Miracle-dz/UniFAR-FTUs huggingface dataset:
Couplons in rat atria form distinct subgroups defined by their molecular partners

Standard local control theory, which describes Ca2+ release during excitation–contraction coupling (ECC), assumes that all ryanodine receptor 2 (RyR2) complexes are equivalent. Findings from our laboratory have called this assumption into question. Specifically, we have shown that the RyR2 complexes in ventricular myocytes are different, depending on their location within the cell. This has led us to hypothesize that similar differences occur within the rat atrial cell. To test this hypothesis, we have triple-labelled enzymatically isolated fixed myocytes to examine the distribution and colocalization of RyR2, calsequestrin (Casq), voltage-gated Ca2+ channels (Cav1.2), the sodium–calcium exchanger (Ncx) and caveolin-3 (Cav3). A number of different surface RyR2 populations were identified, and one of these groups, in which RyR2, Cav1.2 and Ncx colocalized, might provide the structural basis for ‘eager’ sites of Ca2+ release in atria. A small percentage of the dyads containing RyR2 and Cav1.2 were colocalized with Cav3, and therefore could be influenced by the signalling molecules it anchors. The majority of the RyR2 clusters were tightly linked to Cav1.2, and, whereas some were coupled to both Ca 1.2 and Ncx, none were with Ncx alone. This suggests that Cav1.2-mediated Ca2+ -induced Ca2+ release is the primary method of ECC. The two molecules studied that were found in the interior of atrial cells, RyR2 and Casq, showed significantly less colocalization and a reduced nearest-neighbour distance in the interior, compared with the surface of the cell. These differences might result in a higher excitability for RyR2 in the interior of the cells, facilitating the spread of excitation from the periphery to the centre. We also present morphometric data for all of the molecules studied, as well as for those colocalizations found to be significant.
Standard metabolic rate predicts growth trajectory of juvenile Chinese crucian carp (Carassius auratus) under changing food availability

ABSTRACT Phenotypic traits vary greatly within populations and can have a significant influence on aspects of performance. The present study aimed to investigate the effects of individual variation in standard metabolic rate (SMR) on growth rate and tolerance to food deprivation in juvenile Chinese crucian carp (Carassius auratus) under varying levels of food availability. To address this issue, 19 high and 16 low SMR individuals were randomly assigned to a satiation diet for 3 weeks, whereas another 20 high and 16 low SMR individuals were assigned to a restricted diet (approximately 50% of satiation) for the same period. Then, all fish were completely food-deprived for another 3 weeks. High SMR individuals showed a higher growth rate when fed to satiation, but this advantage of SMR did not exist in food-restricted fish. This result was related to improved feeding efficiency with decreased food intake in low SMR individuals, due to their low food processing capacity and maintenance costs. High SMR individuals experienced more mass loss during food deprivation as compared to low SMR individuals. Our results here illustrate context-dependent costs and benefits of intraspecific variation in SMR whereby high SMR individuals show increased growth performance under high food availability but had a cost under stressful environments (i.e. food shortage). Summary: Our study documented how the relationship between variation in standard metabolic rate and growth is altered by the food availability in fish.
Differences in the Cooling Behavior of Strange Quark Matter Stars and Neutron Stars

The general statement that hypothetical strange quark matter stars cool more rapidly than neutron stars is investigated in greater detail. It is found that the direct Urca process can be forbidden not only in neutron stars, but also in strange-matter stars. In this case, strange-matter stars cool slowly and their surface temperatures are more or less indistinguishable from those of slowly cooling neutron stars. We investigate the case of enhanced cooling again. We find that strange-matter stars cool significantly more rapidly than neutron stars within the first ~30 yr after birth. This result may become particularly interesting if continued observation of SN 1987A reveals the temperature of the pulsar that may reside at its center.
PEGylated Single-Walled Carbon Nanotubes as Nanocarriers for Cyclosporin A Delivery

