The synaptonemal complex (SC) is a meiosis-specific scaffold that links homologous chromosomes from end to end during meiotic prophase and is required for the formation of meiotic crossovers. ...Assembly of SC components is regulated by a combination of associated nonstructural proteins and post-translational modifications, such as SUMOylation, which together coordinate the timing between homologous chromosome pairing, double-strand-break formation and recombination. In addition, transcriptional and translational control mechanisms ensure the timely disassembly of the SC after crossover resolution and before chromosome segregation at anaphase I.
Ferroelectricity in HfO
2
-based materials, especially Hf
0.5
Zr
0.5
O
2
(HZO), is today one of the most attractive topics because of its wide range of applications in ferroelectric random-access ...memory, ferroelectric field-effect transistors, ferroelectric tunneling junctions, steep-slope devices, and synaptic devices. The main reason for this increasing interest is that, when compared with conventional ferroelectric materials, HZO is compatible with complementary metal–oxide–semiconductor flow even back-end of the line thermal budget and can exhibit robust ferroelectricity even at extremely thin (< 10 nm) thicknesses. In this report, recent advances in the ferroelectric properties of HZO thin films since the first report in 2011, including doping effects, mechanical stress effects, interface effects, and ferroelectric film thickness effects, are comprehensively reviewed.
Family Caregiving for Older Adults Schulz, Richard; Beach, Scott R; Czaja, Sara J ...
Annual review of psychology,
01/2020, Letnik:
71, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Family members are the primary source of support for older adults with chronic illness and disability. Thousands of published empirical studies and dozens of reviews have documented the psychological ...and physical health effects of caregiving, identified caregivers at risk for adverse outcomes, and evaluated a wide range of intervention strategies to support caregivers. Caregiving as chronic stress exposure is the conceptual driver for much of this research. We review and synthesize the literature on the impact of caregiving and intervention strategies for supporting caregivers. The impact of caregiving is highly variable, driven largely by the intensity of care provided and the suffering of the care recipient. The intervention literature is littered with many failures and some successes. Successful interventions address both the pragmatics of care and the emotional toll of caregiving. We conclude with both research and policy recommendations that address a national agenda for caregiving.
Hepatic steatosis, the excess storage of intrahepatic lipids, is a rampant clinical problem associated with the obesity epidemic. Hepatic steatosis is linked to increased risk for insulin resistance, ...type 2 diabetes, and cardiovascular and advanced liver disease. Accumulating evidence shows that physical activity, exercise, and aerobic capacity have profound effects on regulating intrahepatic lipids and mediating susceptibility for hepatic steatosis. Moreover, exercise can effectively reduce hepatic steatosis independent of changes in body mass. In this perspective, we highlight
) the relationship between obesity and metabolic pathways putatively driving hepatic steatosis compared with changes induced by exercise;
) the impact of physical activity, exercise, and aerobic capacity compared with caloric restriction on regulating intrahepatic lipids and steatosis risk;
) the effects of exercise training (modalities, volume, intensity) for treatment of hepatic steatosis, and
) evidence for a sustained protection against steatosis induced by exercise. Overall, evidence clearly indicates that exercise powerfully regulates intrahepatic storage of fat and risk for steatosis.
Biomimetic Self-Healing Diesendruck, Charles E.; Sottos, Nancy R.; Moore, Jeffrey S. ...
Angewandte Chemie (International ed.),
September 1, 2015, Letnik:
54, Številka:
36
Journal Article
Recenzirano
Odprti dostop
Self‐healing is a natural process common to all living organisms which provides increased longevity and the ability to adapt to changes in the environment. Inspired by this fitness‐enhancing ...functionality, which was tuned by billions of years of evolution, scientists and engineers have been incorporating self‐healing capabilities into synthetic materials. By mimicking mechanically triggered chemistry as well as the storage and delivery of liquid reagents, new materials have been developed with extended longevity that are capable of restoring mechanical integrity and additional functions after being damaged. This Review describes the fundamental steps in this new field of science, which combines chemistry, physics, materials science, and mechanical engineering.
On the mend: Evolution has endowed biological organisms with the ability to self‐heal. Inspired by the principles of nature, scientists have been trying to create synthetic materials with self‐healing capabilities that can regenerate their mechanical integrity and specific functions after damage.
MRI-guided pulsed focused ultrasound (pFUS) combined with systemic infusion of ultrasound contrast agent microbubbles (MB) causes localized blood–brain barrier (BBB) disruption that is currently ...being advocated for increasing drug or gene delivery in neurological diseases. The mechanical acoustic cavitation effects of opening the BBB by low-intensity pFUS+MB, as evidenced by contrast-enhanced MRI, resulted in an immediate damage-associated molecular pattern (DAMP) response including elevations in heat-shock protein 70, IL-1, IL-18, and TNFα indicative of a sterile inflammatory response (SIR) in the parenchyma. Concurrent with DAMP presentation, significant elevations in proinflammatory, antiinflammatory, and trophic factors along with neurotrophic and neurogenesis factors were detected; these elevations lasted 24 h. Transcriptomic analysis of sonicated brain supported the proteomic findings and indicated that the SIR was facilitated through the induction of the NFκB pathway. Histological evaluation demonstrated increased albumin in the parenchyma that cleared by 24 h along with TUNEL⁺ neurons, activated astrocytes, microglia, and increased cell adhesion molecules in the vasculature. Infusion of fluorescent beads 3 d before pFUS+MB revealed the infiltration of CD68⁺ macrophages at 6 d postsonication, as is consistent with an innate immune response. pFUS+MB is being considered as part of a noninvasive adjuvant treatment for malignancy or neurodegenerative diseases. These results demonstrate that pFUS+MB induces an SIR compatible with ischemia or mild traumatic brain injury. Further investigation will be required before this approach can be widely implemented in clinical trials.
