Pluripotent stem cells (PSCs) are highly proliferative cells characterized by robust metabolic demands to power rapid division. For many years considered a passive component or “passenger” of ...cell-fate determination, cell metabolism is now starting to take center stage as a driver of cell fate outcomes. This review provides an update and analysis of our current understanding of PSC metabolism and its role in self-renewal, differentiation, and somatic cell reprogramming to pluripotency. Moreover, we present evidence on the active roles metabolism plays in shaping the epigenome to influence patterns of gene expression that may model key features of early embryonic development.
•Partial volume effects influence studies of brain perfusion.•Systematic and random effects on perfusion can occur within and between groups.•Partial volume correction strategies are available, but ...underused.
The mismatch in the spatial resolution of Arterial Spin Labeling (ASL) MRI perfusion images and the anatomy of functionally distinct tissues in the brain leads to a partial volume effect (PVE), which in turn confounds the estimation of perfusion into a specific tissue of interest such as gray or white matter. This confound occurs because the image voxels contain a mixture of tissues with disparate perfusion properties, leading to estimated perfusion values that reflect primarily the volume proportions of tissues in the voxel rather than the perfusion of any particular tissue of interest within that volume. It is already recognized that PVE influences studies of brain perfusion, and that its effect might be even more evident in studies where changes in perfusion are co-incident with alterations in brain structure, such as studies involving a comparison between an atrophic patient population vs control subjects, or studies comparing subjects over a wide range of ages. However, the application of PVE correction (PVEc) is currently limited and the employed methodologies remain inconsistent.
In this article, we outline the influence of PVE in ASL measurements of perfusion, explain the main principles of PVEc, and provide a critique of the current state of the art for the use of such methods. Furthermore, we examine the current use of PVEc in perfusion studies and whether there is evidence to support its wider adoption.
We conclude that there is sound theoretical motivation for the use of PVEc alongside conventional, ‘uncorrected’, images, and encourage such combined reporting. Methods for PVEc are now available within standard neuroimaging toolboxes, which makes our recommendation straightforward to implement. However, there is still more work to be done to establish the value of PVEc as well as the efficacy and robustness of existing PVEc methods.
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Southern Hemisphere humpback whales (Megaptera novaeangliae) generally undertake annual migrations from polar summer feeding grounds to winter calving and nursery grounds in subtropical and tropical ...coastal waters. Evidence for such migrations arises from seasonality of historic whaling catches by latitude, Discovery and natural mark returns, and results of satellite tagging studies. Feeding is generally believed to be limited to the southern polar region, where Antarctic krill (Euphausia superba) has been identified as the primary prey item. Non-migrations and / or suspended migrations to the polar feeding grounds have previously been reported from a summer presence of whales in the Benguela System, where feeding on euphausiids (E. lucens), hyperiid amphipods (Themisto gaudichaudii), mantis shrimp (Pterygosquilla armata capensis) and clupeid fish has been described. Three recent research cruises (in October/November 2011, October/November 2014 and October/November 2015) identified large tightly-spaced groups (20 to 200 individuals) of feeding humpback whales aggregated over at least a one-month period across a 220 nautical mile region of the southern Benguela System. Feeding behaviour was identified by lunges, strong milling and repetitive and consecutive diving behaviours, associated bird and seal feeding, defecations and the pungent "fishy" smell of whale blows. Although no dedicated prey sampling could be carried out within the tightly spaced feeding aggregations, observations of E. lucens in the region of groups and the full stomach contents of mantis shrimp from both a co-occurring predatory fish species (Thyrsites atun) and one entangled humpback whale mortality suggest these may be the primary prey items of at least some of the feeding aggregations. Reasons for this recent novel behaviour pattern remain speculative, but may relate to increasing summer humpback whale abundance in the region. These novel, predictable, inter-annual, low latitude feeding events provide considerable potential for further investigation of Southern Hemisphere humpback feeding behaviours in these relatively accessible low-latitude waters.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Formal planning and development of what became the first Landsat satellite commenced over 50 years ago in 1967. Now, having collected earth observation data for well over four decades since the 1972 ...launch of Landsat-1, the Landsat program is increasingly complex and vibrant. Critical programmatic elements are ensuring the continuity of high quality measurements for scientific and operational investigations, including ground systems, acquisition planning, data archiving and management, and provision of analysis ready data products. Free and open access to archival and new imagery has resulted in a myriad of innovative applications and novel scientific insights. The planning of future compatible satellites in the Landsat series, which maintain continuity while incorporating technological advancements, has resulted in an increased operational use of Landsat data. Governments and international agencies, among others, can now build an expectation of Landsat data into a given operational data stream. International programs and conventions (e.g., deforestation monitoring, climate change mitigation) are empowered by access to systematically collected and calibrated data with expected future continuity further contributing to the existing multi-decadal record. The increased breadth and depth of Landsat science and applications have accelerated following the launch of Landsat-8, with significant improvements in data quality.
