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Same place, more space : 50 projects to maximize every room in the house
Karl Champley, master carpenter and host of DIY Channel's Wasted Spaces and DIY to the Rescue, offers 50 home-improvement projects to maximize space. Readers will learn to create hidey-holes under floor boards, construct fold-down changing tables, carve out shelving niches between studs in the wall, and much more.
BOOK
Structure and function insights into the NuRD chromatin remodeling complex
Transcription regulation through chromatin compaction and decompaction is regulated through various chromatin-remodeling complexes such as nucleosome remodeling and histone deacetylation (NuRD) complex. NuRD is a 1 MDa multi-subunit protein complex which comprises many different subunits, among which histone deacetylases HDAC1/2, ATP-dependent remodeling enzymes CHD3/4, histone chaperones RbAp46/48, CpG-binding proteins MBD2/3, the GATAD2a (p66α) and/or GATAD2b (p66β) and specific DNA-binding proteins MTA1/2/3. Here, we review the currently known crystal and NMR structures of these subunits, the functional data and their relevance for biomedical research considering the implication of NuRD subunits in cancer and various other diseases. The complexity of this macromolecular assembly, and its poorly understood mode of interaction with the nucleosome, the repeating unit of chromatin, illustrate that this complex is a major challenge for structure–function relationship studies which will be tackled best by an integrated biology approach.
Journal Article
Advances in the Knowledge of the Underlying Airway Remodeling Mechanisms in Chronic Rhinosinusitis Based on the Endotypes: A Review
Chronic rhinosinusitis (CRS) is a chronic inflammatory condition of the nasal and paranasal sinus mucosa that affects up to 10% of the population worldwide. CRS is the most representative disease of the upper respiratory tract where airway remodeling occurs, including epithelial damage, thickening of the basement membrane, fibrosis, goblet cell hyperplasia, subepithelial edema, and osteitis. CRS is divided into two phenotypes according to the presence or absence of nasal polyps: CRS with nasal polyp (CRSwNP) and CRS without nasal polyps (CRSsNP). Based on the underlying pathophysiologic mechanism, CRS is also classified as eosinophilic CRS and non-eosinophilic CRS, owing to Type 2 T helper (Th2)-based inflammation and Type 1 T helper (Th1)/Type 17 T helper (Th17) skewed immune response, respectively. Differences in tissue remodeling in CRS are suggested to be based on the clinical phenotype and endotypes; this is because fibrosis is prominent in CRSsNP, whereas edematous changes occur in CRSwNP, especially in the eosinophilic type. This review aims to summarize the latest information on the different mechanisms of airway remodeling in CRS according to distinct endotypes.
Journal Article
Hormones and brain plasticity
One of the most fascinating developments in the field of neuroscience in the second half of the 20th century was the discovery of the endogenous capacity of the brain for reorganization during adult life. Morphological and functional mechanisms underlying brain plasticity have been extensively explored and characterized. However, our understanding of the functional significance of these plastic changes is still fragmentary. This book shows that brain plasticity plays an essential role in the regulation of hormonal levels. The second aim is to propose that hormones orchestrate the multiple endogenous plastic events of the brain for the generation of adequate physiological and behavioral responses in adaptation to and in prediction of changing life conditions. The book starts by introducing the conceptual backgrounds on the interactions of hormones and brain plasticity. It then devotes itself to the analysis of the role of brain plasticity in the regulation of the activity of endocrine glands. It examines different hormonal influences on brain plasticity. Then, it goes on to cover the interactions of hormones and brain plasticity along the life cycle under physiological and pathological conditions.
eBook
Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study
Summary
We used bone turnover markers to identify women who responded to bisphosphonate treatment for osteoporosis. Response was more likely with alendronate and ibandronate than risedronate. There was a greater decrease in bone markers if baseline bone turnover markers were higher and if the patient took more than 80 % of her medication.
Introduction
Biochemical response to bisphosphonate therapy can be assessed using either a decrease in bone turnover marker beyond the least significant change (LSC) or a reduction to within a reference interval (RI). We compared the performance of these target responses and determined whether response was related to the type of bisphosphonate, compliance and baseline bone turnover markers.
Methods
Biochemical responses to three oral bisphosphonates were assessed in an open, controlled trial comprising 172 postmenopausal osteoporotic women (age 53–84 years), randomised to alendronate, ibandronate or risedronate, plus calcium and vitamin D supplementation for 2 years. The LSC for each marker was derived within the study population, whereas RIs were obtained from a control group of healthy premenopausal women (age 35–40 years).
Results
Over 70 % of women achieved a target response for serum CTX and PINP, irrespective of the approach used. The percentage decrease at 12 weeks was greater for women with baseline PINP above the RI −63 % (difference 13 %, 95 % CI 0 to 27.1,
P
= 0.049) and good compliance −67 % (difference 15.9 %, 95 % CI 6.3 to 25.5,
P
= 0.001). Responders had a greater increase in spine bone density compared to nonresponders; for example 6.2 vs. 2.3 % (difference 3.9 %, 95 % CI 1.6 to 6.3,
P
= 0.0011) for PINP LSC. The magnitude of change in bone markers was greater with ibandronate and alendronate than risedronate.
Conclusions
Both approaches to response identified similar proportions of women as responders. Nonresponders had smaller increases in BMD, and we suggest that biochemical assessment of response is a useful tool for the management of women with postmenopausal osteoporosis.
Journal Article
The chocolate shark shenanigans
\"When a house near Lee and Joe's home goes up for sale, the couple teams up with Lee's aunt and uncle, Nettie and Hogan, to buy it, remodel it, and resell it for a sweet profit. But after the owners of the house, the Baileys, accept their offer, a local developer, Richard \"Spud\" Dirk, suddenly swoops in with a higher one, and it seems their dreams might be snatched away. Lee, never as passionate about the plan as her husband and uncle, is anxious to get back to focusing on managing TenHuis Chocolade. But when a long-hidden gun is found behind a pipe in the Baileys' basement, she begins to suspect a mystery is afoot. And when Spud turns up dead in the Baileys' carport a few days later, it becomes clear there's something rotten at the foundation...\"-- Provided by publisher.
Book
The CHD4-related syndrome: a comprehensive investigation of the clinical spectrum, genotype–phenotype correlations, and molecular basis
Sifrim–Hitz–Weiss syndrome (SIHIWES) is a recently described multisystemic neurodevelopmental disorder caused by de novo variants inCHD4. In this study, we investigated the clinical spectrum of the disorder, genotype–phenotype correlations, and the effect of different missense variants on CHD4 function.
We collected clinical and molecular data from 32 individuals with mostly de novo variants in CHD4, identified through next-generation sequencing. We performed adenosine triphosphate (ATP) hydrolysis and nucleosome remodeling assays on variants from five different CHD4 domains.
The majority of participants had global developmental delay, mild to moderate intellectual disability, brain anomalies, congenital heart defects, and dysmorphic features. Macrocephaly was a frequent but not universal finding. Additional common abnormalities included hypogonadism in males, skeletal and limb anomalies, hearing impairment, and ophthalmic abnormalities. The majority of variants were nontruncating and affected the SNF2-like region of the protein. We did not identify genotype–phenotype correlations based on the type or location of variants. Alterations in ATP hydrolysis and chromatin remodeling activities were observed in variants from different domains.
The CHD4-related syndrome is a multisystemic neurodevelopmental disorder. Missense substitutions in different protein domains alter CHD4 function in a variant-specific manner, but result in a similar phenotype in humans.
Journal Article