bluuebunny/crossref_metadata_2025 huggingface dataset:
Sliding on the surface: bacterial spreading without an active motor
Authors: Hölscher Theresa , Kovács Ákos T.
Published: March 2017

Bacteria are able to translocate over surfaces using different types of active and passive motility mechanisms. Sliding is one of the passive types of movement since it is powered by the pushing force of dividing cells and additional factors facilitating the expansion over surfaces. In this review, we describe the sliding proficient bacteria that were previously investigated in details highlighting the sliding facilitating compounds and the regulation of sliding motility. Besides surfactants that reduce the friction between cells and substratum, other compounds including exopolysaccharides, hydrophobic proteins, or glycopeptidolipids where discovered to promote sliding. Therefore, we present the sliding bacteria in three groups depending on the additional compound required for sliding. Despite recent accomplishments in sliding research there are still many open questions about the mechanisms underlying sliding motility and its regulation in diverse bacterial species.
Physiological and proteomic characterization of light adaptations in marine Synechococcus
Authors: Mackey Katherine R. M. , Post Anton F. , McIlvin Matthew R. , Saito Mak A.
Published: March 2017

Marine Synechococcus thrive over a range of light regimes in the ocean. We examined the proteomic, genomic and physiological responses of seven Synechococcus isolates to moderate irradiances (5–80 μE m−2 s−1), and show that Synechococcus spans a continuum of light responses ranging from low light optimized (LLO) to high light optimized (HLO). These light responses are linked to phylogeny and pigmentation. Marine sub‐cluster 5.1A isolates with higher phycouribilin: phycoerythrobilin ratios fell toward the LLO end of the continuum, while sub‐cluster 5.1B, 5.2 and estuarine Synechococcus with less phycouribilin fell toward the HLO end of the continuum. Global proteomes were highly responsive to light, with > 50% of abundant proteins varying more than twofold between the lowest and highest irradiance. All strains downregulated phycobilisome proteins with increasing irradiance. Regulation of proteins involved in photosynthetic electron transport, carbon fixation, oxidative stress protection (superoxide dismutases) and iron and nitrogen metabolism varied among strains, as did the number of high light inducible protein (Hlip) and DNA photolyase genes in their genomes. All but one LLO strain possessed the photoprotective orange carotenoid protein (OCP). The unique combinations of light responses in each strain gives rise to distinct photophysiological phenotypes that may affect Synechococcus distributions in the ocean.
The Syrian Humanitarian Disaster: Understanding Perceptions and Aspirations in Jordan, Lebanon and Turkey
Authors: Chatty Dawn
Published: March 2017

The modern architecture of international humanitarian assistance has established a template of provisioning for refugees fleeing armed conflict which is based on notions of encampment and vulnerability. The narrowness of that assistance framework coupled with an unsustainable policy of regional containment have created greater poverty and misery for Syrians fleeing the armed conflict in their country. How this has been allowed to happen on the eastern shores of the Mediterranean Sea – where extraordinary social linkages and networks have existed for centuries – lies mainly in the disparities between perceptions, aspirations and behaviour among refugees, practitioners and policy makers in Jordan, Lebanon and Turkey.
Humanitarian Rescue/Sovereign Capture and the Policing of Possible Responses to Violent Borders
Authors: Pallister‐Wilkins Polly
Published: March 2017

Practices of rescue and assistance based on humanitarian concerns for life have increasingly come to shape both state and non‐state action that responds to the mobility of people on the move at the borders of Europe. These processes of rescue are presented as counter to processes of border control concerned with preventing and policing migratory flows. Presented and articulated as an alternative response to the increasingly restrictive and militarised practices that make‐up ‘Fortress Europe’, this humanitarian intervention concerned with saving lives both masks the violence of the border that renders people vulnerable in the first instance and masks the intimate relationship practices of rescue have with processes of capture more traditionally associated with border policing. The ascendancy of rescue as the primary response to irregular mobility also works to police the boundaries of what is considered ethical politics and the possible responses that result. Rescue does this through framing such events as unforeseen tragedies, erasing the structures of the violent border in the process and rendering counter‐narratives mute.
Reversal of hepatorenal syndrome type 1 with terlipressin plus albumin vs. placebo plus albumin in a pooled analysis of the OT‐0401 and REVERSE randomised clinical studies
Authors: Sanyal A. J. , Boyer T. D. , Frederick R. T. , Wong F. , Rossaro L. , Araya V. , Vargas H. E. , Reddy K. R. , Pappas S. C. , Teuber P. , Escalante S. , Jamil K.
Published: March 2017

Background

The goal of hepatorenal syndrome type 1 (HRS‐1) treatment is to improve renal function. Terlipressin, a synthetic vasopressin analogue, is a systemic vasoconstrictor used for the treatment of HRS‐1, where it is available.

Aim

To compare the efficacy of terlipressin plus albumin vs. placebo plus albumin in patients with HRS‐1.

Methods

Pooled patient‐level data from two large phase 3, randomised, placebo‐controlled studies were analysed for HRS reversal [serum creatinine (SCr) value ≤133 μmol/L], 90‐day survival, need for renal replacement therapy and predictors of HRS reversal. Patients received intravenous terlipressin 1–2 mg every 6 hours plus albumin or placebo plus albumin up to 14 days.

