Terrestrial ecosystems often vary dramatically in their responses to drought, but the reasons for this are unclear. With climate change forecasts for more frequent and extensive drought in the ...future, a more complete understanding of the mechanisms that determine differential ecosystem sensitivity to drought is needed. In 2012, the Central US experienced the fourth largest drought in a century, with a regional-scale 40 % reduction in growing season precipitation affecting ecosystems ranging from desert grassland to mesic tallgrass prairie. This provided an opportunity to assess ecosystem sensitivity to a drought of common magnitude in six native grasslands. We tested the prediction that drought sensitivity is inversely related to mean annual precipitation (MAP) by quantifying reductions in aboveground net primary production (ANPP). Long-term ANPP data available for each site (mean length = 16 years) were used as a baseline for calculating reductions in ANPP, and drought sensitivity was estimated as the reduction in ANPP per millimeter reduction in precipitation. Arid grasslands were the most sensitive to drought, but drought responses and sensitivity varied by more than twofold among the six grasslands, despite all sites experiencing 40 % reductions in growing season precipitation. Although drought sensitivity generally decreased with increasing MAP as predicted, there was evidence that the identity and traits of the dominant species, as well as plant functional diversity, influenced sensitivity. A more comprehensive understanding of the mechanisms leading to differences in drought sensitivity will require multi-site manipulative experiments designed to assess both biotic and abiotic determinants of ecosystem sensitivity.
Most breast cancers are driven by a transcription factor called oestrogen receptor (ER). Understanding the mechanisms of ER activity in breast cancer has been a major research interest and recent ...genomic advances have revealed extraordinary insights into how ER mediates gene transcription and what occurs during endocrine resistance. This review discusses our current understanding on ER activity, with an emphasis on several evolving, but important areas of ER biology.
To update the mild traumatic brain injury (MTBI) prognosis review published by the World Health Organization Task Force in 2004.
MEDLINE, PsycINFO, Embase, CINAHL, and SPORTDiscus were searched from ...2001 to 2012. We included published, peer-reviewed studies with more than 30 adult cases.
Controlled trials and cohort and case-control studies were selected according to predefined criteria. Studies had to assess subjective, self-reported outcomes. After 77,914 titles and abstracts were screened, 299 articles were eligible and reviewed for scientific quality. This includes 3 original International Collaboration on MTBI Prognosis (ICoMP) research studies.
Eligible studies were critically appraised using the Scottish Intercollegiate Guidelines Network criteria. Two reviewers independently reviewed each study and tabled data from accepted articles. A third reviewer was consulted for disagreements.
Evidence from accepted studies was synthesized qualitatively into key findings, and prognostic information was prioritized according to design as exploratory or confirmatory. Of 299 reviewed studies, 101 (34%) were accepted and form our evidence base of prognostic studies. Of these, 23 addressed self-reported outcomes in adults, including 2 of the 3 original ICoMP research studies. These studies show that common postconcussion symptoms are not specific to MTBI/concussion and occur after other injuries as well. Poor recovery after MTBI is associated with poorer premorbid mental and physical health status and with more injury-related stress. Most recover over 1 year, but persistent symptoms are more likely in those with more acute symptoms and more emotional stress.
Common subjective symptoms after MTBI are not necessarily caused by brain injury per se, but they can be persistent in some patients. Those with more initial complaints and psychological distress recover slower. We need more high-quality research on these issues.
To synthesize the best available evidence on objective outcomes after adult mild traumatic brain injury (MTBI).
MEDLINE and other databases were searched (2001-2012) for studies related to MTBI. ...Inclusion criteria included published, peer-reviewed articles in English and other languages. References were also identified from the bibliographies of eligible articles.
Randomized controlled trials and cohort and case-control studies were selected according to predefined criteria. Studies had to have a minimum of 30 MTBI cases and assess objective outcomes in adults.
Eligible studies were critically appraised using a modification of the Scottish Intercollegiate Guidelines Network (SIGN) criteria. Two reviewers independently reviewed each study and extracted data from accepted articles into evidence tables.
Evidence was synthesized qualitatively according to modified SIGN criteria, and studies were categorized as exploratory or confirmatory based on the strength of their design and evidence. After 77,914 records were screened, 299 were found to be relevant and critically reviewed, and 101 were deemed scientifically admissible. Of these, 21 studies that were related to the objective outcomes form the basis of this review. Most evidence indicates the presence of cognitive deficits in the first 2 weeks post-MTBI, and some evidence suggests that complete recovery may take 6 months or a year. A small number of studies indicate that MTBI increases the risk of psychiatric illnesses and suicide.
Early cognitive deficits are common, and complete recovery may be prolonged. Conclusions about mortality post-MTBI are limited. This review has implications for expected recovery after MTBI and MTBI-related health sequelae. Well-designed confirmatory studies are needed to understand the medium- to long-term consequences of MTBI and to further evaluate the effect of prior MTBI and injury severity on recovery.
