it similar to Na(v)1.2a. Activation properties were unaffected. The voltage dependence of steady-state inactivation of Na(v)1.5 is 16 mV more negative than that of Na(v)1.2a. The steady-state inactivation curve of Na(v)1.2a was shifted +12 mV in Na(v)1.2/1.5CT, consistent with destabilization of the inactivated state. Conversely, Na(v)1.5/1.2CT was shifted -14 mV relative to Na(v)1.5, consistent with stabilization of the inactivated state. Although these effects of exchanging C termini were consistent with their effects on inactivation kinetics, they magnified the differences in the voltage dependence of inactivation between brain and cardiac channels rather than transferring them. Thus, other parts of these channels determine the basal difference in steady-state inactivation. Deletion of the distal half of either the Na(v)1.2 or Na(v)1.5 CTs accelerated open-state inactivation and negatively shifted steady-state inactivation. Thus, the C terminus has a strong influence on kinetics and voltage dependence of inactivation in brain Na(v)1.2 and cardiac Na(v)1.5 channels and is primarily responsible for their differing rates of channel inactivation.