-
Biophysical Journal Jul 2023The relationship between chromatin architecture and function defines a central problem in biology and medicine. Many computational chromatin models with atomic,...
The relationship between chromatin architecture and function defines a central problem in biology and medicine. Many computational chromatin models with atomic, coarse-grained, mesoscale, and polymer resolution have been used to shed light onto the mechanisms that dictate genome folding and regulation of gene expression. The associated simulation techniques range from Monte Carlo to molecular, Brownian, and Langevin dynamics. Here, we present an efficient Compute Unified Device Architecture (CUDA) implementation of Brownian dynamics (BD) to simulate chromatin fibers at the nucleosome resolution with our chromatin mesoscale model. With the CUDA implementation for computer architectures with graphic processing units (GPUs), we significantly accelerate compute-intensive hydrodynamic tensor calculations in the BD simulations by massive parallelization, boosting the performance a hundred-fold compared with central processing unit calculations. We validate our BD simulation approach by reproducing experimental trends on fiber diffusion and structure as a function of salt, linker histone binding, and histone-tail composition, as well as Monte Carlo equilibrium sampling results. Our approach proves to be physically accurate with performance that makes feasible the study of chromatin fibers in the range of kb or hundreds of nucleosomes (small gene). Such simulations are essential to advance the study of biological processes such as gene regulation and aberrant genome-structure related diseases.
Topics: Histones; Chromatin; Nucleosomes; Molecular Dynamics Simulation; Gene Expression Regulation
PubMed: 36116007
DOI: 10.1016/j.bpj.2022.09.013 -
Menopause (New York, N.Y.) May 2024The increasing attention to the management of perimenopausal and postmenopausal women parallels the growth of the aging population. Although hormone therapy is commonly... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The increasing attention to the management of perimenopausal and postmenopausal women parallels the growth of the aging population. Although hormone therapy is commonly used to alleviate menopausal symptoms, it carries a potential risk of cancer. Recently, mind-body exercises have emerged as innovative approaches for improving menopausal symptoms and bone health. However, research findings have needed to be more consistent, highlighting the significance of this study's systematic review of mind-body exercise effects on perimenopausal and postmenopausal women.
OBJECTIVE
This study aims to evaluate the impact of mind-body exercises, including tai chi, yoga, Pilates, qigong, baduanjin, and mindfulness-based stress reduction, on bone mineral density, sleep quality, anxiety, depression, and fatigue among perimenopausal and postmenopausal women.
EVIDENCE REVIEW
Four electronic databases-PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science-were systematically searched from inception until July 2023. The search focused exclusively on randomized controlled trials to examine the impact of mind-body exercise interventions on perimenopausal and postmenopausal women. The methodological quality of the included studies was evaluated using the Cochrane Bias Risk Assessment tool.
FINDINGS
A total of 11 randomized controlled trials, comprising 1,005 participants, were included in the analysis. Traditional meta-analysis indicated that mind-body exercise significantly enhanced bone mineral density in perimenopausal and postmenopausal women compared with control groups, with a standardized mean difference (SMD) of 0.41 (95% CI, 0.17 to 0.66; P = 0.001, I2 = 7%). In addition, significant improvements were observed in sleep quality (SMD, -0.48; 95% CI, -0.78 to -0.17; P = 0.002, I2 = 76%), anxiety reduction (SMD, -0.80; 95% CI, -1.23 to -0.38; P = 0.0002, I2 = 84%), depressive mood (SMD, -0.80; 95% CI, -1.17 to -0.44; P < 0.0001, I2 = 79%), and fatigue (SMD, -0.67; 95% CI, -0.97 to -0.37; P < 0.0001, I2 = 0%).
CONCLUSIONS AND RELEVANCE
The findings of this meta-analysis demonstrate that mind-body exercise positively influences bone mineral density, sleep quality, anxiety, depression, and fatigue among perimenopausal and postmenopausal women.
Topics: Humans; Female; Perimenopause; Postmenopause; Bone Density; Mind-Body Therapies; Middle Aged; Depression; Sleep Quality; Randomized Controlled Trials as Topic; Anxiety; Fatigue; Exercise; Tai Ji; Yoga
PubMed: 38669625
DOI: 10.1097/GME.0000000000002336 -
Journal of Medical Education and... 2024We created a serious game to teach first year anesthesiology (CA-1) residents to perform general anesthesia for cesarean delivery. We aimed to investigate resident...
