bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of realimentation after nutrient restriction during mid‐ to late gestation on pancreatic digestive enzymes, serum insulin and glucose levels, and insulin‐containing cell cluster morphology
Authors: Keomanivong F. E. , Camacho L. E. , Lemley C. O. , Kuemper E. A. , Yunusova R. D. , Borowicz P. P. , Kirsch J. D. , Vonnahme K. A. , Caton J. S. , Swanson K. C. 
Published: April 2016

SummaryThis study examined effects of stage of gestation and nutrient restriction with subsequent realimentation on maternal and foetal bovine pancreatic function. Dietary treatments were assigned on day 30 of pregnancy and included: control (CON; 100% requirements; n = 18) and restricted (R; 60% requirements; n = 30). On day 85, cows were slaughtered (CON, n = 6; R, n = 6), remained on control (CC; n = 12) and restricted (RR; n = 12), or realimented to control (RC; n = 11). On day 140, cows were slaughtered (CC, n = 6; RR, n = 6; RC, n = 5), remained on control (CCC, n = 6; RCC, n = 5) or realimented to control (RRC, n = 6). On day 254, the remaining cows were slaughtered and serum samples were collected from the maternal jugular vein and umbilical cord to determine insulin and glucose concentrations. Pancreases from cows and foetuses were removed, weighed, and subsampled for enzyme and histological analysis. As gestation progressed, maternal pancreatic α‐amylase activity decreased and serum insulin concentrations increased (p ≤ 0.03). Foetal pancreatic trypsin activity increased (p < 0.001) with advancing gestation. Foetal pancreases subjected to realimentation (CCC vs. RCC and RRC) had increased protein and α‐amylase activity at day 254 (p ≤ 0.02), while trypsin (U/g protein; p = 0.02) demonstrated the opposite effect. No treatment effects were observed for maternal or foetal pancreatic insulin‐containing cell clusters. Foetal serum insulin and glucose levels were reduced with advancing gestation (p ≤ 0.03). The largest maternal insulin‐containing cell cluster was not influenced by advancing gestation, while foetal clusters grew throughout (p = 0.01). These effects indicate that maternal digestive enzymes are influenced by nutrient restriction and there is a potential for programming of increased foetal digestive enzyme production resulting from previous maternal nutrient restriction.
Uncertainty, Flexible Labour Relations and R&D
Authors: Di Cintio Marco , Grassi Emanuele 
Published: April 2016

AbstractThis paper examines the effects of uncertainty and flexible labour contracts on the Research and Development (R&D) intensity. Using a panel of Italian manufacturing firms, we find a hump‐shaped relationship between workforce flexibility and R&D intensity. Moreover, as predicted by the real options theory, our results suggest that product market uncertainty reduces R&D efforts and that flexible labour contracts countervail the adverse effect of uncertainty on R&D.
Reloca Slide: an ~24 km3 submarine mass‐wasting event in response to over‐steepening and failure of the central Chilean continental slope
Authors: Contreras‐Reyes Eduardo , Völker David , Bialas Jörg , Moscoso Eduardo , Grevemeyer Ingo 
Published: April 2016

AbstractReloca Slide is the relict of an ~24‐km3 submarine slope collapse at the base of the convergent continental margin of central Chile. Bathymetric and seismic data show that directly to the north and south of the slide the lower continental slope is steep (~10°), the deformation front is shifted landwards by 10–15 km, and the frontal accretionary prism is uplifted. In contrast, ~80 km to the north the lower continental margin presents a lower slope angle of about 4° and a wide frontal accretionary prism. We propose that high effective basal friction conditions at the base of the accretionary prism favoured basal accretion of sediment and over‐steepening of the continental slope, producing massive submarine mass wasting in the Reloca region. This area also spatially correlates with a zone of low coseismic slip of the 2010 Maule megathrust earthquake, which is consistent with high basal frictional coefficients.
Two human immunodeficiency virus Type 2 cases in US blood donors including serologic, molecular, and genomic characterization of an epidemiologically unusual case
Authors: Stramer Susan L. , Yu Guixia , Herron Ross , Espinoza Norma , Foster Gregory A. , Naccache Samia N. , Brodsky Jaye P. , Ong Edgar , Linnen Jeffrey M. , Dyer Nicole , Styer Linda M. , Parker Monica M. , Chiu Charles Y. 
Published: April 2016

