bluuebunny/crossref_metadata_2025 huggingface dataset:
Prepectoral Breast Reconstruction Without the Use of Acellular Dermal Matrix: A 3-Year Review
Authors: Poveromo Luke P. , Franck Philipp , Ellison Angela , Janhofer David E. , Asadourian Paul A. , Otterburn David M.
Published: May 2022

Introduction

Acellular dermal matrix (ADM) is frequently used during prepectoral tissue expander–based breast reconstruction. However, there has been a paucity of literature describing the experience of prepectoral reconstruction without the accompanying use of ADM. We seek to highlight our institutional experience with immediate prepectoral tissue expander placement without the use of ADM in breast reconstruction.

Methods

A retrospective, single-institution review of patient records was performed to identify all patients who underwent either skin sparing or nipple-sparing mastectomy with immediate tissue expander placement without the use of ADM. Demographics including age, body mass index, comorbidities, history of smoking or steroid use, perioperative radiation or chemotherapy, intraoperative details, and complication profiles during the tissue expander stage were retrospectively collected and analyzed. At the time of tissue expander placement, all mastectomy flaps were evaluated clinically and with indocyanine green laser angiography. Postoperative outcomes were tracked.

Results

Between 2017 and 2020, 63 patients (for a total of 108 breasts) underwent either skin sparing (16%) or nipple-sparing mastectomy (84%) with immediate prepectoral tissue expander without ADM placement. Fourteen percent of breasts developed postoperative cellulitis, 19% of breasts developed skin compromise, and 5% required a postoperative revisional procedure that did not result in immediate expander explant. There was a 13% (n = 14 breasts) explant rate occurring at a mean time of 74 days. Of those breasts that developed skin compromise, 45% went on to require eventual explant. Patients in the study were followed for an average of 6.3 months.

Conclusions

Immediate prepectoral breast reconstruction using tissue expanders without ADM offers a viable alternative to established reconstructive paradigms. The major complication rate for prepectoral reconstruction without the use of ADM (17%) was found to be comparable with our historical subpectoral tissue expander reconstruction with ADM use. Tissue expander explant rates were also comparable between the prepectoral without ADM (13%) and the subpectoral with ADM cohorts. These preliminary data suggest that immediate breast reconstruction with tissue expander placement without accompanying ADM is viable alternative in the breast reconstructive algorithm.
A Social Media Analysis of Wellness Culture in Plastic Surgery Residency
Authors: Maisner Rose S. , Kapadia Kailash , Keenan Emily , Ravikumar Vaishali , Ayyala Haripriya S. , Lee Edward S.
Published: May 2022

Background

Burnout, “a psychological syndrome of emotional exhaustion, depersonalization, and reduced personal accomplishment”, afflicts approximately one third of plastic surgery attending surgeons and residents. Burnout can be detrimental to resident training and patient outcomes. Therefore, cultivating wellness during residency is essential. In fact, the Accreditation Council for Graduate Medical Education requires residency programs to create learning and working environments that optimize faculty and resident wellness. With increasing social media use by plastic surgery residency programs, this study aimed to analyze their posts for wellness-related content.

Methods

Integrated plastic surgery residency programs were obtained from the American Council of Academic Plastic Surgeons Web site, and their associated social media accounts were identified. The authors reviewed all post images, captions, and comments made by the program's account, until July 3, 2021. Any hashtags relating to wellness were also recorded.

Results

Of 82 programs, 76 (92.7%) had active Instagram accounts, 31 (37.8%) had active Facebook accounts, and 30 (36.6%) had active Twitter accounts. Instagram had higher rates of engagement than Facebook and Twitter (P < 0.001). Across all platforms, the mean percent of total posts related to wellness was 18.87%. The most common wellness content showcased resident work-life balance (48.73%), followed by educational events incorporating wellness activities (27.61%), attention to physical health (17.71%), healthy work environments (5.29%), wellness-specific activities (3.25%), team building activities (2.40%), and images implying but not directly showing resident wellness (1.46%). Programs did not vary significantly in percentages of total posts related to wellness by geographic region, ranking, or accreditation length. In total, 1893 wellness-related hashtags were used on Instagram, 253 on Facebook, and 72 on Twitter. The most used wellness-related hashtag was #residentlife. Only 40.8% to 50.8% of posts using wellness hashtags met at least 1 wellness criterion.

Conclusion

Despite the importance of burnout prevention during plastic surgery residency, less than a quarter of residency program social media content promote wellness. Social media can demonstrate how residency programs are incorporating wellness into their curricula, but whether residencies lack sufficient wellness initiatives or are not advertising such programming on their social media accounts remains to be studied.
Incisional Negative Pressure Wound Therapy Is Protective Against Postoperative Cardiothoracic Wound Infection
Authors: Nguyen Kaitlin A. , Taylor George A. , Webster Theresa K. , Jenkins Rachel A. , Houston Nicklaus S. , Kahler Dylan L. , Gassman Andrew A. , Jones Christine M.
Published: May 2022

Background

Sternal wound infections are a rare but life-threatening complication of cardiothoracic surgery. Prior literature has supported the use of negative pressure wound therapy to decrease sternal wound infections and promote healing. This study sought to determine whether closed incision negative pressure therapy reduced wound infection and improved outcomes in cardiothoracic surgery.

