bluuebunny/crossref_metadata_2025 huggingface dataset:
Silica nanoparticles as a tool for fluorescence collection efficiency enhancement
Authors: Krajnik Bartosz , Gajda-Rączka Magdalena , Piątkowski Dawid , Nyga Piotr , Jankiewicz Bartłomiej , Hofmann Eckhard , Mackowski Sebastian
Published: March 2013

In this work we demonstrate enhancement of the fluorescence collection efficiency for chlorophyll-containing photosynthetic complexes deposited on SiO2 spherical nanoparticles. Microscopic images of fluorescence emission reveal ring-like emission patterns associated with chlorophyll-containing complexes coupled to electromagnetic modes within the silica nanoparticles. The interaction leaves no effect upon the emission spectra of the complexes, and the transient behavior of the fluorescence also remains unchanged, which indicates no influence of the silica nanoparticles on the radiative properties of the fluorophores. We interpret this enhancement as a result of efficient scattering of electromagnetic field by the dielectric nanoparticles that increases collection efficiency of fluorescence emission.
Characterising the biology of novel lytic bacteriophages infecting multidrug resistant Klebsiella pneumoniae
Authors: Kęsik-Szeloch Agata , Drulis-Kawa Zuzanna , Weber-Dąbrowska Beata , Kassner Jerzy , Majkowska-Skrobek Grażyna , Augustyniak Daria , Łusiak-Szelachowska Marzanna , Żaczek Maciej , Górski Andrzej , Kropinski Andrew M
Published: March 2013

Background

Members of the genusKlebsiellaare among the leading microbial pathogens associated with nosocomial infection. The increased incidence of antimicrobial resistance in these species has propelled the need for alternate/combination therapeutic regimens to aid clinical treatment. Bacteriophage therapy forms one of these alternate strategies.

Methods

Electron microscopy, burst size, host range, sensitivity of phage particles to temperature, chloroform, pH, and restriction digestion of phage DNA were used to characterizeKlebsiellaphages.

Results and conclusions

Of the 32 isolated phages eight belonged to the familyMyoviridae, eight to theSiphoviridaewhilst the remaining 16 belonged to thePodoviridae. The host range of these phages was characterised against 254 clinicalEnterobacteriaceaestrains including multidrug resistantKlebsiellaisolates producing extended-spectrum beta-lactamases (ESBLs). Based on their lytic potential, six of the phages were further characterised for burst size, physicochemical properties and sensitivity to restriction endonuclease digestion. In addition, five were fully sequenced. Multiple phage-encoded host resistance mechanisms were identified. TheSiphoviridaephage genomes (KP16 and KP36) contained low numbers of host restriction sites similar to the strategy found in T7-like phages (KP32). In addition, phage KP36 encoded its own DNA adenine methyltransferase. The φKMV-like KP34 phage was sensitive to all endonucleases used in this study. Dam methylation of KP34 DNA was detected although this was in the absence of an identifiable phage encoded methyltransferase. TheMyoviridaephages KP15 and KP27 both carried Dam and Dcm methyltransferase genes and other anti-restriction mechanisms elucidated in previous studies. No other anti-restriction mechanisms were found, e.g. atypical nucleotides (hmC or glucosyl hmC), althoughMyoviridaephage KP27 encodes an unknown anti-restriction mechanism that needs further investigation.
Role of Voltage Gated Ca2+ Channels in Rat Visceral Hypersensitivity Change Induced by 2, 4, 6-Trinitrobenzene Sulfonic Acid
Authors: Qian Aihua , Song Dandan , Li Yong , Liu Xinqiu , Tang Dong , Yao Weiyan , Yuan Yaozong
Published: March 2013

Background

Visceral pain is common symptom involved in many gastrointestinal disorders such as inflammatory bowel disease. The underlying molecular mechanisms remain elusive. We investigated the molecular mechanisms and the role for voltage gated calcium channel (VGCC) in the pathogenesis in a rat model of 2, 4, 6-trinitrobenzenesulfonic acid (TNBS) induced visceral inflammatory hypersensitivity.

Results

Using Agilent cDNA arrays, we found 172 genes changed significantly in dorsal root ganglia (DRG) of TNBS treated rats. Among these changed genes, Cav1.2 and Cav2.3 were significantly up-regulated. Then the RT-PCR and Western blot further confirmed the up-regulation of Cav1.2 and Cav2.3. The whole cell patch clamp recording of acutely dissociated colonic specific DRG neurons showed that the peak IBa density was significantly increased in colonic neurons of TNBS treated rats compared with control rats (−127.82 ± 20.82 pA/pF Vs −91.67 ± 19.02 pA/pF, n = 9, *P < 0.05). To distinguish the different type of calcium currents with the corresponding selective channel blockers, we found that L-type (−38.56 ± 3.97 pA/pF Vs −25.75 ± 3.35 pA/pF, n = 9, * P < 0.05) and R-type (−13.31 ± 1.36 pA/pF Vs −8.60 ± 1.25 pA/pF, n = 9, * P < 0.05) calcium current density were significantly increased in colonic DRG neurons of TNBS treated rats compared with control rats. In addition, pharmacological blockade with L-type antagonist (nimodipine) and R-type antagonist (SNX-482) with intrathecal injection attenuates visceral pain in TNBS induced inflammatory visceral hypersensitivity.

