bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mixing selects for predation resistance in lab-evolved communities of bacterial prey and social predatorMyxococcus xanthus
Authors: Saha Saheli , Bhat Bhoomika , Laloo Jessica Mellicent , Goyal Akshit , Pande Samay 
Published: March 2023

AbstractPopulation mixing, and transmission modes strongly influence social interactions. However, the impact of repeated mixing on the evolutionary dynamics of microbial predator-prey interactions remains underexplored1,2. Hence, we conducted a laboratory evolution experiment with bacterial predator-prey communities under two transfer regimens: repeated mixing (horizontal transfer) versus no mixing (vertical transfer). For this,Myxococcus xanthusserved as the generalist predator3,4andEscherichiacoli as prey. We show that prey populations from vertical regimen were less resistant to predation than the ones from horizontal regimen. This was because prey isolates in the vertical treatment showed varying resistance levels relative to ancestors, while those in the horizontal treatment demonstrated less variation. Moreover, analysis of prey populations over evolutionary time revealed that the populations from horizontal treatment showed increasing levels of resistance to predation over time, whereas the ones from vertical treatment did not show similar trend. The differences in the outcomes of the two treatments was because the variants better at intraspecies competition, can only be maintained in the vertical treatment, whereas in horizontal treatment the benefits of superior intraspecies competitive fitness are nullified because of population mixing, as predicted by mathematical modeling approach. These predictions were empirically confirmed. Moreover, contrary to our expectations, predatory efficiency of evolvedM. xanthusisolates was either the same or lesser than the ancestor. Together, we demonstrate that mixing affects the evolution of prey bacteria but has little effect on the hunting ability of the social predatorM. xanthus.
Inhibition of CDK12 elevates cancer cell dependence on P-TEFb by stimulation of RNA polymerase II pause release
Authors: Wang Zhijia , Himanen Samu V. , Haikala Heidi M. , Friedel Caroline C. , Vihervaara Anniina , Barborič Matjaž 
Published: March 2023

ABSTRACTP-TEFb and CDK12 facilitate transcriptional elongation by RNA polymerase II. Given the prominence of both kinases in cancer, gaining a better understanding of their interplay could inform the design of novel anti-cancer strategies. While down-regulation of DNA repair genes in CDK12-targeted cancer cells is being explored therapeutically, little is known about mechanisms and significance of transcriptional induction upon inhibition of CDK12. We show that selective targeting of CDK12 in colon cancer-derived cells activates P-TEFb via its release from the inhibitory 7SK snRNP. In turn, P-TEFb stimulates Pol II pause release at thousands of genes, most of which become newly dependent on P-TEFb. Amongst the induced genes are those stimulated by hallmark pathways in cancer, including p53 and NF-κB. Consequently, CDK12-inhibited cancer cells exhibit hypersensitivity to inhibitors of P-TEFb. While blocking P-TEFb triggers their apoptosis in a p53-dependent manner, it impedes cell proliferation irrespective of p53 by preventing induction of genes downstream of the DNA damage-induced NF-κB signaling. In summary, stimulation of Pol II pause release at the signal-responsive genes underlies the functional dependence of CDK12-inhibited cancer cells on P-TEFb. Our study establishes the mechanistic underpinning for combinatorial targeting of CDK12 with either P-TEFb or the induced oncogenic pathways in cancer.
Effects of recurrent summer droughts on arbuscular mycorrhizal and total fungal communities in experimental grasslands differing in plant diversity and community composition
Authors: Albracht Cynthia , Eisenhauer Nico , Vogel Anja , Wagg Cameron , Buscot François , Heintz-Buschart Anna 
Published: March 2023

