Symmetry breaking in the female germline cyst Nashchekin, D; Busby, L; Jakobs, M ...
Science (American Association for the Advancement of Science),
11/2021, Letnik:
374, Številka:
6569
Journal Article
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In mammals and flies, only one cell in a multicellular female germline cyst becomes an oocyte, but how symmetry is broken to select the oocyte is unknown. Here, we show that the microtubule (MT) ...minus end-stabilizing protein Patronin/CAMSAP marks the future
oocyte and is required for oocyte specification. The spectraplakin Shot recruits Patronin to the fusome, a branched structure extending into all cyst cells. Patronin stabilizes more MTs in the cell with the most fusome material. Our data suggest that this weak asymmetry is amplified by Dynein-dependent transport of Patronin-stabilized MTs. This forms a polarized MT network, along which Dynein transports oocyte determinants into the presumptive oocyte. Thus, Patronin amplifies a weak fusome anisotropy to break symmetry and select one cell to become the oocyte.
Polydimethylsiloxane (PDMS) elastomers are extensively used for soft lithographic replication of microstructures in microfluidic and micro-engineering applications. Elastomeric microstructures are ...commonly required to fulfil an explicit mechanical role and accordingly their mechanical properties can critically affect device performance. The mechanical properties of elastomers are known to vary with both curing and operational temperatures. However, even for the elastomer most commonly employed in microfluidic applications, Sylgard 184, only a very limited range of data exists regarding the variation in mechanical properties of bulk PDMS with curing temperature. We report an investigation of the variation in the mechanical properties of bulk Sylgard 184 with curing temperature, over the range 25 °C to 200 °C. PDMS samples for tensile and compressive testing were fabricated according to ASTM standards. Data obtained indicates variation in mechanical properties due to curing temperature for Young's modulus of 1.32-2.97 MPa, ultimate tensile strength of 3.51-7.65 MPa, compressive modulus of 117.8-186.9 MPa and ultimate compressive strength of 28.4-51.7 GPa in a range up to 40% strain and hardness of 44-54 ShA.
Antibiotic resistance is a global challenge that impacts all pharmaceutically used antibiotics. The origin of the genes associated with this resistance is of significant importance to our ...understanding of the evolution and dissemination of antibiotic resistance in pathogens. A growing body of evidence implicates environmental organisms as reservoirs of these resistance genes; however, the role of anthropogenic use of antibiotics in the emergence of these genes is controversial. We report a screen of a sample of the culturable microbiome of Lechuguilla Cave, New Mexico, in a region of the cave that has been isolated for over 4 million years. We report that, like surface microbes, these bacteria were highly resistant to antibiotics; some strains were resistant to 14 different commercially available antibiotics. Resistance was detected to a wide range of structurally different antibiotics including daptomycin, an antibiotic of last resort in the treatment of drug resistant Gram-positive pathogens. Enzyme-mediated mechanisms of resistance were also discovered for natural and semi-synthetic macrolide antibiotics via glycosylation and through a kinase-mediated phosphorylation mechanism. Sequencing of the genome of one of the resistant bacteria identified a macrolide kinase encoding gene and characterization of its product revealed it to be related to a known family of kinases circulating in modern drug resistant pathogens. The implications of this study are significant to our understanding of the prevalence of resistance, even in microbiomes isolated from human use of antibiotics. This supports a growing understanding that antibiotic resistance is natural, ancient, and hard wired in the microbial pangenome.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Predictions of the anisotropic magnetic susceptibility χ below the antiferromagnetic (AFM) ordering temperatures T(N) of local moment Heisenberg AFMs have been made previously using molecular field ...theory (MFT) but are very limited in their applicability. Here a MFT calculation of χ(T ≤ T(N)) is presented for a wide variety of collinear and noncollinear Heisenberg AFMs containing identical crystallographically equivalent spins without recourse to magnetic sublattices. The results are expressed in terms of directly measurable experimental parameters and are fitted with no adjustable parameters to experimental χ(T ≤ T(N)) data from the literature for several collinear and noncollinear AFMs. The influence of spin correlations and fluctuations beyond MFT is quantified by the deviation of the theory from the data. The origin of the universal χ(T ≤ T(N)) observed for triangular lattice AFMs exhibiting coplanar noncollinear 120° AFM ordering is clarified.
