Rejuvenation of meiotic cohesion in oocytes during prophase I is required for chiasma maintenance and accurate chromosome segregation.
Chromosome segregation errors in human oocytes are the leading cause of birth defects, and the risk of aneuploid pregnancy increases dramatically as women age. Accurate segregation demands that sister chromatid cohesion remain intact for decades in human oocytes, and gradual loss of the original cohesive linkages established in fetal oocytes is proposed to be a major cause of age-dependent segregation errors. Here we demonstrate that maintenance of meiotic cohesion in Drosophila oocytes during prophase I requires an active rejuvenation program, and provide mechanistic insight into the molecular events that underlie rejuvenation. Gal4/UAS inducible knockdown of the cohesion establishment factor Eco after meiotic S phase, but before oocyte maturation, causes premature loss of meiotic cohesion, resulting in destabilization of chiasmata and subsequent missegregation of recombinant homologs. Reduction of individual cohesin subunits or the cohesin loader Nipped B during prophase I leads to similar defects. These data indicate that loading of newly synthesized replacement cohesin rings by Nipped B and establishment of new cohesive linkages by the acetyltransferase Eco must occur during prophase I to maintain cohesion in oocytes. Moreover, we show that rejuvenation of meiotic cohesion does not depend on the programmed induction of meiotic double strand breaks that occurs during early prophase I, and is therefore mechanistically distinct from the DNA damage cohesion re-establishment pathway identified in G2 vegetative yeast cells. Our work provides the first evidence that new cohesive linkages are established in Drosophila oocytes after meiotic S phase, and that these are required for accurate chromosome segregation. If such a pathway also operates in human oocytes, meiotic cohesion defects may become pronounced in a woman's thirties, not because the original cohesive linkages finally give out, but because the rejuvenation program can no longer supply new cohesive linkages at the same rate at which they are lost.


Flux Connections Between Gluconate Pathway, Glycolysis, and Pentose-Phosphate Pathway During Carbohydrate Metabolism in Bacillus megaterium QM B1551.
Bacillus megaterium is a bacterium of great importance as a plant-beneficial bacterium in agricultural applications and in industrial bioproduction of proteins. Understanding intracellular processing of carbohydrates in this species is crucial to predicting natural carbon utilization as well as informing strategies in metabolic engineering. Here, we applied stable isotope-assisted metabolomics profiling and metabolic flux analysis to elucidate, at high resolution, the connections of the different catabolic routes for carbohydrate metabolism immediately following substrate uptake in B. megaterium QM B1551. We performed multiple 13C tracer experiments to obtain both kinetic and long-term 13C profiling of intracellular metabolites. In addition to the direct phosphorylation of glucose to glucose-6-phosphate (G6P) prior to oxidation to 6-phosphogluconate (6P-gluconate), the labeling data also captured glucose catabolism through the gluconate pathway involving glucose oxidation to gluconate followed by phosphorylation to 6P-gluconate. Our data further confirmed the absence of the Entner-Doudoroff pathway in B. megaterium and showed that subsequent catabolism of 6P-gluconate was instead through the oxidative pentose-phosphate (PP) pathway. Quantitative flux analysis of glucose-grown cells showed equal partition of consumed glucose from G6P to the Embden-Meyerhof-Parnas (EMP) pathway and from G6P to the PP pathway through 6P-gluconate. Growth on fructose alone or xylose alone was consistent with the ability of B. megaterium to use each substrate as a sole source of carbon. However, a detailed 13C mapping during simultaneous feeding of B. megaterium on glucose, fructose, and xylose indicated non-uniform intracellular investment of the different carbohydrate substrates. Flux of glucose-derived carbons dominated the gluconate pathway and the PP pathway, whereas carbon flux from both glucose and fructose populated the EMP pathway; there was no assimilatory flux of xylose-derived carbons. Collectively, our findings provide new quantitative insights on the contribution of the different catabolic routes involved in initiating carbohydrate catabolism in B. megaterium and related Bacillus species.


Adaptive radiation, correlated and contingent evolution, and net species diversification in Bromeliaceae.
We present an integrative model predicting associations among epiphytism, the tank habit, entangling seeds, C₃ vs. CAM photosynthesis, avian pollinators, life in fertile, moist montane habitats, and net rates of species diversification in the monocot family Bromeliaceae. We test these predictions by relating evolutionary shifts in form, physiology, and ecology to time and ancestral distributions, quantifying patterns of correlated and contingent evolution among pairs of traits and analyzing the apparent impact of individual traits on rates of net species diversification and geographic expansion beyond the ancestral Guayana Shield. All predicted patterns of correlated evolution were significant, and the temporal and spatial associations of phenotypic shifts with orogenies generally accorded with predictions. Net rates of species diversification were most closely coupled to life in fertile, moist, geographically extensive cordilleras, with additional significant ties to epiphytism, avian pollination, and the tank habit. The highest rates of net diversification were seen in the bromelioid tank-epiphytic clade (D(crown) = 1.05 My⁻¹), associated primarily with the Serra do Mar and nearby ranges of coastal Brazil, and in the core tillandsioids (D(crown) = 0.67 My⁻¹), associated primarily with the Andes and Central America. Six large-scale adaptive radiations and accompanying pulses of speciation account for 86% of total species richness in the family. This study is among the first to test a priori hypotheses about the relationships among phylogeny, phenotypic evolution, geographic spread, and net species diversification, and to argue for causality to flow from functional diversity to spatial expansion to species diversity.


Computed relationships between the inherent and apparent optical properties of a flat homogeneous ocean.
Monte Carlo simulations of the transfer of radiation in the ocean are used to compute the apparent optical properties of a flat homogeneous ocean as a function of the inherent optical properties. The data are used to find general relationships between the inherent and apparent optical properties for optical depths tau </= 4. The results indicate that the apparent optical properties depend on the phase function only through the back scattering probability. It is shown that these relations can be used with measurements of the upwelling and downwelling irradiance, the beam attenuation coefficient, and the incident radiance distribution to determine the absorption coefficient, the scattering coefficient, and the backward and forward scattering probabilities.


New CT-based diagnoses of torso cancer is low in the emergency department setting.
The incidence of new CT-based torso cancer diagnoses and the most commonly diagnosed cancer types in the emergency department (ED) setting are unknown. The purpose of our study was to determine the incidence and types of new CT-based torso cancer diagnoses in the ED. A total of 19,496 CT reports including all or parts of the torso from 2017 were searched for the keywords: "mass", "tumor", "neoplasm", "malignancy", or "cancer". Each report and corresponding medical record was evaluated for presence of a new cancer. Cases were scored as no cancer, subcentimeter lung nodule, known cancer, new cancer, or suspicious, but unconfirmed for new cancer. Each mass was characterized as symptom-related or incidental. At least one keyword was found in 2086 reports. Of these 706, 126 and 905 were known cancer cases, subcentimeter lung nodules, and non-cancerous cases, respectively. There were 251 confirmed new cancers and 98 suspicious cases which lacked adequate diagnostic workup. Depending on whether only definite or definite and suspicious cases were included together, the number of new cancer cases per 100 torso CT exams was 1.3 or 1.8, respectively. Gastrointestinal, lung, pancreaticobiliary, urinary, and gynecologic cancers were most common. Only 58 of the confirmed cases (23%) were deemed as incidental findings. CT-diagnosis of new torso cancers was uncommon in our setting. Still, while extensive knowledge of cancer staging may not be necessary for ED radiologists, knowledge of the most common types of cancer including gastrointestinal, lung, pancreaticobiliary, urinary, and gynecologic cancers may improve sensitivity for these diagnoses and may expedite appropriate referrals for the newly diagnosed patients.


Age- and ability-related differences in young readers' use of conjunctions.
Two studies investigating young readers' use of conjunctions are reported. In Study One, 145 eight- to ten-year-olds completed one of two narrative cloze tasks in which different types of conjunction were deleted. Performance for additive conjunctions was not affected by age in this study, but older children were more likely to select the target conjunction than were younger children for temporal, causal, and adversative terms. Performance was superior in the cloze task in which they were given a restricted choice of responses (three vs. seven). In Study Two, 35 eight- and nine-year-old good and poor comprehenders completed the three-choice cloze task. The poor comprehenders were less likely to select the target terms in general. Sentence-level comprehension skills did not account for their poor performance. The results indicate that understanding of the semantic relations expressed by conjunctions is still developing long after these terms are used correctly in children's speech. The findings are discussed in relation to the role of conjunctions in text comprehension.


Recovery from COVID-19 in a B-cell-depleted multiple sclerosis patient.
Approximately 200,000 multiple sclerosis (MS) patients worldwide receive B-cell-depleting immunotherapy with rituximab (anti-CD20), which eliminates the ability to generate an antibody response to new infections. As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies might help viral clearance, these patients could be at risk of severe complications if infected. Here, we report on an MS patient who had received rituximab for ~3 years. The patient was examined 5 days before the onset of coronavirus disease 2019 (COVID-19) symptoms and was admitted to the hospital 2 days after. She recovered 14 days after symptom onset despite having a 0% B lymphocyte count and not developing SARS-CoV-2 immunoglobulin G (IgG) antibodies.


[Effect of culture supernatant of Toxoplasma gondii on the proliferation and apoptosis of BGC-823 cells].
To investigate the effect of culture supernatant of Toxoplasma gondii on the proliferation and Toxoplasma gondii tachyzoites with seed counts of 2 x 10(7)/ml, apoptosis of human gastric cancer BGC-823 cells. 4 x 10(7)/ml, and 8 x 10(7)/ml harvested from infected mice were cultured for 24 h, and then the culture supernatant was collected. BGC-823 cells (5 x 10(4)/ml) at mid-exponential phase were incubated with different concentrations of culture supernatants of Toxoplasma gondii tachyzoites. While in control group, the same volume of DMEM was given. At 24, 48 and 72 h after incubation, the measurement of tumor cell growth inhibition rate was performed by using CCK-8 kit. Cell apoptosis was observed under a fluorescence microscope after 24 h incubation. The DNA ladder zone of apoptosis cells was analyzed with the method of agarose gel electrophoresis. Flow cytometric analysis was used to analyze cell cycle for cell proliferation index and the expression of p53 and Bcl-2. The culture supernatant of Toxoplasma tachyzoites inhibited the proliferation of BGC-823 cells and the growth inhibition rates increased with the time and the concentration. The highest rate reached at the 72nd hour when the concentration of Toxoplasma tachyzoites was 8 x 10(7)/ml. Apoptotic bodies were found in experimental group. The amount of apoptotic body was positively associated with the tachyzoite concentration. DNA fragment in the treated cells after 24 h incubation was revealed by agarose electrophoresis. When the proportion of BGC-823 cells in G0/G1 phase increased, the proportion of cells in S phase decreased. Cell proliferation index decreased with the increase of the concentration of tachyzoites. The proliferation index (0.36) of the cells cultured with culture supernatant of 8 x 10(7)/ml tachyzoites was significantly lower than that of control group (0.6, P < 0.05). p53 protein expression was higher in experiment group than that of the control, whereas Bcl-2 protein expression in experiment group was lower than that of the control (P < 0.05). The culture supernatant of Toxoplasma gondii can inhibit the proliferation of BGC-823 cells and cause apoptosis of BGC-823 cells, which may be related with up-regulating p53 expression and down-regulating Bcl-2 expression.


