A Catalog of Coding Sequence Variations in Salivary Proteins’ Genes Occurring during Recent Human Evolution

Saliva houses over 2000 proteins and peptides with poorly clarified functions, including proline-rich proteins, statherin, P-B peptides, histatins, cystatins, and amylases. Their genes are poorly conserved across related species, reflecting an evolutionary adaptation. We searched the nucleotide substitutions fixed in these salivary proteins’ gene loci in modern humans compared with ancient hominins. We mapped 3472 sequence variants/nucleotide substitutions in coding, noncoding, and 5′-3′ untranslated regions. Despite most of the detected variations being within noncoding regions, the frequency of coding variations was far higher than the general rate found throughout the genome. Among the various missense substitutions, specific substitutions detected in PRB1 and PRB2 genes were responsible for the introduction/abrogation of consensus sequences recognized by convertase enzymes that cleave the protein precursors. Overall, these changes that occurred during the recent human evolution might have generated novel functional features and/or different expression ratios among the various components of the salivary proteome. This may have influenced the homeostasis of the oral cavity environment, possibly conditioning the eating habits of modern humans. However, fixed nucleotide changes in modern humans represented only 7.3% of all the substitutions reported in this study, and no signs of evolutionary pressure or adaptative introgression from archaic hominins were found on the tested genes

Pannexin 3 deletion reduces fat accumulation and inflammation in a sex-specific manner

Background: Pannexin 3 (PANX3) is a channel-forming glycoprotein that enables nutrient-induced inflammation in vitro, and genetic linkage data suggest that it regulates body mass index. Here, we characterized inflammatory and metabolic parameters in global Panx3 knockout (KO) mice in the context of forced treadmill running (FEX) and high-fat diet (HFD). Methods: C57BL/6N (WT) and KO mice were randomized to either a FEX running protocol or no running (SED) from 24 until 30 weeks of age. Body weight was measured biweekly, and body composition was measured at 24 and 30 weeks of age. Male WT and KO mice were fed a HFD from 12 to 28 weeks of age. Metabolic organs were analyzed for a panel of inflammatory markers and PANX3 expression. Results: In females there were no significant differences in body composition between genotypes, which could be due to the lack of PANX3 expression in female white adipose tissue, while male KOs fed a chow diet had lower body weight and lower fat mass at 24 and 30 weeks of age, which was reduced to the same extent as 6 weeks of FEX in WT mice. In addition, male KO mice exhibited significantly lower expression of multiple pro-inflammatory genes in white adipose tissue compared to WT mice. While on a HFD body weight differences were insignificant, multiple inflammatory genes were significantly different in quadriceps muscle and white adipose tissue resulting in a more anti-inflammatory phenotype in KO mice compared to WT. The lower fat mass in male KO mice may be due to significantly fewer adipocytes in their subcutaneous fat compared to WT mice. Mechanistically, adipose stromal cells (ASCs) cultured from KO mice grow significantly slower than WT ASCs. Conclusion: PANX3 is expressed in male adult mouse adipose tissue and may regulate adipocyte numbers, influencing fat accumulation and inflammation

Improving Phase Change Memory Performance with Data Content Aware Access

A prominent characteristic of write operation in Phase-Change Memory (PCM) is that its latency and energy are sensitive to the data to be written as well as the content that is overwritten. We observe that overwriting unknown memory content can incur significantly higher latency and energy compared to overwriting known all-zeros or all-ones content. This is because all-zeros or all-ones content is overwritten by programming the PCM cells only in one direction, i.e., using either SET or RESET operations, not both. In this paper, we propose data content aware PCM writes (DATACON), a new mechanism that reduces the latency and energy of PCM writes by redirecting these requests to overwrite memory locations containing all-zeros or all-ones. DATACON operates in three steps. First, it estimates how much a PCM write access would benefit from overwriting known content (e.g., all-zeros, or all-ones) by comprehensively considering the number of set bits in the data to be written, and the energy-latency trade-offs for SET and RESET operations in PCM. Second, it translates the write address to a physical address within memory that contains the best type of content to overwrite, and records this translation in a table for future accesses. We exploit data access locality in workloads to minimize the address translation overhead. Third, it re-initializes unused memory locations with known all-zeros or all-ones content in a manner that does not interfere with regular read and write accesses. DATACON overwrites unknown content only when it is absolutely necessary to do so. We evaluate DATACON with workloads from state-of-the-art machine learning applications, SPEC CPU2017, and NAS Parallel Benchmarks. Results demonstrate that DATACON significantly improves system performance and memory system energy consumption compared to the best of performance-oriented state-of-the-art techniques.Comment: 18 pages, 21 figures, accepted at ACM SIGPLAN International Symposium on Memory Management (ISMM

Service failure-recovery in online shops in Iran

Present article focuses on service failure and recovery in the online shops in Iran. The article investigates interaction between service failure and online shops readiness for service recovery and resulting impact on customer reaction. The data was collected by an e-questionnaire from 615 Iranian online shoppers. The findings suggest, although many online shops are severely breaching few fundamental business principles, defection is not happening as vast as in other similar studies. Furthermore, winning the customers back via service recovery seems to be depended rather on the process than the outcome of service recovery, which is very similar to the findings of another study in Chinese environment. Discussion of the findings suggests the researchers and managers to be conscious of the possible impact of the culture and environment on customer's responses to service failure and service recovery states.Godkänd; 2008; 20080911 (hakan_p);License fulltext:  CC BY</p