Results

The pooled analysis comprised 308 patients (terlipressin: n = 153; placebo: n = 155). HRS reversal was significantly more frequent with terlipressin vs. placebo (27% vs. 14%; P = 0.004). Terlipressin was associated with a more significant improvement in renal function from baseline until end of treatment, with a mean between‐group difference in SCr concentration of −53.0 μmol/L (P < 0.0001). Lower SCr, lower mean arterial pressure and lower total bilirubin and absence of known precipitating factors for HRS were independent predictors of HRS reversal and longer survival in terlipressin‐treated patients.

Conclusions

Terlipressin plus albumin resulted in a significantly higher rate of HRS reversal vs. albumin alone in patients with HRS‐1. Terlipressin treatment is associated with improved renal function. (ClinicalTrials.gov identifier: OT‐0401, NCT00089570; REVERSE, NCT01143246).
Polycystic ovary syndrome with hyperandrogenism as a risk factor for non‐obese non‐alcoholic fatty liver disease
Authors: Kim J. J. , Kim D. , Yim J. Y. , Kang J. H. , Han K. H. , Kim S. M. , Hwang K. R. , Ku S. Y. , Suh C. S. , Kim S. H. , Choi Y. M.
Published: March 2017

Background

Non‐alcoholic fatty liver disease (NAFLD) is known to be associated with polycystic ovary syndrome (PCOS). However, most studies investigated the prevalence of NAFLD in obese PCOS patients.

Aim

To compare the prevalence of non‐obese NAFLD in women with or without PCOS, and to assess an independent association between PCOS and NAFLD in a non‐obese Asian cohort.

Methods

This was a case–control study using a prospective PCOS cohort. After subjects with other potential causes of chronic liver disease were excluded, 275 non‐obese women with PCOS and 892 non‐obese controls were enrolled. NAFLD was determined by hepatic ultrasonography. Main outcomes were the prevalence of NAFLD on hepatic ultrasonography between non‐obese women with or without PCOS, and an independent association between non‐obese NAFLD and PCOS.

Results

Non‐obese women with PCOS had a significantly higher prevalence of NAFLD than those without PCOS (5.5% vs. 2.8%, P = 0.027). PCOS was associated with non‐obese NAFLD (odds ratio: 2.62, 95% confidence intervals: 1.25–5.48) after adjustment for age and body mass index (BMI). In women with PCOS, the level of androgenicity represented by free testosterone or free androgen index was associated with NAFLD after adjustment for age, BMI, lipid profile, insulin resistance or glycaemic status.

Conclusions

Non‐obese NAFLD is more prevalent in women with polycystic ovary syndrome than in those without. In non‐obese patients with polycystic ovary syndrome, hyperandrogenemia may be an independent risk factor for non‐obese NAFLD.
Biased agonism and allosteric modulation of G protein‐coupled receptor 183 – a 7TM receptor also known as Epstein–Barr virus‐induced gene 2
Authors: Daugvilaite Viktorija , Madsen Christian Medom , Lückmann Michael , Echeverria Clara Castello , Sailer Andreas Walter , Frimurer Thomas Michael , Rosenkilde Mette Marie , Benned‐Jensen Tau
Published: March 2017

Background and Purpose

The GPCR Epstein–Barr virus‐induced gene 2 (EBI2, also known as GPR183) is activated by oxysterols and plays a pivotal role in the regulation of B cell migration during immune responses. While the molecular basis of agonist binding has been addressed in several studies, the concept of biased agonism of the EBI2 receptor has not been explored.

Experimental Approach

We investigated the effects of the EBI2 endogenous agonist 7α,25‐dihydroxycholesterol (7α,25‐OHC) on G protein‐dependent and ‐independent pathways as well as sodium ion allosterism using site‐directed mutagenesis and functional studies. Moreover, we generated a homology model of the EBI2 receptor to investigate the structural basis of the allosteric modulation by sodium.

Key Results

Residue N114, located in the middle of transmembrane‐III at position III:11/3.35, was found to function as an efficacy switch. Thus, substituting N114 with an alanine (N114A) completely abolished heterotrimeric G protein subunit Gi α activation by 7α,25‐OHC even though the specific binding of [3H]‐7α,25‐OHC increased. In contrast, the N114A mutant was still able to recruit β‐arrestin and even had an enhanced potency (18.7‐fold) compared with EBI2 wild type. Sodium had a negative allosteric effect on oxysterol binding that was mediated via N114, verifying the key role of N114. This was further supported by molecular modelling of the ion binding site based on a EBI2 receptor homology model.

Conclusions and Implications

Collectively, our data point to N114 as a key residue for EBI2 signalling controlling the balance between G protein‐dependent and ‐independent pathways and facilitating sodium binding.
National time trend changes in psychotropic medication of child and adolescent psychiatric inpatients across Finland
Authors: Kronström Kim , Kuosmanen Lauri , Ellilä Heikki , Kaljonen Anne , Sourander Andre
Published: March 2017

Background

There have been no comprehensive studies on trends in psychotropic medication use in child and adolescent inpatient settings. The aim of this nationwide study was to report changes in the psychotropic medication given to child and adolescent psychiatric inpatients across Finland and the factors associated with those changes.

Methods

We asked the psychiatrist responsible for each inpatient to complete a questionnaire that included questions about the pharmacological treatment and background information. The data were collected on all inpatients on one selected study day in 2000 and 2011. Changes in the use of regular psychotropic medication were studied by comparing the data on 504 patients in 2000 and 412 patients in 2011.

