bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel insights into L-serine exporters in Corynebacterium glutamicum from gene mining and functional analysis
Authors: Gao Yujie , Zhang Xiaomei , Xu Guoqiang , Zhang Xiaojuan , Li Hui , Shi Jinsong , Xu Zhenghong 
Published: July 2022

ABSTRACTAmino acid exporters play an important role in regulating amino acid production by Corynebacterium glutamicum, and over 90% of amino acid export is attributed to exporters in this species. ThrE was reported to be an l-serine exporter, and SerE was identified as an l-serine exporter in our previous study. However, when both ThrE and SerE were deleted, the l-serine titer was decreased by 60%, suggesting other l-serine exporters may exist. In the present study, NCgl0254 and NCgl0255 were identified as novel l-serine exporters through comparative transcriptomics and gene functional analyses. The contributions of the four exporters (ThrE, SerE, NCgl0254 and NCgl0255) in l-serine export were studied by gene deletion, gene overexpression, amino acid export assay and real-time quantitative PCR (RT-qPCR). The results showed that SerE is the major l-serine exporter in C. glutamicum. Fermentation and amino acid export assays of SSAAI, SSAAI-serE-thrE-ncgl0254-ncgl0255 and SSAAIΔserEΔthrEΔncgl0254Δncgl0255 indicated that the four l-serine exporters undertake most of the l-serine export, and their overexpression enhanced export of l-serine in SSAAI. When one l-serine exporter was deleted, the transcription level of the other three exporters was upregulated. However, the decrease in l-serine titer caused by deletion of one exporter was not fully compensated by upregulation of the other three exporters at the transcription level, indicating that l-serine production by C. glutamicum may be determined by cooperative efficiency of all four l-serine exporters, with each being interdependent.IMPORTANCEThis work identified the novel l-serine exporters NCgl0254 and NCgl0255, and revealed their roles in l-serine export alongside the l-serine exporters. All four l-serine exporters are interdependent and undertake most of the l-serine export, but SerE is the major l-serine exporter. The findings expand our knowledge of amino acid exporters in C. glutamicum, and the approach can be employed for exploring of bacterial exporters of unknown function.
Influence of genetic ancestry on breast stromal cells provides biologic basis for increased incidence of metaplastic breast cancer in women of African descent
Authors: Kumar Brijesh , Batic Katie , Bhat-Nakshatri Poornima , Granatir Maggie M , Addison Rebekah Joann , Szymanski Megan , Baldridge Lee Ann , Temm Constance J. , Sandusky George , Althouse Sandra K , Storniolo Anna Maria , Nakshatri Harikrishna 
Published: July 2022

ABSTRACTThe biologic basis of genetic ancestry-dependent variability in disease incidence and outcome is just beginning to be explored. We recently reported enrichment of a population of ZEB1-expressing cells located adjacent to the ductal epithelial cells in the normal breast of women of African Ancestry (AA) compared to European Ancestry (EA). By establishing and characterizing cell lines corresponding to these cells and validating in vitro findings with tissue microarrays of healthy breast tissue from AA, EA and Latina Ancestry (LA) women, we demonstrate that these cells have the properties of fibroadipogenic/mesenchymal stromal cells that express PROCR and PDGFRα. PROCR+/ZEB1+/PDGFRα+ cells, hence renamed as PZP cells, are enriched in the normal breast tissues of AA compared to EA or LA women. In vitro, PZP cells trans-differentiated into adipocytes or osteocytes. In co-culture conditions, PZP:epithelial cell communication resulted in luminal epithelial cells acquiring basal/stem cell characteristics and increased expression of IL-6 suggesting the impact of this communication on breast epithelial hierarchy and the microenvironment. Consistent with this possibility, the level of phospho-STAT3, which is a downstream target of IL-6, was higher in the normal and cancerous breast tissues of AA compared to EA women. PZP cells transformed with HRasG12V ± SV40-T/t antigens generated metaplastic carcinoma in NSG mice suggesting that these cells could be the cell-of-origin of metaplastic breast cancers. Collectively, these results identify a stromal cell component that could influence the biology of breast cancer in AA women.
Novavax NVX-COV2373 triggers potent neutralization of Omicron sub-lineages
Authors: Bhiman Jinal N. , Richardson Simone I. , Lambson Bronwen E. , Kgagudi Prudence , Mzindle Nonkululeko , Kaldine Haajira , Crowther Carol , Gray Glenda , Bekker Linda-Gail ,   Novavax trial clinical lead author group, Shinde Vivek , Bennett Chijioke , Glenn Gregory M. , Madhi Shabir , Moore Penny L. 
Published: July 2022

