bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of deep-inspiration breath-hold system that monitors the position of the chest wall using infrared rangefinder
Authors: Oshima Masaki , Shikama Naoto , Usui Keisuke , Nojiri Shuko , Isobe Akira , Muramoto Yoichi , Kawamoto Terufumi , Yamaguchi Nanae , Kosugi Yasuo , Sasai Keisuke
Published: December 2022

We conducted a prospective study to quantitatively evaluate the movement of the chest wall to establish the simple and reproducible deep-inspiration breath-hold (DIBH) method. The left nipple position was monitored to confirm the inspiratory state. Planning computed tomography (CT) was performed under DIBH and free-breath. We conducted radiation plans with DIBH and free-breath CT and evaluated organ at risk (OAR) and target doses according to two different plans. The relationship between positioning errors of the chest wall and patient factors was evaluated using univariate analysis and fixed-effects models. Twenty-three patients aged ≤ 60 years were enrolled during January–August 2021; 358 daily radiation treatments were evaluated. The median time of treatment room occupancy was 16 minutes (interquartile range, 14–20). The area of the planning target volume (PTV) surrounded by the 95% isodose line was more extensive in DIBH than in free breathing (71.6% vs 69.5%, P < 0.01), whereas the cardiac and left anterior descending (LAD) artery doses were lower (both P < 0.01). In the fixed-effects model analysis, the occupation time of the treatment room was correlated with positioning error. The difference between the planned and irradiated dose was the largest in the LAD branch of the coronary artery (−2.5 Gy), although the OAR dose decreased owing to positional error. The current DIBH method, wherein a single point on the chest wall is monitored to confirm that the patient is in an inspiratory state, allows radiation to be performed in a short time with a small dose error.
Non-operative management of a large Morgagni hernia—an alternative approach?
Authors: Archer Jack Peter , Williams Nicholas
Published: December 2022

Morgagni’s hernia (MH) is a congenital diaphragmatic hernia with a small percentage of cases diagnosed in adulthood. The average age of diagnosis is 57 years, with 61% being female and 10–28% being asymptomatic. It is common practice to complete surgical repair of MH regardless of symptomology or size of the defect despite a paucity of evidence. This paper highlights the potential for non-operative management as a reasonable treatment option in large asymptomatic MH. A female in her 40s was referred following an abnormal spirometry result as a part of a routine pre-employment check. She subsequently had imaging, which showed a large MH with abdominal contents within the thoracic cavity. Following discussion at a multidisciplinary team meeting, it was decided that the risk of perioperative morbidity likely exceeded the risk of strangulation while asymptomatic, and thus surveillance was recommended.
The impact of the initial core temperature on protostellar disc fragmentation
Authors: Sigalotti L Di G , Cruz F , Hareter M , Gabbasov R , Klapp J , Fierro-Santillán C R , Ramírez-Velásquez J M , Zsargó J
Published: December 2022

Ground-based and satellite observations have revealed dust temperatures as low as ∼5−7 K in the centre of low-mass, pre-stellar cloud cores, where star formation takes place. However, external heating may rise the outer core temperatures up to ∼15−20 K. Such low temperatures at the centre of pre-stellar cores are a key factor to constrain the conditions that lead to the formation of gravitationally bound protostellar systems as was recently captured by highly-resolved Atacama large millimeter/submillimeter array observations. Here, we report consistent smoothed particle hydrodynamics collapse calculations of cold cores that demonstrate the formation of close protobinary systems via small-scale fragmentation of a gravitationally unstable protostellar disc. The results indicate that mean binary separations, of tens of astronomical units, are a consequence of disc fragmentation in cold pre-stellar cores. Cloud cores initially with temperatures ≤6 K and a low amplitude (a = 0.1), m = 2 density perturbation formed close protobinaries that were followed deep into the non-isothermal collapse for several orbital periods and appeared to survive as independent stellar entities. At temperatures ≥7 K disc fragmentation is no longer observed and the calculations terminate with the formation of a wide protobinary, which may occasionally be accompanied by small substellar objects emerging by fragmentation of the circumbinary disc. When the perturbation amplitude is raised to a = 0.25, disc fragmentation occurs again only in cores with initial temperatures ≤6 K. Therefore, increasing the perturbation amplitude does not necessarily imply that there will be disc fragmentation at higher core temperatures.
Accretion geometry of the neutron star low mass X-ray binary Cyg X-2 from X-ray polarization measurements
Authors: Farinelli R , Fabiani S , Poutanen J , Ursini F , Ferrigno C , Bianchi S , Cocchi M , Capitanio F , De Rosa A , Gnarini A , Kislat F , Matt G , Mikusincova R , Muleri F , Agudo I , Antonelli L A , Bachetti M , Baldini L , Baumgartner W H , Bellazzini R , Bongiorno S D , Bonino R , Brez A , Bucciantini N , Castellano S , Cavazzuti E , Ciprini S , Costa E , Del Monte E , Di Gesu L , Di Lalla N , Di Marco A , Donnarumma I , Doroshenko V , Dovčiak M , Ehlert S R , Enoto T , Evangelista Y , Ferrazzoli R , Garcia J A , Gunji S , Hayashida K , Heyl J , Iwakiri W , Jorstad S G , Karas V , Kitaguchi T , Kolodziejczak J J , Krawczynski H , La Monaca F , Latronico L , Liodakis I , Maldera S , Manfreda A , Marin F , Marscher A P , Marshall H L , Mitsuishi I , Mizuno T , Ng C-Y , O’Dell S L , Omodei N , Oppedisano C , Papitto A , Pavlov G G , Peirson A L , Perri M , Pesce-Rollins M , Petrucci P O , Pilia M , Possenti A , Puccetti S , Ramsey B D , Rankin J , Ratheesh A , Romani R W , Sgrò C , Slane P , Soffitta P , Spandre G , Tamagawa T , Tavecchio F , Taverna R , Tawara Y , Tennant A F , Thomas N E , Tombesi F , Trois A , Tsygankov S S , Turolla R , Vink J , Weisskopf M C , Wu K , Xie F , Zane S
Published: December 2022

