bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extent of Molecular Chaperone Association Might Determine Fates of Membraneless Organelles during Aging in C. elegans
Authors: Mukherjee Pritam , Panda Prajnadipta , Kasturi Prasad 
Published: December 2021

ABSTRACTProteome imbalance can lead to protein misfolding and aggregation which is associated with pathologies. Protein aggregation can also be an active, organized process and can be exploited by cells as a survival strategy. In adverse conditions, it is beneficial to deposit the proteins in a condensate rather degrading and resynthesizing. Membraneless organelles (MLOs) are biological condensates formed through liquid–liquid phase separation (LLPS), involving cellular components such as nucleic acids and proteins. LLPS is a regulated process, which when perturbed, can undergo a transition from a physiological liquid condensate to pathological solid-like protein aggregates.To understand how the MLO-associated proteins (MLO-APs) behave during aging, we performed a comparative meta-analysis with age related proteome of C. elegans. We found that the MLO-APs are highly abundant throughout the lifespan. Interestingly, they are aggregating more in long-lived mutant worms compared to the age matched wildtype worms. GO term analysis revealed that the cell cycle and embryonic development are among the top enriched processes in addition to RNP components in insoluble proteome. Considering antagonistic pleotropic nature of these developmental genes and post mitotic status of C. elegans, we assume that these proteins phase transit during post development. As the organism ages, these MLO-APs either mature to become more insoluble or dissolve in uncontrolled manner. However, in the long-lived daf-2 mutant worms, the MLOs may attain protective states due to extended availability and association of molecular chaperones.
Dynamic cell cycle-dependent phosphorylation modulates CENP-L-CENP-N centromere recruitment
Authors: Navarro Alexandra P. , Cheeseman Iain M. 
Published: December 2021

AbstractThe kinetochore is a macromolecular structure that is required to ensure proper chromosome segregation during each cell division. The kinetochore is assembled upon a platform of the 16-subunit Constitutive Centromere Associated Network (CCAN), which is present at centromeres throughout the cell cycle. The nature and regulation of CCAN assembly, interactions, and dynamics required to facilitate changing centromere properties and requirements remain to be fully elucidated. The CENP-LN CCAN sub-complex displays a unique cell cycle-dependent localization behavior, peaking in S phase. Here, we demonstrate that phosphorylation of CENP-L and CENP-N controls CENP-LN complex formation and localization in a cell cycle-dependent manner. Mimicking constitutive phosphorylation of either CENP-L or CENP-N or simultaneously preventing phosphorylation of both proteins prevents CENP-LN localization and disrupts chromosome segregation. Together, our work suggests that cycles of phosphorylation and dephosphorylation are critical for CENP-LN complex recruitment and dynamics at centromeres to enable cell cycle-dependent CCAN reorganization.
Evidence for widespread cytoplasmic structuring into mesoscopic condensates
Authors: Keber Felix C. , Nguyen Thao , Brangwynne Clifford P. , Wühr Martin 
Published: December 2021

AbstractEukaryotic cytoplasm organizes itself via both membrane-bound organelles and membrane-less biomolecular condensates (BMCs). Known BMCs exhibit liquid-like properties and are typically visualized on the scale of ~1 μm. They have been studied mostly by microscopy, examining select individual proteins. Here, we investigate the global organization of native cytoplasm with quantitative proteomics, using differential pressure filtration, size exclusion, and dilution experiments. These assays reveal that BMCs form throughout the cytosplasm, predominantly at the mesoscale of ~100 nm. Our data indicate that at least 18% of the proteome is organized via such mesoscale BMCs, suggesting that cells widely employ dynamic liquid-like clustering to organize their cytoplasm, at surprisingly small length scales.
The measurement properties and acceptability of a new parent-infant bonding tool (‘Me and My Baby’) designed for use in a universal healthcare setting in the UK
Authors: Bywater T. , Dunn A. , Endacott C. , Smith K. , Tiffin P. A , Blower S. , Price M. 
Published: December 2021

