bluuebunny/crossref_metadata_2025 huggingface dataset:
Adoptability and effectiveness of livestock emission reduction techniques in Australia’s temperate high-rainfall zone
Authors: James Adrian R. , Harrison Matthew T.
Published: February 2016

Significant research has been conducted on greenhouse gas emissions mitigation techniques for ruminant livestock farming, however putting these techniques into practice on-farm requires consideration of adoptability by livestock producers. We modelled the adoptability of a range of livestock greenhouse gas abatement techniques using data from farm case studies and industry surveys, then compared the effectiveness of several techniques in reducing emissions intensity and net farm emissions. The influence of the Australian Government Emissions Reduction Fund on adoptability was included by modelling techniques with and without the requirements of an Australian Government Emissions Reduction Fund project. Modelled adoption results were compared with data obtained from surveys of livestock farmers in northern Tasmania, Australia. Maximum adoption levels of the greenhouse gas mitigation techniques ranged from 34% to 95% and the time required to reach 90% of the peak adoption levels ranged from 3.9 to 14.9 years. Techniques with the lowest adoption levels included providing supplements to optimise rumen energy : protein ratio and feeding high-lipid diets. Techniques with the highest adoptability involved improved ewe reproductive efficiency, with more fertile flocks having higher adoption rates. Increasing liveweight gain of young stock so animals reached slaughter liveweight 5–7 weeks earlier (early finishing) and joining maiden ewes at 8 months instead of 18 months had the fastest adoption rates. Techniques which increased net emissions and reduced emissions per liveweight sold (emissions intensity) had higher adoptability due to profit advantages associated with greater meat and wool production, whereas some techniques that reduced both net emissions and emissions intensity had lower adoptability and/or longer delays before peak adoption because of complexity and costs associated with implementation, or lack of extension information. Techniques that included an Australian Government Emissions Reduction Fund project had reduced maximum adoption levels and reduced rate of adoption due to difficulty of implementation and higher cost. Adopting pastures with condensed tannins reduced net emissions, emissions intensity and had high adoption potential, but had a long delay before peak adoption levels were attained, suggesting the technique may be worthy of increased development and extension investment. These results will be of benefit to livestock farmers, policymakers and extension practitioners. Programs designed to mitigate livestock greenhouse gas should consider potential adoption rates by agricultural producers and time of implementation before embarking on new research themes.
Quantifying effects of grassland management on enteric methane emission
Authors: Bannink A. , Warner D. , Hatew B. , Ellis J. L. , Dijkstra J.
Published: February 2016

Data on the effect of grassland management on the nutritional characteristics of fresh and conserved grass, and on enteric methane (CH4) emission in dairy cattle, are sparse. In the present study, an extant mechanistic model of enteric fermentation was evaluated against observations on the effect of grassland management on CH4 emission in three trials conducted in climate-controlled respiration chambers. Treatments were nitrogen fertilisation rate, stage of maturity of grass and level of feed intake, and mean data of a total of 18 treatments were used (4 grass herbage treatments and 14 grass silage treatments). There was a wide range of observed organic matter (OM) digestibility (from 68% to 84%) and CH4 emission intensity (from 5.6% to 7.3% of gross energy intake; from 27.4 to 36.9 g CH4/kg digested OM; from 19.7 to 24.6 g CH4/kg dry matter) among treatment means. The model predicted crude protein, fibre and OM digestibility with reasonable accuracy (root of mean square prediction errors as % of observed mean, RMSPE, 6.8%, 7.5% and 3.9%, respectively). For grass silages only, the model-predicted CH4 correlated well (Pearson correlation coefficient 0.73) with the observed CH4 (which varied from 5.7% to 7.2% of gross energy intake), after predicted CH4 was corrected for nitrate consumed with grass silage, acting as hydrogen sink in the rumen. After nitrate correction, there was a systematic under-prediction of 18%, which reduced to 9% when correcting the erroneously predicted rumen volatile fatty acid (VFA) profile (RMSPE 15%). Although a small over-prediction of 3% was obtained for the grass herbages, this increased to 14% when correcting VFA profile. The model predictions showed a systematic difference in CH4 emission from grass herbages and grass silages, which was not supported by the observed data. This is possibly related to the very high content of soluble carbohydrates in grass herbage (an extra 170 g/kg dry matter compared with grass silages) and an erroneous prediction of its fate and contribution to CH4 in the rumen. Erroneous prediction of the VFA profile is likely to be due to different types of diets included in the empirical database used to parameterise VFA yield in the model from those evaluated here. Model representations of feed digestion and VFA profile are key elements to predict enteric CH4 accurately, and with further evaluations, the latter aspect should be emphasised in particular.
Efficacy of methane-reducing supplements in beef cattle rations
Authors: Caetano M. , Wilkes M. J. , Pitchford W. S. , Lee S. J. , Hynd P. I.
Published: February 2016