Effects of Bay k 8644 and nifedipine on isolated dog cerebral, coronary and mesenteric arteries.
Vasoconstrictor effects of Bay k 8644, a dihydropyridine Ca++ agonist, and vasorelaxant effects of nifedipine were investigated in helical strips of dog cerebral (basilar, posterior cerebral and middle cerebral) and peripheral (coronary and mesenteric) arteries. The addition of Bay k 8644 produced a dose-dependent contraction in the absence of any contractile agent in the basilar artery with a pD2 value of 8.53. Similar sensitivity to Bay k 8644 was observed in the posterior cerebral, middle cerebral or coronary artery. Bay k 8644 was much less effective in producing a contraction in the mesenteric artery. An elevation of the concentration of extracellular K+ eliminated the difference between the responses to Bay k 8644 in the basilar and mesenteric artery. Contractile responses of the basilar artery to Bay k 8644 were antagonized competitively by nifedipine (pA2 = 8.17), but non-competitively by diltiazem. The pA2 values for nifedipine antagonism of Bay k 8644 responses with the elevated K+ were the same between the basilar and mesenteric arteries. Increased sensitivity to exogenously added K+ also was observed in cerebral and coronary arteries when compared with the mesenteric artery. The addition of nifedipine to an unstimulated strip produced a dose-dependent relaxation in cerebral and coronary arteries, but not in the mesenteric artery. When the cerebral and peripheral arteries were contracted with K+ to the same magnitude, nifedipine produced similar relaxations among these arteries. Nifedipine was less efficacious in antagonizing the contractile response to Bay k 8644 compared with the contractile response to K+ in cerebral arteries. These results suggest that 1) the voltage-dependent Ca++ channels in the cerebral and coronary arteries are in different states of activation from those in the mesenteric artery, 2) Bay k 8644 contracts the cerebral and coronary arteries by acting primarily on the same site, presumably dihydropyridine receptors of the voltage-dependent Ca++ channels at which nifedipine acts, 3) the dihydropyridine receptors were the same between the basilar and mesenteric arteries and 4) there may be a difference in the state of the Ca++ channel in the arteries between the stimulation with Bay k 8644 and K+-depolarization.


A situational picture of HIV/AIDS and injection drug use in Vinnitsya, Ukraine.
New and explosive HIV epidemics are being witnessed in certain countries of Eastern Europe, including Ukraine, as well as a rapid and dramatic increase in the supply, use, and negative public health consequences of illicit drugs. A majority of registered HIV cases in Ukraine occur among injection drug users (IDUs), large numbers of whom report HIV risk behaviors such as needle sharing. The purpose of this study was to apply the World Health Organization's Rapid Assessment and Response on Injection Drug Use (IDU-RAR) guide to create a situational picture in the Vinnitsya Oblast, Ukraine, a region with very scarce information about the HIV/AIDS and injection drug use (IDU) epidemics. The IDU-RAR uses a combination of qualitative data collection techniques commonly employed in social science and evaluation research to quickly depict the extent and nature of the given health problem and propose locally relevant recommendations for improvement. The investigators focused their assessment on the contextual factors, drug use, and intervention and policy components of the IDU-RAR. A combination of network and block sampling techniques was used. Data collection methods included direct observation, review of existing data, structured and unstructured interviews, and focus group discussions. Key informants and locations were visited until no new information was being generated. The number of registered HIV cases in Vinnitsya has increased from 3 (1987-1995) to 860 (1999-10/2004), 57 of whom have already died. Ten percent of annual admissions to the area's Regional Narcological Dispensary were for opiate disorders, and the number of registered IDUs rose by 20% from 1999 to 2000. The level of HIV/AIDS awareness is generally poor among the general population but high among high-risk populations. Both HIV/AIDS and injection drug use carry a strong stigma in the community, even among medical professionals. There was very little evidence of primary HIV/AIDS prevention efforts, and IDU prevention efforts focused on promotion of anti-drug messages in the schools. Given that Ukraine has sparse resources to be devoted to this problem, action recommendations should be prioritized, realistic, and initially targeted to persons in greatest need. The following action recommendations are prioritized by the following categories: First priority: Voluntary Counseling and Testing; Second Priority: Prevention and Education; and Third Priority: Harm Reduction and Treatment. They are provided in this sequence based on what response can realistically be implemented first with limited additional resources and can make the greatest immediate impact. The persons at greatest risk, HIV positive persons and IDUs, should be attended to first.


Cloned fusion product from a rare t(15;19)(q13.2;p13.1) inhibit S phase in vitro.
Somatically acquired chromosomal translocation is a common mechanism of oncogene activation in many haematopoietic tumours and sarcomas. However, very few recurrent chromosomal translocations have been reported in more common epithelial tumours such as lung carcinomas. We established a cell line HCC2429 from an aggressive, metastatic lung cancer arising in a young, non-smoking woman, demonstrating a t(15;19)(q13.2;p13.1). The breakpoints on chromosomes 15 and 19 were cloned using long distance inverse PCR and we determined by RT-PCR that the translocation results in a novel fusion transcript in which the 3' end Brd4 on chromosome 19p is fused to the 5' end of NUT on chromosome 15q. In total, 128 lung cancer tissues were screened using fluorescent in situ hybridisation, but none of the tumours screened demonstrated t(15;19), suggesting that this translocation is not commonly found in lung cancer. Consistent with previous literature, ectopic expression of wild type Brd4 was shown to inhibit G(1) to S progression. However, we also found that the Brd4-NUT fusion augments the inhibition of progression to S phase compared with wild type Brd4. Alteration in cell cycle kinetics is important in tumorigenesis, although the exact role of Brd4-NUT fusion protein in the pathogenesis of lung cancers remains unclear and need to be further elucidated.


Amyloid fibril protein nomenclature: 2012 recommendations from the Nomenclature Committee of the International Society of Amyloidosis.
The Nomenclature Committee of the International Society of Amyloidosis (ISA) met during the XIIIth International Symposium, May 6-10, 2012, Groningen, The Netherlands, to formulate recommendations on amyloid fibril protein nomenclature and to consider newly identified candidate amyloid fibril proteins for inclusion in the ISA Amyloid Fibril Protein Nomenclature List. The need to promote utilization of consistent and up to date terminology for both fibril chemistry and clinical classification of the resultant disease syndrome was emphasized. Amyloid fibril nomenclature is based on the chemical identity of the amyloid fibril forming protein; clinical classification of the amyloidosis should be as well. Although the importance of fibril chemistry to the disease process has been recognized for more than 40 years, to this day the literature contains clinical and histochemical designations that were used when the chemical diversity of amyloid diseases was poorly understood. Thus, the continued use of disease classifications such as familial amyloid neuropathy and familial amyloid cardiomyopathy generates confusion. An amyloid fibril protein is defined as follows: the protein must occur in body tissue deposits and exhibit both affinity for Congo red and green birefringence when Congo red stained deposits are viewed by polarization microscopy. Furthermore, the chemical identity of the protein must have been unambiguously characterized by protein sequence analysis when so is practically possible. Thus, in nearly all cases, it is insufficient to demonstrate mutation in the gene of a candidate amyloid protein; the protein itself must be identified as an amyloid fibril protein. Current ISA Amyloid Fibril Protein Nomenclature Lists of 30 human and 10 animal fibril proteins are provided together with a list of inclusion bodies that, although intracellular, exhibit some or all of the properties of the mainly extracellular amyloid fibrils.


Striding out with Parkinson disease: evidence-based physical therapy for gait disorders.
Although Parkinson disease (PD) is common throughout the world, the evidence for physical therapy interventions that enable long-term improvement in walking is still emerging. This article critiques the major physical therapy approaches related to gait rehabilitation in people with PD: compensatory strategies, motor skill learning, management of secondary sequelae, and education to optimize physical activity and reduce falls. The emphasis of this review is on gait specifically, although balance and falls are of direct importance to gait and are addressed in that context. Although the researchers who have provided the evidence for these approaches grounded their studies on different theoretical paradigms, each approach is argued to have a valid place in the comprehensive management of PD generally and of gait in particular. The optimal mix of interventions for each individual varies according to the stage of disease progression and the patient's preferred form of exercise, capacity for learning, and age.


Expression and cellular localization of vascular endothelial growth factor A and its receptors in acute and chronic leukemias: an immunohistochemical study.
We aimed to study the expression of phosphorylated vascular endothelial growth factor receptor 2 (pVEGFR-2), a membrane-bound tyrosine kinase receptor to vascular endothelial growth factor, in 76 cases of leukemia and nonneoplastic myeloproliferative disease and in 8 reactive bone marrows. The microvessel density (MVD) and the expression of both pVEGFR-2 and its ligand, VEGFA, were evaluated in these cases. We used archival cases and immunohistochemistry with a monoclonal antibody generated by us to the autophosphorylation sites in the cytoplasmic tail of VEGFR-2 and von Willebrand factor antibody to evaluate MVD. Our results demonstrate increased expression of this phosphorylated receptor in the neoplastic cells in acute myeloid and lymphoblastic leukemias. This correlated with increased MVD and VEGFA expression by the neoplastic cells. Interestingly, there was nuclear relocation of this receptor in these diseases. This raises the possibility that pVEGFR-2 may be involved in the transcriptional regulation of these leukemias. Small molecule inhibitors to this receptor may therefore be a useful adjunct in the therapy for these diseases.


