Adaptation to high ethanol reveals complex evolutionary pathways

Tolerance to high levels of ethanol is an ecologically and industrially relevant phenotype of microbes, but the molecular mechanisms underlying this complex trait remain largely unknown. Here, we use long-term experimental evolution of isogenic yeast populations of different initial ploidy to study adaptation to increasing levels of ethanol. Whole-genome sequencing of more than 30 evolved populations and over 100 adapted clones isolated throughout this two-year evolution experiment revealed how a complex interplay of de novo single nucleotide mutations, copy number variation, ploidy changes, mutator phenotypes, and clonal interference led to a significant increase in ethanol tolerance. Although the specific mutations differ between different evolved lineages, application of a novel computational pipeline, PheNetic, revealed that many mutations target functional modules involved in stress response, cell cycle regulation, DNA repair and respiration. Measuring the fitness effects of selected mutations introduced in non-evolved ethanol-sensitive cells revealed several adaptive mutations that had previously not been implicated in ethanol tolerance, including mutations in PRT1, VPS70 and MEX67. Interestingly, variation in VPS70 was recently identified as a QTL for ethanol tolerance in an industrial bio-ethanol strain. Taken together, our results show how, in contrast to adaptation to some other stresses, adaptation to a continuous complex and severe stress involves interplay of different evolutionary mechanisms. In addition, our study reveals functional modules involved in ethanol resistance and identifies several mutations that could help to improve the ethanol tolerance of industrial yeasts

Location prediction based on a sector snapshot for location-based services

In location-based services (LBSs), the service is provided based on the users' locations through location determination and mobility realization. Most of the current location prediction research is focused on generalized location models, where the geographic extent is divided into regular-shaped cells. These models are not suitable for certain LBSs where the objectives are to compute and present on-road services. Such techniques are the new Markov-based mobility prediction (NMMP) and prediction location model (PLM) that deal with inner cell structure and different levels of prediction, respectively. The NMMP and PLM techniques suffer from complex computation, accuracy rate regression, and insufficient accuracy. In this paper, a novel cell splitting algorithm is proposed. Also, a new prediction technique is introduced. The cell splitting is universal so it can be applied to all types of cells. Meanwhile, this algorithm is implemented to the Micro cell in parallel with the new prediction technique. The prediction technique, compared with two classic prediction techniques and the experimental results, show the effectiveness and robustness of the new splitting algorithm and prediction technique

Unusual Thermodynamics on the Fuzzy 2-Sphere

Higher spin Dirac operators on both the continuum sphere($S^2$) and its fuzzy analog($S^2_F$) come paired with anticommuting chirality operators. A consequence of this is seen in the fermion-like spectrum of these operators which is especially true even for the case of integer-spin Dirac operators. Motivated by this feature of the spectrum of a spin 1 Dirac operator on $S_F^2$, we assume the spin 1 particles obey Fermi-Dirac statistics. This choice is inspite of the lack of a well defined spin-statistics relation on a compact surface such as $S^2$. The specific heats are computed in the cases of the spin $\frac{1}{2}$ and spin 1 Dirac operators. Remarkably the specific heat for a system of spin $\frac{1}{2}$ particles is more than that of the spin 1 case, though the number of degrees of freedom is more in the case of spin 1 particles. The reason for this is inferred through a study of the spectrums of the Dirac operators in both the cases. The zero modes of the spin 1 Dirac operator is studied as a function of the cut-off angular momentum $L$ and is found to follow a simple power law. This number is such that the number of states with positive energy for the spin 1 and spin $\frac{1}{2}$ system become comparable. Remarks are made about the spectrums of higher spin Dirac operators as well through a study of their zero-modes and the variation of their spectrum with degeneracy. The mean energy as a function of temperature is studied in both the spin $\frac{1}{2}$ and spin 1 cases. They are found to deviate from the standard ideal gas law in 2+1 dimensions.Comment: 19 pages, 7 figures. The paper has been significantly modified. Main results are unchange

Recent advancement in drug delivery system

Abstract Ease of drug administration, safety, affordability and effi cacy are the major concerns in pharmacotherapy leading to exploration of better drug delivery systems. Liposomes are lyotropic liquid crystals composed mainly of ampiphilic bilayers and these are more frequently used as drug carriers. Liposomes help reduce the toxicity and deliver the drug to the target tissue. So far, liposomes have been the most intensively studied lipid-based delivery system. In liposomes, a hydrophilic drug can be trapped in aqueous interior or channels between successive phospholipids bilayers whereas a hydrophobic drug can reside with the bilayer itself. The non-toxic and nonimmunogenic bilayers dissipate allowing the diffusion of the drug into the tissues. Attachment of polyethyl glycol to the surface of liposome (known as stealth liposome) aids in the better targeting of the drug to the tissues. Pegylated proteins and polymers of lactic and glycolic acids have been well studied as drug carriers and found to be resistant to phagocytosis and complement activation. Newer DNA based strategies including DNA vaccination and antisense oligonucleotides and immunomodulation show good results for new therapeutic systems. Though the DNA based therapeutic systems have high selectivity and specifi city with few adverse effects, these systems are so far restricted to animal models and clinical trials