Circadian rhythms act to optimise many aspects of our biology and thereby ensure that physiological processes are occurring at the most appropriate time. The importance of this temporal control is ...demonstrated by the strong associations between circadian disruption, morbidity and disease pathology. There is now a wealth of evidence linking the circadian timing system to metabolic physiology and nutrition. Relationships between these processes are often reciprocal, such that the circadian system drives temporal changes in metabolic pathways and changes in metabolic/nutritional status alter core molecular components of circadian rhythms. Examples of metabolic rhythms include daily changes in glucose homeostasis, insulin sensitivity and postprandial response. Time of day alters lipid and glucose profiles following individual meals whereas, over a longer time scale, meal timing regulates adiposity and body weight; these changes may occur via the ability of timed feeding to synchronise local circadian rhythms in metabolically active tissues. Much of the work in this research field has utilised animal and cellular model systems. Although these studies are highly informative and persuasive, there is a largely unmet need to translate basic biological data to humans. The results of such translational studies may open up possibilities for using timed dietary manipulations to help restore circadian synchrony and downstream physiology. Given the large number of individuals with disrupted rhythms due to, for example, shift work, jet-lag, sleep disorders and blindness, such dietary manipulations could provide widespread improvements in health and also economic performance.
Rising seawater temperature and ocean acidification threaten the survival of coral reefs. The relationship between coral physiology and its microbiome may reveal why some corals are more resilient to ...these global change conditions. Here, we conducted the first experiment to simultaneously investigate changes in the coral microbiome and coral physiology in response to the dual stress of elevated seawater temperature and ocean acidification expected by the end of this century. Two species of corals, Acropora millepora containing the thermally sensitive endosymbiont C21a and Turbinaria reniformis containing the thermally tolerant endosymbiont Symbiodinium trenchi, were exposed to control (26.5°C and pCO2 of 364 μatm) and treatment (29.0°C and pCO2 of 750 μatm) conditions for 24 days, after which we measured the microbial community composition. These microbial findings were interpreted within the context of previously published physiological measurements from the exact same corals in this study (calcification, organic carbon flux, ratio of photosynthesis to respiration, photosystem II maximal efficiency, total lipids, soluble animal protein, soluble animal carbohydrates, soluble algal protein, soluble algal carbohydrate, biomass, endosymbiotic algal density, and chlorophyll a). Overall, dually stressed A. millepora had reduced microbial diversity, experienced large changes in microbial community composition, and experienced dramatic physiological declines in calcification, photosystem II maximal efficiency, and algal carbohydrates. In contrast, the dually stressed coral T. reniformis experienced a stable and more diverse microbiome community with minimal physiological decline, coupled with very high total energy reserves and particulate organic carbon release rates. Thus, the microbiome changed and microbial diversity decreased in the physiologically sensitive coral with the thermally sensitive endosymbiotic algae but not in the physiologically tolerant coral with the thermally tolerant endosymbiont. Our results confirm recent findings that temperature-stress tolerant corals have a more stable microbiome, and demonstrate for the first time that this is also the case under the dual stresses of ocean warming and acidification. We propose that coral with a stable microbiome are also more physiologically resilient and thus more likely to persist in the future, and shape the coral species diversity of future reef ecosystems.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The tumour-associated microbiota is an intrinsic component of the tumour microenvironment across human cancer types
. Intratumoral host-microbiota studies have so far largely relied on bulk tissue ...analysis
, which obscures the spatial distribution and localized effect of the microbiota within tumours. Here, by applying in situ spatial-profiling technologies
and single-cell RNA sequencing
to oral squamous cell carcinoma and colorectal cancer, we reveal spatial, cellular and molecular host-microbe interactions. We adapted 10x Visium spatial transcriptomics to determine the identity and in situ location of intratumoral microbial communities within patient tissues. Using GeoMx digital spatial profiling
, we show that bacterial communities populate microniches that are less vascularized, highly immuno‑suppressive and associated with malignant cells with lower levels of Ki-67 as compared to bacteria-negative tumour regions. We developed a single-cell RNA-sequencing method that we name INVADEseq (invasion-adhesion-directed expression sequencing) and, by applying this to patient tumours, identify cell-associated bacteria and the host cells with which they interact, as well as uncovering alterations in transcriptional pathways that are involved in inflammation, metastasis, cell dormancy and DNA repair. Through functional studies, we show that cancer cells that are infected with bacteria invade their surrounding environment as single cells and recruit myeloid cells to bacterial regions. Collectively, our data reveal that the distribution of the microbiota within a tumour is not random; instead, it is highly organized in microniches with immune and epithelial cell functions that promote cancer progression.