We report spectro-polarimetric results of an observational campaign of the bright neutron star low-mass X-ray binary Cyg X-2 simultaneously observed by IXPE, NICER, and INTEGRAL. Consistently with previous results, the broad-band spectrum is characterized by a lower-energy component, attributed to the accretion disc with kTin ≈ 1 keV, plus unsaturated Comptonization in thermal plasma with temperature kTe = 3 keV and optical depth τ ≈ 4, assuming a slab geometry. We measure the polarization degree in the 2–8 keV band P = 1.8 ± 0.3 per cent and polarization angle ϕ = 140° ± 4°, consistent with the previous X-ray polarimetric measurements by OSO-8 as well as with the direction of the radio jet which was earlier observed from the source. While polarization of the disc spectral component is poorly constrained with the IXPE data, the Comptonized emission has a polarization degree P = 4.0 ± 0.7 per cent and a polarization angle aligned with the radio jet. Our results strongly favour a spreading layer at the neutron star surface as the main source of the polarization signal. However, we cannot exclude a significant contribution from reflection off the accretion disc, as indicated by the presence of the iron fluorescence line.
High-resolution cryo-EM structure of the junction region of the native cardiac thin filament in relaxed state
Authors: Risi Cristina M , Belknap Betty , White Howard D , Dryden Kelly , Pinto Jose R , Chase P Bryant , Galkin Vitold E
Published: December 2022

Cardiac contraction depends on molecular interactions among sarcomeric proteins coordinated by the rising and falling intracellular Ca2+ levels. Cardiac thin filament (cTF) consists of two strands composed of actin, tropomyosin (Tm), and equally spaced troponin (Tn) complexes forming regulatory units. Tn binds Ca2+ to move Tm strand away from myosin-binding sites on actin to enable actomyosin cross-bridges required for force generation. The Tn complex has three subunits—Ca2+-binding TnC, inhibitory TnI, and Tm-binding TnT. Tm strand is comprised of adjacent Tm molecules that overlap “head-to-tail” along the actin filament. The N-terminus of TnT (e.g., TnT1) binds to the Tm overlap region to form the cTF junction region—the region that connects adjacent regulatory units and confers to cTF internal cooperativity. Numerous studies have predicted interactions among actin, Tm, and TnT1 within the junction region, although a direct structural description of the cTF junction region awaited completion. Here, we report a 3.8 Å resolution cryo-EM structure of the native cTF junction region at relaxing (pCa 8) Ca2+ conditions. We provide novel insights into the “head-to-tail” interactions between adjacent Tm molecules and interactions between the Tm junction with F-actin. We demonstrate how TnT1 stabilizes the Tm overlap region via its interactions with the Tm C- and N-termini and actin. Our data show that TnT1 works as a joint that anchors the Tm overlap region to actin, which stabilizes the relaxed state of the cTF. Our structure provides insight into the molecular basis of cardiac diseases caused by missense mutations in TnT1.
Save, Spend, or Give? A Model of Housing, Family Insurance, and Savings in Old Age
Authors: Barczyk Daniel , Fahle Sean , Kredler Matthias
Published: December 2022

How do housing and family shape the savings, spending, and inter-generational transfer behaviour of the elderly? Using the Health and Retirement Study, we document that inter-generational transfers to children are substantially backloaded, that homeowners dis-save much more slowly than renters but often sell their houses when entering a nursing home, and that care by children slows down nursing home entry and is linked to larger bequests, particularly of housing. To rationalise these facts, we develop a dynamic, non-cooperative model of the family with an indivisible housing asset and joint bargaining between elderly parents and their children over the housing and care arrangements of the parents. The model generates realistic savings and care choices and matches the timing of transfers and home liquidations. A key novelty is the housing-as-commitment channel: In the absence of long-run family contracts, housing provides a commitment device for more efficient savings. We find that this channel increases homeownership in old age by one-third and families’ willingness to pay for houses by 5–10%. This mechanism also facilitates informal care, slows down spending, and leads to larger bequests, implications that we support empirically.
The effects of topical anesthesia on outcomes and glucose control in diabetic patients treated with split-thickness skin graft surgery
Authors: Chang Dun-Hao , Lin Shen-Che , Lin Yi-Ting , Chang Ke-Chung , Chan Chien-Lung
Published: December 2022

Background:

Using split-thickness skin grafting to treat diabetic foot and leg ulcers is common. Diabetic patients usually exhibit multiple comorbidities and high risks of adverse responses to general and spinal anesthesia. Topical anesthesia can be an alternative to avoid these risks. In this study, the clinical experience of split-thickness skin grafting under topical anesthesia was demonstrated, to evaluate its effectiveness and benefits in diabetic patients.

