bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating Contributions of Nitrate and Herbicides From Groundwater to Headwater Streams, Northern Atlantic Coastal Plain, United States1
Authors: Ator Scott W. , Denver Judith M.
Published: September 2012

Abstract:  Groundwater transport often complicates understanding of surface‐water contamination. We estimated the regional flux of nitrate and selected herbicides from groundwater to nontidal headwater streams of the Atlantic Coastal Plain (New Jersey through North Carolina) based on late‐winter or spring base‐flow samples from 174 streams. Sampled streams were selected randomly, and flux estimates are based on resulting population estimates rather than on empirical models, which have been used previously for similar estimates. Base‐flow flux in the estimated 8,834 headwater streams of the study area are an estimated 21,200 kg/day of nitrate (as N) and 5.83, 0.565, and 20.7 kg/day of alachlor, atrazine, and metolachlor (and selected degradates), respectively. Base‐flow flux of alachlor and metolachlor is <3% of the total base‐flow flux of those compounds plus degradates. Base‐flow flux of nitrate and herbicides as a percentage of applications is typically highest in well‐drained areas and lowest in areas with abundant poor drainage and anoxic conditions. In Coastal Plain watersheds of Albemarle and Pamlico Sounds, <2% of applied nitrogen reaches headwater streams as base flow. On the Delmarva Peninsula part of the Chesapeake Bay watershed, however, more than 10% of such applications are transported through groundwater to streams, and base‐flow nitrate flux represents 70% of total nitrogen flux in headwater streams.
Inhibition of ocular neovascularization by a novel peptide derived from human placenta growth factor‐1
Authors: Zheng Ying , Gu Qing , Xu Xun
Published: September 2012

Purpose:  To evaluate the effect of ZY1, a novel 21‐amino acid peptide from human placenta growth factor‐1 (PlGF‐1), against ocular neovascularization, and to study its possible toxicity to the retina and the underlying mechanism of antiangiogenic effect.

Methods:  MTS assays, a modified Boyden chamber and Matrigel™ were used to evaluate the effect of ZY1 on the proliferation, migration and tube formation of RF/6A rhesus macaque choroid‐retina endothelial cells induced by vascular endothelial growth factor (VEGF) in vitro. The antiangiogenic effect of ZY1 was also studied with corneal micropocket angiogenesis assays and oxygen‐induced retinopathy (OIR) assays in mice. Electrophysiological tests and histological examinations were used to study the possible toxicity of ZY1 against mouse neuroretina. Competitive ELISA and Western blotting were performed to elucidate the underlying mechanism of ZY1.

Results:  ZY1 inhibited VEGF‐induced RF/6A proliferation, migration and tube formation. It also inhibited ocular neovascularization when applied to the corneal micropocket angiogenesis assays and OIR assays in mice. Electrophysiological tests and histological examinations revealed no evident functional or morphologic abnormalities in mouse neuroretina after ZY1 injection. ZY1 competed for binding to VEGFR‐1 against PlGF and VEGF and inhibited VEGFR‐1/ERK/AKT activation.

Conclusion:  It is concluded that the novel peptide ZY1 is an effective inhibitor of ocular pathologic angiogenesis and may provide a promising alternative for ocular antiangiogenic therapy.
Nutritional management contributes to improvement in minimal hepatic encephalopathy and quality of life in patients with liver cirrhosis: A preliminary, prospective, open‐label study
Authors: Kato Akinobu , Tanaka Hiroto , Kawaguchi Takumi , Kanazawa Hidenori , Iwasa Motoh , Sakaida Isao , Moriwaki Hisataka , Murawaki Yoshikazu , Suzuki Kazuyuki , Okita Kiwamu
Published: September 2012

Aim

Problems in patients with minimal hepatic encephalopathy (MHE) include episodes such as falls and deficient driving skills, without any recognition of neurophysiological dysfunction. Patients with MHE are also more likely to develop overt hepatic encephalopathy. However, there is not yet any interventional strategy for MHE involving nutritional management. We conducted a preliminary study to investigate the proportion of positive MHE and the effects of nutritional management on MHE.

Methods

Patients with viral liver cirrhosis and abnormal neuropsychological tests were included. Nutritional consultations were conducted periodically by a dietitian, who recommended 30–35 kcal with 1.0–1.5 g of protein/kg of ideal bodyweight/day. The primary end‐point was to evaluate the proportion of patients who recovered from MHE. The secondary end‐point was to evaluate the improvement in the patients' quality of life (QOL).

Results

Thirty‐two (30.1%) of 106 patients were diagnosed with MHE. Nineteen patients were enrolled in the study. Eleven of 19 patients became non‐MHE after 4 weeks, and 13 of 19 patients (68.4%, P < 0.001) after 8 weeks. The mental summary scores were significantly improved at 8 weeks (P = 0.0413). Changes in albumin levels from week 0 to week 8 were 0.15 ± 0.16 g/dL in the improved MHE group and −0.28 ± 0.33 g/dL in the non‐improved MHE group, which differ significantly (P = 0.0130).

Conclusion

Periodical nutritional management improved MHE and QOL. Improving the patient's nutritional condition may be one approach to treating MHE.
Diuretics aggravate zinc deficiency in patients with liver cirrhosis by increasing zinc excretion in urine
Authors: Chiba Miho , Katayama Kazuhiro , Takeda Risato , Morita Rie , Iwahashi Kiyoshi , Onishi Yoshiki , Kita Hisaaki , Nishio Akira , Kanno Tomoyo , Saito Tamiko , Maeda Kosaku , Naito Masafumi , Michida Tomoki , Ito Toshifumi
Published: September 2012

Aim

Liver cirrhosis is often accompanied by zinc deficiency. The exact mechanisms underlying zinc deficiency remain unclear. This study was undertaken to clarify the influence of diuretics on blood zinc levels and zinc excretion in urine in liver cirrhosis.