Cells generate unpaired electrons, typically via oxygen- or nitrogen-based by-products during normal cellular respiration and under stressed situations. These pro-oxidant molecules are highly ...unstable and may oxidize surrounding cellular macromolecules. Under normal conditions, the reactive oxygen or nitrogen species can be beneficial to cell survival and function by destroying and degrading pathogens or antigens. However, excessive generation and accumulation of the reactive pro-oxidant species over time can damage proteins, lipids, carbohydrates, and nucleic acids. Over time, this oxidative stress can contribute to a range of aging-related degenerative diseases such as cancer, diabetes, macular degeneration, and Alzheimer's, and Parkinson's diseases. It is well accepted that natural compounds, including vitamins A, C, and E, β-carotene, and minerals found in fruits and vegetables are powerful anti-oxidants that offer health benefits against several different oxidative stress induced degenerative diseases, including Alzheimer's disease (AD). There is increasing interest in developing anti-oxidative therapeutics to prevent AD. There are contradictory and inconsistent reports on the possible benefits of anti-oxidative supplements; however, fruits and vegetables enriched with multiple anti-oxidants (e.g., flavonoids and polyphenols) and minerals may be highly effective in attenuating the harmful effects of oxidative stress. As the physiological activation of either protective or destructive pro-oxidant behavior remains relatively unclear, it is not straightforward to relate the efficacy of dietary anti-oxidants in disease prevention. Here, we review oxidative stress mediated toxicity associated with AD and highlight the modulatory roles of natural dietary anti-oxidants in preventing AD.
Androgen receptor (AR) signaling exerts an antiestrogenic, growth-inhibitory influence in normal breast tissue, and this role may be sustained in estrogen receptor α (ERα)-positive luminal breast ...cancers. Conversely, AR signaling may promote growth of a subset of ERα-negative, AR-positive breast cancers with a molecular apocrine phenotype. Understanding the molecular mechanisms whereby androgens can elicit distinct gene expression programs and opposing proliferative responses in these two breast cancer phenotypes is critical to the development of new therapeutic strategies to target the AR in breast cancer.
Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) is a high-risk subtype characterized by genomic alterations that activate cytokine receptor and kinase signaling. We examined ...the frequency and spectrum of targetable genetic lesions in a retrospective cohort of 1389 consecutively diagnosed patients with childhood B-lineage ALL with high-risk clinical features and/or elevated minimal residual disease at the end of remission induction therapy. The Ph-like gene expression profile was identified in 341 of 1389 patients, 57 of whom were excluded from additional analyses because of the presence of BCR-ABL1 (n = 46) or ETV6-RUNX1 (n = 11). Among the remaining 284 patients (20.4%), overexpression and rearrangement of CRLF2 (IGH-CRLF2 or P2RY8-CRLF2) were identified in 124 (43.7%), with concomitant genomic alterations activating the JAK-STAT pathway (JAK1, JAK2, IL7R) identified in 63 patients (50.8% of those with CRLF2 rearrangement). Among the remaining patients, using reverse transcriptase polymerase chain reaction or transcriptome sequencing, we identified targetable ABL-class fusions (ABL1, ABL2, CSF1R, and PDGFRB) in 14.1%, EPOR rearrangements or JAK2 fusions in 8.8%, alterations activating other JAK-STAT signaling genes (IL7R, SH2B3, JAK1) in 6.3% or other kinases (FLT3, NTRK3, LYN) in 4.6%, and mutations involving the Ras pathway (KRAS, NRAS, NF1, PTPN11) in 6% of those with Ph-like ALL. We identified 8 new rearrangement partners for 4 kinase genes previously reported to be rearranged in Ph-like ALL. The current findings provide support for the precision-medicine testing and treatment approach for Ph-like ALL implemented in Children's Oncology Group ALL trials.
•Ph-like ALL is characterized by a diverse array of genetic alterations activating cytokine receptor and tyrosine kinase signaling.•Pediatric patients with Ph-like ALL can be identified in real time for effective treatment stratification.
This report compares biomimetic hydrogen evolution reaction catalysts with and without the amine cofactor (adtNH): Fe2(adtNH)(CO)2(dppv)2 (1 NH ) and Fe2(pdt)(CO)2(dppv)2 (2) (adtNH)2– = HN(CH2S)2 ...2–, pdt2– = 1,3-(CH2)3S2 2–, and dppv = cis-C2H2(PPh2)2. These compounds are spectroscopically, structurally, and stereodynamically very similar but exhibit very different catalytic properties. Protonation of 1 NH and 2 gives three isomeric hydrides each, beginning with the kinetically favored terminal hydride, which converts sequentially to sym and unsym isomers of the bridging hydrides. In the case of 1 NH , the corresponding ammonium hydrides are also observed. In the case of the terminal amine hydride t-H1 NH BF4, the ammonium/amine hydride equilibrium is sensitive to counteranions and solvent. The species t-H1 NH2 (BF4)2 represents the first example of a crystallographically characterized terminal hydride produced by protonation. The NH---HFe distance of 1.88(7) Å indicates dihydrogen-bonding. The bridging hydrides μ-H1 NH + and μ-H2+ reduce near −1.8 V, about 150 mV more negative than the reductions of the terminal hydride t-H1 NH + and t-H2+ at −1.65 V. Reductions of the amine hydrides t-H1 NH + and t-H1 NH2 2+ are irreversible. For the pdt analogue, the t-H2+/0 couple is unaffected by weak acids (pK a MeCN = 15.3) but exhibits catalysis with HBF4·Et2O, albeit with a turnover frequency (TOF) around 4 s–1 and an overpotential greater than 1 V. The voltammetry of t-H1 NH + is strongly affected by relatively weak acids and proceeds at 5000 s–1 with an overpotential of 0.7 V. The ammonium hydride t-H1 NH2 2+ is a faster catalyst, with an estimated TOF of 58 000 s–1 and an overpotential of 0.5 V.
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