The warmest water reaching the east and west coast of Greenland is found between 200 and 600 m. While important for melting Greenland's outlet glaciers, limited winter observations of this layer ...prohibit determination of its seasonality. To address this, temperature data from Argo profiling floats, a range of sources within the World Ocean Database, and unprecedented coverage from marine‐mammal borne sensors have been analyzed for the period 2002–2011. A significant seasonal range in temperature (~1‐2°C) is found in the warm layer, in contrast to most of the surrounding ocean. The phase of the seasonal cycle exhibits considerable spatial variability, with the warmest water found near the eastern and southwestern shelf break toward the end of the calendar year. High‐resolution ocean model trajectory analysis suggests the timing of the arrival of the year's warmest water is a function of advection time from the subduction site in the Irminger Basin.
Key Points
Seasonal temperature cycle found in the subsurface warm layer around GreenlandThere is a distinctive spatial variability to the phase of the seasonal cyclePhase of seasonal cycle related to water's travel time from the Irminger Sea
During flagellum assembly by motile enterobacteria, flagellar axial proteins destined for polymerization into the cell surface structure are thought to be exported through the 25–30 Å flagellum ...central channel as partially unfolded monomers. How are premature folding and oligomerization in the cytosol prevented? We have shown previously using hyperflagellated Proteus mirabilis and a motile but non‐swarming flgN transposon mutant that the apparently cytosolic 16.5 kDa flagellar protein FlgN facilitates efficient flagellum filament assembly. Here, we investigate further whether FlgN, predicted to contain a C‐terminal amphipathic helix typical of type III export chaperones, acts as a chaperone for axial proteins. Incubation of soluble radiolabelled FlgN from Salmonella typhimurium with nitrocellulose‐immobilized cell lysates of wild‐type S. typhimurium and a non‐flagellate class 1 flhDC mutant indicated that FlgN binds to flagellar proteins. Identical affinity blot analysis of culture supernatants from the wild‐type and flhDC, flgI, flgK, flgL, fliC or fliD flagellar mutants showed that FlgN binds to the flagellar hook‐associated proteins (HAPs) FlgK and FlgL. This was confirmed by blotting artificially expressed individual HAPs in Escherichia coli. Analysis of axial proteins secreted into the culture medium by the original P. mirabilis flgN mutant demonstrated that export of FlgK and FlgL was specifically reduced, with concomitant increased release of unpolymerized flagellin (FliC), the immediately distal component of the flagellum. These data suggest that FlgN functions as an export chaperone for FlgK and FlgL. Parallel experiments showed that FliT, a similarly small (14 kDa), potentially helical flagellar protein, binds specifically to the flagellar filament cap protein, FliD (HAP2), indicating that it too might be an export chaperone. Flagellar axial proteins all contain amphipathic helices at their termini. Removal of the HAP C‐terminal helical domains abolished binding by FlgN and FliT in each case, and polypeptides comprising each of the HAP C‐termini were specifically bound by FlgN and FliT. We suggest that FlgN and FliT are substrate‐specific flagellar chaperones that prevent oligomerization of the HAPs by binding to their helical domains before export.
We have mapped in vitro nucleosome positioning on the sheep β-lactoglobulin gene using high-throughput sequencing to characterise the DNA sequences recovered from reconstituted nucleosomes. This ...methodology surpasses previous approaches for coverage, accuracy and resolution and, most importantly, offers a simple yet rapid and relatively inexpensive method to characterise genomic DNA sequences in terms of nucleosome positioning capacity. We demonstrate an unambiguous correspondence between in vitro and in vivo nucleosome positioning around the promoter of the gene; identify discrete, sequence-specific nucleosomal structures above the level of the canonical core particle—a feature that has implications for regulatory protein access and higher-order chromatin packing; and reveal new insights into the involvement of periodically organised dinucleotide sequence motifs of the type GG and CC and not AA and TT, as determinants of nucleosome positioning—an observation that supports the idea that the core histone octamer can exploit different patterns of sequence organisation, or structural potential, in the DNA to bring about nucleosome positioning.
Auger-ionized free-carriers in a one-dimensional semiconductor are predicted to result in a strong band-gap renormalization. Isolated single-walled carbon nanotubes (SWCNT) under high-intensity laser ...irradiation exhibit strong nonlinear photoluminescence (PL) due to exciton-exciton annihilation (EEA). The presence of exciton disassociation during the rapid Auger-ionization caused by EEA would lead to a strong nonlinear absorption. By simultaneously measuring SWCNT-PL and optical absorption of isolated SWCNT clusters in the PL saturation regime, we give evidence that Auger-ionized excitons do not disassociate but remain bound.
A review, outlining the origins and subsequent development of the triketone class of herbicidal 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors.
A review, outlining the origins and subsequent ...development of the triketone class of herbicidal 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors.
