bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation of serum fructosamine and recurrent pregnancy loss: Case–control study
Authors: Romero Stephanie T. , Sharshiner Rita , Stoddard Gregory J. , Ware Branch D. , Silver Robert M.
Published: March 2016

Aim

Pre‐gestational diabetes is associated with an elevated risk of pregnancy loss, but it is unclear whether subclinical glucose intolerance is associated with pregnancy loss, especially recurrent pregnancy loss (RPL). The aim of this study was therefore to compare maternal serum fructosamine (a marker of glycemic control) in patients with and without RPL.

Methods

A case–control study was carried out of 117 women with unexplained RPL, defined as two or more pregnancy losses with no more than one live birth, and 117 age‐matched controls with at least one full‐term uncomplicated pregnancy and no more than one pregnancy loss. No RPL patients or controls had a clinical diagnosis of pre‐gestational or gestational diabetes. Maternal serum was analyzed for fructosamine on quantitative spectrophotometry.

Results

Mean body mass index (BMI) of RPL patients was 26.0 ± 6.4 kg/m2 compared with 26.6 ± 5.8 kg/m2 (P = 0.40). Fructosamine was higher in women with RPL (224.1 ± 28.79 μmol/mL) compared with controls (188.9 ± 19.3 μmol/mL, P < 0.001). This difference persisted when RPL patients and controls were stratified by BMI. The proportion of women with elevated fructosamine considered diagnostic of diabetes (>285 μmol/L) was similar in RPL patients and controls.

Conclusion

The RPL patients and controls had a similar proportion of women with elevated fructosamine considered diagnostic of diabetes. Serum fructosamine was increased in women with RPL compared with controls. Thus, subclinical glucose intolerance may be associated with an increased risk of RPL. These data support further investigation into the mechanisms of RPL associated with glucose intolerance, but do not support testing for subclinical glucose intolerance in women with RPL.
Brain Volume Loss During the First Year of Interferon‐Beta Treatment in Multiple Sclerosis: Baseline Inflammation and Regional Brain Volume Dynamics
Authors: Vidal‐Jordana Angela , Sastre‐Garriga Jaume , Pérez‐Miralles Francisco , Pareto Deborah , Rio Jordi , Auger Cristina , Tintoré Mar , Rovira Alex , Montalban Xavier
Published: March 2016

OBJECTIVE

A pseudoatrophy effect, mostly affecting white matter, can be observed in patients with multiple sclerosis (MS) early on natalizumab therapy. We aimed to investigate whether a similar pattern could be found after interferon‐beta treatment onset.

METHODS

From a prospective, ongoing cohort, 123 patients treated with interferon‐beta were included. A brain MRI was performed at baseline (3 months prior) and 12 months after therapy onset in all patients. SPM8 software was used for volumetric analysis. Brain parenchymal, gray and white matter volumes at baseline and follow‐up were obtained, allowing calculation of percentage of volume changes (BVc, GMVc, and WMVc, respectively). Descriptive statistics and linear regression models were performed.

RESULTS

Eighty‐four patients were analyzed (39 patients were excluded mostly due to incomplete MRI protocol or segmentation errors); baseline mean age was 33.6 years (SD 8.7), median disease duration was 2.8 years (.3‐14), and median EDSS was 1.5 (0‐6). Forty‐nine patients (58.3%) had baseline gadolinium‐enhancing (Gd+) lesions with a median number of 1 (0‐18). The regression analysis (adjusted by the number of Gd+ at follow‐up MRI, age, disease duration, and baseline EDSS) showed that a higher baseline number of Gd+ lesions was predictive of larger decreases in BVc and WMVc (P = .013 and P = .003, respectively) but not GMVc (P = .777).

CONCLUSION

Concurrent inflammation has an impact on brain volume measurements (especially white matter) during the first year of interferon‐beta therapy, and should be taken into account when interpreting early brain volume changes on therapy.
Effects of monensin and essential oils on immunological, haematological and biochemical parameters of cows during the transition period
Authors: Drong C. , Meyer U. , von Soosten D. , Frahm J. , Rehage J. , Schirrmeier H. , Beer M. , Dänicke S.
Published: March 2016

Using a model to generate experimental groups with different manifestations of post‐partum (p.p.) fat mobilization and ketogenesis, the effects of a dietary and a medical intervention on biochemical and haematological parameters, antibody titre, leucocytes subsets and function of transition cows were examined. In total, 60 German Holstein cows were allocated 6 weeks antepartum (a.p.) to 3 high‐body condition score (BCS) groups (BCS 3.95) and 1 low‐BCS group (LC, BCS 2.77). High‐BCS cows received a monensin controlled‐release capsule (HC/MO) or a blend of essential oils (HC/EO) or formed a control group (HC). Parameters were evaluated in 3 periods (day (d) −42 until calving, 1 until 14 days in milk (DIM), 15 until 56 DIM).

Over the course of trial, various parameters were influenced by period with greatest variability next to calving. White blood cell count was higher in the HC (8.42 × 103/μl) and HC/EO (8.38 × 103/μl) groups than in the HC/MO group (6.81 × 103/μl) considering the whole trial. Supplementation of monensin decreased aspartate aminotransferase in comparison with the HC group similar to LC treatment. Bilirubin concentration was nearly doubled in all high‐BCS cows in period 2. In period 3, essential oils increased γ‐glutamyltransferase (80.4 Units/l) in comparison with all other groups and glutamine dehydrogenase (61 Units/l) in comparison with the LC (19 Units/l) and the HC/MO group (18 Units/l).