Conclusion

Cav1.2 and Cav2.3 in colonic primary sensory neurons play an important role in visceral inflammatory hyperalgesia, which maybe the potential therapeutic targets.
Delayed ventricular septal rupture complicating acute inferior wall myocardial infarction
Authors: Cho Jae Hyung , Sattiraju Srinivasan , Mehta Sanjay , Missov Emil
Published: March 2013

Background

Ventricular septal rupture is a potentially fatal complication of acute myocardial infarction. Its incidence has declined with modern reperfusion therapy. In the era of percutaneous coronary interventions, it occurs a median of 18–24 hours after myocardial infarction and is most commonly associated with anterior myocardial infarction. We present a case of delayed ventricular septal rupture complicating acute inferior wall myocardial infarction.

Case presentation

A 53-year-old Caucasian male presented with epigastric pain for three days and electrocardiographic evidence for an acute inferior wall myocardial infarction. Coronary angiography revealed a total occlusion of the proximal right coronary artery. Reperfusion was achieved by balloon angioplasty followed by placement of a bare metal stent. On hospital day six, the patient developed acute respiratory distress, a new loud pansystolic murmur, and hemodynamic instability. Echocardiography revealed the presence of a large defect in the inferobasal interventricular septum with significant left-to-right shunt consistent with ventricular septal rupture. The patient underwent emergent surgical repair with a bovine pericardial patch.

Conclusion

Ventricular septal rupture after myocardial infarction should be suspected in the presence of new physical findings and hemodynamic compromise regardless of revascularization therapy.
Colonization of Anopheles cracens: a malaria vector of emerging importance
Authors: Amir Amirah , Sum Jia Siang , Lau Yee Ling , Vythilingam Indra , Fong Mun Yik
Published: March 2013

Background

Anopheles cracens has been incriminated as a vector for the simian malaria parasite, Plasmodium knowlesi, that is the fifth Plasmodium species infecting humans. Little experimental data exists on this mosquito species due to the lack of its availability in laboratories.

Findings

The population of An. cracens, collected from Kuala Lipis, Pahang was maintained at the insectary of the Department of Parasitology, Faculty of Medicine, University Malaya at 24-26°C and 60-80% relative humidity. The mosquitoes were maintained with artificial mating and blood-fed on humans and hamsters. The colony has been established since November 2011 and to date has reached its sixth generation.

Conclusion

This is the first description of maintaining the Malaysian strain An. cracens colony by artificial mating. Colonization of An. cracens will provide fundamental information for genetic studies and will be useful in assessing comparative susceptibility to Plasmodium parasites.
The epidemiology of anaphylaxis in Europe: protocol for a systematic review
Authors: Panesar Sukhmeet S , Nwaru Bright I , Hickstein Lennart , Rader Tamara , Hamadah Hala , Ali Dana Fawzi Ibrahim , Patel Bhavesh , Muraro Antonella , Roberts Graham , Worm Margitta , Sheikh Aziz ,   European Academy of Allergy and Clinical Immunology Food Allergy and Anaphylaxis Guidelines group
Published: March 2013

Background

The European Academy of Allergy and Clinical Immunology is in the process of developing its Guideline for Food Allergy and Anaphylaxis, and this systematic review is one of seven inter‐linked evidence syntheses that are being undertaken in order to provide a state‐of‐the‐art synopsis of the current evidence base in relation to epidemiology, prevention, diagnosis and clinical management and impact on quality of life, which will be used to inform clinical recommendations.

The aims of this systematic review will be to understand and describe the epidemiology of anaphylaxis, i.e. frequency, risk factors and outcomes of anaphylaxis, and describe how these characteristics vary by person, place and time.

Methods

A highly sensitive search strategy has been designed to retrieve all articles combining the concepts of anaphylaxis and epidemiology from electronic bibliographic databases.

Discussion

This review will aim to provide some estimates of the incidence and prevalence of anaphylaxis in Europe. The occurrence of anaphylaxis can have a profound effect on the quality of life of the sufferer and their family. Estimates of disease frequency will help us to ascertain the burden of anaphylaxis and provide useful comparators for management strategies.
Expression of quiescin sulfhydryl oxidase 1 is associated with a highly invasive phenotype and correlates with a poor prognosis in Luminal B breast cancer
Authors: Katchman Benjamin A , Ocal I Tolgay , Cunliffe Heather E , Chang Yu-Hui , Hostetter Galen , Watanabe Aprill , LoBello Janine , Lake Douglas F
Published: March 2013

Introduction

Quiescin sulfhydryl oxidase 1 (QSOX1) oxidizes sulfhydryl groups to form disulfide bonds in proteins. Tumor specific expression of QSOX1 has been reported for numerous tumor types. In this study, we investigate QSOX1 as a marker of breast tumor progression and evaluate the role of QSOX1 as it relates to breast tumor growth and metastasis.

Methods

Correlation of QSOX1 expression with breast tumor grade, subtype and estrogen receptor (ER) status was gathered through informatic analysis using the "Gene expression based Outcome for Breast cancer Online" (GOBO) web-based tool. Expression of QSOX1 protein in breast tumors tissue microarray (TMA) and in a panel of breast cancer cell lines was used to confirm our informatics analysis. To investigate malignant cell mechanisms for which QSOX1 might play a key role, we suppressed QSOX1 protein expression using short hairpin (sh) RNA in ER+ Luminal A-like MCF7, ER+ Luminal B-like BT474 and ER- Basal-like BT549 breast cancer cell lines.

