bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulatory cascade and biological activity of
Beauveria bassiana
oosporein that limits bacterial growth after host death
Authors: Fan Yanhua , Liu Xi , Keyhani Nemat O. , Tang Guirong , Pei Yan , Zhang Wenwen , Tong Sheng 
Published: February 2017

Significance
Since the discovery of oosporein more than 70 years ago, there have been conflicting reports on its potential antimicrobial and insecticidal activities. Our results indicate that oosporein is unlikely to function as an insect toxin or to be involved in early to mid-infection processes, including penetration and immune evasion. Instead, oosporein most likely functions after death of the host to thwart bacterial competition on a host cadaver, allowing the fungus to maximally use host nutrients and complete its life cycle. Our data also reveal that oosporein production is regulated by a cascade of transcription factors, with BbSmr1 acting as an upstream negative regulator, targeting the expression of OpS3, which in turn acts as a positive regulator of the oosporein biosynthetic gene cluster.
Contribution of epigenetic mechanisms to variation in cancer risk among tissues
Authors: Klutstein Michael , Moss Joshua , Kaplan Tommy , Cedar Howard 
Published: February 2017

Significance
It is well-known that the risk of cancer varies widely between different tissues of the body with some cell types (e.g., colon, breast) being prone to cancer, whereas others (e.g., brain, bone) only rarely develop tumors, but the mechanism of this phenomenon has not been elucidated. Recently, it was shown that this risk coefficient may actually be related to the inherent number of stem-cell divisions that go into generating each individual cell type during development. In this work, we demonstrate that cancer risk is highly correlated with the degree of aberrant age-dependent methylation in normal tissues, clearly supporting the idea that cell-type tumor susceptibility may be influenced by biologically intrinsic epigenetic factors.
Multiple-scale neuroendocrine signals connect brain and pituitary hormone rhythms
Authors: Romanò Nicola , Guillou Anne , Hodson David J. , Martin Agnès O , Mollard Patrice 
Published: February 2017

Significance
The hypothalamo–pituitary axis controls a wide range of homeostatic processes, including growth, stress, and reproduction. Despite this fact, the hypothalamic neuron firing patterns that lead to slowly evolving pituitary hormone rhythms remain enigmatic. Here, we used in vivo amperometric recordings in freely behaving mice to investigate how tuberoinfundibular neurons release dopamine (DA) at the median eminence (ME) to control pituitary prolactin secretion. Using this approach, we show that DA release occurs as multiple locally generated and time-scaled secretory events, which are integrated over a range of minutes across the ME. These results provide a broad physiological mechanism for the dialogue that occurs between the brain and pituitary to dictate hormone rhythms over multiple timescales, from ultradian to seasonal.
Ontogeny of collective behavior reveals a simple attraction rule
Authors: Hinz Robert C. , de Polavieja Gonzalo G. 
Published: February 2017

Significance
Different interaction rules among animals can produce patterns of collective motion similar to those observed in bird flocks or fish schools. To help distinguish which rules are implemented in animal collectives, we studied the birth of the interaction rule in zebrafish during development from hatching to the juvenile stage. We used newly developed machine vision algorithms to track each animal in a group without mistakes. A weak attraction starts after hatching and gets stronger every day during development. Attraction consists in each larva moving toward one other larva chosen effectively at random and then switching to another one. This rule, simply by statistics, makes each individual move to regions of high density of individuals to produce collective motion.
Interleukin 37 reverses the metabolic cost of inflammation, increases oxidative respiration, and improves exercise tolerance
Authors: Cavalli Giulio , Justice Jamie N. , Boyle Kristen E. , D’Alessandro Angelo , Eisenmesser Elan Z. , Herrera Jonathan J. , Hansen Kirk C. , Nemkov Travis , Stienstra Rinke , Garlanda Cecilia , Mantovani Alberto , Seals Douglas R. , Dagna Lorenzo , Joosten Leo A. B. , Ballak Dov B. , Dinarello Charles A. 
Published: February 2017