Results suggest that parameters were generally characterized by a high variability around calving. Based on biochemical characteristics, it appeared that the HC cows seemed to have compromised hepatocyte integrity when compared to the LC cows. From the immune parameters investigated, the BVDV antibody response was more pronounced in HC/MO compared to HC/EO.
Rhodenigma contortum, an obscure new genus and species of Rhodogorgonales (Rhodophyta) from Western Australia
Authors: West John A. , Zuccarello Giuseppe C. , de Goër Susan Loiseaux , Stavrias Lambros A. , Verbruggen Heroen
Published: March 2016

An unknown microscopic, branched filamentous red alga was isolated into culture from coral fragments collected in Coral Bay, Western Australia. It grew well unattached or attached to glass with no reproduction other than fragmentation of filaments. Cells of some branch tips became slightly contorted and digitated, possibly as a substrate‐contact‐response seen at filament tips of various algae. Attached multicellular compact disks on glass had a very different cellular configuration and size than the free filaments. In culture the filaments did not grow on or in coral fragments. Molecular phylogenies based on four markers (rbcL,cox1, 18S, 28S) clearly showed it belongs to the order Rhodogorgonales, as a sister clade ofRenouxia. Based on these results, the alga is described as the new genus and speciesRhodenigma contortumin the Rhodogorgonaceae. It had no morphological similarity to either of the other genera in Rhodogorgonaceae and illustrates the unknown diversity in cryptic habitats such as tropical coral rubble.
Temperature‐dependent phagotrophy and phototrophy in a mixotrophic chrysophyte
Authors: Princiotta Sarah DeVaul , Smith Brian T. , Sanders Robert W.
Published: March 2016

The roles of temperature and light on grazing and photosynthesis were examined for Dinobryon sociale, a common freshwater mixotrophic alga. Photosynthetic rate was determined for D. sociale adapted to temperatures of 8, 12, 16, and 20°C under photosynthetically active radiation light irradiances of 25, 66, and 130 μmol photons · m−2 · s−1, with concurrent measurement of bacterial ingestion at all temperatures under medium and high light (66 and 130 μmol photons · m−2 · s−1). Rates of ingestion and photosynthesis increased with temperature to a maximum at 16°C under the two higher light regimes, and declined at 20°C. Although both light and temperature had a marked effect on photosynthesis, there was no significant difference in bacterivory at medium and high irradiances at any given temperature. At the lowest light condition (25 μmol photons · m−2 · s−1), photosynthesis remained low and relatively stable at all temperatures. D. sociale acquired the majority of carbon from photosynthesis, although the low photosynthetic rate without a concurrent decline in feeding rate at 8°C suggested 20%–30% of the carbon budget could be attributed to bacterivory at low temperatures. Grazing experiments in nutrient‐modified media revealed that this mixotroph had increased ingestion rates when either dissolved nitrogen or phosphorus was decreased. This work increases our understanding of environmental effects on mixotrophic nutrition. Although the influence of abiotic factors on phagotrophy and phototrophy in pure heterotrophs and phototrophs has been well studied, much less is known for mixotrophic organisms.
Impact of smoking on experimental gingivitis. A clinical, microbiological and immunological prospective study
Authors: Peruzzo D. C. , Gimenes J. H. , Taiete T. , Casarin R. C. V. , Feres M. , Sallum E. A. , Casati M. Z. , Kantovitz K. R. , Nociti F. H.
Published: March 2016

Objective

The present study assessed the effect of smoking on clinical, microbiological and immunological parameters in an experimental gingivitis model.

Material and Methods

Twenty‐four healthy dental students were divided into two groups: smokers (n = 10); and nonsmokers (n = 14). Stents were used to prevent biofilm removal during brushing. Visible plaque index (VPI) and gingival bleeding index (GBI) were determined 5‐ on day ‐7 (running phase), baseline, 21 d (experimental gingivitis) and 28 d (resolution phase). Supragingival biofilm and gingival crevicular fluid were collected and assayed by checkerboard DNA–DNA hybridization and a multiplex analysis, respectively. Intragroup comparison was performed by Friedman and Dunn's multiple comparison tests, whereas the Mann–Whitney U‐test was applied for intergroup analyses.

Results

Cessation of oral hygiene resulted in a significant increase in VPI, GBI and gingival crevicular fluid volume in both groups, which returned to baseline levels 7 d after oral hygiene was resumed. Smokers presented lower GBI than did nonsmokers (p < 0.05) at day 21. Smokers had higher total bacterial counts and higher proportions of red‐ and orange complex bacteria, as well as lower proportions of Actinomyces spp., and of purple‐ and yellow‐complex bacteria (p < 0.05). Furthermore, the levels of key immune‐regulatory cytokines, including interleukin (IL)‐8, IL‐17 and interferon‐γ, were higher in smokers than in nonsmokers (p < 0.05).