Results

The study showed that there had been a significant increase in the use of psychotropic medication from 2000 to 2011. According to the multivariate analysis, the increase in psychotropic medication was associated with the study year (in 2000 39%, in 2011 58%), but could not be explained by changes in diagnostic profiles, age distribution, suicidality, violence or the Children′s Global Assessment Scale scores. The use of combined psychotropic medication increased from 9% in 2000 to 25% in 2011. The increase in the use of antipsychotics among child inpatients was particularly noteworthy, with an increase from 10% to 32%.

Conclusions

There is a need for evidence‐based studies to clarify recommendations for indications and treatment practices when using psychotropic medication in children and adolescents. Cross‐cultural studies of the use of psychotropic medication are warranted.
Faster insulin action is associated with improved glycaemic outcomes during closed‐loop insulin delivery and sensor‐augmented pump therapy in adults with type 1 diabetes
Authors: Ruan Yue , Thabit Hood , Leelarathna Lalantha , Hartnell Sara , Wilinska Malgorzata E. , Tauschmann Martin , Dellweg Sibylle , Benesch Carsten , Mader Julia K. , Holzer Manuel , Kojzar Harald , Evans Mark L. , Pieber Thomas R. , Arnolds Sabine , Hovorka Roman ,   on behalf of AP@home consortium
Published: March 2017

We aimed to evaluate the relationship between insulin pharmacodynamics and glycaemic outcomes during closed‐loop insulin delivery and sensor‐augmented pump therapy. We retrospectively analysed data from a multicentre randomized control trial involving 32 adults with type 1 diabetes receiving day‐and‐night closed‐loop insulin delivery and sensor‐augmented pump therapy over 12 weeks. We estimated time‐to‐peak insulin action (t
max,

IA
) and insulin sensitivity (
S

I
) during both interventions, and correlated these with demographic factors and glycaemic outcomes. During both interventions, t
max,

IA
was positively correlated with pre‐ and post‐intervention HbA1c (r = 0.50‐0.52,
P
 < .01) and mean glucose (r = 0.45‐0.62,
P
 < .05), and inversely correlated with time sensor glucose, which was in target range 3.9 to 10 mmol/L (r = −0.64 to −0.47,
P
 < .05). Increased body mass index was associated with higher t
max,

I
and lower
S

I
(both
P
 < .05). During closed‐loop insulin delivery, t
max,

IA
was positively correlated with glucose variability (
P
 < .05). Faster insulin action is associated with improved glycaemic control during closed‐loop insulin delivery and sensor‐augmented pump therapy.
Risk, success, and failure: female entrepreneurship in late Victorian and Edwardian England
Authors: Aston Jennifer , Di Martino Paolo
Published: March 2017

This article analyses female entrepreneurship in late Victorian and Edwardian England. Traditional views on female entrepreneurship in nineteenth‐ and twentieth‐century England point towards a decline in the number and relevance of women as business owners in comparison to the eighteenth century, and their retreat into a ‘separate sphere’ away from the world of trade and production. Recent studies, however, have deeply challenged this view, suggesting that women still played an important role as entrepreneurs during industrialization and beyond. Nevertheless, a number of questions remain unanswered with regard to the features of female entrepreneurship during these phases of British history, and issues such as scale of operation, attitude to risk, credit structure, and managerial styles are still widely debated. Using original sources, this article provides a novel view on these issues, analysing female entrepreneurship from the perspective of bankruptcy. Analysing statistics on women's bankruptcy derived from Board of Trade reports, as well as a sample of archival cases, this article argues that overall female business owners traded in ways similar to their male counterparts in terms of business size, risk‐taking, and, eventually, success.
Native vs. second language discrimination in the modulation of the N400/N400m
Authors: Anurova Irina , Immonen Perttu
Published: March 2017

The N400 evoked response component, initially proposed as a marker of semantic incongruity, was later demonstrated to be evoked by various potentially meaningful stimuli, such as words or pseudowords. The present study tested whether the N400 elicited by isolated words and pseudowords was modulated by task instructions thus reflecting controlled processing of linguistic information. In two language discrimination tasks, Finnish adults with English as their second language detected either Finnish or English nouns in a list of Finnish and English words and pseudowords. The same set of stimuli, presented in a random order, was used for both tasks. The amplitudes of both the evoked potentials and their magnetic counterparts were task‐language dependent. In both tasks, task‐language pseudowords elicited more negative evoked potentials (N400 and P600) than non‐task‐language pseudowords or words. The left temporal source of the evoked magnetic field was activated more strongly by English than Finnish pseudowords in the English task. This source was also activated more strongly by English pseudowords in the English task than in the Finnish task. However, no similar enhancement of the evoked magnetic field by Finnish pseudowords was observed in the Finnish task. This finding suggests that at the level of multimodal temporal cortex around the superior temporal sulcus, the native language is processed more automatically than the second language and that the controlled processing of linguistic information reflected by the N400 potential is accomplished by a broader neural network extending beyond the association temporal areas.
Community structure of the gut microbiota in sympatric species of wild Drosophila
Authors: Martinson Vincent G. , Douglas Angela E. , Jaenike John
Published: March 2017