AbstractBiodiversity loss and climate change have been determined as major global drivers affecting ecosystems and their functioning. In this context, drought was shown to have negative effects on ecosystems by disrupting ecological processes, which could be buffered in more biodiverse systems. Many studies, however, focus on effects on aboveground communities of single drought events, while dynamics of soil-borne communities are still widely unclear, despite their important roles in ecosystem functioning.To elucidate the effect of recurrent summer drought periods on fungal communities in a long-term grassland biodiversity experiment, roof shelters were installed on grassland plots ranging in plant species richness from 1 to 16 species and plant functional group richness (1-4 groups) and composition. After 9 years of summer droughts, bulk soil was sampled and used for Illumina sequencing of the ITS2 and SSU genes to characterize the total fungal and arbuscular mycorrhizal fungal (AMF) communities, respectively.We found shifts of AMF and total fungi community structures caused by recurrent drought and plant species richness, but no buffering of drought effects by plant diversity. Alpha-diversity (VT or ASV richness) of both AMF and total fungi increased with plant species richness but was not significantly affected by drought. Even though drought overall had minimal long-lasting effects, we foundDiversisporaandParaglomusamong the AMF andPenicilliumamong total fungal communities to be more abundant after the drought treatment. AMF communities were affected by the presence of individual plant functional groups, reacting stronger to presence of legumes under drought, while total fungal interaction with plant communities were similar under drought as control. AMF α-diversity differed between plant functional groups in control conditions but was independent of plant community composition under drought. In contrast, total fungi α-diversity was increased by presence of herbs and legumes only under drought.From our results, we conclude that recurring moderate summer droughts do not strongly affect soil fungal communities. All shifts can be explained by indirect effects through the plant community and its top-down effect on soils altered by drought. Further, AMF are not less affected than total fungal communities, but rather respond differently by interacting more strongly with legumes in response to drought. Consequently, not plant species richness, but plant functional composition, dominates in shaping fungal communities under recurrent droughts.
Energy-Saving Pretreatments Affect PelagicSargassumComposition and DNA Metabarcoding Analysis Reveals the Microbial Community Involved in Methane Yield
Authors: Salgado-Hernández Enrique , Alvarado-Lassman Alejandro , Martínez-Hernández Sergio , Velázquez-Fernández Jesús B. , Dorantes-Acosta Ana E. , Rosas-Mendoza Erik S. , Ortiz-Ceballos Ángel I. 
Published: March 2023

AbstractSargassumspp. floods the Caribbean coastlines, causing damage to the local economy and environment. These macroalgae have a low methane yield that makes the anaerobic digestion (AD) process unviable, so low-cost pretreatments are required. This research investigated the efficiency of energy-saving pretreatments, such as water washing, that had not been evaluated for these species. The microbial communities involved in AD of the best and worst-performing systems were also analyzed by high-throughput sequencing. The results showed that water washing pretreatment modified the content of inorganic compounds, fibers, and C:N ratio and increased the methane yield by 38%. The bacterial phyla Bacteroidota, Firmicutes, and Thermotogota, as well as the archaea generaMethanosarcina,RumEn_M2, andBathyarchaeia, dominated the microbial communities. This study is the first to show the microbial community structure involved in the AD ofSargassumspp. The pretreatments presented in this study may help overcome the previously reported limitations.
A tale of two pumps: Blue light and ABA alter Arabidopsis leaf hydraulics via bundle sheath cells’ H+-pumps and channels
Authors: Torne-Srivastava Tanmayee , Grunwald Yael , Rosenwald Mercedes , Dalal Ahan , Yaaran Adi , Shebtaev Veronica , Moshelion Menachem , Moran Nava 
Published: March 2023