AbstractThe SARS-CoV-2 Omicron (B.1.1.529) Variant of Concern (VOC) and its sub-lineages (including BA.2, BA.4/5, BA.2.12.1) contain spike mutations that confer high level resistance to neutralizing antibodies. The NVX-CoV2373 vaccine, a protein nanoparticle vaccine, has value in countries with constrained cold-chain requirements. Here we report neutralizing titers following two or three doses of NVX-CoV2373. We show that after two doses, Omicron sub-lineages BA.1 and BA.4 were resistant to neutralization by 72% (21/29) and 59% (17/29) of samples. However, after a third dose of NVX-CoV2373, we observed high titers against Omicron BA.1 (GMT: 1,197) and BA.4 (GMT: 582), with responses similar in magnitude to those triggered by three doses of an mRNA vaccine. These data are of particular relevance as BA.4 is emerging to become the dominant strain in many locations, and highlight the potential utility of the NVX-CoV2373 vaccine as a booster in resource-limited environments.
Interlimb coordination in Parkinson’s Disease is minimally affected by a visuospatial dual task
Authors: Hill Allen , Nantel Julie 
Published: July 2022

AbstractParkinson’s disease (PD) leads to reduced spatial and temporal interlimb coordination during gait as well as reduced coordination in the upper or lower limbs. Multi-tasking when walking is common during real-world activities, and affects some gait characteristics, like gait speed and variability. However, the impact of a dual task (DT) on intra and interlimb coordination of both lower and upper limbs when walking in people with PD remains unknown. Seventeen volunteers with mild to moderate PD (11 males, 65 ± 8 years, 173 ± 8 cm, 74 ± 20 kg, Unified Parkinson’s Disease Rating Scale motor section 10 ± 5) participated in gait trials in an Extended-CAREN system, which includes a treadmill, 12-camera Vicon motion capture system, and a 180° field-of-view virtual reality projection screen. Participants completed a 3 min walking trial and a 2 min visuospatial word recognition DT trial at their preferred walking pace. Single and DT were compared with a paired t-test, and the less and more affected (LA, MA) sides were tested for equivalence in sensitivity to the DT. During the DT, we found the LA shoulder ROM decreased by 1.5°, and the LA shoulder peak flexion decreased by 1.1° (p<.028, gav>.12). The LA and MA hip ROM were differently affected by the dual task (p=.023), and intralimb coordination was affected by dual tasking equivalently between sides (p=.004). These results suggest that during normal single-task gait, people with PD use attentional resources to compensate for reduced arm swing. Furthermore, our results indicate that any effect of DT on lower intralimb coordination is not meaningfully different between the LA and MA sides.Statements and DeclarationsThe authors have no relevant financial or non-financial interests to disclose.
Modeling the genetic footprint of fluctuating balancing selection: From the local to the genomic scale
Authors: Wittmann Meike J. , Mousset Sylvain , Hermisson Joachim 
Published: July 2022

