bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal transcriptomic dysregulation in the peripheral blood of transgenic Huntington’s disease monkeys
Authors: Kocerha Jannet , Liu Yuhong , Willoughby David , Chidamparam Kumaravel , Benito Joseph , Nelson Kate , Xu Yan , Chi Tim , Engelhardt Heidi , Moran Sean , Yang Shang-Hsun , Li Shi-Hua , Li Xiao-Jiang , Larkin Katherine , Neumann Adam , Banta Heather , Yang Jin Jing , Chan Anthony WS
Published: August 2013

Background

Huntington’s Disease (HD) is a progressive neurodegenerative disorder caused by an expansion in the polyglutamine (polyQ) region of the Huntingtin (HTT) gene. The clinical features of HD are characterized by cognitive, psychological, and motor deficits. Molecular instability, a core component in neurological disease progression, can be comprehensively evaluated through longitudinal transcriptomic profiling. Development of animal models amenable to longitudinal examination enables distinct disease-associated mechanisms to be identified.

Results

Here we report the first longitudinal study of transgenic monkeys with genomic integration of various lengths of the human HTT gene and a range of polyQ repeats. With this unique group of transgenic HD nonhuman primates (HD monkeys), we profiled over 47,000 transcripts from peripheral blood collected over a 2 year timespan from HD monkeys and age-matched wild-type control monkeys.

Conclusions

Messenger RNAs with expression patterns which diverged with disease progression in the HD monkeys considerably facilitated our search for transcripts with diagnostic or therapeutic potential in the blood of human HD patients, opening up a new avenue for clinical investigation.
Transurethral marking incision of the bladder neck: a helpful technique in robot-assisted laparoscopic radical prostatectomy involving post-transurethral resection of the prostate and cancers protruding into the bladder neck
Authors: Kurokawa Satoshi , Tozawa Keiichi , Umemoto Yukihiro , Yasui Takahiro , Mizuno Kentaro , Okada Atsushi , Kawai Noriyasu , Hayashi Yutaro , Kohri Kenjiro
Published: August 2013

Background

Bladder neck transection is one of the most difficult procedures for robot-assisted laparoscopic radical prostatectomy (RALP), particularly in patients who have undergone previous transurethral resection of the prostate (TUR-P), and in those with large median lobes or prostate cancer protruding into the bladder neck. To ensure negative surgical margins and safely preserve the ureteral orifices during bladder neck transection, we propose the use of the transurethral resectoscope for making the incision in the bladder neck before initiating RALP. Thus, we developed a technique for bladder neck transection to facilitate this operation in such patients.

Case presentation

Two Japanese men, aged 61 and 63 years, who were diagnosed with prostate cancer, received a transurethral marking incision of the bladder neck before starting RALP; prostate cancer developed in one patient after TUR-P and the other patient had cancer protruding into the bladder neck. A transurethral resectoscope was used to closely observe the ureteral orifices and bladder necks; the bladder necks were marked to indicate the depth from the mucosa to the muscular layer. During the RALP, the bladder necks were dissected to indicate the depth of the marking incision. The surgical margins were negative and perioperative complications did not occur. The Foley catheters were removed on postoperative day 6, according to the usual protocol. No urinary leakage from the anastomosis sites was observed.

Conclusion

This technique, involving the use of an ordinary transurethral resectoscope, may be an easy procedure to ensure negative surgical margins, safely preserve the ureteral orifices, avoid increasing the bladder neck diameter, and achieve a good quality vesicourethral anastomosis that prevents the risk of suture-related tissue tears.
Cryopreservation of glucose-6-phosphate dehydrogenase activity inside red blood cells: developing a specimen repository in support of development and evaluation of glucose-6-phosphate dehydrogenase deficiency tests
Authors: Kahn Maria , LaRue Nicole , Bansil Pooja , Kalnoky Michael , McGray Sarah , Domingo Gonzalo J
Published: August 2013

Background

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common human enzyme deficiency. It is characterized by abnormally low levels of G6PD activity. Individuals with G6PD deficiency are at risk of undergoing acute haemolysis when exposed to 8‒aminoquinoline-based drugs, such as primaquine. For this reason it is imperative to identify individuals with G6PD deficiency prior to administering these anti-malarial drugs. There is a need for the development and evaluation of point-of-care G6PD deficiency screening tests suitable for areas of the developing world where malarial treatments are frequently administered. The development and evaluation of new G6PD tests will be greatly assisted with the availability of specimen repositories.

Methods

Cryopreservation of erythrocytes was evaluated as a means to preserve G6PD activity. Blood specimens from 31 patients including ten specimens with normal G6PD activity, three with intermediate activity, and 18 with deficient activity were cryopreserved for up to six months.

Results

Good correlation in G6PD activity between fresh and cryopreserved specimens (R2 = 0.95). The cryopreserved specimens show an overall small drop in mean G6PD activity of 0.23 U/g Hb (P=0.23). Cytochemical staining showed that intracellular G6PD activity distribution within the red blood cell populations is preserved during cryopreservation. Furthermore, the mosaic composition of red blood cells in heterozygous women is also preserved for six months or more. The fluorescent spot and the BinaxNOW qualitative tests for G6PD deficiency also showed high concordance in G6PD status determination between cryopreserved specimens and fresh specimens.

