Understanding the relative importance of top-down and bottom-up regulation of ecosystem structure is a fundamental ecological question, with implications for fisheries and water-quality management. ...For the Laurentian Great Lakes, where, since the early 1970s, nutrient inputs have been reduced, whereas top-predator biomass has increased, we describe trends across multiple trophic levels and explore their underlying drivers. Our analyses revealed increasing water clarity and declines in phytoplankton, native invertebrates, and prey fish since 1998 in at least three of the five lakes. Evidence for bottom-up regulation was strongest in Lake Huron, although each lake provided support in at least one pair of trophic levels. Evidence for top-down regulation was rare. Although nonindigenous dreissenid mussels probably have large impacts on nutrient cycling and phytoplankton, their effects on higher trophic levels remain uncertain. We highlight gaps for which monitoring and knowledge should improve the understanding of food-web dynamics and facilitate the implementation of ecosystem-based management.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Medulloblastoma is the most common pediatric malignant brain tumor. Although current therapies improve survival, these regimens are highly toxic and are associated with significant morbidity. Here, ...we report that placental growth factor (PlGF) is expressed in the majority of medulloblastomas, independent of their subtype. Moreover, high expression of PlGF receptor neuropilin 1 (Nrp1) correlates with poor overall survival in patients. We demonstrate that PlGF and Nrp1 are required for the growth and spread of medulloblastoma: PlGF/Nrp1 blockade results in direct antitumor effects in vivo, resulting in medulloblastoma regression, decreased metastasis, and increased mouse survival. We reveal that PlGF is produced in the cerebellar stroma via tumor-derived Sonic hedgehog (Shh) and show that PlGF acts through Nrp1—and not vascular endothelial growth factor receptor 1—to promote tumor cell survival. This critical tumor-stroma interaction—mediated by Shh, PlGF, and Nrp1 across medulloblastoma subtypes—supports the development of therapies targeting PlGF/Nrp1 pathway.
Display omitted
► PlGF is expressed in medulloblastomas, regardless of their genetic subtype ► The majority of PlGF protein is secreted by cerebellar stromal cells ► Stromal PlGF production is stimulated by paracrine Shh secretion from cancer cells ► Targeting PlGF/Nrp1 pathway suppresses growth and spread of medulloblastoma
Placental growth factor (PlGF) and its receptor neuropilin 1 are required for the growth of medulloblastoma, the most common malignant brain tumor in children. Experiments in mice suggest that inhibition of PlGF or neuropilin may be an effective therapeutic strategy for suppressing the growth of these tumors.
Smart Thermally Actuating Textiles Sanchez, Vanessa; Payne, Christopher J.; Preston, Daniel J. ...
Advanced materials technologies,
August 2020, Letnik:
5, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Soft robots have attracted attention for biomedical and consumer devices. However, most of these robots are pneumatically actuated, requiring a tether and thus limiting wearable applications that ...require multiple controlled actuators. By pairing liquid‐vapor phase change actuation with a textile‐based laminated manufacturing method, smart thermally actuating textiles (STATs) eliminate the need for a pneumatic tether. STATs are lightweight and unobtrusive for wearable applications and exploit a facile manufacturing approach that supports arbitrary customization of the form factor and easy creation of connected arrays of individual robotic modules. Through integrated sensing and heating elements, STATs demonstrate closed‐loop feedback that enables dynamic pressure control in the presence of environmental temperature fluctuations.
This work presents a thermally actuated robotic textile driven by liquid‐vapor phase change. A laminated batch fabrication process enables manufacturing of customizable individual and arrayed soft robotic textile modules incorporating a resistive textile heater and a capacitive textile pressure sensor. These modular robotic textiles actuate with pressure‐based feedback, allowing them to maintain actuation profiles during environmental uncertainty.
To estimate the direct and indirect cost burden of untreated insomnia among younger adults (age 18-64), and to estimate the direct costs of untreated insomnia for elderly patients (age 65 and over).
...A retrospective, observational study comparing insomnia patients to matched samples without insomnia.
Self-insured, employer sponsored health insurance plans in the U.S.
138,820 younger adults and 75,558 elderly patients with insomnia, plus equal-sized, matched comparison groups.
NA.
Direct costs included inpatient, outpatient, pharmacy, and emergency room costs for all diseases, for six months before an index date. The index date for insomnia patients was the date of diagnosis with or the onset of prescription treatment for insomnia, some-time during July 1, 1999-June 30, 2003. Non-insomnia patients were assigned the same index dates as the insomnia patients to whom they were matched. Indirect costs included costs related to absenteeism from work and the use of short-term disability programs. Propensity score matching was used to find insomnia and non-insomnia patients who had similar demographics, location, health plan type, comorbidities, and drug use patterns. Regression analyses controlled for factors that were different even after matching was completed. We found that average direct and indirect costs for younger adults with insomnia were about $1,253 greater than for patients without insomnia. Among the elderly, direct costs were about $1,143 greater for insomnia patients.
Insomnia is associated with a significant economic burden for younger and older patients.
