Spatial and temporal variations of atmospheric CO 2 concentrations contain information about surface sources and sinks, which can be quantitatively interpreted through tracer transport inversion. Previous CO 2 inversion calculations obtained differing results due to different data, methods and transport models used. To isolate the sources of uncertainty, we have conducted a set of annual mean inversion experiments in which 17 different transport models or model variants were used to calculate regional carbon sources and sinks from the same data with a standardized method. Simulated transport is a significant source of uncertainty in these calculations, particularly in the response to prescribed "background" fluxes due to fossil fuel combustion, a balanced terrestrial biosphere, and air-sea gas exchange. Individual model-estimated fluxes are often a direct reflection of their response to these background fluxes. Models that generate strong surface maxima near background exchange locations tend to require larger uptake near those locations. Models with weak surface maxima tend to have less uptake in those same regions but may infer small sources downwind. In some cases, individual model flux estimates cannot be analyzed through simple relationships to background flux responses but are

Spermatogenesis generates mature male gametes and is critical for the proper transmission of genetic information between generations. However, the developmental landscapes of human spermatogenesis remain unknown. Here, we performed single-cell RNA sequencing (scRNA-seq) analysis for 2,854 testicular cells from donors with normal spermatogenesis and 174 testicular cells from one nonobstructive azoospermia (NOA) donor. A hierarchical model was established, which was characterized by the sequential and stepwise development of three spermatogonia subtypes, seven spermatocyte subtypes, and four spermatid subtypes. Further analysis identified several stage-specific marker genes of human germ cells, such as HMGA1, PIWIL4, TEX29, SCML1, and CCDC112. Moreover, we identified altered gene expression patterns in the testicular somatic cells of one NOA patient via scRNA-seq analysis, paving the way for further diagnosis of male infertility. Our work allows for the reconstruction of transcriptional programs inherent to sequential cell fate transition during human spermatogenesis and has implications for deciphering male-related reproductive disorders.

[1] Using an atmospheric inversion approach, we estimate methane surface emissions for different methane regional sources between 1996 and 2001. Data from 13 high-frequency and 79 low-frequency CH 4 observing sites have been averaged into monthly mean values with associated errors arising from instrumental precision, mismatch error, and sampling frequency. Simulated methane mole fractions are generated using the 3-D global chemical transport model (MATCH), driven by NCEP analyzed observed meteorology (T62 resolution), which accounts for the impact of synoptic and interannually varying transport on methane observations. We adapted the Kalman filter to optimally estimate methane flux magnitudes and uncertainties from seven seasonally varying (monthly varying flux) and two aseasonal sources (constant flux). We further tested the sensitivity of the inversion to different observing sites, filtered versus unfiltered observations, different model sampling strategies, and alternative emitting regions. Over the 1996-2001 period the inversion reduces energy emissions and increases rice and biomass burning emissions relative to the a priori emissions. The global seasonal emission peak is shifted from August to July because of increased rice and wetland emissions from southeast Asia. The inversion also attributes the large 1998 increase in atmospheric CH 4 to global wetland emissions. The current CH 4 observational network can significantly constrain northern emitting regions but not tropical emitting regions. Better estimates of global OH fluctuations are also necessary to fully describe interannual methane observations. This is evident in the inability of the optimized emissions to fully reproduce the observations at Samoa.

Neddylation, the covalent attachment of ubiquitin-like protein Nedd8, of the Cullin-RING E3 ligase family regulates their ubiquitylation activity. However, regulation of HECT ligases by neddylation has not been reported to date. Here we show that the C2-WW-HECT ligase Smurf1 is activated by neddylation. Smurf1 physically interacts with Nedd8 and Ubc12, forms a Nedd8-thioester intermediate, and then catalyses its own neddylation on multiple lysine residues. Intriguingly, this autoneddylation needs an active site at C426 in the HECT N-lobe. Neddylation of Smurf1 potently enhances ubiquitin E2 recruitment and augments the ubiquitin ligase activity of Smurf1. The regulatory role of neddylation is conserved in human Smurf1 and yeast Rsp5. Furthermore, in human colorectal cancers, the elevated expression of Smurf1, Nedd8, NAE1 and Ubc12 correlates with cancer progression and poor prognosis. These findings provide evidence that neddylation is important in HECT ubiquitin ligase activation and shed new light on the tumour-promoting role of Smurf1.

