bluuebunny/crossref_metadata_2025 huggingface dataset:
Defective FoxP3+ Treg cell differentiation in the gut of Type 1 Diabetic patients
Authors: Badami Ester , Sorini Chiara , Coccia Margherita , Molteni Laura , Bolla Andrea Mario , Scavini Marina , Mariani Alberto , Bosi Emanuele , Falcone Marika
Published: July 2019

Environmental factors that act at the intestinal level such as diet, drugs, and microflora have a high impact on the pathogenesis of autoimmune Type 1 Diabetes (T1D), but it is still unclear how the gut milieu affects autoimmunity outside the intestine. Here we show that peripheral FoxP3+ Treg cell differentiation, a mechanism that takes place in the gut and is crucial to maintain systemic immune tolerance, is impaired in T1D patients. These results provide the first evidence that gut mucosa alteration could predispose to autoimmune T1D by affecting systemic immune regulation.
Resveratrol Increases Intracellular NAD+ Levels Through Up regulation of The NAD+ Synthetic Enzyme Nicotinamide Mononucleotide Adenylyltransferase
Authors: Grant Ross
Published: July 2019

Resveratrol is a polyphenol with major health benefits that is thought to operate through direct activation of the 'anti-aging' enzyme SIRT1. However recent reports have challenged this 'direct-activation' hypothesis, suggesting the mechanism by which resveratrol increases SIRT1 function is still unknown. We report for the first time that resveratrol induces a dose dependent increase in activity of the NAD+ synthetic enzyme nicotinamide mononucleotide adenylyl transferase (NMNAT1). Activation of NMNAT1 by resveratrol in cultured primary human astrocytes and neurons increased NAD+ levels by up to 5 fold. As SIRT1 requires NAD+ as a substrate to perform its gene silencing function, higher NAD+ levels will enhance SIRT1 activity. This finding suggests that resveratrol may promote SIRT1 function by enhancing NAD+ synthesis in whole cell systems without requiring direct activation.
Ediacaran Macro Body Fossils
Authors: Huang Timothy , Shaw Jei-Fu , Zheng Liang , Huang Chun-Lan , Chang YiLung , Yang ChuanWei
Published: July 2019

This paper, Ediacaran Macro Body Fossils, reports a new discovery of well preserved three dimensional macro body fossils of the Ediacaran Period in central YunNan province in the People's Republic of China. These body fossils will enable more detailed and in-depth exploration of the evolution of multi-cellular macro organisms on this planet, whereas in the past, researches could only rely on cast or imprint fossils.
Effect of p21Waf1 and p27Kip1 on centrosome replication and proliferation of breast cancer cell
Authors: Li Fu-Nian , Jiang Dan-Dan , Liu Xiang-Ping , Ge Yin-Lin , Cao Ming-Zhi , Wang Xin-Gang
Published: July 2019

Aberrant centrosome numbers are detected in virtually all cancersincreasing the risk for cell division errors and chromosomal instability. Deregulation of the centrosome duplication cycle is considered as the major contributing factor for abnormal amplification of centrosomes. p21Waf1 and p27Kip1, general CDK inhibitors by inhibiting cyclin-dependent kinase 2 (CDK2)/cyclin E and cyclin A complexes, controlled the initiation and progress of centrosome duplication . We transfected p21 Waf1, p27 Kip1 or p21 Waf1- p27 Kip1 genes into MCF-7 cells by lipofection to explore the effect of the genes on centrosome duplication and proliferation of breast cancer cell. The result shows that the cell growth was obviously inhibited after being transfected, resulting in an accumulation of cells in G1 and the proportion of cells which contained abnormal centrosomes was obviously decreased. Comparing with p21 Waf1or p27 Kip1, the effects of p21Waf1- p27 Kip1 genes are more significative. These results suggest that p21Waf1 and p27Kip1 genes could inhibit the growth of human breast cancer cells and reverse abnormal duplication of centrosomes. p21Waf1 and p27Kip1 cooperate to regulate centrosome duplication and cell cycle progress, indicating p21 Waf1- p27 Kip1 combined gene might be potential therapeutic agents of breast cancer which reveals suppressed p21Waf1 and p27Kip1 expression.
Cellular delivery of antibodies: effective targeted subcellular imaging and new therapeutic tool
Authors: Massignani Marzia , Canton Irene , Patikarnmonthon Nisa , Warren Nicholas , Armes Steven , Lewis Andrew , Battaglia Giuseppe
Published: July 2019

It is already more than a century since the pioneering work of the Nobel Laureate Ehrlich gave birth to the side chain theory1, which helped to define antibodies and their ability to target specific biological sites. However, the use of antibodies is still restricted to the extracellular space due to the lack of a suitable delivery vehicle for the efficient transport of antibodies into live cells without inducing toxicity. In this work, we report the efficient encapsulation and delivery of antibodies into live cells with no significant loss of cell viability or any deleterious affect on the cell metabolic activity. This delivery system is based on poly(2-(methacryloyloxy)ethyl phosphorylcholine)-block-(2-(diisopropylamino)ethyl methacrylate), (PMPC-PDPA), a pH sensitive diblock copolymer that self-assembles to form nanometer-sized vesicles, also known as polymersomes, at physiological pH. These polymersomes can successfully deliver relatively high antibody payloads within live cells. Once inside the cells, we demonstrate that these antibodies can target their epitope by immune-labelling of cytoskeleton, Golgi, and transcription factor proteins in live cells. We also demonstrate that this effective antibody delivery mechanism can be used to control specific subcellular events, as well as modulate cell activity and pro-inflammatory process.
Thermal signatures of human pheromones in sexual and reproductive behaviour
Authors: Mazzatenta Andrea , Romani Gian Luca , Tommasi Luca , Merla Arcangelo
Published: July 2019