Conclusion

Smokers and nonsmokers developed gingival inflammation after supragingival biofilm accumulation, but smokers had less bleeding, higher proportions of periodontal pathogens and distinct host‐response patterns during the course of experimental gingivitis.
Therapeutic outcome of 6198 interferon‐naïve Egyptian patients with chronic hepatitis C: a real‐life experience and lessons to be learned in DAAs’ era
Authors: Zayed N. , Gamal Eldeen H. , Elmakhzangy H. , Seif M. , El‐Akel W. , Awad T. , Esmat G. , Mabrouk M.
Published: March 2016

Antiviral therapy for HCV infection has been validated in randomized controlled clinical trials, but its value in the real world is less well studied. There is relatively little data on real‐world responses to interferon‐based therapies for patients with genotype 4 infection. We aimed to examine experience with large‐scale access to antiviral therapy in chronic HCV in a real‐life clinical setting in Egypt. Detailed pretreatment data of 6198 IFN‐naïve chronic HCV patients who had received PEG‐IFN/RBV therapy at Cairo‐Fatemic Hospital, Egypt, between 2009 and 2012 were obtained from the HCV database. At week 12, 95.7% of patients had undetectable HCV RNA, and by week 24 and 48, breakthrough was 6% and 4%, respectively. However, 43.7% of patients discontinued treatment prematurely, and intent to treat end of treatment response was 44.6% (79.3% per protocol). Sustai‐ned response data were available from only 1281 patients and was 84.9%. Haematological abnormalities were comparable in patients who did or did not comply with therapy. This is the first real‐world, large‐scale experience of antiviral therapy in chronic HCV in Egypt. Suboptimal response in HCV predominantly genotype 4 was mainly driven by noncompliance as well as gaps in the healthcare system leading to treatment discontinuation. These results need to be considered in the era of all oral antiviral regimes.
Should surveillance for liver cancer be modified in hepatitis C patients after treatment‐related cirrhosis regression?
Authors: D'Ambrosio Roberta , Colombo Massimo
Published: March 2016

Surveillance of hepatocellular carcinoma (HCC) with abdominal ultrasound (US) is recommended for patients with advanced liver fibrosis because of hepatitis C virus (HCV) infections who achieve a sustained virological response (SVR) to antiviral therapy. HCC, in fact, may still develop following SVR as a consequence of long‐standing carcinogenic activity of either HCV or hepatic fibrosis, whereas HCC risk in non‐viraemic patients may also be driven by cofactors like alcohol abuse or diabetes. This explains the debate on whether surveillance for HCC should be continued in patients with documented cirrhosis regression following a SVR too. While regression of cirrhosis was documented to occur in a majority of patients with compensated cirrhosis 5 years after an SVR to interferon, it should be noted that this clinical benefit could be the consequence of treating a selected population with well‐compensated liver disease who in fact were interferon able. This may not be the case for most real‐life patients with advanced cirrhosis receiving direct antivirals, in whom liver fibrosis may have reached a point of no‐return thus potentially preventing the recovery of a normal liver architecture following SVR. Both invasive and non‐invasive tools have suboptimal diagnostic accuracy for fibrosis regression in non‐viraemic patients, and this prompts to follow international societies’ recommendation to perform surveillance in patients with advanced liver fibrosis achieving a SVR, independently on liver histology outcome.
Anthropogenic impacts on nitrogen fixation rates between restored and natural Mediterranean salt marshes
Authors: Moseman‐Valtierra Serena , Levin Lisa A. , Martin Rose M.
Published: March 2016

To test the effects of site and successional stage on nitrogen fixation rates in salt marshes of the Venice Lagoon, Italy, acetylene reduction assays were performed with Salicornia veneta‐ and Spartina townsendii‐vegetated sediments from three restored (6–14 years) and two natural marshes. Average nitrogen fixation (acetylene reduction) rates ranged from 31 to 343 μmol C2H4·m−2·h−1 among all marshes, with the greatest average rates being from one natural marsh (Tezze Fonde). These high rates are up to six times greater than those reported from Southern California Spartina marshes of similar Mediterranean climate, but substantially lower than those found in moister climates of the Atlantic US coast. Nitrogen fixation rates did not consistently vary between natural and restored marshes within a site (Fossei Est, Tezze Fonde, Cenesa) but were negatively related to assayed plant biomass within the acetylene reduction samples collected among all marshes. Highest nitrogen fixation rates were found at Tezze Fonde, the location closest to the city of Venice, in both natural and restored marshes, suggesting possible site‐specific impacts of anthropogenic stress on marsh succession.
Case of intermittent claudication as a result of cervical myelopathy presenting with ankle clonus induced by the gait loading test
Authors: Sawamura Masanori , Murata Oki , Ogawa Masafumi
Published: March 2016

Spinal lesions can cause intermittent claudication. A 67‐year‐old man was referred to our department with a 3‐year history of progressive intermittent claudication. Spinal magnetic resonance imaging showed only moderate cervical canal stenosis, but not severe lumbar canal stenosis, which could cause intermittent claudication. The gait loading test reproduced tightness and weakness in the lower extremities, as well as an induced pyramidal tract sign that included Achilles tendon hyperreflexia and right ankle clonus. He was therefore diagnosed with spinal intermittent claudication. Two weeks later, sudden lower limb paralysis with urinary retention appeared without a traumatic event. After cervical spine surgery, the intermittent claudication disappeared. Spinal claudication is rare, and a relatively unknown symptom. As such, it is therefore a diagnostic challenge. Here, we highlight the importance of a full clinical report and the usefulness of the gait loading test for determining the clinical diagnosis.
Imaginatively‐Colored Perception: Walton on Pictorial Experience
Authors: Chasid Alon
Published: March 2016

This paper develops Kendall Walton's account of pictorial experience. Walton argues that the key feature of that experience is that it is imaginatively‐penetrated experience. I argue that this idea, as put forward by Walton, has various shortcomings. After discussing these limitations, I suggest, on the basis of a more general phenomenon of cognitive penetration, a refinement of Walton's account. I then show how the revised account explains various features of pictorial experience. Specifically, I show that, given the manner in which imaginings influence perceptual experience, Walton can dispense with the thesis that pictorial experience is twofold.
Transactive Memory Reconstructed: Rethinking Wegner's Research Program
Authors: Huebner Bryce
Published: March 2016