Details of electro-optic terahertz detection with a chirped probe pulse.
By revisiting the theory of terahertz pulse detection schemes employing a chirped optical probe pulse, we address and resolve a conflict that exists in literature. In this report, we show that the equation governing the detected field depends upon the experimental scheme, and in the limit of small bandwidth, that this expression differs from the conventionally used equation through a phase factor. We experimentally verify this equation using a spectral in-line interferometry approach. We also briefly discuss the implications of our new equations for single-shot terahertz retrieval schemes.


FOCS: a novel method for analyzing enhancer and gene activity patterns infers an extensive enhancer-promoter map.
Recent sequencing technologies enable joint quantification of promoters and their enhancer regions, allowing inference of enhancer-promoter links. We show that current enhancer-promoter inference methods produce a high rate of false positive links. We introduce FOCS, a new inference method, and by benchmarking against ChIA-PET, HiChIP, and eQTL data show that it results in lower false discovery rates and at the same time higher inference power. By applying FOCS to 2630 samples taken from ENCODE, Roadmap Epigenomics, FANTOM5, and a new compendium of GRO-seq samples, we provide extensive enhancer-promotor maps ( http://acgt.cs.tau.ac.il/focs ). We illustrate the usability of our maps for deriving biological hypotheses.


RNA Structure-A Neglected Puppet Master for the Evolution of Virus and Host Immunity.
The central dogma of molecular biology describes the flow of genetic information from DNA to protein via an RNA intermediate. For many years, RNA has been considered simply as a messenger relaying information between DNA and proteins. Recent advances in next generation sequencing technology, bioinformatics, and non-coding RNA biology have highlighted the many important roles of RNA in virtually every biological process. Our understanding of RNA biology has been further enriched by a number of significant advances in probing RNA structures. It is now appreciated that many cellular and viral biological processes are highly dependent on specific RNA structures and/or sequences, and such reliance will undoubtedly impact on the evolution of both hosts and viruses. As a contribution to this special issue on host immunity and virus evolution, it is timely to consider how RNA sequences and structures could directly influence the co-evolution between hosts and viruses. In this manuscript, we begin by stating some of the basic principles of RNA structures, followed by describing some of the critical RNA structures in both viruses and hosts. More importantly, we highlight a number of available new tools to predict and to evaluate novel RNA structures, pointing out some of the limitations readers should be aware of in their own analyses.


Safety and efficacy of the early introduction of everolimus with reduced-exposure cyclosporine a in de novo kidney recipients.
Everolimus and cyclosporine A (CsA) exhibit synergistic immunosuppressive activity when used in combination. We examined the safety and efficacy of the use of everolimus with a cyclosporine-sparing strategy in de novo renal transplant recipients. A comparative, parallel, randomized, open-label 1-year study has been performed in 148 patients from five transplant centers to compare the efficacy and tolerability of everolimus and reduced exposure CsA (the investigational group) or enteric-coated mycophenolate sodium and standard-exposure CsA (the control group) in combination with basiliximab and steroids. The eligible subjects were randomly assigned at 1 month after transplantation. Efficacy failure (biopsy-proven acute rejection, death, graft loss, or loss to follow-up), safety, and renal function were evaluated. One graft loss has been reported in the control group and no patient death were reported in either group. The incidence of biopsy-proven acute rejection until 12 months after transplantation of the investigational group was 7.5%, compared to 11.1% of the control group (P=0.565). The mean estimated glomerular filtration rates of the investigational group at 12 months after transplantation was significantly higher (68.1 ± 16.8 ml/min/1.73 m(2)) than that of the control group (60.6 ± 15.8 ml/min/1.73 m(2); P=0.016). There was no significant difference (P>0.05) in the incidence of discontinuations and serious adverse events between the groups. The results of this study provide the evidences that (1) the calcineurin inhibitor (CNI) minimization by the introduction of everolimus after 1-month posttransplantation keeps the incidences of acute rejection and additional risks as low as the conventional immunosuppression; (2) it allows minimizing CNI exposure, consequently reducing CNI nephrotoxicity and preserving renal function.


Frataxin acts as an iron chaperone protein to modulate mitochondrial aconitase activity.
Numerous degenerative disorders are associated with elevated levels of prooxidants and declines in mitochondrial aconitase activity. Deficiency in the mitochondrial iron-binding protein frataxin results in diminished activity of various mitochondrial iron-sulfur proteins including aconitase. We found that aconitase can undergo reversible citrate-dependent modulation in activity in response to pro-oxidants. Frataxin interacted with aconitase in a citrate-dependent fashion, reduced the level of oxidant-induced inactivation, and converted inactive [3Fe-4S]1+ enzyme to the active [4Fe-4S]2+ form of the protein. Thus, frataxin is an iron chaperone protein that protects the aconitase [4Fe-4S]2+ cluster from disassembly and promotes enzyme reactivation.


Effect of grape seed extract ointment on cesarean section wound healing: A double-blind, randomized, controlled clinical trial.
and purpose: Complications of the delayed recovery of cesarean section (CS) wound can include stress, discomfort, and dissatisfaction of the mother in the postpartum period. This study tried to determine the effect of grape seed extract ointment on CS wound healing. This is a double-blind, randomized, controlled clinical trial incorporating 129 women eligible for CS in eastern Iran. Participants were selected through convenience sampling method and were subsequently randomly assigned into three groups: 2.5% grape seed extract ointment, 5% grape seed extract ointment, and petrolatum. CS wound healing indices were assessed before the intervention, and 6 and 14 days after the intervention using the REEDA scale (redness, edema, ecchymosis, discharge, and approximation). The mean scores on days 6 and 14 after intervention were respectively 2.02 ± 0.52 and 0.98 ± 0.61 in the 5% ointment group, 2.83 ± 0.54 and 1.58 ± 0.67 in the 2.5% ointment group, and 2.91 ± 0.51 and 1.55 ± 0.74 in the petrolatum group. While the mean score in the 5% ointment group was significantly different from those of 2.5% ointment and petrolatum groups (P < 0.001), the mean score in the 2.5% ointment group was not significantly different from that of the petrolatum group on days 6 and 14 after intervention (P = 0.38 and P = 0.79, respectively). The current results suggest that 5% grape seed extract may have beneficial therapeutic effects in promoting CS wound healing.


"Tap and twist": preventing deep vein thrombosis in neuroscience patients through foot and ankle range-of-motion exercises.
Neurosurgical patients tend to have the highest rate of deep vein thrombosis (DVT) rate among other postsurgical patients. The methods and timing of DVT prevention and treatment continue to be debated among neurointensivists. The greatest opportunity to intervene is early during the stay in the intensive care unit. There are many factors, however, that can make this the most neglected time for aggressive prevention measures. For large university teaching hospitals, the target of the University Health System Consortium is to achieve an average DVT rate at or below half that of previous reported rates. The current recommendations are effective only if there is compliance with these measures during the majority of the patients' hospitalization. Our hypothesis states that without changing any of the current measures to prevent DVT, a structured program of foot and ankle range-of-motion (ROM) exercises will decrease the incidence of DVT in the neuroscience intensive care patient population. This quasi-experimental study was a quality improvement project examining 315 individuals over the age of 18 years, who were admitted to the neurospine intensive care unit and who received a new program of foot exercises as a method of DVT prevention. Data for the outcome measures were derived from bedside measurement of lower extremity doppler, the percentage of time the exercises were performed, patient history, and standard DVT prevention measures. Overall, there was no difference in DVT rates for those receiving the foot ROM intervention during the study period in 2008-2009 compared with the usual nursing practice for the previous year. However, during the study period, those who developed DVT had a significantly lower compliance rate with the ROM exercises (38.7%) than did those who did not develop DVT (58.4%; p < .001). Therefore, foot and ankle ROM exercises may have a promising role in reducing the incidence of DVT in neuroscience intensive care patients when there is diligent performance of the exercises.


[Public Health Genomics. The integration of genome-based knowledge into public health research, policies and health services].
Which consequences can be drawn from genome-based knowledge and how can it be responsibly and timely translated into policies and practice? What are recent developments in genetics and molecular biology, what are the challenges, what are the risks of these developments? Which policies can provide an acceptable balance between providing strong protection of individuals'interests and needs while enabling society to benefit from the genomic advances and empowering individuals? How can molecular medicine contribute to more effective and efficient health care services, and what infrastructures and policies can already now be implemented to assure a benefit for population health? Thus, Public Health Genomics (PHG) tries to answer these challenging questions. This integration of genomics into the aims of public health is called Public Health Genomics (PHG) and is defined as "the responsible and effective translation of genome-based knowledge and technologies into public policy and health services for the benefit of population health".


Two-dimensional Raman mole-fraction and temperature measurements for hydrogen-nitrogen mixture analysis.
A two-dimensional laser Raman technique was developed and applied to directly probe the population number of selected rotational and vibrational energy levels of hydrogen and nitrogen. Using three cameras simultaneously, temperature and mole fraction images could be detected. Three different combinations of rotational and vibrational Raman signals of hydrogen and nitrogen were analyzed to identify the combination that is most suitable for future mixture analysis in hydrogen internal combustion engines. Here the experiments were conducted in an injection chamber where hot hydrogen was injected into room temperature nitrogen at 1.1 MPa.


Diagnosing duplications--can it be done?
New genes arise through duplication and modification of DNA sequences on a range of scales: single gene duplication, duplication of large chromosomal fragments and whole-genome duplication. Each duplication mechanism has specific characteristics that influence the fate of the resulting duplicates, such as the size of the duplicated fragment, the potential for dosage imbalance, the preservation or disruption of regulatory control and genomic context. The ability to diagnose or identify the mechanism that produced a pair of paralogs has the potential to increase our ability to reconstruct evolutionary history, to understand the processes that govern genome evolution and to make functional predictions based on paralogy. The recent availability of large amounts of whole-genome sequence, often from several closely related species, has stimulated a wealth of new computational methods to diagnose gene duplications.