Results

GOBO analysis revealed high levels of QSOX1 RNA expression in ER+ subtypes of breast cancer. In addition, Kaplan Meyer analyses revealed QSOX1 RNA as a highly significant predictive marker for both relapse and poor overall survival in Luminal B tumors. We confirmed this finding by evaluation of QSOX1 protein expression in breast tumors and in a panel of breast cancer cell lines. Expression of QSOX1 in breast tumors correlates with increasing tumor grade and high Ki-67 expression. Suppression of QSOX1 protein slowed cell proliferation as well as dramatic inhibition of MCF7, BT474 and BT549 breast tumor cells from invading through Matrigel™ in a modified Boyden chamber assay. Inhibition of invasion could be rescued by the exogenous addition of recombinant QSOX1. Gelatin zymography indicated that QSOX1 plays an important role in the function of MMP-9, a key mediator of breast cancer invasive behavior.

Conclusions

Taken together, our results suggest that QSOX1 is a novel biomarker for risk of relapse and poor survival in Luminal B breast cancer, and has a pro-proliferative and pro-invasive role in malignant progression partly mediated through a decrease in MMP-9 functional activity.
Genome sequence of ground tit Pseudopodoces humilis and its adaptation to high altitude
Authors: Cai Qingle , Qian Xiaoju , Lang Yongshan , Luo Yadan , Xu Jiaohui , Pan Shengkai , Hui Yuanyuan , Gou Caiyun , Cai Yue , Hao Meirong , Zhao Jinyang , Wang Songbo , Wang Zhaobao , Zhang Xinming , He Rongjun , Liu Jinchao , Luo Longhai , Li Yingrui , Wang Jun
Published: March 2013

Background

The mechanism of high-altitude adaptation has been studied in certain mammals. However, in avian species like the ground tit Pseudopodoces humilis, the adaptation mechanism remains unclear. The phylogeny of the ground tit is also controversial.

Results

Using next generation sequencing technology, we generated and assembled a draft genome sequence of the ground tit. The assembly contained 1.04 Gb of sequence that covered 95.4% of the whole genome and had higher N50 values, at the level of both scaffolds and contigs, than other sequenced avian genomes. About 1.7 million SNPs were detected, 16,998 protein-coding genes were predicted and 7% of the genome was identified as repeat sequences. Comparisons between the ground tit genome and other avian genomes revealed a conserved genome structure and confirmed the phylogeny of ground tit as not belonging to the Corvidae family. Gene family expansion and positively selected gene analysis revealed genes that were related to cardiac function. Our findings contribute to our understanding of the adaptation of this species to extreme environmental living conditions.

Conclusions

Our data and analysis contribute to the study of avian evolutionary history and provide new insights into the adaptation mechanisms to extreme conditions in animals.
CRAC: an integrated approach to the analysis of RNA-seq reads
Authors: Philippe Nicolas , Salson Mikaël , Commes Thérèse , Rivals Eric
Published: March 2013

A large number of RNA-sequencing studies set out to predict mutations, splice junctions or fusion RNAs. We propose a method, CRAC, that integrates genomic locations and local coverage to enable such predictions to be made directly from RNA-seq read analysis. A k-mer profiling approach detects candidate mutations, indels and splice or chimeric junctions in each single read. CRAC increases precision compared with existing tools, reaching 99:5% for splice junctions, without losing sensitivity. Importantly, CRAC predictions improve with read length. In cancer libraries, CRAC recovered 74% of validated fusion RNAs and predicted novel recurrent chimeric junctions. CRAC is available at http://crac.gforge.inria.fr.
Heterozygous inactivation of tsc2 enhances tumorigenesis in p53 mutant zebrafish
Authors: Kim Seok-Hyung , Kowalski Marie L. , Carson Robert P. , Bridges L. Richard , Ess Kevin C.
Published: March 2013

Tuberous sclerosis complex (TSC) is a multi-organ disorder caused by mutations of the TSC1 or TSC2 genes. A key function of these genes is to inhibit mTORC1 (mechanistic target of rapamycin complex 1) kinase signaling. Cells deficient for TSC1 or TSC2 have increased mTORC1 signaling and give rise to benign tumors, although, as a rule, true malignancies are rarely seen. In contrast, other disorders with increased mTOR signaling typically have overt malignancies. A better understanding of genetic mechanisms that govern the transformation of benign cells to malignant ones is crucial to understand cancer pathogenesis. We generated a zebrafish model of TSC and cancer progression by placing a heterozygous mutation of the tsc2 gene in a p53 mutant background. Unlike tsc2 heterozygous mutant zebrafish, which never exhibited cancers, compound tsc2;p53 mutants had malignant tumors in multiple organs. Tumorigenesis was enhanced compared with p53 mutant zebrafish. p53 mutants also had increased mTORC1 signaling that was further enhanced in tsc2;p53 compound mutants. We found increased expression of Hif1-α, Hif2-α and Vegf-c in tsc2;p53 compound mutant zebrafish compared with p53 mutant zebrafish. Expression of these proteins probably underlies the increased angiogenesis seen in compound mutant zebrafish compared with p53 mutants and might further drive cancer progression. Treatment of p53 and compound mutant zebrafish with the mTORC1 inhibitor rapamycin caused rapid shrinkage of tumor size and decreased caliber of tumor-associated blood vessels. This is the first report using an animal model to show interactions between tsc2, mTORC1 and p53 during tumorigenesis. These results might explain why individuals with TSC rarely have malignant tumors, but also suggest that cancer arising in individuals without TSC might be influenced by the status of TSC1 and/or TSC2 mutations and be potentially treatable with mTORC1 inhibitors.
Intrathecal Drug Delivery (ITDD) systems for cancer pain
Authors: Bhatia Gaurav , Lau Mary E , Gulur Padma
Published: March 2013

