Medicine by Alexandros G.Sfakianakis: 07/26/16

Τρίτη 26 Ιουλίου 2016

Correction for Perry et al., Rapid behavioral maturation accelerates failure of stressed honey bee colonies [Correction]

ECOLOGY Correction for "Rapid behavioral maturation accelerates failure of stressed honey bee colonies," by Clint J. Perry, Eirik Søvik, Mary R. Myerscough, and Andrew B. Barron, which appeared in issue 11, March 17, 2015, of Proc Natl Acad Sci USA (112:3427–3432; first published February 9, 2015; 10.1073/pnas.1422089112). The authors note...

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Left cortical tuning to print in preschoolers [Psychological and Cognitive Sciences]

Reading, one of the most important cultural inventions of human society, critically depends on posterior brain areas of the left hemisphere in proficient adult readers. In children, this left hemispheric cortical specialization for letter strings is typically detected only after approximately 1 y of formal schooling and reading acquisition. Here,...

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Allosteric proteins as logarithmic sensors [Systems Biology]

Many sensory systems, from vision and hearing in animals to signal transduction in cells, respond to fold changes in signal relative to background. Responding to fold change requires that the system senses signal on a logarithmic scale, responding identically to a change in signal level from 1 to 3, or...

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ERK inhibition reverses defects in 16p dup neurons [Neuroscience]

The architecture of dendritic arbors contributes to neuronal connectivity in the brain. Conversely, abnormalities in dendrites have been reported in multiple mental disorders and are thought to contribute to pathogenesis. Rare copy number variations (CNVs) are genetic alterations that are associated with a wide range of mental disorders and are...

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Lmx1a/b regulate survival of dopamine neurons [Neuroscience]

The LIM-homeodomain transcription factors Lmx1a and Lmx1b play critical roles during the development of midbrain dopaminergic progenitors, but their functions in the adult brain remain poorly understood. We show here that sustained expression of Lmx1a and Lmx1b is required for the survival of adult midbrain dopaminergic neurons. Strikingly, inactivation of...

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Novel ncRNA, NfiS, optimizes nitrogen fixation [Microbiology]

Unlike most Pseudomonas, the root-associated bacterium Pseudomonas stutzeri A1501 fixes nitrogen after the horizontal acquisition of a nitrogen-fixing (nif) island. A genome-wide search for small noncoding RNAs (ncRNAs) in P. stutzeri A1501 identified the novel P. stutzeri-specific ncRNA NfiS in the core genome, whose synthesis was significantly induced under nitrogen...

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Mammalian ALOX15 evolution [Biochemistry]

ALOX15 (12/15-lipoxygenase) orthologs have been implicated in maturational degradation of intracellular organelles and in the biosynthesis of antiinflammatory and proresolving eicosanoids. Here we hypothesized that lower mammals (mice, rats, pigs) express 12-lipoxygenating ALOX15 orthologs. In contrast, 15-lipoxygenating isoforms are found in higher primates (orangutans, men), and these results suggest an...

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AKAP220 impacts renal water homeostasis [Cell Biology]

Filtration through the kidney eliminates toxins, manages electrolyte balance, and controls water homeostasis. Reabsorption of water from the luminal fluid of the nephron occurs through aquaporin-2 (AQP2) water pores in principal cells that line the kidney-collecting duct. This vital process is impeded by formation of an "actin barrier" that obstructs...

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R-loops, mutant RNase H1, and mtDNA disease [Biochemistry]

The genetic information in mammalian mitochondrial DNA is densely packed; there are no introns and only one sizeable noncoding, or control, region containing key cis-elements for its replication and expression. Many molecules of mitochondrial DNA bear a third strand of DNA, known as "7S DNA," which forms a displacement (D-)...

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Connectivity changes predict deficit after stroke [Neuroscience]

Deficits following stroke are classically attributed to focal damage, but recent evidence suggests a key role of distributed brain network disruption. We measured resting functional connectivity (FC), lesion topography, and behavior in multiple domains (attention, visual memory, verbal memory, language, motor, and visual) in a cohort of 132 stroke patients,...