Many aspects of animal ecology and physiology are influenced by the microbial communities within them. The underlying forces contributing to the assembly and diversity of gut microbiotas include chance events, host‐based selection and interactions among microorganisms within these communities. We surveyed 215 wild individuals from four sympatric species of Drosophila that share a common diet of decaying mushrooms. Their microbiotas consistently contained abundant bacteria that were undetectable or at low abundance in their diet. Despite their deep phylogenetic divergence, all species had similar microbiotas, thus failing to support predictions of the phylosymbiosis hypothesis. Communities within flies were not random assemblages drawn from a common pool; instead, many bacterial operational taxonomic units (OTUs) were overrepresented or underrepresented relative to the neutral expectations, and OTUs exhibited checkerboard distributions among flies. These results suggest that selective factors play an important role in shaping the gut community structure of these flies.
Clinical medication review tool for polypharmacy: Mapping approach for pharmacotherapeutic classifications
Authors: Mizokami Fumihiro , Mizuno Tomohiro , Mori Tomoyo , Nagamatsu Tadashi , Endo Hideharu , Hirashita Tomoyuki , Ichino Takanobu , Akishita Masahiro , Furuta Katsunori
Published: March 2017

Aim

Polypharmacy is an extremely important problem, because it increases the risk of adverse drug reactions. The aim of the current study was to create a clinical medication review tool to detect inappropriate medication use, and assess this new method with elderly Japanese patients.

Methods

The new method involves optimizing prescription drugs from indications, based on the chronic disease‐anatomical therapeutic class code list. The present study investigated the prevalence of potentially inappropriate medications in 5667 Japanese patients aged ≥65 years with polypharmacy (≥5 drugs) in comparison with the Beers criteria 2012.

Results

We propose a new method called the Mapping Approach for Pharmacotherapeutic Classifications: (i) identify the chronic disease‐anatomical therapeutic class code assigned to the prescription drugs; (ii) identify the chronic disease‐anatomical therapeutic class code corresponding to the patient's chronic disease; (iii) compare the prescription drug and patient's chronic disease chronic disease‐anatomical therapeutic class codes; and (iv) identify the appropriateness of medication use based on the comparison (appropriate use is defined as matching codes). The mean number of potentially inappropriate medications detected was significantly different between the mapping approach and Beers criteria 2012 (3.1 ± 2.6 vs 0.6 ± 0.8 drugs, respectively; P < 0.001).

Conclusions

The Mapping Approach for Pharmacotherapeutic Classifications is highly dependent on the chronic condition. Pharmacists should confirm the chronic condition with the treating physician before reducing a patient's medications. We hope this process will further influence prescribing patterns, and decrease the inappropriate use of medications and associated adverse drug reactions in older adults. Geriatr Gerontol Int 2017; 17: 2025–2033.
Korean version of the Fatigue, Resistance, Ambulation, Illnesses and Loss of weight questionnaire versus the Modified Kihon Checklist for Frailty Screening in Community‐Dwelling Older Adults: The Aging Study of PyeongChang Rural Area
Authors: Jang Il‐Young , Jung Hee‐Won , Lee Chang Ki , Jang Kwang Ho , Cho Eun‐Il , Jung Ju Jin , Park Euna , Kim Juyoung , Lee Young Soo , Lee Eunju , Kim Dae Hyun
Published: March 2017

Aim

To compare the five‐item Korean version of the Fatigue, Resistance, Ambulation, Illnesses and Loss of weight (K‐FRAIL) questionnaire versus the 28‐item Kihon + 3 index (the 25‐item original Kihon checklist plus multimorbidity, sensory impairment, and Timed Up and Go test) in identifying prefrail or frail older adults.

Methods

We carried out a cross‐sectional analysis of 212 community‐dwelling older adults (mean age 76 years; 41% male) in PyeongChang County, Korea. We compared the C statistic, sensitivity and specificity of the K‐FRAIL questionnaire (range 0–5; cut‐point ≥1) versus the Kihon + 3 index (range 0–31; cut‐point ≥4) and the original Kihon checklist (range 0–25; cut‐point ≥4) in identifying prefrail or frail individuals according to the Cardiovascular Health Study criteria.

Results

According to the Cardiovascular Health Study criteria, 150 individuals (70.8%) were prefrail or frail. The C statistic of the K‐FRAIL questionnaire in identifying prefrail or frail individuals was lower than that of the Kihon + 3 index (0.77 vs 0.85; P = 0.022) or that of the original Kihon checklist (0.77 vs 0.84; P = 0.046). However, at the a priori cut‐points, the K‐FRAIL questionnaire had sensitivity (0.79 vs 0.85; P = 0.095) and specificity (0.69 vs 0.69; P = 1.000) that were not significantly different from those of the Kihon + 3 index. However, the K‐FRAIL questionnaire was more sensitive (0.79 vs 0.69; P = 0.016), but less specific (0.69 vs 0.86, p = 0.018) than the original Kihon checklist.

Conclusions

For frailty screening in community‐dwelling older adults, the simple K‐FRAIL questionnaire might not be inferior to the current standard of the Kihon + 3 index, and it might be more sensitive and less specific than the original Kihon checklist. Geriatr Gerontol Int 2017; 17: 2046–2052.
Physicochemical, functional, thermal and structural properties of isolated Kabuli chickpea proteins as affected by processing approaches
Authors: Xu Yixiang , Obielodan Mary , Sismour Edward , Arnett Anna , Alzahrani Saeedah , Zhang Baoshan
Published: March 2017