Significance
Interleukin 1 family member IL-37 is a naturally occurring inhibitor of inflammation. In this study, exogenous administration of recombinant human IL-37 reversed the decrease in exercise performance observed during systemic inflammation. IL-37 also increased exercise performance in healthy mice. IL-37 treatment acted through a dual mechanism of suppression of inflammation and modulation of metabolic pathways. The implications of the present findings impact on patients with chronic inflammatory diseases spanning from rheumatoid arthritis to cancer, in which fatigue is often incapacitating, and provide rationale for exploring recombinant IL-37 in the treatment of inflammation-mediated fatigue.
Spontaneous expression of mirror self-recognition in monkeys after learning precise visual-proprioceptive association for mirror images
Authors: Chang Liangtang , Zhang Shikun , Poo Mu-ming , Gong Neng 
Published: February 2017

Significance
Self-awareness is a higher intelligence that can be revealed by mirror self-recognition (MSR) in humans. Testing MSR has become the main approach to examining the existence of self-recognition in animals, and only a few species have passed the test. However, it remains controversial whether failing the MSR test is a result of the lack of an animal’s self-recognition ability or the inadequacy of the mirror test. We found that MSR spontaneously appeared in rhesus monkeys after training for precise visual-proprioceptive association for mirror images. Thus, bodily self-consciousness may be a cognitive ability present in many more species than previously thought, and could be revealed by MSR when the animal acquired visual-proprioceptive association for the images in the mirror.
Systems analysis of protective immune responses to RTS,S malaria vaccination in humans
Authors: Kazmin Dmitri , Nakaya Helder I. , Lee Eva K. , Johnson Matthew J. , van der Most Robbert , van den Berg Robert A. , Ballou W. Ripley , Jongert Erik , Wille-Reece Ulrike , Ockenhouse Christian , Aderem Alan , Zak Daniel E. , Sadoff Jerald , Hendriks Jenny , Wrammert Jens , Ahmed Rafi , Pulendran Bali 
Published: February 2017

Significance
The RTS,S malaria vaccine is the most advanced malaria vaccine candidate to be tested in humans. Despite its promise, there is little understanding of its mechanism of action. In this work, we describe the use of a systems biological approach to identify “molecular signatures” that are induced rapidly after the standard RTS,S vaccination regimen, consisting of three RTS,S immunizations, or with a different regimen consisting of a primary immunization with recombinant adenovirus 35 (Ad35) expressing the circumsporozoite malaria antigen followed by two immunizations with RTS,S. These results reveal important insights about the innate and adaptive responses to vaccination and identify signatures of protective immunity against malaria.
BMP signaling controls buckling forces to modulate looping morphogenesis of the gut
Authors: Nerurkar Nandan L. , Mahadevan L. , Tabin Clifford J. 
Published: February 2017

Significance
During embryogenesis, the dramatic transformation from a seemingly disorganized mass of cells into the fully patterned adult form necessitates stereotyped regulation of forces at the genetic and molecular level. Although great progress has been made in understanding how gene expression and signaling generate biological pattern, little is known about how molecular cues organize forces to sculpt physical patterns during development. The present work identifies BMP signaling as a key pathway in controlling looping of the small intestine, a process driven by mechanical buckling due to elongation of the intestine against the constraint of a neighboring tissue, the dorsal mesentery.
Postural stability, clicker reaction time and bow draw force predict performance in elite recurve archery
Authors: Spratford Wayne , Campbell Rhiannon 
Published: February 2017

AbstractRecurve archery is an Olympic sport that requires extreme precision, upper body strength and endurance. The purpose of this research was to quantify how postural stability variables both pre‐ and post‐arrow release, draw force, flight time, arrow length and clicker reaction time, collectively, impacted on the performance or scoring outcomes in elite recurve archery athletes. Thirty‐nine elite‐level recurve archers (23 male and 16 female; mean age = 24.7 ± 7.3 years) from four different countries volunteered to participate in this study prior to competing at a World Cup event. An AMTI force platform (1000Hz) was used to obtain centre of pressure (COP) measurements 1s prior to arrow release and 0.5s post‐arrow release. High‐speed footage (200Hz) allowed for calculation of arrow flight time and score. Results identified clicker reaction time, draw force and maximum sway speed as the variables that best predicted shot performance. Specifically, reduced clicker reaction time, greater bow draw force and reduced postural sway speed post‐arrow release were predictors of higher scoring shots. It is suggested that future research should focus on investigating shoulder muscle tremors at full draw in relation to clicker reaction time, and the effect of upper body strength interventions (specifically targeting the musculature around the shoulder girdle) on performance in recurve archers.
“Joining the Spots in Adults and Young Tots”: A Clinicopathological Study of Henoch–Schönlein Purpura (IgA Vasculitis)
Authors: Kedia Priyanka P. , Tirumalae Rajalakshmi , Puttegowda Divya , Antony Meryl 
Published: February 2017

Introduction:
Henoch–Schönlein Purpura (HSP; IgA vasculitis), the most common vasculitis of childhood, has a wide spectrum of clinical manifestations ranging from palpable purpura with abdominal pain and arthritis to the more morbid renal involvement.