Intrathecal drug delivery is an effective pain management option for patients with chronic and cancer pain. The delivery of drugs into the intrathecal space provides superior analgesia with smaller doses of analgesics to minimize side effects while significantly improving quality of life. This article aims to provide a general overview of the use of intrathecal drug delivery to manage pain, dosing recommendations, potential risks and complications, and growing trends in the field.
Comparison of outcomes between proximal and distal chevron osteotomy, both with supplementary lateral soft-tissue release, for severe hallux valgus deformity
Authors: Park H-W. , Lee K-B. , Chung J-Y. , Kim M-S.
Published: March 2013

Severe hallux valgus deformity is conventionally treated with proximal metatarsal osteotomy. Distal metatarsal osteotomy with an associated soft-tissue procedure can also be used in moderate to severe deformity. We compared the clinical and radiological outcomes of proximal and distal chevron osteotomy in severe hallux valgus deformity with a soft-tissue release in both. A total of 110 consecutive female patients (110 feet) were included in a prospective randomised controlled study. A total of 56 patients underwent a proximal procedure and 54 a distal operation. The mean follow-up was 39 months (24 to 54) in the proximal group and 38 months (24 to 52) in the distal group. At follow-up the hallux valgus angle, intermetatarsal angle, distal metatarsal articular angle, tibial sesamoid position, American Orthopaedic Foot and Ankle Society (AOFAS) hallux metatarsophalangeal-interphalangeal score, patient satisfaction level, and complications were similar in each group. Both methods showed significant post-operative improvement and high levels of patient satisfaction. Our results suggest that the distal chevron osteotomy with an associated distal soft-tissue procedure provides a satisfactory method for correcting severe hallux valgus deformity.

Cite this article: Bone Joint J 2013;95-B:510–16.
Mid-flexion laxity is greater after posterior-stabilised total knee replacement than with cruciate-retaining procedures
Authors: Hino K. , Ishimaru M. , Iseki Y. , Watanabe S. , Onishi Y. , Miura H.
Published: March 2013

There are several methods for evaluating stability of the joint during total knee replacement (TKR). Activities of daily living demand mechanical loading to the knee joint, not only in full extension, but also in mid-flexion. The purpose of this study was to compare the varus-valgus stability throughout flexion in knees treated with either cruciate-retaining or posterior-stabilised TKR, using an intra-operative navigation technique. A total of 34 knees underwent TKR with computer navigation, during which the investigator applied a maximum varus-valgus stress to the knee while steadily moving the leg from full extension to flexion both before and after prosthetic implantation. The femorotibial angle was measured simultaneously by the navigation system at every 10° throughout the range of movement. It was found that posterior-stabilised knees had more varus-valgus laxity than cruciate-retaining knees at all angles examined, and the differences were statistically significant at 10° (p = 0.0093), 20° (p = 0.0098) and 30° of flexion (p = 0.0252).

Cite this article: Bone Joint J 2013;95-B:493–7.
The use of a zero-profile device compared with an anterior plate and cage in the treatment of patients with symptomatic cervical spondylosis
Authors: Qi M. , Chen H. , Liu Y. , Zhang Y. , Liang L. , Yuan W.
Published: March 2013

In a retrospective cohort study we compared the clinical outcome and complications, including dysphagia, following anterior cervical fusion for the treatment of cervical spondylosis using either a zero-profile (Zero-P; Synthes) implant or an anterior cervical plate and cage. A total of 83 patients underwent fusion using a Zero-P and 107 patients underwent fusion using a plate and cage. The mean follow-up was 18.6 months (sd 4.2) in the Zero-P group and 19.3 months (sd 4.1) in the plate and cage group. All patients in both groups had significant symptomatic and neurological improvement. There were no significant differences between the groups in the Neck Disability Index (NDI) and visual analogue scores at final follow-up. The cervical alignment improved in both groups. There was a higher incidence of dysphagia in the plate and cage group on the day after surgery and at two months post-operatively. All patients achieved fusion and no graft migration or nonunion was observed.

When compared with the traditional anterior cervical plate and cage, the Zero-P implant is a safe and convenient procedure giving good results in patients with symptomatic cervical spondylosis with a reduced incidence of dysphagia post-operatively.

Cite this article: Bone Joint J 2013;95-B:543–7.
The significance of an asymmetric extension gap on routine radiographs after total knee replacement
Authors: Liebs T. R.  , Kloos S-A. , Herzberg W. , Rüther W. , Hassenpflug J.
Published: March 2013

We investigated whether an asymmetric extension gap seen on routine post-operative radiographs after primary total knee replacement (TKR) is associated with pain at three, six, 12 and 24 months’ follow-up. On radiographs of 277 patients after primary TKR we measured the distance between the tibial tray and the femoral condyle on both the medial and lateral sides. A difference was defined as an asymmetric extension gap. We considered three groups (no asymmetric gap, medial-opening and lateral-opening gap) and calculated the associations with the Western Ontario and McMaster Universities osteoarthritis index pain scores over time.

Those with an asymmetric extension gap of ≥ 1.5 mm had a significant association with pain scores at three months’ follow-up; patients with a medial-opening extension gap reported more pain and patients with a lateral-opening extension gap reported less pain (p = 0.036). This effect was still significant at six months (p = 0.044), but had lost significance by 12 months (p = 0.924). When adjusting for multiple cofounders the improvement in pain was more pronounced in patients with a lateral-opening extension gap than in those with a medial-opening extension gap at three (p = 0.037) and six months’ (p = 0.027) follow-up.