Methods

A retrospective cohort study was performed including all adult patients who underwent nontraumatic cardiothoracic surgery at a single institution between 2016 and 2018 (n = 1199). Patient characteristics, clinical variables, and surgical outcomes were compared between those who did and did not receive incisional negative pressure wound therapy intraoperatively. Multivariable logistic regression analysis determined factors predictive or protective of the development of complications.

Results

Incisional negative pressure wound therapy was used in 58.9% of patients. Patients who received this therapy were older with statistically higher rates of hyperlipidemia, statin, and antihypertensive use. The use of negative pressure wound therapy was found to significantly reduce rates of both wound infection (3.0% vs 6.3%, P = 0.01) and readmission for wound infection (0.7% vs 2.6%, P = 0.01). After controlling for confounding variables, negative pressure wound therapy was found to be a protective factor of surgical wound infection (odds ratio, 0.497; 95% confidence interval, 0.262–0.945).

Conclusions

In the largest population studied to date, this study supported the expanded use of negative pressure therapy on sternal wound incisions to decrease infection rates.
The Effect of Presurgical and Postsurgical Topical Tacrolimus on Pedicled Flap Survival in Rats
Authors: Jung Wooram F. , Van Y-vu Robert , Huang Hao , Otterburn David M.
Published: May 2022

Purpose

Our previous rodent studies demonstrated significantly decreased full-thickness necrosis in pedicled dorsal skin flaps with topical tacrolimus as compared with petroleum jelly. Histologically, we found that topical tacrolimus was correlated with increased vascular growth in areas more susceptible to ischemic damage. The purpose of this study was to investigate the potential benefits of pretreatment with tacrolimus. By applying tacrolimus in advance of raising the dorsal skin flaps, we hoped to increase vascularity and thus increase the overall viability of the flaps.

Methods

Twenty Sprague-Dawley rats were initially randomized to 4 groups based on timing of tacrolimus treatment (presurgical/postsurgical treatment): control/control (C/C), control/tacrolimus (C/T), tacrolimus/control (T/C), and tacrolimus/tacrolimus (T/T). Treatments consisted of 0.2 g of the control (topical petroleum jelly) and 0.1% topical tacrolimus to the rat dorsum twice per day. After 7 days of presurgical treatment, a cranially based dorsal skin flap measuring 3 × 10 cm was created. Two rats perished during surgery and were excluded for further analysis. Each rat was treated for a further 7 days and sacrificed. Two blinded reviewers marked the total skin flap area as well as areas of viable tissue, reversible ischemia, and full-thickness necrosis. Percentage areas were calculated using Fiji/ImageJ, and statistical analysis was performed in R.

Results

The average viable areas for C/C, C/T, T/C, and T/T were 31.4%, 31.9%, 35.6%, and 22.6%, respectively. The average reversible ischemic area for C/C, C/T, T/C, and T/T was 53.1%, 54.0%, 54.1%, and 71.5%, respectively. The average necrotic area for C/C, C/T, T/C, and T/T was 15.4%, 14.0%, 10.2%, and 5.9%, respectively. For areas of reversible ischemia, T/T arm had higher areas compared with C/T (P = 0.004) and T/C (P = 0.044). There was no significance between treatment arms for areas of viable and necrotic tissue.

Conclusions

We observed higher areas of reversible ischemia for continuous tacrolimus treatment compared with only pre–tacrolimus application or post–tacrolimus application. This suggests that tacrolimus application before and after surgical insult may be associated with improved ischemic survival of the skin. Although we did not observe decreased areas of necrosis for tacrolimus treatment compared with control, this was likely due to the limited number of rats available in each arm to reach significance. Further study is needed to fully elucidate the encouraging trends that were observed.
Machine-Learning-Based Olfactometry: An Auxiliary System for Human Assessors in Olfactory Measurement
Authors: Shang Liang , Liu Chuanjun , Tang Fengzhen , Chen Bin , Liu Lianqing , Hayashi Kenshi
Published: May 2022

Although gas chromatography/olfactometry (GC/O) has been employed as a powerful analytical tool in odor measurement, its application is limited by the variability, subjectivity, and high cost of the trained panelists who are used as detectors in the system. The advancements in data-driven science have made it possible to predict structure-odor-relationship (SOR) and thus to develop machine-learning-based olfactometry (ML-GCO) in which the human panelists may be replaced by machine learning models to obtain the sensory information of GC-separated chemical compounds. However, one challenge remained in ML-GCO is that there are too many odor descriptors (ODs) being used to describe the sensory characteristics of odorants. It is impractical to build a corresponding model for each OD. To solve this issue, we propose a SOR prediction approach based on odor descriptor clustering. 256 representative ODs are firstly classified into 20 categories using a co-occurrence Bayesian embedding model. The categorization effect is explained according to the semantic relationships using a pre-trained Word2Vec model. Various molecular structure features including molecularly parameters, molecular fingerprints, and molecular 2D graphic features extracted by convolutional neural networks, are employed to predict the aforementioned odor categories. High prediction accuracies (Area under ROC curve was 0.800±0.004) demonstrate the rationality of the proposed clustering scenario and molecular feature extraction. This study makes the ML-GCO models much closer to the practical application since they can be expected as either an auxiliary system or complete replacement of human panelists to perform the olfactory evaluation.
SOX15 regulates stem cell pluripotency and promotes neural fate during differentiation by activating Hes5
Authors: Choi Eun-Bee , Vodnala Munender , Saini Prince , Zerbato Madeleine , Ho Jaclyn J. , Anugula Sharath , Ho Sui Shannan J. , Yoon Joon , Inouye Carla , Fong Yick W.
Published: May 2022