The objective of the present study was to evaluate the effect of including a pellet containing feed components targeted at methane-producing microbes and methane-producing biochemical pathways, into the ration of beef cattle in southern Australia. The so-called ‘methane-reducing supplement’ (MRS) components were chosen from readily available and inexpensive sources to ensure high adoption of the practice if successful. The effect of the pellet on animal performance, diet DM digestibility and gas emissions (measured using an open-circuit gas quantification system) of beef cattle in comparison with animals fed a control diet or high-quality supplement (HQS) was evaluated. In the first trial, there were no differences in DM and digestible energy (DE) intake, but the methane emission in g/day, g/MJ of DE intake (P < 0.01), and in g/kg of DM intake (P = 0.01) were lower for steers fed MRS. There was also a trend to lower carbon dioxide emission (g/MJ of DE intake) in steers fed MRS (P = 0.07). In the second trial, heifers fed the MRS produced 18.7% less carbon dioxide (P < 0.01) and 15.5% less methane (P = 0.01) than heifers on the HQS supplement, when expressed in g per unit supplement intake on a bodyweight basis. There was no difference in growth rate of heifers on the HQS and MRS supplements. Combining methane-inhibiting feedstuffs derived from agro-industrial by-products into supplements for cattle in southern Australia appears to be an effective means of reducing methane output and methane intensity from grazing beef cattle.
The GreenFeed system for measurement of enteric methane emission from cattle
Authors: Hammond K. J. , Waghorn G. C. , Hegarty R. S.
Published: February 2016

Methane measurements from cattle would benefit from an improved capability to measure a larger number of animals, with a lower requirement for specialist technical knowledge, and minimal human interference. The GreenFeed (GF) system (C-Lock Inc., Rapid City, SD, USA) estimates daily methane production (DMP, g/day) by measuring gas concentrations and airflow over 3–7 min from cattle when they visit a GF unit. Although few data are collected per animal per day, over many days of GF visitation estimates of DMP can be established. Published GF estimates of DMP are in agreement with DMP measured by respiration chambers, but there are inconsistencies in comparisons based on estimates using the sulfur hexafluoride tracer method. Circadian patterns of methane emission from cattle suggest spot-sampling of emissions by GF should be distributed over 24 h, or weighted to avoid bias associated with clustering of GF visits at specific times. Up to half of cattle grazing temperate pastures choose not to use GF on a daily basis, so consideration must be given to the number of animals and duration of sampling as well as the proportion and representation of animals using GF for estimating DMP, especially for ranking individuals. All systems for determining DMP from animals constrain the data in some way, and the suitability of the GF system will be affected by the experimental objectives and design. For example, compared with the respiration chamber and sulfur hexafluoride tracer techniques, it takes more time and animals to undertake a treatment comparison of DMP using GF due to higher within-day and within-animal variance, especially if some avoid GF or do not visit each day.
Home range and activity patterns measured with GPS collars in spotted-tailed quolls
Authors: Körtner Gerhard , Holznagel Nerida , Fleming Peter J. S. , Ballard Guy
Published: February 2016

The spotted-tailed quoll (Dasyurus maculatus) is the largest marsupial carnivore on mainland Australia. It usually occurs at relatively low population densities and its cryptic nature makes it exceedingly difficult to observe in its natural habitat. On the mainland the species is also listed as nationally endangered and more information is needed to direct any meaningful conservation effort. In this study we aimed to elucidate quolls’ spatial requirements and activity patterns using GPS collars on 10 males and 4 females. Quolls were predominantly nocturnal but some individuals showed pronounced daytime activity. There was no apparent seasonal shift in the timing of activity. The movement of quolls appeared to be confined to home ranges that were relatively large for predators of their size. Furthermore, males used home ranges about three times as large as that of the smaller females. There appeared to be some spatial segregation between not only females, which have been considered territorial, but also males. Overall, it is likely that the larger areas used by males is partly caused by the sexual dimorphism in body mass that entails differences in prey requirements and spectrum, but probably is also a function of a promiscuous mating system. All of these could explain the observed more unidirectional movement and larger distances travelled per day by males.
Crystallography captures catalytic steps in human methionine adenosyltransferase enzymes
Authors: Murray Ben , Antonyuk Svetlana V. , Marina Alberto , Lu Shelly C. , Mato Jose M. , Hasnain S. Samar , Rojas Adriana L.
Published: February 2016

Significance

X-ray crystallography provides a structural basis for enzyme mechanisms by elucidating information about the chemical reaction occurring within the active site. Crystallographic structures can also aid in rational drug design. A highly conserved family of methionine adenosyltranferases (MATs) produces S-adenosylmethionine (SAMe) via an ATP-driven process. Dysregulation of MAT enzymes has been tightly linked to liver and colon cancer. Here we present crystal structures of human MATα2 proteins containing different ligands within the active site, allowing for a step change in our understanding of how this enzyme uses its substrates, methionine and adenosine, to produce the product SAMe.
Cortical response to categorical color perception in infants investigated by near-infrared spectroscopy
Authors: Yang Jiale , Kanazawa So , Yamaguchi Masami K. , Kuriki Ichiro
Published: February 2016