Methods

Seventy‐nine outpatients with liver cirrhosis were divided into four groups: (i) patients receiving no zinc preparations or diuretics (LC group); (ii) those receiving zinc preparations only (LCZ group); (iii) those receiving diuretics only (LCD group); and (iv) those receiving both zinc preparations and diuretics (LCDZ group). Among these groups, the effects of the administrated drugs on blood zinc levels and urinary zinc excretion were analyzed.

Results

Blood zinc levels were significantly lower in the LCD group (47.8 ± 10.5 μg/dL) than in the other groups (LC: 68.8 ± 17.1 μg/dL, P = 0.0056, post‐hoc test; LCZ: 78.4 ± 18.1, P < 0.0001; LCDZ: 70.3 ± 21.4, P = 0.0008). The creatinine‐adjusted urinary zinc excretion was significantly higher in the LCDZ group (548.1 ± 407.6 μg/mg creatinine) than in the other groups (LC, 58.5 ± 43.7; LCZ, 208.1 ± 227.8; LCD, 105.2 ± 154.4; each P < 0.0001). The fraction of urinary zinc excretion was also significantly higher in the LCDZ group (5.6 ± 2.9%) than in the other groups (LC, 0.6 ± 0.5; LCD, 1.7 ± 1.5; LCZ, 1.6 ± 1.2; each P < 0.0001).

Conclusion

In patients with liver cirrhosis, treatment with diuretics can increase zinc excretion by suppressing the reabsorption of zinc through renal tubules, which might lead to zinc deficiency.
Survival of horses following strangulating large colon volvulus
Authors: SUTHERS J. M. , PINCHBECK G. L. , PROUDMAN C. J. , ARCHER D. C.
Published: September 2012

Reasons for performing study: The pattern of long‐term survival and specific factors associated with long‐term survival have not previously been evaluated in horses with a strangulating large colon volvulus (LCV).

Objectives: To provide data on the long‐term survival of horses with LCV and to identify pre‐, intra‐ and post operative variables associated with survival.

Methods: Clinical data and long‐term follow‐up information were obtained from 116 horses with a strangulating LCV (≥360°) undergoing general anaesthesia. Two multivariable Cox proportional hazards models for post operative survival time were developed: Model 1 included all horses and evaluated preoperative variables and Model 2 included horses that survived anaesthesia and evaluated pre‐, intra‐ and post operative variables.

Results: The study population comprised 116 horses. Eighty‐nine (76.7%) survived general anaesthesia. Of these, the percentage that survived until discharge, to one year and to 2 years was 70.7%, 48.3% and 33.7%, respectively. Median survival time for horses that survived general anaesthesia was 365 days. In Model 1 increased preoperative packed cell volume (PCV) was significantly associated with reduced post operative survival (hazard ratio [HR] 1.08, 95% confidence interval [CI] 1.05–1.11). However, this effect changed over time. In Model 2 abnormal serosal colour intraoperatively (HR 3.61, 95% CI 1.55–8.44), increased heart rate at 48 h post surgery (HR 1.04, 95% CI 1.02–1.06), and colic during post operative hospitalisation (HR 2.63, 95% CI 1.00–6.95), were all significantly associated with reduced post operative survival.

Conclusions: Survival time in horses with a LCV was associated with preoperative PCV, serosal colour, heart rate at 48 h post operatively and colic during post operative hospitalisation.

Potential relevance: This study provides evidence‐based information on the long‐term survival of horses with LCV and identifies parameters that may assist decision‐making by clinicians and owners.
Fine‐scale spatiotemporal patterns of genetic variation reflect budding dispersal coupled with strong natal philopatry in a cooperatively breeding mammal
Authors: Nichols Hazel J. , Jordan Neil R. , Jamie Gabriel A. , Cant Michael A. , Hoffman Joseph I.
Published: September 2012

The relatedness structure of animal populations is thought to be a critically important factor underlying the evolution of mating systems and social behaviours. While previous work has shown that population structure is shaped by many biological processes, few studies have investigated how these factors vary over time. Consequently, we explored the fine‐scale spatiotemporal genetic structure of an intensively studied population of cooperatively breeding banded mongooses (Mungos mungo) over a 10‐year period. Overall population structure was strong (average FST = 0.129) but groups with spatially overlapping territories were not more genetically similar to one another than noncontiguous groups. Instead, genetic differentiation was associated with historical group‐fission (budding) events, with new groups diverging from their parent groups over time. Within groups, relatedness was high within but not between the sexes, although the latter increased over time since group formation due to group founders being replaced by philopatric young. This trend was not mirrored by a decrease in average offspring heterozygosity over time, suggesting that close inbreeding may often be avoided, even when immigration into established groups is virtually absent and opportunities for extra‐group matings are rare. Fine‐scale spatiotemporal population structure could have important implications in social species, where relatedness between interacting individuals is a vital component in the evolution of patterns of inbreeding avoidance, reproductive skew and kin‐selected helping and harming.
Mutations in the essential FAS II β‐hydroxyacyl ACP dehydratase complex confer resistance to thiacetazone in Mycobacterium tuberculosis and Mycobacterium kansasii
Authors: Belardinelli Juan M. , Morbidoni Héctor R.
Published: September 2012