Conclusions

A methodology for establishing a specimen panel for evaluation of G6PD tests is described. The approach is similar to that used in several malaria research facilities for the cryopreservation of parasites in clinical specimens and axenic cultures. Specimens stored in this manner will aid both the development and evaluation of current and emerging G6PD tests. The availability of G6PD tests is a critical bottleneck to broader access to drugs that confer radical cure of Plasmodium vivax, a requirement for elimination of malaria.
Quantum dots incorporated magnetic nanoparticles for imaging colon carcinoma cells
Authors: Ahmed Syed Rahin , Dong Jinhua , Yui Megumi , Kato Tatsuya , Lee Jaebeom , Park Enoch Y
Published: August 2013

Background

Engineered multifunctional nanoparticles (NPs) have made a tremendous impact on the biomedical sciences, with advances in imaging, sensing and bioseparation. In particular, the combination of optical and magnetic responses through a single particle system allows us to serve as novel multimodal molecular imaging contrast agents in clinical settings. Despite of essential medical imaging modalities and of significant clinical application, only few nanocomposites have been developed with dual imaging contrast. A new method for preparing quantum dots (QDs) incorporated magnetic nanoparticles (MNPs) based on layer-by-layer (LbL) self-assembly techniques have developed and used for cancer cells imaging.

Methods

Here, citrate - capped negatively charged Fe3O4 NPs were prepared and coated with positively - charged hexadecyltrimethyl ammonium bromide (CTAB). Then, thiol - capped negatively charged CdTe QDs were electrostatically bound with CTAB. Morphological, optical and magnetic properties of the fluorescent magnetic nanoparticles (FMNPs) were characterized. Prepared FMNPs were additionally conjugated with hCC49 antibodies fragment antigen binding (Fab) having binding affinity to sialylated sugar chain of TAG-72 region of LS174T cancer cells, which was prepared silkworm expression system, and then were used for imaging colon carcinoma cells.

Results

The prepared nanocomposites were magnetically responsive and fluorescent, simultaneously that are useful for efficient cellular imaging, optical sensing and magnetic separation. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) revealed that the particle size is around 50 nm in diameter with inner magnetic core and outer CdTe QDs core-shell structure. Cytotoxicity test of prepared FMNPs indicates high viability in Vero cells. NPs conjugated with anti cancer antibodies were successfully labeled on colon carcinoma cells (LS174) in vitro and showed significant specificity to target cells.

Conclusion

The present report demonstrates a simple synthesis of CdTe QDs-Fe3O4 NPs. The surface of the prepared FMNPs was enabled simple conjugation to monoclonal antibodies by electrostatic interaction. This property further extended their in vitro applications as cellular imaging contrast agents. Such labeling of cells with new fluorescent-magneto nanoprobes for living detection is of interest to various biomedical applications and has demonstrated the potential for future medical use.
Partial response after transcatheter arterial infusion chemotherapy in a patient with systemic chemotherapy-resistant unresectable colon cancer and hepatic metastasis: (case report)
Authors: Sawai Katsuji , Goi Takanori , Koneri Kenji , Katayama Kanji , Yamaguchi Akio
Published: August 2013

We report here a case of partial response to hepatic arterial infusion chemotherapy in a patient who developed serious hepatic failure due to unresectable colorectal cancer and hepatic metastasis and showed resistance to systemic chemotherapy with molecular targeted drugs, mFOLFOX6, and FOLFIRI. The patient was a 60-year-old woman who underwent sigmoidectomy for sigmoid colon cancer, lateral posterior hepatic segmentectomy for metastatic liver cancer, and postoperative radiation therapy for metastatic lung cancer. As first-line systemic chemotherapy, mFOLFOX6 (oxaliplatin, 5-fluorouracil, and leucovorin), bevacizumab + FOLFIRI (irinotecan, 5-fluorouracil, leucovorin), and anti-epidermal growth factor receptor antibody + irinotecan were administered, in that order. However, recurrent hepatic metastasis was exacerbated, which induced serious hepatic failure manifested by general malaise, jaundice, abnormal hepatic function, difficulty in walking due to bilateral lower extremity edema, and decreased appetite. The patient was admitted in a serious condition. After hospitalization, the patient received hepatic arterial infusion chemotherapy with 5-fluorouracil and l-leucovorin. After two complete courses, the symptoms improved. The patient’s performance status also improved, and she was discharged from the hospital. Four months after discharge, the patient had continued outpatient chemotherapy and maintained excellent performance status. Although HAIC is not presently considered an alternative to systemic chemotherapy, it is sometimes effective in patients who show resistance to molecular targeted drug therapy, FOLFOX, and FOLFIRI, and in whom hepatic metastasis is a key factor in determining prognosis and serious hepatic failure. Further studies should be performed in the future to verify these findings.
Factors affecting job satisfaction and retention of medical laboratory professionals in seven countries of Sub-Saharan Africa
Authors: Marinucci Francesco , Majigo Mtebe , Wattleworth Matthew , Paterniti Antonio Damiano , Hossain Mian Bazle , Redfield Robert
Published: August 2013