A Radical Clock Probe Uncouples H Atom Abstraction from Thioether Cross-Link Formation by the Radical S-Adenosyl-l-methionine Enzyme SkfB.
Sporulation killing factor (SKF) is a ribosomally synthesized and post-translationally modified peptide (RiPP) produced by Bacillus. SKF contains a thioether cross-link between the α-carbon at position 40 and the thiol of Cys32, introduced by a member of the radical S-adenosyl-l-methionine (SAM) superfamily, SkfB. Radical SAM enzymes employ a 4Fe-4S cluster to bind and reductively cleave SAM to generate a 5'-deoxyadenosyl radical. SkfB utilizes this radical intermediate to abstract the α-H atom at Met40 to initiate cross-linking. In addition to the cluster that binds SAM, SkfB also has an auxiliary cluster, the function of which is not known. We demonstrate that a substrate analogue with a cyclopropylglycine (CPG) moiety replacing the wild-type Met40 side chain forgoes thioether cross-linking for an alternative radical ring opening of the CPG side chain. The ring opening reaction also takes place with a catalytically inactive SkfB variant in which the auxiliary Fe-S cluster is absent. Therefore, the CPG-containing peptide uncouples H atom abstraction from thioether bond formation, limiting the role of the auxiliary cluster to promoting thioether cross-link formation. CPG proves to be a valuable tool for uncoupling H atom abstraction from peptide modification in RiPP maturases and demonstrates potential to leverage RS enzyme reactivity to create noncanonical amino acids.


History of sexual trauma moderates psychotherapy outcome for posttraumatic stress disorder.
Moderators of differential psychotherapy outcome for posttraumatic stress disorder (PTSD) are rare, yet have crucial clinical importance. We tested the moderating effects of trauma type for three psychotherapies in 110 unmedicated patients with chronic DSM-IV PTSD. Patients were randomized to 14 weeks of prolonged exposure (PE, N = 38), interpersonal psychotherapy (IPT, N = 40), or relaxation therapy (RT, N = 32). The Clinician-Administered PTSD Scale (CAPS) was the primary outcome measure. Moderator candidates were trauma type: interpersonal, sexual, physical. We fit a regression model for week 14 CAPS as a function of treatment (a three-level factor), an indicator of trauma type presence/absence, and their interactions, controlling for baseline CAPS, and evaluated potential confounds. Thirty-nine (35%) patients reported sexual, 68 (62%) physical, and 102 (93%) interpersonal trauma. Baseline CAPS scores did not differ by presence/absence of trauma types. Sexual trauma as PTSD criterion A significantly moderated treatment effect: whereas all therapies had similar efficacy among nonsexually-traumatized patients, IPT had greater efficacy among sexually traumatized patients (efficacy difference with and without sexual trauma: IPT vs. PE and IPT vs. RT P's < .05), specifically in PTSD symptom clusters B and D (P's < .05). Few studies have assessed effects of varying trauma types on effects of differing psychotherapies. In this exploratory study, sexual trauma moderated PTSD outcomes of three therapies: IPT showed greater benefit for sexually traumatized patients than PE or RT. The IPT focuses on affect to help patients determine trust in their current environments may particularly benefit patients who have suffered sexual assault.


Poliovirus.
Despite marked progress in global polio eradication, the threat of polio importation into the United States remains; therefore, all children should be protected against the disease. The standard schedule for poliovirus immunization remains 4 doses of inactivated poliovirus vaccine at 2, 4, and 6 through 18 months and 4 through 6 years of age. The minimum interval between doses 1 and 2 and between doses 2 and 3 is 4 weeks, and the minimum interval between doses 3 and 4 is 6 months. The minimum age for dose 1 is 6 weeks. Minimal age and intervals should be used when there is imminent threat of exposure, such as travel to an area in which polio is endemic or epidemic. The final dose in the inactivated poliovirus vaccine series should be administered at 4 through 6 years of age, regardless of the previous number of doses administered before the fourth birthday, and at least 6 months since the last dose was received.


Quantifying stratosphere-troposphere transport of ozone using balloon-borne ozonesondes, radar windprofilers and trajectory models.
In a series of 10-day campaigns in Ontario and Quebec, Canada, between 2005 and 2007, ozonesondes were launched twice daily in conjunction with continuous high-resolution wind-profiling radar measurements. Windprofilers can measure rapid changes in the height of the tropopause, and in some cases follow stratospheric intrusions. Observed stratospheric intrusions were studied with the aid of a Lagrangian particle dispersion model and the Canadian operational weather forecast system. Definite stratosphere-troposphere transport (STT) events occurred approximately every 2-3 days during the spring and summer campaigns, whereas during autumn and winter, the frequency was reduced to every 4-5 days. Although most events reached the lower troposphere, only three events appear to have significantly contributed to ozone amounts in the surface boundary layer. Detailed calculations find that STT, while highly variable, is responsible for an average, over the seven campaigns, of 3.1% of boundary layer ozone (1.2 ppb), but 13% (5.4 ppb) in the lower troposphere and 34% (22 ppb) in the middle and upper troposphere, where these layers are defined as 0-1 km, 1-3 km, and 3-8 km respectively. Estimates based on counting laminae in ozonesonde profiles, with judicious choices of ozone and relative humidity thresholds, compare moderately well, on average, with these values. The lamina detection algorithm is then applied to a large dataset from four summer ozonesonde campaigns at 18 North American sites between 2006 and 2011. The results show some site-to-site and year-to-year variability, but stratospheric ozone contributions average 4.6% (boundary layer), 15% (lower troposphere) and 26% (middle/upper troposphere). Calculations were also performed based on the TOST global 3D trajectory-mapped ozone data product. Maps of STT in the same three layers of the troposphere suggest that the STT ozone flux is greater over the North American continent than Europe, and much greater in winter and spring than in summer or fall. When averaged over all seasons, magnitudes over North America show similar ratios between levels to the previous calculations, but are overall 3-4 times smaller. This may be because of limitations (trajectory length and vertical resolution) to the current TOST-based calculation.


Accurate predictions of water cluster formation, (H₂O)(n=2-10).
An efficient mixed molecular dynamics/quantum mechanics model has been applied to the water cluster system. The use of the MP2 method and correlation consistent basis sets, with appropriate correction for BSSE, allows for the accurate calculation of electronic and free energies for the formation of clusters of 2-10 water molecules. This approach reveals new low energy conformers for (H(2)O)(n=7,9,10). The water heptamer conformers comprise five different structural motifs ranging from a three-dimensional prism to a quasi-planar book structure. A prism-like structure is favored energetically at low temperatures, but a chair-like structure is the global Gibbs free energy minimum past 200 K. The water nonamers exhibit less complexity with all the low energy structures shaped like a prism. The decamer has 30 conformers that are within 2 kcal/mol of the Gibbs free energy minimum structure at 298 K. These structures are categorized into four conformer classes, and a pentagonal prism is the most stable structure from 0 to 320 K. Results can be used as benchmark values for empirical water models and density functionals, and the method can be applied to larger water clusters.


Consensus Bundle on Prevention of Surgical Site Infections After Major Gynecologic Surgery.
Surgical site infections are the most common complications of surgery in the United States. Of surgeries in women of reproductive age, hysterectomy is one of the most frequently performed, second only to cesarean birth. Therefore, prevention of surgical site infections in women undergoing gynecologic surgery is an ideal topic for a patient safety bundle. The primary purpose of this safety bundle is to provide recommendations that can be implemented into any surgical environment in an effort to reduce the incidence of surgical site infection. This bundle was developed by a multidisciplinary team convened by the Council on Patient Safety in Women's Health Care. The bundle is organized into four domains: Readiness, Recognition and Prevention, Response, and Reporting and Systems Learning. In addition to recommendations for practice, each of the domains stresses communication and teamwork between all members of the surgical team. Although the bundle components are designed to be adaptable to work in a variety of clinical settings, standardization within institutions is encouraged.


Sexual Behaviors and Partner Characteristics by Sexual Identity Among Adolescent Girls.
Data suggest that lesbian and bisexual adolescents engage in risky sexual behaviors at higher rates than heterosexual girls. Whether these findings also apply to girls of other sexual identities is less well understood. Potential differences in risky sexual behaviors reported by lesbian versus bisexual adolescents are also underreported in the literature. Data were collected online in 2010-2011 among 2,823 girls, aged 13-18 years, in the United States. Multinomial logistic regression was used to quantify comparisons of sexual behaviors between (1) lesbian; (2) bisexual; and (3) questioning, unsure, or other (QUO) identity; and (0) heterosexual girls. Logistic regression compared lesbian and bisexual adolescents. Lesbian and bisexual adolescents reported significantly more lifetime and past-year sexual partners than heterosexual girls. Bisexual girls were also more likely to report penile-anal and penile-vaginal sex, whereas lesbians were more likely to report earlier sexual debut for almost all types of sex, as compared to heterosexual girls. Lesbians also were more likely to report infrequent condom use and less likely to have conversations with partners about the use of barriers (e.g., dental dams) before first sex. Relative to lesbians, bisexual girls reported older age at first sex for almost all sexual behaviors and higher lifetime prevalence of recent male partners, penile-vaginal, and penile-anal sex. Few differences were noted between QUO and heterosexual girls. Sexual minority adolescents are not identical in terms of sexual risk. Providers need to be sensitive to these differences and their implications for health and counseling of patients.


Influence of Thermo-Light Curing with Dental Light-Curing Units on the Microhardness of Glass-Ionomer Cements.
The purpose of this study was to verify for various glass-ionomer cement (GIC) products whether the application of thermo-light curing on the initial curing material produces an increase in microhardness, and to determine whether this hardness varies depending on the depths of the GIC samples. The efficacy of various polymerization units on this additional hardening was also examined. The GIC samples were thermo-light cured for 60 seconds with three polymerization units. The Vickers microhardness was measured at three different depths: 2 mm, 3 mm, and 4 mm. Analysis of variance and Newman-Keuls test showed statistically significant differences among tested samples for all three GIC groups (P < .001). The results of linear regression analysis showed a statistically significant relationship between the hardness of the material and the temperature for samples with depths of 2 mm (R = 0.78; P = .0028) and 3 mm (R = 0.59; P = .045). The findings of this study indicate that thermo-light curing of GIC with different polymerization units for 60 seconds during setting reaction increases the microhardness of the GICs at all depths tested and may increase resistance to mastication forces, which can be validated in future clinical studies.


