Primes in short intervals

Contrary to what would be predicted on the basis of Cram\'er's model concerning the distribution of prime numbers, we develop evidence that the distribution of $\psi(x+H)- \psi(x)$, for $0\le x\le N$, is approximately normal with mean $\sim H$ and variance $\sim H\log N/H$, when $N^\delta \le H \le N^{1-\delta}$.Comment: 29 page

Anti-cancer natural products inducing cross-talk between apoptosis and autophagy mutual proteins to regulate cancer cell death: design of future green anticancer therapies

The present letter concerns anti-cancer natural products inducing cross-talk between apoptosis and autophagy mutual proteins to regulate cancer cell death for future cancer green therapeutic approaches. The course of cancer advancement has always been attributed to the defectiveness in cell death mechanisms (Du et al., 2013; Hematulin et al., 2014). These defects act as a shield in protecting tumor cells from drugs and therapies, all at the same time, maintaining a longer life span and prompting their dispersion procedures. Autophagy and apoptosis safeguards cells from cellular damages and maintains proliferation and homeostasis by deporting outgrowth and controlling differentiation of pernicious cells. The autophagic proteins are conventionally found in hindering apoptosis whereas vice versa accounts had been reported for apoptotic-intermediates in preventing autophagic responses

Regulating mitochondrial biogenesis : from herbal remedies to phytomedicine for cancer prevention

Mitochondria are well-adapted endosymbiotic intracellular organelles, acting as the energy supplier for survival and proliferation of cells under aerobic conditions. Moreover, cellular proliferation largely depends on the total number of mitochondria, governed by the process of mitochondrial biogenesis (Davila and Zamorano, 2013; Yoboue et al., 2014)

Mass equidistribution of Hilbert modular eigenforms

Let F be a totally real number field, and let f traverse a sequence of non-dihedral holomorphic eigencuspforms on GL(2)/F of weight (k_1,...,k_n), trivial central character and full level. We show that the mass of f equidistributes on the Hilbert modular variety as max(k_1,...,k_n) tends to infinity. Our result answers affirmatively a natural analogue of a conjecture of Rudnick and Sarnak (1994). Our proof generalizes the argument of Holowinsky-Soundararajan (2008) who established the case F = Q. The essential difficulty in doing so is to adapt Holowinsky's bounds for the Weyl periods of the equidistribution problem in terms of manageable shifted convolution sums of Fourier coefficients to the case of a number field with nontrivial unit group.Comment: 40 pages; typos corrected, nearly accepted for

Seasonal switchgrass ecotype contributions to soil organic carbon, deep soil microbial community composition and rhizodeposit uptake during an extreme drought

The importance of rhizodeposit C and associated microbial communities in deep soil C stabilization is relatively unknown. Phenotypic variability in plant root biomass could impact C cycling through belowground plant allocation, rooting architecture, and microbial community abundance and composition. We used a pulse-chase 13C labeling experiment with compound-specific stable-isotope probing to investigate the importance of rhizodeposit C to deep soil microbial biomass under two switchgrass ecotypes (Panicum virgatum L., Kanlow and Summer) with contrasting root morphology. We quantified root phenology, soil microbial biomass (phospholipid fatty acids, PLFA), and microbial rhizodeposit uptake (13C-PLFAs) to 150 cm over one year during a severe drought. The lowland ecotype, Kanlow, had two times more root biomass with a coarser root system compared to the upland ecotype, Summer. Over the drought, Kanlow lost 78% of its root biomass, while Summer lost only 60%. Rhizosphere microbial communities associated with both ecotypes were similar. However, rhizodeposit uptake under Kanlow had a higher relative abundance of gram-negative bacteria (44.1%), and Summer rhizodeposit uptake was primarily in saprotrophic fungi (48.5%). Both microbial community composition and rhizodeposit uptake shifted over the drought into gram-positive communities. Rhizosphere soil C was greater one year later under Kanlow due to turnover of unlabeled structural root C. Despite a much greater root biomass under Kanlow, rhizosphere δ13C was not significantly different between the two ecotypes, suggesting greater microbial C input under the finer rooted species, Summer, whose microbial associations were predominately saprotrophic fungi. Ecotype specific microbial communities can direct rhizodeposit C flow and C accrual deep in the soil profile and illustrate the importance of the microbial community in plant strategies to survive environmental stress such as drought

Nanoparticulate peptide delivery exclusively to the brain produces tolerance free analgesia

