bluuebunny/crossref_metadata_2025 huggingface dataset:
Incorporating the gut microbiota into models of human and non‐human primate ecology and evolution
Authors: Amato Katherine R.
Published: January 2016

The mammalian gut is home to a diverse community of microbes. Advances in technology over the past two decades have allowed us to examine this community, the gut microbiota, in more detail, revealing a wide range of influences on host nutrition, health, and behavior. These host‐gut microbe interactions appear to shape host plasticity and fitness in a variety of contexts, and therefore represent a key factor missing from existing models of human and non‐human primate ecology and evolution. However, current studies of the gut microbiota tend to include limited contextual data or are clinical, making it difficult to directly test broad anthropological hypotheses. Here, I review what is known about the animal gut microbiota and provide examples of how gut microbiota research can be integrated into the study of human and non‐human primate ecology and evolution with targeted data collection. Specifically, I examine how the gut microbiota may impact primate diet, energetics, disease resistance, and cognition. While gut microbiota research is proliferating rapidly, especially in the context of humans, there remain important gaps in our understanding of host‐gut microbe interactions that will require an anthropological perspective to fill. Likewise, gut microbiota research will be an important tool for filling remaining gaps in anthropological research. Am J Phys Anthropol 159:S196–S215, 2016. © 2016 American Association of Physical Anthropologists
Identifications of ancient Egyptian royal mummies from the 18th Dynasty reconsidered
Authors: Habicht M.E. , Bouwman A.S. , Rühli F.J.
Published: January 2016

For centuries, ancient Egyptian Royal mummies have drawn the attention both of the general public and scientists. Many royal mummies from the New Kingdom have survived. The discoveries of the bodies of these ancient rulers have always sparked much attention, yet not all identifications are clear even nowadays. This study presents a meta‐analysis to demonstrate the difficulties in identifying ancient Egyptian royal mummies. Various methods and pitfalls in the identification of the Pharaohs are reassessed since new scientific methods can be used, such as ancient DNA‐profiling and CT‐scanning. While the ancestors of Tutankhamun have been identified, some identities are still highly controversial (e.g., the mystery of the KV‐55 skeleton, recently most likely identified as the genetic father of Tutankhamun). The meta‐analysis confirms the suggested identity of some mummies (e.g., Amenhotep III, Thutmosis IV, and Queen Tjye). Am J Phys Anthropol 159:S216–S231, 2016. © 2016 American Association of Physical Anthropologists
Accepting, understanding, teaching, and learning (human) evolution: Obstacles and opportunities
Authors: Pobiner Briana
Published: January 2016

Questions about our origin as a species are universal and compelling. Evolution—and in particular human evolution—is a subject that generates intense interest across the world, evidenced by the fact that fossil and DNA discoveries grace the covers of major science journals and magazines as well as other popular print and online media. However, virtually all national polls indicate that the majority of Americans strongly reject biological evolution as a fact‐based, well‐tested, and robust understanding of the history of life. In the popular mind, no topic in all of science is more contentious or polarizing than evolution and media sources often only serve to magnify this polarization by covering challenges to the teaching of evolution. In the realm of teaching, debates about evolution have shaped textbooks, curricula, standards, and policy. Challenges to accepting and understanding evolution include mistrust and denial of science, cognitive obstacles and misconceptions, language and terminology, and a religious worldview, among others. Teachers, who are on the front lines of these challenges, must be armed with the tools and techniques to teach evolution in formal education settings across grades K‐16 in a straightforward, thorough, and sensitive way. Despite the potentially controversial topic of human evolution, growing research is demonstrating that a pedagogical focus on human examples is an effective and engaging way to teach core concepts of evolutionary biology. Am J Phys Anthropol 159:S232–S274, 2016. © 2016 American Association of Physical Anthropologists
Intact recognition, but attenuated adaptation, for biological motion in youth with autism spectrum disorder
Authors: van Boxtel Jeroen J. A. , Dapretto Mirella , Lu Hongjing
Published: January 2016

Given the ecological importance of biological motion and its relevance to social cognition, considerable effort has been devoted over the past decade to studying biological motion perception in autism. However, previous studies have asked observers to detect or recognize briefly presented human actions placed in isolation, without spatial or temporal context. Research on typical populations has shown the influence of temporal context in biological motion perception: prolonged exposure to one action gives rise to an aftereffect that biases perception of a subsequently displayed action. Whether people with autism spectrum disorders (ASD) show such adaptation effects for biological motion stimuli remains unknown. To address this question, this study examined how well youth with ASD recognize ambiguous actions and adapt to recently‐observed actions. Compared to typically‐developing (TD) controls, youth with ASD showed no differences in perceptual boundaries between actions categories, indicating intact ability in recognizing actions. However, children with ASD showed weakened adaptation to biological motion. It is unlikely that the reduced action adaptability in autism was due to delayed developmental trajectory, as older children with ASD showed weaker adaptation to actions than younger children with ASD. Our results further suggest that high‐level (i.e., action) processing weakens with age for children with ASD, but this change may be accompanied by a potentially compensatory mechanism based on more involvement of low‐level (i.e., motion) processing. Autism Res 2016, 9: 1103–1113. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Atypical development of the central auditory system in young children with Autism spectrum disorder
Authors: Yoshimura Yuko , Kikuchi Mitsuru , Hiraishi Hirotoshi , Hasegawa Chiaki , Takahashi Tetsuya , Remijn Gerard B. , Oi Manabu , Munesue Toshio , Higashida Haruhiro , Minabe Yoshio , Kojima Haruyuki
Published: January 2016