Local mobile gene pools rapidly cross species boundaries to create endemicity within global Vibrio cholerae populations.
Vibrio cholerae represents both an environmental pathogen and a widely distributed microbial species comprised of closely related strains occurring in the tropical to temperate coastal ocean across the globe (Colwell RR, Science 274:2025-2031, 1996; Griffith DC, Kelly-Hope LA, Miller MA, Am. J. Trop. Med. Hyg. 75:973-977, 2006; Reidl J, Klose KE, FEMS Microbiol. Rev. 26:125-139, 2002). However, although this implies dispersal and growth across diverse environmental conditions, how locally successful populations assemble from a possibly global gene pool, relatively unhindered by geographic boundaries, remains poorly understood. Here, we show that environmental Vibrio cholerae possesses two, largely distinct gene pools: one is vertically inherited and globally well mixed, and the other is local and rapidly transferred across species boundaries to generate an endemic population structure. While phylogeographic analysis of isolates collected from Bangladesh and the U.S. east coast suggested strong panmixis for protein-coding genes, there was geographic structure in integrons, which are the only genomic islands present in all strains of V. cholerae (Chun J, et al., Proc. Natl. Acad. Sci. U. S. A. 106:15442-15447, 2009) and are capable of acquiring and expressing mobile gene cassettes. Geographic differentiation in integrons arises from high gene turnover, with acquisition from a locally co-occurring sister species being up to twice as likely as exchange with conspecific but geographically distant V. cholerae populations. IMPORTANCE Functional predictions of integron genes show the predominance of secondary metabolism and cell surface modification, which is consistent with a role in competition and predation defense. We suggest that the integron gene pool's distinctness and tempo of sharing are adaptive in allowing rapid conversion of genomes to reflect local ecological constraints. Because the integron is frequently the main element differentiating clinical strains (Chun J, et al., Proc. Natl. Acad. Sci. U. S. A. 106:15442-15447, 2009) and its recombinogenic activity is directly stimulated by environmental stresses (Guerin E, et al., Science 324:1034, 2009), these observations are relevant for local emergence and subsequent dispersal.


Synergy of polypyrrole and carbon x-aerogel in lithium-oxygen batteries.
A crucial step in the development of lithium-oxygen (Li-O2) batteries is to design an oxygen cathode with high catalytic activity and stable porous structure. Achieving such design requires an integrated strategy in which porosity, conductivity, catalytic activity, and mechanical durability are all considered in a battery system. Here, we develop polypyrrole-coated carbon x-aerogels with macroscopic 3D architecture, and demonstrate their potential as oxygen cathodes for Li-O2 batteries. This material, a novel and mechanically strong composite aerogel with polymer-cross-linked structure, not only provides effective pores that allow to store the discharge products and open channels for better oxygen diffusion, but also forms a robust 3D catalytic network that promotes both oxygen reduction and evolution reactions with improved mechanical and electrochemical stability. This work highlights the synergy between the 3D porous, conductive carbon aerogel framework and the polypyrrole catalytic layer, which maintains stable catalytic activity without deactivation and provides a more effective gas-liquid-solid interface for rapid oxygen absorption and diffusion, thereby leading to significant improvements in the capacity, rate capability and cycle life of the cathode.


The Role of Labor Unions in Creating Working Conditions That Promote Public Health.
We sought to portray how collective bargaining contracts promote public health, beyond their known effect on individual, family, and community well-being. In November 2014, we created an abstraction tool to identify health-related elements in 16 union contracts from industries in the Pacific Northwest. After enumerating the contract-protected benefits and working conditions, we interviewed union organizers and members to learn how these promoted health. Labor union contracts create higher wage and benefit standards, working hours limits, workplace hazards protections, and other factors. Unions also promote well-being by encouraging democratic participation and a sense of community among workers. Labor union contracts are largely underutilized, but a potentially fertile ground for public health innovation. Public health practitioners and labor unions would benefit by partnering to create sophisticated contracts to address social determinants of health.


Isotope-specific and amino acid-specific heavy atom substitutions alter barrier crossing in human purine nucleoside phosphorylase.
Computational chemistry predicts that atomic motions on the femtosecond timescale are coupled to transition-state formation (barrier-crossing) in human purine nucleoside phosphorylase (PNP). The prediction is experimentally supported by slowed catalytic site chemistry in isotopically labeled PNP (13C, 15N, and 2H). However, other explanations are possible, including altered volume or bond polarization from carbon-deuterium bonds or propagation of the femtosecond bond motions into slower (nanoseconds to milliseconds) motions of the larger protein architecture to alter catalytic site chemistry. We address these possibilities by analysis of chemistry rates in isotope-specific labeled PNPs. Catalytic site chemistry was slowed for both [2H]PNP and [13C, 15N]PNP in proportion to their altered protein masses. Secondary effects emanating from carbon-deuterium bond properties can therefore be eliminated. Heavy-enzyme mass effects were probed for local or global contributions to catalytic site chemistry by generating [15N, 2H]His8-PNP. Of the eight His per subunit, three participate in contacts to the bound reactants and five are remote from the catalytic sites. [15N, 2H]His8-PNP had reduced catalytic site chemistry larger than proportional to the enzymatic mass difference. Altered barrier crossing when only His are heavy supports local catalytic site femtosecond perturbations coupled to transition-state formation. Isotope-specific and amino acid specific labels extend the use of heavy enzyme methods to distinguish global from local isotope effects.


Elevated monocyte chemotactic protein-1 in amniotic fluid is a risk factor for pregnancy loss.
Pregnancy loss after mid-trimester amniocentesis occurs in 0.5-1% of cases and is frequently attributed to the procedure. Accumulating evidence implicates a pre-existing, but clinically silent, intra-amniotic inflammation in the etiology of adverse pregnancy outcome after mid-trimester amniocentesis. Monocyte chemotactic protein-1 (MCP-1) is a potent chemokine produced by a wide variety of cells during the course of an inflammatory response. This study was designed to assess if the amniotic fluid concentration of this chemokine identifies patients at risk for spontaneous abortion and/or fetal death. A retrospective case-control study of women who had a mid-trimester amniocentesis was designed. Cases (n = 10) consisted of patients who had a spontaneous pregnancy loss after the procedure, while the control group (n = 84) consisted of patients who had a normal pregnancy outcome after mid-trimester amniocentesis. MCP-1 was measured by a specific enzyme immunoassay (sensitivity, 18.3 pg/ml). The Kolmogorov-Smirnov test was utilized to assess normal distribution of the data. Logarithmic transformation was applied to achieve normality. Statistical analysis was performed using Student's t test. A receiver operating characteristic (ROC) curve analysis was used to select a cut-off to dichotomize amniotic fluid concentrations of MCP-1. MCP-1 was detectable in all amniotic fluid samples. Patients who had a mid-trimester amniocentesis and a subsequent pregnancy loss had a higher mean amniotic fluid log MCP-1 concentration than those with a normal pregnancy outcome (pregnancy loss, mean 2.95 +/- 0.19 pg/ml vs. normal outcome, mean 2.78 +/- 0.19 pg/ml; p = 0.01). A cut-off of > 765 pg/ml was selected by ROC curve analysis (area under the curve, 0.74; p = 0.01). An amniotic fluid concentration of MCP-1 above this level was strongly associated with pregnancy loss (odds ratio, 7.35; 95% confidence interval, 1.7-31.1), a sensitivity of 70%, and a specificity of 76%. A subset of women who had a pregnancy loss after a mid-trimester amniocentesis had higher concentrations of the chemokine MCP-1 than those who had a normal pregnancy outcome. Subclinical intra-amniotic inflammation is a risk factor for pregnancy loss after mid-trimester amniocentesis. This observation may have medicolegal and clinical implications. An elevated MCP-1 concentration in amniotic fluid of patients with a pregnancy loss after a mid-trimester amniocentesis indicates that a pathological condition was present at the time of the procedure.


Erythropoietin in patients with traumatic brain injury and extracranial injury-A post hoc analysis of the erythropoietin traumatic brain injury trial.
Erythropoietin (EPO) may reduce mortality after traumatic brain injury (TBI). Secondary brain injury is exacerbated by multiple trauma, and possibly modifiable by EPO. We hypothesized that EPO decreases mortality more in TBI patients with multiple trauma, than in patients with TBI alone. A post hoc analysis of the EPO-TBI randomized controlled trial conducted in 2009 to 2014. To evaluate the impact of injuries outside the brain, we calculated an extracranial Injury Severity Score (ISS) that included the same components of the ISS, excluding head and face components. We defined multiple trauma as two injured body regions with an Abbreviated Injury Scale (AIS) score of 3 or higher. Cox regression analyses, allowing for potential differential responses per the presence or absence of extracranial injury defined by these injury scores, were used to assess the effect of EPO on time to mortality. Of 603 included patients, the median extracranial ISS was 6 (interquartile range, 1-13) and 258 (43%) had an AIS score of 3 or higher in at least two body regions. On Cox regression, EPO was associated with decreased mortality in patients with greater extracranial ISS (interaction p = 0.048) and weakly associated with differential mortality with multiple trauma (AIS score > 3 or in two regions, interaction p = 0.17). At 6 months in patients with extracranial ISS higher than 6, 10 (6.8%) of 147 EPO-treated patients compared with 26 (17%) of 154 placebo-treated patients died (risk reduction, 10%; 95% confidence interval, 2.9-17%; p = 0.007). In this post hoc analysis, EPO administration was associated with a potential differential improvement in 6-month mortality in TBI patients with more severe extracranial injury. These findings need confirmation in future clinical and experimental studies. Therapeutic study, level III.


Meat quality and health implications of organic and conventional beef production.
Recommendation to reduce fat consumption from ruminant meat does not consider the contribution of nutritionally beneficial fatty acids in lean beef. Here we report effects of production system (organic vs conventional) and finishing season on meat and fat quality of sirloin steaks from retail outlets and simulated fatty acid intakes by consumers. There was little difference in meat quality (pH, shear force and colour), but the fat profiles varied considerably between production systems and season. Meat fat from organic and summer finished cattle contained higher concentrations of conjugated linoleic acid, its precursor vaccenic acid and individual omega-3 fatty acids and had a lower ratio of omega-6 to omega-3 fatty acids compared with non-organic and winter finished cattle respectively. The fat profile from summer finished organic beef aligns better to recommended dietary guideline including those for long chain omega-3 fatty acids compared with that from winter finished, non-organic steak.


From preferred to actual mate characteristics: the case of human body shape.
The way individuals pair to produce reproductive units is a major factor determining evolution. This process is complex because it is determined not only by individual mating preferences, but also by numerous other factors such as competition between mates. Consequently, preferred and actual characteristics of mates obtained should differ, but this has rarely been addressed. We simultaneously measured mating preferences for stature, body mass, and body mass index, and recorded corresponding actual partner's characteristics for 116 human couples from France. Results show that preferred and actual partner's characteristics differ for male judges, but not for females. In addition, while the correlation between all preferred and actual partner's characteristics appeared to be weak for female judges, it was strong for males: while men prefer women slimmer than their actual partner, those who prefer the slimmest women also have partners who are slimmer than average. This study therefore suggests that the influences of preferences on pair formation can be sex-specific. It also illustrates that this process can lead to unexpected results on the real influences of mating preferences: traits considered as highly influencing attractiveness do not necessarily have a strong influence on the actual pairing, the reverse being also possible.