AbstractNatural selection not only affects the actual loci under selection but also leaves “footprints” in patterns of genetic variation in linked genetic regions. This offers exciting opportunities for inferring selection and for understanding the processes shaping levels of genetic variation in natural populations. Here we develop analytical approximations based on coalescent theory to characterize the genetic footprint of a complex, but potentially common type of natural selection: balancing selection with seasonally fluctuating allele frequencies. We show that seasonal allele frequency fluctuations can have important (and partly unexpected) consequences for the genetic footprint of balancing selection. As also confirmed by stochastic simulations, fluctuating balancing selection generally leads to an increase in genetic diversity close to the selected site, the effect of balancing selection, but reduces diversity further away from the selected site, which is a consequence of the allele-frequency fluctuations effectively producing recurrent bottlenecks of allelic backgrounds. This negative effect usually outweighs the positive effect when averaging diversity levels across the entire chromosome. Strong fluctuating balancing selection even induces a loss of genetic variation in unlinked regions, e.g. on different chromosomes. If many loci in the genome are simultaneously under fluctuating balancing selection this could lead to substantial genome-wide reductions in genetic diversity. This may be the case, even if allele-frequency fluctuations are so small that individual footprints are hard to detect. Thus, together with genetic drift, selective sweeps and background selection, fluctuating selection could be one of the major forces shaping levels of genetic diversity in natural populations.Article summaryIn some species with multiple generations per year, many loci in the genome experience strong seasonally fluctuating selection, in some cases with stable maintenance of polymorphism. Here we investigate the consequences for levels of genetic diversity at linked neutral sites. Using analytical approximations and stochastic simulations, we find a characteristic local genetic footprint with a diversity peak around the selected site and a diversity valley further away and a substantial reduction in diversity levels chromosome-wide and even genome-wide.
Interpreting Inverse Correlation Time: from Blood flow to Vascular Network
Authors: Fang Qingwei , Jafari Chakameh Z. , Engelmann Shaun , Tomar Alankrit , Dunn Andrew K. 
Published: July 2022

AbstractThe inverse correlation time (ICT) is a key quantity in laser speckle contrast imaging (LSCI) measurements. Traditionally, ICT is regarded as a metric of blood flow, such as speed or perfusion. However, we highlight that ICT not only contains important information about blood flow, but also reflects the underlying structure of the vascular network. In the past, ICT has been found to be correlated with vessel diameter. Here, we further report that ICT exhibits a different sensitivity to blood flow depending on vessel orientation. Specifically, ICT is more sensitive to blood flow speed changes in vessels descending from or arising to the tissue surface, compared with those laying parallel to the surface. Those findings shift our understanding of ICT from purely blood flow to a combination of blood flow and vascular network structure. We also develop theories to facilitate the study of vascular network’s impact on ICT.
Accelerated and Reproducible Fiji for image processing using GPUs on the cloud
Authors: Hung Ling-Hong , Straw Evan , Colburn Zachary , Yeung Ka Yee 
Published: July 2022

AbstractSummaryGraphical processing units can greatly accelerate image processing but adoption has been hampered by the need for specialized hardware and software. The cloud offers inexpensive on-demand instances that can be pre-configured with the necessary software. Specifically, we use the Biodepot-workflow-builder (Bwb) to deploy a containerized version of Fiji that includes the CLIJ package to use GPUs on the cloud. In addition, we provide an Amazon Machine Image (AMI) with the correct drivers and Docker images pre-loaded. We demonstrate the portability and reproducibility of the platform by deploying an interactive Fiji/CLIJ workflow on both Amazon Web Services and IBM cloud. The workflows produce identical results while providing a 29-fold reduction in execution time.
Validity Assessment of Michigan’s Proposed qPCR Threshold Value for Rapid Water-Quality Monitoring of E. coli Contamination
Authors: McNair James N. , Lane Molly J. , Hart John J. , Porter Alexis M. , Briggs Shannon , Southwell Benjamin , Sivy Tami , Szlag David C. , Scull Brian T. , Pike Schuyler , Dreelin Erin , Vernier Chris , Carter Bonnie , Sharp Josh , Nowlin Penny , Rediske Richard R. 
Published: July 2022

AbstractMichigan’s water-quality standards specify that E. coli concentrations at bathing beaches must not exceed 300 E. coli per 100 mL, as determined by the geometric mean of culture-based concentrations in three or more representative samples from a given beach on a given day. Culture-based analyses require 18–24 h to complete, so results are not available for issuing beach notifications (advisories or closings) until the day following collection. This one-day delay is problematic because E. coli concentrations at beaches can change markedly from one day to the next. qPCR-based E. coli concentrations, by contrast, can be obtained in only 3–4 h, making same-day beach notifications possible. Michigan has proposed a qPCR threshold value (qTV) for E. coli of 1.863 log10 gene copies per reaction as a potential equivalent value to the state standard, based on statistical analyses of a set of training data from 2016–2018. The main purpose of the present study is to assess the validity of the proposed qTV by determining whether the implied qPCR-based beach notification decisions agree well with culture-based decisions on two sets of test data (from 2016–2018 and 2019–2020), and whether performance of the proposed threshold is similar on the test and training data. The results show that performance of the proposed qTV on both sets of test data was consistently good (e.g., 95% agreement with culture-based beach notification decisions during 2019–2020) and was at least as good as its performance on the training data set, supporting its use as an equivalent value to the state standard.
eIF3 subunit M regulates blood meal digestion in Rhodnius prolixus affecting ecdysis, reproduction and survival
Authors: Ameijeiras Pilar , Capriotti Natalia , Ons Sheila , Oliveira Pedro L. , Sterkel Marcos 
Published: July 2022