Chemically mediated sexual communication in humans has been largely neglected due to its non-conscious and relatively concealed nature. However, menstrual cycle synchronisation, puberty onset in young pre-pubertal girls exposed to their stepfather, and consanguinity avoidance suggest a function in the physiological regulation of sexual and reproductive behaviour in humans. These phenomena are related to activation of the limbic system by pheromones. On the basis of sexually dimorphic activation of brain hypothalamic areas and the control of body temperature via the hypothalamus, our hypothesis is that human sexual pheromones can induce thermal effects that can be revealed by high-resolution thermal infrared imaging. Here we show that in women, male sexual pheromones induce thermal effects that are linked to the ovarian cycle. These findings suggest a dramatic influence of pheromones on human sexual and reproductive behaviour through neuroendocrine brain control, established on the plesiomorphic nature of chemical communication across species.
Laboratory and field evaluation for the resistance of commonly used woods against Coptotermes heimi (Wasmann).
Authors: Manzoor Farkhanda , Sheikh Nadeem , Zawar Asma
Published: July 2019

The current study was conducted to evaluate the resistance of four wood species (Azadirachta indica, Pinus roxberghii, Dalbergia sissoo and Populus deltoides) against subterranean termite species Coptotermes heimi by choice and no choice field and laboratory trials. Of these four wood species P. roxberghii and D. sissoo proved to be most resistant to termite attack. Taken together these results we can conclude that D. sissoo is the least preferred and P. deltoides is the most preferred wood by the C. heimi. The data obtained from the field choice and no-choice the woods are arranged in order of preference DS>PR>AI>PD whereas in laboratory choice and no-choice trials the order of preference was PD>AI>PR>DS.
Extending the Modern Synthesis: The evolution of ecosystems
Authors: Wallace Rodrick
Published: July 2019

The Modern Evolutionary Synthesis formalizes the role of variation, heredity, differential reproduction and mutation in population genetics. Here we explore a mathematical structure, based on the asymptotic limit theorems of information theory, that instantiates the punctuated dynamic relations of organisms and their embedding environments. The mathematical overhead is considerable, and we conclude that the model must itself be extended even further to allow the possibility of the transfer of heritage information between different classes of organisms. In essence, we provide something of a formal roadmap for the modernization of the Modern Synthesis.
Extending the Modern Synthesis: The evolution of ecosystems
Authors: Wallace Rodrick
Published: July 2019

The Modern Evolutionary Synthesis formalizes the role of variation, heredity, differential reproduction, and mutation in population genetics. Here we explore a mathematical structure, based on the asymptotic limit theorems of communication theory, that instantiates the punctuated dynamic relations of organisms with their embedding environments, including the possibility of the transfer of heritage information between different classes of organisms. In essence, we provide something of a formal roadmap for the modernization of the Modern Synthesis, making application to both relatively rapid evolutionary punctuated equilibrium and to the conservation of ecological interactions across deep evolutionary time.
Global Network Alignment
Authors: Kuchaiev Oleksii , Przulj Natasa
Published: July 2019

Motivation: High-throughput methods for detecting molecular interactions have lead to a plethora of biological network data with much more yet to come, stimulating the development of techniques for biological network alignment. Analogous to sequence alignment, efficient and reliable network alignment methods will improve our understanding of biological systems. Network alignment is computationally hard. Hence, devising efficient network alignment heuristics is currently one of the foremost challenges in computational biology. Results: We present a superior heuristic network alignment algorithm, called Matching-based GRAph ALigner (M-GRAAL), which can process and integrate any number and type of similarity measures between network nodes (e.g., proteins), including, but not limited to, any topological network similarity measure, sequence similarity, functional similarity, and structural similarity. This is efficient in resolving ties in similarity measures and in finding a combination of similarity measures yielding the largest biologically sound alignments. When used to align protein-protein interaction (PPI) networks of various species, M-GRAAL exposes the largest known functional and contiguous regions of network similarity. Hence, we use M-GRAAL’s alignments to predict functions of un-annotated proteins in yeast, human, and bacteria C. jejuni and E. coli. Furthermore, using M-GRAAL to compare PPI networks of different herpes viruses, we reconstruct their phylogenetic relationship and our phylogenetic tree is the same as sequenced-based one.
Generalised and abdominal adiposity are important risk factors for chronic disease in older people: results from a nationally representative survey
Authors: Hirani Vasant
Published: July 2019

Objective:

To look at the trends in prevalence of generalised (body mass index (BMI)&8805; 25 kg/m2) and abdominal obesity (waist circumference (WC) >102cm, men; >88cm, women) among older people from 1993 to 2008, prevalence of chronic disease by overweight/obesity and waist circumference categories in England 2005 and evaluate the association of these measures with chronic diseases. Methods: Analyses of nationally representative cross-sectional population surveys, the Health Survey for England (HSE), including non-institutionalised men and women aged &8805;65years.