We created a serious game to teach first year anesthesiology (CA-1) residents to perform general anesthesia for cesarean delivery. We aimed to investigate resident knowledge gains after playing the game and having received one of 2 modalities of debriefing. We report on the development and validation of scores from parallel test forms for criterion-referenced interpretations of resident knowledge. The test forms were intended for use as pre- and posttests for the experiment. Validation of instruments measuring the study's primary outcome was considered essential for adding rigor to the planned experiment, to be able to trust the study's results. Parallel, multiple-choice test forms development steps included: (1) assessment purpose and population specification; (2) content domain specification and writing/selection of items; (3) content validation by experts of paired items by topic and cognitive level; and (4) empirical validation of scores from the parallel test forms using Classical Test Theory (CTT) techniques. Field testing involved online administration of 52 shuffled items from both test forms to 24 CA-1's, 21 second-year anesthesiology (CA-2) residents, 2 fellows, 1 attending anesthesiologist, and 1 of unknown rank at 3 US institutions. Items from each form yielded near-normal score distributions, with similar medians, ranges, and standard deviations. Evaluations of CTT item difficulty (item p values) and discrimination (D) indices indicated that most items met assumptions of criterion-referenced test design, separating experienced from novice residents. Experienced residents performed better on overall domain scores than novices ( < .05). Kuder-Richardson Formula 20 (KR-20) reliability estimates of both test forms were above the acceptability cut of .70, and parallel forms reliability estimate was high at .86, indicating results were consistent with theoretical expectations. Total scores of parallel test forms demonstrated item-level validity, strong internal consistency and parallel forms reliability, suggesting sufficient robustness for knowledge outcomes assessments of CA-1 residents.
PubMed: 38357687
DOI: 10.1177/23821205241229778 -
Andrology Dec 2023Obtaining functional sperm cells is the first step to treat infertility. With the ever-increasing trend in male infertility, clinicians require access to effective... (Review)
Review
BACKGROUND
Obtaining functional sperm cells is the first step to treat infertility. With the ever-increasing trend in male infertility, clinicians require access to effective solutions that are able to single out the most viable spermatozoa, which would max out the chance for a successful pregnancy. The new generation techniques for sperm selection involve microfluidics, which offers laminar flow and low Reynolds number within the platforms can provide unprecedented opportunities for sperm selection. Previous studies showed that microfluidic platforms can provide a novel approach to this challenge and since then researchers across the globe have attacked this problem from multiple angles.
OBJECTIVE
In this review, we seek to provide a much-needed bridge between the technical and medical aspects of microfluidic sperm selection. Here, we provide an up-to-date list on microfluidic sperm selection procedures and its application in assisted reproductive technology laboratories.
SEARCH METHOD
A literature search was performed in Web of Science, PubMed, and Scopus to select papers reporting microfluidic sperm selection using the keywords: microfluidic sperm selection, self-motility, non-motile sperm selection, boundary following, rheotaxis, chemotaxis, and thermotaxis. Papers published before March 31, 2023 were selected.
OUTCOMES
Our results show that most studies have used motility-based properties for sperm selection. However, microfluidic platforms are ripe for making use of other properties such as chemotaxis and especially rheotaxis. We have identified that low throughput is one of the major hurdles to current microfluidic sperm selection chips, which can be solved via parallelization.
CONCLUSION
Future work needs to be performed on numerical simulation of the microfluidics chip prior to fabrication as well as relevant clinical assessment after the selection procedure. This would require a close collaboration and understanding among engineers, biologists, and medical professionals. It is interesting that in spite of two decades of microfluidics sperm selection, numerical simulation and clinical studies are lagging behind. It is expected that microfluidic sperm selection platforms will play a major role in the development of fully integrated start-to-finish assisted reproductive technology systems.
PubMed: 38148634
DOI: 10.1111/andr.13578 -
Advances in Experimental Medicine and... May 2024Transcriptional control of lipid metabolism uses a framework that parallels the control of lipid metabolism at the protein or enzyme level, via feedback and feed-forward...
Transcriptional control of lipid metabolism uses a framework that parallels the control of lipid metabolism at the protein or enzyme level, via feedback and feed-forward mechanisms. Increasing the substrates for an enzyme often increases enzyme gene expression, for example. A paucity of product can likewise potentiate transcription or stability of the mRNA encoding the enzyme or enzymes needed to produce it. In addition, changes in second messengers or cellular energy charge can act as on/off switches for transcriptional regulators to control transcript (and protein) abundance. Insects use a wide range of DNA-binding transcription factors (TFs) that sense changes in the cell and its environment to produce the appropriate change in transcription at gene promoters. These TFs work together with histones, spliceosomes, and additional RNA processing factors to ultimately regulate lipid metabolism. In this chapter, we will first focus on the important TFs that control lipid metabolism in insects. Next, we will describe non-TF regulators of insect lipid metabolism such as enzymes that modify acetylation and methylation status, transcriptional coactivators, splicing factors, and microRNAs. To conclude, we consider future goals for studying the mechanisms underlying the control of lipid metabolism in insects.
PubMed: 38782870
DOI: 10.1007/5584_2024_808 -
Annual Review of Phytopathology Sep 2023Since the 1950s, there have been major changes in the scope, value, and organization of the ornamental plant industry. With fewer individual producers and a strong trend... (Review)
Review
Since the 1950s, there have been major changes in the scope, value, and organization of the ornamental plant industry. With fewer individual producers and a strong trend toward consolidation and globalization, increasing quantities of diverse plant genera and species are being shipped internationally. Many more ornamentals are propagated vegetatively instead of by seed, further contributing to disease spread. These factors have led to global movement of pathogens to countries where they were not formerly known. The emergence of some previously undescribed pathogens has been facilitated by high-throughput sequencing, but biological studies are often lacking, so their roles in economic diseases are not yet known. Case studies of diseases in selected ornamentals discuss the factors involved in their spread, control measures to reduce their economic impact, and some potential effects on agronomic crops. Advances in diagnostic techniques are discussed, and parallels are drawn to the international movement of human diseases.
