bluuebunny/crossref_metadata_2025 huggingface dataset:
The Price We Pay for Radical Curative Pelvic Exenterations: Prevalence and Management of Pain
Authors: Lim Jessica Shao-Yeung , Koh Cherry E. , Liu Hannah , Solomon Michael J. , Johnstone Charlotte S.H.
Published: February 2018

BACKGROUND:

Pelvic exenterations are extensive surgical procedures for locally advanced or recurrent malignancies of the pelvis. However, this is often at the cost of significant morbidity due to perioperative pain, which has been poorly studied.

OBJECTIVE:

This study aims to review perioperative pain management in patients undergoing pelvic exenteration.

DESIGN:

This is a retrospective review of patients undergoing pelvic exenteration between January 2013 and December 2014. Data were gathered from medical records and a prospectively maintained database.

SETTING:

This study was conducted at a single quaternary referral center for pelvic exenteration.

PATIENTS:

Consecutive patients underwent pelvic exenteration at a single center.

INTERVENTIONS:

Pelvic exenteration was performed in consecutive patients.

MAIN OUTCOMES MEASURES:

Primary outcomes were the prevalence of preoperative pain, preoperative opiate use (type, dosage), and postoperative pain (verbal numerical rating scale). Secondary outcomes included the number of pain consultations and correlations between preoperative opiate use, length of stay, and extent of resection (en bloc sacrectomy and nerve excision).

RESULTS:

Ninety-nine patients underwent pelvic exenteration. Sixty-one patients (61.6%) underwent major nerve resection and/or sacrectomy. Thirty patients (30%) required opiates preoperatively, with a mean daily morphine equivalent of 72.9 mg (SD 65.0 mg). Patients on preoperative opiates were more likely to have worse pain postoperatively and to require higher opiate doses and more pain consultations (9.3 vs 4.8; p < 0.001). Major nerve excision and sacrectomy were not associated with worse postoperative pain. By discharge, 60% still required opiate analgesia.

LIMITATIONS:

Retrospective study design, the subjective nature of pain assessment because of a lack of valid methods to objectively quantify pain, and the lack of long-term follow-up were limitations of this study.

CONCLUSIONS:

Perioperative pain is a significant issue among patients undergoing pelvic exenteration. One in three patients require high-dose opiates preoperatively that is associated with worse pain outcomes. Potential areas to improve pain outcomes in these complex patients could include increased use of regional anesthesia, antineuropathic agents, and opiate-sparing techniques. See Video Abstract at http://links.lww.com/DCR/A572.
White Hairs on the Arms
Authors: Jacob Sharon E. , Gust Peter
Published: February 2018

Teledermatology is a term to describe the provision of dermatologic medical services through telecommunication technology. This is a case of white hairs on the arms.
Assessing Sexually Transmitted Disease Partner Services in State and Local Health Departments
Authors: Cuffe Kendra M. , Leichliter Jami S. , Gift Thomas L.
Published: February 2018

State and local health department sexually transmitted disease (STD) programs provide several partner services to reduce disease transmission. Budget cuts and temporary staff reassignments for public health emergencies may affect the provision of partner services. Determining the impact of staffing reductions on STD rates and public health response should be further assessed.
Retinal Nerve Fiber Layer Thickness in Various Retinal Diseases
Authors: Lim Hyung-Bin , Sung Jae-Yun , Ahn Seung-Il , Jo Young-Joon , Kim Jung-Yeul
Published: February 2018

SIGNIFICANCE

Peripapillary retinal nerve fiber layer (RNFL) thickness measurements may be influenced by the range and severity of lesions that are observed distinctively in each retinal disease.

PURPOSE

We investigated the effects of various macular (central serous chorioretinopathy, macular hole, epiretinal membrane, wet age-related macular degeneration) and retinal vascular (branch retinal vein occlusion, central retinal vein occlusion, diabetic macular edema) diseases on peripapillary RNFL thickness measurements using spectral-domain optical coherence tomography.

METHODS

Six hundred thirty-one eyes from 464 patients with various retinal diseases and 167 controls of similar age were included in this retrospective study. Using spectral-domain optical coherence tomography, we measured the thickness of the macula and the RNFL in both various retinal disease eyes and normal control eyes. Four sectorial and average RNFL thicknesses were compared between each disease and age-matched control eyes. The macular thicknesses were also compared.

RESULTS

In the macular disease group, superior (P = .033) and temporal (P = .024) quadrant RNFL thicknesses of central serous chorioretinopathy and temporal (P < .001) quadrant RNFL thicknesses of epiretinal membrane were greater than the age-matched control eyes. No RNFL measurements in macular hole or wet age-related macular degeneration differed significantly from the controls. In the retinal vascular disease group, all sectorial and average RNFL thicknesses of diabetic macular edema and central retinal vein occlusion were greater than those of the controls (all P < .05). In branch retinal vein occlusion, superior (P = .012) and temporal (P < .001) quadrant RNFL thicknesses were greater than those of the controls.

