bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanistic toxicology in light of genetic compensation
Authors: Elizalde Mary Jane , Gorelick Daniel A
Published: November 2023

Mechanistic toxicology seeks to identify the molecular and cellular mechanisms by which toxicants exert their deleterious effects. One powerful approach is to generate mutations in genes that respond to a particular toxicant, and then test how such mutations change the effects of the toxicant. CRISPR is a rapid and versatile approach to generate mutations in cultured cells and in animal models. Many studies use CRISPR to generate short insertions or deletions in a target gene and then assume that the resulting mutation, such as a premature termination codon, causes a loss of functional protein. However, recent studies demonstrate that this assumption is flawed. Cells can compensate for short insertion and deletion mutations, leading toxicologists to draw erroneous conclusions from mutant studies. In this review, we will discuss mechanisms by which a mutation in one gene may be rescued by compensatory activity. We will discuss how CRISPR insertion and deletion mutations are susceptible to compensation by transcriptional adaptation, alternative splicing, and rescue by maternally derived gene products. We will review evidence that measuring levels of messenger RNA transcribed from a mutated gene is an unreliable indicator of the severity of the mutation. Finally, we provide guidelines for using CRISPR to generate mutations that avoid compensation.
Comment on ‘A standardized terminology of spines in the order Siluriformes (Actinopterygii: Ostariophysi)’ by Ballen and de Pinna (2021)
Authors: Kubicek Kole M , Britz Ralf , Conway Kevin W
Published: November 2023

Homology is the foundation of any comparative evolutionary study, and as structures previously considered homologous are found to be convergent, and vice versa, terminology needs to be changed to reflect homology. The dorsal- and pectoral fin-spines of catfishes (order Siluriformes) are morphologically diverse and ornamentations adorning the anterior and posterior edges of the spines have regularly been used in systematic studies of the group. Building on Vanscoy et al. (2015), Kubicek et al. (2019) showed that some of the ornamentations of siluriform fin-spines previously considered homologous result from two different developmental pathways, and presented a terminology based on the homology of these structures. In their recent paper, Ballen and de Pinna (2021) proposed a new terminology for various catfish fin-spine structures, including fin-spine ornamentation. However, homology was not considered and, instead, their terminology is based on the general shape of the ornamentation to allow for ‘unambiguous use’ in various applications, including the placement of fossil fin-spines into well-defined clades of catfishes. We show that the terminology proposed by Ballen and de Pinna (2021) is problematic as it confuses non-homologous conditions into the same state and thus undermines the usefulness of fin-spine ornamentation as a character in comparative evolutionary studies of siluriforms.
A new genus and species of toad from Mount Kenya illuminates East African montane biogeography
Authors: Liedtke H Christoph , Malonza Patrick K , Wasonga Domnick V , Müller Hendrik , Loader Simon P
Published: November 2023

Discoveries of new species can greatly impact our understanding of the biogeography of a region. For example, groups of amphibian lineages restricted to the Afrotemperate forests of Tanzania and Ethiopia are indicative of a shared biogeographical history of this highly discontinuous ecosystem. Curiously, many of these lineages are absent from the geographically intermediate Kenyan highlands. This phylogeographical interval is generally considered to be attributable to the younger, volcanic origins of much of the Kenyan highlands, and thus an amphibian fauna that is derived largely from recent colonization events rather than comprising older relicts. Contrasting with this view, here we report on the discovery of a single specimen of Bufonidae (true toad) from Mount Kenya. The specimen belongs to a species new to science and deserves recognition at the generic level owing to its notable molecular phylogenetic and morphological divergences from other described taxa. It is most closely related to the Tanzanian genera Churamiti and Nectophrynoides. The discovery of this new toad and its association with Afrotemperate species is significant because it links Kenya to the biogeographically more ancient Tanzanian mountains and supports the potential longevity of the Afrotemperate forests in Kenya. Broadly, it highlights that we are still adding major branches to the phylogeny of anurans.
Implementation of a Fascia Iliaca Compartment Block Program in Geriatric Hip Fractures: The Experience at a Level I Academic Trauma Center
Authors: Ulrich Gary , Kraus Kameron , Polk Seth , Zuelzer David , Matuszewski Paul E.
Published: November 2023

OBJECTIVES:

Determine adherence to a newly implemented protocol of fascia iliaca compartment block (FICB) in geriatric hip fractures.