Effective implementation and sustainability of quality laboratory programmes in Sub-Saharan Africa relies on the development of appropriate staff retention strategies. Assessing the factors responsible for job satisfaction and retention is key for tailoring specific interventions aiming at improving the overall impact of health programmes. A survey was developed to assess these factors among 224 laboratorians working in the laboratory programme the University of Maryland implemented in seven Sub-Saharan African countries. Lack of professional development was the major reason for leaving the previous job for 28% of interviewees who changed jobs in the past five years. Professional development/training opportunities was indicated by almost 90% (195/224) of total interviewees as the most important or a very important factor for satisfaction at their current job. Similarly, regular professional development/opportunities for training was the highest rated incentive to remain at their current job by 80% (179/224). Laboratory professionals employed in the private sector were more likely to change jobs than those working in the public sector (P = 0.002). The findings were used for developing specific strategies for human resources management, in particular targeting professional development, aiming at improving laboratory professionals within the University of Maryland laboratory programme and hence its long-term sustainability.
Virus propagation power of the dynamic network
Authors: Cai Fu , Qingfeng Huang , LanSheng Han , Li Shen , Xiao-Yang Liu
Published: August 2013

With the development of mobile networks, propagation characteristics and defense mechanism of the virus have attracted increasing research attention. But current researches are mainly concerned with static network topology or community structure and some studies focus on characteristics of virus and malware. Little attention is paid to the influence of dynamic changes of network topology to virus propagation. Meanwhile, many studies focus on the threshold rate of the infection (or the immunization rate) for virus outbreak. In this paper, we present a new way to assess and restrain virus propagation by proposing the concepts of propagation power and propagation structure. Three basic propagation structures are presented through which the infection risk can be quantified, and a framework is proposed to assess the impact of virus propagation in different network structures. The relationship between the speed of virus propagation and network structure is also explored. An algorithm is designed to assess the propagation power in a dynamic network with no need to redetect the community under the dynamic network which may significantly improve the efficiency of assessment in a large-scale dynamic network. This study offers a feasible approach for quantifying the risk of virus infection in the network community which is valuable for designing and optimizing the virus defense systems.
Tumor necrosis factor alpha antagonism improves neurological recovery in murine intracerebral hemorrhage
Authors: Lei Beilei , Dawson Hana N , Roulhac-Wilson Briana , Wang Haichen , Laskowitz Daniel T , James Michael L
Published: August 2013

Background

Intracerebral hemorrhage (ICH) is a devastating stroke subtype characterized by a prominent neuroinflammatory response. Antagonism of pro-inflammatory cytokines by specific antibodies represents a compelling therapeutic strategy to improve neurological outcome in patients after ICH. To test this hypothesis, the tumor necrosis factor alpha (TNF-α) antibody CNTO5048 was administered to mice after ICH induction, and histological and functional endpoints were assessed.

Methods

Using 10 to 12-week-old C57BL/6J male mice, ICH was induced by collagenase injection into the left basal ganglia. Brain TNF-α concentration, microglia activation/macrophage recruitment, hematoma volume, cerebral edema, and rotorod latency were assessed in mice treated with the TNF-α antibody, CNTO5048, or vehicle.

Results

After ICH induction, mice treated with CNTO5048 demonstrated reduction in microglial activation/macrophage recruitment compared to vehicle-treated animals, as assessed by unbiased stereology (P = 0.049). This reduction in F4/80-positive cells was associated with a reduction in cleaved caspase-3 (P = 0.046) and cerebral edema (P = 0.026) despite similar hematoma volumes, when compared to mice treated with vehicle control. Treatment with CNTO5048 after ICH induction was associated with a reduction in functional deficit when compared to mice treated with vehicle control, as assessed by rotorod latencies (P = 0.024).

Conclusions

Post-injury treatment with the TNF-α antibody CNTO5048 results in less neuroinflammation and improved functional outcomes in a murine model of ICH.
Antiviral activities of Indonesian medicinal plants in the East Java region against hepatitis C virus
Authors: Wahyuni Tutik Sri , Tumewu Lydia , Permanasari Adita Ayu , Apriani Evhy , Adianti Myrna , Rahman Abdul , Widyawaruyanti Aty , Lusida Maria Inge , Fuad Achmad , Soetjipto  , Nasronudin  , Fuchino Hiroyuki , Kawahara Nobuo , Shoji Ikuo , Deng Lin , Aoki Chie , Hotta Hak
Published: August 2013

Background

Hepatitis C virus (HCV) is a major cause of liver disease and a potential cause of substantial morbidity and mortality worldwide. The overall prevalence of HCV infection is 2%, representing 120 million people worldwide. Current standard treatment using pegylated interferon and ribavirin is effective in only 50% of the patients infected with HCV genotype 1, and is associated with significant side effects. Therefore, it is still of importance to develop new drugs for treatment of HCV. Antiviral substances obtained from natural products, including medicinal plants, are potentially good targets to study. In this study, we evaluated Indonesian medicinal plants for their anti-HCV activities.

Methods

Ethanol extracts of 21 samples derived from 17 species of medicinal plants explored in the East Java region were tested. Anti-HCV activities were determined by a cell culture method using Huh7.5 cells and HCV strains of 9 different genotypes (1a to 7a, 1b and 2b).