Single-walled carbon nanotubes (SWCNTs) have attracted the attention of many researchers due to their remarkable physicochemical features and have been found to be a new family of nanovectors for the delivery of therapeutic molecules. The ability of these nanostructures to load large amounts of drug molecules on their outer surface has been considered as the main advantage by many investigators. Here, we report the development of a PEGylated SWCNT-mediated delivery system for cyclosporin A (CsA) as a potent immunosuppressive agent. The available OH group in the CsA structure was first linked to a bi-functional linker (i.e., succinic anhydride) in order to provide a COOH terminal group. CsA succinylation process was optimized by using the modified simplex method. The resulting compound, CsA–CO–(CH2)2–COOH, was then grafted onto the exterior surface of SWCNTs, previously PEGylated with phospholipid–PEG5000–NH2 conjugates, through the formation of an amide bond with the free amine group of PEGylated SWCNTs. Drug loading, stability of the PEGylated SWCNT–CsA complex, and in vitro release of the drug were evaluated. Loading efficiencies of almost 72% and 68% were achieved by UV spectrophotometry and elemental analysis methods, respectively. It was observed that 57.3% of cyclosporine was released from CsA–Pl–PEG5000–SWCNTs after 3 days. In this investigation, we conjugated CsA to an amine-terminated phospholipid–polyethylene glycol chain attached on SWCNTs via a cleavable ester bond and demonstrated the possible potential of PEGylated SWCNT-based systems for CsA delivery.
Immunodominance of HLA-A2-Restricted Hepatitis C Virus-Specific CD8+ T Cell Responses Is Linked to Naïve-Precursor Frequency

ABSTRACT The impact of naïve-precursor frequency on human virus-specific CD8+ T cell immunodominance is not well understood. Using a recently developed major histocompatibility complex (MHC) class I tetramer enrichment protocol, we found a conserved hierarchy and a >10-fold difference in naïve-precursor frequencies across three HLA-A2-restricted hepatitis C virus (HCV)-specific epitopes. Importantly, the NS31406 epitope with the highest naïve-precursor frequency in healthy donors was also the most frequently targeted epitope in a large cohort of chronically HCV-infected patients, both ex vivo and after in vitro stimulation. These results indicate for the first time that immunodominance in a human viral infection is linked to naïve-precursor frequency.
Postcranial Sex Estimation of Individuals Considered Hispanic

When forensic anthropologists estimate the sex of Hispanic skeletal remains using nonpopulation specific metric methods, initial observations cause males to frequently misclassify as female. To help improve these methods, this research uses postcranial measurements from United States–Mexico border migrant fatalities at the Pima County Office of the Medical Examiner in Tucson, Arizona, as well as Hispanic individuals from the Forensic Anthropology Data Bank. Using a total of 114 males and 28 females, sectioning points and discriminant functions provide classification rates as high as 89.43% for Hispanic individuals. A test sample assessed the reliability of these techniques resulting in accuracy up to 99.65%. The clavicle maximum length measurement provides the best univariate estimate of sex, while the radius provides the best multivariate estimated of sex. The results of this research highlight the need for population specific data in the creation of a biological profile, especially when working with individuals considered Hispanic.
Virtual Screening for LPA2-Specific Agonists Identifies a Nonlipid Compound with Antiapoptotic Actions

Lysophosphatidic acid (LPA) is a highly potent endogenous lipid mediator that protects and rescues cells from programmed cell death. Earlier work identified the LPA2 G protein-coupled receptor subtype as an important molecular target of LPA mediating antiapoptotic signaling. Here we describe the results of a virtual screen using single-reference similarity searching that yielded compounds 2-((9-oxo-9H-fluoren-2-yl)carbamoyl)benzoic acid (NSC12404), 2-((3-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)propyl)thio)benzoic acid (GRI977143), 4,5-dichloro-2-((9-oxo-9H-fluoren-2-yl)carbamoyl)benzoic acid (H2L5547924), and 2-((9,10-dioxo-9,10-dihydroanthracen-2-yl)carbamoyl) benzoic acid (H2L5828102), novel nonlipid and drug-like compounds that are specific for the LPA2 receptor subtype. We characterized the antiapoptotic action of one of these compounds, GRI977143, which was effective in reducing activation of caspases 3, 7, 8, and 9 and inhibited poly(ADP-ribose)polymerase 1 cleavage and DNA fragmentation in different extrinsic and intrinsic models of apoptosis in vitro. Furthermore, GRI977143 promoted carcinoma cell invasion of human umbilical vein endothelial cell monolayers and fibroblast proliferation. The antiapoptotic cellular signaling responses were present selectively in mouse embryonic fibroblast cells derived from LPA1&2 double-knockout mice reconstituted with the LPA2 receptor and were absent in vector-transduced control cells. GRI977143 was an effective stimulator of extracellular signal-regulated kinase 1/2 activation and promoted the assembly of a macromolecular signaling complex consisting of LPA2, Na+-H+ exchange regulatory factor 2, and thyroid receptor interacting protein 6, which has been shown previously to be a required step in LPA-induced antiapoptotic signaling. The present findings indicate that nonlipid LPA2-specific agonists represent an excellent starting point for development of lead compounds with potential therapeutic utility for preventing the programmed cell death involved in many types of degenerative and inflammatory diseases.
Gene Expression Analysis in the Thalamus and Cerebrum of Horses Experimentally Infected with West Nile Virus