Methods:

From 2018 to 2020, diabetic patients with foot or leg wounds undergoing split-thickness skin grafting were reviewed and categorized into two groups according to the anesthesia methods: topical anesthesia and general/spinal anesthesia. Patient demographics, wound characteristics and healing status, postoperative complications, and perioperative blood glucose levels were recorded and analyzed.

Results:

During the study period, 28 patients underwent split-thickness skin grafting under topical anesthesia and 46 under general/spinal anesthesia. The rate of complete wound healing in 4 weeks was similar in both the groups. The topical anesthesia group suffered fewer postoperative infections (3.6% vs 21.7%, p = 0.044), required shorter postoperative hospitalization (8.3 ± 6.2 vs 11.1 ± 7.2 days, p = 0.048), and exhibited lower mean blood glucose levels and less glucose variability than the general/spinal anesthesia group.

Conclusion:

Conducting split-thickness skin grafting under topical anesthesia was shown to be a safe and effective means of treating leg and foot wounds in diabetic patients.
Automated genome mining predicts combinatorial diversity and taxonomic distribution of peptide metallophore structures
Authors: Reitz Zachary L. , Butler Alison , Medema Marnix H.
Published: December 2022

Microbial competition for trace metals shapes their communities and interactions with humans and plants. Many bacteria scavenge trace metals with metallophores, small molecules that chelate environmental metal ions and transport them back into the cell. Our incomplete knowledge of metallophores diversity stymies our ability to fight infectious diseases and harness beneficial microbiome interactions. The majority of known metallophores are non-ribosomal peptides (NRPs), which feature metal-chelating moieties rarely found in other classes of natural products. NRP metallophore production may be predicted by genome mining, where genomes are scanned for homologs of known biosynthetic gene clusters (BGCs). However, accurately detecting NRP metallophore biosynthesis currently requires expert manual inspection. Here, we introduce automated identification of NRP metallophore BGCs through a comprehensive detection algorithm, newly implemented in antiSMASH. Custom-designed profile hidden Markov models detect genes encoding the biosynthesis of most known NRP metallophore chelating moieties (2,3-dihydroxybenzoate, hydroxamates, salicylate, β-hydroxyamino acids, graminine, Dmaq, and the pyoverdine chromophore), achieving 97% precision and 78% recall against manual curation. We leveraged the algorithm, in combination with transporter gene detection, to detect NRP metallophore BGCs in 15,562 representative bacterial genomes and predict that 25% of all non-ribosomal peptide synthetases encode metallophore production. BiG-SCAPE clustering of 2,562 NRP metallophore BGCs revealed that significant diversity remains unexplored, including new combinations of chelating groups. Additionally, we find that Cyanobacteria are severely understudied and should be the focus of more metallophore isolation efforts. The inclusion of NRP metallophore detection in antiSMASH version 7 will aid non-expert researchers and facilitate large-scale investigations into metallophore biology.
E(3) equivariant graph neural networks for robust and accurate protein–protein interaction site prediction
Authors: Roche Rahmatullah , Moussad Bernard , Shuvo Md Hossain , Bhattacharya Debswapna
Published: December 2022

Artificial intelligence-powered protein structure prediction methods have led to a paradigm-shift in computational structural biology, yet contemporary approaches for predicting the interfacial residues (i.e., sites) of protein-protein interaction (PPI) still rely on experimental structures. Recent studies have demonstrated benefits of employing graph convolution for PPI site prediction, but ignore symmetries naturally occurring in 3-dimensional space and act only on experimental coordinates. Here we present EquiPPIS, an E(3) equivariant graph neural network approach for PPI site prediction. EquiPPIS employs symmetry-aware graph convolutions that transform equivariantly with translation, rotation, and reflection in 3D space, providing richer representations for molecular data compared to invariant convolutions. EquiPPIS substantially outperforms state-of-the-art approaches based on the same experimental input, and exhibits remarkable robustness by attaining better accuracy with predicted structural models from AlphaFold2 than what existing methods can achieve even with experimental structures. Freely available athttps://github.com/Bhattacharya-Lab/EquiPPIS, EquiPPIS enables accurate PPI site prediction at scale.
Ploidy effects on the relationship between floral phenotype, reproductive investment and fitness exhibited by an autogamous species complex
Authors: García-Muñoz Ana , Ferrón Camilo , Vaca-Benito Celia , Loureiro João , Castro Sílvia , Muñoz-Pajares A. Jesús , Abdelaziz Mohamed
Published: December 2022

Premise

The relationships between reproductive investment, phenotype and fitness have been broadly studied in cross-pollinated plants in contrast to selfing species, which are considered less interesting in this area because they are supposed to be a dead-end in any evolutionary pathway. Still, selfing plants are unique systems to study these questions since the position of reproductive structures and traits related to flower size play an important role in female and male pollination success.