Dysregulated apoptosis plays a critical role in the development of a number of aberrant cellular processes, including tumorigenesis and chemoresistance. However, the mechanisms that govern the normal ...apoptotic program are not completely understood. Soluble guanylyl cyclase (sGC) and cyclic guanosine monophosphate (cGMP) promote mammalian cell viability via an unknown mechanism and p53 status is a key determinant of cell fate in human ovarian cancer cells. Whether an interaction exists between these two determinants of cell fate is unknown. We hypothesized that basal sGC activity reduces p53 content and attenuates p53-dependent apoptosis in human ovarian cancer cells. Suppression of sGC activity with the specific inhibitor 1H-1,2,4oxadiazolo4,3-aquinoxalin-1-one (ODQ) lowered cGMP content, and increased p53 protein content and induced apoptosis in three ovarian cancer cell lines, effects which were attenuated by the cGMP analog 8-Br-cGMP and by Atrial Natriuretic Factor, an activator of particulate guanylyl cyclase, which circumvent the inhibition of sGC. ODQ prolonged p53 half-life, induced phosphorylation of p53 on Ser15, and upregulated the p53-dependent gene products p21, murine double minute-2, and the proapoptotic, p53-responsive gene product Bax. ODQ activated caspase-3, and ODQ-induced apoptosis was inhibited by overexpression of X-linked inhibitor of apoptosis Protein. Pretreatment with the specific p53 inhibitor pifithrin or downregulation of p53 using a specific small inhibitory RNA significantly attenuated ODQ-induced apoptosis. Moreover, ODQ-induced upregulation of p21 and Bax and ODQ-induced apoptosis were significantly reduced in a p53 mutant cell line relative to the wild-type parental cell line. Thus, the current study establishes that basal sGC/cGMP activity regulates p53 protein stability, content, and function, possibly by altering p53 phosphorylation and stabilization, and promotes cell survival in part through regulation of caspase-3 and p53.
Purpose of Review
Sexual offending perpetrated by women has historically been overlooked and understudied, and the potentially unique impact of that abuse is even more so.
Recent Findings
Women who ...have sexually offended against children typically do so against older boys, use little or no forms of force or coercion during the abuse, and are unlikely to be prosecuted or sentenced following the abuse. Boys whom women have sexually abused are unlikely to report or disclose the abuse that they have experienced, perhaps because social structures surrounding sexual abuse of boys by women are designed to minimize, excuse, or even encourage such sexual contact. The intersection of these unique features may help understand the role of childhood sexual abuse perpetrated by women in subsequent sexual offending among adult men.
Summary
Men who have sexually offended experience high rates of childhood sexual abuse perpetrated by women. The relationship between experienced sexual abuse and subsequent perpetration of sexual abuse is neither linear nor causal; however, the characteristics associated with this form of abuse, such as non-disclosure and lack of sentencing, may contribute to adulthood sexual maladjustment and vulnerability to offending among men.
We have investigated the molecular interactions underlying neural crest formation in Xenopus. Using chordin overexpression to antagonize endogenous BMP signaling in whole embryos and explants, we ...demonstrate that such inhibition alone is insufficient to account for neural crest induction in vivo. We find, however, that chordin-induced neural plate tissue can be induced to adopt neural crest fates by members of the FGF and Wnt families, growth factors that have previously been shown to posteriorize induced neural tissue. Overexpression of a dominant negative XWnt-8 inhibits the expression of neural crest markers, demonstrating the necessity for a Wnt signal during neural crest induction in vivo. The requirement for Wnt signaling during neural crest induction is shown to be direct, whereas FGF-mediated neural crest induction may be mediated by Wnt signals. Overexpression of the zinc finger transcription factor Slug, one of the earliest markers of neural crest formation, is insufficient for neural crest induction. Slug-expressing ectoderm will generate neural crest in the presence of Wnt or FGF-like signals, however, bypassing the need for BMP inhibition in this process. A two-step model for neural crest induction is proposed.
New Findings
What is the topic of this review?
The Zucker Diabetic‐Sprague Dawley (ZDSD) rat is in the early adoption phase of use by researchers in the fields of diabetes, including prediabetes, ...obesity and metabolic syndrome. It is essential that physiology researchers choose preclinical models that model human type 2 diabetes appropriately and are aware of the limitations on experimental design.
What advances does it highlight?
Our review of the scientific literature finds that although sex, age and diets contribute to variability, the ZDSD phenotype and disease progression model the characteristics of humans who have prediabetes and diabetes, including co‐morbidities.
Type 2 diabetes (T2D) is a prevalent disease and a significant concern for global population health. For persons with T2D, clinical treatments target not only the characteristics of hyperglycaemia and insulin resistance, but also co‐morbidities, such as obesity, cardiovascular and renal disease, neuropathies and skeletal bone conditions. The Zucker Diabetic‐Sprague Dawley (ZDSD) rat is a rodent model developed for experimental studies of T2D. We reviewed the scientific literature to highlight the characteristics of T2D development and the associated phenotypes, such as metabolic syndrome, cardiovascular complications and bone and skeletal pathologies in ZDSD rats. We found that ZDSD phenotype characteristics are independent of leptin receptor signalling. The ZDSD rat develops prediabetes, then progresses to overt diabetes that is accelerated by introduction of a timed high‐fat diet. In male ZDSD rats, glycated haemoglobin (HbA1c) increases at a constant rate from 7 to >30 weeks of age. Diabetic ZDSD rats are moderately hypertensive compared with other rat strains. Diabetes in ZDSD rats leads to endothelial dysfunction in specific vasculatures, impaired wound healing, decreased systolic and diastolic cardiac function, neuropathy and nephropathy. Changes to bone composition and the skeleton increase the risk of bone fractures. Zucker Diabetic‐Sprague Dawley rats have not yet achieved widespread use by researchers. We highlight sex‐related differences in the ZDSD phenotype and gaps in knowledge for future studies. Overall, scientific data support the premise that the phenotype and disease progression in ZDSD rats models the characteristics in humans. We conclude that ZDSD rats are an advantageous model to advance understanding and discovery of treatments for T2D through preclinical research.
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