It has recently been shown that the anti‐mycobacterial pro‐drug thiacetazone (TAC) inhibits the conversion of double bonds of mycolic acid precursors into cyclopropyl rings in Mycobacterium bovis var BCG, M. marimum and M. chelonae by affecting the cyclopropyl mycolic acid synthases (CMASs) as judged by the build‐up of unsaturated mycolate precursors. In our hands, TAC inhibits mycolic acid biosynthesis in Mycobacterium tuberculosis and M. kansasii with almost negligible accumulation of those precursors. Our observations that ‘de novo’ biosynthesis of all the mycolic acid families decreased upon TAC treatment prompted us to analyse the role of each one of the Type II Fatty Acid Synthase (FASII) enzymes. Overexpression of the hadABC operon, encoding the essential FASII dehydratase complex, but not of any of the remaining FASII genes acting on the elongation of fatty acyl chains leading to the synthesis of meromycolic acids, resulted in high level of resistance to TAC in M. tuberculosis. Spontaneous M. tuberculosis and M. kansasii TAC‐resistant mutants isolated during this work revealed mutations in the hadABC genes strongly supporting our proposal that these enzymes are new players in the resistance to this anti‐mycobacterial compound.
Unravelling mitochondrial retrograde regulation in the abiotic stress induction of rice ALTERNATIVE OXIDASE 1 genes
Authors: LI CHUN‐RONG , LIANG DAN‐DAN , LI JUAN , DUAN YONG‐BO , LI HAO , YANG YA‐CHUN , QIN RUI‐YING , LI LI , WEI PENG‐CHENG , YANG JIAN‐BO
Published: September 2012

Mitochondrial retrograde regulation (MRR) is the transduction of mitochondrial signals to mediate nuclear gene expression. It is not clear whether MRR is a common regulation mechanism in plant abiotic stress response. In this study, we analysed the early abiotic stress response of the rice OsAOX1 genes, and the induction of OsAOX1a and OsAOX1b (OsAOX1a/b) was selected as a working model for the stress‐induced MRR studies. We found that the induction mediated by the superoxide ion (O2·‐)‐generating chemical methyl viologen was stronger than that of hydrogen peroxide (H2O2). The addition of reactive oxygen species (ROS) scavengers demonstrated that the stress induction was reduced by eliminating O2·‐. Furthermore, the stress induction did not rely on chloroplast‐ or cytosol‐derived O2·‐. Next, we generated transgenic plants overexpressing the superoxide dismutase (SOD) gene at different subcellular locations. The results suggest that only the mitochondrial SOD, OsMSD, attenuated the stress induction of OsAOX1a/b specifically. Therefore, our findings demonstrate that abiotic stress initiates the MRR on OsAOX1a/b and that mitochondrial O2·– is involved in the process.
Hemodialysis Adequacy and the Hospitalized End‐Stage Renal Disease Patient—Raising Awareness
Authors: Kanagasundaram Nigel Suren
Published: September 2012

Assessment of hemodialysis adequacy may require different approaches for the stable, outpatient with end‐stage renal disease (ESRD) and for the sick, inpatient with acute kidney injury (AKI). Variability of urea distribution volume, urea generation, and treatment schedule, for instance, complicates dialysis dosing in the latter group although progress has been made in our understanding of their needs. There is a third population, however, for whom hemodialysis dosing requirements remain unclear—the hospitalized ESRD patient. This commentary discusses the key urea kinetic differences between stable ESRD and AKI to give the context to where, on the intervening spectrum, the hospitalized ESRD patient might lie. The limited literature examining hemodialysis dosing in this population is discussed along with those outstanding questions that might form the basis of a future research agenda.
Specifying and Sustaining Pigmentation Patterns in Domestic and Wild Cats
Authors: Kaelin Christopher B. , Xu Xiao , Hong Lewis Z. , David Victor A. , McGowan Kelly A. , Schmidt-Küntzel Anne , Roelke Melody E. , Pino Javier , Pontius Joan , Cooper Gregory M. , Manuel Hermogenes , Swanson William F. , Marker Laurie , Harper Cindy K. , van Dyk Ann , Yue Bisong , Mullikin James C. , Warren Wesley C. , Eizirik Eduardo , Kos Lidia , O’Brien Stephen J. , Barsh Gregory S. , Menotti-Raymond Marilyn
Published: September 2012

What Kitty Shares with Kings

Although long-studied, the underlying basis of mammalian coat patterns remains unclear. By studying a large number of cat species and varieties,

Kaelin
et al.

(p.
1536
) identified two genes,
Taqpep
and
Edn3
, as critical factors in the development of feline pigment patterns. Mutations in
Taqpep
are responsible for the blotched tabby pattern in domestic cats and the unusual coat of wild king cheetahs. Gene expression patterns in cat and cheetah skin suggest that
Edn3
is a likely regulator of felid hair color. The findings support a common model for coat and pigment pattern formation in domestic and wild cats.
Double Burden of Noncommunicable and Infectious Diseases in Developing Countries
Authors: Bygbjerg I. C.
Published: September 2012

On top of the unfinished agenda of infectious diseases in low- and middle-income countries, development, industrialization, urbanization, investment, and aging are drivers of an epidemic of noncommunicable diseases (NCDs). Malnutrition and infection in early life increase the risk of chronic NCDs in later life, and in adult life, combinations of major NCDs and infections, such as diabetes and tuberculosis, can interact adversely. Because intervention against either health problem will affect the other, intervening jointly against noncommunicable and infectious diseases, rather than competing for limited funds, is an important policy consideration requiring new thinking and approaches.
Pulsating Tubules from Noncovalent Macrocycles
Authors: Huang Zhegang , Kang Seong-Kyun , Banno Motonori , Yamaguchi Tomoko , Lee Dongseon , Seok Chaok , Yashima Eiji , Lee Myongsoo
Published: September 2012

Slip-Sliding Apart

One versatile means of synthesizing nanometer-scale cylinders has been to start with ring-shaped molecules that stack on top of each other.

