Marine sediments from southeastern Brazilian continental shelf: A 1200 year record of upwelling productivity

A sediment core from the Cabo Frio coastal shelf (?23.19 S, ?41.8 W; 117 m depth), was analyzed for TOC, C/N ratio, organic petrography and planktonic foraminiferal content to evaluate variations in local productivity caused by changes in upwelling intensity and its relation to regional and global climatic variations during the last millennium. The Cabo Frio core recorded the last 1200 years of sedimentation, with rates varying from 0.11 to 0.32 mm yr^?1. Foraminiferal and organic geochemical analyses indicate the occurrence of three distinct periods of productivity. From 850 AD until 1070 AD, foraminifera fluxes consisting primarily of Turborotalita quinqueloba indicate stronger South Atlantic Central Water (SACW) transport onto the shelf, which induced high biological productivity that was also recorded by high TOC and marine palynomorphs content and a low C/N atomic ratio. This period coincided with a northward displacement of the atmospheric Intertropical Convergence Zone (ITCZ) and South Atlantic High (SAH) systems driven by positive temperature anomalies in the North Atlantic Ocean during the Medieval Climate Anomaly (MCA). From 1070 until 1500 AD, low TOC flux and planktonic foraminifera fluxes and high C/N atomic ratios suggest a reduction in marine productivity, probably driven by reduced transport of SACW associated with the southward displacement of the SAH and weakening of northeasterly winds. The period between 1500 and 1830 AD, which corresponds to the Little Ice Age, is marked by increased fluxes of planktonic foraminifera, principally of Globigerina bulloides and Globigerinita glutinata. These species mark an increase in productivity linked to SACW upwelling, supported by the enhancement of northeasterly winds and southward displacement of the ITCZ and SAH.     

Population regulation of territorial species: both site dependence and interference mechanisms matter

Spatial patterns of site occupancy are commonly driven by habitat heterogeneity and are thought to shape population dynamics through a site-dependent regulatory mechanism. When examining this, however, most studies have only focused on a single vital rate (reproduction), and little is known about how space effectively contributes to the regulation of population dynamics. We investigated the underlying mechanisms driving density-dependent processes in vital rates in a Mauritius kestrel population where almost every individual was monitored. Different mechanisms acted on different vital rates, with breeding success regulated by site dependence (differential use of space) and juvenile survival by interference (density-dependent competition for resources). Although territorial species are frequently assumed to be regulated through site dependence, we show that interference was the key regulatory mechanism in this population. Our integrated approach demonstrates that the presence of spatial processes regarding one trait does not mean that they necessarily play an important role in regulating population growth, and demonstrates the complexity of the regulatory process.     

Stereotactic ablative radiotherapy for oligometastatic prostate cancer

BackgroundThe present study assessed clinical outcomes of stereotactic body radiotherapy (SBRT) in oligometastatic prostate cancer patients.Materials and methodsBetween 2017 and 2020, 37 lesions (12 osseous and 25 nodal targets) detected with conventional and/or functional imaging, were treated in 29 patients (pts), in different clinical settings: de novo oligometastatic (2 pts), oligorecurrent castration-sensitive (19 pts), castration-resistant (6 pts) prostate cancers and oligoprogressive disease during systemic therapy (2 pts). SBRT was delivered with volumetric modulated arc therapy up to a total dose of 21 Gy given in 3 fractions for bone and 30 Gy in 5 fractions for nodal metastases. A total of 34% of pts received hormonal therapy. We evaluated biochemical control [prostate serum antigen (PSA) increase < 10%)], progression free-survival (PFS) (time from SBRT to biochemical progression), local control (LC) (time from SBRT to in-field radiologic progression), hormone/systemic therapy-free survival, acute and late toxicities.ResultsAt 3 months, biochemical response was observed in 20/29 pts (69%). At a median follow-up of 17 months (range 6–33), 8/20 (40%) of the 3-month responders remained free from progression. Two-year PFS and LC were 37% and 70%, respectively. In-field progression occurred in 3/37 (8%) lesions. Hormone/systemic therapy was delayed by an average of 11.6 months (range 3–28). No significant difference in PFS based on the type of lesion or concomitant endocrine therapy was observed and no toxicity > grade 2 was reported.ConclusionsSBRT for oligometastatic prostate cancer offers a good biochemical/local control and tangible delay of hormone/systemic therapy without major toxicities.     

Biosynthetic origins of the isoprene units of gaudichaudianic acid in Piper gaudichaudianum (Piperaceae)

The biosynthesis of (2S)-2-methyl-2-(4'-methyl-3'-pentenyl)-8-(3'-methyl-2-butenyl)-2H-1-benzopyran-6-carboxylic acid (gaudichaudianic acid), the major metabolite in leaves and roots of Piper gaudichaudianum Kunth (Piperaceae), has been investigated employing [1-(13)C]-D-glucose as precursor. The labelling pattern in the isolated gaudichaudianic acid was determined by quantitative (13)C NMR spectroscopy analysis and was consistent with involvement of both mevalonic acid and 2-C-methyl-D-erythritol-4-phosphate pathways in the formation of the dimethylallyl- and geranyl-derived moieties. The results confirmed that both plastidic and cytoplasmic pathways are able to provide isopentenyl diphosphate units for prenylation of p-hydroxybenzoic acid.     