AbstractNICE guidelines acknowledge the importance of the parent-infant relationship for child development but highlight the need for further research to establish reliable tools for assessment, particularly for parents of children under one year.This study explores the acceptability and psychometric properties of a co-developed tool, ‘Me and My Baby’ (MaMB).Study designA cross-sectional design was applied. The MaMB was administered universally (in two sites) with mothers during routine 6–8-week Health Visitor contacts. The sample comprised 467 mothers (434 MaMB completers and 33 ‘non-completers’). Dimensionality of instrument responses were evaluated via exploratory and confirmatory ordinal factor analyses. Item response modelling was conducted via a Rasch calibration to evaluate how the tool conformed to principles of ‘fundamental measurement’. Tool acceptability was evaluated via completion rates and comparing ‘completers’ and ‘non-completers’ demographic differences on age, parity, ethnicity, and English as an additional language. Free-text comments were summarised. Data sharing agreements and data management were compliant with the General Data Protection Regulation, and University of York data management policies.ResultsHigh completion rates suggested the MaMB was acceptable. Psychometric analyses showed the response data to be an excellent fit to a unidimensional confirmatory factor analytic model. All items loaded statistically significantly and substantially (>0.4) on a single underlying factor (latent variable). The item response modelling showed that most MaMB items fitted the Rasch model. Item reliability was high (0.94) yet the test yielded little information on each respondent, as highlighted by the ‘person separation index’ of 0.1 (=>2.0 is required to reliably discriminate between two groups).Conclusions and next stepsMaMB reliably measures a single construct, likely to be infant bonding. However, further validation work is needed, preferably with ‘enriched population samples’ to include higher-need/risk families. The MaMB tool may benefit from reduced response categories (from four to three) and some modest item wording amendments. Following further validation and reliability appraisal the MaMB may ultimately be used with fathers/other primary caregivers and be potentially useful in research, universal health settings as part of a referral pathway, and clinical practice, to identify dyads in need of additional support/interventions.
A comprehensive systematic review and meta-analysis of the global data involving 61,532 cancer patients with SARS-CoV-2 infection
Authors: Khoury Emma , Nevitt Sarah , Madsen William Rohde , Turtle Lance , Davies Gerry , Palmieri Carlo 
Published: December 2021

AbstractBackgroundSARS-CoV-2 have been shown to be associated with more severe disease and death in cancer patient. A systematic review and meta-analysis was conducted to determine the risk by age, tumour type and treatment of infection with SARS-CoV-2 in cancer patients.MethodsSystematic review by searching PubMed, Web of Science, and Scopus for articles published in English up to June 14, 2021 of SARS-CoV-2 infection in >10 patients with malignant disease. Outcomes included factors in patients with malignant disease that may predict a poor outcome from COVID-19 compared to patients without malignant disease, including patient demographics, tumour subtype and cancer treatments. A meta-analysis was performed using random effects model.Results81 studies were included, totalling 61,532 cancer patients. Haematological malignancies comprised 22.1% (9,672 of 43,676) of cases. Relative risk (RR) of mortality when age and sex matched was 1.69 (95% CI, 1.46-1.95; p<0.001; I2=51%). RR of mortality, versus non-cancer patients, was associated with decreasing age (exp(b)0.96; 95% CI, 0.922–0.994; p=0.028) but not male sex (exp(b)1.89; 95% CI, 0.222–6.366; p=0.83). RR of mortality in those with haematological malignancies versus non-cancer control was 1.81 (95% CI, 1.53-2.95; I2=0.0%). Compared to other cancers, increased risk of death was seen for lung (RR 1.68, 95% CI, 1.45-1.94; p<0.001), genitourinary (RR 1.11; 95% CI, 1.00-1.24; p=0.059) and haematological malignancies (RR 1.42; 95% CI, 1.31-1.54; p<0.001). Breast (RR 0.51; 95% CI, 0.36-0.71; p<0.001) and gynaecological cancers (RR 0.76; 95% CI, 0.62-0.93; p=0.009) had lower risk of death. Receipt of chemotherapy had greatest overall pooled mortality risk of 30% (95% CI, 25-36%; I2=86.97%) and endocrine therapy the lowest at 11% (95% CI, 6-16%; I2=70.7%).ConclusionsCancer patients, particularly younger cancer patients, appear at increased risk of mortality from COVID-19 compared to non-cancer patients. Differences in outcomes were seen based on tumour types and treatment.Highlights-To our knowledge this is the largest review and meta-analysis of COVID-19 in cancer patients with insights into tumour types and therapies.-In unadjusted analysis cancer doubles the risk of COVID-19 related mortality. This decreased when adjusted for age and sex.-Younger cancer patients have the highest risk of mortality when compared to non-cancer COVID-19 patient of a similar age.-Patients with lung, genitourinary and haematological malignancies are at increased risk of mortality, breast and gynaecological cancers are at lower risk.-Patients on chemotherapy have the highest pooled mortality risk with those on endocrine therapy the lowest.
Knowledge, Attitude and Practices towards COVID 19 pandemic among homeless street young adults in Lusaka, Zambia – A Mixed Methods Approach
Authors: Samuyachi K. , Sampa M. , Zambwe M. , Chipimo P.J. 
Published: December 2021