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Protein docking by manifold Fourier transforms [Biophysics and Computational Biology]

Energy evaluation using fast Fourier transforms (FFTs) enables sampling billions of putative complex structures and hence revolutionized rigid protein–protein docking. However, in current methods, efficient acceleration is achieved only in either the translational or the rotational subspace. Developing an efficient and accurate docking method that expands FFT-based sampling to five...

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Mutational analysis of plant triterpene synthases [Plant Biology]

Triterpenes are structurally complex plant natural products with numerous medicinal applications. They are synthesized through an origami-like process that involves cyclization of the linear 30 carbon precursor 2,3-oxidosqualene into different triterpene scaffolds. Here, through a forward genetic screen in planta, we identify a conserved amino acid residue that determines product...

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Tension-based cell division in plants [Biophysics and Computational Biology]

Cell geometry has long been proposed to play a key role in the orientation of symmetric cell division planes. In particular, the recently proposed Besson–Dumais rule generalizes Errera's rule and predicts that cells divide along one of the local minima of plane area. However, this rule has been tested only...

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PI3K inhibitors induce nucleoside depletion [Medical Sciences]

We previously reported that combining a phosphoinositide 3-kinase (PI3K) inhibitor with a poly-ADP Rib polymerase (PARP)-inhibitor enhanced DNA damage and cell death in breast cancers that have genetic aberrations in BRCA1 and TP53. Here, we show that enhanced DNA damage induced by PI3K inhibitors in this mutational background is a...

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Speech-frequency hearing mechanisms [Biophysics and Computational Biology]

Low-frequency hearing is critically important for speech and music perception, but no mechanical measurements have previously been available from inner ears with intact low-frequency parts. These regions of the cochlea may function in ways different from the extensively studied high-frequency regions, where the sensory outer hair cells produce force that...

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Glycated albumin: correlation to HbA1c and preliminary reference interval evaluation

Journal Name: Clinical Chemistry and Laboratory Medicine (CCLM)
Issue: Ahead of print

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Commutable samples with assigned target concentrations may help us harmonise general chemistry results

Journal Name: Clinical Chemistry and Laboratory Medicine (CCLM)
Issue: Ahead of print

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Comparison of Insulin Resistance and β-Cell Dysfunction Between the Young and the Elderly in Normal Glucose Tolerance and Prediabetes Population: A Prospective Study

Horm Metab Res
DOI: 10.1055/s-0042-111325

Insulin resistance and β-cell function are different between the young and elderly diabetes individuals, which are not well elaborated in the nondiabetic persons. The aims of this study were to compare insulin resistance and β-cell function between young and old adults from normal glucose tolerance (NGT) to prediabetes [which was subdivided into isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), and a combination of both (IFG/IGT)], and compare the prevalence of diabetes mellitus (DM) in the above prediabetes subgroups between different age groups after 3 years. A total of 1 374 subjects aged below 40 or above 60 years old with NGT or prediabetes were finally included in this study. Insulin resistance and β-cell function from homeostasis model assessment (HOMA) and interactive, 24-variable homeostatic model of assessment (iHOMA2) were compared between different age groups. The rate of transition to diabetes between different age groups in all pre-diabetes subgroups was also compared. Compared with the old groups, young i-IFG and IFG/IGT groups exhibit higher log HOMA-IR and log HOMA2-S, whereas the young i-IGT groups experienced comparable log HOMA-IR and log HOMA2-S when compared with old i-IFG and IFG/IGT groups. Three prediabetes subgroups all had similar log HOMA-B and log HOMA2-B between different age groups. In addition, the prevalence of diabetes in young i-IFG was statistically higher than that in old i-IFG after 3 years. Age is negatively related to log HOMA2-B in both age groups. Considering an age-related deterioration of β-cell function, young i-IFG, young i-IGT, and young IFG/IGT all suffered a greater impairment in insulin secretion than the old groups. Young i-IFG and IFG/IGT have more severe insulin resistance than the old groups. In addition, young i-IFG characterized with a higher incidence of DM than the old i-IFG. These disparities highlight that the prevention to slow progression from prediabetes to type 2 diabetes should be additionally focused in young prediabetes individuals, especially young i-IFG.
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Article in Thieme eJournals:
Table of contents | Abstract | Full text

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A novel mutation in the CDH1 gene in a Spanish family with hereditary diffuse gastric cancer

Hereditary diffuse gastric cancer (HDGC) is an inherited form of diffuse type gastric cancer. Germline CDH1 mutations have been identified in approximately 15–50 % of affected kindred that meet the clinical crite...