Kabuli chickpea seeds were processed by soaking only and soaking followed either by pressure cooking or roasting. Proteins were isolated from both raw and processed seeds, and the effects of these processing approaches on the physicochemical, functional, thermal and structural properties as well as SDS‐PAGE profiles of the protein isolates were investigated. Thermal processes significantly (P < 0.05) decreased protein yield, content, colour difference, emulsifying properties and protein solubility of the protein isolates, but increased lightness and water and oil absorption capacities. Protein thermal properties, secondary structure and SDS‐PAGE banding patterns were significantly changed in thermal‐processed samples, especially those that were pressure cooked. No endothermic peak was detected in differential scanning calorimetry thermograms, and peak intensity of amide I absorption band at 1600–1700 cm−1 in Fourier transform infrared spectra reduced. The results reveal that pressure cooking had more pronounced effects on the properties of the protein isolates than other processing approaches.
In vitro assessment of a novel, hypothermically stored amniotic membrane for use in a chronic wound environment
Authors: McQuilling John P , Vines Jeremy B , Mowry Katie C
Published: March 2017

Abstract

Chronic wounds require extensive healing time and place patients at risk of infection and amputation. Recently, a fresh hypothermically stored amniotic membrane (HSAM) was developed and has subsequently shown promise in its ability to effectively heal chronic wounds. The purpose of this study is to investigate the mechanisms of action that contribute to wound‐healing responses observed with HSAM. A proteomic analysis was conducted on HSAM, measuring 25 growth factors specific to wound healing within the grafts. The rate of release of these cytokines from HSAMs was also measured. To model the effect of these cytokines and their role in wound healing, proliferation and migration assays with human fibroblasts and keratinocytes were conducted, along with tube formation assays measuring angiogenesis using media conditioned from HSAM. Additionally, the cell–matrix interactions between fibroblasts and HSAM were investigated. Conditioned media from HSAM significantly increased both fibroblast and keratinocyte proliferation and migration and induced more robust tube formation in angiogenesis assays. Fibroblasts cultured on HSAMs were found to migrate into and deposit matrix molecules within the HSAM graft. These collective results suggest that HSAM positively affects various critical pathways in chronic wound healing, lending further support to promising qualitative results seen clinically and providing further validation for ongoing clinical trials.
Phase contrast synchrotron radiation computed tomography of muscle spindles in the mouse soleus muscle
Authors: Zeller‐Plumhoff B. , Roose T. , Katsamenis O. L. , Mavrogordato M. N. , Torrens C. , Schneider P. , Clough G. F.
Published: March 2017

Muscle spindles are skeletal muscle sensory organs involved in the sensation of position and movement of the body. We have explored the capability of phase contrast computed tomography to visualise muscle spindles in murine skeletal muscle. In particular, we have validated the visualisation of nerve fibres through phase contrast computed tomography using light microscopy on stained histological sections. We further present the first three‐dimensional visualisation of muscle spindles in mouse soleus skeletal muscle in conjunction with the neurovascular bundle associated with it.
Melatonin: Antioxidant and modulatory properties in age‐related changes during Trypanosoma cruzi infection
Authors: Brazão Vânia , Santello Fabricia H. , Colato Rafaela P. , Mazotti Tamires T. , Tazinafo Lucas F. , Toldo Míriam Paula A. , do Vale Gabriel T. , Tirapelli Carlos R. , do Prado José C.
Published: March 2017

The purpose of this study was to investigate the effects of melatonin on selected biomarkers of innate and humoral immune response as well as the antioxidant/oxidant status (superoxide dismutase—SOD and reduced glutathione levels (GSH) to understand whether age‐related changes would influence the development of acute Trypanosoma cruzi (T. cruzi) infection. Young‐ (5 weeks) and middle‐aged (18 months) Wistar rats were orally treated with melatonin (gavage) (05 mg/kg/day), 9 days after infection. A significant increase in both SOD activity and GSH levels was found in plasma from all middle‐aged melatonin‐treated animals. Melatonin triggered enhanced expression of major histocompatibility class II (MHC‐II) antigens on antigen‐presenting cell (APC) and peritoneal macrophages in all treated animals. High levels of CD4+CD28‐negative T cells (*P<.05) were detected in middle‐aged control animals. Melatonin induced a significant reduction (***P<.001) in CD28‐negative in CD4+ and CD8+ T cells in middle‐aged control animals. Contrarily, the same group displayed upregulated CD4+CD28+T and CD8+CD28+T cells. Melatonin also triggered an upregulation of CD80 and CD86 expression in all young‐treated groups. Significant percentages of B and spleen dendritic cells in middle‐aged infected and treated animals were observed. Our data reveal new features of melatonin action in inhibiting membrane lipid peroxidation, through the reduction in 8‐isoprostane, upregulating the antioxidant defenses and triggering an effective balance in the antioxidant/oxidant status during acute infection. The ability of melatonin to counteract the immune alterations induced by aging added further support to its use as a potential therapeutic target not only for T. cruzi infection but also for other immunocompromised states.
Effects of developmental conditions on growth, stress and telomeres in black‐legged kittiwake chicks
Authors: Young Rebecca C. , Welcker Jorg , Barger Christopher P. , Hatch Scott A. , Merkling Thomas , Kitaiskaia Evgenia V. , Haussmann Mark F. , Kitaysky Alexander S.
Published: March 2017