Results:

Generalised obesity and abdominal obesity increased among men and women from 1993 to 2008. In 2005, the HSE 2005 focussed on older people. 72% of men and 68% of women aged over 65 were either overweight or obese. Prevalence of raised WC was higher in women (58%) than in men (46%). Multivariate analysis confirmed that generalised and abdominal obesity were independently associated with risk of hypertension, diabetes and arthritis in both men and women. In women only, there was an association between generalised obesity and having a fall in the last year (OR: 1.5), and between abdominal obesity and having a joint replacement (OR: 1.9, p=0.01) Conclusion: Complications of obesity such as diabetes, hypertension and arthritis, are more common in men and women aged over 65 who are overweight or obese, as well as in those with a raised waist circumference. These conditions impact on morbidity, mortality and have cost implications for the health service and are known to improve with weight loss even in old age. Treatment strategies to address these conditions such as weight management and prevention of overweight and obesity are important even in older people. There is a need to ensure that older people are given appropriate advice about keeping physically active and eating sensibly.
Aqueous phase hydration and hydrate acidity of perfluoroalkyl and n:2 fluorotelomer aldehydes
Authors: Rayne Sierra , Forest Kaya
Published: July 2019

Perfluoroalkyl aldehydes (PFAlds) and n:2 fluorotelomer aldehydes (FTAlds) are degradation products of precursor compounds that include fluorotelomer alcohols, iodides, acrylates, phosphate esters, and other derivatives, as well as hydrofluorocarbons and hydrochlorofluorocarbons. The SPARC software program and comparative density functional theory (DFT) calculations were used to investigate the aqueous phase hydration equilibrium constants (K~hyd~) of PFAlds and FTAlds. DFT studies suggest that all PFAlds will be dominantly present as the hydrated form in aqueous solution. While SPARC correctly estimates the K~hyd~ for the C~1~ PFAld, it appears to incorrectly predict a large decline in K~hyd~ (particularly between C~1~ and C~2~) with increasing perfluoroalkyl chain length for this class of compounds. Both SPARC and DFT investigations suggest that FTAlds will not likely be substantially hydrated in aquatic systems or in vivo. Using corrected SPARC estimates, PFAld hydrates are expected to have pK~a~ values in the range of phenols (ca. 9 to 10), whereas n:2 FTAld hydrates are expected to have pK~a~ values ca. 2 to 3 units higher (ca. 12 to 13). Where relevant, the molecular and/or dissociated hydrate forms of PFAlds and FTAlds need to be explicitly considered in environmental, toxicological, and waste treatment investigations.
Calming down the seas: the near collapse of an Atlantic coastal fishery
Authors: Pita Pablo , Freire Juan
Published: July 2019

For years now the estimates of the consequences of overfishing for marine ecosystems have differed greatly within the scientific community^1^. The use of commercial catch statistics to estimate tendencies has been much criticised^2^, but alternative information sources with long time series are rare. Here we employ the historic archive (1953-2007) of the recreational spearfishery in Galicia (NW Spain), which does not have the problems common to other fishery registers, to estimate long-term changes in coastal ecosystems. Using generalized additive regression models (GAM) we estimated decreases of around 83% in the abundances of coastal fish over the last 50 years. In the same period the average body size decreased by 36%. In addition, the relative catch frequency has decreased for the most valuable commercial species. Commercial overfishing has brought these ecosystems so close to the brink of collapse that it is necessary to implement measures that ensure their recovery.
Extensive Viral mimicry of human proteins in AIDS, autoimmune disorders, late-onset and familial Alzheimer's disease and other genetic diseases
Authors: Carter Christopher
Published: July 2019

Peptide stretches within HIV-1 proteins display homology to over 50 components from all compartments of the human immune defence network. The homologous peptides are in most cases immunogenic, suggesting that antibodies to HIV-1 proteins could mount an autoimmune attack against multiple components of the immune system itself. HIV-1 proteins are also homologous to autoantigens in Alzheimer's disease, chronic obstructive pulmonary disorder, multiple sclerosis, Myasthenia Gravis, Pemphigus Vulgaris, Sjogrens syndrome and systemic Lupus Erythematosus, all of which have been associated with HIV-1 infection. This mimicry suggests that HIV-1/AIDS has a major autoimmune component and that HIV-1 antibodies could selectively target the immune system and autoantigens in other autoimmune disorders. This could radically change our conception of how HIV-1 acts, and perhaps lead to novel therapeutic strategies, which, counter intuitively might even involve the use of immunosuppressants in the early stages of the disease. Autoantigens from the human autoimmune diseases mentioned above also align with peptides from other viruses implicated as risk factors in each disease. Mutant peptides from Huntington's disease and other polyglutamine disorders, and from cystic fibrosis also align with common viruses. The London APP717 V&x2192;I mutant in Familial Alzheimer's disease converts the surrounding peptide to matches with Rhinoviruses causing the common cold and to the Norovirus responsible for vomiting sickness. Viral mimicry related autoimmunity may thus play a role in many autoimmune and even human genetic disorders. It is possible that this is a near universal phenomenon, reflecting the idea that viruses are responsible for the origin of higher forms of life, leaving behind a deadly legacy of viral-derived human proteins with homology to antigenic proteins in the current virome that may be responsible for most of our ills.
Characteristics of Staphylococcus aureus infections to consider in designing an effective vaccine.
Authors: Romero-Pastrana Francisco , Hernández-Jáuregui Pablo , Baca Beatriz
Published: July 2019