The P1m component of the auditory evoked magnetic field is the earliest cortical response associated with language acquisition. However, the growth curve of the P1m component is unknown in both typically developing (TD) and atypically developing children. The aim of this study is to clarify the developmental pattern of this component when evoked by binaural human voice stimulation using child‐customized magnetoencephalography. A total of 35 young TD children (32–121 months of age) and 35 children with autism spectrum disorder (ASD) (38–111 months of age) participated in this study. This is the first report to demonstrate an inverted U‐shaped growth curve for the P1m dipole intensity in the left hemisphere in TD children. In addition, our results revealed a more diversified age‐related distribution of auditory brain responses in 3‐ to 9‐year‐old children with ASD. These results demonstrate the diversified growth curve of the P1m component in ASD during young childhood, which is a crucial period for first language acquisition. Autism Res 2016, 9: 1216–1226. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
White matter volume in the brainstem and inferior parietal lobule is related to motor performance in children with autism spectrum disorder: A voxel‐based morphometry study
Authors: Hanaie Ryuzo , Mohri Ikuko , Kagitani‐Shimono Kuriko , Tachibana Masaya , Matsuzaki Junko , Hirata Ikuko , Nagatani Fumiyo , Watanabe Yoshiyuki , Fujita Norihiko , Taniike Masako
Published: January 2016

Many studies have reported poor motor performance in autism spectrum disorder (ASD); however, the underlying brain mechanisms remain unclear. Recent neuroimaging studies have suggested that abnormalities of the white matter (WM) are related to the features of ASD. In this study, we used voxel‐based morphometry (VBM) to investigate which WM regions correlate with motor performance in children with ASD, and whether the WM volume in those brain regions differed between children with ASD and typically developing (TD) children. The subjects included 19 children with ASD and 20 TD controls. Motor performance was assessed using the Movement Assessment Battery for Children 2 (M‐ABC 2). Children with ASD showed poorer motor performance than did the controls. There was a significant positive correlation between the total test score on the M‐ABC 2 and the volume of WM in the brainstem and WM adjacent to the left supramarginal gyrus (SMG). In addition, compared with the TD controls, children with ASD had a decreased volume of WM in the brainstem and adjacent to the left intraparietal sulcus, which is close to the SMG. These findings suggest that structural changes in the WM in the brainstem and left inferior parietal lobule may contribute to poor motor performance in children with ASD. Autism Res 2016, 9: 981–992. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Oxygen transfer rates in shaken culture vessels from Fernbach flasks to microtiter plates
Authors: Running Jeffrey A. , Bansal Karan
Published: January 2016

By a sulfite oxidation method, oxygen transfer rates (OTRs) were determined in 11 types of culture vessels from 2.8‐L Fernbach (FB) flasks to 96‐, 48‐, and 24‐well square deepwell microtiter plates (MTPs). OTRs ranged from 140 mM/h in 250‐mL Ultrayield™ flasks shaken at 300 rpm with a 50 mm diameter shaker throw to 5 mM/h in unbaffled FBs shaken at 200 rpm with a 25 mm throw. Baffles in FBs increased OTRs 6–12‐fold under various shaking conditions, and up to five‐fold in 250‐mL flasks, depending on the type of baffles. Corner‐baffling was superior to bottom‐baffling in glass, 250‐mL flasks. In MTPs, OTRs increased with increasing well size and decreasing fill volume. At 50 mm throw and 300 rpm, 24‐well MTPs had OTRs comparable to corner‐baffled, 250‐mL flasks (∼100 mM/h). The OTRs in unbaffled flasks were relatively insensitive to shaking conditions, increasing less than two‐fold between the most modest and the most vigorous conditions. There was no consistency across vessels as to whether the alternate incubation conditions of 70 mm throw and 250 rpm produced higher OTRs than the 50 mm throw and 300 rpm regimen. No increase in OTR was seen in any MTP when the cover hole diameter was increased beyond 4.5 mm. OTRs decreased as viscosity increased, falling smoothly in unbaffled flasks and 24‐well MTPs, but 48‐well and 96‐well MTPs showed precipitous OTR drops as viscosity increased. Matching the OTRs of screening vessels to the oxygen uptake rates of microbial cultures can greatly reduce the number of false positive strains that are forwarded from microbial screens. Biotechnol. Bioeng. 2016;113: 1729–1735. © 2016 Wiley Periodicals, Inc.
Engineered bacterial polyester hydrolases efficiently degrade polyethylene terephthalate due to relieved product inhibition
Authors: Wei Ren , Oeser Thorsten , Schmidt Juliane , Meier René , Barth Markus , Then Johannes , Zimmermann Wolfgang
Published: January 2016