This is the final version. Available on open access from Elsevier via the DOI in this recordThe delivery of peptide drugs to the brain is challenging, principally due to the blood brain barrier and the low metabolic stability of peptides. Exclusive delivery to the brain with no peripheral exposure has hitherto not been demonstrated with brain quantification data. Here we show that polymer nanoparticles encapsulating leucine5-enkephalin hydrochloride (LENK) are able to transport LENK exclusively to the brain via the intranasal route, with no peripheral exposure and nanoparticle localisation is observed within the brain parenchyma. Animals dosed with LENK nanoparticles (NM0127) showed a strong anti-nociceptive response in multiple assays of evoked and on going pain whereas animals dosed intranasally with LENK alone were unresponsive. Animals did not develop tolerance to the anti-hyperalgesic activity of NM0127 and NM0127 was active in morphine tolerant animals. A microparticulate formulation of clustered nanoparticles was prepared to satisfy regulatory requirements for nasal dosage forms and the polymer nanoparticles alone were found to be biocompatible, via the nasal route, on chronic dosing.The UK Engineering and Physical Sciences Research Council(EP/K502340/1), Nanomerics Ltd.(NM12TSB-NPP) and Innovate UK(16939-124181) are acknowledged for funding

Novel 1-hydroxypyridin-2-one metal chelators prevent and res-cue ubiquitin proteasomal-related neuronal injury in an in vitro model of Parkinson’s disease

Ubiquitin proteasome system (UPS) impairment, excessive cellular oxidative stress and iron dyshomeostasis are key to substantia nigra dopaminergic neuronal de-generation in Parkinson's disease (PD); however, a link between these features remains unconfirmed. By using the proteasome inhibitor lactacystin we confirm that nigral injury via UPS impairment disrupts iron homeostasis, in turn increasing oxi-dative stress and promoting protein aggregation. We demonstrate the neuroprotec-tive potential of two novel 1-hydroxy-2(1H)-pyridinone (1,2-HOPO) iron chelators, compounds C6 and C9, against lactacystin-induced cell death. We demonstrate that this cellular preservation relates to the compounds’ iron chelating capabilities and subsequent reduced capacity of iron to form reactive oxygen species (ROS), where we also show that the ligands act as antioxidant agents. Our results also de-monstrate the ability of C6 and C9 to reduce intracellular lactacystin-induced α-synuclein burden. Stability constant measurements confirmed a high affinity of C6 and C9 for Fe3+ and display a 3:1 HOPO:Fe3+ complex formation at physiological pH. Reducing iron reactivity could prevent the demise of nigral dopaminergic neurons. We provide evidence that the lactacystin model presents with several neuropatho-logical hallmarks of PD related to iron dyshomeostasis and that the novel chelating compounds C6 and C9 can protect against lactacystin-related neurotoxicity

In vitro and in vivo anticandidal activities of alginate-enclosed chitosan-calcium phosphate-loaded Fe-bovine lactoferrin nanocapsules

Aim: To study the in vitro and in vivo anticandidal activity of nanocapsulated bovine lactoferrin. Materials & methods: In vitro and in vivo antimicrobial activities were conducted to study the anticandidal activities of nanocapsules (NCs). Results: The NCs showed good anticandidal activities. The disruption of cell wall and cell membrane was noted via microscopy studies. The NCs changed the normal growth profile of Candida albicans. NCs reduced the colony forming unit in kidney and blood samples. Histopathological examination showed better cell structure and coordination compared with untreated mice kidney. NCs also enhanced the natural killing properties of C. albicans by epithelial cells. Conclusion: NCs have effective anticandidal properties and have the potential as a therapeutic agent against candidiasis

Increasing the reference populations for the 55 AISNP panel: the need and benefits

Ancestry inference for an individual can only be as good as the reference populations with allele frequency data on the SNPs being used. If the most relevant ancestral population(s) does not have data available for the SNPs studied, then analyses based on DNA evidence may indicate a quite distantly related population, albeit one among the more closely related of the existing reference populations. We have added reference population allele frequencies for 14 additional population samples (with >1100 individuals studied) to the 125 population samples previously published for the Kidd Lab 55 AISNP panel. Allele frequencies are now publicly available for all 55 SNPs in ALFRED and FROG-kb for a total of 139 population samples. This Kidd Lab panel of 55 ancestry informative SNPs has been incorporated in commercial kits by both ThermoFisher Scientific and Illumina for massively parallel sequencing. Researchers employing those kits will find the enhanced set of reference populations useful