Conserved roles of C. elegans and human MANFs in sulfatide binding and cytoprotection.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER) protein that can be secreted and protects dopamine neurons and cardiomyocytes from ER stress and apoptosis. The mechanism of action of extracellular MANF has long been elusive. From a genetic screen for mutants with abnormal ER stress response, we identified the gene Y54G2A.23 as the evolutionarily conserved C. elegans MANF orthologue. We find that MANF binds to the lipid sulfatide, also known as 3-O-sulfogalactosylceramide present in serum and outer-cell membrane leaflets, directly in isolated forms and in reconstituted lipid micelles. Sulfatide binding promotes cellular MANF uptake and cytoprotection from hypoxia-induced cell death. Heightened ER stress responses of MANF-null C. elegans mutants and mammalian cells are alleviated by human MANF in a sulfatide-dependent manner. Our results demonstrate conserved roles of MANF in sulfatide binding and ER stress response, supporting sulfatide as a long-sought lipid mediator of MANF's cytoprotection

A Civil Aircraft Cockpit Layout Evaluation Method Based on Layout Design Principles

As technology continues to leap forward and innovations advance, the systems of civil aircraft are becoming increasingly sophisticated and complex. Accordingly, there is a rising amount of information to be processed by pilots in the cockpit, increasing their cognitive burden, which significantly threatens the safety of flight. Thus, designers have formulated cockpit layout principles relating to importance, frequency of use, functional grouping, and operation sequence on the basis of ergonomics, which can effectively reduce the cognitive burden for pilots. The degree to which the cockpit layout of a model conforms to the four design principles can indicate its ergonomic design level. In accordance with the concepts of the above four cockpit layout principles, evaluation methods for determining their respective conformity to the four design principles were proposed in this paper. These methods use the operational sequence of cockpit system controls used in the normal flight mission of the actual aircraft type as the evaluation data source. Subsequently, the total evaluation results for cockpit layout were obtained using the weighted accumulation method. Lastly, the process for evaluating the cockpit layouts of civil aircraft was illustrated using the cockpits of the A320 series and B737NG series as examples. Based on the final evaluation results, the feasibility and effectiveness of the proposed evaluation method was verified

Conserved roles of C. elegans and human MANFs in sulfatide binding and cytoprotection.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER) protein that can be secreted and protects dopamine neurons and cardiomyocytes from ER stress and apoptosis. The mechanism of action of extracellular MANF has long been elusive. From a genetic screen for mutants with abnormal ER stress response, we identified the gene Y54G2A.23 as the evolutionarily conserved C. elegans MANF orthologue. We find that MANF binds to the lipid sulfatide, also known as 3-O-sulfogalactosylceramide present in serum and outer-cell membrane leaflets, directly in isolated forms and in reconstituted lipid micelles. Sulfatide binding promotes cellular MANF uptake and cytoprotection from hypoxia-induced cell death. Heightened ER stress responses of MANF-null C. elegans mutants and mammalian cells are alleviated by human MANF in a sulfatide-dependent manner. Our results demonstrate conserved roles of MANF in sulfatide binding and ER stress response, supporting sulfatide as a long-sought lipid mediator of MANF's cytoprotection

Effect of insemination method (IVF/ICSI) on SSR.

<p>SSR =  secondary sex ratio; IVF =  in vitro fertilization; ICSI =  intracytoplasmic sperm injection; CE =  cleavage stage embryo; BE =  blastocyst embryo.</p

Sex ratio of live birth offspring by different ART procedures and type of birth.

<p>IVF =  <i>in vitro</i> fertilization; ICSI =  intracytoplasmic sperm injection; ET =  embryo transfer; ART =  assisted reproductive technology; SSR =  secondary sex ratio.</p><p>*Insemination method was not clear in 10,365 cycles.</p><p>Sex ratio of live birth offspring by different ART procedures and type of birth.</p

Factors affecting SSR in ART babies by logistic regression analysis.

<p>**<i>P</i><0.001.</p><p>IVF =  <i>in vitro</i> fertilization; ICSI =  intracytoplasmic sperm injection; ET =  embryo transfer; OR =  odds ratio; CI =  confidence interval; ART =  assisted reproductive technology; SSR =  secondary sex ratio.</p><p>Factors affecting SSR in ART babies by logistic regression analysis.</p

Effect of type of birth (singleton/multiple delivery) on SSR.

<p>SSR =  secondary sex ratio; IVF =  in vitro fertilization; ICSI =  intracytoplasmic sperm injection; CE =  cleavage stage embryo; BE =  blastocyst embryo.</p