Recent studies on the enzymatic degradation of synthetic polyesters have shown the potential of polyester hydrolases from thermophilic actinomycetes for modifying or degrading polyethylene terephthalate (PET). TfCut2 from Thermobifida fusca KW3 and LC‐cutinase (LCC) isolated from a compost metagenome are remarkably active polyester hydrolases with high sequence and structural similarity. Both enzymes exhibit an exposed active site in a substrate binding groove located at the protein surface. By exchanging selected amino acid residues of TfCut2 involved in substrate binding with those present in LCC, enzyme variants with increased PET hydrolytic activity at 65°C were obtained. The highest activity in hydrolyzing PET films and fibers were detected with the single variant G62A and the double variant G62A/I213S. Both variants caused a weight loss of PET films of more than 42% after 50 h of hydrolysis, corresponding to a 2.7‐fold increase compared to the wild type enzyme. Kinetic analysis based on the released PET hydrolysis products confirmed the superior hydrolytic activity of G62A with a fourfold higher hydrolysis rate constant and a 1.5‐fold lower substrate binding constant than those of the wild type enzyme. Mono‐(2‐hydroxyethyl) terephthalate is a strong inhibitor of TfCut2. A determination of the Rosetta binding energy suggested a reduced interaction of G62A with 2PET, a dimer of the PET monomer ethylene terephthalate. Indeed, G62A revealed a 5.5‐fold lower binding constant to the inhibitor than the wild type enzyme indicating that its increased PET hydrolysis activity is the result of a relieved product inhibition by mono‐(2‐hydroxyethyl) terephthalate. Biotechnol. Bioeng. 2016;113: 1658–1665. © 2016 Wiley Periodicals, Inc.
Engineering and comparison of non‐natural pathways for microbial phenol production
Authors: Thompson Brian , Machas Michael , Nielsen David R.
Published: January 2016

The non‐renewable petrochemical phenol is used as a precursor to produce numerous fine and commodity chemicals, including various pharmaceuticals and phenolic resins. Microbial phenol biosynthesis has previously been established, stemming from endogenous tyrosine via tyrosine phenol lyase (TPL). TPL, however, suffers from feedback inhibition and equilibrium limitations, both of which contribute to reduced flux through the overall pathway. To address these limitations, two novel and non‐natural phenol biosynthesis pathways, both stemming instead from chorismate, were constructed and comparatively evaluated. The first proceeds to phenol in one heterologous step via the intermediate p‐hydroxybenzoic acid, while the second involves two heterologous steps and the associated intermediates isochorismate and salicylate. Maximum phenol titers achieved via these two alternative pathways reached as high as 377 ± 14 and 259 ± 31 mg/L in batch shake flask cultures, respectively. In contrast, under analogous conditions, phenol production via the established TPL‐dependent route reached 377 ± 23 mg/L, which approaches the maximum achievable output reported to date under batch conditions. Additional strain development and optimization of relevant culture conditions with respect to each individual pathway is ultimately expected to result in further improved phenol production. Biotechnol. Bioeng. 2016;113: 1745–1754. © 2016 Wiley Periodicals, Inc.
Behavioural recovery after treatment for varicose veins
Authors: Cotton S C , MacLennan G , Brittenden J , Prior M , Francis J
Published: January 2016

Background

The aim of this study was to assess behavioural recovery from the patient's perspective as a prespecified secondary outcome in a multicentre parallel-group randomized clinical trial comparing ultrasound-guided foam sclerotherapy (UGFS), endovenous laser ablation (EVLA) and surgery for the treatment of primary varicose veins.

Methods

Participants were recruited from 11 UK sites as part of the CLASS trial, a randomized trial of UGFS, EVLA or surgery for varicose veins. Patients were followed up 6 weeks after treatment and asked to complete the Behavioural Recovery After treatment for Varicose Veins (BRAVVO) questionnaire. This is a 15-item instrument that covers eight activity behaviours (tasks or actions an individual is capable of doing in an idealized situation) and seven participation behaviours (what the individual does in an everyday, real-world situation) that were identified to be important from the patient's perspective.

Results

A total of 798 participants were recruited. Both UGFS and EVLA resulted in a significantly quicker recovery compared with surgery for 13 of the 15 behaviours assessed. UGFS was superior to EVLA in terms of return to full-time work (hazard ratio 1·43, 95 per cent c.i. 1·11 to 1·85), looking after children (1·45, 1·04 to 2·02) and walks of short (1·48, 1·19 to 1·84) and longer (1·32, 1·05 to 1·66) duration.

Conclusion

Both UGFS and EVLA resulted in more rapid recovery than surgery, and UGFS was superior to EVLA for one-quarter of the behaviours assessed. The BRAVVO questionnaire has the potential to provide important meaningful information to patients about their early recovery and what they may expect to be able to achieve after treatment.
Performance of the revised Atlanta and determinant-based classifications for severity in acute pancreatitis
Authors: Bansal S S , Hodson J , Sutcliffe R S , Marudanayagam R , Muiesan P , Mirza D F , Isaac J , Roberts K J
Published: January 2016

Background

Severity classification systems aim to stratify patients with acute pancreatitis reliably into coherent risk groups. Recently, the Atlanta 1992 classification has been revised (Atlanta 2012) and a novel determinant-based classification (DBC) system developed. This study assessed the ability of the three systems to stratify disease severity among patients with acute pancreatitis.

Methods

This was an observational cohort study of patients with acute pancreatitis identified from an institutional database. Cohort characteristics, investigations, interventions and outcomes were identified. Systems were compared using receiver operating characteristic (ROC) analysis and Spearman's correlation coefficients.

Results

The in-hospital mortality rate was 6·6 per cent (15 of 228 patients). All of the outcomes considered correlated significantly with the three systems, with the exception of the need for surgery in Atlanta 1992. Atlanta 2012 and the DBC had higher area under the curve (AUC) values than Atlanta 1992 for all outcomes. The revised Atlanta and DBC systems both performed similarly with regard to ICU admission (AUC 0·927 and 0·917 respectively; both P < 0·001), need for percutaneous drainage (AUC 0·879 and 0·891; both P < 0·001), need for surgery (AUC 0·827 and 0·845; P = 0·006 and P = 0·004 respectively) and in-hospital mortality (0·955 and 0·931; both P < 0·001). However, the critical category in the DBC system identified patients with the most severe disease; seven of eight patients in this group died in hospital, compared with 15 of 34 with severe pancreatitis according to Atlanta 2012.