Huang
et al.

(p.
1521
; see the Perspective by

Zhang and Aida

) took this approach a step further by giving the rings a flexible diameter. Specifically, rings were prepared consisting of six v-shaped building blocks with hydrophobic sides that could slide back and forth along one another and thereby expand or contract the pore at the center. The rings spontaneously stacked to form tubes in dilute aqueous solution, and heating induced contraction of the whole tube in a process that was readily reversible on cooling.
Emerging Anatomy of the BAP1 Tumor Suppressor System
Authors: White Anne E. , Harper J. Wade
Published: September 2012

Analysis of the tumor suppressor BAP1 reveals how its associated transcriptional complex may suppress tumors of different lineages.
Versatility from Protein Disorder
Authors: Babu M. Madan , Kriwacki Richard W. , Pappu Rohit V.
Published: September 2012

Synergy between disordered regions and structured domains increases the functional versatility of proteins and their interaction networks.
Ignition Facility Misses Goal, Ponders New Course
Authors: Clery Daniel
Published: September 2012

The National Ignition Facility looks certain to miss its deadline at the end of this month for achieving ignition, a self-sustaining fusion reaction that yields more energy than was put in to make it happen.
Comparison of Immune Responses to the O-Specific Polysaccharide and Lipopolysaccharide of Vibrio cholerae O1 in Bangladeshi Adult Patients with Cholera
Authors: Johnson Russell A. , Uddin Taher , Aktar Amena , Mohasin M. , Alam Mohammad Murshid , Chowdhury Fahima , Harris Jason B. , LaRocque Regina C. , Kelly Bufano Meagan , Yu Yanan , Wu-Freeman Ying , Leung Daniel T. , Sarracino David , Krastins Bryan , Charles Richelle C. , Xu Peng , Kováč Pavol , Calderwood Stephen B. , Qadri Firdausi , Ryan Edward T.
Published: September 2012

Immunity againstVibrio choleraeO1 is serogroup specific, and serogrouping is defined by the O-specific polysaccharide (OSP) part of lipopolysaccharide (LPS). Despite this, human immune responses toV. choleraeOSP have not previously been characterized. We assessed immune responses againstV. choleraeOSP in adults with cholera caused byV. choleraeO1 El Tor serotype Inaba or Ogawa in Dhaka, Bangladesh, using O1 OSP-core–bovine serum albumin (OSPc:BSA) conjugates; responses targeted OSP in these conjugates. Responses of Inaba-infected patients to Inaba OSP and LPS increased significantly in IgG, IgM, and IgA isotypes from the acute to convalescent phases of illness, and the responses correlated well between OSP and LPS (R= 0.86, 0.73, and 0.91, respectively;P< 0.01). Plasma IgG, IgM, and IgA responses to Ogawa OSP and LPS in Ogawa-infected patients also correlated well with each other (R= 0.60, 0.60, and 0.92, respectively;P< 0.01). Plasma IgM responses to Inaba OSP and Ogawa OSP correlated with the respective serogroup-specific vibriocidal antibodies (R= 0.80 and 0.66, respectively;P< 0.001). Addition of either OSPc:BSA or LPS, but not BSA, to vibriocidal assays inhibited vibriocidal responses in a comparable and concentration-dependent manner. Mucosal IgA immune responses to OSP and LPS were also similar. Our study is the first to characterize anti-OSP immune responses in patients with cholera and suggests that responses targetingV. choleraeLPS, including vibriocidal responses that correlate with protection against cholera, predominantly target OSP. Induction of anti-OSP responses may be associated with protection against cholera, and our results may support the development of a vaccine targetingV. choleraeOSP.
Evidence Supporting a Zoonotic Origin of Human Coronavirus Strain NL63
Authors: Huynh Jeremy , Li Shimena , Yount Boyd , Smith Alexander , Sturges Leslie , Olsen John C. , Nagel Juliet , Johnson Joshua B. , Agnihothram Sudhakar , Gates J. Edward , Frieman Matthew B. , Baric Ralph S. , Donaldson Eric F.
Published: September 2012

The relationship between bats and coronaviruses (CoVs) has received considerable attention since the severe acute respiratory syndrome (SARS)-like CoV was identified in the Chinese horseshoe bat (Rhinolophidae) in 2005. Since then, several bats throughout the world have been shown to shed CoV sequences, and presumably CoVs, in the feces; however, no bat CoVs have been isolated from nature. Moreover, there are very few bat cell lines or reagents available for investigating CoV replication in bat cells or for isolating bat CoVs adapted to specific bat species. Here, we show by molecular clock analysis that alphacoronavirus (α-CoV) sequences derived from the North American tricolored bat (
Perimyotis subflavus
) are predicted to share common ancestry with human CoV (HCoV)-NL63, with the most recent common ancestor between these viruses occurring approximately 563 to 822 years ago. Further, we developed immortalized bat cell lines from the lungs of this bat species to determine if these cells were capable of supporting infection with HCoVs. While SARS-CoV, mouse-adapted SARS-CoV (MA15), and chimeric SARS-CoVs bearing the spike genes of early human strains replicated inefficiently, HCoV-NL63 replicated for multiple passages in the immortalized lung cells from this bat species. These observations support the hypothesis that human CoVs are capable of establishing zoonotic-reverse zoonotic transmission cycles that may allow some CoVs to readily circulate and exchange genetic material between strains found in bats and other mammals, including humans.
Hepatitis C Virus Infection Suppresses GLUT2 Gene Expression via Downregulation of Hepatocyte Nuclear Factor 1α
Authors: Matsui Chieko , Shoji Ikuo , Kaneda Shusaku , Sianipar Imelda Rosalyn , Deng Lin , Hotta Hak
Published: September 2012