Significance

There has been much debate on the Sapir–Wharf hypothesis regarding whether language affects our perceptual world. Despite much research on this topic, there remains no clear consensus on whether and how language affects categorical color perception. Here, we provide the first evidence, to our knowledge, that categorical color perception has a universal starting point prior to language acquisition. We measured the neural correlates of categorical color perception in prelinguistic infants. We found increased brain activities to colors in different categories, but not to colors in the same category. These results indicated that different color categories are differently represented in the visual cortex of prelinguistic infants, which implies that color categories may develop in the visual system before language acquisition.
Do geographically isolated wetlands influence landscape functions?
Authors: Cohen Matthew J. , Creed Irena F. , Alexander Laurie , Basu Nandita B. , Calhoun Aram J. K. , Craft Christopher , D’Amico Ellen , DeKeyser Edward , Fowler Laurie , Golden Heather E. , Jawitz James W. , Kalla Peter , Kirkman L. Katherine , Lane Charles R. , Lang Megan , Leibowitz Scott G. , Lewis David Bruce , Marton John , McLaughlin Daniel L. , Mushet David M. , Raanan-Kiperwas Hadas , Rains Mark C. , Smith Lora , Walls Susan C.
Published: February 2016

Geographically isolated wetlands (GIWs), those surrounded by uplands, exchange materials, energy, and organisms with other elements in hydrological and habitat networks, contributing to landscape functions, such as flow generation, nutrient and sediment retention, and biodiversity support. GIWs constitute most of the wetlands in many North American landscapes, provide a disproportionately large fraction of wetland edges where many functions are enhanced, and form complexes with other water bodies to create spatial and temporal heterogeneity in the timing, flow paths, and magnitude of network connectivity. These attributes signal a critical role for GIWs in sustaining a portfolio of landscape functions, but legal protections remain weak despite preferential loss from many landscapes. GIWs lack persistent surface water connections, but this condition does not imply the absence of hydrological, biogeochemical, and biological exchanges with nearby and downstream waters. Although hydrological and biogeochemical connectivity is often episodic or slow (e.g., via groundwater), hydrologic continuity and limited evaporative solute enrichment suggest both flow generation and solute and sediment retention. Similarly, whereas biological connectivity usually requires overland dispersal, numerous organisms, including many rare or threatened species, use both GIWs and downstream waters at different times or life stages, suggesting that GIWs are critical elements of landscape habitat mosaics. Indeed, weaker hydrologic connectivity with downstream waters and constrained biological connectivity with other landscape elements are precisely what enhances some GIW functions and enables others. Based on analysis of wetland geography and synthesis of wetland functions, we argue that sustaining landscape functions requires conserving the entire continuum of wetland connectivity, including GIWs.
High expression levels of macrophage migration inhibitory factor sustain the innate immune responses of neonates
Authors: Roger Thierry , Schneider Anina , Weier Manuela , Sweep Fred C. G. J. , Le Roy Didier , Bernhagen Jürgen , Calandra Thierry , Giannoni Eric
Published: February 2016

Significance

During pregnancy, high circulating levels of adenosine and prostaglandins reduce the ability of fetal immune cells to mount powerful proinflammatory responses. In contrast, newborns express 10-fold higher levels of the proinflammatory immune regulator migration inhibitory factor (MIF) compared with adults. MIF sustains cell activation and cytokine production and counterregulates adenosine and prostaglandin E2-mediated immunosuppression in newborn monocytes. Yet excessive MIF expression during an established infection worsens the outcome of newborn mice. Thus, we identify a unique role for MIF in regulating neonatal innate immune responses and propose that MIF has a protective role to reduce susceptibility to infection during the neonatal period but may favor uncontrolled inflammation during sepsis, leading to adverse outcomes.
Exceptionally strong easterly wind burst stalling El Niño of 2014
Authors: Hu Shineng , Fedorov Alexey V.
Published: February 2016

Significance

The El Niño–Southern Oscillation is the dominant mode of climate variability in the tropical Pacific, with pronounced global teleconnections. Predicting El Niño and understanding its progression still present a challenge to climate scientists. At the beginning of 2014, many in the scientific community anticipated that a strong El Niño could potentially develop by year end, but the observed warm event barely reached the El Niño threshold. Here, we analyze satellite-based data and numerical simulations to show that an intense easterly wind burst that occurred in June of 2014 was the key dynamical factor that stalled the El Niño development. We discuss our findings in the context of limited El Niño predictability and explore links between intraseasonal wind bursts and decadal climate change.
Brain shape convergence in the adaptive radiation of New World monkeys
Authors: Aristide Leandro , dos Reis Sergio Furtado , Machado Alessandra C. , Lima Inaya , Lopes Ricardo T. , Perez S. Ivan
Published: February 2016

Significance

The evolutionary diversification of brain morphology is one of the most prominent features of the primate adaptive radiation and a likely determinant of primate evolutionary success. However, the ecological factors responsible for the diversification of the primate brain are largely unknown. In this work, we use a comparative approach to study brain diversification during the adaptive radiation of a major primate clade—the New World monkeys. We show that brain morphology evolved in association with the occupation of several ecological niches, and that convergence in brain morphology among clades may be associated with an evolutionary increase in the complexity of social behaviors.
Circadian misalignment increases cardiovascular disease risk factors in humans
Authors: Morris Christopher J. , Purvis Taylor E. , Hu Kun , Scheer Frank A. J. L.
Published: February 2016