Conclusion

The Atlanta 2012 and DBC perform equally well for classification of disease severity in acute pancreatitis. The addition of a critical category in the DBC identifies patients with the most severe disease.
pH monitoring of gastro-oesophageal reflux before and after laparoscopic sleeve gastrectomy
Authors: Thereaux J , Barsamian C , Bretault M , Dusaussoy H , Lamarque D , Bouillot J-L , Czernichow S , Carette C
Published: January 2016

Background

Gastro-oesophageal reflux disease (GORD) is a common obesity-related co-morbidity that is assessed objectively by 24-h pH monitoring. Some concerns have been raised regarding the risk of de novo GORD or exacerbation of pre-existing GORD after laparoscopic sleeve gastrectomy. Here, 24-h pH monitoring was used to assess the influence of laparoscopic sleeve gastrectomy on postoperative GORD in obese patients with or without preoperative GORD.

Methods

From July 2012 to September 2014, all patients scheduled for laparoscopic sleeve gastrectomy were invited to participate in a prospective follow-up. Patients who underwent preoperative 24-h pH monitoring were asked to repeat the examination 6 months after operation. GORD was defined as an oesophageal pH < 4 for at least 4·2 per cent of the total time recorded.

Results

Of 89 patients, 76 had preoperative pH monitoring for GORD evaluation and 50 had postoperative reassessment. Patients without (group 1, 29 patients) or with (group 2, 21 patients) preoperative GORD were similar regarding age, sex ratio and body mass index. In group 1, the median (i.q.r.) total time at pH < 4 was significantly higher after surgery than before: 5·6 (2·5–9·5) versus 1·6 (0·7–2·9) per cent (P < 0·001). Twenty of the 29 patients experienced de novo GORD as determined by 24-h pH monitoring (P < 0·001). In group 2, total time at pH < 4 after surgery was no different from the preoperative value: 5·9 (3·9–10·7) versus 7·7 (5·2–10·3) per cent (P = 0·296).

Conclusion

Laparoscopic sleeve gastrectomy was associated with de novo GORD in over two-thirds of patients, but did not seem to exacerbate existing GORD.
A time and motion study of subcutaneous versus intravenous trastuzumab in patients with HER2‐positive early breast cancer
Authors: De Cock Erwin , Pivot Xavier , Hauser Nik , Verma Sunil , Kritikou Persefoni , Millar Douglas , Knoop Ann
Published: January 2016

Within PrefHer (NCT01401166), patients and healthcare professionals (HCPs) preferred subcutaneous (SC) over intravenous (IV) trastuzumab. We undertook a prospective, observational time and motion study to quantify patients’ time in infusion chairs and active HCP time in PrefHer. Patients with HER2‐positive early breast cancer received four adjuvant cycles of SC trastuzumab (600 mg fixed dose via SC single‐use injection device [SID, Cohort 1] or SC handheld syringe [HHS, Cohort 2]) then four cycles of standard IV trastuzumab or the reverse sequence. Generic case report forms for IV and SC management, both in the treatment room and the drug preparation area, were tailored to reflect center practices. Patient chair time and active HCP time were recorded. We compared pooled Cohort 1 + 2 IV with Cohort 1 SC SID and Cohort 2 SC HHS mean times across eight countries and individually within them utilizing a random intercept generalized linear mixed‐effects model. Per session, the SC SID saved a mean of 57 min of patient chair time versus IV (range across countries: 47–86; P < 0.0001); the SC HHS saved 55 min (40–81; P < 0.0001). Active HCP time was reduced by a mean of 13 min per session with the SC SID (range across countries: 4–16; P < 0.0001) and 17 min with the SC HHS (5–28; P < 0.0001) versus IV. SC trastuzumab, delivered via SID or HHS, saved patient chair and active HCP times versus IV infusion, supporting a transition to either SC method.
How to Avoid Foam Formation in Biogas Plants by Coarse Grain Anaerobic Digestion
Authors: Moeller Lucie , Krieg Frederike , Zehnsdorf Andreas , Müller Roland Arno
Published: January 2016

The grain used in biogas production is generally coarse grain. However, the anaerobic digestion of coarse grain often leads to excessive foam formation in biogas reactors. Comprehensive foaming experiments using six sample grain species, namely, triticale, wheat, rye, barley, oats, and millet, were carried out in order to investigate the reasons for grain‐based foam formation and to develop methods for minimizing foaming problems. It was found that the intensity of foam formation depended not only on the grain species, but also on the processing of the coarse grain: the finer the grain was ground, the higher the foam content in the test bottles. The most intensive foam formation was observed for wheat and triticale. The addition of soybean oil to coarse grain led to a reduction in foam intensity.
Evaluation of Electrolyte Additives for High‐Temperature Polymer Electrolyte Fuel Cells
Authors: Mack Florian , Galbiati Samuele , Gogel Viktor , Jörissen Ludwig , Zeis Roswitha
Published: January 2016

