Chromatin remodeling protein BPTF regulates transcriptional stability in planarian stem cells.

Trimethylation of histone H3 lysine 4 (H3K4me3) correlates strongly with gene expression in many different organisms, yet the question of whether it plays a causal role in transcriptional activity remains unresolved. Although H3K4me3 does not directly affect chromatin accessibility, it can indirectly affect genome accessibility by recruiting the ATP-dependent chromatin remodeling complex NuRF (Nucleosome Remodeling Factor). The largest subunit of NuRF, BPTF/NURF301, binds H3K4me3 specifically and recruits the NuRF complex to loci marked by this modification. Studies have shown that the strength and duration of BPTF binding likely also depends on additional chromatin features at these loci, such as lysine acetylation and variant histone proteins. However, the exact details of this recruitment mechanism vary between studies and have largely been tested in vitro. Here, we use stem cells isolated directly from live planarian animals to investigate the role of BPTF in regulating chromatin accessibility in vivo. We find that BPTF operates at gene promoters and is most effective at facilitating transcription at genes marked by Set1-dependent H3K4me3 peaks, which are significantly broader than those added by the lysine methyltransferase MLL1/2. Moreover, BPTF is essential for planarian stem cell biology and its loss of function phenotype mimics that of Set1 knockdown. Together, these data suggest that BPTF and H3K4me3 are important mediators of both transcription and in vivo stem cell function.

Solution Shearing of Zirconium (Zr)-Based Metal-Organic Frameworks NU-901 and MOF-525 Thin Films for Electrocatalytic Reduction Applications.

Solution shearing, a meniscus-guided coating process, can create large-area metal-organic framework (MOF) thin films rapidly, which can lead to the formation of uniform membranes for separations or thin films for sensing and catalysis applications. Although previous work has shown that solution shearing can render MOF thin films, examples have been limited to a few prototypical systems, such as HKUST-1, Cu-HHTP, and UiO-66. Here, we expand on the applicability of solution shearing by making thin films of NU-901, a zirconium-based MOF. We study how the NU-901 thin film properties (i.e., crystallinity, surface coverage, and thickness) can be controlled as a function of substrate temperature and linker concentration. High fractional surface coverage of small-area (∼1 cm2) NU-901 thin films (0.88 ± 0.06) is achieved on a glass substrate for all conditions after one blade pass, while a low to moderate fractional surface coverage (0.73 ± 0.18) is obtained for large-area (∼5 cm2) NU-901 thin films. The crystallinity of NU-901 crystals increases with temperature and decreases with linker concentration. On the other hand, the adjusted thickness of NU-901 thin films increases with both increasing temperature and linker concentration. We also extend the solution shearing technique to synthesize MOF-525 thin films on a transparent conductive oxide that are useful for electrocatalysis. We show that Fe-metalated MOF-525 films can reduce CO2 to CO, which has implications for CO2 capture and utilization. The demonstration of thin film formation of NU-901 and MOF-525 using solution shearing on a wide range of substrates will be highly useful for implementing these MOFs in sensing and catalytic applications.

Sympathovagal Balance and Body Shape Index in Elite and Amateur Athletes: The Relationship Unraveled.

Background Heart rate variability (HRV) is one piece among a complex network of adaptations existent in athletes that help them gain a better understanding of their own physiology. Sympathovagal balance is one of the spectral components of HRV analysis and is used to assess the frequently changing oscillations of a healthy heart, which can help in gauging the response of cardiac function towards physiological stress during exercise. This index is extensively used in appraising cardiac autonomic modulation. An evaluation of body composition in athletes has become a critical consideration when tracking HRV, as it helps practitioners understand the role of the autonomic nervous system (ANS) in obesity. The body shape index (BSI), which is based on waist circumference (WC), is an anthropometric parameter with decent predictive ability when measuring centripetal obesity. In this regard, the current study is an attempt to unravel the relationship between BSI and sympathovagal balance during exercise performed on two different instruments (treadmill and ergometer) by elite and amateur athletes. Methods It was an observational case-control study that included 30 elite and 120 amateur athletes. Symptom-limited exercise testing was performed by athletes on a motorized treadmill and ergometer in the sports physiology laboratory of a rural medical college in central India. Different anthropometric parameters like BSI and body surface area (BSA) were also recorded. Short-term HRV extracted from electrocardiogram (ECG) recordings was obtained using the Power Lab system and HRV analysis by LabChart software. Results The sympathovagal ratio, i.e., ratio of low frequency (LF) to high frequency (HF) in elite and amateur male populations showed a higher value than that in females, indicating a dominant sympathetic response in the males. There was a significant (p=0.042) positive correlation (r=0.24) between BSI and LF/HF Ratio in amateur females during treadmill exercise, whereas a significant (p=0.049) negative correlation (r=-0.27) was obtained in amateur males during ergometer exercise. Hence, increased weight and BSI were found to be associated with high sympathetic dominance, indicating a sympathovagal imbalance. Conclusion We attempted to explore the interaction between BSI and LF/HF during exercise performed on two different instruments (treadmill and ergometer) by elite and amateur athletes, which can help in testing the response of cardiac function to stress experienced during exercise. The study's uniqueness stems from discovering the relationship between BSI and HRV and how this relationship impacts sports performance. BSI measurement in athletes, both elite and amateur, allows for the assessment and forecasting of potential autonomic activity under exercise-induced stress by linking HRV with BSI.

Assessment of response of neoadjuvant chemotherapy in carcinoma breast patients by high-frequency ultrasound.