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Effect of skin infiltration with ropivacaine on postoperative pain in patients undergoing craniotomy

Local anesthetic infiltration has been used to manage postoperative pain in various surgeries. The present study was aimed to investigate the effect of skin infiltration with 0.5 % ropivacaine on postoperative...

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Novel technique of vulvo-vaginal rejuvenation by lipofilling and injection of combined platelet-rich-plasma and hyaluronic acid: a case-report

To describe a new surgical procedure and its results: the vulvo-vaginal rejuvenation by lipofilling and an injection of combined platelet-rich-plasma (PRP) and hyaluronic acid (HA). Sexual life for women is a...

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Unaltered pneumococcal carriage prevalence due to expansion of non-vaccine types of low invasive potential 8years after vaccine introduction in Stockholm, Sweden

Publication date: Available online 26 July 2016
Source:Vaccine
Author(s): Ann Lindstrand, Ilias Galanis, Jessica Darenberg, Eva Morfeldt, Pontus Naucler, Margareta Blennow, Tobias Alfvén, Birgitta Henriques-Normark, Åke Örtqvist
ObjectiveTo evaluate the carriage prevalence, serotype distribution, and antibiotic resistance for pneumococcal carriage isolates collected 4–8years after introduction of pneumococcal conjugate vaccines (PCVs) in Stockholm, Sweden, and to identify risk factors for carriage and calculate the invasive disease potential for emerging serotypes.MethodsNasopharyngeal aspirates were collected from 3024 children aged 0–<5years at regular visits at 23 Child Health Centers in Stockholm County in 2011–2015, and from 787 parents in 2014–2015. The invasive disease potential was calculated for serotypes using invasive disease isolates from 824 patients of all ages identified in the Stockholm County during the same time period as the carriage isolates.ResultsA total carriage prevalence of 30% did not change during the study period. Non-vaccine types (NVT) dominated (94% by 2015) and the most common serotypes in descending order were 11A, 23B, 35F and 21. Risk factors for carriage were: age ⩾3months–<3years, having siblings, attending day-care and having travelled abroad the last 3months. Antibiotic resistance remained low. The invasive disease potential was high for NVT 8, 9N, 12F, and 22F, while low for a majority of emerging NVTs in carriage.ConclusionThe carriage prevalence remained the same 4–8years after vaccine introduction, but serotype replacement became almost complete. A majority of emerging NVTs in carriage showed a low invasive disease potential. Carriage studies are an important complement to invasive disease surveillance to understand the full effect of PCV vaccine programs.

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Incompatibility of lyophilized inactivated polio vaccine with liquid pentavalent whole-cell-pertussis-containing vaccine

Publication date: Available online 26 July 2016
Source:Vaccine
Author(s): Heleen Kraan, Rimko ten Have, Larissa van der Maas, Gideon Kersten, Jean-Pierre Amorij
A hexavalent vaccine containing diphtheria toxoid, tetanus toxoid, whole cell pertussis, Haemophilius influenza type B, hepatitis B and inactivated polio vaccine (IPV) may: (i) increase the efficiency of vaccination campaigns, (ii) reduce the number of injections thereby reducing needlestick injuries, and (iii) ensure better protection against pertussis as compared to vaccines containing acellular pertussis antigens. An approach to obtain a hexavalent vaccine might be reconstituting lyophilized polio vaccine (IPV-LYO) with liquid pentavalent vaccine just before intramuscular delivery. The potential limitations of this approach were investigated including thermostability of IPV as measured by D-antigen ELISA and rat potency, the compatibility of fluid and lyophilized IPV in combination with thimerosal and thimerosal containing hexavalent vaccine.The rat potency of polio type 3 in IPV-LYO was 2 to 3-fold lower than standardized on the D-antigen content, suggesting an alteration of the polio type 3 D-antigen particle by lyophilization. Type 1 and 2 had unaffected antigenicity/immunogenicity ratios. Alteration of type 3 D-antigen could be detected by showing reduced thermostability at 45°C compared to type 3 in non-lyophilized liquid controls.Reconstituting IPV-LYO in the presence of thimerosal (TM) resulted in a fast temperature dependent loss of polio type 1-3 D-antigen. The presence of 0.005% TM reduced the D-antigen content by ∼20% (polio type 2/3) and ∼60% (polio type 1) in 6h at 25°C, which are WHO open vial policy conditions. At 37°C, D-antigen was diminished even faster, suggesting that very fast, i.e., immediately after preparation, intramuscular delivery of the conceived hexavalent vaccine would not be a feasible option. Use of the TM-scavenger, l-cysteine, to bind TM (or mercury containing TM degradation products), resulted in a hexavalent vaccine mixture in which polio D-antigen was more stable.