Aims and Objectives:
To study and correlate the clinical presentation, laboratory values, skin and renal histopathology and immunofluoroscence findings in HSP.

Material and Methods:
A total of 44 cases of HSP from March 2011 to February 2014 were studied for the above features along with their clinical outcomes.

Results:
The mean age of the patients at presentation was 28.4 years (range 4.5–69 years) with 26.2% being children younger than 15 years. Purpura at presentation was seen in all with 77.1% cases exhibiting extracutaneous involvement. Skin biopsy revealed leukocytoclastic vasculitis in all cases, dominant IgA deposition in the papillary dermal vessels in 43 cases (97.7%), associated C3 in 10 cases (23.3%), and full-house positivity in 1 case. One case without skin immunofluorescence had renal mesangial IgA deposits. Nine cases (20.9%) with an average age of 39 years had renal symptoms and displayed varied histology from focal mesangioproliferative glomerulonephritis to crescentic. All of them had dominant mesangial IgA deposits, majority falling into International Study of Kidney Disease in Children (ISKDC) class IIIb. Peritubular capillaritis was noted in 3 cases. Two patients (4.5%) progressed to end stage renal disease, one of whom had cellular crescents at presentation.

Conclusions:
HSP was seen both in children and adults. Renal involvement was seen in 20.9% cases, all older than 14 years, and 66.7% with extracutaneous manifestations. The outcome in this series was favorable in 96% cases.
The Histopathology of Urticaria Revisited—Clinical Pathological Study
Authors: Barzilai Aviv , Sagi Lior , Baum Sharon , Trau Henri , Schvimer Michael , Barshack Iris , Solomon Michal 
Published: February 2017

Background:
The classic histopathological findings of urticaria include dermal edema and a sparse perivascular infiltrate of neutrophils, eosinophils, macrophages, and lymphocytes. However, this pattern is inconsistently described.

Objective:
To describe the histological and immunofluorescence characteristics of urticaria and to identify distinctive patterns.

Methods:
A retrospective study was performed in which the medical files and biopsy specimens of 58 patients with acute and chronic classical urticaria were reviewed. Pathological parameters were quantified.

Results:
We recognized 2 distinctive patterns of urticaria: lymphocyte and neutrophil predominant; the former was characterized by a perivascular location, whereas the latter was associated with an interstitial location and a denser infiltrate. Mast cells were relatively sparse, better demonstrated with special stains. Tryptase stain demonstrated more mast cells than Giemsa stain. Extravasated erythrocytes were present in 50% of the cases, but vasculitis was not observed.

Conclusions:
Histological findings in classical urticaria show a spectrum of findings from a sparse superficial perivascular to a deep perivascular and interstitial infiltrate. Distinctive groups based on the dominant cell type can be identified, accounting for the similarity to neutrophilic urticarial dermatosis. Lesions may have a purpuric appearance, but leukocytoclastic vasculitis is never present.
Role of Skin Biopsies in the Diagnosis of Hemophagocytic Lymphohistiocytosis
Authors: Santos-Arroyo Aileen , Barrera-Llaurador Julián , Sánchez Julio E. , Martín-García Rafael , Sánchez Jorge L. 
Published: February 2017

Abstract:
This is a report of a 15-year-old female who presented with a skin eruption and clinical features consistent with severe sepsis and septic shock. A diagnosis of acquired hemophagocytic lymphohistiocytosis (HLH) was made and confirmed by bone marrow analysis. Skin biopsy showed hemophagocytosis and CD163-positive staining of macrophages. We briefly review the clinical, histologic, and laboratory findings of hemophagocytic lymphohistiocytosis in addition to the potential role of skin biopsies in this condition.
Cardioprotective Effects of Carvedilol in Inhibiting Doxorubicin-induced Cardiotoxicity
Authors: Nabati Maryam , Janbabai Ghasem , Baghyari Saideh , Esmaili Khadige , Yazdani Jamshid 
Published: February 2017

Purpose:
Anthracyclines (ANTs) are a class of active antineoplastic agents with topoisomerase-interacting activity that are considered the most active agents for the treatment of breast cancer. We investigated the efficacy of carvedilol in the inhibition of ANT-induced cardiotoxicity.

