bluuebunny/crossref_metadata_2025 huggingface dataset:
Does structural connectivity influence tree species distributions and abundance in a naturally discontinuous tropical forest formation?
Authors: Das Arundhati Abin , John Robert , Anand Madhur
Published: October 2016

Aims

The study of naturally discontinuous forest systems could help further our understanding of the relative roles of abiotic factors and spatial connectivity in influencing species turnover and plant metacommunity structure, compared to continuous forest formations, where local communities are often arbitrarily defined and where ‘mass effects’ and source–sink dynamics tend to confound the roles of dispersal and environment. Here we studied a tropical montane landscape where old‐growth evergreen forest occurs as patchy formations in a matrix of natural grasslands, to test the influence of environment and connectivity on species turnover and woody plant metacommunity structure.

Location

Western and southern regions of the Upper Nilgiri Plateau, Western Ghats, southern India.

Methods

We sampled 85 vegetation plots located across a 600‐km2 landscape, assembled environmental data, constructed contrasting spatial connectivity models, including models for the effects of topography on structural connectivity, and used RDA‐based variation partitioning to assess the relative influence of environment and space on woody plant metacommunity structure.

Results

Considering several environmental and multi‐scale spatial predictors, we could explain half of the variation in plant community structure. Environmental and habitat factors such as precipitation, temperature seasonality, elevation, fragment size and landscape context play a dominant role, explaining approximately 40% of variation. Spatial predictors based on Euclidean distance performed better than those that accounted for topographic resistance. Spatial predictors accounted for only 9% of the variation in plant metacommunity structure.

Conclusion

Our results support the species sorting paradigm of metacommunity structure, as abiotic effects and biotic interactions play dominant roles in influencing community structure and species turnover in these old‐growth forests, with a comparatively small influence of spatial connectivity. Effective management of woody species diversity would therefore require conservation of these forests across the range of environmental conditions under which they occur.
The putative Walker A and Walker B motifs of Rrp2 are required for the growth of Borrelia burgdorferi
Authors: Ouyang Zhiming , Zhou Jianli
Published: October 2016

Rrp2 encodes a putative bacterial enhancer binding protein (bEBP) in Borrelia burgdorferi. Point mutation (G239C) of Rrp2 abolishes the transcriptional activation of σ54‐dependent rpoS. In contrast to canonical bEBPs that are dispensable for bacterial growth, Rrp2 is essential for borrelial growth in BSK medium. It has been believed that Rrp2's ATPase activity is not required for cell growth, but experimental evidence supporting this notion has been lacking. In particular, it has remained unclear whether the residue G239 is involved in Rrp2's presumptive ATPase activity. To address these information gaps, we examined the roles of Rrp2's potential strategic signatures including the G239 residue and the putative Walker A and Walker B motifs. Herein it was showed that Rrp2 has ATP binding and hydrolysis activities engendered by the Walker A and B motifs respectively. However, these activities were not significantly impaired by a G239C mutation. Further mutagenesis analyses indicated that Rrp2's Walker A and B motifs are required for borrelial growth; mutations of key residues in these two motifs were lethal to B. burgdorferi. The combined data suggest that the Walker A and Walker B motifs of Rrp2 are involved in the control of another unknown RpoS‐independent gene product(s) associated with borrelial replication.
Developmental regulation and modulation of apoptotic genes expression in sheep oocytes and embryos cultured in vitro with L‐carnitine
Authors: Mishra A , Reddy IJ , Gupta PSP , Mondal S
Published: October 2016

Contents

The objective of this study was to find out the impact of L‐carnitine (10 mM) on developmental regulation of preimplantation sheep embryos cultured in vitro when supplemented in maturation medium and post‐fertilization medium separately. Subsequent objective was to observe the L‐carnitine‐mediated alteration in expression of apoptotic genes (Bcl2, Bax, Casp3 and PCNA) in sheep oocytes and developing embryos produced in vitro. Oocytes matured with L‐carnitine showed significantly (p < .05) higher cleavage (67.23% vs 43.12%), morula (47.65% vs 28.58%) and blastocysts (32.12% vs 13.24%) percentage as compared to presumptive zygotes cultured with L‐carnitine during post‐fertilization period. So it is suggested to use L‐carnitine during maturation than post‐fertilization period. Antiapoptotic and proliferative effects of L‐carnitine were confirmed by inducing culture medium with actinomycin D (apoptotic agent) and TNFα (antiproliferative agent), respectively, with and without L‐carnitine. Oocytes and embryos cultured with actinomycin D and TNFα showed developmental arrest with significant (p < .05) decrease in morula and blastocysts percentage but supplementation of L‐carnitine to actinomycin D and TNFα induced culture medium showed similar result as that of control. L‐carnitine supplementation during IVM significantly (p < .05) upregulated the expression of Bcl2 and PCNA genes in majority of the developmental stages. Although L‐carnitine upregulated the expression of Bax in initial developmental stages but downregulated at latter part, whereas the expression of Casp3 was upregulated upto 16‐cell stage but after that there was no difference in expression. Expression of GAPDH gene was not affected by L‐carnitine supplementation. In conclusion, L‐carnitine acted as an antiapoptotic and proliferative compound during embryo development and supplementation of L‐carnitine during IVM altered the expression of apoptotic genes in the developmental stages of embryos.
Molecular phylogeny of Sericostomatoidea (Trichoptera) with the establishment of three new families
Authors: JOHANSON KJELL ARNE , MALM TOBIAS , ESPELAND MARIANNE
Published: October 2016

