bluuebunny/crossref_metadata_2025_split huggingface dataset:
GMI1, a structural‐maintenance‐of‐chromosomes‐hinge domain‐containing protein, is involved in somatic homologous recombination in Arabidopsis
Authors: Böhmdorfer Gudrun , Schleiffer Alexander , Brunmeir Reinhard , Ferscha Stefan , Nizhynska Viktoria , Kozák Jaroslav , Angelis Karel J. , Kreil David P. , Schweizer Dieter 
Published: April 2011

SummaryDNA double‐strand breaks (DSBs) pose one of the most severe threats to genome integrity, potentially leading to cell death. After detection of a DSB, the DNA damage and repair response is initiated and the DSB is repaired by non‐homologous end joining and/or homologous recombination. Many components of these processes are still unknown in Arabidopsis thaliana. In this work, we characterized γ‐irradiation and mitomycin C induced 1 (GMI1), a member of the SMC‐hinge domain‐containing protein family. RT‐PCR analysis and promoter‐GUS fusion studies showed that γ‐irradiation, the radio‐mimetic drug bleocin, and the DNA cross‐linking agent mitomycin C strongly enhance GMI1 expression particularly in meristematic tissues. The induction of GMI1 by γ‐irradiation depends on the signalling kinase Ataxia telangiectasia‐mutated (ATM) but not on ATM and Rad3‐related (ATR). Epistasis analysis of single and double mutants demonstrated that ATM acts upstream of GMI1 while the atr gmi1‐2 double mutant was more sensitive than the respective single mutants. Comet assay revealed a reduced rate of DNA double‐strand break repair in gmi1 mutants during the early recovery phase after exposure to bleocin. Moreover, the rate of homologous recombination of a reporter construct was strongly reduced in gmi1 mutant plants upon exposure to bleocin or mitomycin C. GMI1 is the first member of its protein family known to be involved in DNA repair.
Expression of rice SUB1A and SUB1C transcription factors in Arabidopsis uncovers flowering inhibition as a submergence tolerance mechanism
Authors: Peña‐Castro Julián M. , van Zanten Martijn , Lee Seung C. , Patel Mohini R. , Voesenek Laurentius A. J. C. , Fukao Takeshi , Bailey‐Serres Julia 
Published: April 2011

SummarySubmergence of plant organs perturbs homeostasis by limiting diffusion of oxygen, carbon dioxide and ethylene. In rice (Oryza sativa L.), the haplotype at the multigenic SUBMERGENCE1 (SUB1) locus determines whether plants survive prolonged submergence. SUB1 encodes two or three transcription factors of the group VII ethylene response factor family: SUB1A, SUB1B and SUB1C. The presence of SUB1A‐1 and its strong submergence‐triggered ethylene‐mediated induction confers submergence tolerance through a quiescence survival strategy that inhibits gibberellin (GA)‐induced carbohydrate consumption and elongation growth. SUB1C is invariably present and acts downstream of the enhancement of GA responsiveness during submergence. In this study, heterologous ectopic expression of rice SUB1A and SUB1C in Arabidopsis thaliana was used to explore conserved mechanisms of action associated with these genes using developmental, physiological and molecular metrics. As in rice transgenic plants that ectopically express SUB1A‐1, Arabidopsis transgenic plants that constitutively express SUB1A displayed GA insensitivity and abscisic acid hypersensitivity. Ectopic SUB1C expression had more limited effects on development, stress responses and the transcriptome. Observation of a delayed flowering phenotype in lines over‐expressing SUB1A led to the finding that inhibition of floral initiation is a component of the quiescence survival strategy in rice. Together, these analyses demonstrate conserved as well as specific roles for group VII ethylene response factors in integration of abiotic responses with development.
The auxin responsive AP2/ERF transcription factor CROWN ROOTLESS5 is involved in crown root initiation in rice through the induction of OsRR1, a type‐A response regulator of cytokinin signaling
Authors: Kitomi Yuka , Ito Hiroko , Hobo Tokunori , Aya Koichiro , Kitano Hidemi , Inukai Yoshiaki 
Published: April 2011