SOX2 and SOX15 are Sox family transcription factors enriched in embryonic stem cells (ESCs). The role of SOX2 in activating gene expression programs essential for stem cell self-renewal and acquisition of pluripotency during somatic cell reprogramming is well-documented. However, the contribution of SOX15 to these processes is unclear and often presumed redundant with SOX2 because both transcription factors display similar DNA binding specificity. Here, we show that SOX15 contributes to stem cell maintenance by cooperating with ESC-enriched transcriptional coactivators to ensure optimal expression of pluripotency-associated genes. We demonstrate that SOX15 depletion compromises reprogramming of fibroblasts to pluripotency which cannot be compensated by SOX2. Ectopic expression of SOX15 promotes the reversion of a post-implantation, epiblast stem cell state back to a pre-implantation, ESC-like identity even though SOX2 is expressed in both cell states. We also uncover a role of SOX15 in lineage specification, by showing that loss of SOX15 leads to defects in commitment of ESCs to neural fates. SOX15 promotes neural differentiation by binding to and activating a previously uncharacterized distal enhancer of a key neurogenic regulator, Hes5. Together, these findings identify a multifaceted role of SOX15 in induction and maintenance of pluripotency and neural differentiation.
Optimal thromboprophylaxis strategies in non-critically ill patients with COVID-19 pneumonia. The PROTHROMCOVID Randomized Controlled Trial
Authors: Muñoz-Rivas Nuria , Aibar Jesús , Gabara-Xancó Cristina , Trueba-Vicente Ángela , Urbelz-Pérez Ana , Gómez-Del Olmo Vicente , Demelo-Rodriguez Pablo , Rivera-Gallego Alberto , Bosch-Nicolau Pau , Perez-Pinar Montserrat , Rios-Prego Mónica , Madridano-Cobo Olga , Ramos-Alonso Laura , Alonso-Carrillo Jesús , Francisco-Albelsa Iria , Martí-Saez Edelmira , Maestre-Peiró Ana , Méndez-Bailón Manuel , Hernández-Rivas José Ángel , Torres-Macho Juan ,   The PROTHROMCOVID Trial investigators
Published: May 2022

Background

Hospitalized patients with COVID-19 are at increased risk for thrombosis, acute respiratory distress syndrome and death. The optimal dosage of thromboprophylaxis is unknown.

Objective

To evaluate the efficacy and safety of tinzaparin in prophylactic, intermediate, and therapeutic doses in non-critical patients admitted for COVID-19 pneumonia.

Design, setting, and participants

Randomized controlled, multicenter trial (PROTHROMCOVID) enrolling non-critical, hospitalized adult patients with COVID-19 pneumonia.

Interventions

Patients were randomized to prophylactic (4500 IU), intermediate (100 IU/kg), or therapeutic (175 IU/kg) doses of tinzaparin during hospitalization, followed by 7 days of prophylactic tinzaparin at discharge.

Measurements

The primary efficacy outcome was a composite endpoint of symptomatic systemic thrombotic events, need for invasive or non-invasive mechanical ventilation, or death within 30 days. The main safety outcome was major bleeding at 30 days.

Results

Of the 311 subjects randomized, 300 were included in the analysis (mean [SD] age, 56.7 [14.6] years; males, 182 [60.7%]. The composite endpoint at 30 days from randomization occurred in 58 patients (19.3%) of the total population; 19 (17.1 %) in the prophylactic group, 20 (22.1%) in the intermediate group, and 19 (18.5%) in the therapeutic dose group (P= 0.72). No major bleeding event was reported; non-major bleeding was observed in 3.7% of patients, with no intergroup differences.

Conclusions

In non-critically ill COVID-19 patients, intermediate or full-dose tinzaparin compared to standard prophylactic doses did not appear to increase benefit regarding the likelihood of thrombotic event, non-invasive ventilation or high-flow oxygen, or death.

Trial Registration

ClinicalTrials.gov Identifier (NCT04730856).

Funding

This independent research initiative was supported by Leo-Pharma; Tinzaparin was provided by Leo Pharma.
Knockout of mitogen-activated protein kinase 3 causes barley root resistance against Fusarium graminearum
Authors: Basheer Jasim , Vadovič Pavol , Šamajová Olga , Melicher Pavol , Komis George , Křenek Pavel , Králová Michaela , Pechan Tibor , Ovečka Miroslav , Takáč Tomáš , Šamaj Jozef
Published: May 2022