Early‐life conditions can drive ageing patterns and life history strategies throughout the lifespan. Certain social, genetic and nutritional developmental conditions are more likely to produce high‐quality offspring: those with good likelihood of recruitment and productivity. Here, we call such conditions “favoured states” and explore their relationship with physiological variables during development in a long‐lived seabird, the black‐legged kittiwake (Rissa tridactyla). Two favoured states were experimentally generated by manipulation of food availability and brood size, while hatching order and sex were also explored as naturally generating favoured states. Thus, the favoured states we explored were high food availability, lower levels of sibling competition, hatching first and male sex. We tested the effects of favoured developmental conditions on growth, stress, telomere length (a molecular marker associated with lifespan) and nestling survival. Generation of favoured states through manipulation of both the nutritional and social environments furthered our understanding of their relative contributions to development and phenotype: increased food availability led to larger body size, reduced stress and higher antioxidant status, while lower sibling competition (social environment) led to lower telomere loss and longer telomere lengths in fledglings. Telomere length predicted nestling survival, and wing growth was also positively correlated with telomere length, supporting the idea that telomeres may indicate individual quality, mediated by favoured states.
Persistence of historical population structure in an endangered species despite near‐complete biome conversion in California's San Joaquin Desert
Authors: Richmond Jonathan Q. , Wood Dustin A. , Westphal Michael F. , Vandergast Amy G. , Leaché Adam D. , Saslaw Lawrence R. , Butterfield H. Scott , Fisher Robert N.
Published: March 2017

Genomic responses to habitat conversion can be rapid, providing wildlife managers with time‐limited opportunities to enact recovery efforts that use population connectivity information that reflects predisturbance landscapes. Despite near‐complete biome conversion, such opportunities may still exist for the endemic fauna and flora of California's San Joaquin Desert, but comprehensive genetic data sets are lacking for nearly all species in the region. To fill this knowledge gap, we studied the rangewide population structure of the endangered blunt‐nosed leopard lizard Gambelia sila, a San Joaquin Desert endemic, using restriction site‐associated DNA (RAD), microsatellite and mtDNA data to test whether admixture patterns and estimates of effective migration surfaces (EEMS) can identify land areas with high population connectivity prior to the conversion of native xeric habitats. Clustering and phylogenetic analyses indicate a recent shared history between numerous isolated populations and EEMS reveals latent signals of corridors and barriers to gene flow over areas now replaced by agriculture and urbanization. Conflicting histories between the mtDNA and nuclear genomes are consistent with hybridization with the sister species G. wislizenii, raising important questions about where legal protection should end at the southern range limit of G. sila. Comparative analysis of different data sets also adds to a growing list of advantages in using RAD loci for genetic studies of rare species. We demonstrate how the results of this work can serve as an evolutionary guidance tool for managing endemic, arid‐adapted taxa in one of the world's most compromised landscapes.
The role of allochrony in speciation
Authors: Taylor Rebecca S. , Friesen Vicki L.
Published: March 2017

The importance of sympatric speciation – the evolution of reproductive isolation between codistributed conspecific individuals – in generating biodiversity is highly controversial. Allochrony, or differences in breeding time (phenology) between conspecific individuals, has the potential to lead to reproductive isolation and therefore speciation. We critically review the literature to test the importance of allochronic speciation over the three timescales over which allochrony can occur – over the day, between seasons or between years – and explore what is known about genomic mechanisms underlying allochrony in the diverse taxa in which it is found. We found that allochrony can be a key contributor to reproductive isolation, especially if populations have little overlap in breeding time and therefore little potential for gene flow, and may sometimes be the initial or key driver of speciation. Shifts in phenology can be caused by several factors, including a new ecological opportunity, environmental change, or reinforcement. The underlying genomic basis of allochrony has been studied mostly in insects, highlighting the need for genomic studies in other taxa; nonetheless, results to date indicate that several cases of allochrony involve changes in circadian genes. This review provides the first comprehensive discussion of the role of allochrony in speciation and demonstrates that allochrony as a contributor to divergence may be more widespread than previously thought. Understanding genomic changes and adaptations allowing organisms to breed at new times may be key in the light of phenological changes required under climate change.
Benefits of polyandry: Molecular evidence from field‐caught dung beetles
Authors: McCullough Erin L. , Buzatto Bruno A. , Simmons Leigh W.
Published: March 2017

When females mate with multiple males, they set the stage for postcopulatory sexual selection via sperm competition and/or cryptic female choice. Surprisingly little is known about the rates of multiple mating by females in the wild, despite the importance of this information in understanding the potential for postcopulatory sexual selection to drive the evolution of reproductive behaviour, morphology and physiology. Dung beetles in the genus Onthophagus have become a laboratory model for studying pre‐ and postcopulatory sexual selection, yet we still lack information about the reproductive behaviour of female dung beetles in natural populations. Here, we develop microsatellite markers for Onthophagus taurus and use them to genotype the offspring of wild‐caught females and to estimate natural rates of multiple mating and patterns of sperm utilization. We found that O. taurus females are highly polyandrous: 88% of females produced clutches sired by at least two males, and 5% produced clutches with as many as five sires. Several females (23%) produced clutches with significant paternity skew, indicating the potential for strong postcopulatory sexual selection in natural populations. There were also strong positive correlations between the number of offspring produced and both number of fathers and paternity skew, which suggests that females benefit from mating polyandrously by inciting postcopulatory mechanisms that bias paternity towards males that can sire more viable offspring. This study evaluates the fitness consequences of polyandry for an insect in the wild and provides strong evidence that female dung beetles benefit from multiple mating under natural conditions.
New insights on the antibacterial efficacy of miconazole in vitro
Authors: Nenoff P. , Koch D. , Krüger C. , Drechsel C. , Mayser P.
Published: March 2017