Significance

Shift work is a risk factor for hypertension, inflammation, and cardiovascular disease, even after controlling for traditional risk factors. Shift workers frequently undergo circadian misalignment (i.e., misalignment between the endogenous circadian system and 24-h environmental/behavioral cycles). This misalignment has been proposed to explain, in part, why shift work is a risk factor for hypertension, inflammation, and cardiovascular disease. However, the impact of circadian misalignment per se on 24-h blood pressure and inflammatory markers is poorly understood. We show—under highly controlled laboratory conditions—that short-term circadian misalignment increases 24-h blood pressure and inflammatory markers in healthy adults. Our findings may help explain why shift work increases hypertension, inflammation, and cardiovascular disease risk.
Seasonality in human cognitive brain responses
Authors: Meyer Christelle , Muto Vincenzo , Jaspar Mathieu , Kussé Caroline , Lambot Erik , Chellappa Sarah L. , Degueldre Christian , Balteau Evelyne , Luxen André , Middleton Benita , Archer Simon N. , Collette Fabienne , Dijk Derk-Jan , Phillips Christophe , Maquet Pierre , Vandewalle Gilles
Published: February 2016

Significance

Evidence for seasonality in humans is limited. Mood probably stands as the aspect of human brain function most acknowledged as being affected by season. Yet, the present study provides compelling evidence for previously unappreciated annual variations in the cerebral activity required to sustain ongoing cognitive processes in healthy volunteers. The data further show that this annual rhythmicity is cognitive-process-specific (i.e., the phase of the rhythm changes between cognitive tasks), speaking for a complex impact of season on human brain function. Annual variations in cognitive brain function may contribute to explain intraindividual cognitive changes that could emerge at specific times of year.
Respiratory virus transmission dynamics determine timing of asthma exacerbation peaks: Evidence from a population-level model
Authors: Eggo Rosalind M. , Scott James G. , Galvani Alison P. , Meyers Lauren Ancel
Published: February 2016

Significance

Asthma exacerbations are frequently triggered by common cold infections. Whereas prior studies have swabbed individual patients to detect viruses, we take a population level approach to investigate common cold circulation and its consequences for asthmatics. We introduce a dynamic model of common cold transmission with different contact patterns for adults and children, which are modified by school vacations. By jointly fitting this and an asthma risk model to daily hospitalization rates in eight large cities in Texas, we found that the common cold is a primary driver of asthma exacerbations, and both are predictably influenced by the school calendar. This provides actionable insight for assessing asthma hospitalization risk and targeting preventive measures.
Vasopressin increases human risky cooperative behavior
Authors: Brunnlieb Claudia , Nave Gideon , Camerer Colin F. , Schosser Stephan , Vogt Bodo , Münte Thomas F. , Heldmann Marcus
Published: February 2016

Significance

Most forms of cooperative behavior take place in a mutually beneficial context where cooperation is risky as its success depends on unknown actions of others. In two pharmacological experiments, we show that intranasal administration of arginine vasopressin (AVP), a hormone that regulates mammalian social behaviors such as monogamy and aggression, increases humans’ tendency to engage in mutually beneficial cooperation. Several control tasks ruled out that AVP’s effects were driven by increased willingness to bare risks in the absence of social context, beliefs about the actions of one’s partner, or altruistic concerns. Our findings provide novel causal evidence for a biological factor underlying cooperation and are in accord with previous findings that cooperation is intrinsically rewarding for humans.
Positive-strand RNA viruses stimulate host phosphatidylcholine synthesis at viral replication sites
Authors: Zhang Jiantao , Zhang Zhenlu , Chukkapalli Vineela , Nchoutmboube Jules A. , Li Jianhui , Randall Glenn , Belov George A. , Wang Xiaofeng
Published: February 2016

Significance

Positive-strand RNA viruses [(+)RNA viruses] include many important human, animal, and plant pathogens. A highly conserved and indispensable feature of (+)RNA virus infection is that these viruses proliferate and reorganize host membranes to assemble viral replication complexes (VRCs). We show that brome mosaic virus (BMV) stimulates phosphatidylcholine (PC) synthesis at the viral replication sites. BMV recruits a host enzyme involved in PC synthesis to support proper VRC formation and genomic replication. We further show that hepatitis C virus and poliovirus also promote accumulation of PC at the viral replication sites, revealing a feature common to a group of (+)RNA viruses. This virus-specific step can be targeted to develop a broad-spectrum antiviral strategy with the least side effects on host growth.
Microstructure provides insights into evolutionary design and resilience of
Coscinodiscus
sp. frustule
Authors: Aitken Zachary H. , Luo Shi , Reynolds Stephanie N. , Thaulow Christian , Greer Julia R.
Published: February 2016

Significance

Diatoms are unicellular algae that form an intricate silica cell wall. A protective shell that is light enough to prevent sinking while simultaneously offering strength against predators is of interest to the design of lightweight structural materials. Using three-point bending experiments, we show that the diatom shell has the highest specific strength of all previously reported biological materials. Fracture analysis and finite element simulations also suggest functional differentiation between the shell layers and features to mitigate fracture. These results demonstrate the natural development of architecture in live organisms to simultaneously achieve light weight, strength, and structural integrity and may provide insight into evolutionary design.
Pliocene reversal of late Neogene aridification
Authors: Sniderman J. M. Kale , Woodhead Jon D. , Hellstrom John , Jordan Gregory J. , Drysdale Russell N. , Tyler Jonathan J. , Porch Nicholas
Published: February 2016