In this paper, I argue that recent research on episodic memory supports a limited defense of the phenomena that Daniel Wegner has termed transactive memory. Building on psychological and neurological research, targeting both individual and shared memory, I argue that individuals can collaboratively work to construct shared episodic memories. In some cases, this yields memories that are distributed across multiple individuals instead of being housed in individual brains.
Open‐Mindedness as Engagement
Authors: Kwong Jack M. C.
Published: March 2016

Open‐mindedness is an under‐explored topic in virtue epistemology, despite its assumed importance for the field. Questions about it abound and need to be answered. For example, what sort of intellectual activities are central to it? Can one be open‐minded about one's firmly held beliefs? Why should we strive to be open‐minded? This paper aims to shed light on these and other pertinent issues. In particular, it proposes a view that construes open‐mindedness as engagement, that is, a willingness to entertain novel ideas in one's cognitive space and to accord them serious consideration.
Lockean Empathy
Authors: Marshall Colin
Published: March 2016

This paper offers an epistemic defense of empathy, drawing on John Locke's theory of ideas. Locke held that ideas of shape, unlike ideas of color, had a distinctive value: resembling qualities in their objects. I argue that the same is true of empathy, as when someone is pained by someone's pain. This means that empathy has the same epistemic value or objectivity that Locke and other early modern philosophers assigned to veridical perceptions of shape. For this to hold, pain and pleasure must be a primary quality of the mind, just as shape is a primary quality of bodies. Though Locke did not make that claim, I argue that pain and pleasure satisfy his criteria for primary qualities. I consider several objections to the analogy between empathy and shape‐perception and show how Locke's theory has resources for answering them. In addition, the claim that empathetic ideas are object‐matching sidesteps Berkeley's influential objection to Locke's theory of resemblance. I conclude by briefly considering the prospects for a similar defense of empathy in contemporary terms.
What is wrong with ethics review, the impact on teaching anthropology, and how to fix it: results of an empirical study
Authors: Wynn L.L.
Published: March 2016

There is no empirical evidence that ethics review protects anthropologists’ research participants, but there is ample evidence that it is stifling research agendas and reshaping how we teach anthropological research methods, entrenching a positivist, clinical model of what constitutes research. This paper examines the impact of ethics review on student research in Australia, based on interviews conducted at 14 Australian universities. The data clearly show that the risks posed by student research are minor, and vastly overestimated by ethics committees. To avoid problems with ethics committees, we shepherd students into undertaking low‐risk, and consequently low‐impact, research. Many departments are abandoning research‐led teaching altogether because of the obstacle of ethics review. One solution would be to locate ethics discussions in disciplines and departments, radically restructuring the encounter to reconceptualise it as collegial debate about ethics dilemmas rather than ‘ethics review’.
The role of PLDα1 in providing specificity to signal‐response coupling by heterotrimeric G‐protein components in Arabidopsis
Authors: Roy Choudhury Swarup , Pandey Sona
Published: March 2016

Heterotrimeric G‐proteins comprised of Gα, Gβ and Gγ subunits are important signal transducers in all eukaryotes. In plants, G‐proteins affect multiple biotic and abiotic stress responses, as well as many developmental processes, even though their repertoire is significantly limited compared with that in metazoan systems. One canonical and three extra‐large Gα, 1 Gβ and 3 Gγ proteins represent the heterotrimeric G‐protein complex in Arabidopsis, and a single regulatory protein, RGS1, is one of the few known biochemical regulators of this signaling complex. This quantitative disparity between the number of signaling components and the range of processes they influence is rather intriguing. We now present evidence that the phospholipase Dα1 protein is a key component and modulator of the G‐protein complex in affecting a subset of signaling pathways. We also show that the same G‐protein subunits and their modulators exhibit distinct physiological and genetic interactions depending on specific signaling and developmental pathways. Such developmental plasticity and interaction specificity likely compensates for the lack of multiplicity of individual subunits, and helps to fine tune the plants' responses to constantly changing environments.
Fusion of Enveloped Viruses in Endosomes
Authors: White Judith M. , Whittaker Gary R.
Published: March 2016

Ari Helenius launched the field of enveloped virus fusion in endosomes with a seminal paper in the Journal of Cell Biology in 1980. In the intervening years, a great deal has been learned about the structures and mechanisms of viral membrane fusion proteins as well as about the endosomes in which different enveloped viruses fuse and the endosomal cues that trigger fusion. We now recognize three classes of viral membrane fusion proteins based on structural criteria and four mechanisms of fusion triggering. After reviewing general features of viral membrane fusion proteins and viral fusion in endosomes, we delve into three characterized mechanisms for viral fusion triggering in endosomes: by low pH, by receptor binding plus low pH and by receptor binding plus the action of a protease. We end with a discussion of viruses that may employ novel endosomal fusion‐triggering mechanisms. A key take‐home message is that enveloped viruses that enter cells by fusing in endosomes traverse the endocytic pathway until they reach an endosome that has all of the environmental conditions (pH, proteases, ions, intracellular receptors and lipid composition) to (if needed) prime and (in all cases) trigger the fusion protein and to support membrane fusion.
Sudden acquired retinal degeneration in dogs: breed distribution of 495 canines
Authors: Heller Amanda R. , van der Woerdt Alexandra , Gaarder James E. , Sapienza John S. , Hernandez‐Merino Elena , Abrams Kenneth , Church Melanie L. , La Croix Noelle
Published: March 2016

Purpose

The purpose of this study was to describe breed, age, gender, and weight distribution of dogs affected with sudden acquired retinal degeneration (SARD) and to investigate whether SARD is more common in small breed dogs.