CONCLUSIONS

Peripapillary RNFL thickness measurements may be influenced by the range and severity of lesions that are observed distinctively in each retinal disease. It also appeared that macular disease had a local effect on RNFL thickness, whereas retinal vascular disease had a diffuse effect on RNFL thickness.
An Unusual Presentation of Conjunctival Dermolipoma With a Skin Tag
Authors: Zloto Ofira , Rosner Mordechai
Published: February 2018

Dermolipoma is considered the second most common benign conjunctival tumor in children after nevus. Usually, dermolipoma located just deep in the superotemporal bulbar and forniceal conjunctiva. The authors describe an uncommon presentation of dermolipoma that arise in the conjunctiva as well as in the skin of the lateral canthus. A 5-month-old baby with lateral limbal lesion involving the conjunctiva and the skin underwent excision biopsy. The pathological examination found a dermolipoma in the conjunctiva as well as in the dermis. The outcomes of the excision were satisfactorily functional and cosmetic.

This is only the second case of dermolipoma in the dermis in normal baby that described those far in the literature. This case should raise the awareness that dermolipoma should be considered in differential diagnosis of lesions of the lateral cantus and the periocular skins near it.
Purely Spinal Epidural Capillary Hemangiomas
Authors: Xu Hu , Tong Minfeng , Liu Jihong , Zhou Gezhi , Chen Feng
Published: February 2018

Capillary hemangiomas (CAs) are benign endothelial cell neoplasms that are often encountered superficially in the soft tissues of the head and neck region. Most of the reported purely spinal epidural hemangiomas have been of cavernous type, and the occurrence of purely spinal epidural CA is exceedingly rare, and there are only 12 reported cases of spinal epidural CAs in the English literature. Herein, the authors report the 13th case of purely spinal epidural CAs, and the clinical characteristics, histopathological features, and treatment were also investigated.
Current indirect fitness and future direct fitness are not incompatible
Authors: Brahma Anindita , Mandal Souvik , Gadagkar Raghavendra
Published: February 2018

In primitively eusocial insects, many individuals function as workers despite being capable of independent reproduction. Such altruistic behaviour is usually explained by the argument that workers gain indirect fitness by helping close genetic relatives. The focus on indirect fitness has left open the question of whether workers are also capable of getting direct fitness in the future in spite of working towards indirect fitness in the present. To investigate this question, we recorded behavioural profiles of all wasps on six naturally occurring nests of
Ropalidia marginata
, and then isolated all wasps in individual plastic boxes, giving them an opportunity to initiate nests and lay eggs. We found that 41% of the wasps successfully did so. Compared to those that failed to initiate nests, those that did were significantly younger, had significantly higher frequency of self-feeding behaviour on their parent nests but were not different in the levels of work performed in the parent nests. Thus ageing and poor feeding, rather than working for their colonies, constrain individuals for future independent reproduction. Hence, future direct fitness and present work towards gaining indirect fitness are not incompatible, making it easier for worker behaviour to be selected by kin selection or multilevel selection.
Persistence of an extracellular systemic infection across metamorphosis in a holometabolous insect
Authors: Duneau David F. , Lazzaro Brian P.
Published: February 2018

Organisms with complex life cycles can differ markedly in their biology across developmental life stages. Consequently, distinct life stages can represent drastically different environments for parasites. This difference is especially striking with holometabolous insects, which have dramatically different larval and adult life stages, bridged by a complete metamorphosis. There is no
a priori
guarantee that a parasite infecting the larval stage would be able to persist into the adult stage. In fact, to our knowledge, transstadial transmission of extracellular pathogens has never been documented in a host that undergoes complete metamorphosis. We tested the hypothesis that a bacterial parasite originally sampled from an adult host could infect a larva, then survive through metamorphosis and persist into the adult stage. As a model, we infected the host
Drosophila melanogaster
with a horizontally transmitted, extracellular bacterial pathogen,
Providencia rettgeri
. We found that this natural pathogen survived systemic infection of larvae (L3) and successfully persisted into the adult host. We then discuss how it may be adaptive for bacteria to transverse life stages and even minimize virulence at the larval stage in order to benefit from adult dispersal.
How humans transmit language: horizontal transmission matches word frequencies among peers on Twitter
Authors: Bryden John , Wright Shaun P. , Jansen Vincent A. A.
Published: February 2018

Language transmission, the passing on of language features such as words between people, is the process of inheritance that underlies linguistic evolution. To understand how language transmission works, we need a mechanistic understanding based on empirical evidence of lasting change of language usage. Here, we analysed 200 million online conversations to investigate transmission between individuals. We find that the frequency of word usage is inherited over conversations, rather than only the binary presence or absence of a word in a person's lexicon. We propose a mechanism for transmission whereby for each word someone encounters there is a chance they will use it more often. Using this mechanism, we measure that, for one word in around every hundred a person encounters, they will use that word more frequently. As more commonly used words are encountered more often, this means that it is the frequencies of words which are copied. Beyond this, our measurements indicate that this per-encounter mechanism is neutral and applies without any further distinction as to whether a word encountered in a conversation is commonly used or not. An important consequence of this is that frequencies of many words can be used in concert to observe and measure language transmission, and our results confirm this. These results indicate that our mechanism for transmission can be used to study language patterns and evolution within populations.
A down-shifting Eu
3+
-doped Y
2
WO
6
/TiO
2
photoelectrode for improved light harvesting in dye-sensitized solar cells
Authors: Llanos J. , Brito I. , Espinoza D. , Sekar Ramkumar , Manidurai P.
Published: February 2018

