Converting to Open Access in Obstetrics and Gynaecology Journal: A Bibliometric Analysis.

For various reasons, journals may convert from subscription-based to open-access (OA) publishing models, commonly referred to as flipping. In 2022, the Acta Obstetricia et Gynecologica Scandinavica flipped to OA. We performed a bibliometric analysis of authorship patterns in this journal during and after the flipping period. A total of 898 research articles were included. In the period after flipping to OA, there were more publications by authors in various countries, including from China (7.2% vs. 3.3%, P = 0.001). Accordingly, the flip to OA in a leading obstetrics and gynaecology journal seemed to impact the authorship locale.

Decoding allosteric regulation by the acyl carrier protein.

Enzymes in multistep metabolic pathways utilize an array of regulatory mechanisms to maintain a delicate homeostasis [K. Magnuson, S. Jackowski, C. O. Rock, J. E. Cronan, Jr, Microbiol. Rev. 57, 522-542 (1993)]. Carrier proteins in particular play an essential role in shuttling substrates between appropriate enzymes in metabolic pathways. Although hypothesized [E. Ploskon et al., Chem. Biol. 17, 776-785 (2010)], allosteric regulation of substrate delivery has never before been demonstrated for any acyl carrier protein (ACP)-dependent pathway. Studying these mechanisms has remained challenging due to the transient and dynamic nature of protein-protein interactions, the vast diversity of substrates, and substrate instability [K. Finzel, D. J. Lee, M. D. Burkart, ChemBioChem 16, 528-547 (2015)]. Here we demonstrate a unique communication mechanism between the ACP and partner enzymes using solution NMR spectroscopy and molecular dynamics to elucidate allostery that is dependent on fatty acid chain length. We demonstrate that partner enzymes can allosterically distinguish between chain lengths via protein-protein interactions as structural features of substrate sequestration are translated from within the ACP four-helical bundle to the protein surface, without the need for stochastic chain flipping. These results illuminate details of cargo communication by the ACP that can serve as a foundation for engineering carrier protein-dependent pathways for specific, desired products.

Base flipping mechanism and binding strength of methyl-damaged DNA during the interaction with AGT.

Methyl damage to DNA bases is common in the cell nucleus. O6-alkylguanine-DNA alkyl transferase (AGT) may be a promising candidate for direct damage reversal in methylated DNA (mDNA) at the O6 point of the guanine. Indeed, atomic-level investigations in the contact region of AGT-DNA complex can provide an in-depth understanding of their binding mechanism, allowing to evaluate the silico-drug nature of AGT and its utility in removing methyl damage in DNA. In this study, molecular dynamics (MD) simulation was utilized to examine the flipping of methylated nucleotide, the binding mechanism between mDNA and AGT, and the comparison of binding strength prior and post methyl transfer to AGT. The study reveals that methylation at the O6 atom of guanine weakens the hydrogen bond (H-bond) between guanine and cytosine, permitting for the flipping of such nucleotide. The formation of a H-bond between the base pair of methylated nucleotide (i.e., cytosine) and the intercalated arginine of AGT also forces the nucleotide to rotate. Following that, electrostatics and van der Waals contacts as well as hydrogen bonding contribute to form the complex of DNA and protein. The stronger binding of AGT with DNA before methyl transfer creates the suitable condition to transfer methyl adduct from DNA to AGT.

Unique anticodon loop conformation with the flipped-out wobble nucleotide in the crystal structure of unbound tRNAVal.

During protein synthesis on ribosome, tRNA recognizes its cognate codon of mRNA through base-pairing with the anticodon. The 5'-end nucleotide of the anticodon is capable of wobble base-pairing, offering a molecular basis for codon degeneracy. The wobble nucleotide is often targeted for post-transcriptional modification, which affects the specificity and fidelity of the decoding process. Flipping-out of a wobble nucleotide in the anticodon loop has been proposed to be necessary for modifying enzymes to access the target nucleotide, which has been captured in selective structures of protein-bound complexes. Meanwhile, all other structures of free or ribosome-bound tRNA display anticodon bases arranged in stacked conformation. We report the X-ray crystal structure of unbound tRNAVal1 to a 2.04 Å resolution showing two different conformational states of wobble uridine in the anticodon loop, one stacked on the neighboring base and the other swiveled out toward solvent. In addition, the structure reveals a rare magnesium ion coordination to the nitrogen atom of a nucleobase, which has been sampled very rarely among known structures of nucleic acids.