Miconazole is a broad‐spectrum antifungal used in topical preparations. In the present investigation the minimal inhibitory concentration (MIC) of miconazole for eighty wild type strains of gram‐positive and gram‐negative bacteria isolated from infected skin lesions was assessed using a modified agar dilution test (adapted to CLSI, Clinical Laboratory Standards Institute). 14 ATCC reference strains served as controls. Miconazole was found efficacious against gram‐positive aerobic bacteria (n=62 species), the MICs against Staphylococcus (S.) aureus, S. spp., Streptococcus spp. und Enterococcus spp. ranged between 0.78 and 6.25 μg/mL. Interestingly, there were no differences in susceptibility between methicillin‐susceptible (MSSA, 3) methicillin‐resistant (MRSA, 6) and fusidic acid‐resistant (FRSA, 2) S. aureus isolates. Strains of Streptococcus pyogenes (A‐streptococci) (8) were found to be slightly more sensitive (0.78‐1.563 μg/mL), while for gram‐negative bacteria, no efficacy was found within the concentrations tested (MIC >200 μg/mL). In conclusion, for the gram‐positive aerobic bacteria the MICs of miconazole were found within a range which is much lower than the concentration of miconazole used in topical preparations (2%). Thus topically applied miconazole might be a therapeutic option in skin infections especially caused by gram‐positive bacteria even by those strains which are resistant to antibiotics.
Human skeletal muscle fibroblasts stimulate in vitro myogenesis and in vivo muscle regeneration
Authors: Mackey Abigail L. , Magnan Mélanie , Chazaud Bénédicte , Kjaer Michael
Published: March 2017

Key points

Accumulation of skeletal muscle extracellular matrix is an unfavourable characteristic of many muscle diseases, muscle injury and sarcopenia.

The extent of cross‐talk between fibroblasts, as the source of matrix protein, and satellite cells in humans is unknown. We studied this in human muscle biopsies and cell‐culture studies.

We observed a strong stimulation of myogenesis by human fibroblasts in cell culture.

In biopsies collected 30 days after a muscle injury protocol, fibroblast number increased to four times control levels, where fibroblasts were found to be preferentially located immediately surrounding regenerating muscle fibres.

These novel findings indicate an important role for fibroblasts in supporting the regeneration of muscle fibres, potentially through direct stimulation of satellite cell differentiation and fusion, and contribute to understanding of cell–cell cross‐talk during physiological and pathological muscle remodelling.

Accumulation of skeletal muscle extracellular matrix is an unfavourable characteristic of many muscle diseases, muscle injury and sarcopenia. In addition to the indispensable role satellite cells play in muscle regeneration, there is emerging evidence in rodents for a regulatory influence on fibroblast activity. However, the influence of fibroblasts on satellite cells and muscle regeneration in humans is unknown. The purpose of this study was to investigate this in vitro and during in vivo regeneration in humans. Following a muscle injury protocol in young healthy men (n = 7), the number of fibroblasts (TCF7L2+), satellite cells (Pax7+), differentiating myogenic cells (myogenin+) and regenerating fibres (neonatal/embryonic myosin+) was determined from biopsy cross‐sections. Fibroblasts and myogenic precursor cells (MPCs) were also isolated from human skeletal muscle (n = 4) and co‐cultured using different cell ratios, with the two cell populations either in direct contact with each other or separated by a permeable membrane. MPC proliferation, differentiation and fusion were assessed from cells stained for BrdU, desmin and myogenin. On biopsy cross‐sections, fibroblast number was seen to increase, along with myogenic cell number, by d7 and increase further by d30, where fibroblasts were observed to be preferentially located immediately surrounding regenerating muscle fibres. In vitro, the presence of fibroblasts in direct contact with MPCs was found to moderately stimulate MPC proliferation and strongly stimulate both MPC differentiation and MPC fusion. It thus appears, in humans, that fibroblasts exert a strong positive regulatory influence on MPC activity, in line with observations during in vivo skeletal muscle regeneration.
Aging increases cell-to-cell transcriptional variability upon immune stimulation
Authors: Martinez-Jimenez Celia Pilar , Eling Nils , Chen Hung-Chang , Vallejos Catalina A. , Kolodziejczyk Aleksandra A. , Connor Frances , Stojic Lovorka , Rayner Timothy F. , Stubbington Michael J. T. , Teichmann Sarah A. , de la Roche Maike , Marioni John C. , Odom Duncan T.
Published: March 2017

Single-cell sequencing of mouse immune cells reveals how aging destabilizes a conserved transcriptional activation program.
Mars’ atmospheric history derived from upper-atmosphere measurements of
38
Ar/
36
Ar
Authors: Jakosky B. M. , Slipski M. , Benna M. , Mahaffy P. , Elrod M. , Yelle R. , Stone S. , Alsaeed N.
Published: March 2017

Measurements of Mars’ atmosphere show that 66% has been lost to space, leading to changes in the planet’s climate.
Biodiversity redistribution under climate change: Impacts on ecosystems and human well-being
Authors: Pecl Gretta T. , Araújo Miguel B. , Bell Johann D. , Blanchard Julia , Bonebrake Timothy C. , Chen I-Ching , Clark Timothy D. , Colwell Robert K. , Danielsen Finn , Evengård Birgitta , Falconi Lorena , Ferrier Simon , Frusher Stewart , Garcia Raquel A. , Griffis Roger B. , Hobday Alistair J. , Janion-Scheepers Charlene , Jarzyna Marta A. , Jennings Sarah , Lenoir Jonathan , Linnetved Hlif I. , Martin Victoria Y. , McCormack Phillipa C. , McDonald Jan , Mitchell Nicola J. , Mustonen Tero , Pandolfi John M. , Pettorelli Nathalie , Popova Ekaterina , Robinson Sharon A. , Scheffers Brett R. , Shaw Justine D. , Sorte Cascade J. B. , Strugnell Jan M. , Sunday Jennifer M. , Tuanmu Mao-Ning , Vergés Adriana , Villanueva Cecilia , Wernberg Thomas , Wapstra Erik , Williams Stephen E.
Published: March 2017