METHODS

Design:

Retrospective review

Setting:

Level I trauma center

Patient Selection Criteria:

Patients with a hip fracture treated with cephallomedullary nailing or hemiarthroplasty (CPT Codes 27245 or 27236).

Outcome Measures and Comparisons: Adherence to a protocol for FICB, time intervals between emergency department arrival, FICB, and surgery stratified by time of admission.

RESULTS:

380 patients were studied (average age 78, 70% female). 53.2% of patients received a FICB, which was less than a pre-defined acceptable adherence rate of 75% (p<0.001). 5.0% received a FICB within 4 hours and 17.3% within 6 hours from admission. Admission during daylight hours (7am-7pm) when compared to evening hours (7pm-7am) was associated with improved timeliness ([8.3% vs 0% within 4 hours, p<0.001], [27.5% vs 2.4% within 6 hours, p<0.001]). Improved adherence to the protocol was observed over time (OR: 1.0013, 95% CI: 1.0001, 1.0025, p=0.0388).

CONCLUSIONS:

FICB implementation was poor but gradually improved over time. Few patients received a FICB promptly, especially during night hours. Overall, this study demonstrates that implementation of a FICB program at a level I academic trauma center can be difficult however, many hurdles can be overcome with institutional support and dedication of resources such as staff, space and additional training.
The Case for Operative Efficiency in Adult Spinal Deformity Surgery
Authors: Daniels Alan H. , Daher Mohammad , Singh Manjot , Balmaceno-Criss Mariah , Lafage Renaud , Diebo Bassel G. , Hamilton D. Kojo , Smith Justin S. , Eastlack Robert K. , Fessler Richard G. , Gum Jeffrey L. , Gupta Munish C. , Hostin Richard , Kebaish Khaled M. , Klineberg Eric O. , Lewis Stephen J. , Line Breton G. , Nunley Pierce D. , Mundis Gregory M. , Passias Peter G. , Protopsaltis Themistocles S. , Buell Thomas , Scheer Justin K. , Mullin Jeffrey P. , Soroceanu Alex , Ames Christopher P. , Lenke Lawrence G. , Bess Shay , Shaffrey Christopher I. , Burton Douglas C. , Lafage Virginie , Schwab Frank J. ,   International Spine Study Group
Published: November 2023

Study Design.

Retrospective review of prospectively collected data

Objective.

To analyze the impact of operative room (OR) time in adult spinal deformity (ASD) surgery on patient outcomes

Background.

It is currently unknown if OR time in ASD patients matched for deformity severity and surgical invasiveness is associated with patient outcomes.

Methods.

ASD patients with baseline and 2-year postoperative radiographic and patient reported outcome measures (PROM) data, undergoing posterior only approach for long fusion (> L1- Ilium) were included. Patients were grouped into Short OR Time (<40th percentile: <359 min) and Long OR Time (>60th percentile: > 421 min). Groups were matched by age, baseline deformity severity, and surgical invasiveness. Demographics, radiographic, PROM data, fusion rate, and complications were compared between groups at baseline and 2-years follow-up.

Results.

In total, 270 patients were included for analysis: mean OR time was 286 minutes in the Short OR group vs 510 minutes in the Long OR group (P<0.001). Age, gender, percent of revision cases, surgical invasiveness, PI-LL, SVA and PT were comparable between groups (P>0.05). Short OR had a slightly lower BMI than the short OR group (P<0.001) and decompression was more prevalent in the long OR time (P=0.042). Patients in the Long group had greater hospital length of stay (LOS) (P=0.02); blood loss (P<0.001); proportion requiring ICU (P=0.003); higher minor complication rate (P=0.001); with no significant differences for major complications or revision procedures (P>0.5). Both groups had comparable radiographic fusion rates (P=0.152) and achieved improvement in sagittal alignment measures, ODI and SF36 (P<0.001).

Conclusion.