Hepatitis C virus (HCV) infection causes not only intrahepatic diseases but also extrahepatic manifestations, including type 2 diabetes. We previously reported that HCV replication suppresses cellular glucose uptake by downregulation of cell surface expression of glucose transporter 2 (GLUT2) (D. Kasai et al., J. Hepatol. 50:883–894, 2009). GLUT2 mRNA levels were decreased in both HCV RNA replicon cells and HCV J6/JFH1-infected cells. To elucidate molecular mechanisms of HCV-induced suppression of GLUT2 gene expression, we analyzed transcriptional regulation of the GLUT2 promoter using a series of GLUT2 promoter-luciferase reporter plasmids. HCV-induced suppression of GLUT2 promoter activity was abrogated when the hepatocyte nuclear factor 1α (HNF-1α)-binding motif was deleted from the GLUT2 promoter. HNF-1α mRNA levels were significantly reduced in HCV J6/JFH1-infected cells. Furthermore, HCV infection remarkably decreased HNF-1α protein levels. We assessed the effects of proteasome inhibitor or lysosomal protease inhibitors on the HCV-induced reduction of HNF-1α protein levels. Treatment of HCV-infected cells with a lysosomal protease inhibitor, but not with a proteasome inhibitor, restored HNF-1α protein levels, suggesting that HCV infection promotes lysosomal degradation of HNF-1α protein. Overexpression of NS5A protein enhanced lysosomal degradation of HNF-1α protein and suppressed GLUT2 promoter activity. Immunoprecipitation analyses revealed that the region from amino acids 1 to 126 of the NS5A domain I physically interacts with HNF-1α protein. Taken together, our results suggest that HCV infection suppresses GLUT2 gene expression via downregulation of HNF-1α expression at transcriptional and posttranslational levels. HCV-induced downregulation of HNF-1α expression may play a crucial role in glucose metabolic disorders caused by HCV.
Complete Genome Sequence of the Enterobacter cancerogenus Bacteriophage Enc34
Authors: Kazaks Andris , Dislers Andris , Lipowsky Gerd , Nikolajeva Vizma , Tars Kaspars
Published: September 2012

Enterobacter cancerogenus
is widely distributed in nature and is generally recovered from environmental or vegetal sources. In some cases, it has also been associated with human infections. In this study, the complete genomic sequence of virulent
E. cancerogenus
bacteriophage Enc34 was determined. The Enc34 genome is 60,364 bp in length and contains 80 open reading frames. To our knowledge, this is the first report of a bacteriophage infecting
E. cancerogenus
.
Overexpression of the Ubiquitin-Specific Protease 7 Resulting from Transfection or Mutations in the ICP0 Binding Site Accelerates Rather than Depresses Herpes Simplex Virus 1 Gene Expression
Authors: Kalamvoki Maria , Gu Haidong , Roizman Bernard
Published: September 2012

Earlier studies reported that ICP0, a key regulatory protein encoded by herpes simplex virus 1 (HSV-1), binds ubiquitin-specific protease 7 (USP7). The fundamental conclusion of these studies is that depletion of USP7 destabilized ICP0, that ICP0 mediated the degradation of USP7, and that amino acid substitutions in ICP0 that abolished binding to USP7 significantly impaired the ability of HSV-1 to replicate. We show here that, indeed, depletion of USP7 leads to reduction of ICP0 and that USP7 is degraded in an ICP0-dependent manner. However, overexpression of USP7 or substitution in ICP0 of a single amino acid to abolish binding to USP7 accelerated the accumulation of viral mRNAs and proteins at early times after infection and had no deleterious effect on virus yields. A clue as to why USP7 is degraded emerged from the observation that, notwithstanding the accelerated expression of viral genes, the plaques formed by the mutant virus were very small, implying a defect in virus transmission from cell to cell.
Complete Genome Sequence of Canine Papillomavirus Type 10
Authors: Luff Jennifer , Moore Peter , Zhou Dan , Wang Jingang , Usuda Yukari , Affolter Verena , Schlegel Richard , Yuan Hang
Published: September 2012

Papillomaviruses are epitheliotropic, nonenveloped, circular, double-stranded DNA viruses within the family
Papillomaviridae
that are associated with benign and malignant tumors in humans and animals. We report the complete genome sequence of canine papillomavirus type 10 identified from a pigmented plaque located on the head of a mixed-breed bloodhound.
Double-barrel extracranial–intracranial bypass surgery followed by endovascular carotid artery occlusion in a patient with an extracranial giant internal carotid artery aneurysm due to Ehlers–Danlos syndrome
Authors: Perrin Jason Michael , Turowski Bernd , Steiger Hans-Jakob , Hänggi Daniel
Published: September 2012

Objective

In this case report we describe a successful interdisciplinary approach (including flow redirection and endovascular occlusion) applied to a patient with a continuously growing extracranial giant aneurysm of the right internal carotid artery (ICA) due to known Ehlers–Danlos syndrome.

Case presentation

A 42-year-old man with a continuously growing extracranial giant aneurysm of the right ICA sought treatment after failed surgery of a similar lesion of the left ICA. A multidisciplinary consultation was held at the end of 2008.