Method

Erysimum incanum s.l. is a selfing species complex exhibiting three levels of ploidy: diploids, tetraploids and hexaploids. This species complex shows traits typically associated with the selfing syndrome. Here, we used 1609 plants belonging to these three ploidies to characterize floral phenotype and spatial configuration of reproductive structures, reproductive investment (pollen and ovules production) and plant fitness. Then, we explored the relationship between all these variables using structural equation modelling across ploidy levels.

Key Results

An increase in ploidy level leads to bigger flowers with more exerted stamens and a greater amount of pollen and ovules. In addition, hexaploid plants exhibit higher absolute values for herkogamy which is positively correlated with fitness. Phenotypic traits and pollen production are indirectly selected by the relationship among ovules and fitness, maintained across ploidies.

Conclusions

Changes in floral phenotypes, reproductive investment and fitness with the ploidy level suggests that genome duplication can be a driver for the reproductive strategy transitions by modifying the investment in pollen and ovules and linking them with plant phenotype and fitness.
Effect of Hydromethanolic Seed Extract of Garcinia Kola on Male Reproductive Hormones
Authors: Harry Tamunotonye
Published: December 2022

Reproduction is central to the continued existence of mankind on earth, while infertility presents both a social and a public health concern, with male factor infertility present in 20% – 50% of all cases of infertility among couples. As part of the solution for male fertility disorders, drugs including those that are plant-based are being employed to address such issues. Hence, this study was focused on the effect of the administration of hydro-methanol seed extract ofG. kolaon the reproductive hormone of adult male Wistar rats. The plant material was procured, identified, and extracted while a total of 36 adult male rats were procured and distributed equally into three groups which were subdivided into two. Animals in group 1 served as the control while groups 2 and 3 served as the extract-treated groups which received 100 and 200 mg/kg BW of the extract respectively. Those in subgroups A and B were treated for 14 and 30 days respectively after which the animals were sacrificed and the blood collected via cardiac puncture into the appropriate bottles for hormonal profile assay. The result showed that the administration of the extract resulted in a reduction in the level of FSH and LH but increased the level of Testosterone, with a significant increase recorded in the 200 mg/kg group, while the level of prolactin was increased in the 100 mg/kg group but decreased in the 200mg/kg group. Hence, Garcinia kola might not be the best solution to aid fertility in males
Mirage2’s high-quality spliced protein-to-genome mappings produce accurate multiple-sequence alignments of isoforms
Authors: Nord Alex J. , Wheeler Travis J.
Published: December 2022

The organization of homologous protein sequences into multiple sequence alignments (MSAs) is a cornerstone of modern analysis of proteins. Recent focus on the importance of alternatively-spliced isoforms in disease and cell biology has highlighted the need for MSA software that can appropriately account for isoforms and the exon-length insertions or deletions that isoforms may have relative to each other. We previously developedMirage, a software package for generating MSAs for isoforms spanning multiple species. Here, we presentMirage2, which retains the fundamental algorithms of the originalMirageimplementation while providing substantially improved translated mapping and improving several aspects of usability. We demonstrate thatMirage2is highly effective at mapping proteins to their encoding exons, and that these protein-genome mappings lead to extremely accurate intron-aware alignments. Additionally,Mirage2implements a number of engineering improvements that simplify installation and use.
Unsupervized identification of prognostic copy-number alterations using segmentation and lasso regularization
Authors: Cleynen Alice , Avet-Loiseau Hervé , Corre Jill
Published: December 2022

Identifying copy-number alteration with prognostic impact is typically done in a supervised approach, were candidate regions are user-selected (chomosome arms, oncogenes, etc). Yet CNA events may range from whole chromosome alterations to small focal amplifications or deletions, with no available approach to combine the potential prognostic impact of different aberration ranges. We propose and compare different statistical models to integrate the effects of multi-scale CNA events by exploiting the longitudinal structure of the genome, and assume that the survival distribution follows a Cox-proportional hazard model. These methods are adaptable to any cohorts screened for CNA by genome-wide assays such as CGH-array or whole-genome sequencing technologies, and with sufficient follow-up time. We show that combining a segmentation in the survival odds strategy with a lasso-regularization selection approach provides the best results in terms of recovering the true significant CNA regions as well as predicting survival outcomes. In particular, as shown on a 551 Multiple Myeloma patient cohort, this method allows to refine previously identified regions to exhibit potential novel driver genes.
Identifying indels from WGS short reads of haploid genomes distinguishes variant-calling algorithms
Authors: Seah Yee Mey , Stewart Mary K. , Hoogestraat Daniel , Ryder Molly , Cookson Brad T. , Salipante Stephen J. , Hoffman Noah G.
Published: December 2022

Identification of clinically relevant strains of bacteria increasingly relies on whole genome sequencing. The downstream bioinformatics steps necessary for calling variants from short read sequences are well-established but seldom validated against haploid genomes. We devised anin silicoworkflow to introduce single nucleotide polymorphisms (SNP) and indels into bacterial reference genomes, and computationally generate sequencing reads based on the mutated genomes. We then applied the method toMycobacterium tuberculosisH37Rv and used the synthetic reads as truth sets for evaluating several popular variant callers. Insertions proved especially challenging for most variant callers to correctly identify, relative to deletions and single nucleotide polymorphisms. With adequate read depth, however, variant callers that use high quality soft-clipped reads and base mismatches to perform local realignment consistently had the highest precision and recall in identifying medium-length insertions and deletions.
How do we explain painful chronic non-traumatic knee conditions to children and adolescents? A multiple-method study to develop credible explanations
Authors: Djurtoft C , Bruun MK , Riel H , Hoegh MS , Darlow B , Rathleff MS
Published: December 2022