Identification of CLEC12B, an inhibitory receptor on myeloid cells

Activation of immune cells has to be tightly controlled to prevent detrimental hyperactivation. In this regulatory process molecules of the C-type lectin-like family play a central role. Here we describe a new member of this family, CLEC12B. The extracellular domain of CLEC12B shows considerable homology to the activating natural killer cell receptor NKG2D, but unlike NKG2D, CLEC12B contains an immunoreceptor tyrosine-based inhibition motif in its intracellular domain. Despite the homology, CLEC12B does not appear to bind NKG2D ligands and therefore does not represent the inhibitory counterpart of NKG2D. However, CLEC12B has the ability to counteract NKG2D-mediated signaling, and we show that this function is dependent on the immunoreceptor tyrosine-based inhibition motif and the recruitment of the phosphatases SHP-1 and SHP-2. Using monoclonal anti-CLEC12B antibodies we found de novo expression of this receptor on in vitro generated human macrophages and on the human myelo-monocytic cell line U937 upon phorbol 12-myristate 13-acetate treatment, suggesting that this receptor plays a role in myeloid cell function.     

Multi-locus real-time PCR for quantitation of bacteria in the environment reveals Exiguobacterium to be prevalent in permafrost

We developed a multi-locus quantitative PCR approach to minimize problems of precision, sensitivity and primer specificity for quantifying a targeted microbial group in nature. This approach also avoids a systematic error in population quantitation when 16S rRNA genes are used because of copy number heterogeneity. Specific primers were designed to assess the abundance of psychrotrophic and mesophilic Exiguobacterium spp. that excluded the thermophilic members of the genus. The chosen primers targeted genes for DNA gyrase B (gyrB), the beta subunit of the RNA polymerase gene (rpoB) and a hypothetical gene so far found only in this group. The results demonstrate that the multiple primer approach provides a more reliable estimate of population density; that the targeted Exiguobacterium group is found at a median density of 50,000 gene copies per mug of total community DNA in 27 of 29 permafrost soils but was found in only one of the four temperate and tropical soils tested.     

Polyphenolic compounds from Artemisia dracunculus L. inhibit PEPCK gene expression and gluconeogenesis in an H4IIE hepatoma cell line

An ethanolic extract of Russian tarragon, Artemisia dracunculus L., with antihyperglycemic activity in animal models was reported to decrease phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression in STZ-induced diabetic rats. A quantitative polymerase chain reaction (qPCR) assay was developed for the bioactivity-guided purification of the compounds within the extract that decrease PEPCK expression. The assay was based on the inhibition of dexamethasone-stimulated PEPCK upregulation in an H4IIE hepatoma cell line. Two polyphenolic compounds that inhibited PEPCK mRNA levels were isolated and identified as 6-demethoxycapillarisin and 2',4'-dihydroxy-4-methoxydihydrochalcone with IC(50) values of 43 and 61 muM, respectively. The phosphoinositide-3 kinase (PI3K) inhibitor LY-294002 showed that 6-demethoxycapillarisin exerts its effect through the activation of the PI3K pathway, similarly to insulin. The effect of 2',4'-dihydroxy-4-methoxydihydrochalcone is not regulated by PI3K and dependent on activation of AMPK pathway. These results indicate that the isolated compounds may be responsible for much of the glucose-lowering activity of the Artemisia dracunculus extract.     

An intermediate structure in the thermal unfolding of the GTPase domain of human septin 4 (SEPT4/Bradeion-beta) forms amyloid-like filaments in vitro

SEPT4 is a member of the mammalian septin family of GTPases. Mammalian septins are conserved proteins which form heteropolymers in vivo and which are implicated in a variety of cellular functions such as cytokinesis, exocytosis, and vesicle trafficking. However, their structural properties and modes of action are largely unknown. There is a limited, but as yet inconclusive, amount of experimental data suggesting that SEPT4 may accumulate in tau-based filamentous deposits and cytoplasmic inclusions in Alzheimer's and Parkinson's disease, respectively. Here we report an intermediate structure of the GTPase domain of human SEPT4 (SEPT4-G) during unfolding transitions induced by temperature. This partially unfolded intermediate, which is rich in beta-sheet and free of bound nucleotide, was plagued by irreversible aggregation. The aggregates have the ability to bind specific dyes such as Congo red and thioflavin-T, suggesting they are amyloid in nature. Under electron microscopy, fibers of variable diameter extending for several micrometers in length can be visualized. This is the first report of amyloid formation by a septin or domain thereof, and the capacity of SEPT4-G to form such fibrillar aggregates may shed some light on the current discussion concerning the formation of homo- and heteropolymers of septins in vitro.