ABSTRACTThis study focuses on the cellular mechanism underlying the co-regulation of the leaf hydraulic conductance (Kleaf) by blue light (BL) and the stress hormone ABA inArabidopsis thaliana. Our previous work has demonstrated that (1) Kleafincreased by BL signaling within the leaf bundle sheath cells (BSCs), which activated their plasmalemma (PM) H+-ATPase (AHA2), acidifying the xylem sap; (2) external acidification enhanced the BSCs’ Kleafand their osmotic water permeability (Pf); (3) ABA decreased both Kleafand Pfby reducing the BSCs’ PM aquaporins activity.We now show, using pH and EM(membrane potential) probes combined with H+-pumps inhibitors and manipulations of cytosolic and external Ca2+concentrations ([Ca2+]CYT,[Ca2+]EXT,respectively), that, in the BSCs: (a) under BL, ABA inhibits AHA2, depolarizing the BSCs and alkalinizing the xylem sap, (b) ABA stimulates the BSCs’ vacuolar H+-ATPase (VHA), alkalinizing their cytosol; (c) each pumpstimulation, AHA2 by BL and VHA by ABA, requires [Ca2+]CYTelevation. ABA-effect-mimicking conditions in patch-clamp experiments activate the BSCs’ K+-release channels (SKOR and/or GORK). ABA decreased the Kleafofskormutants less than WT’s, while during water deprivation stress,skorplants transpired more and their leaves lost relatively less K+than WT. This suggests a role for SKOR in water conservation under drought.
Personalized Neuroimaging Reveals the Impact of Children’s Interests on Language Processing in the Brain
Authors: Olson Halie A. , Johnson Kristina T. , Nishith Shruti , Frosch Isabelle R. , Gabrieli John D.E. , D’Mello Anila M. 
Published: March 2023

ABSTRACTCognition is shaped by individual experiences and interests. However, to study cognition in the brain, researchers typically use generic stimuli that are the same across all individuals. Language, in particular, is animated and motivated by several highly personal factors that are typically not accounted for in neuroimaging study designs, such as “interest” in a topic. Due to its inherently personal and idiosyncratic nature, it is unknown how interest in a topic modulates language processing in the brain. We conducted functional magnetic resonance imaging (fMRI) in 20 children (ages 6.98-12.01 years, mean(SD)=9.35(1.52), 5 female/15 male) as they listened to personalized narratives about a topic of specific interest, as well as to non-personalized generic narratives. We found that personalized narratives about a topic of interest increased activation in canonical language areas, as well as in reward and self-reference regions. Strikingly, we found that activation patterns elicited by topics of personal interest were more consistent across children, despite their idiosyncratic nature, than activation patterns elicited by narratives about an identical generic topic. These results reinforce the critical role that personal interests play in language processing in the human brain, and demonstrate the feasibility of using a personalized neuroimaging approach to study the effects of individually-varying factors such as interest in the brain.
Epidermal GIGANTEA adjusts the response to shade at dusk by directly impinging on PHYTOCHROME INTERACTING FACTOR 7 function
Authors: Martínez-Vasallo Carlos , Cole Benjamin , Gallego-Bartolomé Javier , Chory Joanne , Kay Steve A. , Nohales Maria A. 
Published: March 2023

ABSTRACTFor plants adapted to bright light, a decrease in the amount of light received can be detrimental to their growth and survival. Consequently, in response to shade from surrounding vegetation, they initiate a suite of molecular and morphological changes known as the shade avoidance response (SAR) through which stems and petioles elongate in search for light. Under sunlight-night cycles, the plant’s responsiveness to shade varies across the day, being maximal at dusk time. While a role for the circadian clock in this regulation has long been proposed, mechanistic understanding of how it is achieved is incomplete. Here we show that the clock component GIGANTEA (GI) directly interacts with the transcriptional regulator PHYTOCHROME INTERACTING FACTOR 7 (PIF7), a key player in the response to shade. GI represses PIF7 transcriptional activity and the expression of its target genes in response to shade, thereby fine-tuning the magnitude of the response to limiting light conditions. We find that, under light/dark cycles, this function of GI is required to adequately modulate the gating of the response to shade at dusk. Importantly, we also show that GI expression in epidermal cells is sufficient for proper SAR regulation.SIGNIFICANCEPlants have a remarkable capacity to adapt to and cope with changes in environmental conditions. Because of the importance of light to their survival, plants have evolved sophisticated mechanisms to optimize responses to light. An outstanding adaptive response in terms of plant plasticity in dynamic light environments is the shade avoidance response which sun-loving plants deploy to escape canopy and grow towards the light. This response is the result of a complex signaling network in which cues from different pathways are integrated, including light, hormone, and circadian signaling. Within this framework, our study provides a mechanistic model of how the circadian clock contributes to this complex response by temporalizing the sensitivity to shade signals towards the end of the light period. In light of evolution and local adaptation, this work gives insights into a mechanism through which plants may have optimized resource allocation in fluctuating environments.
Sequence independent activity of a predicted long disordered segment of the human papillomavirus L2 capsid protein during virus entry
Authors: Oh Changin , Buckley Patrick M , Choi Jeongjoon , Hierro Aitor , DiMaio Daniel 
Published: March 2023