Shorter OR time for ASD correction is associated with lower minor complication rate, lower EBL, fewer ICU admissions, and shorter hospital LOS without sacrificing alignment correction or PROMS. Maximizing operative efficiency by minimizing OR time in ASD surgery has the potential to benefit patients, surgeons, and hospital systems.
Impact of Test Instructions on 6-min Walk Distance in Adults With Chronic Respiratory Disease
Authors: Mellerick Christie R. , Burge Angela T. , Hill Catherine J. , Cox Narelle S. , Bondarenko Janet , Holland Anne E.
Published: November 2023

Purpose:

The 6-min walk test (6MWT) is commonly used to assess functional exercise capacity in people with chronic respiratory disease in both clinical and research settings. However, two tests are required to achieve accurate results, due to a well-documented learning effect for the 6-min walk distance (6MWD). Whether it is possible to reduce or eliminate the learning effect by optimizing 6MWT instructions is not known.

Methods:

People with chronic respiratory disease referred to pulmonary rehabilitation undertook two 6MWT with random allocation to modified instructions (fast—walk as fast as possible; n = 46) or usual instructions (far—walk as far as possible; n = 49). The primary outcome was the learning effect, defined as the difference in the 6MWD between test one and test two. Subgroup analyses investigated whether effects varied in those who were naïve to the 6MWT or according to diagnosis (chronic obstructive pulmonary disease, interstitial lung disease, and bronchiectasis).

Results:

A learning effect was present in both groups, with a mean improvement in the 6MWD on the second test of 14 m in the fast (modified) group (95% CI, 6-22) and 11 m in the far (usual) group (95% CI, 4-19). There was no statistically or clinically significant difference between groups in the magnitude of the learning effect (between-group difference −3 m, 95% CI, −14 to 8). There was no significant effect of naivety to the 6MWT or diagnosis.

Conclusion:

The current recommended procedures for the 6MWT, including standardized instructions and performance of two tests on each occasion, should be retained.
Clostridioides difficile infections; new treatments and future perspectives
Authors: Normington Charmaine , Chilton Caroline H. , Buckley Anthony M.
Published: November 2023

Purpose of review

As a significant cause of global morbidity and mortality, Clostridioides difficile infections (CDIs) are listed by the Centres for Disease Control and prevention as one of the top 5 urgent threats in the USA. CDI occurs from gut microbiome dysbiosis, typically through antibiotic-mediated disruption; however, antibiotics are the treatment of choice, which can result in recurrent infections. Here, we highlight new treatments available and provide a perspective on different classes of future treatments.

Recent findings

Due to the reduced risk of disease recurrence, the microbiome-sparing antibiotic Fidaxomicin has been recommended as the first-line treatment for C. difficile infection. Based on the success of faecal microbiota transplantations (FMT) in treating CDI recurrence, defined microbiome biotherapeutics offer a safer and more tightly controlled alterative as an adjunct to antibiotic therapy. Given the association between antibiotic-mediated dysbiosis of the intestinal microbiota and the recurrence of CDI, future prospective therapies aim to reduce the dependence on antibiotics for the treatment of CDI.

With current first-in-line antibiotic therapy options associated with high levels of recurrent CDI, the availability of new generation targeted therapeutics can really impact treatment success. There are still unknowns about the long-term implications of these new CDI therapeutics, but efforts to expand the CDI treatment toolbox can offer multiple solutions for clinicians to treat this multifaceted infectious disease to reduce patient suffering.
More is Different: Constructing the Most Comprehensive Human Protein High-Order Interaction Dataset
Authors: Lu Yuntao , Huang Yongfeng , Li Tao
Published: November 2023

In biological systems, protein-protein interactions (PPI) weave intricate network patterns that are fundamental to the structural and functional integrity of organisms. While the majority of existing research has been anchored in the study of pairwise PPIs, the realm of high-order interactions remains relatively untapped. This oversight could potentially obscure the deeper intricacies embedded within biological networks. To address this gap, this study formulates a scientific task aimed at predicting high-order protein-protein interactions and introduces a multi-level comprehensive dataset focused on triadic high-order interactions within PPI networks. This dataset incorporates more than 80% of the known human protein interaction relationships and partitions into 60 subsets across a diverse range of functional contexts and confidence. Through meticulous evaluation using cutting-edge high-order network prediction tools and benchmark PPI prediction methodologies, our findings resonate with the principle that “more is different”. Triadic high-order interactions offer a more enriched and detailed informational canvas than their pairwise counterparts, paving the way for a deeper comprehension of the intricate dynamics at play in biological systems. In summary, this research accentuates the critical importance of high-order PPI interactions in biological systems and furnishes invaluable resources for subsequent scholarly investigations. The dataset is poised to catalyze future research endeavors in protein-protein interaction networks, elucidating their pivotal roles in both health and disease states.
A single-sample workflow for joint metabolomic and proteomic analysis of clinical specimens
Authors: Gegner Hagen M. , Naake Thomas , Aljakouch Karim , Dugourd Aurelien , Kliewer Georg , Müller Torsten , Schilling Dustin , Schneider Marc A. , Kunze-Rohrbach Nina , Grünewald Thomas G.P. , Hell Rüdiger , Saez-Rodriguez Julio , Huber Wolfgang , Poschet Gernot , Krijgsveld Jeroen
Published: November 2023