Consequences of shifting species distributions

Climate change is causing geographical redistribution of plant and animal species globally. These distributional shifts are leading to new ecosystems and ecological communities, changes that will affect human society. Pecl
et al.
review these current and future impacts and assess their implications for sustainable development goals.

Science
, this issue p.
eaai9214
Inhibitors of PEX14 disrupt protein import into glycosomes and kill
Trypanosoma
parasites
Authors: Dawidowski M. , Emmanouilidis L. , Kalel V. C. , Tripsianes K. , Schorpp K. , Hadian K. , Kaiser M. , Mäser P. , Kolonko M. , Tanghe S. , Rodriguez A. , Schliebs W. , Erdmann R. , Sattler M. , Popowicz G. M.
Published: March 2017

A drug that inhibits trafficking of proteins into a peroxisome-like organelle in trypanosomes causes lethal metabolic catastrophe.
Gene bivalency at Polycomb domains regulates cranial neural crest positional identity
Authors: Minoux Maryline , Holwerda Sjoerd , Vitobello Antonio , Kitazawa Taro , Kohler Hubertus , Stadler Michael B. , Rijli Filippo M.
Published: March 2017

Epigenetic regulation of craniofacial development in mice is discussed.
Mechanized creatures
Robots
Ben Russell, Curator
Science Museum London. Through 3 September 2017.
Authors: Sareh Pooya , Kovac Mirko
Published: March 2017

A new exhibition surveys five centuries of robotic invention
Impact of Contaminating DNA in Whole-Genome Amplification Kits Used for Metagenomic Shotgun Sequencing for Infection Diagnosis
Authors: Thoendel Matthew , Jeraldo Patricio , Greenwood-Quaintance Kerryl E. , Yao Janet , Chia Nicholas , Hanssen Arlen D. , Abdel Matthew P. , Patel Robin
Published: March 2017

Whole-genome amplification (WGA) is a useful tool for amplification of very small quantities of DNA for many uses, including metagenomic shotgun sequencing for infection diagnosis. Depending on the application, background DNA from WGA kits can be problematic. Three WGA kits were tested for their utility in a metagenomics approach to identify the pathogens in sonicate fluid comprised of biofilms and other materials dislodged from the surfaces of explanted prosthetic joints using sonication. The Illustra V2 Genomiphi, Illustra single cell Genomiphi, and Qiagen REPLI-g single cell kits were used to test identical sonicate fluid samples. Variations in the number of background reads, the genera identified in the background, and the number of reads from known pathogens known to be present in the samples were observed between kits. These results were then compared to those obtained with a library preparation without prior WGA using an NEBNext Ultra II paired-end kit, which requires a very small amount of input DNA. This approach also resulted in the presence of contaminant bacterial DNA and yielded fewer reads from the known pathogens. These findings highlight the impact that WGA kit selection can have on metagenomic analysis of low-biomass samples and the importance of the careful selection and consideration of the implications of using these tools.
SGTA-Dependent Regulation of Hsc70 Promotes Cytosol Entry of Simian Virus 40 from the Endoplasmic Reticulum
Authors: Dupzyk Allison , Williams Jeffrey M. , Bagchi Parikshit , Inoue Takamasa , Tsai Billy
Published: March 2017

Membrane penetration by nonenveloped viruses remains enigmatic. In the case of the nonenveloped polyomavirus simian virus 40 (SV40), the virus penetrates the endoplasmic reticulum (ER) membrane to reach the cytosol and then traffics to the nucleus to cause infection. We previously demonstrated that the cytosolic Hsc70-SGTA-Hsp105 complex is tethered to the ER membrane, where Hsp105 and SGTA facilitate the extraction of SV40 from the ER and transport of the virus into the cytosol. We now find that Hsc70 also ejects SV40 from the ER into the cytosol in a step regulated by SGTA. Although SGTA's N-terminal domain, which mediates homodimerization and recruits cellular adaptors, is dispensable during ER-to-cytosol transport of SV40, this domain appears to exert an unexpected post-ER membrane translocation function during SV40 entry. Our study thus establishes a critical function of Hsc70 within the Hsc70-SGTA-Hsp105 complex in promoting SV40 ER-to-cytosol membrane penetration and unveils a role of SGTA in controlling this step.

IMPORTANCE
How a nonenveloped virus transports across a biological membrane to cause infection remains mysterious. One enigmatic step is whether host cytosolic components are co-opted to transport the viral particle into the cytosol. During ER-to-cytosol membrane transport of the nonenveloped polyomavirus SV40, a decisive infection step, a cytosolic complex composed of Hsc70-SGTA-Hsp105 was previously shown to associate with the ER membrane. SGTA and Hsp105 have been shown to extract SV40 from the ER and transport the virus into the cytosol. We demonstrate here a critical role of Hsc70 in SV40 ER-to-cytosol penetration and reveal how SGTA controls Hsc70 to impact this process.