Improving the quality of protein structure models by selecting from alignment alternatives

Background  

In the area of protein structure prediction, recently a lot of effort has gone into the development of Model Quality Assessment Programs (MQAPs). MQAPs distinguish high quality protein structure models from inferior models. Here, we propose a new method to use an MQAP to improve the quality of models. With a given target sequence and template structure, we construct a number of different alignments and corresponding models for the sequence. The quality of these models is scored with an MQAP and used to choose the most promising model. An SVM-based selection scheme is suggested for combining MQAP partial potentials, in order to optimize for improved model selection.     

FRASS: the web-server for RNA structural comparison

Background  

The impressive increase of novel RNA structures, during the past few years, demands automated methods for structure comparison. While many algorithms handle only small motifs, few techniques, developed in recent years, (ARTS, DIAL, SARA, SARSA, and LaJolla) are available for the structural comparison of large and intact RNA molecules.     

TGF-β modulates the functionality of tumor-infiltrating CD8<Superscript>+</Superscript> T cells through effects on TCR signaling and Spred1 expression

This study demonstrates that CD8⁺ T cells in the tumor microenvironment display reduced functionality and hyporesponsiveness. TGF-β contributed markedly to the tumor-infiltrating CD8⁺ T cells’ (TILs) reduced functionality, which could be reversed using a small molecule TGF-β inhibitor. Upon T-cell receptor (TCR) activation, the activation of ITK and ERK kinases were reduced in CD8⁺ TILs, as compared to splenic CD8⁺ T cells: TGF-β inhibitor could reverse this phenomenon. This study demonstrates for the first time the association of the Spred-1 gene, an inhibitor of the Ras/MAPK pathway, with CD8⁺ TILs and TGF-β activity. Spred-1 was upregulated in CD8⁺ TILs and TGF-β enhanced the expression of Spred-1 in effector/memory CD8⁺ T cells and not in rested/memory CD8⁺ T cells. Based on these findings, this study supports the hypothesis that TGF-β mediates an inhibitory mechanism on CD8⁺ TILs involving TCR-signaling blockade and the upregulation of Spred-1, thus implicating Spred-1 as a potential new target for future anti-tumor immune studies. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. M. G. di Bari and M. E. C. Lutsiak contributed equally to this work.     

Age,growth and reproductive life-history characteristics infer a high population productivity for the sustainably fished protogynous hermaphroditic yellowspotted rockcod (Epinephelus areolatus) in north-western Australia

The yellowspotted rockcod, Epinephelus areolatus, is a small-sized grouper that is widely distributed throughout the Indo-Pacific, where it forms a valuable component of the harvest derived from multispecies fisheries along continental and insular shelves. Samples of E. areolatus were collected from 2012 to 2018 from commercial catches and research surveys in the Kimberley, Pilbara and Gascoyne regions of north-western Australia to improve the understanding of the life history, inherent vulnerability and stock status of this species. Histological analysis of gonads (n = 1889) determined that E. areolatus was a monandric protogynous hermaphrodite. Non-functional spermatogenic crypts were dispersed within the ovaries of 23% of mature functioning females; nonetheless, these crypts were not observed during the immature female phase. The length and age at which 50% of females matured were 266 mm total length (L_T) and 2.7 years, respectively. The spawning period was protracted over 10–12 months of the year with biannual peaks at the start of spring and autumn (i.e., September and March) when the photoperiod was at its mid-range (i.e., 12.1 h). Estimates of the lengths and ages at which 50% of E. areolatus change sex from female to male were very similar (i.e., <5% difference) between the Kimberley and Pilbara regions, i.e., of 364 and 349 mm L_T and of 7.9 and 7.3 years, respectively. A maximum age of 19 years was observed in all three regions, but there was significant regional variation in growth. These variations in growth were not correlated with latitude; instead a parabolic relationship was evident, where the smallest mean length-at-age and fastest growth rates (k) occurred in the mid-latitudes of the Pilbara region. In the Kimberley and Pilbara regions, individuals were not fully selected by commercial fish traps until 5–6 years of age, hence, several years after reaching maturity. These life-history characteristics infer a high population productivity, which underpins the sustainable harvest of this species, despite comprising the largest catches of all epinephelids in the multispecies tropical fisheries across north-western Australia.     

Age estimation and otolith characteristics of an unusually old, red emperor snapper (Lutjanus sebae) captured off the Kimberley coast of north-western Australia

In October 2006, an unusually old, red emperor snapper, Lutjanus sebae , was captured using fish traps off the north coast of Western Australia. Despite being very old the specimen was not exceptionally large, measuring 516 mm fork length. Of particular note was the fact the specimen was female, as female L. sebae do not attain the large sizes at age of male fish. Interpretation of the sectioned sagittal otolith was used to estimate an age of approximately 40 years. This is the oldest recorded age for an individual L. sebae and further contributes towards the knowledge of the demography of this species. The advanced age recorded for this specimen also confirms the low rates of natural mortality for L. sebae and therefore low population productivity and supports the precautionary management arrangements for this species in north-western Australia.     

Longitudinal study of outcome of chronic fatigue syndrome.

OBJECTIVE--To examine the predictors of long term outcome for patients with the chronic fatigue syndrome. DESIGN--Cohort study. SUBJECTS--139 subjects previously enrolled in two treatment trials; 103 (74%) were reassessed a mean of 3.2 years after start of the trials. SETTING--University hospital referral centre. MAIN OUTCOME MEASURES--Age at onset, duration of illness, psychological and immunological status at initial assessment. Ongoing symptom severity, levels of disability, and immunological function at follow up. RESULTS--65 subjects had improved but only six reported no current symptoms. An alternative medical diagnosis had been made in two and psychiatric illness diagnosed in 20. The assignment of a primary psychiatric diagnosis at follow up and the strength of the belief that a physical disease process explained all symptoms at entry to the trials both predicted poor outcome. Age at onset of illness, duration of illness, neuroticism, premorbid psychiatric diagnoses, and cell mediated immune function did not predict outcome. CONCLUSION--Though most patients with the chronic fatigue syndrome improve, a substantial proportion remain functionally impaired. Psychological factors such as illness attitudes and coping style seem more important predictors of long term outcome than immunological or demographic variables.