Understanding the interplay of the proteome and the metabolome aids in understanding cellular phenotypes. To enable more robust inferences from such multi-omics analyses, combining proteomic and metabolomic datasets from the same sample provides major benefits by reducing technical variation between extracts during the pre-analytical phase, decreasing sample variation due to varying cellular content between aliquots, and limiting the required sample amount. We evaluated the advantages, practicality and feasibility of a single-sample workflow for combined proteome and metabolome analysis. In the workflow, termed MTBE-SP3, we combined a fully automated protein lysis and extraction protocol (autoSP3) with a semi-automated biphasic 75% EtOH/MTBE extraction for quantification of polar/non-polar metabolites. Additionally, we compared the resulting proteome of various biological matrices (FFPE tissue, fresh-frozen tissue, plasma, serum and cells) between autoSP3 and MTBE-SP3. Our analysis revealed that the single-sample workflow provided similar results to those obtained from autoSP3 alone, with an 85-98% overlap of proteins detected across the different biological matrices. Additionally, it provides distinct advantages by decreasing (tissue) heterogeneity by retrieving metabolomics and proteomic data from the identical biological material, and limiting the total amount of required material. Lastly, we applied MTBE-SP3 to a lung adenocarcinoma cohort of 10 patients. Integrating the metabolic and proteomic alterations between tumour and non-tumour adjacent tissue yielded consistent data independent of the method used. This revealed mitochondrial dysfunction in tumor tissue through deregulation of OGDH, SDH family enzymes and PKM. In summary, MTBE-SP3 enables the facile and confident parallel measurement of proteins and metabolites obtained from the same sample. This workflow is particularly applicable for studies with limited sample availability and offers the potential to enhance the integration of metabolomic and proteomic datasets.
Feeding disruptions lead to a significant increase in disease modules in adult mice
Authors: Mou Xiaoqin , Nie Pengxing , Chen Renrui , Cheng Yang , Wang Guang-Zhong
Published: November 2023

Feeding disruption is intimately associated with numerous diseases, yet its molecular mechanisms remain to be elucidated in circadian biology. We discovered that in the liver of adult mice, feeding disruption can lead to a substantial increase in disease modules in the transcriptome. This increase in disease modules occurs far earlier than the individual’s aging and disease onset. In contrast, calorie restriction significantly reduces the formation of disease modules. This offers a critical missing link between feeding disruption and the molecular systems mechanisms of disease.
Divergence time and environmental similarity predict the strength of morphological convergence in stick and leaf insects
Authors: Boisseau Romain P. , Bradler Sven , Emlen Douglas J.
Published: November 2023

Independent evolution of similar traits in lineages inhabiting similar environments (convergent evolution) is often taken as evidence for adaptation by natural selection, and used to illustrate the predictability of evolution. Yet convergence is rarely perfect. Environments may not be as similar as they appear (e.g., habitats scored the same may be heterogenous to the organisms). And lineages can evolve in different ways even when submitted to the same environmental challenges, because responses to selection are contingent upon available genetic variation and independent lineages may differ in the alleles, genetic backgrounds, and even the developmental mechanisms responsible for the phenotypes in question. Both impediments to convergence are predicted to increase as the length of time separating two lineages increases, making it difficult to discern their relative importance. We quantified environmental similarity and the extent of convergence to show how habitat and divergence time each contribute to observed patterns of morphological evolution in stick and leaf insects (order Phasmatodea). Dozens of phasmid lineages independently colonized similar habitats, repeatedly evolving in parallel directions on a 26-trait morphospace, though the magnitude and direction of these shifts varied. Lineages converging towards more similar environments ended up closer on the morphospace, as did closely related lineages, and closely related lineages followed more parallel trajectories to arrive there. Remarkably, after accounting for habitat similarity, we show that divergence time reduced convergence at a constant rate across more than 60 million years of separation, suggesting even the magnitude of contingency can be predictable, given sufficient spans of time.