We inferred the phylogenetic relationships among 58 genera of Sericostomatoidea, representing all previously accepted families as well as genera that were not placed in established families. The analyses were based on five fragments of the protein coding genes carbamoylphosphate synthetase (CPSase of CAD), isocitrate dehydrogenase (IDH), Elongation factor 1a (EF‐1a), RNA polymerase II (POL II) and cytochrome oxidase I (COI). The data set was analysed using Bayesian methods with a mixed model, raxml, and parsimony. The various methods generated slightly different results regarding relationships among families, but the shared results comprise support for: (i) a monophyletic Sericostomatoidea; (ii) a paraphyletic Parasericostoma due to inclusion of Myotrichia murina, leading to synonymization of Myotrichia with Parasericostoma; (iii) a polyphyletic Sericostomatidae, which is divided into two families, Sericostomatidae sensu stricto and Parasericostomatidae fam.n.; (iv) a polyphyletic Helicophidae which is divided into Helicophidae sensu stricto and Heloccabucidae fam.n.; (v) hypothesized phylogenetic placement of the former incerta sedis genera Ngoya, Seselpsyche and Karomana; (vi) a paraphyletic Costora (Conoesucidae) that should be divided into several genera after more careful examination of morphological data; (vii) reinstatement of Gyrocarisa as a valid genus within Petrothrincidae. A third family, Ceylanopsychidae fam.n., is established based on morphological characters alone. A hypothesis of the relationship among 14 of the 15 families in the superfamily is presented. A key to the families is presented based on adults (males). Taxonomic history, diagnosis, habitat preference and distribution data for all sericostomatoid families are presented.

This published work has been registered in ZooBank,
http://zoobank.org/urn:lsid:zoobank.org:pub:CF6A6B9F‐6A72‐4265‐BD09‐3A710DFCD7B1.
A Comparative Assessment of Simplified Models for Simulating Parametric Roll
Authors: Somayajula Abhilash S. , Falzarano Jeffrey
Published: October 2016

The motion of a ship/offshore platform at sea is governed by a coupled set of nonlinear differential equations. In general, analytical solutions for such systems do not exist and recourse is taken to time-domain simulations to obtain numerical solutions. Each simulation is not only time consuming but also captures only a single realization of the many possible responses. In a design spiral when the concept design of a ship/platform is being iteratively changed, simulating multiple realizations for each interim design is impractical. An analytical approach is preferable as it provides the answer almost instantaneously and does not suffer from the drawback of requiring multiple realizations for statistical confidence. Analytical solutions only exist for simple systems, and hence, there is a need to simplify the nonlinear coupled differential equations into a simplified one degree-of-freedom (DOF) system. While simplified methods make the problem tenable, it is important to check that the system still reflects the dynamics of the complicated system. This paper systematically describes two of the popular simplified parametric roll models in the literature: Volterra GM and improved Grim effective wave (IGEW) roll models. A correction to the existing Volterra GM model described in current literature is proposed to more accurately capture the restoring forces. The simulated roll motion from each model is compared against a corresponding simulation from a nonlinear coupled time-domain simulation tool to check its veracity. Finally, the extent to which each of the models captures the nonlinear phenomenon accurately is discussed in detail.
What Gramsci Can Tell Sport Communication Scholars About How Civic Leaders Sell Sports to Their Communities: A Look at the Braves’ Move to Atlanta
Authors: Anderson Bill
Published: October 2016

Antonio Gramsci argued that ruling classes stayed in power as much through cultural hegemony as through economic hegemony or brute force. Gramsci maintained that the dominant class established and maintained this cultural hegemony through negotiation and persuasion. Gramsci’s theory offers much to sport communication scholars who try to ascertain why certain communities (especially their civic leaders) build stadiums to attract major-league sports teams and events despite mounting economic evidence that these ventures often fail to yield the financial benefits touted by their advocates. This paper uses Gramsci’s theory to examine how the civic leaders of Atlanta enticed the populace and sporting press to use public funds to build a new sports stadium in the mid-1960s. Atlanta’s leaders used the sports stadium not only to lure a Major League Baseball team to the city but also to persuade the city’s populace that this move made the metropolis “big league.”
The social costs of nitrogen
Authors: Keeler Bonnie L. , Gourevitch Jesse D. , Polasky Stephen , Isbell Forest , Tessum Chris W. , Hill Jason D. , Marshall Julian D.
Published: October 2016

Nitrogen negatively affects health, climate, and water quality with costs that vary across space.
Webinar | Key signaling pathways in cancer: Emerging trends in immunometabolism
Authors: Pearce Erika L. , O'Neill Luke
Published: October 2016

Immune cells divide rapidly when mounting an immune response against a pathogen, for example, or when initiating a wound-healing response. To accommodate the increased energy requirements to mount the immune response, these cells may employ metabolic pathways similar to those engaged by cancer cells—pathways such as aerobic glycolysis. This correlation presents the intriguing possibility that understanding immune cell metabolism will provide new and actionable insights into the behavior of tumor cells. In this webinar, our expert speakers will explore how this phenomenon is being studied and describe how it could enable the development of new strategies in the fight against cancer.