Development and proof of concept of a blended physiotherapeutic intervention for patients with non-specific low back pain.
To develop a blended physiotherapeutic intervention for patients with non-specific low back pain (e-Exercise LBP) and evaluate its proof of concept. Focus groups with patients, physiotherapists, and eHealth and LBP experts were conducted to investigate values according to the development of e-Exercise LBP. Proof of concept was evaluated in a multicentre study. Dutch primary care physiotherapy practices (n=21 therapists). Adults with non-specific LBP (n=41). e-Exercise LBP was developed based on clinical LBP guidelines and the focus groups, using the Center for eHealth Research Roadmap. Face-to-face physiotherapy sessions were integrated with a web application consisting of 12 information lessons, video-supported exercises and a physical activity module with the option to gradually increase individuals' level of physical activity. The intervention could be tailored to patients' risk of persistent disabling LBP, according to the STarT Back Screening Tool. Functional disability, pain, physical activity, sedentary behaviour and fear-avoidance beliefs, measured at baseline and 12 weeks. After 12 weeks, improvements were found in functional disability [Quebec Back Pain Disability Scale: mean difference (MD) -12.2/100; 95% confidence interval (CI) 8.3 to 16.1], pain (Numeric Pain Rating Scale: MD -2.8/10; 95% CI 2.1 to 3.6), subjective physical activity (Short Questionnaire to Assess Health Enhancing Physical Activity: MD 11.5minutes/day; 95% CI -47.8 to 24.8) and objective sedentary behaviour (ActiGraph: MD -23.0minutes/day; 95% CI -8.9 to 55.0). Small improvements were found in objective physical activity and fear-avoidance beliefs. The option to gradually increase physical activity was activated for six patients (15%). On average, patients received seven face-to-face sessions alongside the web application. The results of this study provide the first indication of the effectiveness of e-Exercise LBP, particularly for disability and pain among patients with LBP. Future studies will focus on end-user experiences and (cost-) effectiveness.


Extranodal nonorbital indolent lymphomas of the head and neck: relationship between tumor control and radiotherapy.
To review our experience managing extranodal nonorbital indolent lymphomas of the head and neck. A retrospective review was made of 40 patients with indolent lymphomas of the head and neck evaluated at Stanford. The tumor head-and-neck location was Waldeyer's ring, 14; salivary glands, 16; thyroid, 4; and other sites, 6. Twenty-five were Stage I-IIE. Pathology was re-reviewed in 37. The most common histologies were marginal zone lymphoma and follicular grade 2. Patients received combinations of surgery, chemotherapy, and radiotherapy. Local therapy included surgery alone in 6 patients, radiotherapy alone in 7, and surgery plus radiotherapy in 12. Median follow-up was 70.5 months. Freedom from local progression was 86%, and freedom from progression was 61% at 5 years. Patients with radiotherapy had significantly better freedom from local progression (5-year, 100% vs. 72% for patients without radiotherapy, p = 0.006) and freedom from progression (5-year, 90% vs. 34% for patients without radiotherapy, p = 0.001). Improvement in freedom from progression with radiotherapy was statistically significant for Stage I-II patients (88% vs. 50%, p = 0.02) and of borderline significance in Stage III-IV patients (100% vs. 23%, p = 0.07). Overall survival at 10 years was 70%. Multivariate analysis revealed that significant prognostic factors for survival were tumor site (favoring salivary and thyroid, p = 0.02) and age (favoring younger, p = 0.04). Survival is excellent in patients with indolent lymphomas of the head and neck. Patients with salivary and thyroid primary tumors had better survival compared with others. Early use of radiotherapy resulted in significantly higher rates of freedom from progression and freedom from local progression in early-stage patients.


Nonmuscle myosin IIA-dependent force inhibits cell spreading and drives F-actin flow.
Nonmuscle myosin IIA (NMM-IIA) is involved in the formation of focal adhesions and neurite retraction. However, the role of NMM-IIA in these functions remains largely unknown. Using RNA interference as a tool to decrease NMM-IIA expression, we have found that NMM-IIA is the major myosin involved in traction force generation and retrograde F-actin flow in mouse embryonic fibroblast cells. Quantitative analyses revealed that approximately 60% of traction force on fibronectin-coated surfaces is contributed by NMM-IIA and approximately 30% by NMM-IIB. The retrograde F-actin flow decreased dramatically in NMM-IIA-depleted cells, but seemed unaffected by NMM-IIB deletion. In addition, we found that depletion of NMM-IIA caused cells to spread at a higher rate and to a greater area on fibronectin substrates during the early spreading period, whereas deletion of NMM-IIB appeared to have no effect on spreading. The distribution of NMM-IIA was concentrated on the dorsal surface and approached the ventral surface in the periphery, whereas NMM-IIB was primarily concentrated around the nucleus and to a lesser extent at the ventral surface in cell periphery. Our results suggest that NMM-IIA is involved in generating a coherent cytoplasmic contractile force from one side of the cell to the other through the cross-linking and the contraction of dorsal actin filaments.


Divergence between the Drosophila pseudoobscura and D. persimilis genome sequences in relation to chromosomal inversions.
As whole-genome sequence assemblies accumulate, a challenge is to determine how these can be used to address fundamental evolutionary questions, such as inferring the process of speciation. Here, we use the sequence assemblies of Drosophila pseudoobscura and D. persimilis to test hypotheses regarding divergence with gene flow. We observe low differentiation between the two genome sequences in pericentromeric and peritelomeric regions. We interpret this result as primarily a remnant of the correlation between levels of variation and local recombination rate observed within populations. However, we also observe lower differentiation far from the fixed chromosomal inversions distinguishing these species and greater differentiation within and near these inversions. This finding is consistent with models suggesting that chromosomal inversions facilitate species divergence despite interspecies gene flow. We also document heterogeneity among the inverted regions in their degree of differentiation, suggesting temporal differences in the origin of each inverted region consistent with the inversions arising during a process of divergence with gene flow. While this study provides insights into the speciation process using two single-genome sequences, it was informed by lower throughput but more rigorous examinations of polymorphism and divergence. This reliance highlights the need for complementary genomic and population genetic approaches for tackling fundamental evolutionary questions such as speciation.


Plastic reproductive strategies in a clonal marine invertebrate.
Plastic reproductive allocation may allow individuals to maximize their fitness when conditions vary. Mate availability is one condition that may determine the fitness of an individual's allocation strategy. Using a variety of methods, I detected evidence of plastic allocation to asexual (clonal) reproduction in response to mate availability in the brittle star Ophiactis savignyi. There were more mature individuals in populations in which both sexes were present, and clones from these populations had fewer clone-mates than clones from single-sex populations. Animals placed with mates in a field experiment divided less frequently than animals without a mate. These findings demonstrate that animals reduce their allocation to asexual reproduction when mates are present and when a loss of fecundity associated with cloning would decrease offspring production. This plasticity is probably adaptive because it maximizes sexual-reproductive potential when fertilization is more likely, but maximizes survival of the clone when mates are absent and gametes are unlikely to be converted to offspring.


Genome-wide association mapping of seedling and adult plant response to stem rust in a durum wheat panel.
Many of the major stem rust resistance genes deployed in commercial wheat (Triticum spp.) cultivars and breeding lines become ineffective over time because of the continuous emergence of virulent races. A genome-wide association study (GWAS) was conducted using 26,439 single nucleotide polymorphism (SNP) markers and 280 durum wheat [Triticum turgidum L. subsp. Durum (Desf.) Husnot] lines from CIMMYT to identify genomic regions associated with seedling resistance to races TTKSK, TKTTF, JRCQC, and TTRTF and field resistance to TKTTF and JRCQC. The phenotypic data analysis across environments revealed 61-91 and 59-77% of phenotypic variation was explained by the genotypic component for seedling and adult plant response of lines, respectively. For seedling resistance, mixed linear model (MLM) identified eight novel and nine previously reported quantitative trait loci (QTL) while a fixed and random model circulating probability unification (FarmCPU) detected 12 novel and eight previously reported QTL. For field resistance, MLM identified 12 novel and seven previously reported loci while FarmCPU identified seven novel and nine previously reported loci. The regions of Sr7a, Sr8155B1, Sr11, alleles of Sr13, Sr17, Sr22/Sr25, and Sr49 were identified. Novel loci on chromosomes 3B, 4A, 6A, 6B, 7A, and 7B could be used as sources of resistance to the races virulent on durum wheat. Two large-effect markers on chromosome 6A could potentially be used to differentiate resistant haplotypes of Sr13 (R1 and R3). Allelism tests for Sr13, breaking the deleterious effect associated with Sr22/Sr25 and retaining the resistance allele at the Sr49 locus, are needed to protect future varieties from emerging races.


In vivo characterization and therapeutic efficacy of a C5-specific inhibitor from the soft tick Ornithodoros moubata.
The involvement of complement (C) in inflammatory diseases has driven the search for agents capable of inhibiting dysregulated complement activation. Many of these reagents inhibit the C3 convertases during the early stages of the cascade. However, a drawback of total systemic C inhibition, particularly in longterm treatment of chronic disease, is potentiation of infection and immune complex disease due to an inability to opsonize complexes and foreign cells and to lyse pathogens. Recent identification of a C5-binding protein in the salivary gland of the soft tick Ornithodoros moubata has enabled development of a terminal pathway-specific reagent, OmCI, with potential to ameliorate disease while leaving key physiological processes unaffected. Here we demonstrated that OmCI has broad cross-species activity. When given intravenously to rodents, OmCI totally ablated complement hemolytic activity, which gradually restored as C5 was resynthesized. The circulating half-life of OmCI was 30 h, demonstrating a much slower clearance than other small, biological agents. Using C5-sufficient and C5-deficient mice we showed that prolonged half-life was due to binding to plasma C5. Surface plasmon resonance analysis of C5 binding to OmCI confirmed a high binding affinity with a slow dissociation rate. OmCI was effective in preventing experimental autoimmune myasthenia gravis induced by passive transfer in normal Lewis rats. OmCI ablated clinical disease, reduced C3 and C9 deposition at the neuro-muscular junction, and effected a marked reduction in cellular infiltration at this site. These data offer exciting prospects for targeted treatment of complement-mediated diseases without the detrimental inhibition of the opsonic roles of complement.