Campylobacter jejuni remains a major cause of bacterial diarrhea worldwide and is associated with numerous sequelae, including Guillain Barré Syndrome, inflammatory bowel disease, reactive arthritis, and irritable bowel syndrome. C. jejuni is unusual for an intestinal pathogen in its ability to coat its surface with a polysaccharide capsule (CPS). These capsular polysaccharides vary in sugar composition and linkage, especially those involving heptoses of unusual configuration and O-methyl phosphoramidate linkages. This structural diversity is consistent with CPS being the major serodeterminant of the Penner scheme, of which there are 47 C. jejuni serotypes. Both CPS expression and expression of modifications are subject to phase variation by slip strand mismatch repair. Although capsules are virulence factors for other pathogens, the role of CPS in C. jejuni disease has not been well defined beyond descriptive studies demonstrating a role in serum resistance and for diarrhea in a ferret model of disease. However, perhaps the most compelling evidence for a role in pathogenesis are data that CPS conjugate vaccines protect against diarrheal disease in non-human primates. A CPS conjugate vaccine approach against this pathogen is intriguing, but several questions need to be addressed, including the valency of CPS types required for an effective vaccine. There have been numerous studies of prevalence of CPS serotypes in the developed world, but few studies from developing countries where the disease incidence is higher. The complexity and cost of Penner serotyping has limited its usefulness, and a recently developed multiplex PCR method for determination of capsule type offers the potential of a more rapid and affordable method. Comparative studies have shown a strong correlation of the two methods and studies are beginning to ascertain CPS-type distribution worldwide, as well as examination of correlation of severity of illness with specific CPS types.

The formation of the complex network architecture of neural systems is subject to multiple structural and functional constraints. Two obvious but apparently contradictory constraints are low wiring cost and high processing efficiency, characterized by short overall wiring length and a small average number of processing steps, respectively. Growing evidence shows that neural networks are results from a trade-off between physical cost and functional value of the topology. However, the relationship between these competing constraints and complex topology is not well understood quantitatively. We explored this relationship systematically by reconstructing two known neural networks, Macaque cortical connectivity and C. elegans neuronal connections, from combinatory optimization of wiring cost and processing efficiency constraints, using a control parameter , and comparing the reconstructed networks to the real networks. We found that in both neural systems, the reconstructed networks derived from the two constraints can reveal some important relations between the spatial layout of nodes and the topological connectivity, and match several properties of the real networks. The reconstructed and real networks had a similar modular organization in a broad range of , resulting from spatial clustering of network nodes. Hubs emerged due to the competition of the two constraints, and their positions were close to, and partly coincided, with the real hubs in a range of values. The degree of nodes was correlated with the density of nodes in their spatial neighborhood in both reconstructed and real networks. Generally, the rebuilt network matched a significant portion of real links, especially short-distant ones. These findings provide clear evidence to support the hypothesis of trade-off between multiple constraints on brain networks. The two constraints of wiring cost and processing efficiency, however, cannot explain all salient features in the real networks. The discrepancy suggests that there are further relevant factors that are not yet captured here.

Many individuals with autism tend to focus on details. It has been suggested that this cognitive style may underlie the presence of stereotyped routines, repetitive interests and behaviours, and both relate in some way to sensory abnormalities. Twenty-nine children with diagnosis of high functioning autism or Asperger syndrome completed the Embedded Figures Test (EFT), and their parents the Short Sensory Profile and Childhood Routines Inventory. Significant correlations were found between degree of sensory abnormalities and amount of restricted and repetitive behaviours reported. Repetitive behaviours, age and IQ significantly predicted completion time on the EFT. The results suggest a cognitive link between an individual's detail-focused cognitive style and their repetitiveness. No such relationship was found with sensory processing abnormalities, which may arise at a more peripheral level of functioning.

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