View the Webinar
U.S. charges journal publisher with misleading authors
Authors: Bohannon John
Published: October 2016

OMICS Group Inc. has drawn numerous complaints about allegedly shady editorial practices and meetings.
A nuclease that mediates cell death induced by DNA damage and poly(ADP-ribose) polymerase-1
Authors: Wang Yingfei , An Ran , Umanah George K. , Park Hyejin , Nambiar Kalyani , Eacker Stephen M. , Kim BongWoo , Bao Lei , Harraz Maged M. , Chang Calvin , Chen Rong , Wang Jennifer E. , Kam Tae-In , Jeong Jun Seop , Xie Zhi , Neifert Stewart , Qian Jiang , Andrabi Shaida A. , Blackshaw Seth , Zhu Heng , Song Hongjun , Ming Guo-li , Dawson Valina L. , Dawson Ted M.
Published: October 2016

DNA damage-activated nuclease identified

Cells that experience stresses and accumulate excessive damage to DNA undergo cell death mediated by a nuclear enzyme known as PARP-1. During this process, apoptosis-inducing factor (AIF) translocates to the nucleus and activates one or more nucleases to cleave DNA. Wang
et al.
found that macrophage migration inhibitory factor (MIF) is an AIF-associated endonuclease that contributes to PARP-1-induced DNA fragmentation (see the Perspective by Jonas). In mouse neurons in culture, loss of MIF protected neurons from cell death caused by excessive stimulation. Targeting MIF could thus provide a therapeutic strategy against diseases in which PARP-1 activation is excessive.

Science
, this issue p.
82
; see also p.
36
Localized seismic deformation in the upper mantle revealed by dense seismic arrays
Authors: Inbal Asaf , Ampuero Jean Paul , Clayton Robert W.
Published: October 2016

Earthquakes get a more flexible source

Earth's surface deforms in part as a result of ruptures along brittle crustal faults that generate earthquakes. Understanding rock deformation in the ductile lower crust and mantle is challenging. Using the densest seismic arrays in the world, Inbal
et al.
have found an unexpected localization of seismicity at these depths under the Newport-Inglewood fault in southern California. The seismicity points to a type of earthquake that may help us understand how ductile deformation operates in this region of Earth.

Science
, this issue p.
88
Going global by adapting local: A review of recent human adaptation
Authors: Fan Shaohua , Hansen Matthew E. B. , Lo Yancy , Tishkoff Sarah A.
Published: October 2016

The spread of modern humans across the globe has led to genetic adaptations to diverse local environments. Recent developments in genomic technologies, statistical analyses, and expanded sampled populations have led to improved identification and fine-mapping of genetic variants associated with adaptations to regional living conditions and dietary practices. Ongoing efforts in sequencing genomes of indigenous populations, accompanied by the growing availability of “-omics” and ancient DNA data, promises a new era in our understanding of recent human evolution and the origins of variable traits and disease risks.
Ultrafast many-body interferometry of impurities coupled to a Fermi sea
Authors: Cetina Marko , Jag Michael , Lous Rianne S. , Fritsche Isabella , Walraven Jook T. M. , Grimm Rudolf , Levinsen Jesper , Parish Meera M. , Schmidt Richard , Knap Michael , Demler Eugene
Published: October 2016

Sluggish turmoil in the Fermi sea

The nonequilibrium dynamics of many-body quantum systems are tricky to study experimentally or theoretically. As an experimental setting, dilute atomic gases offer an advantage over electrons in metals. In this environment, the heavier atoms make collective processes that involve the entire Fermi sea occur at the sluggish time scale of microseconds. Cetina
et al.
studied these dynamics by using a small cloud of
40
K atoms that was positioned at the center of a far larger
6
Li cloud. Controlling the interactions between K and Li atoms enabled a detailed look into the formation of quasiparticles associated with K “impurity” atoms.

Science
, this issue p.
96
Writ large: Genomic dissection of the effect of cellular environment on immune response
Authors: Yosef Nir , Regev Aviv
Published: October 2016

Cells of the immune system routinely respond to cues from their local environment and feed back to their surroundings through transient responses, choice of differentiation trajectories, plastic changes in cell state, and malleable adaptation to their tissue of residence. Genomic approaches have opened the way for comprehensive interrogation of such orchestrated responses. Focusing on genomic profiling of transcriptional and epigenetic cell states, we discuss how they are applied to investigate immune cells faced with various environmental cues. We highlight some of the emerging principles on the role of dense regulatory circuitry, epigenetic memory, cell type fluidity, and reuse of regulatory modules in achieving and maintaining appropriate responses to a changing environment. These provide a first step toward a systematic understanding of molecular circuits in complex tissues.
Realization of two-dimensional spin-orbit coupling for Bose-Einstein condensates
Authors: Wu Zhan , Zhang Long , Sun Wei , Xu Xiao-Tian , Wang Bao-Zong , Ji Si-Cong , Deng Youjin , Chen Shuai , Liu Xiong-Jun , Pan Jian-Wei
Published: October 2016

Spin-orbit coupling in an optical lattice

Studying topological matter in cold-atom systems may bring fresh insights, thanks to the intrinsic purity and controllability of this experimental setting. However, the necessary spin-orbit coupling can be tricky to engineer. Wu
et al.
conceived and experimentally demonstrated a simple scheme that involves only a single laser source and can be continuously tuned between one- and two-dimensional spin-orbit coupling (see the Perspective by Aidelsburger). Although this experiment used bosonic atoms, it is expected that the setup would also work for fermions.