BACKGROUNDBlood donation screening for human immunodeficiency virus Type 2 (HIV‐2) has been in place in the United States since 1992. However, only three HIV‐2 antibody–positive donors have been reported to date, all detected via HIV‐1 cross‐reactivity.STUDY DESIGN AND METHODSHere we identify two additional HIV‐2–positive donors by routine anti‐HIV‐1 and anti‐HIV‐2 screening, including a first‐time male donor living in Georgia having recently immigrated to the United States from West Africa (from a 1998 donation) and a Taiwanese female repeat donor (nurse) living in California with no travel outside of Taiwan or apparent connections to West Africa (from a 2015 donation). Neither donor acknowledged any risk factors, and both remained asymptomatic through follow‐up. The second donor was further investigated by serologic, molecular, and genomic assays because of her unusual demographics. She was documented to harbor HIV‐2 RNA, albeit sporadically by HIV‐2–specific nucleic acid tests (35%‐100% of replicates) and at very low levels (<9.6 IU/mL). Metagenomic next‐generation sequencing (mNGS) confirmed the identification of a Group B HIV‐2 strain, with recovered reads covering 46.9% of the predicted genome.CONCLUSIONSThe estimated frequency of an HIV‐2–positive blood donor in the United States is one in 57 million donations. Due to the low frequency and low pathogenicity of HIV‐2, public health and blood donation screening efforts must focus on HIV‐1 detection and prevention. However, detection of HIV‐2 infection in a donor with no apparent link to West Africa suggests that the United States must remain vigilant for HIV‐2 virus infections. Ultradeep mNGS may be useful in the future for comprehensive identification of rare transfusion‐transmissible agents.
Postnatal cytomegalovirus infection: a pilot comparative effectiveness study of transfusion safety using leukoreduced‐only transfusion strategy
Authors: Delaney Meghan , Mayock Dennis , Knezevic Andrea , Norby‐Slycord Colette , Kleine Elizabeth , Patel Ravi , Easley Kirk , Josephson Cassandra 
Published: April 2016

BACKGROUNDThe optimal mitigation strategy to prevent transfusion transmission of cytomegalovirus (TT‐CMV) in preterm very low birthweight infants remains debated. Hospitals caring for this patient population have varied practices.STUDY DESIGN AND METHODSA prospective observational comparative effectiveness pilot study was conducted to determine the feasibility for a larger study. The pilot was carried out at hospitals using a leukoreduction (LR)‐only transfusion strategy. Specimen and data collection for this study was performed in a similar approach to a study completed at Emory University that employed the CMV‐seronegative plus LR approach. All testing was performed at one laboratory. The rates of TT‐CMV using the two transfusion strategies were compared.RESULTSZero incidence of TT‐CMV was detected in infants (n = 20) transfused with LR‐only blood (0/8; 95% confidence interval [CI], 0‐25.3%) and is consistent with the previously reported zero incidence of TT‐CMV finding in a cohort of infants transfused with CMV‐negative plus LR blood (0/310; 95% CI, 0%‐0.9%). The seroprevalence rate among enrolled mothers (n = 17) was 60%. Forty percent of those infants (8/20) received 43 transfusions; five were transfused with one or more CMV‐seropositive blood components. One infant had tested positive for CMV before receiving blood transfusions; the infant's mother was CMV immunoglobulin (Ig)G positive and IgM negative.CONCLUSIONSUsing the LR‐only transfusion approach, zero cases of TT‐CMV were detected in this pilot study. A larger study is needed to reliably determine the most effective strategy for prevention of TT‐CMV in this population.
Hair transplantation in mice: Challenges and solutions
Authors: Asgari Azar Z , Rufaut Nicholas. W. , Morrison Wayne A. , Dilley Rodney. J. , Knudsen Russle , Jones Leslie N. , Sinclair Rodney. D. 
Published: April 2016