ABSTRACTObjectiveTo determine the knowledge, attitude and practices towards COVID-19 among homeless street young adults in Lusaka district, Zambia.MethodsA total of 89 young street adults aged between 16-35 years were sampled. A concurrent mixed methods approach was used, Structured questionnaires and focused group discussion, to achieve the objectives. STATA 13 was used to produce Descriptive statistics while thematic analysis was used to analyze the qualitative data.ResultsMajority of the survey participants were male 67(78%), 55(62%) were single while 53(59%) had attained a Primary School Education. The majority of the participants received the COVID-19 information through the radio (61%). Only 44 (49%)% had adequate knowledge on Covid-19 of whom 70 (78.6%) had a positive attitude towards COVID-19. However, the 65(73%) had a low risk perception of contracting the disease. Further, 66 (74.2%) had a positive attitude towards the effectiveness of precautionary behaviors and measures. The finding also revealed that only 3(3.3%) had good practice towards the Covid-19 preventative measures overall with (SD:0).ConclusionKnowledge and attitudes towards COVID-19 were quite high among homeless street adults. However, their good practices were alarmingly low. Specific strategies for them being a vulnerable group are required.
The early-stage comprehensive costs of routine PrEP implementation and scale-up in Zambia
Authors: Hendrickson Cheryl , Long Lawrence C , van Rensburg Craig , Claassen Cassidy W , Njelesani Mwansa , Moyo Crispin , Mulenga Lloyd , O’Bra Heidi , Russell Colin A , Nichols Brooke E 
Published: December 2021

AbstractIntroductionPre-exposure prophylaxis (PrEP) is effective at preventing HIV infection, but PrEP cost-effectiveness is sensitive to PrEP implementation and program costs. Preliminary studies indicate that, in addition to direct delivery cost, PrEP provision requires substantial demand creation and user support to encourage PrEP initiation and persistence. We estimated the cost of providing PrEP in Zambia through different PrEP delivery models.MethodsTaking a guidelines-based approach for visits, labs and drugs assuming fidelity to the expanded 2018 Zambian PrEP guidelines, we estimated the annual cost of providing PrEP per client for five delivery models: one focused on key populations (men-who-have-sex-with-men (MSM) and female sex workers (FSW), one on adolescent girls and young women (AGYW), and three integrated programs (operated within the HIV counselling and testing service at primary healthcare centres). Program start-up, provider, and user support costs were based on program expenditure data and number of PrEP sites and clients in 2018. PrEP clinic visit costs were based on micro-costing at two PrEP delivery sites (in 2018 USD).ResultsThe annual cost per PrEP client varied greatly by program type, from $394 (AGYW) to $760 in an integrated program. Cost differences were driven largely by volume (i.e. the number of clients initiated/model/site) which impacted the relative costs of program support and technical assistance assigned to each PrEP client. Direct service delivery costs, including staff and overheads, labs and monitoring, drugs and consumables ranged narrowly from $208-217/PrEP-user. Service delivery costs were a key component in the cost of PrEP, representing 36-65% of total costs. Reductions in service delivery costs per PrEP client are expected with further scale-up.ConclusionsThe results show that, even when integrated into full service delivery models, accessing vulnerable, marginalised populations at substantial risk of HIV infection is likely to cost more than previously estimated due to the programmatic costs involved in community sensitization and user support. Improved data on individual client resource usage (e.g. drugs, labs, visits) and outcomes (e.g. initiation, persistence) is required to get a better understanding of the true resource utilization, cost and expected outcomes and annual costs of different PrEP programs in Zambia.
Speech-driven Facial Animations Improve Speech-in-Noise Comprehension of Humans
Authors: Varano Enrico , Vougioukas Konstantinos , Ma Pingchuan , Petridis Stavros , Pantic Maja , Reichenbach Tobias 
Published: December 2021