Methods

Medical records of dogs diagnosed with SARD confirmed by an electroretinogram were reviewed. Breed, age, gender, and weight were recorded when available. The same data were obtained for dogs with SARD described in the veterinary literature.

Results

Three hundred and two dogs were included from the ophthalmology practices and 193 dogs from the veterinary literature. Sixty breeds were present in the study. Mixed‐breed dogs were the most common at 108 dogs (21.8%), followed by the Dachshund (68, 13.7%), Chinese Pug (44, 8.9%), Miniature Schnauzer (39, 7.9%), Maltese (23, 4.6%), Cocker Spaniel (22, 4.4%), Bichon Frise (18, 3.6%), Beagle (16, 3.2%), Brittany (15, 3.0%), and Pomeranian (10, 2.0%). Fifty other breeds were represented by 1–9 dogs each. The median age was 9 years (range = 10 months–16 years). The weight was known for 197 dogs. About 60.9% of dogs were less than 25 pounds, 31.5% were between 25 and 50 pounds, and 7.6% were greater than 50 pounds. Gender was recorded in 393 dogs: 217 female dogs and 176 male dogs.

Conclusions

As previously reported, SARD is most common in middle‐aged to older dogs. Smaller dogs of less than 25 pounds appear overrepresented, while large/giant breed dogs of greater than 50 pounds are infrequently diagnosed. In this study, there was no statistical significance between female and male dogs.
Cryptic speciation in the narrow‐headed vole Lasiopodomys (Stenocranius) gregalis (Rodentia: Cricetidae)
Authors: Petrova Tatyana V. , Tesakov Alexey S. , Kowalskaya Yulia M. , Abramson Natalia I.
Published: March 2016

Recent study on Lasiopodomys (Stenocranius) gregalis has revealed four clear mitochondrial lineages with differences exceeding the species level. The most divergent is the clade from south‐eastern Transbaikalia. Multilocus (six nuclear genes), morphological (dental characters of m1 and M3) and behavioural (breeding experiments) analyses were conducted to test the hypothesis that L. gregalis is a complex of two cryptic species. All of the applied methods distinguish the independent status of voles from south‐eastern Transbaikalia. This clade occupies a portion of the distribution range of the currently valid subspecies L. g. raddei including its terra typica. According to the results of cyt b analysis, the lectotype of L. g. raddei belongs to the Transbaikal clade. We re‐establish the species status for the taxon Lasiopodomys raddei including populations from south‐eastern Transbaikalia, as a cryptic species of the narrow‐headed vole complex.
Maximal expiratory pressure and Valsalva manoeuvre do not produce similar cardiovascular responses in healthy men
Authors: Minatel Vinicius , Takahashi Anielle C. M. , Perseguini Natália Maria , Milan Juliana Cristina , Castello‐Simões Viviane , Gomes Ellen C. , Borghi‐Silva Audrey , Catai Aparecida Maria
Published: March 2016

New Findings

What is the central question of this study?

This is the first study to evaluate and describe the cardiovascular responses during maximal expiratory pressure compared with the Valsalva manoeuvre, and whether those responses are similar.

What is the main finding and its importance?

This study showed that the duration of the manoeuvres appears to be responsible for the different physiological mechanisms involved in the cardiovascular responses to each manoeuvre and that the intensity of expiratory effort was related to the response in maximal expiratory pressure. These results are important to identify the risks to which subjects are exposed when performing these manoeuvres.

The main purpose of this study was to compare the cardiovascular responses between the Valsalva manoeuvre (VM) and maximal expiratory pressure (MEP) and to evaluate the effect of age on these responses. Twenty‐eight healthy men were evaluated and divided into two groups, younger (n = 15, 25 ± 5 years) and middle aged (n = 13, 50 ± 5 years), and they performed the VM and MEP measurement. The VM consisted of an expiratory effort (40 mmHg) against a manometer for 15 s, and the MEP was performed according to American Thoracic Society guidelines. The cardiovascular responses were analysed at rest, isotime (3 s), peak, nadir and recovery, and the cardiovascular variations (Δ) were calculated as peak or isotime minus resting values. For the statistical analysis, we used two‐way ANOVA (P < 0.05). We observed that MEP and the VM generate similar changes in cardiac output (P > 0.05), but MEP presents higher values for mean arterial pressure (MAPPeak, MAPIsotime, ΔMAP and ΔMAPIsotime) than those observed in the VM (P < 0.05). The execution time of the manoeuvres (VM ∼15 s and MEP ∼5 s) appears to be largely responsible for the activation of different physiological mechanisms involved in the cardiovascular control for each manoeuvre, and the intensity of expiratory effort is related to the higher response of MAP and peripheral vascular resistance (PVRIsotime and ΔPVRIsotime) during MEP (P < 0.05). Moreover, it appears that age affects only the heart rate and PVR responses (P < 0.05), which were higher in the young and middle‐aged group, respectively. Based on these findings, we can conclude that MEP and the VM do not generate similar cardiovascular responses, except for cardiac output.
‘Patient Zero’ no more
Authors: Cohen Jon
Published: March 2016

Sleuthing clarifies HIV's history.
Slow burn
Authors: Normile Dennis
Published: March 2016