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Immunogenicity and safety of a fully liquid aluminum phosphate adjuvanted Haemophilus influenzae type b PRP-CRM197-conjugate vaccine in healthy Japanese children: A phase III, randomized, observer-blind, multicenter, parallel-group study

Publication date: Available online 26 July 2016
Source:Vaccine
Author(s): Takehiro Togashi, Nodoka Mitsuya, Osamu Kogawara, Shuji Sumino, Yohei Takanami, Kayoko Sugizaki
BackgroundBroad use of monovalent Haemophilus influenzae type b (Hib) conjugate vaccines based on the capsular polysaccharide polyribosyl-ribitol phosphate (PRP), has significantly reduced invasive Hib disease burden in children worldwide, particularly in children aged <1year. In Japan, PRP conjugated to tetanus toxoid (PRP-T) vaccine has been widely used since the initiation of public funding programs followed by a routine vaccination designation in 2013.MethodsWe compared the immunogenicity and safety of PRP conjugated to a non-toxic diphtheria toxin mutant (PRP-CRM197) vaccine with the PRP-T vaccine when administered subcutaneously to healthy Japanese children in a phase III study. Additionally, we evaluated the immunogenicity and safety profiles of a diphtheria–tetanus acellular pertussis (DTaP) combination vaccine when concomitantly administered with either PRP-CRM197 or PRP-T vaccines. The primary endpoint was the "long-term seroprotection rate", defined as the group proportion with anti-PRP antibody titers ⩾1.0μg/mL, after the primary series.ResultsLong-term seroprotection rates were 99.3% in the PRP-CRM197 group and 95.6% in the PRP-T group. The intergroup difference (PRP-CRM197 group – PRP-T group) was 3.7% (95% confidence interval: 0.099–7.336), demonstrating that PRP-CRM197 vaccine was non-inferior to PRP-T vaccine (p<0.0001). Furthermore, the "short-term seroprotection rate" (anti-PRP antibody titer ⩾0.15μg/mL) before booster vaccination was higher in the PRP-CRM197 group than in PRP-T. Concomitant administration of PRP-CRM197 vaccine with DTaP vaccine showed no differences in terms of immunogenicity compared with concomitant vaccination with PRP-T vaccine and DTaP vaccine. Although CRM197 vaccine had higher local reactogenicity, overall, both Hib vaccines had acceptable safety and tolerability profiles.ConclusionThe immunogenicity of PRP-CRM197 vaccine administered subcutaneously as a three-dose primary series in children followed by a booster vaccination 1year after the primary series induced protective levels of Hib antibodies with no safety or tolerability concerns.Clinical trial registry: Registered on ClinicalTrials.gov: NCT01379846

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High-dose influenza vaccine favors acute plasmablast responses rather than long-term cellular responses