Cite this article: Bone Joint J 2013;95-B:472–7.
Behind Closed Doors: Medication Storage and Disposal in the Home
Authors: Wieczorkiewicz Sarah M , Kassamali Zahra , Danziger Larry H
Published: March 2013

BACKGROUND

More than half of all medications are inappropriately prescribed, dispensed, or sold and only 50% of patients take their medications correctly. Oftentimes, unwanted or expired medications are saved for later use, stored indefinitely, or disposed via the sink, toilet, or garbage.

OBJECTIVE

To determine how residents in Cook County, Illinois, use, store, and dispose of their medications to assess the possible impact of these medications on health care and the environment.

METHODS

Researchers at the University of Illinois conducted a survey of Cook County residents over a 13-week period. Residents were surveyed regarding their use, storage, and disposal of prescription and nonprescription medications.

RESULTS

From 3954 telephone numbers generated through random-digit dialing, 445 telephone interviews were completed. Eighty-one and a half percent of respondents had prescription medications and 92.4% had nonprescription medications in their homes. On average, respondents possessed 4.4 distinct prescription and 5.5 distinct nonprescription medications. Despite possessing a number of medications, approximately 30% of respondents stated that they took no medication on a regular basis; 59% of respondents reported disposing medications in the household garbage and 31% flushed them down the toilet or sink. Over 80% of respondents stated that they had never received information about proper medication disposal. Thirty-seven percent reported having leftover unexpired medications from a previous illness. Of these, 63% stopped taking their medications because they believed that they no longer needed them or because they felt better. Thirty-two percent of respondents expected to have leftover prescription medications within the next 6 months.

CONCLUSIONS

Almost all respondents had excess and leftover medications in their homes. This may be a result of both overprescribing and poor medication adherence. In addition to the potential human health risk of nonadherence, disposal of excess medication raises concerns about their environmental impact and safety.
Acute Pulmonary Emboli in a Patient on Long-Term Dabigatran Therapy
Authors: Rafferty Joseph A , Prom Rathasen , Kujawski Stephanie Z
Published: March 2013

OBJECTIVE

To describe the case of a patient who developed acute pulmonary emboli (PE) despite long-term anticoagulation with dabigatran.

CASE SUMMARY

A 69-year-old obese woman was hospitalized for worsening shortness of breath, dyspnea on exertion, and left pleuritic chest pain. On admission, a computed tomography angiogram revealed acute bilateral PE, despite use of dabigatran for atrial fibrillation for approximately 5 years prior to admission. Dabigatran was stopped and therapeutic enoxaparin was initiated concomitantly with warfarin. An investigation into possible causes for the development of the PE, including hypercoagulability, was unrevealing. Since dabigatran should have protected against PE, the patient was questioned regarding adherence to her regimen. She stated that she was adherent but reported using a pillbox. The patient was discharged home on warfarin with an enoxaparin bridge until her international normalized ratio was at least 2.0.

DISCUSSION

The underlying cause for the patient's acute PE is unknown but could possibly be attributed to obesity and reduced mobility. Although dabigatran should have prevented PE, the presence of interacting drugs, patient-specific pharmacokinetics, suboptimal medication storage, and laboratory abnormalities may have resulted in reduced dabigatran exposure and protection. This is a reasonable hypothesis; however, the patient did not develop a stroke while receiving dabigatran.

CONCLUSIONS

Our patient developed acute bilateral PE despite receiving long-term anticoagulation with dabigatran. While it is possible that patient-specific factors resulted in reduced dabigatran exposure and efficacy, conclusions cannot be made.
What's at Stake in the Lives of People With Intellectual Disability? Part I: The Power of Naming, Defining, Diagnosing, Classifying, and Planning Supports
Authors: Schalock Robert L. , Luckasson Ruth
Published: March 2013

This article focuses on the power of naming, defining, diagnosing, classifying, and planning supports for people with intellectual disability. The article summarizes current thinking regarding these five functions, states the essential question addressed by the respective function, and provides an overview of the high stakes involved for people with intellectual disability, their families, and the field of intellectual disability.
Depression, obesity, and smoking were independently associated with inadequate glycemic control in patients with type 1 diabetes
Authors: Melin Eva O , Thunander Maria , Svensson Ralph , Landin-Olsson Mona , Thulesius Hans O
Published: March 2013

Objective

The aim of this study was to explore the associations between inadequate glycemic control of diabetes and psychological, anthropometric, and lifestyle variables in a population-based cohort of type 1 diabetes patients.

Design

Cross-sectional study.

Methods

In this study, 292 patients with type 1 diabetes, aged 18–59 years, participated. Psychological data were assessed by self-report instruments: Hospital Anxiety and Depression Scale and Toronto Alexithymia Scale-20. Anthropometrics, blood analyses, data from medical records, and data from the Swedish National Diabetes Registry were collected.

Results

Self-reported depression (adjusted odds ratio (AOR) 4.8), obesity (AOR 4.3), and smoking (AOR 3.0) were independently associated with inadequate glycemic control of diabetes (HbA1c>8.6%). Gender-stratified analyses showed that self-reported depression (AOR 19.8) and obesity (AOR 7.0) in women and smoking in men (AOR 4.2) were associated with HbA1c>8.6%. Alexithymia, antidepressant medication, and physical inactivity were associated with HbA1c>8.6% only in bivariate analyses. Alexithymia, self-rated anxiety, physical inactivity, and absence of abdominal obesity were associated with self-reported depression.