AbstractHair follicle cells contribute to wound healing, skin circulation, and skin diseases including skin cancer, and hair transplantation is a useful technique to study the participation of hair follicle cells in skin homeostasis and wound healing. Although hair follicle transplantation is a well‐established human hair‐restoration procedure, follicular transplantation techniques in animals have a number of shortcomings and have not been well described or optimized. To facilitate the study of follicular stem and progenitor cells and their interaction with surrounding skin, we have established a new murine transplantation model, similar to follicular unit transplantation in humans. Vibrissae from GFP transgenic mice were harvested, flip‐side microdissected, and implanted individually into needle hole incisions in the back skin of immune‐deficient nude mice. Grafts were evaluated histologically and the growth of transplanted vibrissae was observed. Transplanted follicles cycled spontaneously and newly formed hair shafts emerged from the skin after 2 weeks. Ninety percent of grafted vibrissae produced a hair shaft at 6 weeks. After pluck‐induced follicle cycling, growth rates were equivalent to ungrafted vibrissae. Transplanted vibrissae with GFP‐positive cells were easily identified in histological sections. We established a follicular vibrissa transplantation method that recapitulates human follicular unit transplantation. This method has several advantages over current protocols for animal hair transplantation. The method requires no suturing and minimizes the damage to donor follicles and recipient skin. Vibrissae are easier to microdissect and transplant than pelage follicles and, once transplanted, are readily distinguished from host pelage hair. This facilitates measurement of hair growth. Flip‐side hair follicle microdissection precisely separates donor follicular tissue from interfollicular tissue and donor cells remain confined to hair follicles. This makes it possible to differentiate migration of hair follicle cells from interfollicular epidermis in lineage tracing wound experiments using genetically labeled donor follicles.
Structure of the maximal -local geometry point-line collinearity graph
Authors: Rowley Peter , Wright Ben 
Published: April 2016

The point-line collinearity graph${\mathcal{G}}$of the maximal 2-local geometry for the largest simple Fischer group,$Fi_{24}^{\prime }$, is extensively analysed. For an arbitrary vertex$a$of${\mathcal{G}}$, the$i\text{th}$-disc of$a$is described in detail. As a consequence, it follows that${\mathcal{G}}$has diameter$5$. The collapsed adjacency matrix of${\mathcal{G}}$is given as well as accompanying computer files which contain a wealth of data about${\mathcal{G}}$.Supplementary materials are available with this article.
Extrusion versus diffusion: mechanisms for recovery from sodium loads in mouse CA1 pyramidal neurons
Authors: Mondragão Miguel A. , Schmidt Hartmut , Kleinhans Christian , Langer Julia , Kafitz Karl W. , Rose Christine R. 
Published: April 2016

Key points
Neuronal activity causes local or global sodium signalling in neurons, depending on the pattern of synaptic activity.
Recovery from global sodium loads critically relies on Na+/K+‐ATPase and an intact energy metabolism in both somata and dendrites.
For recovery from local sodium loads in dendrites, Na+/K+‐ATPase activity is not required per se. Instead, recovery is predominately mediated by lateral diffusion, exhibiting rates that are 10‐fold higher than for global sodium signals.
Recovery from local dendritic sodium increases is still efficient during short periods of energy deprivation, indicating that fast diffusion of sodium to non‐stimulated regions strongly reduces local energy requirements.
AbstractExcitatory activity is accompanied by sodium influx into neurones as a result of the opening of voltage‐ and ligand‐activated channels. Recovery from resulting sodium transients has mainly been attributed to Na+/K+‐ATPase (NKA). Because sodium ions are highly mobile, diffusion could provide an additional pathway. We tested this in hippocampal neurones using whole‐cell patch‐clamp recordings and sodium imaging. Somatic sodium transients induced by local glutamate application recovered at a maximum rate of 8 mm min−1 (∼0.03 mm min−1 μm−2). Somatic sodium extrusion was accelerated at higher temperature and blocked by ouabain, emphasizing its dependence on NKA. Moreover, it was slowed down during inhibition of glycolysis by sodium fluoride (NaF). Local glutamate application to dendrites revealed a 10‐fold higher apparent dendritic sodium extrusion rate compared to somata. Recovery was almost unaltered by increased temperature, ouabain or NaF. We found that sodium diffused along primary dendrites with a diffusion coefficient of ∼330 μm²/s. During global glutamate application, impeding substantial net diffusion, apparent dendritic extrusion rates were reduced to somatic rates and also affected by NaF. Numerical simulations confirmed the essential role of NKA for the recovery of somatic, but not dendritic sodium loads. Our data show that sodium export upon global sodium increases is largely mediated by NKA and depends on an intact energy metabolism. For recovery from local dendritic sodium increases, diffusion dominates over extrusion, operating efficiently even during short periods of energy deprivation. Although sodium will eventually be extruded by the NKA, its diffusion‐based fast dissemination to non‐stimulated regions might reduce local energy requirements.
Compression Garments, Muscle Contractile Function, and Economy in Trail Runners
Authors: Vercruyssen Fabrice , Gruet Mathieu , Colson Serge S. , Ehrstrom Sabine , Brisswalter Jeanick 
Published: April 2016