Herein, we describe the programmatic developments and institutional context for the Landsat program and the unique ability of Landsat to meet the needs of national and international programs. We then present the key trends in Landsat science that underpin many of the recent scientific and application developments and follow-up with more detailed thematically organized summaries. The historical context offered by archival imagery combined with new imagery allows for the development of time series algorithms that can produce information on trends and dynamics. Landsat-8 has figured prominently in these recent developments, as has the improved understanding and calibration of historical data. Following the communication of the state of Landsat science, an outlook for future launches and envisioned programmatic developments are presented. Increased linkages between satellite programs are also made possible through an expectation of future mission continuity, such as developing a virtual constellation with Sentinel-2. Successful science and applications developments create a positive feedback loop—justifying and encouraging current and future programmatic support for Landsat.
•Landsat program approaching 50 years of continuous global data collection.•Landsat-8 successfully on-orbit; Landsat-9 under development; Landsat-10 being scoped.•Open data has accelerated science and application developments.•Value of calibrated data shown for science, applications, and towards virtual constellations.•Time series analysis of Landsat offering new insights on earth system and human activity.
Biological pretreatment of lignocellulosic biomass by white-rot fungus can represent a low-cost and eco-friendly alternative to harsh physical, chemical or physico-chemical pretreatment methods to ...facilitate enzymatic hydrolysis. However, fungal pretreatment can cause carbohydrate loss and it is, therefore, necessary to use the appropriate fungal strain-biomass type combination. In this work, 26 white-rot fungal strains were evaluated under solid state cultivation at 74% moisture level at 28 °C for 30 days for fermentable sugar production from corn stover after enzymatic hydrolysis of each fungal pretreated corn stover using a cocktail of 3 commercial enzyme (cellulase, β-glucosidase, hemicellulase) preparations. The best result was obtained with Cyathus stercoreus NRRL-6573 which gave a sugar yield of 394 ± 13 mg/g of pretreated stover followed by Pycnoporus sanguineus FP-10356-Sp (393 ± 17 mg/g) and Phlebia brevispora NRRL-13108 (383 ± 13 mg/g).
•White-rot fungal pretreatment increased the enzymatic hydrolysis of corn stover.•Appropriate fungal strain selection is important for a specific biomass pretreatment.•Fungal pretreatment caused carbohydrate loss in addition to lignin loss.•Delignification ability of white-rot fungal strains varied widely among species.
The physiological changes that occur immediately following cancer surgeries initiate a chain of events that ultimately result in a short pro-, followed by a prolonged anti-, inflammatory period. ...Natural Killer (NK) cells are severely affected during this period in the recovering cancer patient. NK cells play a crucial role in anti-tumour immunity because of their innate ability to differentiate between malignant versus normal cells. Therefore, an opportunity arises in the aftermath of cancer surgery for residual cancer cells, including distant metastases, to gain a foothold in the absence of NK cell surveillance. Here, we describe the post-operative environment and how the release of sympathetic stress-related factors (e.g., cortisol, prostaglandins, catecholamines), anti-inflammatory cytokines (e.g., IL-6, TGF-β), and myeloid derived suppressor cells, mediate NK cell dysfunction. A snapshot of current and recently completed clinical trials specifically addressing NK cell dysfunction post-surgery is also discussed. In collecting and summarizing results from these different aspects of the surgical stress response, a comprehensive view of the NK cell suppressive effects of surgery is presented. Peri-operative therapies to mitigate NK cell suppression in the post-operative period could improve curative outcomes following cancer surgery.