Publication date: Available online 26 July 2016
Source:Vaccine
Author(s): Jin Hyang Kim, H. Keipp Talbot, Margarita Mishina, Yuwei Zhu, Jufu Chen, Weiping Cao, Adrian J. Reber, Marie R. Griffin, David K. Shay, Sarah M. Spencer, Suryaprakash Sambhara
High-dose (HD) influenza vaccine shows improved relative efficacy against influenza disease compared to standard-dose (SD) vaccine in individuals ⩾65years. This has been partially credited to superior serological responses, but a comprehensive understanding of cell-mediated immunity (CMI) of HD vaccine remains lacking. In the current study, a total of 105 participants were randomly administered HD or SD vaccine and were evaluated for serological responses. Subsets of the group (n=12–26 per group) were evaluated for B and T cell responses at days 0, 7, 14 and 28 post-vaccination by flow cytometry or ELISPOT assay. HD vaccine elicited significantly higher hemagglutination inhibition (HI) titers than SD vaccine at d28, but comparable titers at d365 post-vaccination. HD vaccine also elicited higher vaccine-specific plasmablast responses at d7 post-vaccination than SD vaccine. However, long-lived memory B cell induction, cytokine-secreting T cell responses and persistence of serological memory were comparable regardless of vaccine dose. More strategies other than increased Ag amount may be needed to improve CMI in older adults.Trial Registration: ClinicalTrials.gov NCT 01189123

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Prediction of influenza B vaccine effectiveness from sequence data

Publication date: Available online 26 July 2016
Source:Vaccine
Author(s): Yidan Pan, Michael W. Deem
Influenza is a contagious respiratory illness that causes significant human morbidity and mortality, affecting 5–15% of the population in a typical epidemic season. Human influenza epidemics are caused by types A and B, with roughly 25% of human cases due to influenza B. Influenza B is a single-stranded RNA virus with a high mutation rate, and both prior immune history and vaccination put significant pressure on the virus to evolve. Due to the high rate of viral evolution, the influenza B vaccine component of the annual influenza vaccine is updated, roughly every other year in recent years. To predict when an update to the vaccine is needed, an estimate of expected vaccine effectiveness against a range of viral strains is required. We here introduce a method to measure antigenic distance between the influenza B vaccine and circulating viral strains. The measure correlates well with effectiveness of the influenza B component of the annual vaccine in humans between 1979 and 2014. We discuss how this measure of antigenic distance may be used in the context of annual influenza vaccine design and prediction of vaccine effectiveness.

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Concurrent hyperthyroidism and papillary thyroid cancer: a fortuitous and ambiguous case report from a resource-poor setting

Concurrent thyroid cancer (TC) and hyperthyroidism (HT) is rare though increasingly being reported. HT due to TC is much rarer and more challenging especially in Africa where TC and HT have significant case fa...

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Pyosalpinx causing acute appendicitis in a 32-year-old Cameroonian female: a case report

Pyosalpinx as a cause of acute appendicitis is very rare. We report the first case of a right pyosalpinx causing an extrinsic compression of the appendiceal lumen and consequently an acute appendicitis followi...

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Erratum to: 'Chinese medicine combined with calcipotriol betamethasone and calcipotriol ointment for Psoriasis vulgaris (CMCBCOP): study protocol for a randomized controlled trial'

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Patient Preferences for Oral Anticoagulation Therapy in Atrial Fibrillation: A Systematic Literature Review

Abstract

Objectives

Since the introduction of non-vitamin K antagonist (VKA) oral anticoagulants (NOACs), an additional treatment option, apart from VKAs, has become available for stroke prevention in patients with atrial fibrillation (AF). For various reasons, it is important to consider patients' preferences regarding type of medication, particularly in view of the established relationship between preferences towards treatment, associated burden of treatment, and treatment adherence. This review aimed to systematically analyse the scientific literature assessing the preferences of AF patients with regard to long-term oral anticoagulant (OAC) treatment.

Methods

We searched the MEDLINE, Scopus and EMBASE databases (from 1980 to 2015), added records from reference lists of publications found, and conducted a systematic review based on all identified publications. Outcomes of interest included any quantitative information regarding the opinions or preferences of AF patients towards OAC treatment, ideally specified according to different clinical or convenience attributes describing different OAC treatment options.

Results

Overall, 27 publications describing the results of studies conducted in 12 different countries were included in our review. Among these, 16 studies analysed patient preferences towards OACs in general. These studies predominantly assessed which benefits (mainly lower stroke risk) AF patients would require to tolerate harms (mainly higher bleeding risk) associated with an OAC. Most studies showed that patients were willing to accept higher bleeding risks if a certain threshold in stroke risk reduction could be reached. Nevertheless, most of the publications also showed that the preferences of AF patients towards OACs may differ from the perspective of clinical guidelines or the perspective of physicians. The remaining 11 studies included in our review assessed the preferences of AF patients towards specific OAC medication options, namely NOACs versus VKAs. Our review showed that AF patients prefer easy-to-administer treatments, such as treatments that are applied once daily without any food/drug interactions and without the need for bridging and frequent blood controls.