Conclusions

Depression was the only psychological factor independently associated with HbA1c>8.6%. The association was of comparable importance as obesity and smoking, well-known risk factors for inadequate glycemic control and diabetes complications. The association between depression and HbA1c>8.6% was particularly strong for women. Alexithymia, which is a relatively stable personality trait, was associated with depression. In the future care of patients with diabetes, psychological aspects should be considered alongside anthropometrics and lifestyle factors in order to achieve the goals for HbA1c.
Rat Gnrhr promoter directs species-specific gene expression in the pituitary and testes of transgenic mice
Authors: Ishaq Muhammad , Schang Anne-Laure , Magre Solange , Laverrière Jean-Noël , Guillou Aurélien , Coudouel Noëlline , Wargnier Richard , Cohen-Tannoudji Joëlle , Counis Raymond
Published: March 2013

The GnRH receptor (GnRHR) is expressed in several non-pituitary tissues, notably in gonads. However, mechanisms underlying the gonad-specific expression ofGnrhrare not well understood. Here,Gnrhrexpression was analysed in the developing testes and pituitaries of rats and transgenic mice bearing the human placental alkaline phosphatase reporter gene (ALPP) under the control of the ratGnrhrpromoter. We showed that the 3.3 kb, but not the pituitary-specific 1.1 kb promoter, directsALPPexpression exclusively to testis Leydig cells from embryonic day 12 onwards. Real-time PCR analysis revealed that promoter activity displayed the same biphasic profile as marker genes in Leydig cells, i.e. abrupt declines after birth followed by progressive rises after a latency phase, in coherence with the differentiation and evolution of foetal and adult Leydig cell lineages. Interestingly, the developmental profile of transgene expression showed high similarity with the endogenousGnrhrprofile in the rat testis, while mouseGnrhrwas only poorly expressed in the mouse testis. In the pituitary, both transgene andGnrhrwere co-expressed at measurable levels with similar ontogenetic profiles, which were markedly distinct from those in the testis. Castration that induced pituitaryGnrhrup-regulation in rats did not affect the mouseGnrhr. However, it duly up-regulated the transgene. In addition, in LβT2 cells, the rat, but not mouse,Gnrhrpromoter was sensitive to GnRH agonist stimulation. Collectively, our data highlight inter-species variations in the expression and regulation ofGnrhrin two different organs and reveal that the rat promoter sequence contains relevant genetic information that dictates rat-specific gene expression in the mouse context.
Human heterochromatin protein 1 isoforms regulate androgen receptor signaling in prostate cancer
Authors: Itsumi Momoe , Shiota Masaki , Yokomizo Akira , Kashiwagi Eiji , Takeuchi Ario , Tatsugami Katsunori , Inokuchi Junichi , Song YooHyun , Uchiumi Takeshi , Naito Seiji
Published: March 2013

Androgen receptor (AR) signaling is critical for the tumorigenesis and development of prostate cancer, as well as the progression to castration-resistant prostate cancer. We previously showed that the heterochromatin protein 1 (HP1) β isoform plays a critical role in transactivation of AR signaling as an AR coactivator that promotes prostate cancer cell proliferation. However, the roles of other HP1 isoforms, HP1α and HP1γ, in AR expression and prostate cancer remain unclear. Here, we found that knockdown of HP1γ, but not HP1α, reduced AR expression and cell proliferation by inducing cell cycle arrest at G1 phase in LNCaP cells. Conversely, overexpression of full-length HP1α and its C-terminal deletion mutant increased AR expression and cell growth, whereas overexpression of HP1γ had no effect. Similarly, HP1α overexpression promoted 22Rv1 cell growth, whereas HP1γ knockdown reduced the proliferation of CxR cells, a castration-resistant LNCaP derivative. Taken together, HP1 isoforms distinctly augment AR signaling and cell growth in prostate cancer. Therefore, silencing of HP1β and HP1γ may be a promising therapeutic strategy for treatment of prostate cancer.
Parents Without Partners:Drosophilaas a Model for Understanding the Mechanisms and Evolution of Parthenogenesis
Authors: Markow Therese Ann
Published: March 2013

Of 40 Drosophila species screened to date, a majority have shown some ability to at least initiate parthenogenetic development. In one case, Drosophila mangebeirai, natural populations are entirely female, making it the only obligate parthenogenetic species of Drosophila. Only a few of the species that exhibit the ability to undergo early embryonic development of unfertilized eggs successfully respond to selection for parthenogenetic production of adult flies. Laboratory strains of parthenogenetic Drosophila mercatorum have been created by artificial selection on multiple occasions, but the proportion of eggs undergoing development to adulthood has never exceeded 8%. Selection produces gains in the number of unfertilized eggs undergoing early development, but the majority arrest at the embryonic or first larval instar stages. Four components to successful parthenogenesis include (1) a female’s propensity to lay unfertilized eggs, (2) the ability of the eggs to restore diploidy, (3) the ability of the parthenogenetically produced diploid embryo to complete larval development and pupation, and (4) the existence of genetic variability within and among Drosophila species in the frequency of parthenogenesis suggests the existence of multiple steps in its evolution and offers a way to explore the genetics of this unusual reproductive strategy.
Distribution of Long-Range Linkage Disequilibrium and Tajima’s D Values in Scandinavian Populations of Norway Spruce (Picea abies)
Authors: Larsson Hanna , Källman Thomas , Gyllenstrand Niclas , Lascoux Martin
Published: March 2013