The roles of mitogen-activated protein kinases (MAPKs) in plant-fungal pathogenic interactions are less understood in crops. Here, microscopic, phenotyping, proteomic and biochemical analyses revealed that independent TALEN-based knockout lines of Hordeum vulgare MITOGEN-ACTIVATED PROTEIN KINASE 3 (HvMPK3 KO) were resistant against Fusarium graminearum infection. When co-cultured with roots of the HvMPK3 KO lines, F. graminearum hyphae were excluded to the extracellular space, the growth pattern of hyphae was considerably deregulated, mycelia development was less efficient and number of appressoria and their penetration potential were significantly reduced. Intracellular penetration of hyphae was preceded by the massive production of reactive oxygen species (ROS) in attacked cells of the wild type, but it was mitigated in the HvMPK3 KO lines. Suppression of ROS production in these lines coincided with the elevated abundances of catalase and ascorbate peroxidase. Moreover, differential proteomic analysis revealed downregulation of defense-related proteins in wild type, and the upregulation of peroxidases, lipid transfer proteins, and cysteine proteases in HvMPK3 KO lines after 24h of F. graminearum inoculation. Consistently with proteomic analysis, microscopic observations showed an enhanced suberin accumulation in roots of HvMPK3 KO lines, most likely contributing to the arrested infection by F. graminearum. These results suggest that TALEN-based knockout of HvMPK3 leads to the barley root resistance against Fusarium root rot.
Statin intolerance – Prevalence and practical management in a specialized lipid clinic
Authors: Turdo Yannick , Collet Tinh-Hai
Published: May 2022

Aims

Statins are recommended as first-line treatment to prevent cardiovascular disease, but high rates of adverse events and subsequent discontinuation can prevent effective treatment in some patients. We aimed to describe the intensity, nature and frequency of adverse effects caused by statins and other lipid-lowering drugs, and to assess their association with clinical predictors and treatment strategies.

Methods

This is a retrospective study of 121 consecutive unselected patients followed at a specialized lipid referral clinic in Lausanne University Hospital, Switzerland, in 2018 whose clinical data spanned 2016 until 2019.

Results

Adverse effects were reported by 58% of patients, causing musculoskeletal (72%), neurologic (40%), gastrointestinal (25%) and other (25%) symptoms. Gastrointestinal symptoms affected 35% of women, but only 12% of men (p=0.06). Statins caused more adverse effects than other drugs, with atorvastatin (63%) and simvastatin (64%) achieving the lowest rates, pravastatin (87%) and fluvastatin (100%) the highest. Fenofibrate was associated with significantly less frequent adverse effects than statins (22% vs. 57%, p=0.006). Adaptation and termination of the treatment led to 86% and 88% lower intensity of symptoms, respectively.

Conclusion

While the predominance of musculoskeletal symptoms caused by lipid-lowering drugs is known, symptoms affecting other organ systems should not be ignored. Statins were the lipid-lowering drug class with the highest rates of adverse effects. To maintain compliance and cardiovascular prevention, treatment strategies such as a change of dosage, frequency of administration, daily timing, or switching active substance can contribute to better tolerance of statin treatment. Further investigation is needed to establish specific treatment strategies for individual patient profiles.
Non-invasive Fluorescence Imaging of Gut Commensal Bacteria in Live Mice
Authors: Apostolos Alexis J. , Chordia Mahendra D. , Kolli Sree H. , Rutkowski Melanie R. , Pires Marcos M.
Published: May 2022

In mammals, gut commensal microbiota interact extensively with the host and the same interactions can be dysregulated in diseased states. The development of methods to monitor gut microbiota in vivo can lead to improved foundational understanding of the biological events underpinning these interactions. The current standard for non-invasive monitoring of gut bacteria entails classification by 16S rRNA sequencing from fecal samples. This method has many advantages but also has serious limitations, especially for monitoring dynamic changes in the gut of live animals. In recent years, several imaging techniques have been widely adopted that afford non-invasive assessment of animal subjects – most notably in cancer biology; however, these technical gains have not translated to the imaging of gut bacterial communities. Herein, we describe a method to non-invasively image commensal bacteria based on the specific metabolic labeling of bacterial cell walls to illuminate the gut bacteria of live mice. This tagging strategy may additionally provide unprecedented insight into cell wall turnover of gut commensals, which has implications for bacterial cellular growth and division, in a live animal.
Temporal and spatial patterns of vertebrate extinctions during the Anthropocene
Authors: Pincheira-Donoso Daniel , Harvey Lilly P. , Guirguis Jacinta , Goodyear Luke E. B. , Finn Catherine , Johnson Jack V. , Grattarola Florencia
Published: May 2022

The human-induced annihilation of modern biodiversity is dragging the planet into a mass extinction that has already altered patterns of life globally. Among vertebrates, over 500 species have become extinct or possibly extinct in the last five centuries – an extinction rate that would have taken several millennia without human intervention. Vertebrate extinctions have often been quantified as cumulative counts that reveal sharp increases in losses over time. Here, we quantify global tetrapod extinctions since the 1400s using numbers of species losses across successive and independent time periods until present. Our results reveal that extinctions were low and fundamentally restricted to islands in pre-industrial times, experiencing a significant increase and spread over continental mainland following the onset of the industrial revolution. Recent amphibian extinctions alarmingly exceed the extinctions of all tetrapods, while extinctions of island birds account for a third of all extinctions. Finally, we quantified the relationship between human population growth (HPG, as a proxy for aggregate human effects on the environment) and extinctions between 1800-2000, to then predict that an estimated 838 tetrapod species will go extinct between 2030-2100 based on United Nations HPG projections. These findings further warn humanity about the need to sustainably control HPG and the destructive impacts of rapid environmental change on ecosystems worldwide.
Dynamic regulation of neural variability during working memory reflects dopamine, functional integration, and decision-making
Authors: Garrett Douglas D. , Kloosterman Niels A. , Epp Samira , Chopurian Vivien , Kosciessa Julian Q. , Waschke Leonhard , Skowron Alexander , Shine James. M. , Perry Alistair , Salami Alireza , Rieckmann Anna , Papenberg Goran , Wåhlin Anders , Karalija Nina , Andersson Micael , Riklund Katrine , Lövdén Martin , Bäckman Lars , Nyberg Lars , Lindenberger Ulman
Published: May 2022