Significance

The warm climates of the Pliocene epoch are considered our best analog for a future anthropogenic greenhouse world. However, understanding of the nature of Pliocene climate variability and change on land is currently limited by the poor age control of most existing terrestrial climate archives. We present a radiometrically dated history of the evolution of Southern Hemisphere vegetation and hydroclimate from the latest Miocene to the middle Pliocene. These data reveal a sharp increase in precipitation in the Early Pliocene, which drove complete vegetation turnover. The development of warm, wet early Pliocene climates clearly reversed a long-term Southern Hemisphere trend of late Neogene cooling and aridification, highlighting the question of what initiated this sustained, ∼1.5-My-long interval of warmth.
Endocytosis separates EGF receptors from endogenous fluorescently labeled HRas and diminishes receptor signaling to MAP kinases in endosomes
Authors: Pinilla-Macua Itziar , Watkins Simon C. , Sorkin Alexander
Published: February 2016

Significance

How endocytosis regulates intracellular signaling is a major unsolved question. In this study, we labeled Ras, which plays a central role in normal and oncogenic signaling, with the fluorescent protein by gene editing, and for the first time (to our knowledge) examined the localization of endogenous Ras in living cells stimulated with epidermal growth factor (EGF). Microscopy imaging of living cells demonstrated that, although activated EGF receptors are rapidly internalized into endosomes, Ras is not present in these endosomes and mainly located in the plasma membrane. Therefore, EGF receptors signal to MAP kinases through Ras exclusively from the plasma membrane.
Visualizing the origins of selfish de novo mutations in individual seminiferous tubules of human testes
Authors: Maher Geoffrey J. , McGowan Simon J. , Giannoulatou Eleni , Verrill Clare , Goriely Anne , Wilkie Andrew O. M.
Published: February 2016

Significance

A major goal in genetics is to understand the processes that shape the frequency of new mutations, particularly those causing human disease. Here, we focus on specific mutations in the male germline that, although initially rare, confer a growth or survival advantage to the stem cell, leading to clonal expansion over time: a process similar to early tumor growth and currently described only in humans. Previous studies supporting this “selfish” selection quantified mutations in sperm or testis pieces using methods that destroyed their cellular origins. Here, we pinpoint and identify pathogenic mutations directly within individual seminiferous tubules, the structures that generate spermatozoa. This methodology provides unprecedented precision in documenting the spectrum and prevalence of selfish mutations in men’s testes.
Sleep deprivation and false confessions
Authors: Frenda Steven J. , Berkowitz Shari R. , Loftus Elizabeth F. , Fenn Kimberly M.
Published: February 2016

Significance

False confessions occur surprisingly frequently in the context of interrogations and criminal investigations. Indeed, false confessions are thought to account for approximately 15–25% of wrongful convictions in the United States. Here we demonstrate that sleep deprivation increases the likelihood that a person will falsely confess to wrongdoing that never occurred. Furthermore, our data suggest that it may be possible to identify certain individuals who are especially likely to falsely confess while sleep deprived. The present research is a crucial step toward understanding the role of sleep deprivation in the problem of false confession and, in turn, raises complex questions about the use of sleep deprivation in the interrogation of innocent and guilty suspects.
Slow dissolving of emotional distress contributes to hyperarousal
Authors: Wassing Rick , Benjamins Jeroen S. , Dekker Kim , Moens Sarah , Spiegelhalder Kai , Feige Bernd , Riemann Dieter , van der Sluis Sophie , Van Der Werf Ysbrand D. , Talamini Lucia M. , Walker Matthew P. , Schalkwijk Frans , Van Someren Eus J. W.
Published: February 2016

Significance

Decades of research into the cause of chronic insomnia have identified hyperarousal as the key factor, but mechanisms underlying hyperarousal have remained elusive. The present findings suggest that hyperarousal can result from an inadequate resolution of emotional distress, which, in turn, is likely due to restless rapid-eye-movement sleep.
Clonally expanded CD4
+
T cells can produce infectious HIV-1 in vivo
Authors: Simonetti Francesco R. , Sobolewski Michele D. , Fyne Elizabeth , Shao Wei , Spindler Jonathan , Hattori Junko , Anderson Elizabeth M. , Watters Sarah A. , Hill Shawn , Wu Xiaolin , Wells David , Su Li , Luke Brian T. , Halvas Elias K. , Besson Guillaume , Penrose Kerri J. , Yang Zhiming , Kwan Richard W. , Van Waes Carter , Uldrick Thomas , Citrin Deborah E. , Kovacs Joseph , Polis Michael A. , Rehm Catherine A. , Gorelick Robert , Piatak Michael , Keele Brandon F. , Kearney Mary F. , Coffin John M. , Hughes Stephen H. , Mellors John W. , Maldarelli Frank
Published: February 2016

Significance

Reservoirs of HIV-infected cells persist during antiretroviral therapy, and understanding persistence is essential to develop HIV curative strategies. During replication, HIV integrates into the host genome; most proviruses are not infectious, but some with replication-competent HIV persist. Cells with integrated HIV can proliferate, potentially expanding the reservoir, but whether cells with replication-competent HIV actually undergo expansion is unknown. HIV reactivation is often lethal to infected cells, and others have reported finding no replication-competent HIV in expanded populations. We describe a highly expanded clone containing infectious HIV that was the source of viremia for years in a patient. Clonally expanded populations can represent a long-lived reservoir of HIV. Curative strategies will require targeting this persistence mechanism.
Variable priming of a docked synaptic vesicle
Authors: Jung Jae Hoon , Szule Joseph A. , Marshall Robert M. , McMahan Uel J.
Published: February 2016