Inhibitors of UHRF1 base flipping activity showing cytotoxicity against cancer cells.

Ubiquitin-like containing PHD and RING finger domain 1 (UHRF1) is a nuclear multi-domain protein overexpressed in numerous human cancer types. We previously disclosed the anthraquinone derivative UM63 that inhibits UHRF1-SRA domain base-flipping activity, although having DNA intercalating properties. Herein, based on the UM63 structure, new UHRF1-SRA inhibitors were identified through a multidisciplinary approach, combining molecular modelling, biophysical assays, molecular and cell biology experiments. We identified AMSA2 and MPB7, that inhibit UHRF1-SRA mediated base flipping at low micromolar concentrations, but do not intercalate into DNA, which is a key advantage over UM63. These molecules prevent UHRF1/DNMT1 interaction at replication forks and decrease the overall DNA methylation in cells. Moreover, both compounds specifically induce cell death in numerous cancer cell lines, displaying marginal effect on non-cancer cells, as they preferentially affect cells with high level of UHRF1. Overall, these two compounds are promising leads for the development of anti-cancer drugs targeting UHRF1.

Practical Basis of the Geometric Mean Fitness and its Application to Risk-Spreading Behavior.

Temporal variations in population size under unpredictable environments are of primary concern in evolutionary ecology, where time scale enters as an important factor while setting up an optimization problem. Thus, short-term optimization with traditional (arithmetic) mean fitness may give a different result from long-term optimization. In the long-term optimization, the concept of geometric mean fitness has been received well by researchers and applied to various problems in ecology and evolution. However, the limit of applicability of geometric mean has not been addressed so far. Here we investigate this problem by analyzing numerically the probability distribution of a random variable obeying stochastic multiplicative growth. According to the law of large number, the expected value (i.e., arithmetic mean) manifests itself as a proper measure of optimization as the number of random processes increases to infinity. We show that the finiteness of this number plays a crucial role in arguing for the relevance of geometric mean. The geometric mean provides a satisfactory picture of the random variation in a long term above a crossover time scale that is determined by this number and the standard deviation of the randomly varying growth rates. We thus derive the applicability condition under which the geometric mean fitness is valid. We explore this condition in some examples of risk-spreading behavior.

Recent Advances on DNA Base Flipping: A General Mechanism for Writing, Reading, and Erasing DNA Modifications.

The modification of DNA bases is a classic hallmark of epigenetics. Four forms of modified cytosine-5-methylcytosine, 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine-have been discovered in eukaryotic DNA. In addition to cytosine carbon-5 modifications, cytosine and adenine methylated in the exocyclic amine-N4-methylcytosine and N6-methyladenine-are other modified DNA bases discovered even earlier. Each modified base can be considered a distinct epigenetic signal with broader biological implications beyond simple chemical changes. Since 1994, several crystal structures of proteins and enzymes involved in writing, reading, and erasing modified bases have become available. Here, we present a structural synopsis of writers, readers, and erasers of the modified bases from prokaryotes and eukaryotes. Despite significant differences in structures and functions, they are remarkably similar regarding their engagement in flipping a target base/nucleotide within DNA for specific recognitions and/or reactions. We thus highlight base flipping as a common structural framework broadly applied by distinct classes of proteins and enzymes across phyla for epigenetic regulations of DNA.

Spontaneous Polarity Flipping in a 2D Heterobilayer Induced by Fluctuating Interfacial Carrier Flows.

Polarity often refers to the charge carrier type of a semiconductor or the charging state of a functional group, generally dominating their functionality and performance. Herein we uncover a spontaneous and stochastic polarity-flipping phenomenon in monolayer WSe2, which randomly switches between the n-type and p-type states and is essentially triggered by fluctuating carrier flows from or to the adjacent WS2 monolayer. We have traced such fluctuating carrier flows by interfacial photocurrent measurements in a zero-bias two-terminal device. Such polarity flipping results in switching between the negative and positive correlations between the emission intensities of WS2 and WSe2 in the heterobilayer, which is further well-controlled by the electrostatic gate-tuning experiments in a capacitor-structure device. Our work not only demonstrates giant and intermittent carrier flows through long-range coupling in 2D heterostructures and a consequent spontaneous polarity flipping phenomenon but also provides a two-emitter system with a switchable correlation sign that could project future applications in optical logic devices.

An Enhanced Belief Propagation Flipping Decoder for Polar Codes with Stepping Strategy.