In this study, perfluoroalkyl phosphonic acids CF3PO3H2 and C2F5PO3H2 are investigated as additives to phosphoric acid to improve the oxygen reduction reaction (ORR) of high‐temperature polymer electrolyte (PEM) fuel cells. A comprehensive characterization of acid mixtures composed of 20 wt % additive and 80 wt % concentrated phosphoric acid is presented, ranging from ex situ measurements to in situ tests in operating high‐temperature PEM fuel cells. CF3PO3H2 and C2F5PO3H2 additives exhibit excellent thermal stability and are found to improve the wetting of the electrode. The fuel cell's output power increases consistently (240/270 mW cm−2 vs. 180 mW cm−2), owing to a decrease in the oxygen reduction reaction charge‐transfer resistance.
Formation and Reactivity of Organo‐Functionalized Tin Selenide Clusters
Authors: Rinn Niklas , Eußner Jens P. , Kaschuba Willy , Xie Xiulan , Dehnen Stefanie
Published: January 2016

Reactions of R1SnCl3 (R1=CMe2CH2C(O)Me) with (SiMe3)2Se yield a series of organo‐functionalized tin selenide clusters, [(SnR1)2SeCl4] (1), [(SnR1)2Se2Cl2] (2), [(SnR1)3Se4Cl] (3), and [(SnR1)4Se6] (4), depending on the solvent and ratio of the reactants used. NMR experiments clearly suggest a stepwise formation of 1 through 4 by subsequent condensation steps with the concomitant release of Me3SiCl. Furthermore, addition of hydrazines to the keto‐functionalized clusters leads to the formation of hydrazone derivatives, [(Sn2(μ‐R3)(μ‐Se)Cl4] (5, R3=[CMe2CH2CMe(NH)]2), [(SnR2)3Se4Cl] (6, R2=CMe2CH2C(NNH2)Me), [(SnR4)3Se4][SnCl3] (7, R4=CMe2CH2C(NNHPh)Me), [(SnR2)4Se6] (8), and [(SnR4)4Se6] (9). Upon treatment of 4 with [Cu(PPh3)3Cl] and excess (SiMe3)2Se, the cluster fragments to form [(R1Sn)2Se2(CuPPh3)2Se2] (10), the first discrete Sn/Se/Cu cluster compound reported in the literature. The derivatization reactions indicate fundamental differences between organotin sulfide and organotin selenide chemistry.
Water‐Soluble Luminescent Hybrid Composites Consisting of Oligosilsesquioxanes and Lanthanide Complexes and their Sensing Ability for Cu2+
Authors: Xu Qianqian , Li Zhiqiang , Li Huanrong
Published: January 2016

Water‐soluble hybrid composites with great potential for selective and sensitive sensing and that are obtained through simple, rapid, and environmentally friendly methods are highly desirable and remain a challenging task. Herein, we present luminescent hybrid composites that were realized by linking Na3[Ln(dpa)3] (dpa=2,6‐pyridinedicarboxylic acid) to octa‐amino functionalized polyhedral oligomeric silsesquioxane (POSS‐NH2) through hydrogen‐bonding interactions between the oxygen atoms of the carboxylate groups of dpa and the hydrogen‐bond‐donor amino groups. The resulting hybrid composites Ln(dpa)3@POSS‐NH2 are highly soluble in aqueous solutions and the quantum yield of Eu(dpa)3@POSS‐NH2 is as high as 56.5 % or 46.3 % in the solid state and in aqueous solution, respectively, as determined by using the integrating sphere method. The novel water‐soluble luminescent hybrid composites exhibit high thermal and photostability, and the emitted colors of the resulting hybrid composite can be finely tuned by changing the Eu3+/Tb3+ ratio. Interestingly, Eu(dpa)3@POSS‐NH2 hybrid composites exhibited an effective switch‐off fluorescence response to Cu2+ over other common metal ions in aqueous media.
Asymmetric Brønsted Base Catalyzed and Directed [3+2] Cycloaddition of 2‐Acyl Cycloheptatrienes with Azomethine Ylides
Authors: Lauridsen Vibeke H. , Ibsen Lise , Blom Jakob , Jørgensen Karl Anker
Published: January 2016

Conjugated cyclic trienes have the potential for different types of cycloaddition reactions. In the present work, we will, in a novel asymmetric cycloaddition reaction, demonstrate that the organocatalytic reaction of 2‐acyl cycloheptatrienes with azomethine ylides proceeds as a [3+2] cycloaddition, which is in contrast to the Lewis acid‐catalyzed reaction, in which a [3+6] cycloaddition takes place. In the presence of a chiral organosuperbase, 2‐acyl cycloheptatrienes react in a highly enantioselective manner in the [3+2] cycloaddition with azomethine ylides, providing the 1,3‐dipolar cycloaddition product in high yields and up to 99 % ee. It is also shown that the diene formed by the reaction can undergo stereoselective dihydroxylation, bromination, and cycloaddition reactions. Finally, based on experimental observations, some mechanistic considerations are discussed.
Effect of Remote Ischaemic Conditioning in Oncology Patients Undergoing Chemotherapy: Rationale and Design of the ERIC‐ONC Study—A Single‐Center, Blinded, Randomized Controlled Trial
Authors: Chung Robin , Maulik Angshuman , Hamarneh Ashraf , Hochhauser Daniel , Hausenloy Derek J. , Walker J. Malcolm , Yellon Derek M.
Published: January 2016