Significance

After synaptic vesicles dock at an active zone on the presynaptic plasma membrane of axon terminals, the vesicles become primed for fusion with the membrane, an essential step in synaptic impulse transmission. We used electron tomography to examine nanometer-scale variations in structural relationships of docked vesicles at the simply arranged active zones of frog neuromuscular junctions. The results, together with prior biochemical and electrophysiological concepts, lead to the hypothesis that priming is regulated by variation in force generated by the shortening and lengthening of macromolecules in the common active zone organelle “active zone material” that links docked vesicles to presynaptic membrane components. Knowledge of mechanisms that regulate synaptic transmission is required for understanding how different synapses accomplish their specialized tasks.
A critical role for alternative polyadenylation factor CPSF6 in targeting HIV-1 integration to transcriptionally active chromatin
Authors: Sowd Gregory A. , Serrao Erik , Wang Hao , Wang Weifeng , Fadel Hind J. , Poeschla Eric M. , Engelman Alan N.
Published: February 2016

Significance

HIV-1 requires integration for efficient gene expression, and the local chromatin environment significantly influences the level of HIV-1 transcription. Silent, integrated proviruses constitute the latent HIV reservoir. As HIV-1 commandeers cellular factors to dictate its preferred integration sites, these interactions consequentially influence latency. We examined the impact of polyadenylation specificity factor CPSF6, which binds HIV-1 capsid, and the integrase-binding chromatin reader LEDGF/p75 on viral infection and integration site distribution. Integration sites were determined in cells knocked down or knocked out for one or both host factors. Our data indicate that CPSF6 directs HIV-1 to transcriptionally active chromatin, where LEDGF/p75 predominantly directs the positions of integration within genes. These findings clarify the roles of cellular forces that dictate HIV-1 integration preferences and hence virus pathogenesis.
Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting
Authors: Ma Xuanyi , Qu Xin , Zhu Wei , Li Yi-Shuan , Yuan Suli , Zhang Hong , Liu Justin , Wang Pengrui , Lai Cheuk Sun Edwin , Zanella Fabian , Feng Gen-Sheng , Sheikh Farah , Chien Shu , Chen Shaochen
Published: February 2016

Significance

The great challenge to developing an in vitro liver model lies in the limitation of current approaches to recapitulate the sophisticated liver microenvironment contributed by the complex microarchitecture and diverse cell combination. We demonstrate an innovative advancement toward simulating natural complexity by integrating a rapid 3D bioprinting technology with tissue engineering to develop a microscale hepatic construct consisting of physiologically relevant hexagonal units of liver cells and supporting cells. The entire construct is fabricated within several seconds on minimal UV illumination. The model enables the structural and functional improvements of human induced pluripotent stem cell-derived hepatic progenitor cells and therefore can be used in early personalized drug screening and liver pathophysiology studies in vitro.
Translation quality control is critical for bacterial responses to amino acid stress
Authors: Bullwinkle Tammy J. , Ibba Michael
Published: February 2016

Significance

Recent studies showing that both high-accuracy protein synthesis and low-accuracy protein synthesis are critical for cellular growth and survival under different growth conditions suggest that the translation quality-control machinery may function in cellular processes other than protein synthesis. We explored this possibility and found that inhibition of misacylated-tRNA quality control suppressed the synthesis of the starvation-inducible second messenger guanosine tetraphosphate and limited the induction of stringent response-dependent gene expression. These findings show that translation quality control is a single checkpoint for both accurate protein synthesis and transcriptional responses to stress.
Ribosome Protein L4 is essential for Epstein–Barr Virus Nuclear Antigen 1 function
Authors: Shen Chih-Lung , Liu Cheng-Der , You Ren-In , Ching Yung-Hao , Liang Jun , Ke Liangru , Chen Ya-Lin , Chen Hong-Chi , Hsu Hao-Jen , Liou Je-Wen , Kieff Elliott , Peng Chih-Wen
Published: February 2016

Significance

Epstein–Barr Virus (EBV) Nuclear Antigen 1 (EBNA1) is essential for establishing long-term EBV infection in human cells and is implicated in EBV-related malignancies. The maintenance of the EBV genome and viral gene expression from the episome are specifically driven by EBNA1 through binding to origin of plasmid replication (oriP). This study finds that EBNA1 complexes with Ribosome Protein L4 (RPL4) and Nucleolin to stabilize EBNA1 binding to oriP. Cooperation of RPL4’s N terminus with Nucleolin K429 is necessary for EBNA1 oriP binding and episome maintenance, whereas RPL4's C-terminal K380 and K393 induce H3K4me2, which promotes EBNA1 transactivation of oriP. These discoveries enhance our understanding of the complexity of EBNA1’s interactions with host proteins and EBV episomes and reveal new targets for inhibition of EBV genome persistence.
Early and multiple origins of metastatic lineages within primary tumors
Authors: Zhao Zi-Ming , Zhao Bixiao , Bai Yalai , Iamarino Atila , Gaffney Stephen G. , Schlessinger Joseph , Lifton Richard P. , Rimm David L. , Townsend Jeffrey P.
Published: February 2016