The Belief Propagation (BP) algorithm has the advantages of high-speed decoding and low latency. To improve the block error rate (BLER) performance of the BP-based algorithm, the BP flipping algorithm was proposed. However, the BP flipping algorithm attempts numerous useless flippings for improving the BLER performance. To reduce the number of decoding attempts needed without any loss of BLER performance, in this paper a metric is presented to evaluate the likelihood that the bits would correct the BP flipping decoding. Based on this, a BP-Step-Flipping (BPSF) algorithm is proposed which only traces the unreliable bits in the flip set (FS) to flip and skips over the reliable ones. In addition, a threshold ß is applied when the magnitude of the log-likelihood ratio (LLR) is small, and an enhanced BPSF (EBPSF) algorithm is presented to lower the BLER. With the same FS, the proposed algorithm can reduce the average number of iterations efficiently. Numerical results show the average number of iterations for EBPSF-1 decreases by 77.5% when N = 256, compared with the BP bit-flip-1 (BPF-1) algorithm at Eb/N0 = 1.5 dB.

Suspicion Distillation Gradient Descent Bit-Flipping Algorithm.

We propose a novel variant of the gradient descent bit-flipping (GDBF) algorithm for decoding low-density parity-check (LDPC) codes over the binary symmetric channel. The new bit-flipping rule is based on the reliability information passed from neighboring nodes in the corresponding Tanner graph. The name SuspicionDistillation reflects the main feature of the algorithm-that in every iteration, we assign a level of suspicion to each variable node about its current bit value. The level of suspicion of a variable node is used to decide whether the corresponding bit will be flipped. In addition, in each iteration, we determine the number of satisfied and unsatisfied checks that connect a suspicious node with other suspicious variable nodes. In this way, in the course of iteration, we "distill" such suspicious bits and flip them. The deterministic nature of the proposed algorithm results in a low-complexity implementation, as the bit-flipping rule can be obtained by modifying the original GDBF rule by using basic logic gates, and the modification is not applied in all decoding iterations. Furthermore, we present a more general framework based on deterministic re-initialization of the decoder input. The performance of the resulting algorithm is analyzed for the codes with various code lengths, and significant performance improvements are observed compared to the state-of-the-art hard-decision-decoding algorithms.

Controversial Variable Node Selection-Based Adaptive Belief Propagation Decoding Algorithm Using Bit Flipping Check for JSCC Systems.

An end-to-end joint source-channel (JSC) encoding matrix and a JSC decoding scheme using the proposed bit flipping check (BFC) algorithm and controversial variable node selection-based adaptive belief propagation (CVNS-ABP) decoding algorithm are presented to improve the efficiency and reliability of the joint source-channel coding (JSCC) scheme based on double Reed-Solomon (RS) codes. The constructed coding matrix can realize source compression and channel coding of multiple sets of information data simultaneously, which significantly improves the coding efficiency. The proposed BFC algorithm uses channel soft information to select and flip the unreliable bits and then uses the redundancy of the source block to realize the error verification and error correction. The proposed CVNS-ABP algorithm reduces the influence of error bits on decoding by selecting error variable nodes (VNs) from controversial VNs and adding them to the sparsity of the parity-check matrix. In addition, the proposed JSC decoding scheme based on the BFC algorithm and CVNS-ABP algorithm can realize the connection of source and channel to improve the performance of JSC decoding. Simulation results show that the proposed BFC-based hard-decision decoding (BFC-HDD) algorithm (ζ = 1) and BFC-based low-complexity chase (BFC-LCC) algorithm (ζ = 1, η = 3) can achieve about 0.23 dB and 0.46 dB of signal-to-noise ratio (SNR) defined gain over the prior-art decoding algorithm at a frame error rate (FER) = 10-1. Compared with the ABP algorithm, the proposed CVNS-ABP algorithm and BFC-CVNS-ABP algorithm achieve performance gains of 0.18 dB and 0.23 dB, respectively, at FER = 10-3.

Moderate-density parity-check codes from projective bundles.

New constructions for moderate-density parity-check (MDPC) codes using finite geometry are proposed. We design a parity-check matrix for the main family of binary codes as the concatenation of two matrices: the incidence matrix between points and lines of the Desarguesian projective plane and the incidence matrix between points and ovals of a projective bundle. A projective bundle is a special collection of ovals which pairwise meet in a unique point. We determine the minimum distance and the dimension of these codes, and we show that they have a natural quasi-cyclic structure. We consider alternative constructions based on an incidence matrix of a Desarguesian projective plane and compare their error-correction performance with regards to a modification of Gallager's bit-flipping decoding algorithm. In this setting, our codes have the best possible error-correction performance after one round of bit-flipping decoding given the parameters of the code's parity-check matrix.