Staphylococcus aureus is a very versatile and adaptable microorganism. It can potentially infect virtually any host tissue. Given the appropriate conditions it can become a life-threatening pathogen, or a commensal colonizer of the nose. Extensive antibiotic use for infection control facilitated the rise of antibiotic resistance, stressing the need for alternate forms of control. Vaccine efforts in other pathogens have proved successful, but so far S. aureus candidate vaccines have not been as effective. Here we review S. aureus factors involved in pathogenesis that could help develop a successful vaccine, like host nasal colonization and immune evasion factors. An effective multicomponent vaccine could incorporate antigenic fragments from several S. aureus proteins, preferably involved in colonization, immune evasion and/or toxicity.
The Shape and Dimensionality of Phylogenetic Tree-Space Based on Mitochondrial Genomes
Authors: Wilgenbusch James , Huang Wen , Gallivan Kyle
Published: July 2019

Phylogenetic analyses of large and diverse data sets generally result in large sets of competing phylogenetic trees. Consensus tree methods used to summarize sets of competing trees discard important information regarding the similarity and distribution of competing trees. A more fine grain approach is to use a dimensionality reduction method to project tree-to-tree distances in 2D or 3D space. In this study, we systematically evaluate the performance of several nonlinear dimensionality reduction (NLDR) methods on tree-to-tree distances obtained from independent nonparametric bootstrap analyses of genes from three mid- to large-sized mitochondrial genome alignments.
Isotope fractionation during impacts
Authors: Huang Hua
Published: July 2019

Evaporation-condensation, a significant process, happens during impact events. Of special interest, this process can lead to significant isotope fractionations e.g. C, O, Mg, Si, S, Fe,and Cr.The nature of mass-independent fractionation of sulphur of the sulfur isotopes is that the fractionation of isotope is still mass dependent during impacts, which means the measured nonzero ⊿33S values of Archean sulfide- and sulfate-bearing minerals indicate that their different condensation sequences.
Free Will or Not: Causality Preserved but Access to Motor Decisions Obscured
Authors: Gorea Andrei , Grzeczkowski Lukasz , Rider Delphine
Published: July 2019

Empirical studies having addressed the free-will issue suffer from controversial methodologies and interpretations. We present a new paradigm involving a synchronization task where the time interval to synchronize with is randomly within and without subject's synchronization capabilities and ask subjects to retrospectively evaluate (Q1) which of the two occurred or (Q2) whether their motor response had had been reactive/speeded or delayed. Contrary to the non-FW view, Q1-judgments correlate with the actual duration of the synchronization interval rather than with subjects's motor response latencies. Instead of postidictively reshuffling their judgment to make it match the outcome of their actions, subjects preserve the causal chain of events having entailed them. When answering Q2 subjects' judgments also correlate with the synchronization interval, proof that they cannot decide on the intentionality of their actions. Hence the present results reveal the intrinsic duality of the free-will concept.
Critical Concentration Gradient Model of Bacterial Cell Division
Authors: Rashid Aijaz , Sing Perminder
Published: July 2019

Critical concentration gradient model is helpful in understanding the mechanism of Z-ring formation. The distribution of positive and negative regulators of Z-ring formation in cell is not random but well programmed. The positive and negative regulators in cell lead to a critical concentration gradient from mid cell to the poles. The critical concentration of FtsZ required for Z-ring assembly at the centre of cell is less than that at the poles. So FtsZ starts polymerizing at cell centre and afterwards by cooperative association of more and more monomers leads to the Z-ring formation. Simultaneously during Z-ring formation the recruitment of other accessory proteins takes place, leading to the formation of a stable divisome complex.
Familial and late-onset Alzheimer's disease: Autoimmune disorders triggered by viral, microbial and allergen mimics of beta-amyloid and APP mutants ?
Authors: Carter Christopher
Published: July 2019