Treatment strategy

The treatment strategy consisted of flow redirection in order to secure sufficient cerebral perfusion prior to surgical trapping of the carotid aneurysm. Flow redirection was achieved by placement of a double-barrel extracranial–intracranial bypass. Subsequent surgical trapping failed due to the extreme size of the aneurysm, making certain identification of surrounding structures impossible. The aneurysm was then successfully occluded by neuroradiological intervention. In a further procedure, a large intra-aneurysmal hematoma was surgically removed to reduce the remaining bulging aneurysm sac.

Conclusions

This case report describes a successful interdisciplinary approach for the treatment of a rare giant extracranial ICA aneurysm in a patient with Ehlers–Danlos syndrome. Treatment options for this type are few and carry high risks. Flow redirection via extracranial–intracranial bypass followed by endovascular occlusion appears to be a good treatment approach.
ON THE MOTION OF A TEST PARTICLE AROUND A GLOBAL MONOPOLE IN A MODIFIED GRAVITY
Authors: CARAMÊS T. R. P. , BEZERRA DE MELLO E. R. , GUIMARÃES M. E. X.
Published: September 2012

In this paper we suggest an approach to analyze the motion of a test particle in the spacetime of a global monopole within a f(R)-like modified gravity. The field equations are written in a simplified form in terms of [Formula: see text]. Since we are dealing with a spherically symmetric metric, we express F(R) as a function of the radial coordinate only, e.g., [Formula: see text]. So, the choice of a specific form for f(R) will be equivalent to adopt an Ansatz for [Formula: see text] . By choosing an explicit functional form for [Formula: see text], we obtain the weak field solutions for the metric tensor also compute the time-like geodesics and analyze the motion of a massive test particle. An interesting feature is an emerging attractive force exerted by the monopole on the particle.
The Juvenile Hormone Signaling Pathway in Insect Development
Authors: Jindra Marek , Palli Subba R. , Riddiford Lynn M.
Published: September 2012

The molecular action of juvenile hormone (JH), a regulator of vital importance to insects, was until recently regarded as a mystery. The past few years have seen an explosion of studies of JH signaling, sparked by a finding that a JH-resistance gene, Methoprene-tolerant (Met), plays a critical role in insect metamorphosis. Here, we summarize the recently acquired knowledge on the capacity of Met to bind JH, which has been mapped to a particular ligand-binding domain, thus establishing this bHLH-PAS protein as a novel type of an intracellular hormone receptor. Next, we consider the significance of JH-dependent interactions of Met with other transcription factors and signaling pathways. We examine the regulation and biological roles of genes acting downstream of JH and Met in insect metamorphosis. Finally, we discuss the current gaps in our understanding of JH action and outline directions for future research.
Understanding the Relationship Between Brain Gene Expression and Social Behavior: Lessons from the Honey Bee
Authors: Zayed Amro , Robinson Gene E.
Published: September 2012

Behavior is a complex phenotype that is plastic and evolutionarily labile. The advent of genomics has revolutionized the field of behavioral genetics by providing tools to quantify the dynamic nature of brain gene expression in relation to behavioral output. The honey bee Apis mellifera provides an excellent platform for investigating the relationship between brain gene expression and behavior given both the remarkable behavioral repertoire expressed by members of its intricate society and the degree to which behavior is influenced by heredity and the social environment. Here, we review a linked series of studies that assayed changes in honey bee brain transcriptomes associated with natural and experimentally induced changes in behavioral state. These experiments demonstrate that brain gene expression is closely linked with behavior, that changes in brain gene expression mediate changes in behavior, and that the association between specific genes and behavior exists over multiple timescales, from physiological to evolutionary.
Identity by Descent Between Distant Relatives: Detection and Applications
Authors: Browning Sharon R. , Browning Brian L.
Published: September 2012

Short segments of identity by descent (IBD) between individuals with no known relationship can be detected using genome-wide single nucleotide polymorphism data and recently developed statistical methodology. Emerging applications for the detected IBD segments include IBD mapping, haplotype phase inference, genotype imputation, and inference of population structure. In this review, we explain the principles behind methods for IBD segment detection, describe recently developed methods, discuss approaches to comparing methods, and give an overview of applications.
Network News: The Replication of Kinetoplast DNA
Authors: Jensen Robert E. , Englund Paul T.
Published: September 2012

One of the most fascinating and unusual features of trypanosomatids, parasites that cause disease in many tropical countries, is their mitochondrial DNA. This genome, known as kinetoplast DNA (kDNA), is organized as a single, massive DNA network formed of interlocked DNA rings. In this review, we discuss recent studies on kDNA structure and replication, emphasizing recent developments on replication enzymes, how the timing of kDNA synthesis is controlled during the cell cycle, and the machinery for segregating daughter networks after replication.
Peroxisome Assembly and Functional Diversity in Eukaryotic Microorganisms
Authors: Pieuchot Laurent , Jedd Gregory
Published: September 2012

Peroxisomes are core eukaryotic organelles that generally function in lipid metabolism and detoxification of reactive oxygen species, but they are increasingly associated with taxa-specific metabolic, cellular, and developmental functions. Here, we present a brief overview of peroxisome assembly, followed by a discussion of their functional diversification. Matrix protein import occurs through a remarkable translocon that can accommodate folded and even oligomeric proteins. Metabolically specialized peroxisomes include glycosomes of trypanosomes, which have come to compartmentalize most of the glycolytic pathway and play a role in developmental signal transduction. The differentiation of physically distinct subcompartments also contributes to peroxisome diversification; in the clade of filamentous ascomycetes, dense-core Woronin bodies bud from peroxisomes to gate cell-to-cell channels. Here, the import of oligomeric cargo is central to the mechanism of subcompartment specification. In general, the acquisition of a tripeptide peroxisome targeting signal by nonperoxisomal proteins appears to be a recurrent step in the evolution of peroxisome diversity.
Physiology and Diversity of Ammonia-Oxidizing Archaea
Authors: Stahl David A. , de la Torre José R.
Published: September 2012