SummaryCytokinin is known to have negative effects on de novo auxin‐induced root formation. However, the regulatory mechanisms of root initiation by both cytokinin and auxin are poorly understood. In this study, we characterized a rice mutant, termed crown rootless5 (crl5), which produced fewer crown roots and displayed impaired initiation of crown root primordia. The expression of CRL5, which encodes a member of the large AP2/ERF transcription factor family protein, was observed in the stem region where crown root initiation occurs. Exogenous auxin treatment induced CRL5 expression without de novo protein biosynthesis, which also required the degradation of AUX/IAA proteins. A putative auxin response element in the CRL5 promoter region specifically interacted with a rice ARF, demonstrating that CRL5 may be a direct target of an ARF, similar to CRL1/ADVENTITIOUS ROOTLESS1 (ARL1) that also regulates crown root initiation. A crl1 crl5 double mutant displayed an additive phenotype, indicating that these two genes function in different genetic pathways for crown root initiation. In addition, ProACT:CRL5/WT showed a cytokinin‐resistant phenotype for crown root initiation, and also up‐regulated the expression of two negative regulators of cytokinin signaling, OsRR1 and OsRR2, which were downregulated in crl5. Transgenic plants that over‐expressed OsRR1 under the control of the CRL5 promoter in a crl5 mutant background produced a higher number of crown roots than the crl5 plant. Taken together, these results indicate that auxin‐induced CRL5 promotes crown root initiation through repression of cytokinin signaling by positively regulating type‐A RR, OsRR1.
Pharmacokinetic modeling of subcutaneous heroin and its metabolites in blood and brain of mice
Authors: Boix Fernando , Andersen Jannike M. , Mørland Jørg 
Published: April 2011

ABSTRACTHigh blood–brain permeability and effective delivery of morphine to the brain have been considered as explanations for the high potency of heroin. Results from Andersen et al. indicate that 6‐monoacetylmorphine (6‐MAM), and not morphine, is the active metabolite responsible for the acute effects observed for heroin. Here, we use pharmacokinetic modeling on data from the aforementioned study to calculate parameters of the distribution of heroin, 6‐MAM and morphine in blood and brain tissue after subcutaneous heroin administration in mice. The estimated pharmacokinetic parameters imply that the very low heroin and the high 6‐MAM levels observed both in blood and brain in the original experiment are likely to be caused by a very high metabolic rate of heroin in blood. The estimated metabolic rate of heroin in brain was much lower and cannot account for the low heroin and high 6‐MAM levels in the brain, which would primarily reflect the concentrations of these compounds in blood. The very different metabolic rates for heroin in blood and brain calculated by the model were confirmed by in vitro experiments. These results show that heroin's fast metabolism in blood renders high concentrations of 6‐MAM which, due to its relatively good blood–brain permeability, results in high levels of this metabolite in the brain. Thus, it is the high blood metabolism rate of heroin and the blood–brain permeability to 6‐MAM, and not to heroin, which could account for the highly efficient delivery of active metabolites to the brain after heroin administration.
Mucopolysaccharidosis I mutations in Chinese patients: identification of 27 novel mutations and 6 cases involving prenatal diagnosis
Authors: Wang X , Zhang W , Shi H , Qiu Z , Meng Y , Yao F , Wei M 
Published: April 2011

Wang X, Zhang W, Shi H, Qiu Z, Meng Y, Yao F, Wei M. Mucopolysaccharidosis I mutations in Chinese patients: identification of 27 novel mutations and 6 cases involving prenatal diagnosis.Mucopolysaccharidosis I (MPS I) is a lysosomal storage disease that results from the deficiency of α‐l‐iduronidase and is transmitted in an autosomally recessive manner. This report describes the first systematic screening for mutations in Chinese MPS I patients from mainland China, wherein we have summarized the phenotype/genotype correlation of the individuals in Chinese MPS I patients. Mutational analyses were performed in 57 unrelated Chinese MPS I patients. Overall, 105 mutant alleles were identified from a set of 41 different mutations. Notably, of these 41 mutations, 27 were novel mutations that consisted of 8 splicing mutations (c.1‐2C>G, c.296+4G>A, c.300‐1G>C, c.792+1G>C, c.973‐4G>A, c.1189+5G>T, c.1402+1G>T and c.1402+2T>G), 1 nonsense mutation (p.W41X), 1 insertion (c.668‐670ins GCG), 5 duplications (c.531dupT, c.657dupG, c.883dupC, c.1147dupG and c.1225dupG), 3 deletions (c.349delT, c.1593delG and c.1244‐1271del27),1 nucleotide substitution c.2T>C and 8 missense mutations (p.H33P,p.F52L, p.G168V,p.T179R,p. E182D, p.L237R, p.L238R and p.L421P). The missense mutations p.A79V and p.L346R, which accounted for 16.7% (19/114) and 12.3% (14/114) respectively, were the common mutations in Chinese patients but were rare in the mutational profiles reported for other populations. These results indicate that Chinese MPS I patients may have a different mutational spectrum compared to those of other populations. Moreover, for the first time in China, molecular genetic methods were used for prenatal diagnosis of six cases in five families.
Maternal uniparental disomy of chromosome 4 in a patient with limb‐girdle muscular dystrophy 2E confirmed by SNP array technology
Authors: Cottrell CE , Mendell J , Hart‐Kothari M , Ell D , Thrush DL , Astbury C , Pastore M , Gastier‐Foster JM , Pyatt RE 
Published: April 2011