Significance

The knowledge that cancer is an evolutionary process is old, but only recently can sequencing technology provide data for clinically relevant evolutionary analyses of cancer. Approaches developed for evolutionary biology can reveal the relationship among clonal lineages, the ancestral states of gene sequences, and the timing of evolutionary events. We performed whole exome sequencing of cancer tissues from multiple sites of dozens of subjects, demonstrating nonlinear patterns of tumor progression and early origins of metastatic lineages and quantifying the times of occurrence of driver mutations. These findings direct research attention away from the search for genes that induce metastasis toward genes that are mutated early in tumorigenesis, providing therapeutic targets effective against both primary tumors and metastases.
Structure–function analysis of myomaker domains required for myoblast fusion
Authors: Millay Douglas P. , Gamage Dilani G. , Quinn Malgorzata E. , Min Yi-Li , Mitani Yasuyuki , Bassel-Duby Rhonda , Olson Eric N.
Published: February 2016

Significance

Fusion of myoblasts is required for proper skeletal muscle formation during embryonic development and adult muscle regeneration. Despite the central role for plasma membrane fusion, the molecules and mechanisms that govern this process have remained elusive. Myomaker is the only identified muscle-specific protein required for myoblast fusion; however, the mechanisms by which this multipass membrane protein governs fusion are not understood. Through structure–function analysis and development of cell-based fusion assays, we begin to delineate the domains of the myomaker protein required for fusion.
Kalirin and Trio proteins serve critical roles in excitatory synaptic transmission and LTP
Authors: Herring Bruce E. , Nicoll Roger A.
Published: February 2016

Significance

Long-term potentiation (LTP), a form of synaptic plasticity that results in the strengthening of glutamatergic synapses, is believed to be the cellular mechanism underlying learning and memory. LTP is induced by calcium influx through NMDA receptors, which in turn activates CaMKII; however, the substrates that CaMKII phosphorylate that ultimately give rise to LTP have been the subject of debate for more than two decades. Here we show that the RhoGEF proteins Kalirin and Trio are the substrates of CaMKII responsible for LTP induction. Furthermore, we show that glutamatergic synapses require Kalirin and Trio, given that such synapses no longer exist in the absence of these proteins.
Membrane translocation of TRPC6 channels and endothelial migration are regulated by calmodulin and PI3 kinase activation
Authors: Chaudhuri Pinaki , Rosenbaum Michael A. , Sinharoy Pritam , Damron Derek S. , Birnbaumer Lutz , Graham Linda M.
Published: February 2016

Significance

Endothelial cell migration is required for vessel repair after damage during angioplasty. Migration is inhibited by lipid oxidation products, including lysophosphatidylcholine (lysoPC), that are abundant in atherosclerotic plaques. Inhibition of migration is dependent on Ca
2+
entering through canonical transient receptor potential 6 (TRPC6) channels externalized by lysoPC's action. Here we uncover an unappreciated role for activation of PI3K by calmodulin (CaM) requiring phosphorylation of its Tyr
99
. Phosphatidylinositol (3,4,5)-trisphosphate (PIP3) formed by PI3K facilitates insertion of endocellular TRPC6 channels into the plasma membrane. The CaM-PI3K signaling mechanism may also operate in externalization of additional TRPC channels and for other membrane functions residing primarily on endomembranes prior to stimulation by extracellular signals, including glucose transporter 4 in response to insulin, and aquaporin-2 in response to vasopressin.
Genetically encoded sensors enable real-time observation of metabolite production
Authors: Rogers Jameson K. , Church George M.
Published: February 2016

Significance

Advances in biotechnology are enabling engineers to harness natural processes for the production of valuable new chemicals and materials. Cells engineered for chemical production act as renewable factories and redefine what is possible in industries as diverse as manufacturing, pharmaceuticals, and energy. Despite this potential, long and uncertain timelines for biobased product development hinder progress. Engineering cells for chemical production is challenging because the complexity of biology necessitates many attempted designs before an optimal combination of genetic elements or culture conditions is discovered. In this work, we develop a framework that allows design evaluation to be performed with fluorescence such that microbial chemical production can be monitored in real time without the need for sample preparation or laborious analytical techniques.
Pathophysiological implication of CaV3.1 T-type Ca2+channels in trigeminal neuropathic pain
Authors: Choi Soonwook , Yu Eunah , Hwang Eunjin , Llinás Rodolfo R.
Published: February 2016

Significance

Understanding the pathophysiological mechanism of central neuropathic pain has attracted much attention, especially because neuropathic pain is often unresponsive to existing medical treatments. In this study, we investigated the role of CaV3.1 T-type Ca2+channels in the development of trigeminal neuropathic pain (TNP) in mice. Our results show that, intriguingly, CaV3.1 knockout mice had attenuated TNP. Specifically, we demonstrate that increased low-frequency rhythmicity and widely spread noncolumnar activity were present in wild-type TNP mice but not in knockout TNP mice. Moreover, abnormally pronounced coupling between low-frequency and high-frequency rhythms in the thalamocortical network of wild-type mice was absent in CaV3.1 knockout mice. Our results clearly imply that the presence of CaV3.1 channels is a crucial element in the pathophysiology of TNP.
Kinetic properties and substrate inhibition of α-galactosidase from Aspergillus niger
Authors: Liao Julan , Okuyama Masayuki , Ishihara Keigo , Yamori Yoshinori , Iki Shigeo , Tagami Takayoshi , Mori Haruhide , Chiba Seiya , Kimura Atsuo
Published: February 2016