Cancer survival continues to improve, and thus cardiovascular consequences of chemotherapy are increasingly important determinants of long‐term morbidity and mortality. Conventional strategies to protect the heart from chemotherapy have important hemodynamic or myelosuppressive side effects. Remote ischemic conditioning (RIC) using intermittent limb ischemia‐reperfusion reduces myocardial injury in the setting of percutaneous coronary intervention. Anthracycline cardiotoxicity and ischemia‐reperfusion injury share common biochemical pathways in cardiomyocytes. The potential for RIC as a novel treatment to reduce subclinical myocyte injury in chemotherapy has never been explored and will be investigated in the Effect of Remote Ischaemic Conditioning in Oncology (ERIC‐ONC) trial (clinicaltrials.gov NCT 02471885). The ERIC‐ONC trial is a single‐center, blinded, randomized, sham‐controlled study. We aim to recruit 128 adult oncology patients undergoing anthracycline‐based chemotherapy treatment, randomized in a 1:1 ratio into 2 groups: (1) sham procedure or (2) RIC, comprising 4, 5‐minute cycles of upper arm blood pressure cuff inflations and deflations, immediately before each cycle of chemotherapy. The primary outcome measure, defining cardiac injury, will be high‐sensitivity troponin‐T over 6 cycles of chemotherapy and 12 months follow‐up. Secondary outcome measures will include clinical, electrical, structural, and biochemical endpoints comprising major adverse cardiovascular clinical events, incidence of cardiac arrhythmia over 14 days at cycle 5/6, echocardiographic ventricular function, N‐terminal pro‐brain natriuretic peptide levels at 3 months follow‐up, and changes in mitochondrial DNA, micro‐RNA, and proteomics after chemotherapy. The ERIC‐ONC trial will determine the efficacy of RIC as a novel, noninvasive, nonpharmacological, low‐cost cardioprotectant in cancer patients undergoing anthracycline‐based chemotherapy.
Different Binding Modes of Small and Large Binders of GAT1
Authors: Wein Thomas , Petrera Marilena , Allmendinger Lars , Höfner Georg , Pabel Jörg , Wanner Klaus T.
Published: January 2016

Well‐known inhibitors of the γ‐aminobutyric acid (GABA) transporter GAT1 share a common scaffold of a small cyclic amino acid linked by an alkyl chain to a moiety with two aromatic rings. Tiagabine, the only FDA‐approved GAT1 inhibitor, is a typical example. Some small amino acids such as (R)‐nipecotic acid are medium‐to‐strong binders of GAT1, but similar compounds, such as proline, are very weak binders. When substituted with 4,4‐diphenylbut‐3‐en‐1‐yl (DPB) or 4,4‐bis(3‐methylthiophen‐2‐yl)but‐3‐en‐1‐yl (BTB) groups, the resulting compounds have similar pKi and pIC50 values, even though the pure amino acids have very different values. To investigate if small amino acids and their substituted counterparts share a similar binding mode, we synthesized butyl‐, DPB‐, and BTB‐substituted derivatives of small amino acids. Supported by the results of docking studies, we propose different binding modes not only for unsubstituted und substituted, but also for strong‐ and weak‐binding amino acids. These data lead to the conclusion that following a fragment‐based approach, not pure but N‐butyl‐substituted amino acids should be used as starting points, giving a better estimate of the activity when a BTB or DPB substituent is added.
Hitting a Moving Target: How Does an N‐Methyl Group Impact Biological Activity?
Authors: Koay Yen Chin , Richardson Nicole L. , Zaiter Samantha S. , Kho Jessica , Nguyen Sheena Y. , Tran Daniel H. , Lee Ka Wai , Buckton Laura K. , McAlpine Shelli R.
Published: January 2016

Macrocycles have several advantages over small‐molecule drugs when it comes to addressing specific protein–protein interactions as therapeutic targets. Herein we report the synthesis of seven new cyclic peptide molecules and their biological activity. These macrocycles were designed to understand how moving an N‐methyl moiety around the peptide backbone impacts biological activity. Because the lead non‐methylated structure inhibits the oncogenic regulator heat‐shock protein 90 (Hsp90), two of the most potent analogues were evaluated for their Hsp90 inhibitory activity. We show that incorporating an N‐methyl moiety controls the conformation of the macrocycle, which dramatically impacts cytotoxicity and binding affinity for Hsp90. Thus, the placement of an N‐methylated amino acid within a macrocycle generates an unpredictable change to the compound's conformation and hence biological activity.
Monitoring the Intracellular Distribution and ROS Scavenging Potential of Carbon Dot–Cerium Oxide Nanocomposites in Fibroblast Cells
Authors: Sachdev Abhay , Gopinath P.
Published: January 2016

In the present work, cerium oxide (CeO2)‐based nanocomposites integrating fluorescent carbon dots (CDs) were synthesized by a hydrothermal method. The formation and cellular uptake of these nanocomposites was studied by various analytical techniques. The therapeutic and imaging aspects of CDs‐CeO2 nanocomposites were validated using NIH3T3 fibroblast cells as a model system. The antioxidant potency of CDs‐CeO2 nanocomposites was also evaluated in cells treated with H2O2, a major reactive oxygen species (ROS) species, using a 2′,7′‐dichlorofluorescin diacetate (DCFH‐DA) assay. Tracking the intracellular fluorescence of CDs‐CeO2 nanocomposites by microscopy and flow cytometry made it possible to examine the capabilities of CeO2 for abatement of H2O2‐mediated oxidative stress. Taken together, the present study motivates the use of therapeutic nanocomposites whilst monitoring their uptake, which holds clinical relevance for ROS‐related diseases.
Extensive juvenile “babysitting” facilitates later adult maternal responsiveness, decreases anxiety, and increases dorsal raphe tryptophan hydroxylase‐2 expression in female laboratory rats
Authors: Harding Kaitlyn M. , Lonstein Joseph S.
Published: January 2016