Beta-amyloid (A[beta]) autoantibodies are common in Alzheimer's disease. Some may be derived from Herpes simplex and 68 other virus proteins matching an immunogenic and fibrillogenic VGGVV A[beta] sequence.Many other viral, microbial and allergenic proteins (particularly from dust mites) align with A[beta] as do proteins from C.Neoformans which has been associated with a rare but curable form of the disorder. Immune-related proteins are present in amyloid plaques and the complement membrane attack complex in neurones in Alzheimer's disease brains. Alzheimer's disease may thus be an autoimmune disorder triggered by pathogenic antigens homologous to A[beta], whose antibodies target and kill A[beta] containing neurones, via immune activation and complement-related lysis. This scenario explains many epidemiological observations in Alzheimer's disease, which is more common in women and Afro-Americans, as is HSV-2 seroprevalence; related to the number of pregnancies (exposure to childhood infections) and less severe in nuns (low exposure to sexually transmitted diseases). Atopy and autoimmune disorders are common in Alzheimer's disease in accord with allergen homology to A[beta], and anti-inflammatory agents reduce Alzheimer's disease risk. Cancer-causing, and plant viruses from Mediterranean diet components align with the A[beta] sequence targeted by catalytic autoantibodies, perhaps explaining the inverse association of diet and cancer with Alzheimer's disease. As a papillomavirus vaccine already exists, it may have a role to play in Alzheimer's disease. This scenario is also relevant to familial Alzheimer's disease. Mutant forms of APP~717~ and the Swedish mutant convert the surrounding peptide to matches with commensal bacteria (E.Coli, E. Faecalis, P.Gingivalis) and to viruses with very high seroprevalence (HHV-6, norovirus, influenza and the common cold). Late-onset and Familial Alzheimer's disease may both be autoimmune disorders caused by diverse common pathogens and allergens homologous to A[beta] or mutant APP fragments. Immunosuppressants, vaccination and pathogen elimination may be of benefit in both conditions.
The stroboscopic human vision
Authors: Bouman Maarten
Published: July 2019

When the frequency of seeing light from a pair of point flashes is beyond the probability summation of the separate flashes, the surplus is due to the successful interaction of subliminal responses from the different flashes. Experiments with various distances and various periods of the pair show thet successful interaction occurs when in each of two successive time-quanta of 0.04 seconds and in each of two adjacent distinct receptor groups at least one subliminal receptor response occurs. An autonomous source produces the time-quanta. It serves the time-processing of the central nervous system and of the motor system. Posdsibly, action potentials from the purkinje cells of the myocardium play a role. Hyper acuity in direction and in depth, flicker fusion, perceptual rivalry and ather phenomena follow from the quantized spatiotemporal signal processing.
Two 'protein folding codes' can be inferred from empirical classifications using Tlusty's topological approach
Authors: Wallace Rodrick
Published: July 2019

Tlusty's topological arguments regarding the genetic code are applied to the classification of tertiary irregular protein symmetries. Unlike the genetic case, two protein folding codes are found, a 'normal' globular and a 'pathological' amyloid version. The underlying normal 'protein folding code error network' is found to have one major, highly dominant, 'spherical' component, a minor attachment handle in the Morse Theory sense, and as many as three additional subminor handles. The basic amyloid folding code error network appears to be more complicated, of genus two, giving the eightfold symmetry of the steric zipper. Like many before us, we conjecture that the elaborate cellular regulatory machinery associated with the endoplasmic reticulum and heat shock proteins is needed to prevent transition between these two thermodynamically 'natural' sets of protein conformations, and that its corrosion by aging accounts for the subsequent onset of many protein folding disorders. These results suggest markedly different evolutionary trajectories for the genetic and protein folding codes.
Many in vivo 'protein folding codes' can be inferred from empirical classifications using Tlusty's topological approach
Authors: Wallace Rodrick
Published: July 2019

Tlusty's topological rate distortion approach to the genetic code is applied to the problem of protein symmetries and to the analysis of protein folding rates. Unlike the genetic case, numerous 'protein folding codes' can be identified from empirical classifications. Protein folding rates follow from a topologically-driven rate distortion argument. These results imply markedly different evolutionary trajectories for the genetic and protein folding codes, and suggest that the 'protein folding code' is, in fact, a complicated composite, distributed across protein production and a cellular, or higher, regulatory apparatus acting as a canalizing catalyst that drives the system to converge on particular transitive components within a significantly larger 'protein folding groupoid'.
Prebiotic Organic Globules
Authors: Bassez Marie-Paule , Takano Yoshinori
Published: July 2019

Analogs of organic globules observed in carbonaceous chondrite meteorites and in interplanetary dust particles and of rod to spherical structures observed in terrestrial archean microstructures have been synthesized in our experiments conducted with proton irradiation on a mixture of simple inorganic constituants, CO, N2 and H2O. Our analyses of these laboratory organic globules show that the proton irradiation residue contains proteinous and non-proteinous amino acid precursors. On the basis of morphology, of hydrothermal and mineral environment, we suggest that the meteoritic organic globules and the archean carbon microstructures could be composed of amino acid precursors.
TLR-9 Expression in Human Bronchial Epithelial Cells induced with Lipopolysaccharide
Authors: Dharmalingam Sangeetha , Saravanabhavan Shanmuga
Published: July 2019

The study conducted here was to investigate the gene and protein expression of Toll like receptor 9 when human bronchial epithelial cells were induced by lipopolysaccharide. TLRs are pattern recognition receptor (PRR) which plays a key role in innate immunity. They recognise the molecules that are shared by pathogens but distinguishes from the host which is referred to as pathogen associated molecular patterns (PAMPs). The HBECs were first cultured and once it becomes confluent they were induced with 10ng/ml of LPS. In order to find out whether the gene was expressed in the cells, the RNA was isolated and RT-PCR was carried out. Before carrying out the RT-PCR, RNA gel electrophoresis was carried out to show the 28S and 18S bands. Once the gene expression was analysed protein expression was carried out by extracting the protein using RIPA buffer and running the SDS-PAGE followed by staining. Silver staining and western blotting results revealed clear bands at 116kDa illustrating that the TLR9 protein had been expressed. RT-PCR results showed that a smear of bands for TLR9 and the in protein expression bands were seen in TLR9 protein region which indicates that TLR9 was expressed in the HBEC by LPS.
Obesity care pathway
Authors: Hobson Phillipa , Mangoud Abdallah
Published: July 2019