Y
1.86
Eu
0.14
WO
6
phosphors were prepared using a solid-state reaction method. Their optical properties were analysed, and they was mixed with TiO
2
, sintered, and used as a photoelectrode (PE) in dye-sensitized solar cells (DSSCs). The as-prepared photoelectrode was characterized by photoluminescence spectroscopy, diffuse reflectance, electrochemical impedance spectroscopy (EIS) and X-ray diffraction. The photoelectric conversion efficiency of the DSSC with TiO
2
:Y
1.86
Eu
0.14
WO
6
(100:2.5) was 25.8% higher than that of a DSCC using pure TiO
2
as PE. This high efficiency is due to the ability of the luminescent material to convert ultraviolet radiation from the sun to visible radiation, thus improving the solar light harvesting of the DSSC.
Mate limitation and sex ratio evolution
Authors: Lehtonen Jussi , Schwanz Lisa E.
Published: February 2018

Sex ratio evolution has been one of the most successful areas of evolutionary theory. Pioneered by Düsing and Fisher under panmixia, and later extended by Hamilton to cover local mate competition (LMC), these models often assume, either implicitly or explicitly, that all females are fertilized. Here, we examine the effects of relaxing this assumption, under both panmictic and LMC models with diploid genetics. We revisit the question of the mathematical relationship between sex ratio and probability of fertilization, and use these results to model sex ratio evolution under risk of incomplete fertilization. We find that (i) under panmixia, mate limitation has no effect on the evolutionarily stable strategy (ESS) sex allocation; (ii) under LMC, mate limitation can make sex allocation less female-biased than under complete fertilization; (iii) contrary to what is occasionally stated, a significant fraction of daughters can remain unfertilized at the ESS in LMC with mate limitation; (iv) with a commonly used mating function, the fraction of unfertilized daughters can be quite large, and (v) with more realistic fertilization functions, the deviation becomes smaller. The models are presented in three equivalent forms: individual selection, kin selection and group selection. This serves as an example of the equivalence of the methods, while each approach has their own advantages. We discuss possible extensions of the model to haplodiploidy.
An adaptable but threatened big cat: density, diet and prey selection of the Indochinese leopard (Panthera pardus delacouri) in eastern Cambodia
Authors: Rostro-García Susana , Kamler Jan F. , Crouthers Rachel , Sopheak Keo , Prum Sovanna , In Visattha , Pin Chanratana , Caragiulo Anthony , Macdonald David W.
Published: February 2018

We studied the Indochinese leopard (Panthera pardus delacouri) in eastern Cambodia, in one of the few potentially remaining viable populations in Southeast Asia. The aims were to determine the: (i) current leopard density in Srepok Wildlife Sanctuary (SWS) and (ii) diet, prey selection and predation impact of leopard in SWS. The density, estimated using spatially explicit capture–recapture models, was 1.0 leopard/100 km2, 72% lower than an estimate from 2009 at the same site, and one of the lowest densities ever reported in Asia. Dietary analysis of 73 DNA confirmed scats showed leopard consumed 13 prey species, although ungulates comprised 87% of the biomass consumed (BC). The overall main prey (42% BC) was banteng (Bos javanicus), making this the only known leopard population whose main prey had adult weight greater than 500 kg. Consumption of wild pig (Sus scrofa) was also one of the highest ever reported (22% BC), indicating leopard consistently predated on ungulates with some of the largest adult weights in SWS. There were important differences in diet and prey selection between sexes, as males consumed mostly banteng (62% BC) in proportion to availability, but few muntjac (Muntiacus vaginalis; 7% BC), whereas females selectively consumed muntjac (56% BC) and avoided banteng (less than 1% BC). Predation impact was low (0.5–3.2% of populations) for the three ungulate species consumed. We conclude that the Indochinese leopard is an important apex predator in SWS, but this unique population is declining at an alarming rate and will soon be eradicated unless effective protection is provided.
On the feasibility of the computational modelling of the endoluminal vacuum-assisted closure of an oesophageal anastomotic leakage
Authors: Comellas Ester , Bellomo Facundo J. , Rosales Iván , del Castillo Luis F. , Sánchez Ricardo , Turon Pau , Oller Sergio
Published: February 2018

Endoluminal vacuum-assisted closure (E-VAC) is a promising therapy to treat anastomotic leakages of the oesophagus and bowel which are associated with high morbidity and mortality rates. An open-pore polyurethane foam is introduced into the leakage cavity and connected to a device that applies a suction pressure to accelerate the closure of the defect. Computational analysis of this healing process can advance our understanding of the biomechanical mechanisms at play. To this aim, we use a dual-stage finite-element analysis in which (i) the structural problem addresses the cavity reduction caused by the suction and (ii) a new constitutive formulation models tissue healing via permanent deformations coupled to a stiffness increase. The numerical implementation in an in-house code is described and a qualitative example illustrates the basic characteristics of the model. The computational model successfully reproduces the generic closure of an anastomotic leakage cavity, supporting the hypothesis that suction pressure promotes healing by means of the aforementioned mechanisms. However, the current framework needs to be enriched with empirical data to help advance device designs and treatment guidelines. Nonetheless, this conceptual study confirms that computational analysis can reproduce E-VAC of anastomotic leakages and establishes the bases for better understanding the mechanobiology of anastomotic defect healing.
Degradation of clofibric acid in UV/chlorine disinfection process: kinetics, reactive species contribution and pathways
Authors: Tang Yuqing , Shi Xueting , Liu Yongze , Feng Li , Zhang Liqiu
Published: February 2018