Pregnancy and parturition can dramatically affect female neurobiology and behavior. This is especially true for laboratory‐reared rodents, in part, because such rearing prevents a host of developmental experiences that females might undergo in nature, including juvenile alloparenting. We examined the effect of chronic exposure to pups during post‐weaning juvenile life (days 22–36) on adult maternal responsiveness, anxiety‐related behaviors, and dorsal raphe tryptophan hydroxylase‐2 (TPH2) and serotonin transporter (SERT) levels in nulliparous rats. Adult females with juvenile alloparental experience showed significantly faster sensitized maternal responsiveness, less anxiety, and more dorsal raphe TPH2. Juvenile alloparenting did not affect females’ later social novelty and preference behaviors toward adults, suggesting their increased interest in pups did not extend to all social partners. In a second experiment, suckling a pregnant dam (achieved by postpartum estrus reinsemination), interacting with her after standard laboratory weaning age, and a 3‐day exposure to younger siblings also reduced juvenile females’ later anxiety but did not affect maternal responsiveness or TPH2. Thus, extensive juvenile “babysitting” can have long‐term effects reminiscent of pregnancy and parturition on maternal responsiveness and anxiety, and these effects may be driven by upregulated serotonin. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58: 492–508, 2016.
Response of pest control by generalist predators to local‐scale plant diversity: a meta‐analysis
Authors: Dassou Anicet Gbèblonoudo , Tixier Philippe
Published: January 2016

Disentangling the effects of plant diversity on the control of herbivores is important for understanding agricultural sustainability. Recent studies have investigated the relationships between plant diversity and arthropod communities at the landscape scale, but few have done so at the local scale. We conducted a meta‐analysis of 32 papers containing 175 independent measures of the relationship between plant diversity and arthropod communities. We found that generalist predators had a strong positive response to plant diversity, that is, their abundance increased as plant diversity increased. Herbivores, in contrast, had an overall weak and negative response to plant diversity. However, specialist and generalist herbivores differed in their response to plant diversity, that is, the response was negative for specialists and not significant for generalists. While the effects of scale remain unclear, the response to plant diversity tended to increase for specialist herbivores, but decrease for generalist herbivores as the scale increased. There was no clear effect of scale on the response of generalist predators to plant diversity. Our results suggest that the response of herbivores to plant diversity at the local scale is a balance between habitat and trophic effects that vary according to arthropod specialization and habitat type. Synthesis and applications. Positive effects of plant diversity on generalist predators confirm that, at the local scale, plant diversification of agroecosystems is a credible and promising option for increasing pest regulation. Results from our meta‐analysis suggest that natural control in plant‐diversified systems is more likely to occur for specialist than for generalist herbivores. In terms of pest management, our results indicate that small‐scale plant diversification (via the planting of cover crops or intercrops and reduced weed management) is likely to increase the control of specialist herbivores by generalist predators.
Relb acts downstream of medullary thymic epithelial stem cells and is essential for the emergence of RANK+ medullary epithelial progenitors
Authors: Baik Song , Sekai Miho , Hamazaki Yoko , Jenkinson William E. , Anderson Graham
Published: January 2016

Thymic epithelial cells (TECs) provide essential signals for αβT‐cell development, and medullary TECs (mTECs) control T‐cell tolerance through both negative selection and Foxp3+ regulatory T (Treg) cell development. Although heterogeneity within the mTEC compartment is well studied, the molecular regulators of specific stages of mTEC development are still poorly understood. Given the importance of the RANK‐RANKL axis in thymus medulla formation, we have used RANK Venus reporter mice to analyze the ontogeny of RANK+ TECs during development and correlated RANK expression with mTEC stem cells defined by SSEA‐1. In addition, we have investigated how requirements for the key regulators Foxn1 and Relb map to specific stages of mTEC development. Here, we show SSEA‐1+ mTEC stem cells emerge prior to RANK expression and are present in both nude and Relb−/− mice, providing direct evidence that mTEC lineage specification occurs independently of Foxn1 and Relb. In contrast, we show that Relb is necessary for the effective production of downstream RANK+ mTEC progenitors. Collectively, our work defines stage‐specific requirements for critical TEC regulators during medulla development, including the timing of Relb dependency, and provides new information on mechanisms controlling mTEC specification.
Globalisation and global concern: Developing a social psychology of human responses to global challenges
Authors: Reese Gerhard , Rosenmann Amir , McGarty Craig
Published: January 2016

The process of globalisation has gained tremendous momentum over recent decades, resulting in unprecedented human interconnectedness and awareness of global concerns. The current special issue of the European Journal of Social Psychology brings together 10 papers that address this development. This special issue showcases different perspectives on the psychological processes that underlie the cognitive and behavioural responses to the global challenges humankind has created and is now facing. In introducing these contributions, we identified three emerging topics for social psychological theorising and application vis‐à‐vis globalisation and global concerns: (i) supranational identification and attachment, (ii) political and ideological responses to globalisation and global concerns, and (iii) global protest and change. We integrate these topics by highlighting some future prospects of this emerging field of research and its significance for understanding social change in these tumultuous times.
Greenhouse gas emissions from domestic hot water: heat pumps compared to most commonly used systems
Authors: Hong Bongghi , Howarth Robert W.
Published: January 2016