INTRODUCTION

Perceived diagnostic uncertainty can leave adolescents confused about their condition and impede their ability to understand“what’s wrong with me”. Our aim is to develop credible explanations (trustworthy and understandable explanation of the condition) for adolescents suffering from chronic non-traumatic knee pain.

METHODS

This multiple-method study integrated findings from a systematic literature search of qualitative studies, an Argumentative Delphi with international experts (n=16) and think-aloud sessions with adolescents (n=7). Experts provided feedback with arguments on how to communicate credible explanations to meet adolescents’ needs. We analyzed feedback using thematic analysis before tailoring explanations to end-users.

RESULTS

We screened 3.239 titles/abstracts and included 16 papers which explored diagnostic uncertainty from adolescents’ and parents’ perspectives. Five themes emerged: (1) Understanding causes and contributors to the pain experience, (2) Feeling stigmatized for having an invisible condition, (3) Having a name for pain, Controllability of pain, and (5) Worried about something being missed. The Argumentative Delphi revealed the following themes: (1) Multidimensional perspective, (2) Tailored to adolescents, (3) Validation and reassurance, and (4) Careful wording. Merging findings from the systematic search and the Delphi revealed three essential domains to address in credible explanations: “What is non-traumatic knee pain and what does it mean?”, “What is causing my knee pain?” and “How do I manage my knee pain?”.

CONCLUSIONS

Six credible explanations for the six most common diagnoses of chronic non-traumatic knee pain were developed. We identified three domains to consider when tailoring credible explanations to adolescents experiencing non-traumatic knee pain.
Development of a 1:1-binding biparatopic anti-TNFR2 antagonist by epitope selection
Authors: Akiba Hiroki , Fujita Junso , Ise Tomoko , Nishiyama Kentaro , Miyata Tomoko , Kato Takayuki , Namba Keiichi , Ohno Hiroaki , Kamada Haruhiko , Nagata Satoshi , Tsumoto Kouhei
Published: December 2022

Conventional bivalent antibodies against cell surface receptors often initiate unwanted signal transduction by crosslinking two antigen molecules. Biparatopic antibodies (BpAbs) bind to two different epitopes on the same antigen, thus altering crosslinking ability. In this study, we developed BpAbs against tumor necrosis factor receptor 2 (TNFR2), which is an attractive immune checkpoint target. Using different pairs of variable regions specific to topographically distinct TNFR2 epitopes, we successfully regulated the size of BpAb-TNFR2 immunocomplexes to result in controlled agonistic activities. One particular antagonist BpAb bound TNFR2 in 1:1 ratio without unwanted signal transduction, with its structural basis revealed by cryo-electron microscopy. This antagonist suppressed the proliferation of regulatory T cells expressing TNFR2. Therefore, the BpAb format would be useful in designing specific and distinct antibody functions.
A pH-sensitive switch activates virulence inSalmonella
Authors: Shetty Dasvit , Kenney Linda J.
Published: December 2022

The transcriptional regulator SsrB acts as a switch between virulent and biofilm lifestyles of non-typhoidalSalmonella entericaserovar Typhimurium. During infection, phosphorylated SsrB activates genes onSalmonellaPathogenicity Island-2 (SPI-2) essential for survival and replication within the macrophage. Low pH inside the vacuole is a key inducer of expression and SsrB activation. Previous studies demonstrated an increase in SsrB protein levels and DNA-binding affinity at low pH; the molecular basis was unknown (Liew et al., 2019). This study elucidates its underlying mechanism andin vivosignificance. Employing single-molecule and transcriptional assays, we report that the SsrB DNA binding domain alone (SsrBc) is insufficient to induce acid pH sensitivity. Instead, His12, a conserved residue in the receiver domain, confers pH sensitivity to SsrB allosterically. Acid-dependent DNA binding was highly cooperative, suggesting a new configuration of SsrB oligomers at SPI-2-dependent promoters. His12 plays a role in SsrB phosphorylation; substituting His12 reduced phosphorylation at neutral pH and abolished pH-dependent differences. Failure to flip the switch in SsrB rendersSalmonellaavirulent and represents a potential means of controlling virulence.
Presaccadic attention depends on eye movement direction and is related to V1 cortical magnification
Authors: Hanning Nina M. , Himmelberg Marc M. , Carrasco Marisa
Published: December 2022

With every saccadic eye movement, humans bring new information into their fovea to be processed with high visual acuity. Notably, perception is enhanced already before a relevant item is foveated: During saccade preparation,presaccadic attentionshifts to the upcoming fixation location, which can be measured via behavioral correlates such as enhanced visual performance or modulations of sensory feature tuning. The coupling between saccadic eye movements and attention is assumed to be robust and mandatory, and considered a mechanism facilitating the integration of pre- and post-saccadic information. However, until recently it had not been investigated as a function of saccade direction. Here, we measured contrast response functions during fixation and saccade preparation in male and female observers and found that the pronounced response gain benefit typically elicited by presaccadic attention is selectively lacking before upward saccades at the group level – some observers even showed a cost. Individual observers’ sensitivity before upward saccades was negatively related to their amount of surface area in primary visual cortex representing the saccade target, suggesting a potential compensatory mechanism that optimizes the use of the limited neural resources processing the upper vertical meridian. Our results raise the question how perceptual continuity is achieved and upward saccades can be accurately targeted despite the lack of – theoretically required– presaccadic attention.