Five years after the meltdowns at the Fukushima atomic plant, evacuees face the prospect of living near a nuclear disaster zone for decades to come.
Epidemic of fear
Authors: Normile Dennis
Published: March 2016

A bumper crop of thyroid abnormalities in Fukushima children, including cancer, has perplexed scientists and alarmed locals.
The brain’s functional network architecture reveals human motives
Authors: Hein Grit , Morishima Yosuke , Leiberg Susanne , Sul Sunhae , Fehr Ernst
Published: March 2016

Brain activity shows underlying motives

In humans, two completely different motives may nevertheless lead to exactly the same behavior. Because we can't directly observe motives, modern economists often completely disregard them. However, Hein
et al.
, using fMRI, show that different human motives can yield observable responses in the brain (see the Perspective by Gluth and Fontanesi). In empathy-based and reciprocity-based altruistic behavior, the direction and the strength of functional connectivity between specific brain regions were different for each motive. Moreover, the connectivity patterns were independent of the behavioral implications of the motives.

Science
, this issue p.
1074
; see also p.
1028
Expression homeostasis during DNA replication
Authors: Voichek Yoav , Bar-Ziv Raz , Barkai Naama
Published: March 2016

Doubling DNA but not expression

As the genome replicates, and before the cell divides, the copy number of the replicated portions of the genome doubles. In bacteria and archaea, gene expression tracks with gene dosage, both of which increase after DNA replication. Voichek
et al.
, however, show that an increase in DNA dosage after replication does not increase gene expression in budding yeast. This expression buffering is mediated by the acetylation of newly synthesized histone H3 deposited on the replicated DNA. This acetylation helps suppress transcription from the excess DNA.

Science
, this issue p.
1087
Cryo-EM structure of a native, fully glycosylated, cleaved HIV-1 envelope trimer
Authors: Lee Jeong Hyun , Ozorowski Gabriel , Ward Andrew B.
Published: March 2016

A more complete look at the HIV-1 envelope

HIV-1 uses its envelope protein (Env), a large glycoprotein present on the viral surface, to enter target cells. Env forms trimers on the viral surface. Structural studies of solubilized Env trimers have provided important insights into viral entry and antibody binding, but soluble trimers lack several important insoluble regions of the native protein. Lee
et al.
used cryo–electron microscopy to solve the structure of a trimeric Env protein of HIV-1, missing only its cytoplasmic tail, in complex with broadly neutralizing antibodies. A more complete understanding of Env's structure may aid in vaccine design ef orts.

Science
, this issue p.
1043
Activation of PKA leads to mesenchymal-to-epithelial transition and loss of tumor-initiating ability
Authors: Pattabiraman Diwakar R. , Bierie Brian , Kober Katharina Isabelle , Thiru Prathapan , Krall Jordan A. , Zill Christina , Reinhardt Ferenc , Tam Wai Leong , Weinberg Robert A.
Published: March 2016

Have cancer stem cells MET their match?

Solid tumors have been hypothesized to contain a subset of highly aggressive cells that fuel tumor growth and metastasis. The search is on for drugs that selectively kill or diminish the malignant properties of these tumor-initiating cells (TICs; previously called “cancer stem cells”). Pattabiraman
et al.
hypothesized that compounds that induce TICs to undergo a phenotypic change called the mesenchymal-to-epithelial transition (MET) would therefore cause TICs to lose their tumor-initiating ability. Indeed, drugs activating the protein kinase A signaling pathway triggered an epigenetic reprogramming of TICs that resulted in the cells acquiring a more benign epithelial-like phenotype.

Science
, this issue p.
10.1126/science.aad3680
Regulatory evolution of innate immunity through co-option of endogenous retroviruses
Authors: Chuong Edward B. , Elde Nels C. , Feschotte Cédric
Published: March 2016

Regulatory use of endogenous retroviruses

Mammalian genomes contain many endogenous retroviruses (ERVs), which have a range of evolutionary ages. The propagation and maintenance of these genetic elements have been attributed to their ability to contribute to gene regulation. Chuong
et al.
demonstrate that some ERV families are enriched in regulatory elements, so that they act as independently evolved enhancers for immune genes in both humans and mice (see the Perspective by Lynch). The analysis revealed a primate-specific element that orchestrates the transcriptional response to interferons. Selection can therefore act on selfish genetic elements to generate novel gene networks.

Science
, this issue p.
1083
see also p.
1029
Liberating field science samples and data
Authors: McNutt Marcia , Lehnert Kerstin , Hanson Brooks , Nosek Brian A. , Ellison Aaron M. , King John Leslie
Published: March 2016

Promote reproducibility by moving beyond “available upon request”
Comment on “Estimating the reproducibility of psychological science”
Authors: Gilbert Daniel T. , King Gary , Pettigrew Stephen , Wilson Timothy D.
Published: March 2016

A paper from the Open Science Collaboration (Research Articles, 28 August 2015, aac4716) attempting to replicate 100 published studies suggests that the reproducibility of psychological science is surprisingly low. We show that this article contains three statistical errors and provides no support for such a conclusion. Indeed, the data are consistent with the opposite conclusion, namely, that the reproducibility of psychological science is quite high.
The future of memory
When We Are No More How Digital Memory Is Shaping Our Future
Abby Smith Rumsey
Bloomsbury, 2016. 246 pp.
Authors: Anderson Clifford B.
Published: March 2016