Methods:
In this randomized, single-blind, placebo-controlled study, 91 women with recently diagnosed breast cancer undergoing ANT therapy were randomly assigned to groups treated with either carvedilol (n = 46) or placebo (n = 45). Echocardiography was performed before and at 6 months after randomization, and absolute changes in the mean left ventricular ejection fraction, left ventricular end diastolic volume, and left ventricular end systolic volume were determined. Furthermore, the percentage change in the left atrial (LA) diameter and other variables of left ventricular (LV) diastolic function, such as transmitral Doppler parameters, including early (E wave) and late (A wave) diastolic velocities, E/A ratio and E wave deceleration time, pulmonary venous Doppler signals, including forward systolic (S wave) and diastolic (D wave) velocities into LA, late diastolic atrial reversal velocity, and early diastolic tissue Doppler mitral annular velocity (e') were measured. In addition, tissue Doppler mitral annular systolic (s') velocity, as a marker of early stage of LV systolic dysfunction, E/e' ratio, as a determinant of LV filling pressure, and troponin I level, as a marker of myocardial necrosis were measured.

Results:
At the end of follow-up period, left ventricular ejection fraction did not change in the carvedilol group. However, this parameter was significantly reduced in the control group (P < 0.001). Echocardiography showed that both left ventricular end systolic volume and LA diameter were significantly increased compared with the baseline measures in the control group. In pulse Doppler studies, pulmonary venous peak atrial reversal flow velocity was significantly increased in the control group. Moreover, a significant decrease in the mitral annuli early diastolic (e') and peak systolic (s') velocities and a significant increase in the E (the peak early diastolic velocity)/e' ratio in the control group were also observed. However, none of these variables were adversely changed at the end of follow-up in the carvedilol group. Furthermore, the TnI level was significantly higher in the control group than in the carvedilol group (P = 0.036) at 30 days after the initiation of chemotherapy.

Conclusions:
Prophylactic use of carvedilol may inhibit the development of anthracycline-induced cardiotoxicity, even at low doses.
Early Treatment With Zofenopril and Ramipril in Combination With Acetyl Salicylic Acid in Patients With Left Ventricular Systolic Dysfunction After Acute Myocardial Infarction: Results of a 5-Year Follow-up of Patients of the SMILE-4 Study
Authors: Borghi Claudio , Omboni Stefano , Novo Salvatore , Vinereanu Dragos , Ambrosio Giuseppe , Ambrosioni Ettore ,   on behalf of the SMILE-4 Working Party
Published: February 2017

Abstract:
The SMILE-4 study showed that in patients with left ventricular dysfunction (LVD) after acute myocardial infarction, early treatment with zofenopril plus acetyl salicylic acid is associated with an improved 1-year survival, free from death or hospitalization for cardiovascular (CV) causes, as compared to ramipril plus acetyl salicylic acid. We now report CV outcomes during a 5-year follow-up of the patients of the SMILE-4 study. Three hundred eighty-six of the 518 patients completing the study (51.2%) could be tracked after the study end and 265 could be included in the analysis. During the 5.5 (±2.1) years of follow-up, the primary endpoint occurred in 27.8% of patients originally randomized and treated with zofenopril and in 43.8% of patients treated with ramipril [odds ratio (OR) and 95% confidence interval, 0.65 (0.43–0.98), P = 0.041]. Such a result was achieved through a significantly larger reduction in CV hospitalization under zofenopril [OR: 0.61 (0.37–0.99), P = 0.047], whereas reduction in mortality rate with zofenopril did not achieve statistical significance versus ramipril [OR: 0.75 (0.36–1.59), P = 0.459]. These results were in line with those achieved during the initial 1-year follow-up. Benefits of early treatment of patients with LVD after acute myocardial infarction with zofenopril are sustained over many years as compared to ramipril.
Free androgen index as a determinant of arterial stiffness in menopause: a mediation analysis
Authors: Lambrinoudaki Irene , Georgiopoulos Georgios A. , Athanasouli Fani , Armeni Elena , Rizos Demetrios , Augoulea Areti , Chatzidou Sofia , Koutli Evangelia , Makris Nikolaos , Kanakakis Ioannis , Stamatelopoulos Kimon 
Published: February 2017