Science
, this issue p.
83
; see also p.
35
Extensive migration of young neurons into the infant human frontal lobe
Authors: Paredes Mercedes F. , James David , Gil-Perotin Sara , Kim Hosung , Cotter Jennifer A. , Ng Carissa , Sandoval Kadellyn , Rowitch David H. , Xu Duan , McQuillen Patrick S. , Garcia-Verdugo Jose-Manuel , Huang Eric J. , Alvarez-Buylla Arturo
Published: October 2016

Building the human brain

As the brain develops, neurons migrate from zones of proliferation to their final locations, where they begin to build circuits. Paredes
et al.
have discovered that shortly after birth, a group of neurons that proliferates near the ventricles migrates in chains alongside circulatory vessels into the frontal lobes (see the Perspective by McKenzie and Fishell). Young neurons that migrate postnatally into the anterior cingulate cortex then develop features of inhibitory interneurons. The number of migratory cells decreases over the first 7 months of life, and by 2 years of age, migratory cells are not evident. Any damage during migration, such as hypoxia, may affect the child's subsequent physical and behavioral development.

Science
, this issue p.
81
; see also p.
38
The impact of training informal health care providers in India: A randomized controlled trial
Authors: Das Jishnu , Chowdhury Abhijit , Hussam Reshmaan , Banerjee Abhijit V.
Published: October 2016

Delivering health care to mystery patients

Many families in developing countries do not have access to medical doctors and instead receive health care from informal providers. Das
et al.
used “mystery” patients (trained actors) to test whether a 9-month training program improved the quality of care delivered by informal providers in West Bengal (see the Perspective by Powell-Jackson). The patients did not identify themselves to the providers and were not told which providers had participated in the training program. The results of this blinded assessment showed that medical doctors delivered better care than informal providers but that the training program closed much of the gap.

Science
, this issue p.
80
; see also p.
34
Social norms as solutions
Authors: Nyborg Karine , Anderies John M. , Dannenberg Astrid , Lindahl Therese , Schill Caroline , Schlüter Maja , Adger W. Neil , Arrow Kenneth J. , Barrett Scott , Carpenter Stephen , Chapin F. Stuart , Crépin Anne-Sophie , Daily Gretchen , Ehrlich Paul , Folke Carl , Jager Wander , Kautsky Nils , Levin Simon A. , Madsen Ole Jacob , Polasky Stephen , Scheffer Marten , Walker Brian , Weber Elke U. , Wilen James , Xepapadeas Anastasios , de Zeeuw Aart
Published: October 2016

Policies may influence large-scale behavioral tipping
Human brains teach us a surprising lesson
Authors: McKenzie Melissa , Fishell Gord
Published: October 2016

Young interneurons continue migrating to the frontal lobe during the first few months of life

[Also see Research Article by

Paredes
et al.

]
Screening for Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus, and Treponema pallidum by Blood Testing Using a Bio-Flash Technology-Based Algorithm before Gastrointestinal Endoscopy
Authors: Jun Zhou , Zhen Chen , QuiuLi Zhang , YuanQi An , Casado Verónica Vocero , Fan Yuan
Published: October 2016

Currently, conventional enzyme immunoassays which use manual gold immunoassays and colloidal tests (GICTs) are used as screening tools to detect
Treponema pallidum
(syphilis), hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus type 1 (HIV-1), and HIV-2 in patients undergoing surgery. The present observational, cross-sectional study compared the sensitivity, specificity, and work flow characteristics of the conventional algorithm with manual GICTs with those of a newly proposed algorithm that uses the automated Bio-Flash technology as a screening tool in patients undergoing gastrointestinal (GI) endoscopy. A total of 956 patients were examined for the presence of serological markers of infection with HIV-1/2, HCV, HBV, and
T. pallidum
. The proposed algorithm with the Bio-Flash technology was superior for the detection of all markers (100.0% sensitivity and specificity for detection of anti-HIV and anti-HCV antibodies, HBV surface antigen [HBsAg], and
T. pallidum
) compared with the conventional algorithm based on the manual method (80.0% sensitivity and 98.6% specificity for the detection of anti-HIV, 75.0% sensitivity for the detection of anti-HCV, 94.7% sensitivity for the detection of HBsAg, and 100% specificity for the detection of anti-HCV and HBsAg) in these patients. The automated Bio-Flash technology-based screening algorithm also reduced the operation time by 85.0% (205 min) per day, saving up to 24 h/week. In conclusion, the use of the newly proposed screening algorithm based on the automated Bio-Flash technology can provide an advantage over the use of conventional algorithms based on manual methods for screening for HIV, HBV, HCV, and syphilis before GI endoscopy.
Heterodimers as the Structural Unit of the T=1 Capsid of the Fungal Double-Stranded RNA Rosellinia necatrix Quadrivirus 1
Authors: Luque Daniel , Mata Carlos P. , González-Camacho Fernando , González José M. , Gómez-Blanco Josué , Alfonso Carlos , Rivas Germán , Havens Wendy M. , Kanematsu Satoko , Suzuki Nobuhiro , Ghabrial Said A. , Trus Benes L. , Castón José R.
Published: October 2016