Significance statement

Phasmids (stick and leaf insects) exemplify the extraordinary power of natural selection to shape organismal phenotypes. The animals themselves are charismatic champions of crypsis and masquerade; and our characterization of their adaptive radiation reveals dozens of instances of convergence, as lineages adapted to similar changes in habitat by repeatedly evolving similar body forms. Our findings show that the similarity of environmental conditions experienced by the organisms – the closeness of the invaded niches – and the extent of elapsed time since divergence, both predict the strength of morphological convergence. The phasmid radiation reveals an evolutionary process that is surprisingly predictable, even when lineages have been evolving independently for tens of millions of years.
In-silicoanalysis of Myocardial Infarction-related missense SNPs to identify novel biomarkers to predict susceptibility
Authors: Tarlochan Fiza Faris , Rasool Saad
Published: November 2023

Myocardial Infarction (MI), commonly known as a heart attack, stands as a formidable global health challenge, responsible for a substantial burden of morbidity and mortality. This study embarked on a comprehensive exploration of the genetic underpinnings of MI, recognizing the pivotal role of genetic factors in determining an individual’s susceptibility to this life-threatening condition. The objective of our research was to investigate missense single nucleotide polymorphisms (SNP) associated with MI to determine whether the changes in amino acid sequences have potential implications for the risk of MI. Employing a multifaceted approach, we leveraged an array of computational tools and databases to scrutinize specific missense SNP and meticulously analyzed their potential effects on protein structure stability and function. Our analysis has confirmed a total of 4 missense SNP in ALDH2, APOE, IGFBP1, and PCSK1 genes to be damaging to protein structure and hence, the function. An extensive literature review was then performed to determine the functional roles of these genes in the regulation of the cardiac system-related pathways. Our analysis confirmed that all 2 of these genes are directly involved in pathways related to the cardiac system, while the other 2 genes play other roles. We have further analyzed their interactions and underlying biological processes to determine their potential role in the incidence of MI. These findings collectively offer a profound understanding of the intricate genetic landscape underlying MI. They not only enhance our comprehension of the multifaceted genetic factors influencing MI susceptibility but also set the stage for future experimental investigations. Importantly, these insights hold the potential to guide future research and the development of therapeutic strategies, to improve the prevention and management of this critical cardiovascular condition.
An urbanized phantom tributary subsidizes river-riparian communities of mainstem gravel-bed river
Authors: Negishi JN , Song YY , Matsubara I , Morisaki N
Published: November 2023

Urbanization transforms natural river channels, and some rivers become invisible over time. How and whether the subsurface domains of the original waterways and aquifers connecting them (a phantom of historical landscape) are functional is not known. This study examined the effects of tributary groundwater (GW) inflow on the response of river-riparian organisms in an alluvial mainstem river in northern Japan, where the tributary disappeared over the course of urban landscape transformation.

A 2.8-km long lowland segment of the mainstem gravel-bed river was examined for water properties and the river-riparian food web. In addition, watershed-wide water sampling was conducted to isotopically distinguish several types of groundwater that contributed to the hyporheic water in the study segment. There was a clear effect of altitude on the hydrogen/oxygen stable isotope ratios in the river water collected across the watershed.

Groundwater unique both in chemical sand isotopic signatures in several spots occurred within the study segment, and its properties resembled to and its upwelling locations matched groundwater from a tributary river whose surface channel has disappeared 60 years ago. Positive numerical increases in abundance and/or a sign of nitrogen transfer in river riparian communities (algae, invertebrates, and riparian trees) originating from groundwater high in nitrate with elevated nitrogen stable isotope ratios were found.