The regulation of moment-to-moment neural variability may permit effective responses to changing cognitive demands. However, the mechanisms that support variability regulation are unknown. In the context of working memory, we leverage the largest available PET and fMRI dataset to jointly consider three lenses through which neural variability regulation could be understood: dopamine capacity, network-level functional integration, and flexible decision processes. We show that with greater working memory load, upregulation of variability was associated with elevated dopamine capacity and heightened functional integration, effects dominantly expressed in the striato-thalamic system rather than cortex. Strikingly, behavioral modeling revealed that working memory load evoked substantial decision biases during evidence accumulation, and those who jointly expressed a more optimal decision bias and higher dopamine capacity were most likely to upregulate striato-thalamic variability under load. We argue that the ability to align striato-thalamic variability to level of demand may be a hallmark of a well-functioning brain.
Minute-scale Periodicity of Neuronal Firing in the Human Entorhinal Cortex
Authors: Aghajan Zahra M. , Kreiman Gabriel , Fried Itzhak
Published: May 2022

Grid cells in the entorhinal cortex demonstrate spatially periodic firing patterns, which are thought to provide a map of space on behaviorally relevant length scales. It is unknown, however, whether such periodicity exists for behaviorally relevant time scales in the human brain. Here we investigated neuronal firing during a temporally continuous uninterrupted experience by presenting fourteen neurosurgical patients with an audiovisual video while recording single neuron activity from multiple brain regions. We report on a set of units that modulate their activity in a strikingly periodic manner across different timescales—from seconds to many minutes. These cells were most prevalent in the entorhinal cortex. Time within the video could be decoded from their population activity. Furthermore, these cells remapped their dominant periodicity to shorter timescales during a subsequent recognition memory task. When the audiovisual sequence was presented at two different speeds (regular and faster), a significant percentage of these temporally periodic cells (TPCs) maintained their timescales, suggesting a degree of invariance with respect to the narrative content. The temporal periodicity of TPCs may complement the spatial periodicity of grid cells Whether these cells provide scalable spatiotemporal metrics for encoding and retrieval of human experience warrants future investigations.
A quantitative eDNA-based method to monitor fish spawning in lakes: application to European perch and whitefish
Authors: Vautier Marine , Chardon Cécile , Goulon Chloé , Guillard Jean , Domaizon Isabelle
Published: May 2022

There is an urgent need to evaluate the effects of anthropogenic pressures and climatic change on fish populations’ dynamics. When monitored in lakes, the spawning of fish is generally assessed using traditional, mostly destructive or damaging, methods as gillnetting and collection of fertilized eggs.

Over the last decade, environmental DNA (eDNA) based methods have been widely developed for the detection of aquatic species, offering a non-invasive alternative method to conventional biomonitoring tools. In particular, the emergence of new methods as the droplet digital PCR (ddPCR) offer the possibility to quantify an absolute eDNA signal in a very sensitive way and at a low cost.

Here, we developed and implemented a quantitative eDNA method to monitor the spawning activity of two fish species, European perch and whitefish. ddPCR protocols were formalized based on existing and newly designed COI primers, and were applied during four spawning periods in lake Geneva.

The results demonstrate the efficiency of eDNA coupled with ddPCR to identify the timing and duration of the spawning periods, as well as the peak of the spawning activity for the targeted species. In addition, the use of a control species (i.e., quantification of the eDNA signal of a fish that does not reproduce during the monitoring period) was shown to be relevant to clearly discriminate fluctuations of the eDNA signal associated to the spawning activity from the baseline eDNA signal. For future implementation, we recommend using an integrative sampling strategy (e.g., pooled samples for a give station) to smooth the local variability of the eDNA signal. These results show that we reached an operational level to use these non-invasive eDNA methods to monitor the spawning periods of these two fish species in large lakes.
RanBP1 plays an essential role in directed migration of neural crest cells during development
Authors: Barriga Elias H , Alasaadi Delan N , Mencarelli Chiara , Mayor Roberto , Pichaud Franck
Published: May 2022

Collective cell migration is essential for embryonic development, tissue regeneration and repair, and has been implicated in pathological conditions such as cancer metastasis. It is, in part, directed by external cues that promote front-to-rear polarity in individual cells. However, our understanding of the pathways that underpin the directional movement of cells in response to external cues remains incomplete. To examine this issue we made use of neural crest cells (NC), which migrate as a collective during development to generate vital structures including bones and cartilage. Using a candidate approach, we found an essential role for Ran-binding protein 1 (RanBP1), a key effector of the nucleocytoplasmic transport pathway, in enabling directed migration of these cells. Our results indicate that RanBP1 is required for establishing front-to-rear polarity, so that NCs are able to chemotax. Moreover, our work suggests that RanBP1 function in chemotaxis involves the polarity kinase LKB1/PAR4. We envisage that regulated nuclear export of LKB1 through Ran/RanBP1 is a key regulatory step required for establishing front-to-rear polarity and thus chemotaxis, during NC collective migration.
Pathophysiology of Dyt1 dystonia is mediated by spinal cord dysfunction
Authors: Pocratsky Amanda M. , Nascimento Filipe , Özyurt M. Görkem , White Ian J. , Sullivan Roisin , O’Callaghan Benjamin J. , Smith Calvin C. , Surana Sunaina , Beato Marco , Brownstone Robert M.
Published: May 2022