Abstract

Objective:
Associations of endogenous androgens in menopause with blood pressure (BP) and indices of arterial stiffness are reported, but directional relationships are not clear. Structural equation modeling is a contemporary statistical method, which allows assessment of such relationships and improves pathway understanding.

Methods:
We recruited 411 consecutive apparently healthy postmenopausal women who underwent noninvasive vascular evaluation. This included pulse wave analysis (aortic pressures and arterial wave reflections [augmentation index]), measurement of aortic stiffness by pulse wave velocity (PWV), stiffness index (SI), and flow-mediated dilatation. A cumulative marker combining PWV and SI (combined local and aortic arterial stiffness [CAS]) was also assessed. Free androgen index (FAI) was calculated from circulating total testosterone and sex hormone-binding globulin.

Results:
FAI was an independent determinant of systolic BP (SBP) (P = 0.032), SI (P = 0.042), and PWV (P = 0.027). Under structural equation modeling analysis, FAI was a direct predictor for PWV (beta = 0.149, P = 0.014), SI (beta = 0.154, P = 0.022), and CAS (beta = 0.193, P = 0.02), whereas SBP was a parallel mediator of androgen's vascular effects on PWV (beta = 0.280, P < 0.001) and CAS (beta = 0.248, P = 0.004), but not SI (beta = 0.024, P = 0.404). FAI-induced increase in arterial stiffness via flow-mediated dilatation was not established. FAI was not a determinant of augmentation index.

Conclusions:
In healthy postmenopausal women, FAI was directly associated with PWV, SI, and CAS. FAI also directly correlated with SBP, which in turn concurrently increased PWV and CAS. The directional correlations found herein, imply that endogenous androgens may be causally associated with indices of arterial stiffness both directly and indirectly. This hypothesis should be confirmed in further studies with causal design.
Association of follicle-stimulating hormone levels and risk of type 2 diabetes in older postmenopausal women
Authors: Bertone-Johnson Elizabeth R. , Virtanen Jyrki K , Niskanen Leo , Nurmi Tarja , Ronkainen Kimmo , Voutilainen Sari , Mursu Jaakko , Kauhanen Jussi , Tuomainen Tomi-Pekka 
Published: February 2017

Abstract

Objective:
Recent studies of perimenopausal women have observed associations of follicle-stimulating hormone (FSH) levels with markers of insulin resistance, independent of estradiol. Whether FSH is related to type 2 diabetes (T2D) in older women who have completed the menopause transition remains unknown. We assessed the association of FSH levels with diabetes and measures of insulin resistance among 588 postmenopausal Finnish women.

Methods:
Study participants were aged 53 to 73 years and not using hormone therapy at baseline (1998-2001) when FSH was measured. Prevalence of T2D was assessed at baseline, along with fasting insulin and glucose levels. Incident T2D, and insulin and glucose levels were assessed 7 to 9 years later at follow-up examination.

Results:
After adjustment for age, estradiol, body mass index, smoking, lipids levels, and other factors, women with higher FSH (>50 IU/L) had a lower prevalence of T2D (odds ratio 0.49, 95% confidence interval [CI] 0.28-0.86) than women with lower FSH. Each 1 unit increase in FSH level was associated with a significant 1.9% lower risk of T2D (95% CI 0.966-0.997, P = 0.02). Higher FSH was associated with marginally significant lower incidence of T2D at follow-up (hazard ratio 0.53, 95% CI 0.27-1.02). Baseline FSH levels were inversely correlated with fasting insulin and glucose levels at both baseline and follow-up visits (all P < 0.05). After adjustment, FSH was modestly associated with fasting insulin at baseline (P = 0.01) and at follow-up (P = 0.11).

Conclusions:
Higher postmenopausal FSH levels were associated with lower prevalent and incident T2D and fasting insulin levels. These findings warrant replication in larger prospective studies.