Cottrell CE, Mendell J, Hart‐Kothari M, Ell D, Thrush DL, Astbury C, Pastore M, Gastier‐Foster JM, Pyatt RE. Maternal uniparental disomy of chromosome 4 in a patient with limb‐girdle muscular dystrophy 2E confirmed by SNP array technology.The limb‐girdle muscular dystrophies (LGMDs) are a heterogenous group of diseases characterized by shoulder‐girdle and pelvic muscle weakness and wasting. LGMD 2E is an autosomal recessively inherited form of the disease caused by mutations in the β‐sarcoglycan (SGCB) gene located at 4q12. In this report, we describe a patient who demonstrates non‐Mendelian inheritance of a homozygous missense mutation in SGCB resulting in disease expression. A combination of single‐nucleotide polymorphism (SNP) array technology and microsatellite analysis revealed the occurrence of maternal uniparental disomy (UPD) for chromosome 4 in the patient. As a consequence of segmental isodisomy at 4q12, the patient inherited two identical SGCB alleles carrying a missense mutation predicted to result in abnormal protein function. SNP array technology proved to be an elegant means to determine the most probable mechanism of UPD formation in this case, and enabled us to determine the location of recombination events along chromosome 4. In our patient, UPD likely arose from a trisomy rescue event due to maternal meiotic non‐disjunction that we speculate may have been caused by abnormal recombination at the pericentromeric region. Maternal UPD 4 is a rare finding, and to our knowledge this is the first reported case of UPD in association with LGMD.
Role of Na+/H+ exchanger 3 in the acidification of the male reproductive tract and male fertility
Authors: Pholpramool Chumpol , Borwornpinyo Suparerk , Dinudom Anuwat 
Published: April 2011

Summary1. Male fertility is a complex process that is dependent on sex hormones and the normal function of the reproductive organs. Defects of these organs result in abnormal sperm production and function, which, in turn, lead to infertility.2. Spermatozoa released from the testis are unable to move and fertilize with eggs. These features, known as sperm maturation, are acquired during their transit through the epididymis.3. Among several processes that take place in the epididymis, absorption and acidification of the luminal fluid are essential for sperm maturation, sperm storage and fertility. Currently, the mechanism by which acidification occurs in the epididymis is still not fully understood.4. The epididymis is fully equipped with the proteins required for acid/base transport, such as Na+/H+ exchanger 3 (NHE3, SLC9A3), vacuolar‐type adenosine triphosphatase (V‐ATPase) and various isoforms of enzyme carbonic anhydrase (CA).5. Most studies, so far, have focused on the role of V‐ATPase on H+ secretion and acidification of the epididymis. The involvement of NHE3 in creating the acidic environment of the epididymal spermatozoa receives little attention.6. This review presents evidence for and discusses the role of NHE3 in the acidification of the male reproductive tract and its requirement for male fertility.
Erythrocyte sedimentation rate kinetics as a marker of treatment response and predictor of prognosis in Chinese metastatic renal cell carcinoma patients treated with sorafenib
Authors: Zhang Hai‐Liang , Zhu Yao , Wang Chao‐Fu , Yao Xu‐Dong , Zhang Shi‐Lin , Dai Bo , Shen Yi‐Jun , Zhu Yi‐Ping , Shi Guo‐Hai , Ye Ding‐Wei 
Published: April 2011