This paper recognises that obesity is a growing problem within the UK with Britain with one of the highest rates for overweight children in Europe and with one in three adults predicted to be obese by 2012. Within the UK, nearly 25 per cent of men and women are now obese which has created enormous implications for health service providers (NICE, 2006). This paper focuses specifically on North East Lincolnshire where life expectancy is less than the national average with males (76) and females (80.8). Within North East Lincolnshire we developed an evidence-based adult obesity care pathway based on the NICE obesity guidance, incorporating local referral criteria and input. The pathway is benefiting patients by helping to reduce obesity through an increase in lifestyle referrals. Since the pathway was developed we have seen a reduction in referrals for unnecessary bariatic surgery which is reducing the cost to the NHS. This paper shares our learning and best practice from stakeholder engagement, partnership working, successfully implementing and evaluating the adult obesity care pathway across all general practices.
A dynamical model of genetic networks describes cell differentiation
Authors: Serra Roberto , Marco Villani , Barbieri Alessia
Published: July 2019

Cell differentiation is a complex phenomenon whereby a stem cell becomes progressively more specialized and eventually gives rise to a specific cell type. Differentiation can be either stochastic or, when appropriate signals are present, it can be driven to take a specific route. Induced pluripotency has also been recently obtained by overexpressing some genes in a differentiated cell. Here we show that a stochastic dynamical model of genetic networks can satisfactorily describe all these important features of differentiation, and others. The model is based on the emergent properties of generic genetic networks, it does not refer to specific control circuits and it can therefore hold for a wide class of lineages. The model points to a peculiar role of cellular noise in differentiation, which has never been hypothesized so far, and leads to non trivial predictions which could be subject to experimental testing.
Rapid antigen detection using the liquid sample as a lens and self-mixer for light scattering detection
Authors: Garcia Antonio , Schneider John
Published: July 2019

Superhydrophobic surfaces, both natural and artificial, cause aqueous drops to bead on them. The most water-repellent surfaces produce nearly perfect spheres with very little contact between water, solutes, and surface due to the roughness of the surface ^1^. However, a related phenomenon that has not been well appreciated until recently, is that colloidal particles in the aqueous drop remain highly mobile, and smaller-sized colloids migrate to the drop surface due to both the driving force of evaporation and the expanded liquid/air interface ^2-3^. A newly identified, third useful optical property resulting from the suspension of an aqueous drop by the superhydrophobic surface is that a spheroidal lens is created. Without any additional energy or instrumentation, the simple placement of an aqueous sample on a superhydrophobic surface followed by the placement of a reagent drop results in very rapid mixing and a means to detect and monitor antigens via agglutination.
The interplay of descriptor-based computational analysis with pharmacophore modeling builds the basis for a novel classification scheme for feruloyl esterases
Authors: Udatha D.B.R.K. Gupta , Kouskoumvekaki Irene , Olsson Lisbeth , Panagiotou Gianni
Published: July 2019

One of the most intriguing groups of enzymes, the feruloyl esterases (FAEs), is ubiquitous in both simple and complex organisms. FAEs have gained importance in biofuel, medicine and food industries due to their capability of acting on a large range of substrates for cleaving ester bonds and synthesizing high-added value molecules through esterification and transesterification reactions. During the past two decades extensive studies have been carried out on the production and partial characterization of FAEs from fungi, while much less is known about FAEs of bacterial or plant origin. Initial classification studies on FAEs were restricted on sequence similarity and substrate specificity on just four model substrates and considered only a handful of FAEs belonging to the fungal kingdom. This study centers on the descriptor-based classification and structural analysis of experimentally verified and putative FAEs; nevertheless, the framework presented here is applicable to every poorly characterized enzyme family. 365 FAE-related sequences of fungal, bacterial and plantae origin were collected and they were clustered using Self Organizing Maps followed by k-means clustering into distinct groups based on amino acid composition and physico-chemical composition descriptors derived from the respective amino acid sequence. A Support Vector Machine model was subsequently constructed for the classification of new FAEs into the pre-assigned clusters. The model successfully recognized 98.2% of the training sequences and all the sequences of the blind test. The underlying functionality of the 12 proposed FAE families was validated against a combination of prediction tools and published experimental data. Another important aspect of the present work involves the development of pharmacophore models for the new FAE families, for which sufficient information on known substrates existed. Knowing the pharmacophoric features of a small molecule that are essential for binding to the members of a certain family opens a window of opportunities for tailored applications of FAEs.
A Micropropagation, Molecular and Physiochemical Analysis of Canola Brassica napus L. From Seeds
Authors: Khan Israr , Shuaib Muhammad , Khan Sikandar , Zia Muhammad Amir , Akbar Haji
Published: July 2019