As a potential endocrine disruptor, clofibric acid (CA) was investigated in this study for its degradation kinetics and pathways in UV/chlorine process. The results showed that CA in both UV photolysis and UV/chlorine processes could be degraded via pseudo-first-order kinetics, while it almost could not be degraded in the dark chlorination process. The observed rate constant (
k
obs
) in UV photolysis was 0.0078 min
−1,
and increased to 0.0107 min
−1
combining with 0.1 mM chlorine. The
k
obs
increased to 0.0447 min
−1
with further increasing the chlorine dosage from 0.1 to 1.0 mM, and reached a plateau at higher dosage (greater than 1.0 mM). The higher
k
obs
was obtained at acid solution rather than basic solution. Moreover, the calculated contributions of radical species to
k
obs
indicated that the HO• contributed significantly to CA degradation in acidic conditions, while the reactive chlorine species and UV direct photolysis dominated in neutral and basic solution. The degradation of CA was slightly inhibited in the presence of

HC

O
3

−

(1 ∼ 50 mM), barely affected by the presence of Cl
−
(1 ∼ 200 mM) and greatly suppressed by humic acid (0 ∼ 5 mg l
−1
). Thirteen main degradation intermediates and three degradation pathways of CA were identified during UV/chlorine process.
Bifunctional fluorescent probes for detection of amyloid aggregates and reactive oxygen species
Authors: Needham Lisa-Maria , Weber Judith , Fyfe James W. B. , Kabia Omaru M. , Do Dung T. , Klimont Ewa , Zhang Yu , Rodrigues Margarida , Dobson Christopher M. , Ghandi Sonia , Bohndiek Sarah E. , Snaddon Thomas N. , Lee Steven F.
Published: February 2018

Protein aggregation into amyloid deposits and oxidative stress are key features of many neurodegenerative disorders including Parkinson's and Alzheimer's disease. We report here the creation of four highly sensitive bifunctional fluorescent probes, capable of H
2
O
2
and/or amyloid aggregate detection. These bifunctional sensors use a benzothiazole core for amyloid localization and boronic ester oxidation to specifically detect H
2
O
2
. We characterized the optical properties of these probes using both bulk fluorescence measurements and single-aggregate fluorescence imaging, and quantify changes in their fluorescence properties upon addition of amyloid aggregates of α-synuclein and pathophysiological H
2
O
2
concentrations. Our results indicate these new probes will be useful to detect and monitor neurodegenerative disease.
Evaluation of sampling frequency, window size and sensor position for classification of sheep behaviour
Authors: Walton Emily , Casey Christy , Mitsch Jurgen , Vázquez-Diosdado Jorge A. , Yan Juan , Dottorini Tania , Ellis Keith A. , Winterlich Anthony , Kaler Jasmeet
Published: February 2018

Automated behavioural classification and identification through sensors has the potential to improve health and welfare of the animals. Position of a sensor, sampling frequency and window size of segmented signal data has a major impact on classification accuracy in activity recognition and energy needs for the sensor, yet, there are no studies in precision livestock farming that have evaluated the effect of all these factors simultaneously. The aim of this study was to evaluate the effects of position (ear and collar), sampling frequency (8, 16 and 32 Hz) of a triaxial accelerometer and gyroscope sensor and window size (3, 5 and 7 s) on the classification of important behaviours in sheep such as lying, standing and walking. Behaviours were classified using a random forest approach with 44 feature characteristics. The best performance for walking, standing and lying classification in sheep (accuracy 95%,
F
-score 91%–97%) was obtained using combination of 32 Hz, 7 s and 32 Hz, 5 s for both ear and collar sensors, although, results obtained with 16 Hz and 7 s window were comparable with accuracy of 91%–93% and
F
-score 88%–95%. Energy efficiency was best at a 7 s window. This suggests that sampling at 16 Hz with 7 s window will offer benefits in a real-time behavioural monitoring system for sheep due to reduced energy needs.
Synthesis of adenosine analogues with indole moiety as human adenosine A
3
receptor ligands
Authors: Xia Yan , Zheng Xiliang , Wang Erkang , Li Dongfeng , Hou Ruibin , Wang Jin
Published: February 2018

Adenosine is an endogenous modulator exerting its functions through the activation of four adenosine receptor (AR) subtypes, termed A
1
, A
2A
, A
2B
and A
3
, which belong to the G-protein-coupled receptor superfamily. The human A
3
AR (hA
3
AR) subtype is implicated in several cytoprotective functions. Therefore, hA
3
AR modulators, and in particular agonists, are sought for their potential application as anti-inflammatory, anti-cancer and cardioprotective agents. Here, we prepared novel adenosine derivatives with indole moiety as hA
3
AR ligands. According to the biological assay, we found that 2-substituents
11
were critical structural determinants for A
3
AR ligands (
K
i
 = 111 nM). The observed structure–affinity relationships of this class of ligands were also exhaustively rationalized using the molecular modelling approach. This allows the investigation on the binding mode of the potential compound in the ligand-binding pocket of the human A
3
receptor. The results demonstrated that
11
can interact with the ASN250, GLN167, PHE168 and VAL178 through hydrogen bonding, which are shown to be important for ligand–receptor interaction.
Preparation of novel polyamine-type chelating resin with hyperbranched structures and its adsorption performance
Authors: Chen Youning , Zhao Wei , Wang Huan , Li Yuhong , Li Chenxi
Published: February 2018