AbstractIn triatomines, blood-feeding triggers many physiological processes, including post-embryonic development and reproduction. Different feeding habits, such as hematophagy, can shape gene functions to meet the challenges of each type of diet. A comparison of transcriptomic and proteomic data indicates that post-transcriptional regulation of gene expression is crucial in triatomines, so we evaluated the impact of RNAi silencing of the eukaryotic translation initiation factors 3 subunit m (eIF3m) in R. prolixus physiology. We showed that eIF3m is essential for correct digestion, affecting the processes triggered by a blood meal. The silencing of this gene inhibited moulting and caused the premature death of nymphs, while in adult females inhibited oviposition and increased resistance to starvation. Male survival was not affected by eIF3m knockdown. The information regarding the eIF3m function in insects is scarce. The phenotypes observed in R. prolixus upon eIF3m gene silencing are different and more severe than those described in Drosophila melanogaster, pointing to the particular importance of this gene in triatomines.Summary statementThe information provided here indicates the importance of mRNA translation in modulating growth, reproduction, lifespan and starvation resistance in triatomine vectors.
Dynamic cortical and tractography atlases of proactive and reactive alpha and high-gamma activities
Authors: Ono Hiroya , Sonoda Masaki , Sakakura Kazuki , Kitazawa Yu , Mitsuhashi Takumi , Firestone Ethan , Luat Aimee F. , Marupudi Neena I. , Sood Sandeep , Asano Eishi 
Published: July 2022

ABSTRACTAlpha waves - posterior-dominant rhythms at 8-12 Hz reactive to eye opening and closure - are among the most fundamental EEG findings in clinical practice and research since Hans Berger first documented them in the early 20th century. Yet, the exact network dynamics of alpha waves in regard to eye movements remains unknown. High-gamma activity at 70-110 Hz is also reactive to eye movements and a summary measure of local cortical activation supporting sensorimotor or cognitive function. We aimed to build the first-ever brain atlases directly visualizing the network dynamics of eye movement-related alpha and high-gamma modulations, at cortical and white matter levels. We studied 28 patients (age: 5-20 years) who underwent intracranial EEG and electrooculography recordings. We measured alpha and high-gamma modulations at 2,170 electrode sites outside the seizure onset zone, interictal spike-generating areas, and MRI-visible structural lesions. Dynamic tractography animated white matter streamlines modulated significantly and simultaneously beyond chance, on a millisecond scale.Before eye closure onset, significant alpha augmentation occurred at the occipital and frontal cortices.After eye closure onset, alpha-based functional connectivity was strengthened, while high gamma-based connectivity was weakened extensively in both intrahemispheric and interhemispheric pathways involving the central visual areas. The inferior fronto-occipital fasciculus supported the strengthened alpha coaugmentation-based functional connectivity between occipital and frontal lobe regions, whereas the posterior corpus callosum supported the interhemispheric functional connectivity between the occipital lobes.After eye opening offset, significant high gamma augmentation and alpha attenuation occurred at occipital, fusiform, and inferior parietal cortices. High gamma coaugmentation-based functional connectivity was strengthened, whereas alpha-based connectivity was weakened in the posterior interhemispheric and intrahemispheric white matter pathways involving central and peripheral visual areas.Proactiveandreactivealpha waves involve extensive, distinct white matter networks that include the frontal lobe cortices, along with low- and high-order visual areas. High-gamma co-attenuation coupled to alpha co-augmentation in shared brain circuitry after eye closure supports the notion of an idling role for alpha waves during eye closure. These dynamic tractography atlases may improve understanding of the significance of EEG alpha waves in assessing the functional integrity of brain networks in clinical practice; they also may help elucidate the effects of eye movements on task-related brain network measures observed in cognitive neuroscience research.
Range Expansion and Breeding of White-cheeked Duck (Anas bahamensis) in the High Andes
Authors: Cisneros-Heredia Diego F. , Izurieta Mirjaya , Peñaherrera Emilia , Musschenga Maartje 
Published: July 2022