Conclusion

Stroke risk reduction and a moderate increase in the risk of bleeding are the most important attributes for an AF patient when deciding whether they are for or against OAC treatment. If different anticoagulation options have similar clinical characteristics, convenience attributes matter to patients. In this review, AF patients favour attribute levels that describe NOAC treatment.

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Dietary ecology of fossil Theropithecus: Inferences from dental microwear textures of extant geladas from ecologically diverse sites

Publication date: October 2016
Source:Journal of Human Evolution, Volume 99
Author(s): Amy E. Shapiro, Vivek V. Venkataraman, Nga Nguyen, Peter J. Fashing
As the only extant graminivorous primate, gelada monkeys (Theropithecus gelada) offer unique insights into how hominins and other extinct primates with strong C4 isotopic signatures may have subsisted on graminoid-rich diets. Fossil Theropithecus species sharing a strong C4 signal (i.e., Theropithecus brumpti, Theropithecus darti, and Theropithecus oswaldi) have been reconstructed as predominantly graminivorous and potentially in ecological competition with contemporaneous hominins. However, inferring the breadth and variation of diet in these species (and therefore hominins) has proven problematic. Understanding how ecological variation within extant geladas impacts microwear and isotopic signatures may contribute to reconstructions of diet in fossil Theropithecus. Here, we build on a recent study at an ecologically intact tall grass ecosystem (Guassa, Ethiopia) that expanded the known diversity of gelada diets by demonstrating lower reliance on graminoids, greater consumption of forbs, and greater dietary species richness than previously described at disturbed sites. We used dental microwear texture analysis to explore how dietary variation among extant geladas may inform our understanding of the diets of fossil Theropithecus. First, we compared the dental microwear textures of geladas at Guassa to those of geladas from other sites. The microwear textures of geladas at Guassa exhibited more complexity, less anisotropy, and more variance in anisotropy and heterogeneity, reflecting the greater dietary diversity of Guassa geladas. Comparing microwear texture variables among this expanded gelada sample to those for T. brumpti, T. oswaldi, and T. darti yielded no significant differences. These results raise the intriguing possibility that data on how ecological variation and diet impact dental microwear and (possibly) isotopic signatures in extant geladas can be used to reconstruct the diets of extinct theropiths and, more broadly, hominins with strong C4 isotopic signatures. We conclude that extant gelada populations offer a powerful analog for inferring dietary variation among predominantly graminivorous fossil primates.

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Conditions de réalisation et description des principales techniques utilisées au cours de l’endoscopie en urgence

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Virtual reconstruction of the Australopithecus africanus pelvis Sts 65 with implications for obstetrics and locomotion

Publication date: October 2016
Source:Journal of Human Evolution, Volume 99
Author(s): Alexander G. Claxton, Ashley S. Hammond, Julia Romano, Ekaterina Oleinik, Jeremy M. DeSilva
Characterizing australopith pelvic morphology has been difficult in part because of limited fossilized pelvic material. Here, we reassess the morphology of an under-studied adult right ilium and pubis (Sts 65) from Member 4 of Sterkfontein, South Africa, and provide a hypothetical digital reconstruction of its overall pelvic morphology. The small size of the pelvis, presence of a preauricular sulcus, and shape of the sciatic notch allow us to agree with past interpretations that Sts 65 likely belonged to a female. The morphology of the iliac pillar, while not as substantial as in Homo, is more robust than in A.L. 288-1 and Sts 14. We created a reconstruction of the pelvis by digitally articulating the Sts 65 right ilium and a mirrored copy of the left ilium with the Sts 14 sacrum in Autodesk Maya. Points along the arcuate line were used to orient the ilia to the sacrum. This reconstruction of the Sts 65 pelvis looks much like a "classic" australopith pelvis, with laterally flared ilia and an inferiorly deflected pubis. An analysis of the obstetric dimensions from our reconstruction shows similarity to other australopiths, a likely transverse or oblique entrance of the neonatal cranium into the pelvic inlet, and a cephalopelvic ratio similar to that found in humans today.