6-phenylpyrrolocytosine as a fluorescent probe to examine nucleotide flipping catalyzed by a DNA repair protein.

Cellular exposure to tobacco-specific nitrosamines causes formation of promutagenic O6 -[4-oxo-4-(3-pyridyl)but-1-yl]guanine (O6 -POB-G) and O6 -methylguanine (O6 -Me-G) adducts in DNA. These adducts can be directly repaired by O6 -alkylguanine-DNA alkyltransferase (AGT). Repair begins by flipping the damaged base out of the DNA helix. AGT binding and base-flipping have been previously studied using pyrrolocytosine as a fluorescent probe paired to the O6 -alkylguanine lesion, but low fluorescence yield limited the resolution of steps in the repair process. Here, we utilize the highly fluorescent 6-phenylpyrrolo-2'-deoxycytidine (6-phenylpyrrolo-C) to investigate AGT-DNA interactions. Synthetic oligodeoxynucleotide duplexes containing O6 -POB-G and O6 -Me-G adducts were placed within the CpG sites of codons 158, 245, and 248 of the p53 tumor suppressor gene and base-paired to 6-phenylpyrrolo-C in the opposite strand. Neighboring cytosine was either unmethylated or methylated. Stopped-flow fluorescence measurements were performed by mixing the DNA duplexes with C145A or R128G AGT variants. We observe a rapid, two-step, nearly irreversible binding of AGT to DNA followed by two slower steps, one of which is base-flipping. Placing 5-methylcytosine immediately 5' to the alkylated guanosine causes a reduction in rate constant of nucleotide flipping. O6 -POB-G at codon 158 decreased the base flipping rate constant by 3.5-fold compared with O6 -Me-G at the same position. A similar effect was not observed at other codons.

Tailoring Interleaflet Lipid Transfer with a DNA-based Synthetic Enzyme.

Lipid membranes, enveloping all living systems, are of crucial importance, and control over their structure and composition is a highly desirable functionality of artificial structures. However, the rational design of protein-inspired systems is still challenging. Here we have developed a highly functional nucleic acid construct that self-assembles and inserts into membranes, enabling lipid transfer between inner and outer leaflets. By designing the structure to account for interactions between the DNA, its hydrophobic modifications, and the lipids, we successfully exerted control over the rate of interleaflet lipid transfer induced by our DNA-based enzyme. Furthermore, we can regulate the level of lipid transfer by altering the concentration of divalent ions, similar to stimuli-responsive lipid-flipping proteins.

DLSTM-Based Successive Cancellation Flipping Decoder for Short Polar Codes.

Polar code has been adopted as the control channel coding scheme for the fifth generation (5G), and the performance of short polar codes is receiving intensive attention. The successive cancellation flipping (SC flipping) algorithm suffers a significant performance loss in short block lengths. To address this issue, we propose a double long short-term memory (DLSTM) neural network to locate the first error bit. To enhance the prediction accuracy of the DLSTM network, all frozen bits are clipped in the output layer. Then, Gaussian approximation is applied to measure the channel reliability and rank the flipping set to choose the least reliable position for multi-bit flipping. To be robust under different codewords, padding and masking strategies aid the network architecture to be compatible with multiple block lengths. Numerical results indicate that the error-correction performance of the proposed algorithm is competitive with that of the CA-SCL algorithm. It has better performance than the machine learning-based multi-bit flipping SC (ML-MSCF) decoder and the dynamic SC flipping (DSCF) decoder for short polar codes.

Reinforcement Learning for Bit-Flipping Decoding of Polar Codes.

A traditional successive cancellation (SC) decoding algorithm produces error propagation in the decoding process. In order to improve the SC decoding performance, it is important to solve the error propagation. In this paper, we propose a new algorithm combining reinforcement learning and SC flip (SCF) decoding of polar codes, which is called a Q-learning-assisted SCF (QLSCF) decoding algorithm. The proposed QLSCF decoding algorithm uses reinforcement learning technology to select candidate bits for the SC flipping decoding. We establish a reinforcement learning model for selecting candidate bits, and the agent selects candidate bits to decode the information sequence. In our scheme, the decoding delay caused by the metric ordering can be removed during the decoding process. Simulation results demonstrate that the decoding delay of the proposed algorithm is reduced compared with the SCF decoding algorithm, based on critical set without loss of performance.