AbstractUnderstanding speech becomes a demanding task when the environment is noisy. Comprehension of speech in noise can be substantially improved by looking at the speaker’s face, and this audiovisual benefit is even more pronounced in people with hearing impairment. Recent advances in AI have allowed to synthesize photorealistic talking faces from a speech recording and a still image of a person’s face in an end-to-end manner. However, it has remained unknown whether such facial animations improve speech-in-noise comprehension. Here we consider facial animations produced by a recently introduced generative adversarial network (GAN), and show that humans cannot distinguish between the synthesized and the natural videos. Importantly, we then show that the end- to-end synthesized videos significantly aid humans in understanding speech in noise, although the natural facial motions yield a yet higher audiovisual benefit. We further find that an audiovisual speech recognizer benefits from the synthesized facial animations as well. Our results suggest that synthesizing facial motions from speech can be used to aid speech comprehension in difficult listening environments.
Song Richness Index: A measure to understand the diversity and repetition of notes in a birdsong
Authors: Sawant Suyash , Arvind Chiti , Joshi Viral , Robin V. V. 
Published: December 2021

AbstractBirdsong plays an important role in mate attraction and territorial defense. Many birds, especially Passerines, produce varying sequences of multiple notes resulting in complex songs. Studying the diversity of notes within these songs can give insights into an individual’s reproductive fitness. We first looked at the previously described and commonly used diversity measures to understand the possible case-specific limitations. We then developed a new diversity measure-Song Richness Index (SRI). We compared SRI with three measures of diversity using all possible combinations of notes to understand the case-specific advantages and limitations of all approaches. Simulating all possible combinations gave us insights into how each diversity measure works in a real scenario. SRI showed an advantage over conventional measures of diversity like Note Diversity Index (NDI), Shannon’s Equitability (SH), and Simpson’s Diversity (SI), especially in the cases where songs are made up of only one type of repetitive note.
Visualizing translation dynamics at atomic detail inside a bacterial cell
Authors: Xue Liang , Lenz Swantje , Zimmermann-Kogadeeva Maria , Tegunov Dimitry , Cramer Patrick , Bork Peer , Rappsilber Juri , Mahamid Julia 
Published: December 2021

AbstractTranslation is the fundamental process of protein synthesis and is catalysed by the ribosome in all living cells. Here, we use cryo-electron tomography and sub-tomogram analysis to visualize the dynamics of translation inside the prokaryote Mycoplasma pneumoniae. We first obtain an in-cell atomic model for the M. pneumoniae ribosome that reveals distinct extensions of ribosomal proteins. Classification then resolves thirteen ribosome states that differ in conformation and composition and reflect intermediates during translation. Based on these states, we animate translation elongation and demonstrate how antibiotics reshape the translation landscape inside cells. During translation elongation, ribosomes often arrange in a defined manner to form polysomes. By mapping the intracellular three-dimensional organization of translating ribosomes, we show that their association into polysomes exerts a local coordination mechanism that is mediated by the ribosomal protein L9. Our work demonstrates the feasibility of visualizing molecular processes at atomic detail inside cells.
Chromosome remodelling by SMC/Condensin in B. subtilis is regulated by Soj/ParA during growth and sporulation
Authors: Roberts David M. , Anchimiuk Anna , Kloosterman Tomas G. , Murray Heath , Wu Ling Juan , Gruber Stephan , Errington Jeff 
Published: December 2021

AbstractSMC complexes, loaded at ParB-parS sites, are key mediators of chromosome organization in bacteria. ParA/Soj proteins interact with ParB/Spo0J in a pathway involving ATP-dependent dimerization and DNA binding, leading to chromosome segregation and SMC loading. In Bacillus subtilis, ParA/Soj also regulates DNA replication initiation, and along with ParB/Spo0J is involved in cell cycle changes during endospore formation. The first morphological stage in sporulation is the formation of an elongated chromosome structure called an axial filament. We now show that a major redistribution of SMC complexes drives axial filament formation, in a process regulated by ParA/Soj. Unexpectedly, this regulation is dependent on monomeric forms of ParA/Soj that cannot bind DNA or hydrolyse ATP. These results reveal a new role for ParA/Soj proteins in the regulation of SMC dynamics in bacteria, and yet further complexity in the web of interactions involving chromosome replication, segregation, and organization, controlled by ParAB and SMC.
Kinesin-II motors differentially impact biogenesis of distinct extracellular vesicle subpopulations shed fromC. eleganssensory cilia
Authors: Clupper Michael , Gill Rachael , Elsayyid Malek , Touroutine Denis , Caplan Jeffrey L. , Tanis Jessica E. 
Published: December 2021