Antiretroviral therapy is highly effective in suppressing human immunodeficiency virus (HIV)
. However, eradication of the virus in individuals with HIV has not been possible to date
. Given that HIV ...suppression requires life-long antiretroviral therapy, predominantly on a daily basis, there is a need to develop clinically effective alternatives that use long-acting antiviral agents to inhibit viral replication
. Here we report the results of a two-component clinical trial involving the passive transfer of two HIV-specific broadly neutralizing monoclonal antibodies, 3BNC117 and 10-1074. The first component was a randomized, double-blind, placebo-controlled trial that enrolled participants who initiated antiretroviral therapy during the acute/early phase of HIV infection. The second component was an open-label single-arm trial that enrolled individuals with viraemic control who were naive to antiretroviral therapy. Up to 8 infusions of 3BNC117 and 10-1074, administered over a period of 24 weeks, were well tolerated without any serious adverse events related to the infusions. Compared with the placebo, the combination broadly neutralizing monoclonal antibodies maintained complete suppression of plasma viraemia (for up to 43 weeks) after analytical treatment interruption, provided that no antibody-resistant HIV was detected at the baseline in the study participants. Similarly, potent HIV suppression was seen in the antiretroviral-therapy-naive study participants with viraemia carrying sensitive virus at the baseline. Our data demonstrate that combination therapy with broadly neutralizing monoclonal antibodies can provide long-term virological suppression without antiretroviral therapy in individuals with HIV, and our experience offers guidance for future clinical trials involving next-generation antibodies with long half-lives.
Nostoc sp. PCC 7120 are filamentous cyanobacteria capable of both oxygenic photosynthesis and nitrogen fixation, with the latter taking place in specialized cells known as heterocysts that terminally ...differentiate from vegetative cells under conditions of nitrogen starvation. Cyanobacteria have existed on earth for more than 2 billion years and are thought to be responsible for oxygenation of the earth's atmosphere. Filamentous cyanobacteria such as Nostoc sp. PCC 7120 may also represent the oldest multicellular organisms on earth that undergo cell differentiation. Pentapeptide repeat proteins (PRPs), which occur most abundantly in cyanobacteria, adopt a right‐handed quadrilateral β‐helical structure, also referred to as a repeat five residue (Rfr) fold, with four‐consecutive pentapeptide repeats constituting a single coil in the β‐helical structure. PRPs are predicted to exist in all compartments within cyanobacteria including the thylakoid and cell‐wall membranes as well as the cytoplasm and thylakoid periplasmic space. Despite their intriguing structure and importance to understanding ancient cyanobacteria, the biochemical function of PRPs in cyanobacteria remains largely unknown. Here we report the crystal structure of Alr1298, a PRP from Nostoc sp. PCC 7120 predicted to reside in the cytoplasm. The structure displays the typical right‐handed quadrilateral β‐helical structure and includes a four‐α‐helix cluster capping the N‐terminus and a single α‐helix capping the C‐terminus. A gene cluster analysis indicated that Alr1298 may belong to an operon linked to cell proliferation and/or thylakoid biogenesis. Elevated alr1298 gene expression following nitrogen starvation indicates that Alr1298 may play a role in response to nitrogen starvation and/or heterocyst differentiation.
Initial cell attachment of rotavirus (RV) to specific cell surface glycan receptors, which is the essential first step in RV infection, is mediated by the VP8* domain of the spike protein VP4. ...Recently, human histo-blood group antigens (HBGAs) have been identified as receptors or attachment factors for human RV strains. RV strains in the P4 and P8 genotypes of the PII genogroup share common recognition of the Lewis b (Leb) and H type 1 antigens, however, the molecular basis of receptor recognition by the major human P8 RVs remains unknown due to lack of experimental structural information. Here, we used nuclear magnetic resonance (NMR) spectroscopy-based titration experiments and NMR-derived high ambiguity driven docking (HADDOCK) methods to elucidate the molecular basis for P8 VP8* recognition of the Leb (LNDFH I) and type 1 HBGAs. We also used X-ray crystallography to determine the molecular details underlying P6 recognition of H type 1 HBGAs. Unlike P6/P19 VP8*s that recognize H type 1 HBGAs in a binding surface composed of an α-helix and a β-sheet, referred as the "βα binding site", the P8 and P4 VP8*s bind Leb HBGAs in a previously undescribed pocket formed by the edges of two β-sheets, referred to as the "ββ binding site". Importantly, the P8 and P4 VP8*s retain binding capability to non-Leb type 1 HBGAs using the βα binding site. The presence of two distinct binding sites for Leb and non-Leb HBGA glycans in the P8 and P4 VP8* domains suggests host-pathogen co-evolution under structural and functional adaptation of RV pathogens to host glycan polymorphisms. Assessment and understanding of the precise impact of this co-evolutionary process in determining RV host ranges and cross-species RV transmission should facilitate improved RV vaccine development and prediction of future RV strain emergence and epidemics.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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![Molecular basis of P[II] ma...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1553-7374_1553-7366/small "Molecular basis of P[II] major human rotavirus VP8 domain recognition of histo-blood group antigens")