Canola is important for its oil, anticarcinogenic phytochemicals and low saturated fat content and has wide scope for further improvement through genetic transformations. Micropropagation is the practice of rapidly multiplying stock plant material to produce a large number of disease free progeny plants, using modern asceptic plant tissue culture methods and also to conserve germ plasm. A combination of auxin and cytikinin and a shock on growth regulator free medium is used for micropropagation. Molecular and physiochemical analysis done to know variation in seeds protein content and electric conductivity.
Transcriptional coupling of neighbouring genes and gene expression noise: evidence that gene orientation and non-coding transcripts are modulators of noise
Authors: Wang Guang-Zhong , Lercher Martin , Hurst Laurence
Published: July 2019

For some genes, notably essential genes, expression when expression is needed is vital hence low noise in expression is favourable. For others noise is necessary for coping with stochasticity or for providing dice-like mechanisms to control cell fate. But how is noise in gene expression modulated? We hypothesise that gene orientation may be crucial, as for divergently organized gene pairs expression of one gene could affect chromatin of a neighbour thereby reducing noise. Transcription of antisense non-coding RNA from a shared promoter is similarly argued to be a noise-reduction mechanism. Stochastic simulation models confirm the expectation. The model correctly predicts: that protein coding genes with bi-promoter architecture, including those with a ncRNA partner, have lower noise than other genes; divergent gene pairs uniquely have correlated expression noise; distance between promoters predicts noise; ncRNA divergent transcripts are associated with genes that a priori would be under selection for low noise; essential genes reside in divergent orientation more than expected; bi-promoter pairs are rare subtelomerically, cluster together and are enriched in essential gene clusters. We conclude that gene orientation and transcription of ncRNAs, even if unstable, are candidate modulators of noise levels.
Immunogens and Antigen Processing: Report from a Global HIV Vaccine Enterprise Working Group
Authors: Mascola John , King Richter , Steinman Ralph , Working Group convened by the Globa the
Published: July 2019

The Global HIV Vaccine Enterprise convened a meeting of a Working Group in July 2009 to discuss recent progress in rational design of the components of an HIV vaccine, such as inserts, vectors and adjuvants,and in understanding antigen processing and presentation to T and B cells. This Report summarizes the key points of that discussion, and subsequent discussions with the Chairs of the other Enterprise Working Groups, the Enterprise Science Committee, the Enterprise Council and the broader scientific community during open sessions at scientific conferences.
Novel approaches, including systems biology, to HIV vaccine research and development: Report from a Global HIV Vaccine Enterprise Working Group
Authors: Pulendran Bali , Rappuoli Rino , Aderem Alan , Working Group convened by the Globa the
Published: July 2019

The Global HIV Vaccine Enterprise convened a two-day workshop on August 10-11 2009, at the Fred Hutchison Cancer Research Center offices in Seattle, WA, to discuss the application of novel approaches,including systems biology, to HIV vaccine research and development. The goals of this Working Group were to identify key scientific issues and opportunities that have emerged since the Enterprise Scientific Strategic Plan1 was published in 2005, and to make recommendations to Enterprise stakeholders.
Bridging the Gaps between Fundamental, Preclinical and Clinical Research: Report from a Global HIV Vaccine Enterprise Working Group
Authors: Corey Lawrence , Autran Brigitte , Picker Louis , Working Group convened by the Globa the
Published: July 2019

The Global HIV Vaccine Enterprise (the Enterprise) convened a two-day workshop on 17-18 September 2009, at the Enterprise offices in New York; to discuss approaches to bridging the gaps between fundamental,preclinical and clinical HIV vaccine research. The topic of this Working Group originated from discussions of the Enterprise Science Committee,which proposed that more effective collaboration between these three areas of HIV vaccine research is needed in order to accelerate the pace of scientific progress in the field. Because the meeting took place before the release of the RV144 trial results held in Thailand, the conclusions reached during the meeting were further discussed during consultations at scientific conferences and at a joint meeting of the Science Committee and Chairs of all five Working Groups. Thus, this Report reflects both the original discussions of the Working Group and subsequent discussions that took place after the release of the RV144 trial results.
Studies on Endogenous Hormonal Changes during Grain Development in Wheat Genotypes (PhD Thesis)
Authors: Gutam Sridhar
Published: July 2019