The discovery of ammonia-oxidizing archaea (AOA), now generally recognized to exert primary control over ammonia oxidation in terrestrial, marine, and geothermal habitats, necessitates a reassessment of the nitrogen cycle. In particular, the unusually high affinity of marine and terrestrial AOA for ammonia indicates that this group may determine the oxidation state of nitrogen available to associated micro- and macrobiota, altering our current understanding of trophic interactions. Initial comparative genomics and physiological studies have revealed a novel, and as yet unresolved, primarily copper-based pathway for ammonia oxidation and respiration distinct from that of known ammonia-oxidizing bacteria and possibly relevant to the production of atmospherically active nitrogen oxides. Comparative studies also provide compelling evidence that the lineage of Archaea with which the AOA affiliate is sufficiently divergent to justify the creation of a novel phylum, the Thaumarchaeota.
Bringing the Laboratory and Clinic to the Community: Mobile Technologies for Health Promotion and Disease Prevention
Authors: Kaplan Robert M. , Stone Arthur A.
Published: September 2012

Health-related information collected in psychological laboratories may not be representative of people's everyday health. For at least 70 years, there has been a call for methods that sample experiences from everyday environments and circumstances. New technologies, including cell phones, sensors, and monitors, now make it possible to collect information outside of the laboratory in environments representative of everyday life. We review the role of mobile technologies in the assessment of health-related behaviors, physiological responses, and self-reports. Ecological momentary assessment offers a wide range of new opportunities for ambulatory assessment and evaluation. The value of mobile technologies for interventions to improve health is less well established. Among 21 randomized clinical trials evaluating interventions that used mobile technologies, more than half failed to document significant improvements on health outcomes or health risk factors. Theoretical and practical issues for future research are discussed.
Chronic hypoxia and VEGF differentially modulate abundance and organization of myosin heavy chain isoforms in fetal and adult ovine arteries
Authors: Hubbell Margaret C. , Semotiuk Andrew J. , Thorpe Richard B. , Adeoye Olayemi O. , Butler Stacy M. , Williams James M. , Khorram Omid , Pearce William J.
Published: September 2012

Chronic hypoxia increases vascular endothelial growth factor (VEGF) and thereby promotes angiogenesis. The present study explores the hypothesis that hypoxic increases in VEGF also remodel artery wall structure and contractility through phenotypic transformation of smooth muscle. Pregnant and nonpregnant ewes were maintained at sea level (normoxia) or 3,820 m (hypoxia) for the final 110 days of gestation. Common carotid arteries harvested from term fetal lambs and nonpregnant adults were denuded of endothelium and studied in vitro. Stretch-dependent contractile stresses were 32 and 77% of normoxic values in hypoxic fetal and adult arteries. Hypoxic hypocontractility was coupled with increased abundance of nonmuscle myosin heavy chain (NM-MHC) in fetal (+37%) and adult (+119%) arteries. Conversely, hypoxia decreased smooth muscle MHC (SM-MHC) abundance by 40% in fetal arteries but increased it 123% in adult arteries. Hypoxia decreased colocalization of NM-MHC with smooth muscle α-actin (SM-αA) in fetal arteries and decreased colocalization of SM-MHC with SM-αA in adult arteries. Organ culture with physiological concentrations (3 ng/ml) of VEGF-A165 similarly depressed stretch-dependent stresses to 37 and 49% of control fetal and adult values. The VEGF receptor antagonist vatalanib ablated VEGF's effects in adult but not fetal arteries, suggesting age-dependent VEGF receptor signaling. VEGF replicated hypoxic decreases in colocalization of NM-MHC with SM-αA in fetal arteries and decreases in colocalization of SM-MHC with SM-αA in adult arteries. These results suggest that hypoxic increases in VEGF not only promote angiogenesis but may also help mediate hypoxic arterial remodeling through age-dependent changes in smooth muscle phenotype and contractility.
Elevated steady-state bladder preload activates myosin phosphorylation: detrusor smooth muscle is a preload tension sensor
Authors: Southern Jordan B. , Frazier Jasmine R. , Miner Amy S. , Speich John E. , Klausner Adam P. , Ratz Paul H.
Published: September 2012

In rabbit bladder wall (detrusor) muscle, the degree of tone induced during physiological filling (filling tone) is the sum of adjustable preload tension and autonomous contractile tension. The present study was designed to determine whether the level of filling tone is dependent on detrusor muscle length. Maximum active tension induced by KCl was parabolic in relation to length [tension increased from 70% to 100% of a reference length ( Lref) and decreased at longer muscle lengths]. Filling tone, however, increased in a linear fashion from 70% to 120% Lref. In the presence of ibuprofen to abolish autonomous contraction and retain adjustable preload tension, tension was reduced in strength but remained linearly dependent on length from 70% to 120% Lref. In the absence of autonomous contraction, stretching detrusor muscle from 80% to 120% Lref still caused an increase in tone during PGE2-induced rhythmic contraction, suggesting that muscle stretch caused increases in detrusor muscle contractile sensitivity rather than in prostaglandin release. In the absence of autonomous contraction, the degree of adjustable preload tension and myosin phosphorylation increased when detrusor was stretched from 80% to 120% Lref, but also displayed length-hysteresis, indicating that detrusor muscle senses preload rather than muscle length. Together, these data support the hypothesis that detrusor muscle acts as a preload tension sensor. Because detrusor muscle is in-series with neuronal mechanosensors responsible for urinary urgency, a more thorough understanding of detrusor muscle filling tone may reveal unique targets for therapeutic intervention of contractile disorders such as overactive bladder.
Increased production of superoxide anion contributes to dysfunction of the arteriovenous fistula
Authors: Tsapenko Mykola V. , d'Uscio Livius V. , Grande Joseph P. , Croatt Anthony J. , Hernandez Melissa C. , Ackerman Allan W. , Katusic Zvonimir S. , Nath Karl A.
Published: September 2012