The site frequency spectrum of mutations (SFS) and linkage disequilibrium (LD) are the two major sources of information in population genetics studies. In this study we focus on the levels of LD and the SFS and on the effect of sample size on summary statistics in 10 Scandinavian populations of Norway spruce. We found that previous estimates of a low level of LD were highly influenced by both sampling strategy and the fact that data from multiple loci were analyzed jointly. Estimates of LD were in fact heterogeneous across loci and increased within individual populations compared with the estimate from the total data. The variation in levels of LD among populations most likely reflects different demographic histories, although we were unable to detect population structure by using standard approaches. As in previous studies, we also found that the SFS-based test Tajima’s D was highly sensitive to sample size, revealing that care should be taken to draw strong conclusions from this test when sample size is small. In conclusion, the results from this study are in line with recent studies in other conifers that have revealed a more complex and variable pattern of LD than earlier studies suggested and with studies in trees and humans that suggest that Tajima’s D is sensitive to sample size. This has large consequences for the design of future association and population genetic studies in Norway spruce.
Population Structure in a Comprehensive Genomic Data Set on Human Microsatellite Variation
Authors: Pemberton Trevor J , DeGiorgio Michael , Rosenberg Noah A
Published: March 2013

Over the past two decades, microsatellite genotypes have provided the data for landmark studies of human population-genetic variation. However, the various microsatellite data sets have been prepared with different procedures and sets of markers, so that it has been difficult to synthesize available data for a comprehensive analysis. Here, we combine eight human population-genetic data sets at the 645 microsatellite loci they share in common, accounting for procedural differences in the production of the different data sets, to assemble a single data set containing 5795 individuals from 267 worldwide populations. We perform a systematic analysis of genetic relatedness, detecting 240 intra-population and 92 inter-population pairs of previously unidentified close relatives and proposing standardized subsets of unrelated individuals for use in future studies. We then augment the human data with a data set of 84 chimpanzees at the 246 loci they share in common with the human samples. Multidimensional scaling and neighbor-joining analyses of these data sets offer new insights into the structure of human populations and enable a comparison of genetic variation patterns in chimpanzees with those in humans. Our combined data sets are the largest of their kind reported to date and provide a resource for use in human population-genetic studies.
The Genomic and Transcriptomic Landscape of a HeLa Cell Line
Authors: Landry Jonathan J M , Pyl Paul Theodor , Rausch Tobias , Zichner Thomas , Tekkedil Manu M , Stütz Adrian M , Jauch Anna , Aiyar Raeka S , Pau Gregoire , Delhomme Nicolas , Gagneur Julien , Korbel Jan O , Huber Wolfgang , Steinmetz Lars M
Published: March 2013

HeLa is the most widely used model cell line for studying human cellular and molecular biology. To date, no genomic reference for this cell line has been released, and experiments have relied on the human reference genome. Effective design and interpretation of molecular genetic studies performed using HeLa cells require accurate genomic information. Here we present a detailed genomic and transcriptomic characterization of a HeLa cell line. We performed DNA and RNA sequencing of a HeLa Kyoto cell line and analyzed its mutational portfolio and gene expression profile. Segmentation of the genome according to copy number revealed a remarkably high level of aneuploidy and numerous large structural variants at unprecedented resolution. Some of the extensive genomic rearrangements are indicative of catastrophic chromosome shattering, known as chromothripsis. Our analysis of the HeLa gene expression profile revealed that several pathways, including cell cycle and DNA repair, exhibit significantly different expression patterns from those in normal human tissues. Our results provide the first detailed account of genomic variants in the HeLa genome, yielding insight into their impact on gene expression and cellular function as well as their origins. This study underscores the importance of accounting for the strikingly aberrant characteristics of HeLa cells when designing and interpreting experiments, and has implications for the use of HeLa as a model of human biology.
Genetic Basis of Ammonium Toxicity Resistance in a Sake Strain of Yeast: A Mendelian Case
Authors: Reisser Cyrielle , Dick Cynthia , Kruglyak Leonid , Botstein David , Schacherer Joseph , Hess David C
Published: March 2013

High concentrations of ammonium at physiological concentrations of potassium are toxic for the standard laboratory strain of Saccharomyces cerevisiae. In the original description of this metabolic phenotype, we focused on the standard laboratory strains of Saccharomyces. In this study, we screened a large collection of S. cerevisiae natural isolates and identified one strain that is resistant to high concentrations of ammonium. This strain, K12, was isolated in sake breweries. When the K12 strain was crossed to the standard laboratory strain (FY4), the resulting tetrads displayed 2:2 segregation of the resistance phenotype, suggesting a single gene trait. Using a bulk segregant analysis strategy, we mapped this trait to a 150-kb region on chromosome X containing the TRK1 gene. This gene encodes a transporter required for high-affinity potassium transport in S. cerevisiae. Data from reciprocal hemizygosity experiments with TRK1 deletion strains in K12 and BY backgrounds, as well as analysis of the deletion of this gene in the K12 strain, demonstrate that the K12 allele of TRK1 is responsible for ammonium toxicity resistance. Furthermore, we determined the minimal amount of potassium required for both the K12 and laboratory strain needed for growth. These results demonstrate that the gene encoded by the K12 allele of TRK1 has a greater affinity for potassium than the standard allele of TRK1 found in Saccharomyces strains. We hypothesize that this greater-affinity allele of the potassium transporter reduces the flux of ammonium into the yeast cells under conditions of ammonium toxicity. These findings further refine our understanding of ammonium toxicity in yeast and provide an example of using natural variation to understand cellular processes.
Involvement of MLPK Pathway in Intraspecies Unilateral Incompatibility Regulated by a Single Locus With Stigma and Pollen Factors
Authors: Takada Yoshinobu , Sato Takahiro , Suzuki Go , Shiba Hiroshi , Takayama Seiji , Watanabe Masao
Published: March 2013