Results

Four of the 21 samples tested showed antiviral activities against HCV: Toona sureni leaves (TSL) with 50% inhibitory concentrations (IC50) of 13.9 and 2.0 μg/ml against the HCV J6/JFH1-P47 and -P1 strains, respectively, Melicope latifolia leaves (MLL) with IC50 of 3.5 and 2.1 μg/ml, respectively, Melanolepis multiglandulosa stem (MMS) with IC50 of 17.1 and 6.2 μg/ml, respectively, and Ficus fistulosa leaves (FFL) with IC50 of 15.0 and 5.7 μg/ml, respectively. Time-of-addition experiments revealed that TSL and MLL inhibited both at the entry and post-entry steps while MMS and FFL principally at the entry step. TSL and MLL inhibited all of 11 HCV strains of all the genotypes tested to the same extent. On the other hand, FFL showed significantly weaker inhibitory activities against the HCV genotype 1a strain, and MMS against the HCV strains of genotypes 2b and 7a to a lesser extent, compared to the other HCV genotypes.

Conclusions

Ethanol extracts of TSL, MLL, MMS and FFL showed antiviral activities against all the HCV genotypes tested with the exception that some genotype(s) showed significant resistance to FFL and to MMS to a lesser extent. These plant extracts may be good candidates for the development of anti-HCV drugs.
Intranasal exposure to amorphous nanosilica particles could activate intrinsic coagulation cascade and platelets in mice
Authors: Yoshida Tokuyuki , Yoshioka Yasuo , Tochigi Saeko , Hirai Toshiro , Uji Miyuki , Ichihashi Ko-ichi , Nagano Kazuya , Abe Yasuhiro , Kamada Haruhiko , Tsunoda Shin-ichi , Nabeshi Hiromi , Higashisaka Kazuma , Yoshikawa Tomoaki , Tsutsumi Yasuo
Published: August 2013

Background

Nanomaterials with particle sizes <100 nm have been already applied in various applications such as cosmetics, medicines, and foods. Therefore, ensuring the safety of nanomaterials is becoming increasingly important. Here we examined the localization and biological responses of intranasally administered amorphous nanosilica particles in mice, focusing on the coagulation system.

Methods

We used nanosilica particles with diameters of 30, 70, or 100 nm (nSP30, nSP70, or nSP100 respectively), and conventional microscale silica particles with diameters of 300 or 1000 nm (mSP300 or mSP1000, respectively). BALB/c mice were intranasally exposed to nSP30, nSP70, nSP100, mSP300, or mSP1000 at concentrations of 500 μg/mouse for 7 days. After 24 hours of last administration, we performed the in vivo transmission electron microscopy analysis, hematological examination and coagulation tests.

Results

In vivo transmission electron microscopy analysis showed that nanosilica particles with a diameter <100 nm were absorbed through the nasal cavity and were distributed into liver and brain. Hematological examination and coagulation tests showed that platelet counts decreased and that the activated partial thromboplastin time was prolonged in nSP30 or nSP70-treated groups of mice, indicating that nanosilica particles might have activated a coagulation cascade. In addition, in in vitro activation tests of human plasma, nanosilica particles had greater potential than did conventional microscale silica particles to activate coagulation factor XII. In nanosilica-particle-treated groups, the levels of soluble CD40 ligand, and von Willebrand factor which are involved in stimulating platelets tended to slightly increase with decreasing particle size.

Conclusions

These results suggest that intranasally administered nanosilica particles with diameters of 30 and 70 nm could induce abnormal activation of the coagulation system through the activation of an intrinsic coagulation cascade. This study provides information to advance the development of safe and effective nanosilica particles.
A mutation in the serine protease TMPRSS4 in a novel pediatric neurodegenerative disorder
Authors: Lahiry Piya , Racacho Lemuel , Wang Jian , Robinson John F , Gloor Gregory B , Rupar C Anthony , Siu Victoria M , Bulman Dennis E , Hegele Robert A
Published: August 2013

Background

To elucidate the genetic basis of a novel neurodegenerative disorder in an Old Order Amish pedigree by combining homozygosity mapping with exome sequencing.

Methods and results

We identified four individuals with an autosomal recessive condition affecting the central nervous system (CNS). Neuroimaging studies identified progressive global CNS tissue loss presenting early in life, associated with microcephaly, seizures, and psychomotor retardation; based on this, we named the condition Autosomal Recessive Cerebral Atrophy (ARCA). Using two unbiased genetic approaches, homozygosity mapping and exome sequencing, we narrowed the candidate region to chromosome 11q and identified the c.995C > T (p.Thr332Met) mutation in the TMPRSS4 gene. Sanger sequencing of additional relatives confirmed that the c.995C > T genotype segregates with the ARCA phenotype. Residue Thr332 is conserved across species and among various ethnic groups. The mutation is predicted to be deleterious, most likely due to a protein structure alteration as demonstrated with protein modelling.

Conclusions

This novel disease is the first to demonstrate a neurological role for a transmembrane serine proteases family member. This study demonstrates a proof-of-concept whereby combining exome sequencing with homozygosity mapping can find the genetic cause of a rare disease and acquire better understanding of a poorly described protein in human development.
Physiological responses of young thoroughbred horses to intermittent high-intensity treadmill training
Authors: Ohmura Hajime , Matsui Akira , Hada Tetsuro , Jones James H
Published: August 2013

Background

Training of young Thoroughbred horses must balance development of cardiopulmonary function and aerobic capacity with loading of the musculoskeletal system that can potentially cause structural damage and/or lameness. High-speed equine treadmills are sometimes used to supplement exercise on a track in the training of young Thoroughbreds because the horse can run at high speeds but without the added weight of a rider. We tested the hypothesis that intermittent high-intensity exercise on a treadmill of young Thoroughbred horses entering training can enhance development of aerobic capacity (V o2max) and running performance more than conventional training under saddle, and do so without causing lameness.