Vascular access dysfunction causes morbidity in hemodialysis patients. This study examined the generation and pathobiological significance of superoxide anion in a rat femoral arteriovenous fistula (AVF). One week after AVF creation, there was increased production of superoxide anion accompanied by decreased total superoxide dismutase (SOD) and Cu/Zn SOD activities and induction of the redox-sensitive gene heme oxygenase-1. Immunohistochemical studies of nitrotyrosine formation demonstrated that peroxynitrite, a product of superoxide anion and nitric oxide, was present in increased amounts in endothelial and smooth muscle cells in the AVF. Because uncoupled NOS isoforms generate superoxide anion, and NOS coupling requires tetrahydrobiopterin (BH4) as a cofactor, we assessed NOS uncoupling by determining the ratio of BH4 to dihydrobiopterin (BH2); the BH4-to-BH2 ratio was markedly attenuated in the AVF. Because Src is a vasculopathic signaling species upstream and downstream of superoxide anion, such expression was evaluated; expression of Src and phosphorylated Src was both markedly increased in the AVF. Expression of NADPH oxidase (NOX) 1, NOX2, NOX4, cyclooxygenase (COX) 1, COX2, p47phox, and p67phox was all unchanged, as assessed by Western analyses, thereby suggesting that these proteins may not be involved in increased production of superoxide anion. Finally, administration of tempol, a superoxide anion scavenger, decreased neointima formation in the juxta-anastomotic venous segment and improved AVF blood flow. We conclude that the AVF exhibits increased superoxide anion generation that may reflect the combined effects of decreased scavenging by SOD and increased generation by uncoupled NOS, and that enhanced superoxide anion production promotes juxta-anastomotic stenosis and impairs AVF function.
Bicarbonate promotes BK-α/β4-mediated K excretion in the renal distal nephron
Authors: Cornelius Ryan J. , Wen Donghai , Hatcher Lori I. , Sansom Steven C.
Published: September 2012

Ca-activated K channels (BK), which are stimulated by high distal nephron flow, are utilized during high-K conditions to remove excess K. Because BK predominantly reside with BK-β4 in acid/base-transporting intercalated cells (IC), we determined whether BK-β4 knockout mice (β4KO) exhibit deficient K excretion when consuming a high-K alkaline diet (HK-alk) vs. high-K chloride diet (HK-Cl). When wild type (WT) were placed on HK-alk, but not HK-Cl, renal BK-β4 expression increased (Western blot). When WT and β4KO were placed on HK-Cl, plasma K concentration ([K]) was elevated compared with control K diets; however, K excretion was not different between WT and β4KO. When HK-alk was consumed, the plasma [K] was lower and K clearance was greater in WT compared with β4KO. The urine was alkaline in mice on HK-alk; however, urinary pH was not different between WT and β4KO. Immunohistochemical analysis of pendrin and V-ATPase revealed the same increases in β-IC, comparing WT and β4KO on HK-alk. We found an amiloride-sensitive reduction in Na excretion in β4KO, compared with WT, on HK-alk, indicating enhanced Na reabsorption as a compensatory mechanism to secrete K. Treating mice with an alkaline, Na-deficient, high-K diet (LNaHK) to minimize Na reabsorption exaggerated the defective K handling of β4KO. When WT on LNaHK were given NH4Cl in the drinking water, K excretion was reduced to the magnitude of β4KO on LNaHK. These results show that WT, but not β4KO, efficiently excretes K on HK-alk but not on HK-Cl and suggest that BK-α/β4-mediated K secretion is promoted by bicarbonaturia.
Synchronous and asynchronous electrically evoked motor activities during wind-up stimulation are differentially modulated following an acute spinal transection
Authors: Frigon Alain , Hurteau Marie-France , Johnson Michael D. , Heckman C. J. , Telonio Alessandro , Thibaudier Yann
Published: September 2012

In this study, we used a novel technique to study reflex wind-up when the spinal cord is intact and following an acute spinal transection. Specifically, we evaluated reflex responses evoked by a series of 10 electrical pulses to the tibial or superficial peroneal nerves in 9 decerebrate adult cats, before and after an acute spinal transection. Electromyograms were recorded in four hindlimb muscles (lateral gastrocnemius, tibialis anterior, semitendinosus, and sartorius) to evaluate reflex amplitude, duration, and the temporal summation of reflex responses, so-called wind-up. We identified two distinct reflex responses evoked by electrical stimulation of the tibial or superficial peroneal nerves on the basis of their pattern of change following acute spinal transection, a short-latency (∼10 ms) compound action potential (CAP) that was followed by a burst of sustained activity (SA). Wind-up of CAP and SA amplitudes was clearly present when the spinal cord was intact but was drastically reduced after acute spinalization in some muscles. Moreover, CAP and SA reflex responses were differentially modified by the acute spinalization. When the effects of acute spinal transection were significant, CAP responses were increased after acute spinalization, whereas SA responses were reduced, suggesting that the two signals are regulated by different neuronal mechanisms. The present results provide the first assessment of reflex wind-up before and after an acute spinal transection in the same animals and indicate that different reflex components must be considered separately when evaluating changes in neuronal excitability following SCI.