This study demonstrated that tributary groundwater with unique chemical properties manifested by an urban watershed river network continued to have cascading effects on biota across the river-riparian boundary in the mainstem river, even after urbanization transformed the tributary into a historically lost phantom river. We highlighted the legacy effects of landscape transformation in the subsurface domain and the significance of scrutinizing the past landscape and hydrological connectivity at the watershed scale in urban environments.
Surface-sourced eDNA to track deep-diver cetaceans: the study case of Cuvier’s beaked whale (Ziphius cavirostris) at Caprera Canyon and surrounding areas (Western Mediterranean Sea)
Authors: Boldrocchi G. , Conte L. , Galli P. , Bettinetti R. , Valsecchi E.
Published: November 2023

Among cetaceans, the Cuvier’s beaked whale is considered an extreme diver, very challenging to be studied with standard monitoring methods due to its elusive behaviour and a preference for deep offshore waters. These limitations seem to be mitigated by the use of new molecular methodologies capable of intercepting small traces of DNA left in the environment (eDNA) by marine organisms. Moreover, the collection of water from the superficial layer of the sea represents a perfect case study for the targeting of marine mammals, as the constraints imposed by their nature implies periodic and frequent surfacing. Therefore, we designed and tested a taxon-specific primer set to infer the Cuvier’s beaked whale presence, with the aims of 1) examining the effectiveness of the eDNA technique to detect the presence of deep-diving cetacean in open waters, using the Cuvier’s beaked whale as case study; 2) providing data on the spatiotemporal occurrence of this species within the Canyon of Caprera; and 3) assessing the species occurrence in central northern Mediterranean Sea based on molecular traces. Results from this study demonstrated that collection of superficial waters is a valid approach to monitor deep-diving cetacean species, without the need for complementary visual survey monitoring. Specifically, this study provides evidence of the regular presence of the Cuvier’s beaked whale in the Canyon of Caprera, with a preference for bathymetry in the range of 700-1000 m. This study also showed a potential inshore movement of this species during fall, which is possibly related to migration of its cephalopod prey or a shift in prey preferences. Overall, the data presented here are particularly relevant in the optic of proposing the Caprera Canyon as anImportant Marine Mammal Area(IMMA) in the Mediterranean Sea. At a wider level, this study also showed that the stronger positive signals were recorded in sampling stations located on submarine canyon systems, demonstrating the importance of these areas as elective habitats for the Cuvier’s beaked whale, thus the pivotal priority to their conservation.
Cryptic connectivity between hyporheic and riparian zones via winged aquatic insects revealed by DNA barcoding
Authors: Negishi JN , Alam MK , Tojo K , Nakamura F
Published: November 2023

How subsurface hyporheic zone (HZ) of rivers is connected to riparian zones remains largely unknown. We collected benthic macroinvertebrates and adult aquatic insects for six years, including those at 30-cm depth in the HZ to identify insect taxa having a high level of habitat affinity for HZ (HZ taxa). Adults of HZ taxa were identified with the aid of CO1 gene barcoding, and the relative abundance of HZ taxa in the riparian zone was quantified. In addition to the previously known stoneflyAlloperla ishikariana, three species of stonefly Leuctridae and one caddisfly species of Philopotamidae were identified as HZ taxa. At the annual scale, HZ taxa accounted for approximately 38% of the total aquatic insects in the family of stoneflies (Plecoptera), caddisflies (Trichoptera), and mayflies (Ephemeroptera) in abundance and 26% of biomass, with their seasonal peaks in early spring and mid-summer (60% in abundance and 47% in biomass). Few individuals of HZ taxa were found in benthic samples (<0.1%), and hyporheic samples quantified more but erroneously estimated relative abundances of adult HZ taxa, with Leuctridae and Philopotamidae being substantially underrepresented relative to their adult abundance. Cryptic biological connectivity between subsurface and riparian zones via winged HZ-taxa adults is substantial. DNA-based species identification combined with community surveys of adult HZ-taxa complementarily used with benthic data can substantially improve the effectiveness of biomonitoring programs and outcomes of habitat conservation based on more complete picture of ecosystem health.
Plant neighbors differentially alter a focal species’ biotic interactions through changes to resource allocation
Authors: Turner Sophia C. , Schweitzer Jennifer A.
Published: November 2023