Plants have evolved many systems to prevent undesirable fertilization. Among these, incompatibility is a well-organized system in which pollen germination or pollen tube growth is inhibited in pistils. We previously found that a novel one-way pollen–stigma incompatibility response [unilateral incompatibility (UI)] occurred between two self-incompatible Brassica rapa plants, a Turkish line, and a Japanese cultivated hybrid variety, “Osome.” Pollen from the Turkish line is rejected on the stigma of the Osome line, but the reverse cross is compatible; such a UI phenotype closely resembles self-incompatibility (SI). The pollen factor of this UI has been genetically explained by a single locus which is different from the S-locus. In this study, we performed further genetic analyses of this intraspecies UI and showed that the stigma factor was also controlled by a single locus, and we named the loci corresponding to the stigma and pollen factors of the intraspecies UI, stigmatic unilateral incompatibility (SUI), and pollen unilateral incompatibility (PUI) loci, respectively. Interestingly, segregation analyses of SUI and PUI indicated that they are closely linked to each other and behave as a single unit. To investigate the effect of an SI-related gene, MLPK in this UI, we produced segregation lines for SUI and mlpk. A distorted segregation ratio of SUI phenotype in an mlpk background indicated involvement of MLPK in SUI, suggesting the existence of an MLPK-dependent novel pollen–stigma recognition mechanism.
A High-Fidelity Cell Lineage Tracing Method for Obtaining Systematic Spatiotemporal Gene Expression Patterns inCaenorhabditis elegans
Authors: Mace Daniel L , Weisdepp Peter , Gevirtzman Louis , Boyle Thomas , Waterston Robert H
Published: March 2013

Advances in microscopy and fluorescent reporters have allowed us to detect the onset of gene expression on a cell-by-cell basis in a systematic fashion. This information, however, is often encoded in large repositories of images, and developing ways to extract this spatiotemporal expression data is a difficult problem that often uses complex domain-specific methods for each individual data set. We present a more unified approach that incorporates general previous information into a hierarchical probabilistic model to extract spatiotemporal gene expression from 4D confocal microscopy images of developing Caenorhabditis elegans embryos. This approach reduces the overall error rate of our automated lineage tracing pipeline by 3.8-fold, allowing us to routinely follow the C. elegans lineage to later stages of development, where individual neuronal subspecification becomes apparent. Unlike previous methods that often use custom approaches that are organism specific, our method uses generalized linear models and extensions of standard reversible jump Markov chain Monte Carlo methods that can be readily extended to other organisms for a variety of biological inference problems relating to cell fate specification. This modeling approach is flexible and provides tractable avenues for incorporating additional previous information into the model for similar difficult high-fidelity/low error tolerance image analysis problems for systematically applied genomic experiments.
Developmental stage dependency of the effect of drought stress on photosynthesis in winter wheat (Triticum aestivum L.) varieties
Authors: Fábián A. , Jäger K. , Barnabás B.
Published: March 2013

Drought stress frequently occurs in the reproductive stage of wheat, causing significant yield loss. To study the developmental stage dependency of the effect of drought stress on photosynthesis, plants of the drought-tolerant Plainsman V and sensitive Cappelle Desprez winter wheat varieties were grown in phytotron chambers and subjected to water withholding during three phenophases of reproductive development: meiosis, anthesis and early seed development (ESD).Stomatal conductance (gs) and net photosynthesis (Anet) showed similar characteristics. Meiotic-stage drought only decreased the values of Cappelle Desprez significantly. Stressed Plainsman V showed a significantly smaller reduction and better regeneration for these parameters at anthesis. The decreases in gs and Anet were similar in both varieties when drought was applied during ESD. Studies on the intercellular CO2 concentration (Ci) inflexion point implied that metabolic impairment was less typical of stressed Plainsman V than of Cappelle Desprez at meiosis and anthesis. The quantum efficiency of PSII (ΦPSII) did not decline in either genotype during meiotic-stage drought. Stressed Plainsman V showed significantly higher ΦPSII values compared to Cappelle Desprez at anthesis. During ESD, the values for stressed plants of both genotypes decreased to a similar extent.The results indicate that the effect of drought stress on photosynthesis shows developmental stage dependency during the reproductive life cycle of wheat.
Coumarin and salicylic acid activate resistance to Macrophomina phaseolina in Helianthus annuus
Authors: Al-Wakeel S. , Gabr M. , Abu-El-Soud W. , Saleh A.
Published: March 2013

The induction of resistance to charcoal rot disease caused byMacrophomina phaseolina(Tassi) Goidanich in sunflower (Helianthus annuusL.) was studied after seed treatments with coumarin (COU) and salicylic acid (SA) at three different levels (0.3, 1.0 and 3.0 mM). The priming of sunflower seeds with 0.3 mM COU or 1.0 mM SA resulted in decreased disease severity and offered about 50% protection and more than 80% reduction in the length of stem lesions under greenhouse conditions. Both COU and SA treatments induced the accumulation of soluble sugars and phytoalexins, as well as stimulating the activity of β-1,3-glucanase and chitinase.