Topics: Humans; Commerce; Internationality; Bacterial Infections; Crops, Agricultural; Seeds
PubMed: 37257057
DOI: 10.1146/annurev-phyto-021621-114618 -
Attention, Perception & Psychophysics Oct 2023Listeners' use of contour information as a basis for memory of rhythmic patterns was explored in two experiments. Both studies employed a short-term memory paradigm in...
Listeners' use of contour information as a basis for memory of rhythmic patterns was explored in two experiments. Both studies employed a short-term memory paradigm in which listeners heard a standard rhythm, followed by a comparison rhythm, and judged whether the comparison was the same as the standard. Comparison rhythms included exact repetitions of the standard, same contour rhythms in which the relative interval durations of successive notes (but not the absolute durations of the notes themselves) were the same as the standard, and different contour rhythms in which the relative duration intervals of successive notes differed from the standard. Experiment 1 employed metric rhythms, whereas Experiment 2 employed ametric rhythms. D-prime analyses revealed that, in both experiments, listeners showed better discrimination for different contour rhythms relative to same contour rhythms. Paralleling classic work on melodic contour, these findings indicate that the concept of contour is both relevant to one's characterization of the rhythm of musical patterns and influences short-term memory for such patterns.
Topics: Humans; Music; Memory, Short-Term; Hearing; Auditory Perception
PubMed: 36991289
DOI: 10.3758/s13414-023-02700-w -
The British Journal of Dermatology Jul 2023Observations with rituximab suggest B-cell independent mechanisms of cutaneous lupus erythematosus (CLE) in systemic lupus erythematosus (SLE), especially discoid lupus...
Rapid efficacy of anifrolumab across multiple subtypes of recalcitrant cutaneous lupus erythematosus parallels changes in discrete subsets of blood transcriptomic and cellular biomarkers.
BACKGROUND
Observations with rituximab suggest B-cell independent mechanisms of cutaneous lupus erythematosus (CLE) in systemic lupus erythematosus (SLE), especially discoid lupus erythematosus (DLE). Type-I interferon receptor blockade with anifrolumab shows efficacy in SLE, but efficacy for cutaneous disease of specific morphologies has not been studied. Interferon has pleotropic immune effects and it is unknown which of these are critical to therapeutic response.
OBJECTIVES
We evaluated clinical efficacy and quality-of-life impact of type-I interferon-blockade in: (i) rituximab-refractory CLE; (ii) DLE and other morphologies and (iii) transcriptomic and flow cytometric biomarkers.
METHODS
We conducted a prospective single-centre study of anifrolumab in refractory mucocutaneous SLE. CLE Disease Area and Severity Index (CLASI) activity score, health-related quality of life, 96-probe TaqMan® gene expression analysis capturing key SLE blood transcriptome signatures, and eight-colour flow cytometry were undertaken at baseline, 1, 3 and 6 months.
RESULTS
Seven patients [DLE (n = 5), chilblain lupus erythematosus (n = 1), subacute CLE (n = 1)] were evaluated. The median number of prior therapies was six (range 3-15), including rituximab in six of seven patients. Median CLASI-A showed rapid and sustained improvement from 17 at baseline to 6 (P = 0.016) at 1 month and 0 (P < 0.001) by 3 months. The median percentage reduction in CLASI-A at 3 months was 60%. Significant improvements were observed in Dermatology Life Quality Index scores (P < 0.001), EuroQol 5D visual analogue scale (P = 0.002) and LupusQoL fatigue, image and planning domains (P ≤ 0.05). One patient discontinued treatment owing to severe herpes zoster. Clinical responses paralleled discrete suppression of interferon-stimulated genes (ISGs) from SLE blood transcriptome module M1.2 with more varied downregulation in other interferon modules. Myeloid and inflammation-annotated genes remained upregulated throughout treatment. Intermediate monocytes (CD14++CD16+) reduced to normal levels during therapy (P = 0.014), while other flow subsets showed no substantive changes.
CONCLUSIONS
These data indicate rapid efficacy of anifrolumab in DLE and rituximab-resistant CLE. Response is associated with suppression of a subset of ISGs and decline in intermediate monocytes. Suppression of all ISGs or the wider SLE blood transcriptome is not required for response.
Topics: Humans; Transcriptome; Rituximab; Prospective Studies; Quality of Life; Lupus Erythematosus, Cutaneous; Lupus Erythematosus, Discoid; Lupus Erythematosus, Systemic; Gene Expression Profiling; Biomarkers; Interferons
PubMed: 36944572
DOI: 10.1093/bjd/ljad089