Dystonia, a neurological disorder defined by abnormal postures and disorganised movements, is considered to be a neural circuit disorder with dysfunction arising within and between multiple brain regions. Given that spinal circuits constitute the final pathway for motor control, we sought to determine their contribution to the movement disorder. Focusing on the most common inherited dystonia, DYT1-TOR1A, we confined a conditional knockout ofTor1ato the spinal cord and dorsal root ganglia (DRG) and found that these mice recapitulated the phenotype of the human condition, developing early onset generalised torsional dystonia. Physiologically, these mice bore the hallmark features of dystonia: spontaneous contractions at rest, excessive sustained contractions during voluntary movements including co-contractions of motor antagonists, and altered sensory-motor reflexes. Furthermore, spinal locomotor circuits were impaired. Together, these data challenge current understanding of dystonia, and lead to broader insights into spinal cord function and movement disorder pathophysiology.
Manipulating the rapid consolidation periods in a learning task affects general skills more than statistical learning
Authors: Szücs-Bencze Laura , Fanuel Lison , Szabó Nikoletta , Quentin Romain , Nemeth Dezso , Vékony Teodóra
Published: May 2022

Memory consolidation processes have traditionally been investigated from the perspective of hours or days. However, the latest developments in memory research showed that memory consolidation processes could occur even within seconds, possibly due to the neural replay of just-practiced memory traces during short breaks. Here, we investigate this rapid form of consolidation during statistical learning. We aim to answer (a) whether this rapid consolidation occurs in implicit statistical learning and general skill learning and (b) whether the duration of rest periods affects these two learning types differently. Participants performed a widely used statistical learning task - the Alternating Serial Reaction Time (ASRT) task - that enables us to measure implicit statistical and general skill learning separately. The ASRT task consisted of 25 learning blocks with a rest period between the blocks. In a between-subjects design, the length of the rest periods was fixed at 15 or 30 seconds, or the participants could control the length themselves. We found that the duration of rest periods does not affect the amount of statistical knowledge acquired but does change the dynamics of learning. Shorter rest periods led to better learning during the learning blocks, whereas longer rest periods promoted learning also in the between block rest periods, possibly due to the higher amount of replay. Moreover, we found weaker general skill learning in the self-paced group than in the fixed rest period groups. These results suggest that distinct learning processes are differently affected by the duration of short rest periods.
A Versatile Enhanced Freeze-Substitution Protocol for Volume Electron Microscopy
Authors: Bélanger Sébastien , Berensmann Heather , Baena Valentina , Duncan Keith , Meyers Blake C. , Narayan Kedar , Czymmek Kirk J
Published: May 2022

Volume electron microscopy, a powerful approach to generate large three-dimensional cell and tissue volumes at electron microscopy resolutions, is rapidly becoming a routine tool for understanding fundamental and applied biological questions. One of the enabling factors for its adoption has been the development of conventional fixation protocols with improved heavy metal staining. However, freeze-substitution with organic solvent-based fixation and staining has not realized the same level of benefit. Here, we report a straightforward approach including 2% osmium tetroxide, acetone and up to 3% water substitution fluid (compatible with traditional or fast freeze-substitution protocols), warm-up and transition from organic solvent to aqueous 2% OsO4. Once fully hydrated, samples were processed in aqueous based potassium ferrocyanide, thiocarbohydrazide, osmium tetroxide, uranyl acetate and lead acetate before resin infiltration and polymerization. We observed a consistent and substantial increase in heavy metal staining across diverse and difficult-to-fix test organisms and tissue types, including plant tissues, nematodes, yeast, and bacteria. Our approach opens new possibilities to combine the benefits of cryo-preservation with enhanced contrast for volume electron microscopy in diverse organisms.
MobsPy: A Meta-Species Language for Chemical Reaction Networks*
Authors: Cravo Fabricio , Függer Matthias , Nowak Thomas , Prakash Gayathri
Published: May 2022

Chemical reaction networks are widely used to model biochemical systems. However, when the complexity of these systems increases, the chemical reaction networks are prone to errors in the initial modeling and subsequent updates of the model.