Gene expression associated with West Nile virus (WNV) infection was profiled in the central nervous system of horses. Pyrosequencing and library annotation was performed on pooled RNA from the CNS and lymphoid tissues on horses experimentally infected with WNV (vaccinated and naïve) and non-exposed controls. These sequences were used to create a custom microarray enriched for neurological and immunological sequences to quantitate gene expression in the thalamus and cerebrum of three experimentally infected groups of horses (naïve/WNV exposed, vaccinated/WNV exposed, and normal). From the sequenced transcriptome, 41,040 sequences were identified by alignment against five databases. 31,357 good sequence hits (e<10−4) were obtained with 3.1% of the sequences novel to the equine genome project. Sequences were compared to human expressed sequence tag database, with 31,473 equine sequences aligning to human sequences (69.27% contigs, 78.13% seed contigs, 80.17% singlets). This indicated a high degree of sequence homology between human and equine transcriptome (average identity 90.17%). Significant differences (p<0.05) in gene expression were seen due to virus exposure (9,020), survival (7,395), and location (7,649). Pathways analysis revealed many genes that mapped to neurological and immunological categories. Involvement of both innate and adaptive components of immunity was seen, with higher levels of expression correlating with survival. This was highlighted by increased expression of suppressor of cytokine signaling 3 in horses exposed to WNV which functions to suppress innate immunity. Pentraxin 3 was most increased in expression for all horses exposed to WNV. Neurological pathways that demonstrated the greatest changes in gene expression included neurotransmitter and signaling pathways. Decreased expression of transcripts in both the glutamate and dopamine signaling pathways was seen in horses exposed to WNV, providing evidence of possible glutamate excitotoxicity and clinical signs associated with decreased dopamine. Many transcripts mapped to non-infectious neurological disease functions, including mental disorders and degenerative neuropathies.
A hardware-software cosynthesis technique based on heterogeneous multiprocessor scheduling

In this paper, we propose a fast and simple heuristic for the cosynthesis problem targeting the system-on-chip (SOC) design. The proposed algorithm covers from implementation selection and resource sharing problem in SOC design to PE selection problems in distributed heterogeneous embedded (DHE) system design. The proposed solution also considers multiple design objectives. Through benchmark experimentation, it is proven that the proposed solution produces solutions of equivalent quality to the previously published results in the DHE design. Its execution speed is several orders of magnitude smaller for large examples. We envision that the proposed approach will be one of significant cosynthesis researches in the SOC design. In the DHE design, the proposed approach could be used as an initial solution to a probabilistic algorithm guaranteeing to obtain a better solution.
Problem‐solving styles of medical students related to knowledge and personality in simulated clinical situations

Summary. A study of problem‐solving styles, employing a method previously used with general practitioners, was carried out with 40 final‐year medical students. By giving their ratings on a five‐point rating scale of 21–24 statements relating to each of three case histories, an answer index could be computed, expressing each student's tendency to make assertive versus non‐assertive decisions. The relationship of this answer index to knowledge (grades and educational level), personality (Eysenck personality inventory [EPI]), and time used in the exercises was examined. High answer index (high degree of decisiveness in the clinical simulations) was significantly correlated with extroverted personality on the EPI (P<0.05) and negatively correlated with time spent on the exercises (P<0.01), whereas no relationship was found with grades in medical school, educational level, neuroticism on the EPI, or the Students' sex and age. The findings are discussed in relation to previous studies on clinical problem‐solving.
Mobile-assisted language learning: A selected annotated bibliography of implementation studies 1994–2012