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Combined proteomics and transcriptomics identifies sting-related toxins of jellyfish Cyanea nozakii

Publication date: Available online 25 July 2016
Source:Journal of Proteomics
Author(s): Rongfeng Li, Huahua Yu, Yang Yue, Song Liu, Ronge Xing, Xiaolin Chen, Pengcheng Li
Jellyfish sting has become a worldwide issue of critical concern to human health and safety in coastal areas in recent decades. Cyanea nozakii is one of the dominant blooming species and dangerous stingers in China. However, it remains unclear how many and what types of toxins are present in the venom. So, we used a combined transcriptomics and proteomics approach to investigate the venom composition of jellyfish C. nozakii. In total 4,608,524 Illumina valid reads were obtained to de novo assemble to 40,434 unigenes in the transcriptomics analysis. And, a total of 311,635 MS/MS spectra with 12,247 unique MS/MS spectra were generated to 1556 homologous proteins in the proteomics analysis. 174 potential toxin proteins were identified, with 27 proteins homology to the toxins from venomous animals, including phospholipase A2, zinc met0061lloproteinase-disintegrin agkistin, serine protease inhibitor, plancitoxin-1, alpha-latrocrustotoxin-Lt1a, etc. This study described the transcriptomics and venom proteomics of jellyfish C. nozakii for the first time. Our findings provide a comprehensive understanding of the venom composition of C. nozakii. Furthermore, the results may also be very helpful for the discovery of novel bioactive protein, as well as the development of effective treatments for jellyfish stings in the future.Biological significanceJellyfish Cyanea nozakii is one of the most dangerous stingers in the coast of china. Hundreds of thousands of people would be stung every year and victims suffered a severe pain itch swelling inflammation wheal and even more serious consequence. However it remains unclear how many and what types of toxins are present as well as the relationship between the clinical symptoms and toxins. Our combined transcriptomics and proteomics findings can provide a comprehensive understanding of the venom composition of C. nozakii and will also be helpful for the development of effective treatments for jellyfish stings in the future.

Graphical abstract

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Proteomic analysis of soybean root exposed to varying sizes of silver nanoparticles under flooding stress

Publication date: Available online 26 July 2016
Source:Journal of Proteomics
Author(s): Ghazala Mustafa, Katsumi Sakata, Setsuko Komatsu
Silver nanoparticles (Ag-NPs) are excessively used as antibacterial agents; however, environmental interaction specifically with the plants remain uncertain. To study the size-dependent effects of Ag-NPs on soybean under flooding, a proteomic technique was used. Morphological analysis revealed that treatment with Ag-NPs of 15nm promoted soybean growth under flooding compared to 2 and 50–80nm. A total of 228 common proteins that significantly changed in abundance under flooding without and with Ag-NPs of 2, 15, and 50–80nm. Under varying sizes of Ag-NPs, number of protein synthesis related proteins decreased compared to flooding while number of amino acid synthesis related proteins were increased under Ag-NPs of 15nm. Hierarchical clustering identified the ribosomal proteins that increased under Ag-NPs of 15nm while decreased under other sizes. In silico protein-protein interaction indicated the beta ketoacyl reducatse 1 as the most interacted protein under Ag-NPs of 15nm while least interacted under other sizes. The beta ketoacyl reductase 1 was up-regulated under Ag-NPs of 15nm while its enzyme activity was decreased. These results suggest that the different sizes of Ag-NPs might affect the soybean growth under flooding by regulating the proteins related to amino acid synthesis and wax formation.Biological significanceThis study highlighted the response of soybean proteins towards varying sizes of Ag NPs under flooding stress using gel-free proteomic technique. The Ag NPs of 15nm improved the length of root including hypocotyl of soybean. The proteins related to protein metabolism, cell division/organization, and amino acid metabolism were differentially changed under the varying sizes of Ag NPs. The protein synthesis-related proteins were decreased while amino acid metabolism-related proteins were increased under varying sizes of Ag NPs. The ribosomal proteins were increased under Ag NPs of 15nm. The beta ketoacyl reductase 1 was identified as the most interacted protein under varying sizes of Ag NPs. The mRNA expression level of beta ketoacyl reductase was up-regulated under Ag NPs of 15nm while its activity was decreased. These results suggest that the Ag NPs of 15nm improved the soybean growth under flooding stress by increasing the proteins related to amino acid synthesis and waxes formation.