We present the Meta-species-oriented Biochemical Systems Language (MobsPy), a language designed to simplify the definition of chemical reaction networks in Python. MobsPy is built around the notion of meta-species, which are sets of species that can be multiplied to create higher-dimensional orthogonal characteristics spaces and inheritance of reactions. Reactions can modify these characteristics. For reactants, queries allow to select a subset from a meta-species and use them in a reaction. For products, queries specify the dimensions in which a modification occurs. We demonstrate the simplification capabilities of the MobsPy language at the hand of a running example and a circuit from literature. The MobsPy Python package includes functions to perform both deterministic and stochastic simulations, as well as easily configurable plotting. The MobsPy package is indexed in the Python Package Index and can thus be installed via pip.
Get the gist of the story: Neural map of topic keywords in multi-speaker environment
Authors: Park Hyojin , Gross Joachim
Published: May 2022

Neural representation of lexico-semantics in speech processing has been revealed in recent years. However, to date, how the brain makes sense of the higher-level semantic gist (topic keywords) of a continuous speech remains mysterious. Capitalizing on a generative probabilistic topic modelling algorithm on speech materials to which participants listened while their brain activities were recorded by Magnetoencephalography (MEG), here we show spatio-temporal neural representation of topic keywords in a multi-speaker environment where task-relevant (attended) and -irrelevant (unattended) speech co-exits. We report the difference of neural representation between salient and less salient semantic gist of both attended and unattended speech. Moreover, we show that greater sensitivity to semantically salient unattended speech in the left auditory and motor cortices negatively mediates attended speech comprehension.
Optical mapping compendium of structural variants across global cattle breeds
Authors: Talenti A. , Powell J. , Wragg D. , Chepkwony M. , Fisch A. , Ferreira B.R. , Marcadante M.E.Z. , Santos I.M. , Ezeasor C.K. , Obishakin E.T. , Muhanguzi D. , Amanyire W. , Silwamba I. , Muma J.B. , Mainda G. , Kelly R.F. , Toye P. , Connelley T. , Prendergast J.
Published: May 2022

Structural variants (SV) have been linked to important bovine disease phenotypes, but due to the difficulty of their accurate detection with standard sequencing approaches, their role in shaping important traits across cattle breeds is largely unexplored. Optical mapping is an alternative approach for mapping SVs that has been shown to have higher sensitivity than DNA sequencing approaches. The aim of this project was to use optical mapping to develop a high-quality database of structural variation across cattle breeds from different geographical regions, to enable further study of SVs in cattle.

To do this we generated 100X Bionano optical mapping data for 18 cattle of nine different ancestries, three continents and both cattle sub-species. In total we identified 13,457 SVs, of which 1,200 putatively overlap coding regions. This resource provides a high-quality set of optical mapping-based SV calls that can be used across studies, from validating DNA sequencing-based SV calls to prioritising candidate functional variants in genetic association studies and expanding our understanding of the role of SVs in cattle evolution.
Field margins as substitute habitat for the conservation of birds in agricultural wetlands
Authors: Pierre Mallet , Arnaud Béchet , Clélia Sirami , François Mesléard , Thomas Blanchon , François Calatayud , Thomas Dagonet , Elie Gaget , Carole Leray , Thomas Galewski
Published: May 2022

Breeding birds in agricultural landscapes have declined considerably since the 1950s and the beginning of agricultural intensification in Europe. Given the increasing pressure on agricultural land, it is necessary to identify conservation measures that consume little productive land. We tested the compensation hypothesis which states that field margins may represent substitute habitats for bird species in agricultural wetlands. We monitored bird species in 86 crop fields in rice paddy landscapes of Camargue (southern France), a wetland of international importance for birds. We investigated whether the area of three types of field margins (reed strips, grass strips and hedgerows) within a 500 meter buffer around the centroid of each crop fields had an effect on the abundance of bird species from three groups defined based on their primary habitat (reedbeds, grasslands, and forest edge species). We controlled for the area of each type of semi-natural habitat (wetlands, grasslands, and woodlands), crop diversity (rice, wheat, alfalfa, rape, and market gardening) and mean crop field size. Results show partial support of the compensation hypothesis with species-dependent responses to primary and substitute habitat area. Some species within the reedbed and grassland bird guilds are favored by the area of their primary habitat as well as by the area of field margins, in line with the compensation hypothesis. Eurasian reed warbler is favored by the area of both wetlands and reed strips. Corn bunting is favored by grassland and grass strip areas. We could not confirm the compensation hypothesis for other species. However, this may be due to the fact that most of these species did not respond to their primary habitat. These results therefore suggest that field margins may represent substitute habitats for some species but further studies, in contexts where species are strongly associated with their primary habitat, would be needed to confirm the generality of this hypothesis. Our results also suggest that species response to increasing the area of a field margin type may vary among guilds and even within guilds. Therefore, it may be difficult to favor all species within a given landscape and management actions may need to be tailored to whichever species are locally associated with the highest conservation priority. To tackle this challenge, it may be necessary to design landscape management actions at different spatial scales.
Tbx2 is essential for cochlear inner hair cell development and regeneration
Authors: Bi Zhenghong , Li Xiang , Ren Minhui , Gu Yunpeng , Zhu Tong , Li Shuting , Wang Guangqin , Sun Suhong , Sun Yuwei , Liu Zhiyong
Published: May 2022

Atoh1 is essential for the development of outer hair cells (OHCs) and inner hair cells (IHCs) in the mammalian cochlea. Whereas Ikzf2 is necessary for OHC development, the key gene for IHC development remains unknown. We found that deleting Tbx2 in neonatal IHCs led to their trans-differentiation into OHCs, by repressing 26.7% of IHC and inducing 56.3% of OHC genes, including Ikzf2. More importantly, persistent expression of Tbx2 together with transient Atoh1 effectively reprogramed non-sensory supporting cells into new IHCs expressing functional IHC marker vGlut3. The differentiation status of these new IHCs is much more advanced than those previously reported. Thus, Tbx2 is essential for IHC development, and its co-upregulation with Atoh1 in supporting cells represents a new approach for treating IHC degeneration-related deafness.
Auxin Plays a Role in the Adaptation of Rice to Anaerobic Germination and Seedling Establishment
Authors: Lee Kuo-Wei , Chen Jeremy J.W. , Wu Chung-Shen , Chang Ho-Chun , Chen Hong-Yue , Kuo Hsin-Hao , Lee Ya-Shan , Chang Yan-Lun , Chang Hung-Chia , Shiuea Shiau-Yu , Wu Yi-Chen , Ho Yi-Cheng , Chen Peng-Wen
Published: May 2022