Most double-stranded RNA (dsRNA) viruses are transcribed and replicated in a specialized icosahedral capsid with a T=1 lattice consisting of 60 asymmetric capsid protein (CP) dimers. These capsids help to organize the viral genome and replicative complex(es). They also act as molecular sieves that isolate the virus genome from host defense mechanisms and allow the passage of nucleotides and viral transcripts. Rosellinia necatrix quadrivirus 1 (RnQV1), the type species of the family
Quadriviridae
, is a dsRNA fungal virus with a multipartite genome consisting of four monocistronic segments (segments 1 to 4). dsRNA-2 and dsRNA-4 encode two CPs (P2 and P4, respectively), which coassemble into ∼450-Å-diameter capsids. We used three-dimensional cryo-electron microscopy combined with complementary biophysical techniques to determine the structures of RnQV1 virion strains W1075 and W1118. RnQV1 has a quadripartite genome, and the capsid is based on a single-shelled T=1 lattice built of P2-P4 dimers. Whereas the RnQV1-W1118 capsid is built of full-length CP, P2 and P4 of RnQV1-W1075 are cleaved into several polypeptides, maintaining the capsid structural organization. RnQV1 heterodimers have a quaternary organization similar to that of homodimers of reoviruses and other dsRNA mycoviruses. The RnQV1 capsid is the first T=1 capsid with a heterodimer as an asymmetric unit reported to date and follows the architectural principle for dsRNA viruses that a 120-subunit capsid is a conserved assembly that supports dsRNA replication and organization.

IMPORTANCE
Given their importance to health, members of the family
Reoviridae
are the basis of most structural and functional studies and provide much of our knowledge of dsRNA viruses. Analysis of bacterial, protozoal, and fungal dsRNA viruses has improved our understanding of their structure, function, and evolution, as well. Here, we studied a dsRNA virus that infects the fungus
Rosellinia necatrix
, an ascomycete that is pathogenic to a wide range of plants. Using three-dimensional cryo-electron microscopy and analytical ultracentrifugation analysis, we determined the structure and stoichiometry of Rosellinia necatrix quadrivirus 1 (RnQV1). The RnQV1 capsid is a T=1 capsid with 60 heterodimers as the asymmetric units. The large amount of genetic information used by RnQV1 to construct a simple T=1 capsid is probably related to the numerous virus-host and virus-virus interactions that it must face in its life cycle, which lacks an extracellular phase.
Phosphorylation Requirement of Murine Leukemia Virus p12
Authors: Brzezinski Jonathon D. , Felkner Roland , Modi Apexa , Liu Mengdan , Roth Monica J.
Published: October 2016

The p12 protein of murine leukemia virus (MLV) Gag is associated with the preintegration complex (PIC), and mutants of p12 (PM14) exhibit defects in nuclear entry/retention. Mutants of the phosphorylated serine 61 also have been reported to have defects in the early life cycle. Here we show that a phosphorylated peptide motif derived from human papillomavirus 8 (HPV-8), the E2 hinge region including residues 240 to 255, can functionally replace the main phosphorylated motif of MLV p12 and can rescue the viral titer of a strain with the lethal p12-PM14 mutation. Complementation with the HPV-8 E2 hinge motif generated multiple second-site mutations in live viral passage assays. Additional p12 phosphorylation sites were detected, including the late domain of p12 (PPPY) as well as the late domain/protease cleavage site of matrix (LYPAL), by mass spectrometry and Western blotting. Chromatin binding of p12-green fluorescent protein (GFP) fusion protein and functional complementation of p12-PM14 occurred in a manner independent of the E2 hinge region phosphorylation. Replacement of serine 61 by alanine within the minimal tethering domain (
61
SPMASRLRGRR
71
) maintained tethering, but in the context of the full-length p12, mutants with substitutions in S61 remained untethered and lost infectivity, indicating phosphorylation of p12 serine 61 functions to temporally regulate early and late p12 functions.

IMPORTANCE
The p12 protein, required for both early and late viral functions, is the predominant phosphorylated viral protein of Moloney MLV and is required for virus viability. Our studies indicate that the N terminus of p12 represses the early function of the chromatin binding domain and that deletion of the N terminus activates chromatin binding in the wild-type Moloney MLV p12 protein. Mass spectrometry and mutagenesis studies suggest that phosphorylation of both the repression domain and the chromatin binding domain acts to temporally regulate this process at the appropriate stages during infection.
Simian Immunodeficiency Virus-Producing Cells in Follicles Are Partially Suppressed by CD8+CellsIn Vivo
Authors: Li Shengbin , Folkvord Joy M. , Rakasz Eva G. , Abdelaal Hadia M. , Wagstaff Reece K. , Kovacs Katalin J. , Kim Hyeon O. , Sawahata Ryoko , MaWhinney Samantha , Masopust David , Connick Elizabeth , Skinner Pamela J.
Published: October 2016

Human immunodeficiency virus (HIV)- and simian immunodeficiency virus (SIV)-specific CD8+T cells are typically largely excluded from lymphoid B cell follicles, where HIV- and SIV-producing cells are most highly concentrated, indicating that B cell follicles are somewhat of an immunoprivileged site. To gain insights into virus-specific follicular CD8+T cells, we determined the location and phenotype of follicular SIV-specific CD8+T cellsin situ, the local relationship of these cells to Foxp3+cells, and the effects of CD8 depletion on levels of follicular SIV-producing cells in chronically SIV-infected rhesus macaques. We found that follicular SIV-specific CD8+T cells were able to migrate throughout follicular areas, including germinal centers. Many expressed PD-1, indicating that they may have been exhausted. A small subset was in direct contact with and likely inhibited by Foxp3+cells, and a few were themselves Foxp3+. In addition, subsets of follicular SIV-specific CD8+T cells expressed low to medium levels of perforin, and subsets were activated and proliferating. Importantly, after CD8 depletion, the number of SIV-producing cells increased in B cell follicles and extrafollicular areas, suggesting that follicular and extrafollicular CD8+T cells have a suppressive effect on SIV replication. Taken together, these results suggest that during chronic SIV infection, despite high levels of exhaustion and likely inhibition by Foxp3+cells, a subset of follicular SIV-specific CD8+T cells are functional and suppress viral replicationin vivo. These findings support HIV cure strategies that augment functional follicular virus-specific CD8+T cells to enhance viral control.