To enhance the information contained in these references, over 90% of the entries are complemented by a brief (~80 word) summary. To the extent that the publication provides such information, each annotation identifies the country of origin of the study, native language (L1) and/or the second or foreign language (L2) involved, the mobile technology used, the learning area(s) targeted, the type of learners, their numbers, the duration of the study, and a summary of the results (i.e., learning outcomes and survey opinions). Since nearly 60% of MALL implementation studies appear outside of professional journals, in conference proceedings, project reports, academic dissertations, and so forth, locating copies of these publications poses a major challenge in itself. For this reason, where possible, links are included to copies of the works cited.
Life-history strategies affect aphid preference for yellowing leaves

According to the nutrient-translocation hypothesis, yellowing tree leaves are colonized by aphids at the end of the growing season owing to improved availability of nutrients in the phloem sap after chlorophyll degradation. We measured aphid densities on potted Betula pendula seedlings in a field site where a small proportion of foliage rapidly turned yellow before normal autumn coloration as a consequence of root anoxia. The number of adults and nymphs of the birch-feeding specialist aphids Euceraphis betulae, Betulaphis brevipilosa and Callipterinella tuberculata were counted from leaves on each of the 222 plants. Aphids were detected on 19 per cent of green leaves and on 41 per cent of yellow leaves. There was no indication of aphid avoidance of yellow leaves, and the number of winged (alate) viviparous E. betulae adults and their nymphs were significantly higher on yellow leaves than on green leaves, while the numbers of apterous B. brevipilosa and C. tuberculata did not differ between the leaf colour types. Our result suggests that only aphid species with alate generation during colour change can take advantage of yellowing leaves. This may explain the exceptional abundance of E. betulae compared with other aphid species on birches.
Changing patterns and outcome of Dengue infection; report from a tertiary care hospital in Pakistan.

OBJECTIVE To identify predictors of outcome in patients with Dengue Infections at a tertiary care hospital and to analyze that if pattern of Dengue infection is changing in the past two years. METHODS We reviewed 225 cases of confirmed dengue virus infection. The diagnosis was confirmed by presence of IgM antibodies against Dengue by ELISA in addition to fever according to WHO criteria. RESULTS From years 2000-2004, 30 (73%) had Dengue Fever (DF), 10 (24%) had Dengue Haemorrhagic Fever (DHF) and 1(2.4%) had Dengue shock syndrome (DSS) while after 2005, 107 (58%) had DF, 71 (39%) had DHF and 6 (3%) had DSS. Six patients (2.6%) died. Presence of shock (OR 2.9, 95% CI; 1.7-6.2), coma at presentation (OR 1.89, 95% CI; 1.02-3.3) and seizures (OR 1.6, 95% CI; 0.9-3.0) were important predictors of mortality. CONCLUSION These findings are suggestive of a change in pattern and outcome of Dengue at our institution. Larger data set from all around the country is needed to comment on epidemicity and endemicity pattern of the Dengue in Pakistan.
Endovascular Treatment of Bilateral Carotid Artery Occlusion with Concurrent Basilar Apex Aneurysm: A Case Report and Literature Review

We report a case of successful endovascular treatment of bilateral carotid artery occlusion with concurrent basilar apex aneurysm. An elderly female patient with subarachnoid hemorrhage (SAH) onset was admitted to the hospital. Computed tomography (CT) and digital subtraction angiography (DSA) confirmed the presence of bilateral carotid artery occlusion with concurrent basilar apex aneurysm. Brain blood supply was provided by the bilateral vertebral artery through the basilar artery. We treated the aneurysm with the endovascular approach by embolizing the aneurysm with three coils. The patient recovered well after surgery and showed no recanalization of the aneurysm on a one-year follow-up DSA. We also reviewed six similar cases found with a PUBMED database search (1980-2010), including those with bilateral common carotid artery occlusion. In conclusion, by using the endovascular approach, bilateral carotid artery occlusion with concurrent basilar apex aneurysm was efficiently treated.
Effect of C-to-T transition at CpG sites on tumor suppressor genes in tumor development in cattle evaluated by somatic mutation analysis in enzootic bovine leukosis