No stop codons in the antisense strands of the genes for nylon oligomer degradation.
Genes for nylon oligomer-degrading enzymes are unique in the sense that the enzymes encoded by them are found not to have any appropriate substrates during most of the period of their evolution. Furthermore, these nylB genes form a family not related to any other known gene families. The base sequences of these genes were examined and a common characteristic was found: a long stretch of sequence without chain-terminating base triplets, defined as a nonstop frame (NSF), is being maintained on the antisense strand. Moreover, a certain coding frame is open for both the sense and the antisense sequences, while the other frames have many stop codons. The probability of the presence of these NSFs on the antisense strand of a gene is very small (0.0001-0.0018). In addition, another gene for nylon oligomer degradation was found to have a NSF on its antisense strand, and this gene is phylogenically independent of the nylB genes. Therefore, the presence of these NSFs is very rare and improbable. Even if the common ancestral gene of the nylB family was originally endowed with a NSF on its antisense strand, the probability of this original NSF persisting in one of its descendants of today is only 0.007. Unless an unknown force was maintaining the NSF, it would have quickly disappeared by random emergences of chain terminators. Therefore, the presence of such rare NSFs on all three antisense strands of the nylB gene family suggests that there is some special mechanism for protecting these NSFs from mutations that generate the stop codons. Such a mechanism may enable NSFs to evolve into new functional genes and hence seems to be a basic mechanism for the birth of new enzymes.


Lipid and inflammatory cardiovascular risk worsens over 3 years in youth with type 2 diabetes: the TODAY clinical trial.
Type 2 diabetes increases cardiovascular risk. We examined lipid profiles and inflammatory markers in 699 youth with recent-onset type 2 diabetes in the TODAY clinical trial and compared changes across treatment groups: metformin alone (M), metformin plus rosiglitazone (M+R), and metformin plus intensive lifestyle program (M+L). Multiethnic youth with type 2 diabetes received M, M+R, or M+L. Statin drugs were begun for LDL cholesterol (LDL) ≥ 130 mg/dL or triglycerides ≥ 300 mg/dL. Lipids, apolipoprotein B (apoB), LDL particle size, high-sensitivity c-reactive protein (hsCRP), homocysteine, plasminogen activator inhibitor-1 (PAI-1), and HbA1c were measured over 36 months or until loss of glycemic control. LDL, apoB, triglycerides, and non-HDL cholesterol (HDL) rose over 12 months and then stabilized over the next 24 months. Participants with LDL ≥ 130 mg/dL or using LDL-lowering therapy increased from 4.5 to 10.7% over 36 months, while 55.9% remained at LDL goal (<100 mg/dL) over that time. Treatment group did not impact LDL, apoB, or non-HDL. Small dense LDL (particle size, ≤ 0.263 relative flotation rate) was most common in M. Triglycerides were lower in M+L than M, and M+L attenuated the negative effect of hyperglycemia on triglycerides and HDL in females. hsCRP, PAI-1, and homocysteine increased over time. However, hsCRP was lower in M+R compared with M or M+L. Dyslipidemia and chronic inflammation were common in youth with type 2 diabetes and worsened over time. Diabetes treatment, despite some treatment group differences in lipid and inflammatory marker change over time, is generally inadequate to control this worsening risk.


Bidirectional hybrid CATV/radio-over-fiber WDM transport system.
A bidirectional hybrid cable antenna television (CATV)/radio-over-fiber (ROF) wavelength-division-multiplexing (WDM) transport system using injection locking technique to suppress the rf power degradation, tunable optical bandpass filter to generate optical single-sideband format for the CATV signal or only one optical sideband format for the ROF one, and photonic crystal fiber to reduce the net dispersion is proposed and demonstrated. Impressive performances of the carrier-to-noise ratio, the composite second-order, the composite triple beat, and the bit error rate were obtained in our proposed systems.


Are the respiratory health effects found in manufacturers of ceramic fibres due to the dust rather than the exposure to fibres?
To determine whether the respiratory symptoms and decrements in lung function found in manufacturers of ceramic fibres are related to exposure to the respirable fibre or inspirable mass constituents of the air in the working environment. Cross sectional survey of all current European primary producers of ceramic fibre was carried out, with measurement of exposure to respiratory fibres by personal samplers that measured inspirable and total mass, together with a health survey with an expanded respiratory questionnaire and standardised measurement of lung function. Odds ratios were calculated for symptoms and current exposure by multiple logistic regression, and multiple linear regression coefficients for lung function related to cumulative exposures controlled for the effects of respirable fibre and inspirable mass separately and together. Significant effects of current exposure to both inspirable dust and respirable fibres were related to dry cough, stuffy nose, eye and skin irritation and breathlessness. The decrements found in smokers and to some extent in ex-smokers in forced expiratory volume in one second and forced expiratory flow from 25% to 75% of expiratory volume, seem to be related to the respirable fibres rather than the inspirable mass constituents of the environment. Current symptoms were related to both current exposure to inspirable dust and respirable fibre. The decrements in lung function were related to the fibre constituent of the exposure.


Isolation of a protein from human ovarian follicular fluid which exerts major stimulatory effects on in vitro steroid production of testicular, ovarian, and adrenal cells.
We describe the isolation of a steroidogenesis-inducing protein (SIP) from human ovarian follicular fluid and its effects on in vitro steroid synthesis of testicular, ovarian, and adrenal cells. After heating at 60 C, precipitation with 80% ammonium sulfate and dialysis, the human ovarian follicular fluid proteins were fractionated by gel chromatography on Sephacryl S-200. The bioactivity was eluted in the mol wt region between 40 and 60 K. SIP was further purified by affinity chromatography on blue Sepharose (CL-6B), preparative isoelectrofocusing on sucrose density gradients, anion exchange chromatography on Mono Q by using fast protein liquid chromatography system and gel chromatography on Superose 12. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of purified SIP under both reducing and nonreducing conditions revealed a single band with an approximate mol wt of 60 K. SIP exhibited a pI value of 4.8, was heat sensitive, and lost activity upon lyophilization. SIP copurified with albumin in various isolation procedures and was distinct from human serum albumin but may represent a modified form of human albumin. SIP stimulated testosterone production by testicular pieces, interstitial cells, or purified Leydig cells from rats under different in vitro conditions. The SIP also stimulated basal and human CG stimulated in vitro progesterone production of human ovarian granulosa-lutein cells and corticosterone production of rat adrenal cells. The effects of SIP on testicular, ovarian, and adrenal cells were evident in the presence of maximal concentrations of tropic hormones. The steroid-free spent media from human granulosa-lutein cell cultures also stimulated testosterone production by rat interstitial cells, suggesting that granulosa cells may be the cellular source of SIP. In conclusion, human ovarian cells secrete a hitherto unknown albumin-like protein which enhances both basal and tropic hormone stimulated steroidogenesis in gonadal and adrenal cells. This protein may play a significant role in ovarian function by modifying steroidogenesis in the preovulatory follicle.


Protective immunity induced with the RTS,S/AS vaccine is associated with IL-2 and TNF-α producing effector and central memory CD4 T cells.
A phase 2a RTS,S/AS malaria vaccine trial, conducted previously at the Walter Reed Army Institute of Research, conferred sterile immunity against a primary challenge with infectious sporozoites in 40% of the 80 subjects enrolled in the study. The frequency of Plasmodium falciparum circumsporozoite protein (CSP)-specific CD4(+) T cells was significantly higher in protected subjects as compared to non-protected subjects. Intrigued by these unique vaccine-related correlates of protection, in the present study we asked whether RTS,S also induced effector/effector memory (T(E/EM)) and/or central memory (T(CM)) CD4(+) T cells and whether one or both of these sub-populations is the primary source of cytokine production. We showed for the first time that PBMC from malaria-non-exposed RTS,S-immunized subjects contain both T(E/EM) and T(CM) cells that generate strong IL-2 responses following re-stimulation in vitro with CSP peptides. Moreover, both the frequencies and the total numbers of IL-2-producing CD4(+) T(E/EM) cells and of CD4(+) T(CM) cells from protected subjects were significantly higher than those from non-protected subjects. We also demonstrated for the first time that there is a strong association between the frequency of CSP peptide-reactive CD4(+) T cells producing IL-2 and the titers of CSP-specific antibodies in the same individual, suggesting that IL-2 may be acting as a growth factor for follicular Th cells and/or B cells. The frequencies of CSP peptide-reactive, TNF-α-producing CD4(+) T(E/EM) cells and of CD4(+) T(E/EM) cells secreting both IL-2 and TNF-α were also shown to be higher in protected vs. non-protected individuals. We have, therefore, demonstrated that in addition to TNF-α, IL-2 is also a significant contributing factor to RTS,S/AS vaccine induced immunity and that both T(E/EM) and T(CM) cells are major producers of IL-2.


Cognard type V intracranial dural arteriovenous shunt: case reports and literature review with special consideration of the pattern of spinal venous drainage.
Prompt diagnosis of intracranial dural arteriovenous shunt (DAVS) with spinal venous drainage, classified as Cognard type V, is difficult. We investigated the angiographic and magnetic resonance imaging (MRI) characteristics of Cognard type V DAVS to determine the reason for the difficulty in early diagnosis. We systematically reviewed 54 published and 3 new cases of Cognard type V DAVS. The pattern of venous drainage was classified on the basis of relative dominance of the anterior and posterior spinal veins with the use of angiograms. T2-weighted sagittal MRIs were used to detect signal flow voids of enlarged spinal veins. Types of venous drainage were determined in 49 of the 57 cases. Twenty-eight and 8 cases showed a dominance of anterior and posterior spinal venous drainage, respectively. In 13 cases, venous drainage was equally distributed through the anterior and posterior spinal veins. Of 41 cases with an abnormally dilated anterior spinal vein, MRIs were available for 25 cases. Signal flow voids of enlarged anterior spinal veins were detected in 9 cases (36.0%), whereas dilatation of the posterior spinal veins was apparent in 9 of 16 cases (56.3%). Overall, MRI detected enlargement of either anterior or posterior spinal veins in 15 of 41 cases (36.6%). In Cognard type V DAVS, anterior venous drainage is dominant. Because the anterior spinal veins are located subpially, flow voids are less prominent on sagittal T2-weighted MRI. This may lead to difficulties in diagnosing. Evaluation with MR angiography may compensate for these limitations.