IMPORTANCEHIV- and SIV-specific CD8+T cells are typically largely excluded from lymphoid B cell follicles, where virus-producing cells are most highly concentrated, suggesting that B cell follicles are somewhat of an immunoprivileged site where virus-specific CD8+T cells are not able to clear all follicular HIV- and SIV-producing cells. To gain insights into follicular CD8+T cell function, we characterized follicular virus-specific CD8+T cellsin situby using an SIV-infected rhesus macaque model of HIV. We found that subsets of follicular SIV-specific CD8+T cells are able to migrate throughout the follicle, are likely inhibited by Foxp3+cells, and are likely exhausted but that, nonetheless, subsets are likely functional, as they express markers consistent with effector function and show signs of suppressing viral replicationin vivo. These findings support HIV cure strategies that increase the frequency of functional follicular virus-specific CD8+T cells.
Rationally Designed Immunogens Targeting HIV-1 gp120 V1V2 Induce Distinct Conformation-Specific Antibody Responses in Rabbits
Authors: Jiang Xunqing , Totrov Max , Li Wei , Sampson Jared M. , Williams Constance , Lu Hong , Wu Xueling , Lu Shan , Wang Shixia , Zolla-Pazner Susan , Kong Xiang-Peng
Published: October 2016

The V1V2 region of HIV-1 gp120 harbors a major vulnerable site targeted by a group of broadly neutralizing monoclonal antibodies (MAbs) such as PG9 through strand-strand recognition. However, this epitope region is structurally polymorphic as it can also form a helical conformation recognized by RV144 vaccine-induced MAb CH58. This structural polymorphism is a potential mechanism for masking the V1V2 vulnerable site. Designing immunogens that can induce conformation-specific antibody (Ab) responses may lead to vaccines targeting this vulnerable site. We designed a panel of immunogens engrafting the V1V2 domain into trimeric and pentameric scaffolds in structurally constrained conformations. We also fused V1V2 to an Fc fragment to mimic the unconstrained V1V2 conformation. We tested these V1V2-scaffold proteins for immunogenicity in rabbits and assessed the responses by enzyme-linked immunosorbent assay (ELISA) and competition assays. Our V1V2 immunogens induced distinct conformation-specific Ab responses. Abs induced by structurally unconstrained immunogens reacted preferentially with unconstrained V1V2 antigens, suggesting recognition of the helical configuration, while Abs induced by the structurally constrained immunogens reacted preferentially with constrained V1V2 antigens, suggesting recognition of the β-strand conformation. The Ab responses induced by the structurally constrained immunogens were more broadly reactive and had higher titers than those induced by the structurally unconstrained immunogens. Our results demonstrate that immunogens presenting the different structural conformations of the gp120 V1V2 vulnerable site can be designed and that these immunogens induce distinct Ab responses with epitope conformation specificity. Therefore, these structurally constrained V1V2 immunogens are vaccine prototypes targeting the V1V2 domain of the HIV-1 envelope.

IMPORTANCE
The correlates analysis of the RV144 HIV-1 vaccine trial suggested that the presence of antibodies to the V1V2 region of HIV-1 gp120 was responsible for the modest protection observed in the trial. In addition, V1V2 harbors one of the key vulnerable sites of HIV-1 Env recognized by a family of broadly neutralizing MAbs such as PG9. Thus, V1V2 is a key target for vaccine development. However, this vulnerable site is structurally polymorphic, and designing immunogens that present different conformations is crucial for targeting this site. We show here that such immunogens can be designed and that they induced conformation-specific antibody responses in rabbits. Our immunogens are therefore prototypes of vaccine candidates targeting the V1V2 region of HIV-1 Env.
Identification of Interferon-Stimulated Gene Proteins That Inhibit Human Parainfluenza Virus Type 3
Authors: Rabbani M. A. G. , Ribaudo Michael , Guo Ju-Tao , Barik Sailen
Published: October 2016

A major arm of cellular innate immunity is type I interferon (IFN), represented by IFN-α and IFN-β. Type I IFN transcriptionally induces a large number of cellular genes, collectively known as IFN-stimulated gene (ISG) proteins, which act as antivirals. The IFIT (interferon-induced proteins with tetratricopeptide repeats) family proteins constitute a major subclass of ISG proteins and are characterized by multiple tetratricopeptide repeats (TPRs). In this study, we have interrogated IFIT proteins for the ability to inhibit the growth of human parainfluenza virus type 3 (PIV3), a nonsegmented negative-strand RNA virus of the
Paramyxoviridae
family and a major cause of respiratory disease in children. We found that IFIT1 significantly inhibited PIV3, whereas IFIT2, IFIT3, and IFIT5 were less effective or not at all. In further screening a set of ISG proteins we discovered that several other such proteins also inhibited PIV3, including IFITM1, IDO (indoleamine 2,3-dioxygenase), PKR (protein kinase, RNA activated), and viperin (virus inhibitory protein, endoplasmic reticulum associated, interferon inducible)/Cig5. The antiviral effect of IDO, the enzyme that catalyzes the first step of tryptophan degradation, could be counteracted by tryptophan. These results advance our knowledge of diverse ISG proteins functioning as antivirals and may provide novel approaches against PIV3.