AbstractWe review the distribution of White-cheeked DuckAnas bahamensis rubrirostrisin mainland Ecuador and show that the species is expanding its range significantly. Contrary to published records,A. b. rubrirostrishas been present in mainland Ecuador at least since the early 20thcentury, although probably in low numbers. During the 20th century, the species increased its range along the entire coastlands of Ecuador and nowadays, it has reached the coasts of Colombia. The species has also extended its presence along the Andes, and we report the first breeding records ofA. b. rubrirostrisin the Andes at altitudes between 2360–2440 m, the highest across the entire range of the species. We describe the transitioning plumage between duckling–juveniles, which has not been portrayed in detail before.
Development of a bispecific Antibody–Drug Conjugate targeting CD7 and CD33 to treat Acute Myeloid Leukaemia
Authors: Duckworth Andrew D. , Eberlein Cath , Pollard Victoria , Bethell Richard , Schon Oliver , Slupsky Joseph R. , Woolley John F. , Thorn (nee Daniels) Tiffany 
Published: July 2022

AbstractAcute myeloid leukemia (AML) is a heterogeneous malignancy of the bone marrow associated with poor outcomes and limited treatment options available to patients. Recent developments have demonstrated that patient stratification based on disease classification (e.g. somatic mutations) allows for selective treatment regimens and greatly improved outcomes. AML patients can also be stratified based upon the heterogeneous immunophenotype of surface antigen expression on leukemic blasts and stem cells. Here we present data identifying a sub-population of AML patients showing expression of both CD33 and CD7 on their tumour cells, using mass cytometry. This combination of antigens is disease-specific, and is not expressed on healthy haematopoietic cells in patients. We developed a bispecific antibody–drug conjugate (ADC) targeting both CD7 and CD33 and demonstrate that these bispecific ADCs are cytotoxic to AML cells in vitro. Importantly, the anti-CD33/CD7 bispecific ADCs are more selective than single-antigen targeting ADCs and safely discriminate tumour from healthy cells (either myeloid or lymphoid). These anti-CD33/CD7 bispecific ADCs are well tolerated and selectively target AML cells in pre-clinical in vivo studies in mice. This study presents the first proof-of-principle for targeting specific and unique combinations of surface antigens on tumour cells with potential to overcome observed toxicities with current ADCs.
The energetics of rapid cellular mechanotransduction
Authors: Young Michael N. , Sindoni Michael J. , Lewis Amanda H. , Zauscher Stefan , Grandl Jörg 
Published: July 2022

SummaryCells throughout the human body detect mechanical forces. While it is known that the rapid (millisecond) detection of mechanical forces is mediated by force-gated ion channels, a detailed quantitative understanding of cells as sensors of mechanical energy is still lacking. Here, we combine atomic force microscopy with patch-clamp electrophysiology to determine the physical limits of cells expressing the force-gated ion channels Piezo1, Piezo2, TREK1, and TRAAK. We find that, depending on the ion channel expressed, cells can function either as proportional or nonlinear transducers of mechanical energy, detect mechanical energies as little as ∼100 fJ, and with a resolution of up to ∼1 fJ. These specific energetic values depend on cell size, channel density, and cytoskeletal architecture. We also make the surprising discovery that cells can transduce forces either nearly instantaneously (< 1ms), or with substantial time delay (∼10 ms). Using a chimeric experimental approach and simulations we show how such delays can emerge from channel-intrinsic properties and the slow diffusion of tension in the membrane. Overall, our experiments reveal the capabilities and limits of cellular mechanosensing and provide insights into molecular mechanisms that different cell types may employ to specialize for their distinct physiological roles.