Graphical abstract

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Integrative proteomic analysis reveals reprograming tumor necrosis factor signaling in epithelial mesenchymal transition

Publication date: Available online 25 July 2016
Source:Journal of Proteomics
Author(s): Yingxin Zhao, Bing Tian, Rovshan G. Sadygov, Yueqing Zhang, Allan R. Brasier
The airway epithelium is a semi-impermeable barrier whose disruption by growth factor reprogramming is associated with chronic airway diseases of humans. Transforming growth factor beta (TGFβ)-induced epithelial mesenchymal transition (EMT) plays important roles in airway remodeling characteristic of idiopathic lung fibrosis, asthma and chronic obstructive pulmonary disease (COPD). Inflammation of the airways leads to airway injury and tumor necrosis factor alpha (TNFα) plays an important pro-inflammatory role. Little systematic information about the effects of EMT on TNFα signaling is available. Using an in vitro model of TGFβ-induced EMT in primary human small airway epithelial cells (hSAECs), we applied quantitative proteomics and phosphoprotein profiling to understand the molecular mechanism of EMT and the impact of EMT on innate inflammatory responses. We quantified 7925 proteins and 1348 phosphorylation sites by stable isotope labeling with iTRAQ technology. We found that cellular response to TNFα is cell state dependent and the relative TNFα response in mesenchymal state is highly compressed. Combined bioinformatics analyses of proteome and phosphoproteome indicate that the EMT state is associated with reprogramming of kinome, signaling cascade of upstream transcription regulators, phosphor-networks, and NF-κB dependent cell signaling.Biological significanceEpithelial mesenchymal transition and inflammation have important implications for clinical and physiologic manifestations of chronic airway diseases such as severe asthma, COPD, and lung fibrosis. Little systematic information on the interplay between EMT and innate inflammation is available. This study combined quantitative proteomics and phosphorproteomics approach to obtain system-level insight into the upstream transcription regulators involved in the TGFβ-induced EMT in primary human small airway epithelial cells and to elucidate how EMT impacts on the TNFα signaling pathways. The proteomics and phosphoproteomics analysis indicates that many signaling pathways involved in TGFβ-induced EMT and EMT has profound reprogramming effects on innate inflammation response.

Graphical abstract

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Hepatitis B virus X protein impairs α-interferon signaling via up-regulation of suppressor of cytokine signaling 3 and protein phosphatase 2A

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ABSTRACT

Hepatitis B Virus (HBV) causes liver cirrhosis and hepatocellular carcinoma. Standard therapy includes treatment with interferon (IFN); however, its efficacy is limited. HBV has been reported to impair IFN signaling; however, the mechanism is unclear. Here, the relationship between HBV X protein (HBx) and IFN signaling was investigated by establishing HepG2 cells, stably expressing HBx (HepG2/HBx) via retrovirus-mediated gene transfer. Subsequently, IFN negative-regulator expression and its mechanism were studied. HepG2/HBx cells showed reduced expression of IFN-stimulated genes and expressed higher levels of suppressor of cytokine signaling 3 (SOCS3) and protein phosphatase 2A (PP2A) suppressor compared with control cells. Knockdown of SOCS3 and PP2A restored IFN sensitivity. Moreover, HepG2/HBx cells showed higher phosphorylation levels of signal transducers and activators of transcription 3 and endoplasmic reticulum stress, which are inducers of SOCS3 and PP2A, respectively. Additionally, HBx-knockdown restored IFN sensitivity in HepG2.2.15.7 cells. It was also confirmed that SOCS3 and PP2A expression levels were up-regulated in the liver of patients with HBV infection. The results of this study demonstrated that HBx impairs IFN signaling via increased expression of SOCS3 and PP2A, a novel mechanistic insight, providing a potential therapeutic target to enhance the efficiency of IFN therapy. This article is protected by copyright. All rights reserved

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