Results

Twelve yearling Thoroughbreds trained for 8 months with conventional riding (C) only, conventional riding plus a short (2 month, S) interval of once-per-week high-intensity treadmill exercise, or a long (8 month, L) interval of once-per-week high-intensity treadmill exercise. Three treadmill exercise tests evaluated V o2max, oxygen transport and running performance variables in June of the yearling year (only for L), October of the yearling year and April of the 2-year-old year. No horses experienced lameness during the study. Aerobic capacity increased in all groups after training. In both October and April, V o2max in L was higher than in C, but did not differ between L and S or S and C. Running speeds eliciting V o2max also increased in all groups after training, with S (809 ± 3 m/s) and L (804 ± 9 m/s) higher than C (764 ± 27 m/s). Maximum heart rate decreased for all groups after training. Hematocrit and hemoglobin concentration increased for L throughout training.

Conclusions

Young Thoroughbred horses can increase aerobic capacity and running performance more than by strictly using track training under saddle with the addition of intermittent high-intensity treadmill exercise, and they can do so without experiencing lameness. This finding suggests that young racehorses might be able to achieve higher aerobic fitness during training without subjecting their musculoskeletal systems to increased loading and risk of developing lameness. The findings of this preliminary study do not indicate a specific protocol to best achieve this goal.
Microsatellite loci characterized in the leaf-cutter ant Atta laevigata
Authors: Kakazu Sérgio , Sanches Alexandra , Bacci Maurício
Published: August 2013

Background

The leaf-cutter ant Atta laevigata (Formicidae: Attini) is an agricultural pest largely distributed in the Neotropics and a model organism for studies of evolution, speciation and population genetics. Microsatellites are a very powerful tool for these kind of studies, but such markers are not available for studies on A. laevigata. In the present report, we describe the isolation and characterization of nine microsatellite loci in A. laevigata and the testing of these markers across other species of leaf-cutter ants.

Findings

Nine microsatellite loci, consisting of six dinucloeotide, one trinucleotide, one tetranucleotide, and one di/trinucleotide repeat motifs, were isolated and characterized. Primers and protocols were successfully designed to selectively amplify these markers. To test effectiveness of these markers for detailed population genetic studies, we genotyped female workers collected from 36 monogynic nests of A. laevigata and found that eight loci were within Hardy–Weinberg expectations, while the remaining locus had a deficiency of heterozygotes. Micro-Checker analysis of individuals from 55 monogynic nests indicated that loci Alae11, Alae24, Alae18 showed signs of null alleles. For the remaining six loci, the number of alleles per locus ranged between 2 and 11, with expected heterozygosity ranging between 0.07 and 0.88. All of these loci cross-amplified in other species of Atta.

Conclusions

These six polymorphic microsatellite loci should prove useful for future genetic investigations of the pest species Atta laevigata, as well as studies of other species of leaf-cutter ants in the genus Atta.
Antibodies against gonadotropin-releasing hormone (GnRH) in patients with diabetes mellitus is associated with lower body weight and autonomic neuropathy
Authors: Berntorp Kerstin , Frid Anders , Alm Ragnar , Fredrikson Gunilla Nordin , Sjöberg Klas , Ohlsson Bodil
Published: August 2013

Background

Esophageal dysmotility and gastroparesis are common secondary complications in patients with diabetes mellitus. Patients with dysmotility express antibodies against gonadotropin-releasing hormone (GnRH) in serum. The aim of the present study was to scrutinize patients with diabetes mellitus with regard to the presence of GnRH antibodies, and to examine associations between antibodies and clinical findings.

Results

Thirty-nine consecutive patients with diabetes mellitus were included in the study after clinical examination and examination by esophageal manometry and gastric emptying scintigraphy. Serum was analyzed for the presence of antibodies against GnRH using an ELISA, and values are expressed as relative units (RU). Two age- and gender-matched healthy subjects per each patient served as controls. The prevalence of IgM GnRH antibodies in patients was 33% compared to 14% in controls (p = 0.027), with a higher antibody titer; 1.2 (0.6-5.0) and 0.2 (0.1-0.3) RU, respectively (p = 0.000). The expression of IgG antibodies was 15% in patients and none in controls (p = 0.000). Lower body mass index was associated with the presence of IgM antibodies (OR = 0.835, 95% CI = 0.699–0.998), and autonomic neuropathy with the presence IgG antibodies (OR = 9.000, 95% CI = 1.327–61.025). Esophageal dysmotility (69%) or gastroparesis (18%) were not associated with the presence of IgM antibodies (OR = 0.589, 95% CI = 0.143–2.424 and OR = 3.407, 95% CI = 0.633–18.350, respectively). Neither was esophageal dysmotility associated with IgG antibodies (OR = 2.500, 95% CI = 0.259–24.096).