Background:Physiological mechanisms behind the use of compression garments (CGs) during off-road running are unknown.Purpose:To investigate the influence of wearing CGs vs conventional running clothing (CON) on muscle contractile function and running economy before and after short-distance trail running.Methods:Knee-extensor neuromuscular function and running economy assessed from two 5-min treadmill runs (11 and 14 km/h) were evaluated before and after an 18.6-km short-distance trail run in 12 trained athletes wearing either CGs (stocking + short-tight) or CON. Quadriceps neuromuscular function was assessed from mechanical and EMG recording after maximal percutaneous electrical femoral-nerve stimulations (single-twitch doublets at 10 [Db10] and 100 Hz [Db100] delivered at rest and during maximal quadriceps voluntary contraction [MVC]).Results:Running economy (in mL O2 · km–1 · kg–1) increased after trail running independent of the clothing condition and treadmill speeds (P < .001). Similarly, MVC decreased after CON and CGs conditions (–11% and –13%, respectively, P < .001). For both clothing conditions, a significant decrease in quadriceps voluntary activation, Db10, Db100, and the low-to-high frequency doublet ratio were observed after trail running (time effect, all P < .01), without any changes in rectus femoris maximal M-wave.Conclusions:Wearing CGs does not reduce physiological alterations induced during short-distance trail running. Further studies should determine whether higher intensity of compression pressure during exercises of longer duration may be effective to induce any physiological benefits in experienced trail runners.
Amino Acid Substitutions of CrrB Responsible for Resistance to Colistin through CrrC in Klebsiella pneumoniae
Authors: Cheng Yi-Hsiang , Lin Tzu-Lung , Lin Yi-Tsung , Wang Jin-Town 
Published: April 2016

ABSTRACT

Colistin is a last-resort antibiotic for treatment of carbapenem-resistant
Klebsiella pneumoniae
. A recent study indicated that missense mutations in the CrrB protein contribute to colistin resistance. In our previous study, mechanisms of colistin resistance were defined in 17 of 26 colistin-resistant
K. pneumoniae
clinical isolates. Of the remaining nine strains, eight were highly resistant to colistin. In the present study,
crrAB
sequences were determined for these eight strains. Six separate amino acid substitutions in CrrB (Q10L, Y31H, W140R, N141I, P151S, and S195N) were detected. Site-directed mutagenesis was used to generate
crrB
loci harboring individual missense mutations; introduction of the mutated genes into a susceptible strain, A4528, resulted in 64- to 1,024-fold increases in colistin MICs. These
crrB
mutants showed increased accumulation of
H239_3062
,
H239_3059
,
pmrA
,
pmrC
, and
pmrH
transcripts by quantitative reverse transcription (qRT)-PCR. Deletion of
H239_3062
(but not that of
H239_3059
) in the A4528
crrB
(
N141I
) strain attenuated resistance to colistin, and
H239_3062
was accordingly named
crrC
. Similarly, accumulation of
pmrA
,
pmrC
, and
pmrH
transcripts induced by
crrB
(
N141I
) was significantly attenuated upon deletion of
crrC
. Complementation of
crrC
restored resistance to colistin and accumulation of
pmrA
,
pmrC
, and
pmrH
transcripts in a
crrB
(
N141I
) Δ
crrC
strain. In conclusion, novel individual CrrB amino acid substitutions (Y31H, W140R, N141I, P151S, and S195N) were shown to be responsible for colistin resistance. We hypothesize that CrrB mutations induce CrrC expression, thereby inducing elevated expression of the
pmrHFIJKLM
operon and
pmrC
(an effect mediated via the PmrAB two-component system) and yielding increased colistin resistance.
Molecular Epidemiology and Genetic Characteristics of Various
bla
PER
Genes in Shanghai, China
Authors: Xie Lianyan , Wu Jun , Zhang Fangfang , Han Lizhong , Guo Xiaokui , Ni Yuxing , Sun Jingyong 
Published: April 2016