Abstract
Background and Objectives
The coronavirus disease 2019 (COVID-19) pandemic has negatively affected persons with existing chronic health conditions. The pandemic also has the potential to ...exacerbate the stresses of family caregiving. We compare family caregivers with noncaregivers on physical, psychosocial, and financial well-being outcomes during the pandemic and determine family caregivers most at risk for adverse outcomes.
Research Design and Methods
We conducted a cross-sectional online survey of 576 family caregivers and 2,933 noncaregivers from April to May 2020 in Pittsburgh, PA region with a national supplement. Outcome measures included concurrent anxiety, depression, fatigue, sleep disturbance, social participation, and financial well-being and perceived changes due to COVID-19 (loneliness, financial well-being, food security). We also measured sociodemographic, caregiving contextual variables, and COVID-19-related caregiver stressors (COVID Caregiver Risk Index).
Results
Controlling for sociodemographics, family caregivers reported higher anxiety, depression, fatigue, sleep disturbance, lower social participation, lower financial well-being, increased food insecurity (all p < .01), and increased financial worries (p = .01). Caregivers who reported more COVID-19-related caregiver stressors and disruptions reported more adverse outcomes (all p < .01). In addition, caregivers who were female, younger, lower income, providing both personal/medical care, and providing care for cognitive/behavioral/emotional problems reported more adverse outcomes.
Discussion and Implications
Challenges of caregiving are exacerbated by the COVID-19 pandemic. Family caregivers reported increased duties, burdens, and resulting adverse health, psychosocial, and financial outcomes. Results were generally consistent with caregiver stress–health process models. Family caregivers should receive increased support during this serious public health crisis.
Transposable elements (TE) are selfish genetic elements that can cause harmful mutations. In Drosophila, it has been estimated that half of all spontaneous visible marker phenotypes are mutations ...caused by TE insertions. Several factors likely limit the accumulation of exponentially amplifying TEs within genomes. First, synergistic interactions between TEs that amplify their harm with increasing copy number are proposed to limit TE copy number. However, the nature of this synergy is poorly understood. Second, because of the harm posed by TEs, eukaryotes have evolved systems of small RNA-based genome defense to limit transposition. However, as in all immune systems, there is a cost of autoimmunity and small RNA-based systems that silence TEs can inadvertently silence genes flanking TE insertions. In a screen for essential meiotic genes in Drosophila melanogaster, a truncated Doc retrotransposon within a neighboring gene was found to trigger the germline silencing of ald, the Drosophila Mps1 homolog, a gene essential for proper chromosome segregation in meiosis. A subsequent screen for suppressors of this silencing identified a new insertion of a Hobo DNA transposon in the same neighboring gene. Here we describe how the original Doc insertion triggers flanking piRNA biogenesis and local gene silencing. We show that this local gene silencing occurs in cis and is dependent on deadlock, a component of the Rhino-Deadlock-Cutoff (RDC) complex, to trigger dual-strand piRNA biogenesis at TE insertions. We further show how the additional Hobo insertion leads to de-silencing by reducing flanking piRNA biogenesis triggered by the original Doc insertion. These results support a model of TE-mediated gene silencing by piRNA biogenesis in cis that depends on local determinants of transcription. This may explain complex patterns of off-target gene silencing triggered by TEs within populations and in the laboratory. It also provides a mechanism of sign epistasis among TE insertions, illuminates the complex nature of their interactions and supports a model in which off-target gene silencing shapes the evolution of the RDC complex.
The American Society of Colon and Rectal Surgeons is dedicated to ensuring high-quality patient care by advancing the science, prevention, and management of disorders and diseases of the colon, ...rectum, and anus. The Clinical Practice Guidelines Committee is composed of society members who are chosen because they have demonstrated expertise in the specialty of colon and rectal surgery. This committee was created to lead international efforts in defining quality care for conditions related to the colon, rectum, and anus. This is accompanied by developing Clinical Practice Guidelines based on the best available evidence. These guidelines are inclusive and not prescriptive. Their purpose is to provide information on which decisions can be made, rather than to dictate a specific form of treatment. These guidelines are intended for the use of all practitioners, health care workers, and patients who desire information about the management of the conditions addressed by the topics covered in these guidelines. It should be recognized that these guidelines should not be deemed inclusive of all proper methods of care or exclusive of methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of all the circumstances presented by the individual patient.