A deluge of digital data threatens to destroy our collective identity
Selective conversion of syngas to light olefins
Authors: Jiao Feng , Li Jinjing , Pan Xiulian , Xiao Jianping , Li Haobo , Ma Hao , Wei Mingming , Pan Yang , Zhou Zhongyue , Li Mingrun , Miao Shu , Li Jian , Zhu Yifeng , Xiao Dong , He Ting , Yang Junhao , Qi Fei , Fu Qiang , Bao Xinhe
Published: March 2016

Small olefins from syngas

The conversion of coal or natural gas to liquid fuels or chemicals often proceeds through the production of CO and H
2
. This mixture, known as syngas, is then converted to hydrocarbons with Fischer-Tropsch catalysts. For the light olefins (ethylene to butylenes) needed for chemical and polymer synthesis, conventional catalysts are mechanistically limited to <60% conversion and deactivate through carbon buildup. Jiao
et al.
developed a bifunctional catalyst that achieves higher conversions and avoids deactivation (see the Perspective by de Jong). A zinc-chromium oxide creates ketene intermediates that are then coupled over a zeolite.

Science
, this issue p.
1065
, see also p.
1030
Risky business
Strange Glow The Story of Radiation
Timothy J. Jorgensen
Princeton University Press, 2016. 506 pp.
Authors: Creager Angela N.
Published: March 2016

Hard-won lessons shed light on the promise and perils of radiation and nuclear power
Investigation of Linezolid Resistance in Staphylococci and Enterococci
Authors: Doern Christopher D. , Park Jason Y. , Gallegos Michael , Alspaugh Debbie , Burnham Carey-Ann D.
Published: March 2016

The objective of this study was to investigate an apparent increase in linezolid-nonsusceptible staphylococci and enterococci following a laboratory change in antimicrobial susceptibility testing from disk diffusion to an automated susceptibility testing system. Isolates with nonsusceptible results (
n
= 27) from Vitek2 were subjected to a battery of confirmatory testing which included disk diffusion, Microscan broth microdilution, Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution, gradient diffusion (Etest), 23S rRNA gene sequencing, and
cfr
PCR. Our results show that there is poor correlation between methods and that only 70 to 75% of isolates were confirmed as linezolid resistant with alternative phenotypic testing methods (disk diffusion, Microscan broth microdilution, CLSI broth microdilution, and Etest). 23S rRNA gene sequencing identified mutations previously associated with linezolid resistance in 16 (59.3%) isolates, and the
cfr
gene was detected in 3 (11.1%) isolates. Mutations located at positions 2576 and 2534 of the 23S rRNA gene were most common. In addition, two previously undescribed variants (at positions 2083 and 2345 of the 23S rRNA gene) were also identified and may contribute to linezolid resistance.
Effects of Fecal Microbial Transplantation on Microbiome and Immunity in Simian Immunodeficiency Virus-Infected Macaques
Authors: Hensley-McBain Tiffany , Zevin Alexander S. , Manuzak Jennifer , Smith Elise , Gile Jillian , Miller Charlene , Agricola Brian , Katze Michael , Reeves R. Keith , Kraft Colleen S. , Langevin Stanley , Klatt Nichole R.
Published: March 2016

An altered intestinal microbiome during chronic human immunodeficiency virus (HIV) infection is associated with mucosal dysfunction, inflammation, and disease progression. We performed a preclinical evaluation of the safety and efficacy of fecal microbiota transplantation (FMT) as a potential therapeutic in HIV-infected individuals. Antiretroviral-treated, chronically simian immunodeficiency virus (SIV)-infected rhesus macaques received antibiotics followed by FMT. The greatest microbiota shift was observed after antibiotic treatment. The bacterial community composition at 2 weeks post-FMT resembled the pre-FMT community structure, although differences in the abundances of minor bacterial populations remained. Immunologically, we observed significant increases in the number of peripheral Th17 and Th22 cells and reduced CD4+T cell activation in gastrointestinal tissues post-FMT. Importantly, the transplant was well tolerated with no negative clinical side effects. Although this pilot study did not control for the differential contributions of antibiotic treatment and FMT to the observed results, the data suggest that FMT may have beneficial effects that should be further evaluated in larger studies.

IMPORTANCEDue to the immunodeficiency and chronic inflammation that occurs during HIV infection, determination of the safety of FMT is crucial to prevent deleterious consequences if it is to be used as a treatment in the future. Here we used the macaque model of HIV infection and performed FMT on six chronically SIV-infected rhesus macaques on antiretroviral treatment. In addition to providing a preclinical demonstration of the safety of FMT in primates infected with a lentivirus, this study provided a unique opportunity to examine the relationships between alterations to the microbiome and immunological parameters. In this study, we found increased numbers of Th17 and Th22 cells as well as decreased activation of CD4+T cells post-FMT, and these changes correlated most strongly across all sampling time points with lower-abundance taxonomic groups and other taxonomic groups in the colon. Overall, these data provide evidence that changes in the microbiome, particularly in terms of diversity and changes in minor populations, can enhance immunity and do not have adverse consequences.
Novel Role for Protein Inhibitor of Activated STAT 4 (PIAS4) in the Restriction of Herpes Simplex Virus 1 by the Cellular Intrinsic Antiviral Immune Response
Authors: Conn Kristen L. , Wasson Peter , McFarlane Steven , Tong Lily , Brown James R. , Grant Kyle G. , Domingues Patricia , Boutell Chris
Published: March 2016