Objectives:  Previous prognostic factor models for metastatic renal cell carcinoma (mRCC) have not included erythrocyte sedimentation rate (ESR). We designed the present study to evaluate the prognostic value of ESR for mRCC patients treated with sorafenib.Methods:  Sorafenib was given to 83 patients with clear cell mRCC. Serum ESR was tested before treatment and every 4 weeks after first administration of sorafenib. Oncological evaluation was carried out every 8 weeks. Analyzed factors included age, sex, performance status, method of nephrectomy, number of metastatic organs, anemia, lactate dehydrogenase, corrected calcium, albumin, baseline ESR level and ESR kinetics status. Kaplan–Meier and Cox regression analyses on progression‐free survival (PFS) were carried out.Results:  Baseline ESR levels ranged from 3 to 154 mm/h, and 43 (41.0%) patients had an ESR level higher than 40 mm/h. Median PFS was 10.0 months (95% CI 7.6–12.4 months). Dividing the cohort into three groups according to ESR kinetics status, median PFS was 27 months in the decreased ESR group, 12 months in the stable ESR group and 6 months in the increased ESR group. Performance status, time from diagnoses to sorafenib treatment, number of metastatic organs and ESR kinetics were independent predictors for PFS in multivariable Cox regression model analysis, with an area under the curve of 0.865 in a binary logistic regression model of 12‐month PFS probability.Conclusions:  ESR kinetics can be useful to monitor the treatment response and to predict PFS for mRCC patients treated with sorafenib as second‐line therapy.
Postoperative renal function after partial nephrectomy for renal cell carcinoma in patients with pre‐existing chronic kidney disease: A comparison with radical nephrectomy
Authors: Takagi Toshio , Kondo Tsunenori , Iizuka Jyunpei , Kobayashi Hirohito , Hashimoto Yasunobu , Nakazawa Hayakazu , Ito Fumio , Tanabe Kazunari 
Published: April 2011

AbstractWe assessed whether adequately functioning parenchyma is preserved in patients with pre‐existing chronic kidney disease (CKD) after partial nephrectomy (PN) compared with those who underwent radical nephrectomy (RN). A total of 95 patients with pre‐existing CKD who underwent curative surgery for pathological T1a‐T2N0M0 renal cell carcinoma with a follow‐up period of 12 months or more were the subject of the present study. Of these, 51 patients underwent RN, and 44 PN. Renal function was assessed by using the estimated glomerular filtration rate (e‐GFR). We classified the subjects into two groups according to the preoperative e‐GFR: preoperative e‐GFR 45–59 mL/min/1.73 m2 (68 patients); and 30–44 mL/min/1.73 m2 (27 patients). In the former group, the probability of freedom from new onset of e‐GFR <45 mL/min/1.73 m2 stemmed from the significant difference between the PN and RN groups (P = 0.006; PN: 2 years 64%; RN: 2 years 22%). In contrast, in the latter group, the probability of freedom from new onset of e‐GFR <30 mL/min/1.73 m2 was not associated with a significant difference between PN and RN group (P = 0.80). Overall survival and the number of the patients who went on to develop end‐stage renal disease requiring renal replacement therapy between PN and RN were not significantly different in each group. Death from renal cell carcinoma was not noted in either group. PN could significantly prevent development to late‐stage CKD in patients with preoperative e‐GFR 45–59 mL/min/1.73 m2 compared with RN. Patients with preoperative e‐GFR 30–44 mL/min/1.73 m2 should be reviewed in a more strict study.
Clinical significance of immediate urine cytology after transurethral resection of bladder tumor in patients with non‐muscle invasive bladder cancer
Authors: Shin Yu Seob , Kim Sang Deuk , Cha Jai Seong , Kim Myung Ki , Jeong Young Beom , Kim Hyung Jin 
Published: April 2011

Objectives:  To assess the clinical significance of immediate urine cytology (IUC) after transurethral resection of bladder tumor (TURBT) for non‐muscle invasive bladder cancer (NMIBC).Methods:  We reviewed the records of 174 patients who underwent IUC after TURBT for NMIBC. IUC was obtained just before Foley catheter removal after TURBT. The relationship between IUC and tumor stage, grade, size and multiplicity, as well as preoperative urine cytology and immediate intravesical epirubicin therapy, were assessed. The relationship between a positive IUC and cancer recurrence was also assessed. Multivariate Cox proportional hazards regression analysis was carried out, including IUC, tumor stage, tumor grade, tumor size, tumor multiplicity, preoperative urine cytology and immediate intravesical epirubicin therapy.Results:  IUC was positive in 76 patients (43.7%) and negative in 98 patients (56.3%). In the positive IUC group, tumor stage and grade were higher (P = 0.001, <0.001), tumor size was larger (P = 0.001), tumor multiplicity was higher (P = 0.002) and positive preoperative cytology was more likely (P = 0.006) than in the negative IUC group. In the positive IUC group, the cancer recurrence rate was 72.3% and that of the negative IUC group was 30.6% (P < 0.001). In a multivariate Cox proportional hazards regression analysis, positive IUC (HR 1.83, P = 0.019), tumor size (HR 1.72, P = 0.045), tumor multiplicity (HR 3.63, P = 0.015), preoperative urine cytology (HR 1.23, P = 0.043) and immediate intravesical epirubicin therapy (HR 0.171, P = 0.001) were independent prognostic factors for cancer recurrence.Conclusion:  These data suggest that IUC after TURBT for NMIBC can be an independent prognostic factor to predict cancer recurrence.
A one‐port pneumovesicum method in en bloc laparoscopic nephroureterectomy with bladder cuff resection is feasible and safe for upper tract transitional cell carcinoma
Authors: Zou Xiaofeng , Zhang Guoxi , Wang Xiaoning , Yuan Yuanhu , Xiao Rihai , Wu Gengqing , Long Dazhi , Xu Hui , Wu Yuting , Liu Folin 
Published: April 2011