Auxin is well known to stimulate coleoptile elongation and rapid seedling growth in the air. However, its role in regulating rice germination and seedling establishment under submergence is largely unknown. Previous studies have shown that excessive levels of IAA frequently cause the inhibition of plant growth and development. In the present study, the high-level accumulation of endogenous IAA is observed under submergence in the dark, stimulating rice coleoptile elongation but limiting the root and primary leaf growth during anaerobic germination (AG). We found that oxygen and light can reduce IAA levels, promote the seedling establishment and enhance rice AG tolerance. miRNA microarray profiling and RNA gel blot analysis results show that the expression of miR167 is negatively regulated by submergence; it subsequently modulates the accumulation of free IAA through the miR167-ARF-GH3 pathway. TheOsGH3-8encodes an IAA-amido synthetase that functions to prevent free IAA accumulation. Reduced miR167 levels or overexpressingOsGH3-8increase auxin metabolism, reduce endogenous levels of free IAA and enhance rice AG tolerance. The present study reveals that poor seed germination and seedling growth inhibition resulting from excessive IAA accumulation would cause intolerance to submergence in rice, suggesting that a certain threshold level of auxin is essential for rice AG tolerance.
Comparative study between radiofrequency- and muscimol-induced inhibition of cultured net5 works of cortical neuron
Authors: Lemercier Clément E. , Garenne André , Poulletier de Gannes Florence , El Khoueiry Corinne , Arnaud-Cormos Delia , Levêque Philippe , Lagroye Isabelle , Percherancier Yann , Lewis Noëlle
Published: May 2022

bioRxiv has withdrawn this manuscript due to a duplicate posting of https://doi.org/10.1101/2022.04.05.487108.
An interactive mass spectrometry atlas of histone posttranslational modifications in T-cell acute leukemia
Authors: Provez Lien , Van Puyvelde Bart , Corveleyn Laura , Demeulemeester Nina , Verhelst Sigrid , Lintermans Béatrice , Daled Simon , Roels Juliette , Clement Lieven , Martens Lennart , Deforce Dieter , Van Vlierberghe Pieter , Dhaenens Maarten
Published: May 2022

The holistic nature of omics studies makes them ideally suited to generate hypotheses on health and disease. Sequencing-based genomics and mass spectrometry (MS)-based proteomics are linked through epigenetic regulation mechanisms. However, epigenomics is currently mainly focused on DNA methylation status using sequencing technologies, while studying histone posttranslational modifications (hPTMs) using MS is lagging, partly because reuse of raw data is impractical. Yet, targeting hPTMs using epidrugs is an established promising research avenue in cancer treatment. Therefore, we here present the most comprehensive MS-based preprocessed hPTM atlas to date, including 21 T-cell acute lymphoblastic leukemia (T-ALL) cell lines. We present the data in an intuitive and browsable single licensed Progenesis QIP project and provide all essential quality metrics, allowing users to assess the quality of the data, edit individual peptides, try novel annotation algorithms and export both peptide and protein data for downstream analyses, exemplified by the PeptidoformViz tool. This data resource sets the stage for generalizing MS-based histone analysis and provides the first reusable histone dataset for epidrug development.
Hierarchical cue control of drug seeking in the face of cost
Authors: Collins Val , Bornhoft Kaisa N. , Wolff Amy , Sinha Sonal , Saunders Benjamin T.
Published: May 2022

Addiction is characterized by intermittent drug seeking despite rising costs. This behavior is heavily influenced by environmental stimuli that signal drug availability and reinforce seeking. We aimed to establish the relationship between three key aspects of human drug use in rats: the intermittent, binge nature of drug intake, the motivational conflict of drug seeking in the face of escalating negative costs, and the ability of different drug cues to interact to modulate relapse. Rats were trained to self administer cocaine on an intermittent access schedule, where brief drug availability states were signaled by a shift in the ambient lighting of the environment and cocaine delivery was signaled by a separate proximal cue. Rats then went through a conflict procedure, where foot shock intensity associated with cocaine seeking was escalated until intake was suppressed. We completed relapse tests where the drug delivery cue was non contingently presented alone, or in the context of dynamic drug availability state transitions. Intermittent access spurred psychomotor sensitization and binge-like cocaine intake. The intensity of binge-like drug taking during training was predictive of later drug seeking despite escalating costs. In relapse tests, the ability of a proximal drug cue to trigger relapse was gated by the presence of a global cue signaling drug-availability state transitions. Our results suggest that the pattern of drug intake plays a role in many features of addiction, including modifying an individual’s willingness to endure high costs associated with drug seeking. Further, our results indicate that drug-related sensory information can be hierarchically organized to exert a dynamic modulating influence on drug-seeking motivation.