AbstractThe papillomavirus L2 capsid protein protrudes through the endosome membrane into the cytoplasm during virus entry to bind cellular factors required for intracellular virus trafficking. Cytoplasmic protrusion of HPV16 L2, virus trafficking, and infectivity are inhibited by large deletions in an ∼110 amino acid segment of L2 that is predicted to be disordered. The activity of these mutants can be restored by inserting protein segments with diverse compositions and chemical properties into this region, including scrambled sequences, a tandem array of a short sequence, and the intrinsically disordered region of a cellular protein. The infectivity of mutants with small in-frame insertions and deletions in this segment directly correlates with the size of the segment. These results indicate that the length of the disordered segment, not its sequence or its composition, determines its activity during virus entry. Sequence independent but length dependent activity has important implications for protein function and evolution.
Low back pain service utilization and costs: association with timing of first-line services for individuals initially contacting a physician specialist. A retrospective cohort study
Authors: Elton David , Zhang Meng 
Published: March 2023

AbstractBackgroundPhysician specialists (PS) are often the type of healthcare provider initially contacted by an individual with low back pain (LBP). LBP clinical practice guidelines (CPG) recommend a stepped approach to management with an emphasis on first-line non-pharmaceutical and non-interventional services.ObjectiveExamine the association between the incorporation of CPG recommended first-line services, exposure to second- and third-line services and total episode cost for individuals with non-surgical LBP initially contacting a PS.DesignRetrospective observational study with identical design to previous study focused on primary care physicians.Setting/PatientsNational sample of individuals with non-surgical LBP occurring in 2017-2019.MeasurementsIndependent variables were initial contact with a PS, and the timing of incorporation of five types of first-line services. Dependent measures included exposure to thirteen types of health care services and total episode cost.Results91,096 individuals were associated with 98,992 episodes of non-surgical LBP. 36.2% of the 33,277 PS initially contacted for an episode of LBP incorporated any first-line service at any time during an episode. A first-line service was provided in 24.0% of episodes with active care (19.5% of episodes), manual therapy (13.7%) and chiropractic manipulative therapy (6.5%) the most common. 7.3% of non-surgical LBP episodes included a first-line service within seven days of initial contact with a PS. These episodes were associated with a reduction in the use of prescription skeletal muscle relaxants (risk ratio (RR) 0.88) and opioids (RR 0.55), spinal injections (RR 0.84), and CT scans (RR 0.71), with no impact on the use of prescription NSAIDs, radiography, or MRI scans. First-line services were associated with an increase in total episode cost at any time of incorporation with chiropractic manipulation associated with the lowest cost increase. Younger individuals from zip codes with higher adjusted gross income were more likely to receive a first-line service in the first seven days of an episode.LimitationsAs a retrospective observational analysis of associations there are numerous potential confounders and limitations.ConclusionsFor individuals with non-surgical LBP PS provide second- or third-line services more frequently and earlier than CPG recommended first-line services. There is an opportunity to improve concordance with LBP CPGs for individuals with LBP initially contacting a PS.
“We are their eyes and ears here on the ground, yet they do not appreciate us”- Factors influencing the performance of Kenyan community health volunteers working in urban informal settlements
Authors: Ogutu Michael O , Kamui Eric , Abuya Timothy , Muraya Kui 
Published: March 2023