This paper explored the method of combining atom transfer radical polymerization (ATRP) technology and hyperbranched polymer principle to prepare the high capacity chelating resin. First, surface-initiated atom transfer radical polymerization (SI-ATRP) method was used to graft glycidyl methacrylate (GMA) on chloromethylated cross-linked styrene-divinylbenzene resin, and then the novel polyamine chelating resin with a kind of hyperbranched structure was prepared through the amination reaction between amino group of (2-aminoethyl) triamine and epoxy group in GMA. This resin had a selective effect on As(V) and Cr(VI) at a relatively low pH and can be used for the disposal of waste water containing As(V) and Cr(VI). It had a relatively strong adsorption effect on Cu(II), Pb(II), Cd(II) and Cr(III) and can be used for the disposal of heavy metal ion waste water. The finding was that, the adsorption capacity of resin on the studied heavy metal ions was higher than that of the chelating resin synthesized by traditional technology and also higher than that of the resin modified by ATRP technology and bifunctional chelator, indicating that the combination of ATRP and hyperbranched polymer concept is an effective method to prepare chelating resin with high capacity.
MnO
2
–graphene nanosheets wrapped mesoporous carbon/sulfur composite for lithium–sulfur batteries
Authors: Li Zhengzheng
Published: February 2018

MnO
2
–graphene nanosheets wrapped mesoporous carbon/sulfur (MGN@MC/S) composite is successfully synthesized derived from metal–organic frameworks and investigated as cathode for lithium-ion batteries. Used as cathode, MGN@MC/S composite possesses electronic conductivity network for redox electron transfer and strong chemical bonding to lithium polysulfides, which enables low capacity loss to be achieved. MGN@MC/S cathodes exhibit high reversible capacity of 1475 mA h g
−1
at 0.1 C and an ultra-low capacity fading of 0.042% per cycle at 1 C over 450 cycles.
Social structure of the harem-forming promiscuous fruit bat,Cynopterus sphinx, is the harem truly important?
Authors: Garg Kritika M. , Chattopadhyay Balaji , Ramakrishnan Uma
Published: February 2018

Bats are social animals and display a diverse variety of mating and social systems, with most species exhibiting some form of polygyny. Their social organization is fluid and individuals frequently switch partners and roosting sites. While harem-like social organization is observed in multiple tropical species, its importance is contested in many of them. In this study, we investigated the role of harems in the social organization of the old world fruit batCynopterus sphinx. Based on regular behavioural observations over a period of 20 months and genetic data from microsatellite markers, we observed that the social organization is flexible, individuals regularly shift between roosts and the social organization resembles a fission–fusion society. Behavioural and genetic analyses suggest that the harems are not strict units of social structure, and the colony does not show signatures of subdivision with harems as behavioural units. We also observed that there was no correlation between individuals with high association index and pairwise relatedness. Our findings indicate that similar to the mating system, the social organization ofC. sphinxcan also be categorized as a fission–fusion society, and hence the term ‘harem’ is a misnomer. We conclude that the social system ofC. sphinxis flexible, with multi-male multi-female organization, and individuals tend to be loyal to a given area rather than a roost.
Hamiltonian flow over saddles for exploring molecular phase space structures
Authors: Farantos Stavros C.
Published: February 2018

Despite using potential energy surfaces, multivariable functions on molecular configuration space, to comprehend chemical dynamics for decades, the real happenings in molecules occur in phase space, in which the states of a classical dynamical system are completely determined by the coordinates and their conjugate momenta. Theoretical and numerical results are presented, employing alanine dipeptide as a model system, to support the view that geometrical structures in phase space dictate the dynamics of molecules, the fingerprints of which are traced by following the Hamiltonian flow above saddles. By properly selecting initial conditions in alanine dipeptide, we have found internally free rotor trajectories the existence of which can only be justified in a phase space perspective.

This article is part of the theme issue ‘Modern theoretical chemistry’.
HRS1/HHOs GARP transcription factors and reactive oxygen species are regulators of Arabidopsis nitrogen starvation response
Authors: Safi Alaeddine , Medici Anna , Szponarski Wojciech , Marshall-Colon Amy , Ruffel Sandrine , Gaymard Frédéic , Coruzzi Gloria , Lacombe Benoît , Krouk Gabriel
Published: February 2018

Plants need to cope with strong variations in the nitrogen content of the soil solution. Although many molecular actors are being discovered concerning how plants perceive NO3-provision, it is less clear how plants recognize a lack of Nitrogen. Indeed, following N removal plants activate their Nitrogen Starvation Response (NSR) being characterized in particular by the activation of very high affinity nitrate transport systems (NRT2.4, NRT2.5) and other sentinel genes such as GDH3. Here we show using a combination of functional genomics (viaTF perturbation) and molecular physiology studies, that the GARP Transcription Factors (TFs) belonging the HHO sub-family are important regulators of the NSR through two potential mechanisms. First, HHOs directly repressNRT2.4andNRT2.5high-affinity nitrate transporters. Genotypes affected in HHO genes (mutants and overexpressors) display modified high-affinity nitrate transport activities opening interesting perspectives in biotechnology applications. Second, we show that Reactive Oxygen Species (ROS) are important to control NSR in wild type plants and that HRS1 and HHO1 overexpressors are affected in their ROS content, defining a potential feedforward branch of the signaling pathway. Taken together our results define two new classes of molecular actors in the control of NSR including ROS and the first transcription factors to date. This work (i) opens perspectives on a poorly understood nutrient related signaling pathway, and (ii) defines targets for molecular breeding of plants with enhanced NO3-uptake.
Haemolymph removal by the parasite Varroa destructor can trigger the proliferation of the Deformed Wing Virus in mite infested bees (Apis mellifera), contributing to enhanced pathogen virulence
Authors: Annoscia Desiderato , Brown Sam P. , Di Prisco Gennaro , De Paoli Emanuele , Del Fabbro Simone , Zanni Virginia , Galbraith David A. , Caprio Emilio , Grozinger Christina M. , Pennacchio Francesco , Nazzi Francesco
Published: February 2018