Transbilayer phospholipid movement facilitates the translocation of annexin across membranes.

Annexins are cytosolic phospholipid-binding proteins that can be found on the outer leaflet of the plasma membrane. The extracellular functions of annexin include modulating fibrinolysis activity and cell migration. Despite having well-described extracellular functions, the mechanism of annexin transport from the cytoplasmic inner leaflet to the extracellular outer leaflet of the plasma membrane remains unclear. Here, we show that the transbilayer movement of phospholipids facilitates the transport of annexins A2 and A5 across membranes in cells and in liposomes. We identified TMEM16F (also known as anoctamin-6, ANO6) as a lipid scramblase required for transport of these annexins to the outer leaflet of the plasma membrane. This work reveals a mechanism for annexin translocation across membranes which depends on plasma membrane phospholipid remodelling.

Structural Biology of the HEAT-Like Repeat Family of DNA Glycosylases.

DNA glycosylases remove aberrant DNA nucleobases as the first enzymatic step of the base excision repair (BER) pathway. The alkyl-DNA glycosylases AlkC and AlkD adopt a unique structure based on α-helical HEAT repeats. Both enzymes identify and excise their substrates without a base-flipping mechanism used by other glycosylases and nucleic acid processing proteins to access nucleobases that are otherwise stacked inside the double-helix. Consequently, these glycosylases act on a variety of cationic nucleobase modifications, including bulky adducts, not previously associated with BER. The related non-enzymatic HEAT-like repeat (HLR) proteins, AlkD2, and AlkF, have unique nucleic acid binding properties that expand the functions of this relatively new protein superfamily beyond DNA repair. Here, we review the phylogeny, biochemistry, and structures of the HLR proteins, which have helped broaden our understanding of the mechanisms by which DNA glycosylases locate and excise chemically modified DNA nucleobases.

Protein Adsorption on Solid Supported Membranes: Monitoring the Transport Activity of P-Type ATPases.

P-type ATPases are a large family of membrane transporters that are found in all forms of life. These enzymes couple ATP hydrolysis to the transport of various ions or phospholipids across cellular membranes, thereby generating and maintaining crucial electrochemical potential gradients. P-type ATPases have been studied by a variety of methods that have provided a wealth of information about the structure, function, and regulation of this class of enzymes. Among the many techniques used to investigate P-type ATPases, the electrical method based on solid supported membranes (SSM) was employed to investigate the transport mechanism of various ion pumps. In particular, the SSM method allows the direct measurement of charge movements generated by the ATPase following adsorption of the membrane-bound enzyme on the SSM surface and chemical activation by a substrate concentration jump. This kind of measurement was useful to identify electrogenic partial reactions and localize ion translocation in the reaction cycle of the membrane transporter. In the present review, we discuss how the SSM method has contributed to investigate some key features of the transport mechanism of P-type ATPases, with a special focus on sarcoplasmic reticulum Ca2+-ATPase, mammalian Cu+-ATPases (ATP7A and ATP7B), and phospholipid flippase ATP8A2.

Physical fitness improvements of 8-week light vs. heavy tyre flip training in young adults.

This study compared the effects of eight-week tyre flipping training intervention using light and heavy tyres on physical fitness performance. Twenty-nine young physically active males were divided into light (n = 15) and heavy (n = 14) tyre flipping groups evenly according to body weight and height. Body-to-tyre weight ratios were 0.61 ± 0.06 for the light tyre (LTTG) and 1.51 ± 0.16 for the heavy tyre training (HTTG) groups. Fitness parameters were measured before and after the intervention. One-way ANCOVA analysis indicated no significant between-group differences when pre-test values were controlled. Both groups demonstrated within-group improvements in 6RM bench press (ES: 0.98 in LTTG and 1.10 in HTTG), intermittent endurance (ES: 0.45 in LTTG and 0.66 in HTTG), five horizontal jumps (ES: 0.35 in LTTG and 0.26 in HTTG), and agility (ES: 0.34 in LTTG and 0.41 in HTTG). Both groups improved tyre flipping efficiency, through decreasing average set duration and work-rest ratios in the first six training sessions, and reached a plateau starting from the 7th training session. This study provides the first empirical evidence for coaches to justify usage of tyre flip training and the timing to progressive overload for a population with limited weight training and no tyre flip training experience.