Study Type – Therapy (case series)Level of Evidence 4OBJECTIVE• To introduce a modified method for managing the distal ureter in laparoscopic nephroureterectomy (LNU) for upper tract transitional cell carcinoma (TCC) and to evaluate the feasibility and safety of this method.PATIENTS AND METHODS• Six consecutive patients underwent LNU using a one‐port pneumovesicum method for pathologically confirmed upper tract TCC.• Each patient was placed on the operating table in the lithotomy position and the pneumovesicum method was applied with CO2 insufflation. Dissection was performed circumferentially through the entire detrusor muscle to disconnect the ureter from the bladder wall. A 10‐mm trocar was placed into the bladder above the pubic bone. The distal ureter was occluded using a Hem‐o‐lok clip and pushed out of the bladder. Laparoscopic nephroureterectomy was then performed with the patient in the lateral position.• After surgery, all six patients received systemic chemotherapy and follow‐up.RESULTS• All procedures were performed successfully.• The median (range) operating time for the complete procedure was 105 (85–140) min, and the median (range) estimated blood loss was 125 (60–230) mL.• Seven days after surgery, each patient underwent cystography, which confirmed no extravasation of urine.• None of the patients developed bladder tumour recurrence or metastatic disease during follow‐up.CONCLUSIONS• The one‐port pneumovesicum method in LNU, which is applied to manage the distal ureter and bladder cuff, is technically feasible and safe.• The method simplifies management of the distal ureter, reduces the invasiveness of the procedure and improves cosmesis.
Vibrotactile sense in patients with diabetes and carpal tunnel syndrome
Authors: Thomsen N. O. B. , Cederlund R. , Speidel T. , Dahlin L. B. 
Published: April 2011

Diabet. Med. 28, 1401–1406 (2011)AbstractAim  To evaluate vibration perception thresholds of patients with and without diabetes, before and after surgical carpal tunnel release.Methods  In a prospective study, 35 consecutive patients with diabetes and carpal tunnel syndrome were age and gender matched with 31 patients without diabetes having idiopathic carpal tunnel syndrome. Preoperatively, 6, 12 and 52 weeks after surgery, the vibration perception threshold of the index and little finger (median and ulnar nerve, respectively) was measured at seven different frequencies (8, 16, 32, 64, 125, 250 and 500 Hz).Results  At several frequencies, patients with diabetes and carpal tunnel syndrome demonstrated significantly impaired vibration perception thresholds of both the index and the little finger, before as well as after carpal tunnel release, compared with patients without diabetes with idiopathic carpal tunnel syndrome. After surgery, the overall sensibility index improved for the index finger [patients with diabetes and carpal tunnel syndrome (0.79 to 0.91, P < 0.001), patients without diabetes with idiopathic carpal tunnel syndrome (0.91 to 0.96, P > 0.05)] as well as for the little finger [patients with diabetes and carpal tunnel syndrome (0.82 to 0.90, P < 0.008), patients without diabetes with idiopathic carpal tunnel syndrome (0.95 to 0.99, P < 0.05)]. For the index finger, the sensibility index improved to a significantly higher degree for patients with diabetes and carpal tunnel syndrome not having signs of peripheral neuropathy (0.83 to 0.95, P < 0.001) compared with those with neuropathy (0.74 to 0.84, P < 0.02). Vibration perception threshold correlates with age of both patients with diabetes and carpal tunnel syndrome and patients without diabetes with idiopathic carpal tunnel syndrome, while no relationship was found based on duration of diabetes.Conclusions  Vibrotactile sense is significantly impaired in patients with diabetes before and after carpal tunnel release compared with patients without diabetes. However, patients with diabetes obtained significant recovery of vibration perception threshold, particularly those without peripheral neuropathy.