The association between the Deformed Wing Virus and the parasitic mite Varroa destructor has been identified as a major cause of worldwide honey bee colony losses. The mite acts as a vector of the viral pathogen and can trigger its replication in infected bees. However, the mechanistic details underlying this tripartite interaction are still poorly defined, and, in particular, the causes of viral proliferation in mite infested bees.

Here we develop and test a novel hypothesis - grounded in ecological predator-prey theory - that mite feeding destabilizes viral immune control through the removal of both viral ‘prey’ and immune ‘predators’, triggering uncontrolled viral replication. Consistent with this hypothesis, we show that experimental removal of increasing volumes of haemolymph from individual bees results in increasing viral densities. In contrast, we find no support for alternative proposed mechanisms of viral expansion via mite immune-suppression or within-host viral evolution.

Overall, these results provide a new model for the mechanisms driving pathogen-parasite interactions in bees, which ultimately underpin honey bee health decline and colony losses.
Evidence of independent acquisition and adaption of ultra-small bacteria to human hosts across the highly diverse yet reduced genomes of the phylum Saccharibacteria
Authors: McLean Jeffrey S. , Bor Batbileg , To Thao T. , Liu Quanhui , Kerns Kristopher A. , Solden Lindsey , Wrighton Kelly , He Xuesong , Shi Wenyuan
Published: February 2018

Recently, we discovered that a member of the Saccharibacteria/TM7 phylum (strain TM7x) isolated from the human oral cavity, has an ultra-small cell size (200-300nm), a highly reduced genome (705 Kbp) with limited de novo biosynthetic capabilities, and a very novel lifestyle as an obligate epibiont on the surface of another bacterium 1. There has been considerable interest in uncultivated phyla, particularly those that are now classified as the proposed candidate phyla radiation (CPR) reported to include 35 or more phyla and are estimated to make up nearly 15% of the domain Bacteria. Most members of the larger CPR group share genomic properties with Saccharibacteria including reduced genomes (<1Mbp) and lack of biosynthetic capabilities, yet to date, strain TM7x represents the only member of the CPR that has been cultivated and is one of only three CPR routinely detected in the human body. Through small subunit ribosomal RNA (SSU rRNA) gene surveys, members of the Saccharibacteria phylum are reported in many environments as well as within a diversity of host species and have been shown to increase dramatically in human oral and gut diseases. With a single copy of the 16S rRNA gene resolved on a few limited genomes, their absolute abundance is most often underestimated and their potential role in disease pathogenesis is therefore underappreciated. Despite being an obligate parasite dependent on other bacteria, six groups (G1-G6) are recognized using SSU rRNA gene phylogeny in the oral cavity alone. At present, only genomes from the G1 group, which includes related and remarkably syntenic environmental and human oral associated representatives1, have been uncovered to date. In this study we systematically captured the spectrum of known diversity in this phylum by reconstructing completely novel Class level genomes belonging to groups G3, G6 and G5 through cultivation enrichment and/or metagenomic binning from humans and mammalian rumen. Additional genomes for representatives of G1 were also obtained from modern oral plaque and ancient dental calculus. Comparative analysis revealed remarkable divergence in the host-associated members across this phylum. Within the human oral cavity alone, variation in as much as 70% of the genes from nearest oral clade (AAI 50%) as well as wide GC content variation is evident in these newly captured divergent members (G3, G5 and G6) with no environmental relatives. Comparative analyses suggest independent episodes of transmission of these TM7 groups into humans and convergent evolution of several key functions during adaptation within hosts. In addition, we provide evidence from in vivo collected samples that each of these major groups are ultra-small in size and are found attached to larger cells.
Single cell network analysis with a mixture of Nested Effects Models
Authors: Pirkl Martin , Beerenwinkel Niko
Published: February 2018

Motivation

New technologies allow for the elaborate measurement of different traits of single cells. These data promise to elucidate intra-cellular networks in unprecedented detail and further help to improve treatment of diseases like cancer. However, cell populations can be very heterogeneous.

Results

We developed a mixture of Nested Effects Models (M&NEM) for single-cell data to simultaneously identify different cellular sub-populations and their corresponding causal networks to explain the heterogeneity in a cell population. For inference, we assign each cell to a network with a certain probability and iteratively update the optimal networks and cell probabilities in an Expectation Maximization scheme. We validate our method in the controlled setting of a simulation study and apply it to three data sets of pooled CRISPR screens generated previously by two novel experimental techniques, namely Crop-Seq and Perturb-Seq.

Availability

The mixture Nested Effects Model (M&NEM) is available as the R-package mnem at https://github.com/cbgethz/mnem/.