AbstractCommunity Health Volunteers (CHVs) play a crucial role in linking the community with the formal health system, particularly in low- and middle-income countries. Studies in Kenya have focused on the implementation of the Kenya Community Health Strategy (CHS) in rural, nomadic, and peri-urban areas; with limited information on the factors that influence CHV performance in urban informal settlements. This study therefore explored factors that influence CHV performance in urban informal settlements within Nairobi Kenya and ways in which CHVs can be supported to enhance their wellbeing and strengthen community strategies. The study was undertaken in two urban informal settlements within Nairobi County. Thirteen focus group discussions (total of 123 participants) and three key informant interviews were conducted with a range of respondents. Various topics covering the design of the Community Health Strategy (CHS) and broader contextual factors that affect CHVs’ performance, were discussed and the data analysed using a framework analysis approach. The key programme design factors identified as influencing the performance of CHVs working in urban informal setting included: CHV recruitment; training; the availability of supplies and resources; and the remuneration of CHVs. Health system factors that influenced CHVs performance included: nature of relationship between healthcare workers at local referral facilities and community members; the availability of services and perceived corruption at the referral facilities; and CHV referral outside of the local health facility. Whereas the broader contextual factors that affected CHV performance at the community level included: demand for material or financial support; perceived corruption in community programmes; and neighbourhood insecurity. These findings suggest that like other CHVs working in both the rural and peri-urban settings, CHVs working in urban informal settlements in Kenya face a myriad of challenges that impact on their wellbeing and work performance. Therefore, to enhance CHVs’ well-being and improve their performance, the following should be considered: adequate and timely remuneration for CHVs, appropriate holistic training, adequate supportive supervision, and ensuring a satisfactory supply of resources and supplies. Additionally, at the health facility level, healthcare workers should be trained on appropriate and respectful relations with both the community and the CHVs, clarity of roles and scope of work, ensure availability of services, and safeguard against corrupt practices in public health facilities. Lastly, there is a need for improved and adequate security measures at the community level, to ensure safety of CHVs as they undertake their roles.
Cardiac Health Assessment using a wearable device before and after TAVI
Authors: Eerdekens Rob , Zelis Jo M. , Horst Herman ter , Crooijmans Caia , van ‘t Veer Marcel , Keulards Daniëlle C.J. , Kelm Marcus , Archer Gareth , Kuehne Titus , Brueren Guus R.G. , Wijnbergen Inge , Johnson Nils P. , Tonino Pim A.L. 
Published: March 2023

ABSTRACTBackgroundDue to the aging of the population, the prevalence of aortic valve stenosis will increase dramatically in upcoming years. Consequently Transcatheter Aortic Valve Implantation (TAVI) procedures will also expand worldwide. Optimal selection of patients who benefit with improved symptoms and prognosis is key since TAVI is not without risk. Currently we are not able to adequately predict functional outcome after TAVI. Quality of life measurement tools and traditional functional assessment tests do not always agree and can depend on factors unrelated to heart disease. Activity tracking using wearable devices might provide a more comprehensive assessment.ObjectivesIdentify objective parameters from a wearable device (the Philips Health Watch) associated with improvement after TAVI for severe aortic stenosis.Methods and results100 patients undergoing routine TAVI wore a Philips Health Watch for one week before and after the procedure. Watch data were analyzed offline: 97 before and 75 after TAVI. Parameters like the total number of steps and activity time did not change, in contrast to improvements in the six-minute walking test (6MWT) and physical limitation domain of a questionnaire (transformed WHOQOL-BREF).ConclusionsThese findings in an elderly TAVI population show that watch-based parameters like the number of steps do not change after TAVI, unlike traditional 6MWT and QoL assessments that do improve. Basic wearable device parameters might be less appropriate for measurement of treatment effects from TAVI.