We estimate the emissions of the two most important greenhouse gasses (GHG), carbon dioxide (CO2) and methane (CH4), from the use of modern high‐efficiency heat pump water heaters compared to the most commonly used domestic hot water systems: natural gas storage tanks, tankless natural gas demand heaters, electric resistance storage tanks, and tankless electric resistance heaters. We considered both natural gas‐powered electric plants and coal‐powered plants as the source of the electricity for the heat pumps, the thermal electric storage tanks, and the tankless electric demand heaters. The time‐integrated radiative forcing associated with using a heat pump water heater was always smaller than any other means of heating water considered in this study across all time frames including at 20 and 100 years. The estimated amount of CH4 lost during its lifecycle was the most critical factor determining the relative magnitude of the climatic impact. The greatest net climatic benefit within the 20‐year time frame was predicted to be achieved when a storage natural gas water heater (the most common system for domestic hot water in the United States) fueled by shale gas was replaced with a high efficiency heat pump water heater powered by coal‐generated electricity; the heat pump system powered by renewable electricity would have had an even greater climatic benefit, but was not explicitly modeled in this study. Our analysis provides the first assessment of the GHG footprint associated with using a heat pump water heater, which we demonstrate to be an effective and economically viable way of reducing emissions of GHGs.
Beach–dune sediment budgets and dune morphodynamics following coastal dune restoration, Wickaninnish Dunes, Canada
Authors: Darke Ian B. , Walker Ian J. , Hesp Patrick A.
Published: January 2016

The results from three years of surveying and monitoring a dynamic foredune and dunefield restoration effort on Vancouver Island, Canada is presented. Complete removal of foredune vegetation occurred in three phases spaced a year apart in an effort to control invasive Ammophila spp. The collection of airborne LiDAR, orthophotographs, and bi‐monthly topographic surveys provided a means to quantify and examine sediment budgets and geomorphic responses. Three survey swaths, corresponding with each phase of vegetation removal, were established to provide detailed topographic coverage over the impacted beach, foredune, and dunefield landscape units. The swath corresponding with the first phase of removal recorded a positive sediment budget of 1·3 m3 m−2 after three years. A control swath, with data collected for a year prior and two years following removal, exhibited a distinct pulse of sediment delivery into the dunefield unit with a maximum gain of 0·03 m3 m−2 pre‐removal compared to 0·11 m3 m−2 post‐removal. Vegetation analysis zones, associated with each of the three swaths, demonstrate a range of vegetation responses due to variation in the vegetation removal and subsequent re‐invasion or removal methods employed. The first site to be cleared of vegetation, received ongoing invasive re‐growth control, and three years following removal vegetation cover dropped from 57% in 2009 to 13% in 2012 (−44%). An adjacent site was cleared of vegetation two years later (only one year of recovery) but experienced rapid Ammophila re‐invasion and percent cover changed from 61% in 2009 to 26% in 2012 (−35%). The data presented provides insights for improving the application of sediment budget monitoring in dynamic restorations and discusses the potential for detailed spatial–temporal survey data to improve our understanding of meso‐scale landscape morphodynamics following foredune disturbance. Overall, the vegetation removal treatments reduced the extent of invasive grass and increased dunefield mobility and dynamic activity. Copyright © 2016 John Wiley & Sons, Ltd.
Abnormal brain activation and connectivity to standardized disorder‐related visual scenes in social anxiety disorder
Authors: Heitmann Carina Yvonne , Feldker Katharina , Neumeister Paula , Zepp Britta Maria , Peterburs Jutta , Zwitserlood Pienie , Straube Thomas
Published: January 2016

Our understanding of altered emotional processing in social anxiety disorder (SAD) is hampered by a heterogeneity of findings, which is probably due to the vastly different methods and materials used so far. This is why the present functional magnetic resonance imaging (fMRI) study investigated immediate disorder‐related threat processing in 30 SAD patients and 30 healthy controls (HC) with a novel, standardized set of highly ecologically valid, disorder‐related complex visual scenes. SAD patients rated disorder‐related as compared with neutral scenes as more unpleasant, arousing and anxiety‐inducing than HC. On the neural level, disorder‐related as compared with neutral scenes evoked differential responses in SAD patients in a widespread emotion processing network including (para‐)limbic structures (e.g. amygdala, insula, thalamus, globus pallidus) and cortical regions (e.g. dorsomedial prefrontal cortex (dmPFC), posterior cingulate cortex (PCC), and precuneus). Functional connectivity analysis yielded an altered interplay between PCC/precuneus and paralimbic (insula) as well as cortical regions (dmPFC, precuneus) in SAD patients, which emphasizes a central role for PCC/precuneus in disorder‐related scene processing. Hyperconnectivity of globus pallidus with amygdala, anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC) additionally underlines the relevance of this region in socially anxious threat processing. Our findings stress the importance of specific disorder‐related stimuli for the investigation of altered emotion processing in SAD. Disorder‐related threat processing in SAD reveals anomalies at multiple stages of emotion processing which may be linked to increased anxiety and to dysfunctionally elevated levels of self‐referential processing reported in previous studies. Hum Brain Mapp 37:1559‐1572, 2016. © 2016 Wiley Periodicals, Inc.