Oncogenic transformation of normal cells is caused by mutations and chromosomal abnormalities in cancer-related genes. Enzootic bovine leukosis (EBL) is a malignant B-cell lymphoma caused by bovine leukemia virus (BLV) infection in cattle. Although a small fraction of BLV-infected cattle develops EBL after a long latent period, the mechanisms for oncogenesis in EBL cattle remain largely unknown. In this study, we analyzed the types and patterns of somatic mutations in cancer cells from 36 EBL cases, targeting 21 cancer-related genes. Various somatic mutations were identified in 8 genes, TP53, NOTCH1, KMT2D, CREBBP, KRAS, PTEN, CARD11, and MYD88. In addition, TP53 gene was found to be mutated in 69.4% of EBL cases, with most being biallelic mutations. In some cases, associations were observed between the ages at which cattle had developed EBL and somatic mutation patterns; young onset of EBL possibly occurs due to congenital mutations, high impact mutations affecting protein translation, and biallelic mutations. Furthermore, nucleotide substitution patterns indicated that cytosine at CpG sites tended to be converted to thymine in many EBL cases, which was considered to be the result of spontaneous deamination of 5-methylctosine. These results demonstrate how somatic mutations have occurred in cancer cells leading to EBL development, thereby explaining its pathogenic mechanism. These findings will contribute to a better understanding and future elucidation of disease progression in BLV infection. Importance Enzootic bovine leukosis (EBL) is a malignant and lethal disease in cattle. Currently, there are no effective vaccines or therapeutic methods against bovine leukemia virus (BLV) infection, resulting in severe economic losses in livestock industry. This study provides a renewed hypothesis to explain the general mechanisms of EBL onset by combining the previous finding that several integration sites of BLV provirus can affect the increase in survival and proliferation of infected cells. We demonstrate that two additional random events are necessary for oncogenic transformation in infected cell clones, elucidating the reason why only few infected cattle develop EBL. Further exploration of somatic mutation and BLV integration sites could support this hypothesis more firmly, potentially contributing to the development of novel control methods for EBL onset.
Mono- to tetra-alkyl ether cardiolipins in a mesophilic, sulfate-reducing bacterium identified by UHPLC-HRMSn: A novel class of membrane lipids

The composition of membrane lipids varies in a number of ways as adjustment to growth conditions. Variations in head group composition and carbon skeleton and degree of unsaturation of glycerol-bound acyl or alkyl groups results in a high structural complexity of the lipidome of bacterial cells. We studied the lipidome of the mesophilic, sulfate-reducing bacterium, Desulfatibacillum alkenivorans strain PF2803T by ultra-high-pressure liquid chromatography coupled with high-resolution tandem mass spectrometry (UHPLC-HRMSn). This anaerobic and hydrocarbon-utilizing bacterium has been previously shown to produce high amounts of mono- and di-alkyl glycerol ethers as core membrane. Our analyses revealed that these core lipids occur with phosphatidylethanomamine (PE) and phosphatidylglycerol (PG) head groups, representing each approximately one third of the phospholipids. The third class was a novel group of phospholipids, i.e. cardiolipins (CDLs) containing one (monoether/triester) to four (tetraether) ether-linked saturated straight-chain or methyl- branched alkyl chains. Tetraether CDLs have been shown to occur in archaea (with isoprenoid alkyl chains) but have not been previously reported in the bacterial Domain. Structurally related CDLs with one or two alkyl/acyl chains missing, so-called monolyso- and dilyso-CDLs, were also observed. The potential biosynthetic pathway of these novel CDLs was investigated by examining the genome of D. alkenivorans. Three CDL synthases were identified; one catalyzes the condensation of two PGs, the other two are probably involved in the condensation of a PE with a PG. A heterologous gene expression experiment showed the in vivo production of dialkylglycerols upon anaerobic expression of the glycerol ester reductase enzyme of D. alkenivorans in E. coli. Reduction of the ester bonds probably occurs first at the sn-1 and subsequently at the sn-2 position after the formation of PEs and PGs, since PGs possess a much higher percentage of ether bonds than PEs.