Conclusions

Antibodies against GnRH are more common in patients with diabetes mellitus compared with healthy controls. IgM antibodies are associated with lower body mass index and IgG antibodies are associated with autonomic neuropathy.
Ixodes ricinus abundance and its infection with the tick-borne pathogens in urban and suburban areas of Eastern Slovakia
Authors: Pangrácová Lucia , Derdáková Markéta , Pekárik Ladislav , Hviščová Ivana , Víchová Bronislava , Stanko Michal , Hlavatá Helena , Peťko Branislav
Published: August 2013

Background

Raising abundance of ticks and tick-borne diseases in Europe is the result of multiple factors including climate changes and human activities. Herein, we investigated the presence and seasonal activity of Ixodes ricinus ticks from 10 urban and suburban sites in two different geographical areas of southeastern and northeastern Slovakia during 2008–2010. Our aim was to study the abundance of ticks in correlation with the environmental factors and their infection with Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum and Neoehrlichia mikurensis.

Methods

Questing I. ricinus ticks were collected from ten urban and suburban sites in Eastern Slovakia. A total of 670 ticks were further analysed for the presence of B. burgdorferi s.l., A. phagocytophilum and N. mikurensis by molecular methods. Tick site and environmental relations were analysed using General Linear Models (LM). The differences between the number of Lyme borreliosis cases between the Košice and Bardejov regions during a ten-year period were tested by Wilcoxon matched pairs test.

Results

In total, 2921 (1913 nymphs, 1008 adults) I. ricinus ticks were collected from 10 study sites during the main questing season. Tick activity and relative abundance differed between locations and months. Temperature and humidity were the main factors affecting the tick abundance and questing activity. Out of 670 examined ticks, 10.15% were infected with spirochetes from B. burgdorferi s.l. complex (represented by B. afzelii, B. garinii, B.valaisiana and B. burgdorferi s.s.), 2.69% with the A. phagocytophilum and 2.39% with N. mikurensis. The number of Lyme borreliosis cases per 100,000 inhabitants in the Bardejov region was significantly higher than in the Košice region.

Conclusions

Our data indicate that the risk of infection with tick-borne pathogens in Eastern Slovakia is common since 15.2% of ticks were infected at least with one of the tested microorganisms. Even though the abundance of ticks was affected by the microclimatic conditions and the prevalence of pathogens differed between the habitats, the infection risk for humans is also affected by human activities leading to an increased contact with infected ticks.
Fractalkine receptor is expressed in mature ovarian teratomas and required for epidermal lineage differentiation
Authors: Rooper Lisa , Gurler Hilal , Kajdacsy-Balla Andre A , Barbolina Maria V
Published: August 2013

Background

The goal of this study was to determine a predominant cell type expressing fractalkine receptor (CX3CR1) in mature ovarian teratomas and to establish functional significance of its expression in cell differentiation.

Methods

Specimens of ovarian teratoma and human fetal tissues were analyzed by immunohistochemistry for CX3CR1expression. Ovarian teratocarcinoma cell line PA-1 was used as a model for cell differentiation.

Results

We found that the majority of the specimens contained CX3CR1-positive cells of epidermal lineage. Skin keratinocytes in fetal tissues were also CX3CR1- positive. PA-1 cells with downregulated CX3CR1 failed to express a skin keratinocyte marker cytokeratin 14 when cultured on Matrigel in the presence of a morphogen, bone morphogenic protein 4 (BMP-4), as compared to those expressing scrambled shRNA.

Conclusions

Here we demonstrate that CX3CR1 is expressed in both normally (fetal skin) and abnormally (ovarian teratoma) differentiated keratinocytes and is required for cell differentiation into epidermal lineage.
Changes and recovery of soil bacterial communities influenced by biological soil disinfestation as compared with chloropicrin-treatment
Authors: Mowlick Subrata , Inoue Takashi , Takehara Toshiaki , Kaku Nobuo , Ueki Katsuji , Ueki Atsuko
Published: August 2013

Soil bacterial composition, as influenced by biological soil disinfestation (BSD) associated with biomass incorporation was investigated to observe the effects of the treatment on the changes and recovery of the microbial community in a commercial greenhouse setting. Chloropicrin (CP) was also used for soil disinfestation to compare with the effects of BSD. The fusarium wilt disease incidence of spinach cultivated in the BSD- and CP-treated plots was reduced as compared with that in the untreated control plots, showing effectiveness of both methods to suppress the disease. The clone library analyses based on 16S rRNA gene sequences showed that members of the Firmicutes became dominant in the soil bacterial community after the BSD-treatment. Clone groups related to the species in the class Clostridia, such as Clostridium saccharobutylicum, Clostridium tetanomorphum, Clostridium cylindrosporum, Oxobacter pfennigii, etc., as well as Bacillus niacini in the class Bacilli were recognized as the most dominant members in the community. For the CP-treated soil, clones affiliated with the Bacilli related to acid-tolerant or thermophilic bacteria such as Tuberibacillus calidus, Sporolactobacillus laevolacticus, Pullulanibacillus naganoensis, Alicyclobacillus pomorum, etc. were detected as the major groups. The clone library analysis for the soil samples collected after spinach cultivation revealed that most of bacterial groups present in the original soil belonging to the phyla Proteobacteria, Acidobacteria, Bacteroidetes, Gemmatimonadetes, Planctomycetes, TM7, etc. were recovered in the BSD-treated soil. For the CP-treated soil, the recovery of the bacterial groups belonging to the above phyla was also noted, but some major clone groups recognized in the original soil did not recover fully.
Pancreatic Cancer Clinical Trials and Accrual in the United States
Authors: Hoos William A. , James Porsha M. , Rahib Lola , Talley Anitra W. , Fleshman Julie M. , Matrisian Lynn M.
Published: August 2013

Purpose

Pancreatic cancer clinical trials open in the United States and their accrual were examined to identify opportunities to accelerate progress in the treatment of pancreatic cancer.