Contact

martin.pirkl@bsse.ethz.ch, niko.beerenwinkel@bsse.ethz.ch

Supplementary information

Supplementary data are available.online.
Mitochondrial D-loop DNA analyses of Norway Lobster (Nephrops norvegicus) reveals genetic isolation between Atlantic and Mediterranean populations
Authors: Gallagher Jeanne , Finarelli John A. , Jonasson Jónas P. , Carlsson Jens
Published: February 2018

Nephrops norvegicusis a commercially valuable demersal fisheries species. Relatively little is understood about this species’ population dynamics across its distribution with previous mitochondrial and microsatellite studies failing to identify significant population-level differentiation. In this study, sequence variation in the mitochondrial (mtDNA) D-loop was analysed from samples across the distribution range. Analysis of a 375bp fragment of the D-loop revealed significant genetic differentiation between samples from the northeast Atlantic and the East Mediterranean (FST= 0.107, P<0.001). Tau (τ), theta (θ0and θ1) and Fu’s Fsvalues suggest the species spread between 10,500 to 19,000 ybp and subsequently expanded rapidly across the Atlantic.
BDQC: a general-purpose analytics tool for domain-blind validation of Big Data
Authors: Deutsch Eric W. , Kramer Roger , Ames Joseph , Bauman Andrew , Campbell David S. , Chard Kyle , Clark Kristi , D’Arcy Mike , Dinov Ivo D. , Donovan Rory , Foster Ian , Heavner Benjamin D. , Hood Leroy E. , Kesselman Carl , Madduri Ravi , Mi Huaiyu , Muruganujan Anushya , Pa Judy , Price Nathan D. , Robinson Max , Sepehrband Farshid , Toga Arthur W. , Van Horn John , Zhao Lu , Glusman Gustavo
Published: February 2018

Translational biomedical research is generating exponentially more data: thousands of whole-genome sequences (WGS) are now available; brain data are doubling every two years. Analyses of Big Data, including imaging, genomic, phenotypic, and clinical data, present qualitatively new challenges as well as opportunities. Among the challenges is a proliferation in ways analyses can fail, due largely to the increasing length and complexity of processing pipelines. Anomalies in input data, runtime resource exhaustion or node failure in a distributed computation can all cause pipeline hiccups that are not necessarily obvious in the output. Flaws that can taint results may persist undetected in complex pipelines, a danger amplified by the fact that research is often concurrent with the development of the software on which it depends. On the positive side, the huge sample sizes increase statistical power, which in turn can shed new insight and motivate innovative analytic approaches. We have developed a framework for Big Data Quality Control (BDQC) including an extensible set of heuristic and statistical analyses that identify deviations in data without regard to its meaning (domain-blind analyses). BDQC takes advantage of large sample sizes to classify the samples, estimate distributions and identify outliers. Such outliers may be symptoms of technology failure (e.g., truncated output of one step of a pipeline for a single genome) or may reveal unsuspected “ signal” in the data (e.g., evidence of aneuploidy in a genome). We have applied the framework to validate real-world WGS analysis pipelines. BDQC successfully identified data outliers representing various failure classes, including genome analyses missing a whole chromosome or part thereof, hidden among thousands of intermediary output files. These failures could then be resolved by reanalyzing the affected samples. BDQC both identified hidden flaws as well as yielded new insights into the data. BDQC is designed to complement quality software development practices. There are multiple benefits from the application of BDQC at all pipeline stages. By verifying input correctness, it can help avoid expensive computations on flawed data. Analysis of intermediary and final results facilitates recovery from aberrant termination of processes. All these computationally inexpensive verifications reduce cryptic analytical artifacts that could seriously preclude clinical-grade genome interpretation. BDQC is available at https://github.com/ini-bdds/bdqc.
Activity of Antimicrobial Peptides Decreases with Increased Cell Membrane Crossing Free Energy Cost
Authors: Zou Rongfeng , Zhu Xiaomin , Tu Yaoquan , Wu Junchen , Landry Markita P.
Published: February 2018

Antimicrobial peptides (AMPs) are a promising alternative to mitigating bacterial infections in light of increasing bacterial resistance to antibiotics. However, predicting, understanding, and controlling the antibacterial activity of AMPs remains a significant challenge. While peptide intramolecular interactions are known to modulate AMP antimi-crobial activity, peptide intermolecular interactions remain elusive in their impact on peptide bioactivity. Herein, we test the relationship between AMP intermolecular interactions and antibacterial efficacy by controlling AMP intermolecular hydrophobic and hydrogen bonding interactions. Molecular dynamics simulations and Gibbs free energy calculations in concert with experimental assays show that increasing intermolecular interactions via inter-peptide aggregation increases the energy cost for the peptide to cross the bacterial cell membrane, which in turn decreases the AMP antibacterial activity. Our findings provide a route for predicting and controlling the antibacterial activity of AMPs against Gramnegative bacteria via reductions of intermolecular AMP interactions.
Early candidate urine biomarkers for detecting Alzheimer’s disease before beta amyloid plaque deposition in an APP (swe)/PSEN1dE9transgenic mouse model
Authors: Zhang Fanshuang , Wei Jing , Li Xundou , Ma Chao , Gao Youhe
Published: February 2018