Pot culture experiment was conducted in the Rabi seasons of 2001 and 2002 in order to study the genotypic differences in grain growth rates and endogenous hormonal contents in the developing grains. The hexaploid new plant types and extant variety and other tetraploids are taken up for the study. The data on yield and yield components show that the tetraploids had higher ear number per plant but lesser number of seeds per ear and lower seed weight per ear. The most important yield component 1000-grain yield was also possessed by hexaploids. The mean plant height was found to be higher in hexaploids over tetraploids in general, and among them DL- 1266-1 and DL-1266-2 (new plant types) recorded higher plant height. Similarly, the ear length was also higher in these new plant types. But, the tiller number/plant and ear number/plant were significantly higher in tetraploids. The new plant types (hexaploids) possessed maximum grain growth rate at 5–15 DAA. DL-1266-2 recorded highest grain growth rate 0.093 g/g/day. The photosynthetic rate values show that the hexaploids possessed higher rate than tetraploids. At 7 and 15 DAA, in general, photosynthetic rate was more when compared to 25 DAA and 35 DAA. The results showed that the endogenous hormonal contents in grains during grain development had changed in sequence. At 7 DAA, gibberellic acid (GA3) content was at maximum and at 15 DAA (rapid growth phase), indole-acetic acid (IAA) reached maximum and at 25 DAA (dough stage), ABA was at the maximum. At the 35 DAA, ABA reached all time high and GA3 the least, IAA being intermediate. Among the genotypes, hexaploids recorded higher concentrations of endogenous hormones. The total chlorophyll content in flag leaves of hexaploids was higher than tetraploids. The mean total chlorophyll had increased slightly at 20 DAA when compared to 10 DAA and it decreased at 30 DAA. It appears that the high yielding hexaploids (DL-1266-1 & Dl- 1266-2) by the virtue of possessing more 1000-grain weight and leaf area along with endogenous hormones might be responsible for higher yield as compared to tetraploids. It appears that better photosynthetic rate and better mobilization of photosynthates during grain filling stage contributes for higher yield in hexaploids.
African wild ungulates compete with or facilitate cattle depending on season
Authors: Odadi Wilfred , Karachi Moses , Abdulrazak Shaukat , Young Truman
Published: July 2019

Savanna ecosystems are vital for both economic and biodiversity values. In savannas worldwide, management decisions are based on the concept that wildlife and livestock compete for grassland resources[1-4], yet there are virtually no experimental data to support this assumption[1]. Specifically, the critical assessment of whether or not wild ungulates alter livestock performance (e.g., weight gain, reproduction or survival) has rarely been carried out, although diminished performance is an essential prerequisite for inferring competition[1]. Here we use a large-scale experiment in a semi-arid savanna in Kenya to show that wild ungulates do depress cattle performance (weight gain) during the dry season, indicating a competitive effect, but enhance cattle performance during the wet season, signifying facilitation. This is the first experimental demonstration of either competitive or facilitative effects of an assemblage of native ungulates on domestic livestock in a savanna ecosystem, and a unique demonstration of a rainfall-dependent shift in competition-facilitation balance within any herbivore guild. These results are critical for better understanding and management of wildlife-livestock coexistence in savanna ecosystems globally, and especially in the African savanna biome which crucially hosts the last remnants of an intact large herbivore fauna.
Early onset preeclampsia is characterized by altered placental lipid metabolism and a premature increase in circulating FABP4
Authors: Han Victor , Lajoie Gilles , Ballard Jennifer , Booy Aaron , Carruthers Nicholas , Siroen Delfina
Published: July 2019

Preeclampsia is a pregnancy-associated disorder that manifests as a sudden increase in maternal blood pressure accompanied by proteinuria. Because the placenta is a key organ in preeclampsia, we used proteomic and lipidomic analyses to compare placentae from preeclamptic and gestational age matched control pregnancies. Fatty acid binding protein 4 (FABP4), enoyl-CoA dehydrogenase and delta-3,5-delta-2,4-dienoyl-CoA isomerase had altered abundance in preeclamptic placentae compared to controls. FABP4 placental protein and RNA and plasma levels were all increased in early-onset preeclampsia (prior to 28 weeks gestation) compared to controls (6-fold, 3.3-fold and 3.5-fold respectively). After 28 weeks, FABP4 protein in control placenta and plasma increased to the same concentrations as in preeclampsia. Total tetracosapentaenoic acid in preeclamptic placentae was decreased to 0.6 of control levels before 28 weeks. The data indicate a disruption of fatty acid transport and metabolism in the placenta in early onset preeclampsia that is reflected in the maternal plasma.
Life fingerprints of nuclear reactions in the body of animals
Authors: Xie Wen-hui , Liu Ci-yi , Cai Xiao-jia , Zeng Jun , Han Ji-hui , Sun Tao , Su Ji-hui , Sun Qi-yin , Zhang Quan-shi
Published: July 2019

Nuclear reactions are a very important natural phenomenon in the universe. On the earth, cosmic rays constantly cause nuclear reactions. High energy beams created by medical devices also induce nuclear reactions in the human body. The biological role of these nuclear reactions is unknown. Here we show that the in vivo biological systems are exquisite and sophisticated by nature in influence on nuclear reactions and in resistance to radical damage in the body of live animals. In this study, photonuclear reactions in the body of live or dead animals were induced with 50-MeV irradiation. Tissue nuclear reactions were detected by positron emission tomography (PET) imaging of the induced beta+ activity. We found the unique tissue "fingerprints" of beta+ (the tremendous difference in beta+ activities and tissue distribution patterns among the individuals) are imprinted in all live animals. Within any individual, the tissue "fingerprints" of 15O and 11C are also very different. When the animal dies, the tissue "fingerprints" are lost. The biochemical, rather than physical, mechanisms could play a critical role in the phenomenon of tissue "fingerprints". Radiolytic radical attack caused millions-fold increases in 15O and 11C activities via different biochemical mechanisms, i.e. radical-mediated hydroxylation and peroxidation respectively, and more importantly the bio-molecular functions (such as the chemical reactivity and the solvent accessibility to radicals). In practice biologically for example, radical attack can therefore be imaged in vivo in live animals and humans using PET for life science research, disease prevention, and personalized radiation therapy based on an individual's bio-molecular response to ionizing radiation.