Aim: To assess the response of neoadjuvant chemotherapy in carcinoma breast patients by high-frequency ultrasound. Material and Method: The current single blind, observational study was conducted at rural tertiary healthcare center of Acharya Vinoba Bhave Rural Hospital from October 2018 to Sept 2020. We incorporated breast cancer patients with TNM stages IIIA and IIIB who received neoadjuvant chemotherapy with Cyclophosphamide/Adriamycin/5 FU and Paclitaxel respectively followed by standard surgical procedure modified radical mastectomy. Successive ultrasound examination of the breast malignancy and the axilla was done after 21 days of either of any neoadjuvant chemotherapy for 3 cycles. Assessment of response to neoadjuvant chemotherapy was applied in terms of reduction in the breast tumour volume on ultrasound and percentage of tumour response calculated by Response Evaluation Criteria for Solid Tumours (RECIST). Data were analysed using SPSS version 24.0. Results: Higher frequency of patients was invasive ductal breast cancer. In our study, Paclitaxel group showed better response in terms of CR and PR than CAF group. Our study noticed a consistent decrement in tumour volume after every cycle of either CAF or Paclitaxel NACT. Axillary ultrasound was able to predict the response of axillary lymph nodes in terms of increase or decrease in number and morphological changes after 3 cycles of NACT with similarity on final histopathology. Conclusion: It can be concluded from the results of the present study that high-frequency ultrasound is appropriate tool for assessment of response of primary breast malignancy and lymphnode metastasis in the axilla after neoadjuvant chemotherapy.

Autocatalysis and Oriented Attachment Direct the Synthesis of a Metal-Organic Framework.

Synthesis of porous, covalent crystals such as zeolites and metal-organic frameworks (MOFs) cannot be described adequately using existing crystallization theories. Even with the development of state-of-the-art experimental and computational tools, the identification of primary mechanisms of nucleation and growth of MOFs remains elusive. Here, using time-resolved in-situ X-ray scattering coupled with a six-parameter microkinetic model consisting of ∼1 billion reactions and up to ∼100 000 metal nodes, we identify autocatalysis and oriented attachment as previously unrecognized mechanisms of nucleation and growth of the MOF UiO-66. The secondary building unit (SBU) formation follows an autocatalytic initiation reaction driven by a self-templating mechanism. The induction time of MOF nucleation is determined by the relative rate of SBU attachment (chain extension) and the initiation reaction, whereas the MOF growth is primarily driven by the oriented attachment of reactive MOF crystals. The average size and polydispersity of MOFs are controlled by surface stabilization. Finally, the microkinetic model developed here is generalizable to different MOFs and other multicomponent systems.

Patterned microfluidic devices for rapid screening of metal-organic frameworks yield insights into polymorphism and non-monotonic growth.

Metal-organic frameworks (MOFs) are porous crystalline structures that are composed of coordinated metal ligands and organic linkers. Due to their high porosity, ultra-high surface-to-volume ratio, and chemical and structural flexibility, MOFs have numerous applications. MOFs are primarily synthesized in batch reactors under harsh conditions and long synthesis times. The continuous depletion of metal ligands and linkers in batch processes affects the kinetics of the oligomerization reaction and, hence, their nucleation and growth rates. Therefore, the existing screening systems that rely on batch processes, such as microtiter plates and droplet-based microfluidics, do not provide reliable nucleation and growth rate data. Significant challenges still exist for developing a relatively inexpensive, safe, and readily scalable screening device and ensuring consistency of results before scaling up. Here, we have designed patterned-surface microfluidic devices for continuous-flow synthesis of MOFs that allow effective and rapid screening of synthesis conditions. The patterned surface reduces the induction time of MOF synthesis for rapid screening while providing support to capture MOF crystals for growth measurements. The efficacy of the continuous-flow patterned microfluidic device to screen polymorphs, morphology, and growth rates is demonstrated for the HKUST-1 MOF. The effects of solvent composition and pH modulators on the morphology, polymorphs, and size distribution of HKUST-1 are evaluated using the patterned microfluidic device. Additionally, a time-resolved FT-IR analysis coupled with the patterned microfluidic device provides quantitative insights into the non-monotonic growth of MOF crystals with respect to the progression of the bulk oligomerization reaction. The patterned microfluidic device can be used to screen crystals with a longer induction time, such as proteins, covalent-organic frameworks, and MOFs.

Set1 Targets Genes with Essential Identity and Tumor-Suppressing Functions in Planarian Stem Cells.

Tumor suppressor genes (TSGs) are essential for normal cellular function in multicellular organisms, but many TSGs and tumor-suppressing mechanisms remain unknown. Planarian flatworms exhibit particularly robust tumor suppression, yet the specific mechanisms underlying this trait remain unclear. Here, we analyze histone H3 lysine 4 trimethylation (H3K4me3) signal across the planarian genome to determine if the broad H3K4me3 chromatin signature that marks essential cell identity genes and TSGs in mammalian cells is conserved in this valuable model of in vivo stem cell function. We find that this signature is indeed conserved on the planarian genome and that the lysine methyltransferase Set1 is largely responsible for creating it at both cell identity and putative TSG loci. In addition, we show that depletion of set1 in planarians induces stem cell phenotypes that suggest loss of TSG function, including hyperproliferation and an abnormal DNA damage response (DDR). Importantly, this work establishes that Set1 targets specific gene loci in planarian stem cells and marks them with a conserved chromatin signature. Moreover, our data strongly suggest that Set1 activity at these genes has important functional consequences both during normal homeostasis and in response to genotoxic stress.