The recombinant AglB produced by Pichia pastoris exhibited substrate inhibition behavior for the hydrolysis of p-nitrophenyl α-galactoside, whereas it hydrolyzed the natural substrates, including galactomanno-oligosaccharides and raffinose family oligosaccharides, according to the Michaelian kinetics. These contrasting kinetic behaviors can be attributed to the difference in the dissociation constant of second substrate from the enzyme and/or to the ability of the leaving group of the substrates. The enzyme displays the grater kcat/Km values for hydrolysis of the branched α-galactoside in galactomanno-oligosaccharides than that of raffinose and stachyose. A sequence comparison suggested that AglB had a shallow active-site pocket, and it can allow to hydrolyze the branched α-galactosides, but not linear raffinose family oligosaccharides.
Effect of the chelation of metal cation on the antioxidant activity of chondroitin sulfates
Authors: Ajisaka Katsumi , Oyanagi Yutaka , Miyazaki Tatsuo , Suzuki Yasuhiro
Published: February 2016

The antioxidant potencies of chondroitin sulfates (CSs) from shark cartilage, salmon cartilage, bovine trachea, and porcine intestinal mucosa were compared by three representative methods for the measurement of the antioxidant activity; DPPH radical scavenging activity, superoxide radical scavenging activity, and hydroxyl radical scavenging activity. CSs from salmon cartilage and bovine trachea showed higher potency in comparison with CSs from shark cartilage and porcine intestinal mucosa. Next, CS from salmon cartilage chelating with Ca2+, Mg2+, Mn2+, or Zn2+ were prepared, and their antioxidant potencies were compared. CS chelating with Ca2+ or Mg2+ ions showed rather decreased DPPH radical scavenging activity in comparison with CS of H+ form. In contrast, CS chelating with Ca2+ or Mg2+ ion showed remarkably enhanced superoxide radical scavenging activity than CS of H+ or Na+ form. Moreover, CS chelating with divalent metal ions, Ca2+, Mg2+, Mn2+, or Zn2+, showed noticeably higher hydroxyl radical scavenging activity than CS of H+ or Na+ form. The present results revealed that the scavenging activities of, at least, superoxide radical and hydroxyl radical were enhanced by the chelation with divalent metal ions.
Coupling primary and stem cell–derived cardiomyocytes in an in vitro model of cardiac cell therapy
Authors: Aratyn-Schaus Yvonne , Pasqualini Francesco S. , Yuan Hongyan , McCain Megan L. , Ye George J.C. , Sheehy Sean P. , Campbell Patrick H. , Parker Kevin Kit
Published: February 2016

The efficacy of cardiac cell therapy depends on the integration of existing and newly formed cardiomyocytes. Here, we developed a minimal in vitro model of this interface by engineering two cell microtissues (μtissues) containing mouse cardiomyocytes, representing spared myocardium after injury, and cardiomyocytes generated from embryonic and induced pluripotent stem cells, to model newly formed cells. We demonstrated that weaker stem cell–derived myocytes coupled with stronger myocytes to support synchronous contraction, but this arrangement required focal adhesion-like structures near the cell–cell junction that degrade force transmission between cells. Moreover, we developed a computational model of μtissue mechanics to demonstrate that a reduction in isometric tension is sufficient to impair force transmission across the cell–cell boundary. Together, our in vitro and in silico results suggest that mechanotransductive mechanisms may contribute to the modest functional benefits observed in cell-therapy studies by regulating the amount of contractile force effectively transmitted at the junction between newly formed and spared myocytes.
Muscle-on-chip: An in vitro model for donor–host cardiomyocyte coupling
Authors: Dierickx Pieterjan , Van Laake Linda W.
Published: February 2016

A key aspect of cardiac cell–based therapy is the proper integration of newly formed cardiomyocytes into the remnant myocardium after injury. In this issue, Aratyn-Schaus et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201508026) describe an in vitro model for heterogeneous cardiomyocyte coupling in which force transmission between cells can be measured.
Exploring the SERS background using a sandwiched graphene monolayer with gap-plasmon junctions
Authors: Park Won-Hwa , Cheong Hyeonsik
Published: February 2016

We examine the origin of the surface-enhanced Raman scattering (SERS) background mediating with a graphene monolayer at Au nanoparticle-Au thin film junctions. We find the degree of the asymmetric shape of the radial breathing like mode (RBLM) peak at 150 cm−1 is strongly correlated with the accompanied SERS background intensities. The SERS investigation with the out-of-plane modes (300~700 cm−1) of graphene gives significant clues that the SERS background, the degree of the tilted formation from the analysis of the transverse acoustic peaks, and the spectral shape of the RBLM peak are strongly correlated with each other, indicating that electron–phonon coupling plays a crucial role in increasing the SERS background.