Methods

Pancreatic cancer–specific clinical trials open in the United States in the years 2011 and 2012 were obtained from the Pancreatic Cancer Action Network database. Accrual information was obtained from trial sponsors.

Results

The portfolio of pancreatic cancer clinical trials identified by type (adenocarcinoma or neuroendocrine), phase, disease stage, and treatment approach is reported. More than half of trials for patients with pancreatic ductal adenocarcinoma applied biologic insights to new therapeutic approaches, and 38% focused on optimization of radiation or chemotherapy delivery or regimens. In 2011, pancreatic cancer trials required total enrollment of 11,786 patients. Actual accrual to 93.2% of trials was 1,804 patients, an estimated 4.57% of the patients with pancreatic cancer alive in that year. The greatest need was for patients with resectable cancer. Trials open in 2011 enrolled an average of 15% of their total target accrual. Physician recommendations greatly influenced patients' decision to enroll or not enroll onto a clinical trial. Matching to a clinical trial within a 50-mile radius and identifying trials for recurrent/refractory disease were documented as challenges for patient accrual.

Conclusion

Overall trial enrollment indicates that pancreatic cancer trials open in 2011 would require 6.7 years on average to complete accrual. These results suggest that harmonizing patient supply and demand for clinical trials is required to accelerate progress toward improving survival in pancreatic cancer.
Elevated Fetal Adipsin/Acylation-Stimulating Protein (ASP) in Obese Pregnancy: Novel Placental Secretion via Hofbauer Cells
Authors: Sivakumar K. , Bari M. F. , Adaikalakoteswari A. , Guller S. , Weickert M. O. , Randeva H. S. , Grammatopoulos D. K. , Bastie C. C. , Vatish M.
Published: August 2013

Context and Objective:

Obesity in pregnancy is associated with increased risks of obesity in the offspring. We investigated the relationship between obesity in pregnancy and circulating maternal and fetal levels of adipose tissue-derived factors adipsin and acylation stimulating protein (ASP) in lean and obese mothers.

Design:

Paired peripheral and cord blood samples were taken. Paired fat and placenta tissue were taken for explant culture. Media were assayed for secreted adipsin and ASP. Clinical parameters assayed included fasting insulin, glucose, and adipsin.

Setting:

The study was conducted at a university hospital maternity unit.

Patients:

Patients included 35 lean [body mass index (BMI) 19–25 kg/m2, mean age 32 years and 39 obese (BMI) > 30 kg/m2, mean age 32.49 years] pregnant Caucasian women, delivered by cesarean section at term.

Main Outcome Measure:

Identification of placental macrophages [Hofbauer cells (HBCs)], as a source of adipsin and ASP was determined.

Results:

HBCs secreted both adipsin and ASP. Cord levels of adipsin (1663.78 ± 52.76 pg/mL) and ASP (354.48 ± 17.17 ng/mL) were significantly elevated in the offspring of obese mothers compared with their lean controls [1354.66 ± 33.87 pg/mL and 302.63 ± 14.98 ng/mL, respectively (P < .05 for both)]. Placentae from obese mothers released significantly more adipsin and ASP than placentae from lean mothers [546.0 ± 44 pg/mL · g vs 284.56 ± 43 pg/mL · g and 5485.75 ± 163.32 ng/mL · g vs 2399.16 ± 181.83 ng/mL · g, respectively (P < .05 for both)]. Circulating fetal adipsin and ASP positively correlated with maternal BMI (r = 0.611, P < .0001, and r = 0.391, P < .05, respectively). Fetal adipsin correlated positively with maternal (r = 0.482, P < .01) and fetal homeostasis model assessment of insulin resistance (r = 0.465, P < .01).

Conclusions:

We demonstrate novel secretion of adipsin and ASP by placental HBCs.
First Birth Achieved After In Vitro Maturation of Oocytes From a Woman Endowed With Multiple Antral Follicles Unresponsive to Follicle-stimulating Hormone
Authors: Grynberg Michaël , Peltoketo Hellevi , Christin-Maître Sophie , Poulain Marine , Bouchard Philippe , Fanchin Renato
Published: August 2013

Context:

The association of primary amenorrhea, gonadotropin levels at menopausal range, and normal antral follicle endowment is a rare clinical condition that suggests unresponsiveness of antral follicles to FSH. This affection is frequently misdiagnosed ovarian failure and patients are referred to egg donation to treat their infertility. Because these patients notably have an age-compatible number of antral follicles, we hypothesized that in vitro maturation (IVM) of oocytes might constitute a useful approach for treating their infertility.

Objective:

We report the first pregnancy and live birth obtained after IVM of oocytes in a 29-year-old patient suffering from ovarian resistance to FSH.

Design:

This is a case report.

Setting:

The work was conducted in a university hospital.

Patient:

Whereas serum FSH (40.3 and 38.4 mIU/mL) and LH (35.7 and 31.7 mIU/mL) levels were repeatedly around the menopausal range, serum anti-Müllerian hormone (4.50 and 4.36 ng/mL) levels and total counting of antral follicles (23 and 18 follicles) remained normal.

Intervention:

We aspirated antral-stage follicles and subsequently matured the oocytes in vitro.