Significance Statement

When we make a saccadic eye movement to a target location in the visual field, perception improves at the saccade target, already before the eyes start moving. This benefit afforded by presaccadic attention is thought to be mandatory and independent of eye movement direction. We show that this is not the case; moving our eyes horizontally or downwards, but not upwards, enhances contrast sensitivity. At the neural level, however, humans with less V1 cortical tissue representing the target location for upwards saccades have some presaccadic enhancement. The finding that presaccadic attention is dependent upon eye movement direction challenges the view that the presaccadic benefit is automatic and mandatory in nature.
HIV-1 diverts actin debranching mechanisms for particle assembly and release in CD4 T lymphocytes
Authors: Dibsy Rayane , Bremaud Erwan , Mak Johnson , Favard Cyril , Muriaux Delphine
Published: December 2022

Enveloped viruses assemble and bud from the host cell membranes. Possible roles of cortical actin in these processes have often been a source of controversy. Here, we assessed the involvement of the Arp2/3 mediated branched actin in HIV-1 assembly at the membrane of infected CD4 T lymphocytes. Our results show that actin debranching not only increases HIV-1 release but also the number of individual HIV-1 assembly clusters present at the cell plasma membrane unravelling new mechanisms. Indeed, we showed that, in infected T lymphocytes, HIV-1 Gag prefers areas deficient in F-actin for assembly. In vitro, we could reproduce and quantify this mechanism using model systems. Finally, we found that the actin debranching factor, Arpin, an Arp2/3 inhibitor, is recruited by Gag at the cell membrane to promote virus assembly. Altogether, our data show that HIV-1 favors local actin debranching for assembly and release by subverting the host factor Arpin.
Steric Communication between Dynamic Components on DNA nanodevices
Authors: Wang Y. , Sensale S. , Pedrozo M. , Huang C-M. , Poirier M.G. , Arya G. , Castro C.E.
Published: December 2022

Biomolecular nanotechnology has helped emulate basic robotic capabilities such as defined motion, sensing, and actuation in synthetic nanoscale systems. DNA origami is an attractive approach for nanorobotics, as it enables creation of devices with complex geometry, programmed motion, rapid actuation, force application, and various kinds of sensing modalities. Advanced robotic functions like feedback control, autonomy, or programmed routines also require the ability to transmit signals among sub-components. Prior work in DNA nanotechnology has established approaches for signal transmission, for example through diffusing strands or structurally coupled motions. However, soluble communication is often slow and structural coupling of motions can limit the function of individual components, for example to respond to the environment. Here, we introduce a novel approach inspired by protein allostery to transmit signals between two distal dynamic components through steric interactions. These components undergo separate thermal fluctuations where certain conformations of one arm will sterically occlude conformations of the distal arm. We implement this approach in a DNA origami device consisting of two stiff arms each connected to a base platform via a flexible hinge joint. We demonstrate the ability for one arm to sterically regulate both the range of motion as well as the conformational state (latched or freely fluctuating) of the distal arm, results that are quantitatively captured by mesoscopic simulations using experimentally informed energy landscapes for hinge-angle fluctuations. We further demonstrate the ability to modulate signal transmission by mechanically tuning the range of thermal fluctuations and controlling the conformational states of the arms. Our results establish a communication mechanism well-suited to transmit signals between thermally fluctuating dynamic components and provide a path to transmitting signals where the input is a dynamic response to parameters like force or solution conditions.
Explicit and implicit motor simulations are impaired in individuals with aphantasia
Authors: Dupont W. , Papaxanthis C. , Madden-Lombardi C. , Lebon F.
Published: December 2022

Individuals with aphantasia report having difficulties or an inability to generate visual images of objects or events. So far, there is no evidence showing that this condition also impacts the motor system and the generation of motor simulations. We probed the neurophysiological marker of aphantasia during explicit and implicit forms of motor simulation, i.e., motor imagery and action observation, respectively. We tested a group of individuals without any reported imagery deficits (phantasics) as well as a group of individuals self-reporting the inability to form mental images (aphantasics). We instructed the participants to explicitly imagine a maximal pinch movement in the visual and kinesthetic modalities and to observe a video showing a pinch movement. By means of transcranial magnetic stimulation, we triggered motor-evoked potentials (MEP) in the target right index finger. As expected, MEP amplitude, a marker of corticospinal excitability, increased for phantasics during kinaesthetic motor imagery and action observation relative to rest but not during visual motor imagery. Interestingly, MEP amplitude did not increase in either form of motor simulation for the group of aphantasics. This result provides neurophysiological evidence that individuals living with aphantasia have a real deficit in activating the motor system during motor simulations.
Derivation of Steady-State First-order Rate Constant Equations for Enzyme-Substrate Complex Dissociation, as well as Zero-order Rate Constant Equations in Relation to Background Assumptions
Authors: Udema Ikechukwu I.
Published: December 2022