Immunization is key to preventing infectious diseases, a leading cause of death early in life. However, due to age-specific immunity, vaccines often demonstrate reduced efficacy in newborns and young ...infants as compared to adults. Here, we combined
and
approaches to identify adjuvant candidates for early life immunization. We employed newborn and adult bone marrow-derived dendritic cells (BMDCs) to perform a screening of pattern recognition receptor agonists and found that the stimulator of interferon genes ligand 2'3'-cGAMP (hereafter cGAMP) induces a comparable expression of surface maturation markers in newborn and adult BMDCs. Then, we utilized the trivalent recombinant hemagglutinin (rHA) influenza vaccine, Flublok, as a model antigen to investigate the role of cGAMP in adult and early life immunization. cGAMP adjuvantation alone could increase rHA-specific antibody titers in adult but not newborn mice. Remarkably, as compared to alum or cGAMP alone, immunization with cGAMP formulated with alum (Alhydrogel) enhanced newborn rHA-specific IgG2a/c titers ~400-fold, an antibody subclass associated with the development of IFNγ-driven type 1 immunity
and endowed with higher effector functions, by 42 days of life. Highlighting the amenability for successful vaccine formulation and delivery, we next confirmed that cGAMP adsorbs onto alum
. Accordingly, immunization early in life with (cGAMP+alum) promoted IFNγ production by CD4
T cells and increased the proportions and absolute numbers of CD4
CXCR5
PD-1
T follicular helper and germinal center (GC) GL-7
CD138
B cells, suggesting an enhancement of the GC reaction. Adjuvantation effects were apparently specific for IgG2a/c isotype switching without effect on antibody affinity maturation, as there was no effect on rHA-specific IgG avidity. Overall, our studies suggest that cGAMP when formulated with alum may represent an effective adjuvantation system to foster humoral and cellular aspects of type 1 immunity for early life immunization.
The contribution of induction chemotherapy (IC) before preoperative chemoradiation for esophageal cancer (EC) is not known. We hypothesized that IC would increase the rate of pathologic complete ...response (pathCR).
Trimodality-eligibile patients were randomized to receive no IC (Arm A) or IC (oxaliplatin/FU; Arm B) before oxaliplatin/FU/radiation. Surgery was attempted ∼5–6 weeks after chemoradiation. The pathCR rate, post-surgery 30-day mortality, overall survival (OS), and toxic effects were assessed. Bayesian methods and Fisher's exact test were used.
One hundred twenty-six patients were randomized dynamically to balance the two arms for histology, baseline stage, gender, race, and age. Fifty-five patients in Arm A and 54 in Arm B underwent surgery. The median actuarial OS for all patients (54 deaths) was 45.62 months 95% confidence interval (CI), 27.63–NA, with median OS 45.62 months (95% CI 25.56–NA) in Arm A and 43.68 months (95% CI 27.63–NA) in Arm B (P = 0.69). The pathCR rate in Arm A was 13% (7 of 55) and 26% (14 of 54) in Arm B (two-sided Fisher's exact test, P = 0.094). Safety was similar in both arms.
These data suggest that IC produces non-significant increase in the pathCR rate and does not prolong OS. Further development of IC before chemoradiation may not be beneficial.
Clinical trial no.: NCT 00525915 (www.clinicaltrials.gov).
An umpolung 1,4‐addition of aryl iodides to enals promoted by cooperative (terpy)Pd/NHC catalysis was developed that generates various bioactive β,β‐diaryl propanoate derivatives. This system is not ...only the first reported palladium‐catalyzed arylation of NHC‐bound homoenolates but also expands the scope of NHC‐induced umpolung transformations. A diverse array of functional groups such as esters, nitriles, alcohols, and heterocycles are tolerated under the mild conditions. This method also circumvents the use of moisture‐sensitive organometallic reagents.
It takes two: Synergistic catalysis between NHC and palladium catalysts enables the conjugate addition of aryl iodides to enals under redox‐neutral conditions. This method circumvents the use of moisture‐sensitive organometallic reagents, and a diverse array of functional groups such as esters, nitriles, alcohols, and heterocycles are tolerated.
Abstract The purpose of this review is to illustrate the utility and value of employing human self-administration procedures in medication development, including abuse liability assessments of novel ...medications and evaluation of potential pharmacotherapies for substance use disorders. Traditionally, human abuse liability testing has relied primarily on subjective reports describing drug action by use of questionnaires; similarly, drug interactions between putative treatment agents and the drugs of abuse have relied on these measures. Subjective reports are highly valued because they provide qualitative and quantitative information about the characteristics of central and peripheral pharmacodynamic effects as well as safety and tolerability. However, self-administration procedures directly examine the behavior of interest—that is, drug taking. The present paper (1) reviews the most commonly used human self-administration procedures, (2) discusses the concordance of subjective reports and self-administration within the context of medications development for substance use disorders, focusing primarily on illustrative examples from development efforts with opioid and cocaine dependence, and (3) explores the utility of applying self-administration procedures to assess the abuse liability of novel compounds, including “abuse-deterrent” formulations (ADFs). The review will focus on opioid and cocaine dependence because a rich database from both clinical laboratory and clinical trial research exists for these two drug classes. The data reviewed suggest that drug-induced changes in self-administration and subjective effects are not always concordant. Therefore, assessment of self-administration in combination with subjective effects provides a more comprehensive picture that may have improved predictive validity for translating to the clinical setting.
PDF