Main Outcome Measure:

We assessed the competence of oocytes retrieved in a patient suffering from ovarian resistance to FSH.

Results:

Aspiration of antral-stage follicles allowed the retrieval of 15 immature oocytes. Following IVM, 12 of them reached metaphase II. Seven embryos were obtained and three of them were transferred into the uterus. This patient became pregnant and delivered a healthy baby at term.

Conclusions:

We report the first pregnancy and live birth achieved using IVM in a woman whose ovaries were resistant to FSH. This approach was based on the remarkable normalcy of AMH and antral follicle measurements in this patient. Therefore, IVM is a viable alternative to egg donation for women suffering from resistance to FSH. Importantly, this condition should be looked for as it may lurk undetected in women wrongly diagnosed with ovarian failure.
The nucleus of endothelial cell as a sensor of blood flow direction
Authors: Tkachenko Eugene , Gutierrez Edgar , Saikin Semion K. , Fogelstrand Per , Kim Chungho , Groisman Alex , Ginsberg Mark H.
Published: August 2013

Hemodynamic shear stresses cause endothelial cells (ECs) to polarize in the plane of the flow. Paradoxically, under strong shear flows, ECs disassemble their primary cilia, common sensors of shear, and thus must use an alternative mechanism of sensing the strength and direction of flow. In our experiments in microfluidic perfusion chambers, confluent ECs developed planar cell polarity at a rate proportional to the shear stress. The location of Golgi apparatus and microtubule organizing center was biased to the upstream side of the nucleus, i.e. the ECs polarized against the flow. These in vitro results agreed with observations in murine blood vessels, where EC polarization against the flow was stronger in high flow arteries than in veins. Once established, flow-induced polarization persisted over long time intervals without external shear. Transient destabilization of acto-myosin cytoskeleton by inhibition of myosin II or depolymerization of actin promoted polarization of EC against the flow, indicating that an intact acto-myosin cytoskeleton resists flow-induced polarization. These results suggested that polarization was induced by mechanical displacement of EC nuclei downstream under the hydrodynamic drag. This hypothesis was confirmed by the observation that acute application of a large hydrodynamic force to ECs resulted in an immediate downstream displacement of nuclei and was sufficient to induce persistent polarization. Taken together, our data indicate that ECs can sense the direction and strength of blood flow through the hydrodynamic drag applied to their nuclei.
The role ofTal2andTal1in the differentiation of midbrain GABAergic neuron precursors
Authors: Achim Kaia , Peltopuro Paula , Lahti Laura , Tsai Hui-Hsin , Zachariah Alyssa , Åstrand Mia , Salminen Marjo , Rowitch David , Partanen Juha
Published: August 2013

Midbrain- and hindbrain-derived GABAergic interneurons are critical for regulation of sleep, respiratory, sensory-motor and motivational processes, and they are implicated in human neurological disorders. However, the precise mechanisms that underlie generation of GABAergic neuron diversity in the midbrain–hindbrain region are poorly understood. Here, we show unique and overlapping requirements for the related bHLH proteins Tal1 and Tal2 in GABAergic neurogenesis in the midbrain. We show that Tal2 and Tal1 are specifically and sequentially activated during midbrain GABAergic neurogenesis. Similar to Gata2, a post-mitotic selector of the midbrain GABAergic neuron identity, Tal2 expression is activated very early during GABAergic neuron differentiation. Although the expression of Tal2 and Gata2 genes are independent of each other, Tal2 is important for normal midbrain GABAergic neurogenesis, possibly as a partner of Gata2. In the absence of Tal2, the majority of midbrain GABAergic neurons switch to a glutamatergic-like phenotype. In contrast, Tal1 expression is activated in a Gata2 and Tal2 dependent fashion in the more mature midbrain GABAergic neuron precursors, but Tal1 alone is not required for GABAergic neuron differentiation from the midbrain neuroepithelium. However, inactivation of both Tal2 and Tal1 in the developing midbrain suggests that the two factors co-operate to guide GABAergic neuron differentiation in a specific ventro-lateral midbrain domain. The observed similarities and differences between Tal1/Tal2 and Gata2 mutants suggest both co-operative and unique roles for these factors in determination of midbrain GABAergic neuron identities.
Dynamic relationship of the epithelium and mesenchyme during salivary gland initiation: the role of Fgf10
Authors: Wells Kirsty L. , Gaete Marcia , Matalova Eva , Deutsch Danny , Rice David , Tucker Abigail S.
Published: August 2013

Salivary glands provide an excellent model for the study of epithelial–mesenchymal interactions. We have looked at the interactions involved in the early initiation and development of murine salivary glands using classic recombination experiments and knockout mice. We show that salivary gland epithelium, at thickening and initial bud stages, is able to direct salivary gland development in non-gland pharyngeal arch mesenchyme at early stages. The early salivary gland epithelium is therefore able to induce gland development in non-gland tissue. This ability later shifts to the mesenchyme, with non-gland epithelium, such as from the limb bud, able to form a branching gland when combined with pseudoglandular stage gland mesenchyme. This shift appears to involve Fgf signalling, with signals from the epithelium inducing Fgf10 in the mesenchyme. Fgf10 then signals back to the epithelium to direct gland down-growth and bud development. These experiments highlight the importance of epithelial–mesenchymal signalling in gland initiation, controlling where, when and how many salivary glands form.