Alzheimer’s disease (AD) is an incurable age-associated neurodegenerative disorder that is characterized by irreversible progressive cognitive deficits and extensive brain damage. The identification of candidate biomarkers before beta amyloid plaque deposition occurs is therefore of great importance for the early intervention of AD. Urine, which is not regulated by homeostatic mechanisms, theoretically accumulates changes associated with AD earlier than cerebrospinal fluid and blood. In this study, an APP (swe)/PSEN1dE9 transgenic mouse model was used to identify candidate biomarkers for early AD. Urine samples were collected from 4-, 6-, and 8-month-old transgenic mouse models, and the urinary proteomes were profiled using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The levels of 33 proteins differed significantly between wild-type and 4-month-old mice, which had not started to deposit beta amyloid plaque. Among these proteins, 16 have been associated with the mechanisms of AD, while 9 have been suggested as AD biomarkers. Our results indicated that urine proteins enable detecting AD before beta amyloid plaque deposition, which may present an opportunity for intervention.
Divergent PAM Specificity of a Highly-Similar SpCas9 Ortholog
Authors: Chatterjee Pranam , Jakimo Noah , Jacobson Joseph M.
Published: February 2018

RNA-guided DNA endonucleases of the CRISPR-Cas system are widely used for genome engineering and thus have numerous applications in a wide variety of fields. The range of sequences that CRISPR endonucleases can recognize, however, is constrained by the need for a specific protospacer adjacent motif (PAM) flanking the target site. In this study, we demonstrate the natural PAM plasticity of a highly-similar, yet previously uncharacterized, Cas9 fromStreptococcus canis(ScCas9) through rational manipulation of distinguishing motif insertions. To this end, we report a divergent affinity to 5’-NNGT-3’ PAM sequences and demonstrate the editing capabilities of the ortholog in both bacterial and human cells. Finally, we build an automated bioinformatics pipeline, the Search for PAMs by ALignment Of Targets (SPAMALOT), which further explores the microbial PAM diversity of otherwise-overlookedStreptococcusCas9 orthologs. Our results establish that ScCas9 can be utilized both as an alternative genome editing tool and as a functional platform to discover novelStreptococcusPAM specificities.
Sent to the Corner: xylem vessel anatomy not surface area determines megaphyll hydraulics inCecropia obtusaTrécul (Urticaceae)
Authors: Levionnois Sébastien , Coste Sabrina , Nicolini Eric , Stahl Clément , Morel Hélène , Heuret Patrick
Published: February 2018

Corners rule predicts a positive correlation between leaf dimensions and the cross-sectional area of the primary stem. Although this relationship is usually explained by hydraulic and mechanical requirements, these hypotheses have never been tested empirically. However, Corner’s rule is tricky to investigate since rapid secondary growth of the stem prevents a rigorous link being established between a given leaf and the supporting stem. We chose a twig-like leaf model since petiole anatomy is only linked to the attached lamina. We tested the hypothesis that anatomical adjustments to hydraulic requirements related to vessel size enable reduced investment in tissue in the framework of Corner’s rule. We conducted a functional, mechanistic and intraspecific investigation ofCecropia obtusaTrécul, a Neotropical pioneer tree, by integrating morphological, anatomical and theoretical hydraulic traits around the lamina-petiole size relationship. The twig-like structure of the leaf and the strong lamina-petiole correlation of this model tree species made it possible to use the leaf-level model for a rigorous investigation of the functional implications of Corner’s rule. We found a positive correlation between petiole size, lamina size, the ratio of mean vessel area to vessel frequency in the petiole xylem and theoretical specific conductivity in the petiole xylem. Hydraulic function supports Corner’s rule to a lesser extent than previously thought. Variations in vessel dimensions mainly drive xylem hydraulic performances and avoid disproportionate petiole cross-sections to answer to hydraulic requirements associated with lamina size.
Genomes of trombidid mites reveal novel predicted allergens and laterally-transferred genes associated with secondary metabolism
Authors: Dong Xiaofeng , Chaisiri Kittipong , Xia Dong , Armstrong Stuart D. , Fang Yongxiang , Donnelly Martin J. , Kadowaki Tatsuhiko , McGarry John W. , Darby Alistair C. , Makepeace Benjamin L.
Published: February 2018

Background

Trombidid mites have a unique lifecycle in which only the larval stage is ectoparasitic. In the superfamily Trombiculoidea (“chiggers”), the larvae feed preferentially on vertebrates, including humans. Species in the genusLeptotrombidiumare vectors of a potentially fatal bacterial infection, scrub typhus, which affects 1 million people annually. Moreover, chiggers can cause pruritic dermatitis (trombiculiasis) in humans and domesticated animals. In the Trombidioidea (velvet mites), the larvae feed on other arthropods and are potential biological control agents for agricultural pests. Here, we present the first trombidid mites genomes, obtained both for a chigger,Leptotrombidium deliense, and for a velvet mite,Dinothrombium tinctorium.

Results

Sequencing was performed using Illumina technology. A 180 Mb draft assembly forD. tinctoriumwas generated from two paired-end and one mate-pair library using a single adult specimen. ForL. deliense, a lower-coverage draft assembly (117 Mb) was obtained using pooled, engorged larvae with a single paired-end library. Remarkably, both genomes exhibited evidence of ancient lateral gene transfer from soil-derived bacteria or fungi. The transferred genes confer functions that are rare in animals, including terpene and carotenoid synthesis. Thirty-seven allergenic protein families were predicted in theL. deliensegenome, of which nine were unique. Preliminary proteomic analyses identified several of these putative allergens in larvae.

Conclusions

Trombidid mite genomes appear to be more dynamic than those of other acariform mites. A priority for future research is to determine the biological function of terpene synthesis in this taxon and its potential for exploitation in disease control.