ABSTRACT

We describe the genetic characteristics and possible transmission mechanism of
bla
PER
in 25 clinical Gram-negative bacilli in Shanghai.
bla
PER
, including
bla
PER-1
,
bla
PER-3
, and
bla
PER-4
, was located chromosomally or in different plasmids. Tn
1213
harboring
bla
PER-1
was first identified in two
Proteus mirabilis
isolates in China. The other
bla
PER
variants were preceded by an IS
CR1
element inside the complex class 1 integron associated with IS
26
, Tn
21
, Tn
1696
, and a miniature inverted-repeat transposable element.
New Role for FDA-Approved Drugs in Combating Antibiotic-Resistant Bacteria
Authors: Andersson Jourdan A. , Fitts Eric C. , Kirtley Michelle L. , Ponnusamy Duraisamy , Peniche Alex G. , Dann Sara M. , Motin Vladimir L. , Chauhan Sadhana , Rosenzweig Jason A. , Sha Jian , Chopra Ashok K. 
Published: April 2016

ABSTRACT

Antibiotic resistance in medically relevant bacterial pathogens, coupled with a paucity of novel antimicrobial discoveries, represents a pressing global crisis. Traditional drug discovery is an inefficient and costly process; however, systematic screening of Food and Drug Administration (FDA)-approved therapeutics for other indications in humans offers a rapid alternative approach. In this study, we screened a library of 780 FDA-approved drugs to identify molecules that rendered RAW 264.7 murine macrophages resistant to cytotoxicity induced by the highly virulent
Yersinia pestis
CO92 strain. Of these compounds, we identified 94 not classified as antibiotics as being effective at preventing
Y. pestis
-induced cytotoxicity. A total of 17 prioritized drugs, based on efficacy in
in vitro
screens, were chosen for further evaluation in a murine model of pneumonic plague to delineate if
in vitro
efficacy could be translated
in vivo
. Three drugs, doxapram (DXP), amoxapine (AXPN), and trifluoperazine (TFP), increased animal survivability despite not exhibiting any direct bacteriostatic or bactericidal effect on
Y. pestis
and having no modulating effect on crucial
Y. pestis
virulence factors. These findings suggested that DXP, AXPN, and TFP may modulate host cell pathways necessary for disease pathogenesis. Finally, to further assess the broad applicability of drugs identified from
in vitro
screens, the therapeutic potential of TFP, the most efficacious drug
in vivo
, was evaluated in murine models of
Salmonella enterica
serovar Typhimurium and
Clostridium difficile
infections. In both models, TFP treatment resulted in increased survivability of infected animals. Taken together, these results demonstrate the broad applicability and potential use of nonantibiotic FDA-approved drugs to combat respiratory and gastrointestinal bacterial pathogens.
Clomipramine and Benznidazole Act Synergistically and Ameliorate the Outcome of Experimental Chagas Disease
Authors: García Mónica Cristina , Ponce Nicolás Eric , Sanmarco Liliana Maria , Manzo Rubén Hilario , Jimenez-Kairuz Alvaro Federico , Aoki Maria Pilar 
Published: April 2016

ABSTRACTChagas disease is an important public health problem in Latin America, and its treatment by chemotherapy with benznidazole (BZ) or nifurtimox remains unsatisfactory. In order to design new alternative strategies to improve the current etiological treatments, in the present work, we comprehensively evaluated thein vitroandin vivoanti-Trypanosoma cruzieffects of clomipramine (CMP) (a parasite-trypanothione reductase-specific inhibitor) combined with BZ.In vitrostudies, carried out using a checkerboard technique on trypomastigotes (T. cruzistrain Tulahuen), revealed a combination index (CI) of 0.375, indicative of a synergistic effect of the drug combination. This result was correlated with the data obtained in infected BALB/c mice. We observed that during the acute phase (15 days postinfection [dpi]), BZ at 25 mg/kg of body weight/day alone decreased the levels of parasitemia compared with those of the control group, but when BZ was administered with CMP, the drug combination completely suppressed the parasitemia due to the observed synergistic effect. Furthermore, in the chronic phase (90 dpi), mice treated with both drugs showed less heart damage as assessed by the histopathological analysis, index of myocardial inflammation, and levels of heart injury biochemical markers than mice treated with BZ alone at the reference dose (100 mg/kg/day). Collectively, these data support the notion that CMP combined with low doses of BZ diminishes cardiac damage and inflammation during the chronic phase of cardiomyopathy. The synergistic activity of BZ-CMP clearly suggests a potential drug combination for Chagas disease treatment, which would allow a reduction of the effective dose of BZ and an increase in therapeutic safety.