IMPORTANCE
The innate immunity of the host, typified by interferon (IFN), is a major antiviral defense. IFN inhibits virus growth by inducing a large number of IFN-stimulated gene (ISG) proteins, several of which have been shown to have specific antiviral functions. Parainfluenza virus type 3 (PIV3) is major pathogen of children, and no reliable vaccine or specific antiviral against it currently exists. In this article, we report several ISG proteins that strongly inhibit PIV3 growth, the use of which may allow a better antiviral regimen targeting PIV3.
Exercise to prevent falls in older adults: an updated systematic review and meta-analysis
Authors: Sherrington Catherine , Michaleff Zoe A , Fairhall Nicola , Paul Serene S , Tiedemann Anne , Whitney Julie , Cumming Robert G , Herbert Robert D , Close Jacqueline C T , Lord Stephen R
Published: October 2016

Objective

Previous meta-analyses have found that exercise prevents falls in older people. This study aimed to test whether this effect is still present when new trials are added, and it explores whether characteristics of the trial design, sample or intervention are associated with greater fall prevention effects.

Design

Update of a systematic review with random effects meta-analysis and meta-regression.

Data sources

Cochrane Library, CINAHL, MEDLINE, EMBASE, PubMed, PEDro and SafetyLit were searched from January 2010 to January 2016.

Study eligibility criteria

We included randomised controlled trials that compared fall rates in older people randomised to receive exercise as a single intervention with fall rates in those randomised to a control group.

Results

99 comparisons from 88 trials with 19 478 participants were available for meta-analysis. Overall, exercise reduced the rate of falls in community-dwelling older people by 21% (pooled rate ratio 0.79, 95% CI 0.73 to 0.85, p<0.001, I247%, 69 comparisons) with greater effects seen from exercise programmes that challenged balance and involved more than 3 hours/week of exercise. These variables explained 76% of the between-trial heterogeneity and in combination led to a 39% reduction in falls (incident rate ratio 0.61, 95% CI 0.53 to 0.72, p<0.001). Exercise also had a fall prevention effect in community-dwelling people with Parkinson's disease (pooled rate ratio 0.47, 95% CI 0.30 to 0.73, p=0.001, I265%, 6 comparisons) or cognitive impairment (pooled rate ratio 0.55, 95% CI 0.37 to 0.83, p=0.004, I221%, 3 comparisons). There was no evidence of a fall prevention effect of exercise in residential care settings or among stroke survivors or people recently discharged from hospital.

Summary/conclusions

Exercise as a single intervention can prevent falls in community-dwelling older people. Exercise programmes that challenge balance and are of a higher dose have larger effects. The impact of exercise as a single intervention in clinical groups and aged care facility residents requires further investigation, but promising results are evident for people with Parkinson's disease and cognitive impairment.
Experiences of long-term life-limiting conditions among patients and carers: what can we learn from a meta-review of systematic reviews of qualitative studies of chronic heart failure, chronic obstructive pulmonary disease and chronic kidney disease?
Authors: May Carl R , Cummings Amanda , Myall Michelle , Harvey Jonathan , Pope Catherine , Griffiths Peter , Roderick Paul , Arber Mick , Boehmer Kasey , Mair Frances S , Richardson Alison
Published: October 2016

Objectives

To summarise and synthesise published qualitative studies to characterise factors that shape patient and caregiver experiences of chronic heart failure (CHF), chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD).

Design

Meta-review of qualitative systematic reviews and metasyntheses. Papers analysed using content analysis.

Data sources

CINAHL, EMBASE, MEDLINE, PsychINFO, Scopus and Web of Science were searched from January 2000 to April 2015.

Eligibility criteria for selecting studies

Systematic reviews and qualitative metasyntheses where the participants were patients, caregivers and which described experiences of care for CHF, COPD and CKD in primary and secondary care who were aged ≥18 years.

Results

Searches identified 5420 articles, 53 of which met inclusion criteria. Reviews showed that patients' and caregivers' help seeking and decision-making were shaped by their degree of structural advantage (socioeconomic status, spatial location, health service quality); their degree of interactional advantage (cognitive advantage, affective state and interaction quality) and their degree of structural resilience (adaptation to adversity, competence in managing care and caregiver response to demands).

Conclusions

To the best of our knowledge, this is the first synthesis of qualitative systematic reviews in the field. An important outcome of this overview is an emphasis on what patients and caregivers value and on attributes of healthcare systems, relationships and practices that affect the distressing effects and consequences of pathophysiological deterioration in CHF, COPD and CKD. Interventions that seek to empower individual patients may have limited effectiveness for those who are most affected by the combined weight of structural, relational and practical disadvantage identified in this overview. We identify potential targets for interventions that could address these disadvantages.

Systematic review registration number

PROSPERO CRD42014014547.
Symptoms in patients with takotsubo syndrome: a qualitative interview study
Authors: Wallström Sara , Ulin Kerstin , Omerovic Elmir , Ekman Inger
Published: October 2016

Objective

The aim of the study was to investigate the meaning of narrated symptoms in connection to takotsubo syndrome.