Cooling of Dark-Matter Admixed Neutron Stars with density-dependent Equation of State

We propose a dark-matter (DM) admixed density-dependent equation of state where the fermionic DM interacts with the nucleons via Higgs portal. Presence of DM can hardly influence the particle distribution inside neutron star (NS) but can significantly affect the structure as well as equation of state (EOS) of NS. Introduction of DM inside NS softens the equation of state. We explored the effect of variation of DM mass and DM Fermi momentum on the NS EOS. Moreover, DM-Higgs coupling is constrained using dark matter direct detection experiments. Then, we studied cooling of normal NSs using APR and DD2 EOSs and DM admixed NSs using dark-matter modified DD2 with varying DM mass and Fermi momentum. We have done our analysis by considering different NS masses. Also DM mass and DM Fermi momentum are varied for fixed NS mass and DM-Higgs coupling. We calculated the variations of luminosity and temperature of NS with time for all EOSs considered in our work and then compared our calculations with the observed astronomical cooling data of pulsars namely Cas A, RX J0822-43, 1E 1207-52, RX J0002+62, XMMU J17328, PSR B1706-44, Vela, PSR B2334+61, PSR B0656+14, Geminga, PSR B1055-52 and RX J0720.4-3125. It is found that APR EOS agrees well with the pulsar data for lighter and medium mass NSs but cooling is very fast for heavier NS. For DM admixed DD2 EOS, it is found that for all considered NS masses, all chosen DM masses and Fermi momenta agree well with the observational data of PSR B0656+14, Geminga, Vela, PSR B1706-44 and PSR B2334+61. Cooling becomes faster as compared to normal NSs in case of increasing DM mass and Fermi momenta. It is infered from the calculations that if low mass super cold NSs are observed in future that may support the fact that heavier WIMP can be present inside neutron stars.Comment: 24 Pages, 15 Figures and 2 Tables. Version accepted in The European Physical Journal

Isotopic variation of parity violation in atomic ytterbium

We report on measurements of atomic parity violation, made on a chain of ytterbium isotopes with mass numbers A=170, 172, 174, and 176. In the experiment, we optically excite the 6s2 1S0 -> 5d6s 3D1 transition in a region of crossed electric and magnetic fields, and observe the interference between the Stark- and weak-interaction-induced transition amplitudes, by making field reversals that change the handedness of the coordinate system. This allows us to determine the ratio of the weak-interaction-induced electric-dipole (E1) transition moment and the Stark-induced E1 moment. Our measurements, which are at the 0.5% level of accuracy for three of the four isotopes measured, allow a definitive observation of the isotopic variation of the weak-interaction effects in an atom, which is found to be consistent with the prediction of the Standard Model. In addition, our measurements provide information about an additional Z' boson.Comment: 19 pages, 4 figures, 2 table

Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation

NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family

Successful bone marrow transplantation in a patient with Diamond-Blackfan anemia with co-existing Duchenne muscular dystrophy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Diamond-Blackfan anemia and Duchenne muscular dystrophy are two rare congenital anomalies. Both anomalies occurring in the same child is extremely rare. Allogeneic hematopoietic stem cell transplantation is a well-established therapy for Diamond-Blackfan anemia. However, in patients with Duchenne muscular dystrophy, stem cell therapy still remains experimental.</p> <p>Case presentation</p> <p>We report the case of a nine-year-old boy of north Indian descent with Diamond-Blackfan anemia and Duchenne muscular dystrophy who underwent successful allogeneic hematopoietic stem cell transplantation. He is transfusion-independent, and his Duchenne muscular dystrophy has shown no clinical deterioration over the past 45 months. His creatine phosphokinase levels have significantly decreased to 300 U/L from 14,000 U/L pre-transplant. The patient is 100% donor chimera in the hematopoietic system, and his muscle tissue has shown 8% to 10.4% cells of donor origin.</p> <p>Conclusion</p> <p>Our patient's Diamond-Blackfan anemia was cured by allogeneic hematopoietic stem cell transplantation. The interesting clinical observation of a possible benefit in Duchenne muscular dystrophy cannot be ruled out. However, further clinical follow-up with serial muscle biopsies and molecular studies are needed to establish this finding.</p