The maximum velocity (Vmax) of catalysis and the substrate concentration ([ST]) at half theVmax, theKM, are regarded as steady-state (SS) parameters even though they are the outcomes of zero-order kinetics (ZOK). The research was aimed at disputing such a claim with the following objectives: To: 1) carry out an overview of issues pertaining to the validity of assumptions; 2) derive the needed steady-state (SS) equations distinct from Michaelian equations that can be fitted to both experimental variables and kinetic parameters; 3) calculate the SS first-order rate constant for the dissociation of enzyme-substrate complex (ES) to free substrate, S and enzyme, E; 4) derive the equation of rate constant as a function of the reciprocal of the duration of each catalytic event in the reaction pathway. The experimental values of the data were generated by Bernfeld and Lineweaver-Burk methods. The calculated SS 1storder-order rate constant was « the zero-order Michaelian value, and the difference is ≈ 97.59 % of the zero-order value; the SS catalytic rate differed from the zero-order catalytic rate by ≈ 76.41 % of the latter value; and it was ≈ 93.87 % with respect to the 2ndorder rate constant for the formation of enzyme-substrate complex. The equations of time-dependent rate constants,KM, and dissociation constants were derived. The concentration [ST] of the S must be > the concentration ([E0]) of the E for the quasi-steady-state assumption (or approximation) to hold. The SS kinetic parameters are not equivalent to zero-order parameters.
Risk of Infection Due to Airborne Virus in Classroom Environments Lacking Mechanical Ventilation
Authors: Goldblatt Alexandra , Loccisano Michael J. , Mahe Mazharul I. , Dennehy John J. , Spagnolo Fabrizio
Published: December 2022

The COVID-19 pandemic highlighted the role of indoor environments on disease transmission. Enclosed spaces where pathogen-laden aerosols accumulate was strongly linked to increased transmission events. Here we employ a surrogate non-pathogenic virus, the bacteriophage phi6, to interrogate aerosol transmission in classroom environments that do not have any natural or mechanical ventilation in order to determine how effectively aerosols facilitate new infections. We find that virus-laden aerosols establish new infections over all distances tested within minutes and that the time of exposure did not change transmission rate. We further find that humidity, but not temperature nor a UV-based disinfection device, significantly impacted transmission rates. Our data suggest that, even without mechanical ventilation, relative humidity remains a highly effective mitigation strategy while UV air treatment did not.

Practical Implications

Transmission of pathogens through airborne particles is a major source of disease transmission. People now spend much of their time indoors, thus understanding indoor airborne transmission is vital to managing outbreaks. Most classrooms in the U.S. do not have any mechanical ventilation systems and so here, we test airborne transmission of a virus in such classrooms. Infection transmission rates are not greatly impacted by distance, time or even some UV treatment, but are curbed by the amount of moisture in the air.
Light-activated assembly of connexon nanopores in synthetic cells
Authors: Sihorwala Ahmed , Lin Alexander , Stachowiak Jeanne C. , Belardi Brian
Published: December 2022

During developmental processes and wound healing, activation of living cells occurs with spatiotemporal precision and leads to rapid release of soluble molecular signals, allowing communication and coordination between neighbors. Non-living systems capable of similar responsive release hold great promise for information transfer in materials and site-specific drug delivery. One non-living system that offers a tunable platform for programming release is synthetic cells. Encased in a lipid bilayer structure, synthetic cells can be outfitted with molecular conduits that span the bilayer and lead to material exchange. While previous work expressing membrane pore proteins in synthetic cells demonstrated content exchange, user-defined control over release has remained elusive. In mammalian cells, connexon nanopore structures drive content release and have garnered significant interest since they can direct material exchange through intercellular contacts. Here, we focus on connexon nanopores and present activated release of material from synthetic cells in a light-sensitive fashion. To do this, we re-engineer connexon nanopores to assemble after post-translational processing by a protease. By encapsulating proteases in light-sensitive liposomes, we show that assembly of nanopores can be triggered by illumination, resulting in rapid release of molecules encapsulated within synthetic cells. Controlling connexin nanopore activity provides an opportunity for initiating communication with extracellular signals and for transferring molecular agents to the cytoplasm of living cells in a rapid, light-guided manner.
Characterization of Novel Recombinant Mycobacteriophages derived from Homologous Recombination between two Temperate Phages
Authors: Mohammed Hamidu T , Mageeney Catherine , Korenberg Jamie , Graham Lee , Ware Vassie C
Published: December 2022