S
mall
u
biquitin-like
mo
difier (SUMO) is used by the intrinsic antiviral immune response to restrict viral pathogens, such as herpes simplex virus 1 (HSV-1). Despite characterization of the host factors that rely on SUMOylation to exert their antiviral effects, the enzymes that mediate these SUMOylation events remain to be defined. We show that unconjugated SUMO levels are largely maintained throughout infection regardless of the presence of ICP0, the HSV-1 SUMO-targeted ubiquitin ligase. Moreover, in the absence of ICP0, high-molecular-weight SUMO-conjugated proteins do not accumulate if HSV-1 DNA does not replicate. These data highlight the continued importance for SUMO signaling throughout infection. We show that the SUMO ligase protein inhibitor of activated STAT 4 (PIAS4) is upregulated during HSV-1 infection and localizes to nuclear domains that contain viral DNA. PIAS4 is recruited to sites associated with HSV-1 genome entry through SUMO interaction motif (SIM)-dependent mechanisms that are destabilized by ICP0. In contrast, PIAS4 accumulates in replication compartments through SIM-independent mechanisms irrespective of ICP0 expression. Depletion of PIAS4 enhances the replication of ICP0-null mutant HSV-1, which is susceptible to restriction by the intrinsic antiviral immune response. The mechanisms of PIAS4-mediated restriction are synergistic with the restriction mechanisms of a characterized intrinsic antiviral factor, promyelocytic leukemia protein, and are antagonized by ICP0. We provide the first evidence that PIAS4 is an intrinsic antiviral factor. This novel role for PIAS4 in intrinsic antiviral immunity contrasts with the known roles of PIAS proteins as suppressors of innate immunity.

IMPORTANCE
Posttranslational modifications with
s
mall
u
biquitin-like
mo
difier (SUMO) proteins regulate multiple aspects of host immunity and viral replication. The
p
rotein
i
nhibitor of
a
ctivated
S
TAT (PIAS) family of SUMO ligases is predominantly associated with the suppression of innate immune signaling. We now identify a unique and contrasting role for PIAS proteins as positive regulators of the intrinsic antiviral immune response to herpes simplex virus 1 (HSV-1) infection. We show that PIAS4 relocalizes to nuclear domains that contain viral DNA throughout infection. Depletion of PIAS4, either alone or in combination with the intrinsic antiviral factor promyelocytic leukemia protein, significantly impairs the intrinsic antiviral immune response to HSV-1 infection. Our data reveal a novel and dynamic role for PIAS4 in the cellular-mediated restriction of herpesviruses and establish a new functional role for the PIAS family of SUMO ligases in the intrinsic antiviral immune response to DNA virus infection.
The RNA Helicase eIF4A Is Required for Sapovirus Translation
Authors: Hosmillo Myra , Sweeney Trevor R. , Chaudhry Yasmin , Leen Eoin , Curry Stephen , Goodfellow Ian , Cho Kyoung-Oh
Published: March 2016

The eukaryotic initiation factor 4A (eIF4A) is a DEAD box helicase that unwinds RNA structure in the 5′ untranslated region (UTR) of mRNAs. Here, we investigated the role of eIF4A in porcine sapovirus VPg-dependent translation. Using inhibitors and dominant-negative mutants, we found that eIF4A is required for viral translation and infectivity, suggesting that despite the presence of a very short 5′ UTR, eIF4A is required to unwind RNA structure in the sapovirus genome to facilitate virus translation.
Dynamic Phosphorylation of VP30 Is Essential for Ebola Virus Life Cycle
Authors: Biedenkopf Nadine , Lier Clemens , Becker Stephan
Published: March 2016

Ebola virus is the causative agent of a severe fever with high fatality rates in humans and nonhuman primates. The regulation of Ebola virus transcription and replication currently is not well understood. An important factor regulating viral transcription is VP30, an Ebola virus-specific transcription factor associated with the viral nucleocapsid. Previous studies revealed that the phosphorylation status of VP30 impacts viral transcription. Together with NP, L, and the polymerase cofactor VP35, nonphosphorylated VP30 supports viral transcription. Upon VP30 phosphorylation, viral transcription ceases. Phosphorylation weakens the interaction between VP30 and the polymerase cofactor VP35 and/or the viral RNA. VP30 thereby is excluded from the viral transcription complex, simultaneously leading to increased viral replication which is supported by NP, L, and VP35 alone. Here, we use an infectious virus-like particle assay and recombinant viruses to show that the dynamic phosphorylation of VP30 is critical for the cotransport of VP30 with nucleocapsids to the sites of viral RNA synthesis, where VP30 is required to initiate primary viral transcription. We further demonstrate that a single serine residue at amino acid position 29 was sufficient to render VP30 active in primary transcription and to generate a recombinant virus with characteristics comparable to those of wild-type virus. In contrast, the rescue of a recombinant virus with a single serine at position 30 in VP30 was unsuccessful. Our results indicate critical roles for phosphorylated and dephosphorylated VP30 during the viral life cycle.

IMPORTANCE
The current Ebola virus outbreak in West Africa has caused more than 28,000 cases and 11,000 fatalities. Very little is known regarding the molecular mechanisms of how the Ebola virus transcribes and replicates its genome. Previous investigations showed that the transcriptional support activity of VP30 is activated upon VP30 dephosphorylation. The current study reveals that the situation is more complex and that primary transcription as well as the rescue of recombinant Ebola virus also requires the transient phosphorylation of VP30. VP30 encodes six N-proximal serine residues that serve as phosphorylation acceptor sites. The present study shows that the dynamic phosphorylation of serine at position 29 alone is sufficient to activate primary viral transcription. Our results indicate a series of phosphorylation/dephosphorylation events that trigger binding to and release from the nucleocapsid and transcription complex to be essential for the full activity of VP30.