SUMMARYExtracellular vesicles (EVs) are bioactive lipid-bilayer enclosed particles released from nearly all cells. One specialized site for EV shedding is the primary cilium, a conserved signaling organelle. The mechanisms underlying cargo enrichment and biogenesis of heterogeneous EVs shed from cilia are unclear. Here we discover the conserved ion channel CLHM-1 as a new ciliary EV cargo. Using super-resolution microscopy, we imaged EVs released into the environment from sensory neuron cilia ofC. elegansexpressing fluorescently-tagged CLHM-1 and TRP polycystin-2 channel PKD-2 EV cargoes at endogenous levels. We find that these proteins are enriched in distinct EV subpopulations that are differentially shed in response to availability of hermaphrodite mating partners. Both CLHM-1 and PKD-2 localize to the ciliary base and middle segment of the cilium proper, but PKD-2 alone is present in the cilium distal tip and EVs shed from this site. CLHM-1 EVs released into the environment bud from a secondary site, the periciliary membrane compartment at the ciliary base. We show that individual heterotrimeric and homomeric kinesin-II motors have discrete impacts on the colocalization of PKD-2 and CLHM-1 in both cilia and EVs. Total loss of kinesin-II activity significantly decreases shedding of PKD-2 but not CLHM-1 EVs. Our data demonstrate that anterograde kinesin-II-dependent intraflagellar transport is required for selective enrichment of specific protein cargoes into heterogeneous EVs with different signaling potentials.
mRNA-1273 and BNT162b2 mRNA vaccines have reduced neutralizing activity against the SARS-CoV-2 Omicron variant
Authors: Edara Venkata-Viswanadh , Manning Kelly E. , Ellis Madison , Lai Lilin , Moore Kathryn M. , Foster Stephanie L. , Floyd Katharine , Davis-Gardner Meredith E. , Mantus Grace , Nyhoff Lindsay E. , Bechnak Sarah , Alaaeddine Ghina , Naji Amal , Samaha Hady , Lee Matthew , Bristow Laurel , Hussaini Laila , Ciric Caroline Rose , Nguyen Phuong-Vi , Gagne Matthew , Roberts-Torres Jesmine , Henry Amy R. , Godbole Sucheta , Grakoui Arash , Sexton Marybeth , Piantadosi Anne , Waggoner Jesse J. , Douek Daniel C. , Anderson Evan J. , Rouphael Nadine , Wrammert Jens , Suthar Mehul S. 
Published: December 2021

AbstractThe BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines generate potent neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the global emergence of SARS-CoV-2 variants with mutations in the spike protein, the principal antigenic target of these vaccines, has raised concerns over the neutralizing activity of vaccine-induced antibody responses. The Omicron variant, which emerged in November 2021, consists of over 30 mutations within the spike protein. Here, we used an authentic live virus neutralization assay to examine the neutralizing activity of the SARS-CoV-2 Omicron variant against mRNA vaccine-induced antibody responses. Following the 2nd dose, we observed a 30-fold reduction in neutralizing activity against the omicron variant. Through six months after the 2nd dose, none of the sera from naïve vaccinated subjects showed neutralizing activity against the Omicron variant. In contrast, recovered vaccinated individuals showed a 22-fold reduction with more than half of the subjects retaining neutralizing antibody responses. Following a booster shot (3rd dose), we observed a 14-fold reduction in neutralizing activity against the omicron variant and over 90% of boosted subjects showed neutralizing activity against the omicron variant. These findings show that a 3rd dose is required to provide robust neutralizing antibody responses against the Omicron variant.
Efficacy of antiviral drugs against the omicron variant of SARS-CoV-2
Authors: Dabrowska Agnieszka , Szczepanski Artur , Botwina Paweł , Mazur-Panasiuk Natalia , Jiřincová Helena , Rabalski Lukasz , Zajic Tomas , Popowicz Grzegorz , Pyrc Krzysztof 
Published: December 2021

AbstractThe Omicron variant of the SARS-CoV-2 virus was first detected in South Africa in November 2021. The analysis of the sequence data in the context of earlier variants suggested that it may show very different characteristics, including immune evasion and increased transmission. These assumptions were partially confirmed, and the reduction in protection in convalescent patients and vaccinated individuals have been confirmed. Here, we have evaluated the efficacy of antivirals against SARS-CoV-2 variants, Omicron, Delta, and the early 2020 isolate.