Design, method, participants and setting

Qualitative study consisting of 25 interviews, 23 women and 2 men aged 39–84 and living in Region Västra Götaland, Sweden. The transcribed text was analysed with phenomenological hermeneutics.

Results

The interviewees reported a large number of symptoms before, during and after the acute onset of takotsubo syndrome, including pain, affected breathing, lassitude, malaise and nausea. Several of these have not been reported previously. Symptoms before the acute onset were, even if they had been prominent, ignored by the interviewees for various reasons. During the acute phase, the symptoms could no longer be ignored and the interviewees sought healthcare. The remaining residual symptom after discharge from hospital caused a great deal of worry because the interviewees feared that they would be permanent and they felt they could not live this way. On the whole, becoming ill and having a large number of symptoms greatly impacted the lives of the interviewees and made them re-evaluate how they had been living. Furthermore, they reported feeling alone and lost regarding their symptom burden, especially in relation to their residual symptoms, which affected their health and ability to return to daily life.

Conclusions

Acute symptoms, and symptoms before and after the acute ones, are a major part of the illness experience for patients with takotsubo syndrome and affect their health and well-being. Assessment of symptoms should be an integrated part of care to promote health. One way of achieving this is through the patients’ own narratives of their experiences, which are an important component in person-centred care.
Gamification for health promotion: systematic review of behaviour change techniques in smartphone apps
Authors: Edwards E A , Lumsden J , Rivas C , Steed L , Edwards L A , Thiyagarajan A , Sohanpal R , Caton H , Griffiths C J , Munafò M R , Taylor S , Walton R T
Published: October 2016

Objective

Smartphone games that aim to alter health behaviours are common, but there is uncertainty about how to achieve this. We systematically reviewed health apps containing gaming elements analysing their embedded behaviour change techniques.

Methods

Two trained researchers independently coded apps for behaviour change techniques using a standard taxonomy. We explored associations with user ratings and price.

Data sources

We screened the National Health Service (NHS) Health Apps Library and all top-rated medical, health and wellness and health and fitness apps (defined by Apple and Google Play stores based on revenue and downloads). We included free and paid English language apps using ‘gamification’ (rewards, prizes, avatars, badges, leaderboards, competitions, levelling-up or health-related challenges). We excluded apps targeting health professionals.

Results

64 of 1680 (4%) health apps included gamification and met inclusion criteria; only 3 of these were in the NHS Library. Behaviour change categories used were: feedback and monitoring (n=60, 94% of apps), reward and threat (n=52, 81%), and goals and planning (n=52, 81%). Individual techniques were: self-monitoring of behaviour (n=55, 86%), non-specific reward (n=49, 82%), social support unspecified (n=48, 75%), non-specific incentive (n=49, 82%) and focus on past success (n=47, 73%). Median number of techniques per app was 14 (range: 5–22). Common combinations were: goal setting, self-monitoring, non-specific reward and non-specific incentive (n=35, 55%); goal setting, self-monitoring and focus on past success (n=33, 52%). There was no correlation between number of techniques and user ratings (p=0.07; rs=0.23) or price (p=0.45; rs=0.10).

Conclusions

Few health apps currently employ gamification and there is a wide variation in the use of behaviour change techniques, which may limit potential to improve health outcomes. We found no correlation between user rating (a possible proxy for health benefits) and game content or price. Further research is required to evaluate effective behaviour change techniques and to assess clinical outcomes.

Trial registration number

CRD42015029841.
Cohort feasibility study of an intermittent pneumatic compression device within a below-knee cast for the prevention of venous thromboembolism
Authors: Braithwaite Irene , De Ruyter Bernadette , Semprini Alex , Ebmeier Stefan , Kiddle Grant , Willis Nigel , Carter John , Weatherall Mark , Beasley Richard
Published: October 2016

Objectives

To determine the likely enrolment rate of eligible participants into a randomised controlled trial (RCT) in which a within-cast intermittent pneumatic compression device using Jet Impulse Technology (IPC/JIT) is 1 of 3 possible interventions in a RCT for the prevention of venous thromboembolism (VTE) in the clinical setting of isolated lower limb cast immobilisation.

Design

A prospective, open-label feasibility study of the IPC/JIT device placed within a lower limb cast.

Setting

Wellington Regional Hospital Fracture Clinic.

Participants

Individuals aged 18–70 who presented with a lower limb injury requiring a minimum of 4 weeks below-knee cast immobilisation.

Intervention

Placement of an IPC/JIT device within lower limb cast.

Outcome measures

The main outcome measure was the proportion of eligible participants who participated in the feasibility study. Secondary outcome measures included adherence to device usage throughout the study, ease of application of the device and adverse events potentially associated with its use.

Results

The proportion of potentially eligible participants for the IPC/JIT device was only 7/142 (5%), 95% CI 2 to 9.9. Devices were used for a mean (range) of 4.1 (1.9 to 10.2) hours per day and none of 7 participants had adequate adherence to the device. 3 of the 7 participants suffered an adverse event, including 1 deep vein thrombosis, 2 dorsal foot ulcer and 1 skin maceration.

Conclusions

A within-cast IPC/JIT device is unlikely to be a feasible randomisation arm for a RCT assessing possible interventions for the reduction of VTE risk in the clinical setting of lower limb injury requiring below knee cast immobilisation for a minimum of 4 weeks.

Trial registration number

ANZCTR12615000192583.