Tertiary structure is a principal determinant to protein deamidation.
The protein deamidation process involves the conversion of the amide side-chain moieties of asparagine and glutamine residues to carboxyl groups. This conversion is an unusual form of protein modification in that it requires catalysis by an intramolecular reaction where both the substrate (asparagine and glutamine side chains) and "catalytic site" (the peptide nitrogen of the succeeding residue) are constituents of several consecutive residues along the polypeptide chain. The stereochemical factors governing this process were studied with a data base derived from the neutron crystallographic structure of trypsin from which amide groups and oxygen can be unambiguously differentiated because of their different neutron scattering properties. The neutron structure allowed for the direct determination of those residues that were deamidated; 3 of 13 asparagine residues were found to be modified. These modified residues were clearly distinguished by a distinct local conformation and hydrogen-bonding structure in contrast to those observed for the other asparagine residues. No correlation was found between preference to deamidate and the chemical character of residues flanking the site, as had been proposed from previous peptide studies.


Bovine viral diarrhea virus: prevention of persistent fetal infection by a combination of two mutations affecting Erns RNase and Npro protease.
Different genetically engineered mutants of bovine viral diarrhea virus (BVDV) were analyzed for the ability to establish infection in the fetuses of pregnant heifers. The virus mutants exhibited either a deletion of the overwhelming part of the genomic region coding for the N-terminal protease N(pro), a deletion of codon 349, which abrogates the RNase activity of the structural glycoprotein E(rns), or a combination of both mutations. Two months after infection of pregnant cattle with wild-type virus or either of the single mutants, the majority of the fetuses contained virus or were aborted or found dead in the uterus. In contrast, the double mutant was not recovered from fetal tissues after a similar challenge, and no dead fetuses were found. This result was verified with a nonrelated BVDV containing similar mutations. After intrauterine challenge with wild-type virus, mutated viruses, and cytopathogenic BVDV, all viruses could be detected in fetal tissue after 5, 7, and 14 days. Type 1 interferon (IFN) could be detected in fetal serum after challenge, except with wild-type noncytopathogenic BVDV. On days 7 and 14 after challenge, the largest quantities of IFN in fetal serum were induced by the N(pro) and RNase-negative double mutant virus. The longer duration of fetal infection with the double mutant resulted in abortion. Therefore, for the first time, we have demonstrated the essential role of both N(pro) and E(rns) RNase in blocking interferon induction and establishing persistent infection by a pestivirus in the natural host.


Defining Brugia malayi and Wolbachia symbiosis by stage-specific dual RNA-seq.
Filarial nematodes currently infect up to 54 million people worldwide, with millions more at risk for infection, representing the leading cause of disability in the developing world. Brugia malayi is one of the causative agents of lymphatic filariasis and remains the only human filarial parasite that can be maintained in small laboratory animals. Many filarial nematode species, including B. malayi, carry an obligate endosymbiont, the alpha-proteobacteria Wolbachia, which can be eliminated through antibiotic treatment. Elimination of the endosymbiont interferes with development, reproduction, and survival of the worms within the mamalian host, a clear indicator that the Wolbachia are crucial for survival of the parasite. Little is understood about the mechanism underlying this symbiosis. To better understand the molecular interplay between these two organisms we profiled the transcriptomes of B. malayi and Wolbachia by dual RNA-seq across the life cycle of the parasite. This helped identify functional pathways involved in this essential symbiotic relationship provided by the co-expression of nematode and bacterial genes. We have identified significant stage-specific and gender-specific differential expression in Wolbachia during the nematode's development. For example, during female worm development we find that Wolbachia upregulate genes involved in ATP production and purine biosynthesis, as well as genes involved in the oxidative stress response. This global transcriptional analysis has highlighted specific pathways to which both Wolbachia and B. malayi contribute concurrently over the life cycle of the parasite, paving the way for the development of novel intervention strategies.


Plaque excision in the management of lower-limb ischemia of atherosclerosis and in-stent restenosis with the SilverHawk atherectomy catheter.
Aim of the present study was to compare the effectiveness of plaque excision in management of lower limb ischemia of atherosclerosis and in-stent restenosis with the SilverHawk atherectomy catheter. From November 2010, to August 2011, 43 patients were involved and completed follow-up. They were divided into two groups: group A is the atherosclerotic plaque group (16 cases, 37.2%) and group B is the in-stent restenosis/occlusion lesion group (27 cases, 62.8%). The average age of group A was 68.3 years and group B was 72 years, the mean duration was 27.4 months and 26 months, respectively. Intermittent claudication was 8 cases and 16 cases respectively, and rest pain both was 4 cases, foot ulcer was 1 case and 4 cases, toe gangrene both was 3 cases. Ankle Brachial Index (ABI)≤0.4 was 2 in group A and 8 in group B, ABI>0.4 was 12 and 16, ABI=0 was 2 and 3, respectively. Excision with protective devices in 6 cases. Nine cases and 17 cases received treatment for proximal and distal lesions over the same period, respectively, included the proximal iliac artery stenting 1 case in group A and 5 cases in group B, distal calf arteries stenting 6 cases in group A and 11 cases in group B, balloon angioplasty 2 in group A and 1 in group B. Endpoints included postoperative mortality or amputation of target limb. Forty-one operations were successful, the technical success rate was 95.3%, one case in group B suffered above-knee amputation. The target vessels of 41 patients maintain patency after discharge. Postoperative claudication distance increased to 500 meters except for one case in each group, all 4 rest pain patients got alleviated, reduced toe ulcer area happened in 1 and 2 cases respectively, all 3 cases of gangrene dried up/infection controlled in each group. Postoperative ABI result 0.7-0.8: 4 in group A and 5 in group B; 0.81-0.9 was 5 and 8; >0.91 was 6 and 13, respectively. Symptom improvement result had no significant difference between the two groups (P>0.05). Follow-up covered 41 patients, average 17.5±3.3 months. Group A patients stayed in good condition, 7 claudication patients's walking distance above 500 meters remains; rest pain no recurrence, one ulcer healing, 2 of 3 toe gangrene self-shedding and stump healing, 1 toe gangrene removed by surgery and wound healing. Group B, 4 of 15 claudication cases recurrence, and received plaque excision again. Rest pain no recurrence. 3 of 4 ulcer healing, 1 ulcer area reduced significantly. One out of 3 gangrene received below knee amputation (toe osteomyelitis), wound healing. One recurrence, angiography showed in-stent severe restenosis, received plaque excision again. One toe gangrene removed by surgery and wound healing. Plaque excision with "SilverHawk" treatment for lower limb ischemia of atherosclerosis or in-stent restenosis is safe and effective. No significant difference for these two lesions in efficacy. Long term follow-up and larger randomized study is needed for further information on treatment.


Not so fast! Talker variability in serial recall at standard presentation rates.
In serial recall tasks, presenting items in alternating female and male voices impairs performance relative to the single-voice presentation. This phenomenon, termed the talker-variability effect (TVE), was recently reexamined by Hughes, Marsh, and Jones (2009, 2011), who used the effect as confirmatory evidence for their perceptual-gestural account of serial recall performance. Despite the authors' claim of generalisability, the serial recall paradigm employed did not reflect the standard parameters more generally adopted in verbal short-term memory research. Specifically, the presentation rate of the stimuli was almost 3 times that typically used. We sought to determine if the TVE, as observed by Hughes et al., was generalisable to the standard serial recall task by directly comparing recall performance in talker-variable conditions at fast and slow stimulus presentation rates. Experiment 1 employed a systematic replication of the foundational study undertaken by Hughes et al. (2009). Utilising a novel stimulus set, Experiment 2 provided a subsequent test of the generalisability of the TVE, examining the influence of item properties. Both experiments showed a robust TVE at the atypical fast presentation rate; however, for the slower item presentation, the TVE was unreliable. Furthermore, error analysis suggests that item recall also contributes to the TVE, contrary to the current explanation proposed by Hughes et al. (2009, 2011). The challenge of the present data to the perceptual-gestural account of the TVE is explored. Alternative accounts that focus on the resource cost of categorical speech perception in the context of talker variability are posited.


The concept of health: beyond normativism and naturalism.
Philosophical discussions of health and disease have traditionally been dominated by a debate between normativists, who hold that health is an inescapably value-laded concept and naturalists, such as Christopher Boorse, who believe that it is possible to derive a purely descriptive or theoretical definition of health based upon biological function. In this paper I defend a distinctive view which traces its origins in Aristotle's naturalistic ethics. An Arisotelian would agree with Boorse that health and disease are ubiquitous features of the natural world and thus not mere projections of human interests and values. She would differ from him in rejecting the idea that value is a non-natural quality. I conclude my discussion with some comments of the normative character of living systems.


Knee joint loading in knee osteoarthritis: influence of abdominal and thigh fat.
Using three separate models that included total body mass, total lean and total fat mass, and abdominal and thigh fat as independent measures, we determined their association with knee joint loads in older overweight and obese adults with knee osteoarthritis (OA). Fat depots were quantified using computed tomography, and total lean and fat mass were determined with dual energy x-ray absorptiometry in 176 adults (age, 66.3 yr; body mass index, 33.5 kg·m) with radiographic knee OA. Knee moments and joint bone-on-bone forces were calculated using gait analysis and musculoskeletal modeling. Higher total body mass was significantly associated (P ≤ 0.0001) with greater knee compressive and shear forces, compressive and shear impulses (P < 0.0001), patellofemoral forces (P < 0.006), and knee extensor moments (P = 0.003). Regression analysis with total lean and total fat mass as independent variables revealed significant positive associations of total fat mass with knee compressive (P = 0.0001), shear (P < 0.001), and patellofemoral forces (P = 0.01) and knee extension moment (P = 0.008). Gastrocnemius and quadriceps forces were positively associated with total fat mass. Total lean mass was associated with knee compressive force (P = 0.002). A regression model that included total thigh and total abdominal fat found that both were significantly associated with knee compressive and shear forces (P ≤ 0.04). Thigh fat was associated with knee abduction (P = 0.03) and knee extension moment (P = 0.02). Thigh fat, consisting predominately of subcutaneous fat, had similar significant associations with knee joint forces as abdominal fat despite its much smaller volume and could be an important therapeutic target for people with knee OA.