Comparative analyses of mycobacteriophage genomes reveals extensive genetic diversity in genome organization and gene content, contributing to widespread mosaicism. We previously reported that the prophage of mycobacteriophage Butters (cluster N) provides defense against infection by Island3 (subcluster I1). To explore the anti-Island3 defense mechanism, we attempted to isolate Island3 defense escape mutants on a Butters lysogen, but only uncovered phages with recombinant genomes comprised of regions of Butters and Island3 arranged from left arm to right arm as Butters-Island3-Butters (BIBs). Recombination occurs within two distinct homologous regions that encompasslysin A, lysin B, andholingenes in one segment, andRecEandRecTgenes in the other. Structural genes of mosaic BIB genomes are contributed by Butters while the immunity cassette is derived from Island3. Consequently, BIBs are morphologically identical to Butters (as shown by transmission electron microscopy) but are homoimmune with Island3. A reverse experiment where an Island3 lysogen was infected with Butters yielded Butters phages and no recombinants, demonstrating directionality to the recombination phenomenon. Recombinant phages overcome antiphage defense and silencing of the lytic cycle. We leverage this observation to propose a stratagem to generate novel phages for therapeutic use.

GRAPHICAL ABSTRACT
Catching thoughts: self-caught experience sampling preferentially captures characteristic features of off-task experiences across the life span
Authors: Martinon Léa M. , Smallwood Jonathan , Riby Leigh M.
Published: December 2022

Understanding transient states, like off-task mind-wandering, is assumed to be improved by capitalizing on our ability to recognize changes in our stream of thought, a process known as meta-awareness. We test this assumption by comparing mind-wandering content when noticed by the participant (self-caught) against those thoughts reported after externally initiated probes (probe-caught). Thirty-eight older and 36 younger individuals completed a cognitive task. At the same time, multiple feature descriptions of thoughts (task-relevance, temporal focus, and self-referential) were captured using self and probe-caught methods. Using a pattern-learning approach, we established that self-caught experiences produce similar but generally “noisier” estimates compared to those reported at probes. However, self-caught experiences contained more off-task characteristics relative to reports at probes. Importantly, despite reductions in off-task thought, older adults retain the ability to self-catch experiences with these features. Our study establishes self-catching ability as an essential means of revealing the detailed content of off-task states, an ability relatively well maintained into old age.
Carrier based formulation of plant growth promoting Rhizobium species and their effect on albizia procera seedling
Authors: Ghabru Arti , Rana Neerja , Rangot Meenakshi
Published: December 2022

The carrier-based formulation of rhizobial cultures in general, excels to register their effects on various plant growth parameters of Albizia procera seedlings. Carrier based bio-inoculant prepared with rhizobial isolate FA6 of Uttrakhand performed better for all plant growth characteristics. Charcoal based application of rhizobial isolates also increased the N, P, K content of soil. In case of seedlings treated with charcoal-based formulation of rhizobial isolate from Himachal Pradesh maximum available N (323.30 kg/ha), P (38.97 kg/ha) and K (395.9 kg/ha) content was recorded in T2 (Charcoal based formulation of BA2 strain+20kg/ha N) which was significantly superior to T3 and uninoculated control. Among the charcoal-based formulation of rhizobial isolate from Uttrakhand seedlings under treatment T2 (Charcoal based formulation of FA6 strain+20kg/ha N) registered maximum available N (327.7kg/ha), P (39.01 kg/ha) and K (397.4 kg/ha) content in soil. Charcoal based application of rhizobial isolates significantly influenced the activity of soil enzymes (Dehydrogenase and Phosphatase). Application of Carrier based formulation of rhizobial isolate BA2 from Himachal Pradesh showed maximum dehydrogenase (11.20 μg TPF g-1h-1) and phosphatase (536.2 μmolL-1g-1h-1) activity as compare to uninoculated control. Whereas, among the rhizobial isolates from Uttrakhand maximum dehydrogenase (11.39 μg TPFg-1h-1) and phosphatase (545.4 μmol L-1g-1h-1) activity was also recorded with T2 (charcoal-based formulation of strain FA6+20kg/ha N) which was significantly superior to T3 and uninoculated control.
The compact Casπ (Cas12l) ‘bracelet’ provides a unique structural platform for DNA manipulation
Authors: Sun Ao , Li Cheng-Ping , Chen Zhihang , Zhang Shouyue , Li Danyuan , Yang Yun , Li Long-Qi , Zhao Yuqian , Wang Kaichen , Li Zhaofu , Liu Jinxia , Liu Sitong , Wang Jia , Liu Jun-Jie Gogo
Published: December 2022

CRISPR-Cas modules serve as the adaptive nucleic-acid immune systems for prokaryotes, and provide versatile tools for nucleic-acid manipulation in various organisms. Here, we discovered a new miniature type V system, CRISPR-Casπ (Cas12l) (∼860 aa), from the environmental metagenome. Complexed with a large guide-RNA (∼170 nt) comprising the tracrRNA and crRNA, Casπ (Cas12l) recognizes a unique 5’ C-rich PAM for DNA cleavage under a broad range of biochemical conditions, and generates gene editing in mammalian cells. Cryo-EM study reveals a ‘bracelet’ architecture of Casπ effector encircling the DNA target at 3.4-Å resolution, substantially different from the canonical ‘two-lobe’ architectures of Cas12 and Cas9 nucleases. And the large guide-RNA serves as a ‘two-arm’ scaffold for effector assembly. Our study expands the knowledge of DNA targeting mechanisms by CRISPR effectors, and offers an efficient but compact platform for DNA manipulations.