Overcoming primary or secondary endocrine resistance in breast cancer remains critical to further enhancing the benefit of existing therapies such as tamoxifen or an aromatase inhibitor (AI). Much ...progress has been made in understanding the molecular biology associated with secondary endocrine resistance. Cotargeting the estrogen receptor, together with various key intracellular proliferation and cell survival signaling pathways, has been explored as a strategy either to treat endocrine resistance once it develops in the second-line setting or to enhance first-line endocrine responsiveness by preventing secondary resistance from developing via blockade of specific pathways from the outset. While attempts to improve endocrine therapy by adding growth factor inhibitors have been disappointing, success resulting in new drug approvals has been seen in secondary endocrine resistance by treating patients with the mTOR antagonist everolimus in combination with the AI exemestane and, more recently, in the first-line setting, by the addition of the CDK 4/6 inhibitor palbociclib to the AI letrozole. Numerous other therapeutics are being evaluated in combination with endocrine therapies based on supportive preclinical evidence, including inhibitors of PI3K, Akt, HDAC, Src, IGFR-1, and FGFR. Appropriate clinical trial design and patient selection based on prior therapy exposure, together with predictive biomarkers derived through real-time molecular profiling, are needed to enrich future trials and maximize any additional benefit that cotargeting may bring to current endocrine therapies for estrogen receptor-positive breast cancer.
America has a long tradition of middle-class radicalism, albeit one that intellectual orthodoxy has tended to obscure.The Radical Middle Classseeks to uncover the democratic, populist, and even ...anticapitalist legacy of the middle class. By examining in particular the independent small business sector or petite bourgeoisie, using Progressive Era Portland, Oregon, as a case study, Robert Johnston shows that class still matters in America. But it matters only if the politics and culture of the leading player in affairs of class, the middle class, is dramatically reconceived.
This book is a powerful combination of intellectual, business, labor, medical, and, above all, political history. Its author also humanizes the middle class by describing the lives of four small business owners: Harry Lane, Will Daly, William U'Ren, and Lora Little. Lane was Portland's reform mayor before becoming one of only six senators to vote against U.S. entry into World War I. Daly was Oregon's most prominent labor leader and a onetime Socialist. U'Ren was the national architect of the direct democracy movement. Little was a leading antivaccinationist.
The Radical Middle Classfurther explores the Portland Ku Klux Klan and concludes with a national overview of the American middle class from the Progressive Era to the present. With its engaging narrative, conceptual richness, and daring argumentation, it will be welcomed by all who understand that reexamining the middle class can yield not only better scholarship but firmer grounds for democratic hope.
The circadian timing system governs daily biological rhythms, synchronising physiology and behaviour to the temporal world. External time cues, including the light‐dark cycle and timing of food ...intake, provide daily signals for entrainment of the central, master circadian clock in the hypothalamic suprachiasmatic nuclei (SCN), and of metabolic rhythms in peripheral tissues, respectively. Chrono‐nutrition is an emerging field building on the relationship between temporal eating patterns, circadian rhythms, and metabolic health. Evidence from both animal and human research demonstrates adverse metabolic consequences of circadian disruption. Conversely, a growing body of evidence indicates that aligning food intake to periods of the day when circadian rhythms in metabolic processes are optimised for nutrition may be effective for improving metabolic health. Circadian rhythms in glucose and lipid homeostasis, insulin responsiveness and sensitivity, energy expenditure, and postprandial metabolism, may favour eating patterns characterised by earlier temporal distribution of energy. This review details the molecular basis for metabolic clocks, the regulation of feeding behaviour, and the evidence for meal timing as an entraining signal for the circadian system in animal models. The epidemiology of temporal eating patterns in humans is examined, together with evidence from human intervention studies investigating the metabolic effects of morning compared to evening energy intake, and emerging chrono‐nutrition interventions such as time‐restricted feeding. Chrono‐nutrition may have therapeutic application for individuals with and at‐risk of metabolic disease and convey health benefits within the general population.
Chrono‐nutrition is the study of the relationship between temporal eating patterns, circadian rhythms, and metabolic health. Discordance between circadian rhythms and food intake may increase risk for metabolic disease. Timed feeding patterns may thus have implications for improving metabolic health. We provide a comprehensive review of chrono‐nutrition evidence from both animal and human models, including neural and molecular mechanisms of feeding behaviour, the epidemiology of meal patterns in humans, and evidence from interventions targeting timing of food intake for improving metabolic health.
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