Plant resource allocation strategies are thought to be largely a consequence of changing abiotic conditions and evolutionary history. However, biotic interactions also influence how a plant allocates resources. As a result, plants mediate indirect interactions between organisms above- and belowground through resource allocation. Neighboring plants can influence plant fitness directly through competition for resources, and indirectly by altering associated community interactions (associational effects). Given the importance of community interactions for plant success, and the known ability for plant neighbors to change these interactions, the goal of this “pandemic project” was to separate inter- and intraspecific plant associations, above- and belowground, to understand how different plant neighbors alter plant resource allocation, and if this in turn alters biotic interactions. We specifically investigated associational effects on herbivory and soil microbial community interactions. To do so, we established a common garden experiment, manipulating plant neighbors and extent of interactions (aboveground only versus above- and belowground interactions, using customized pot types), and measured changes to a focal plant and its biotic interactions over two growing seasons. We found evidence of both neighbor effects and pot type, showing that neighbor interactions affect a focal plant through both above- and belowground processes, and how the focal plant is affected depends on neighbor identity. Though neighbors did not directly alter herbivory or most soil microbial interactions, they did alter the relationship between belowground microbial communities and plant function. Resource allocation responses were reduced with time, showing the importance of extending experiments beyond a single growing season, and is an important consideration when making predictions about plant responses to changing conditions. This study contributes to a growing body of work showing how the community context affects the above- and belowground interactions of a plant through plant resource allocation strategies.
From initial RNA encoding to the Standard Genetic Code
Authors: Yarus Michael
Published: November 2023

Multiple experiments have shown that RNA binds chemically varied amino acids within specific oligoibonucleotide sequences. The smallest, simplest, and potentially most primitive RNA binding sites frequently contain conserved triplets corresponding to the Standard Genetic Code (SGC). Here, implications of such cognate coding triplets are calculated, combining them with an optimized kinetic model for SGC evolution. RNA-amino acid interactions at observed frequencies choose an SGC-like code, and, using the same mechanism, effectively resist alternative triplet assignments. Resistance to other kinds of coding is evident across varied code initiation scenarios. RNA-mediated assignments at experimental frequencies are sufficient to guide the ‘ribonucleopeotide transition’ (RNPT) to a modern code. This can account for extreme selection of the SGC among its astronomical code possibilities; very SGC-like codes are ca. 1/50 to 1/5 of codes within such a population. Nevertheless, full accounting depends on RNA affinities yet unmeasured. Such a code begins as mostly stereochemical, excludes mismatched assignments, and critically relies on properties characteristic of fusible microbes. After its RNPT in a partially assigned code, evolution accelerates definitively. Other assignment methods (adaptation, co-evolution, revised stereochemistry, LGT) likely complete the modern SGC because stable cellular intermediates with > 1 code exist, allowing compartmental code exchanges. Though initiated using chemical affinities, the 83 order-of-magnitude focus required to find a near-complete SGC among all possible codes was made by sequential evolutionary anthologies, in successive biological settings.
Replication of [AT/TA]25microsatellite sequences by human DNA polymerase δ holoenzymes is dependent on dNTP and RPA levels
Authors: Pytko Kara G. , Dannenberg Rachel L. , Eckert Kristin A. , Hedglin Mark
Published: November 2023

Difficult-to-Replicate Sequences (DiToRS) are natural impediments in the human genome that inhibit DNA replication under endogenous replication. Some of the most widely-studied DiToRS are A+T-rich, high “flexibility regions,” including long stretches of perfect [AT/TA] microsatellite repeats that have the potential to collapse into hairpin structures when in single-stranded DNA (ssDNA) form and are sites of recurrent structural variation and double-stranded DNA (dsDNA) breaks. Currently, it is unclear how these flexibility regions impact DNA replication, greatly limiting our fundamental understanding of human genome stability. To investigate replication through flexibility regions, we utilized FRET to characterize the effects of the major ssDNA-binding complex, RPA, on the structure of perfect [AT/TA]25microsatellite repeats and also re-constituted human lagging strand replication to quantitatively characterize initial encounters of pol δ holoenzymes with A+T-rich DNA template sequences. The results indicate that [AT/TA]25sequences adopt hairpin structures that are unwound by RPA and pol δ holoenzymes support dNTP incorporation through the [AT/TA]25sequences as well as an A+T-rich, non-structure forming sequence. Furthermore, the extent of dNTP incorporation is dependent on the sequence of the DNA template and the concentration of dNTPs. Importantly, the effects of RPA on the replication of [AT/TA]25sequences are dependent on the concentration of dNTPs, whereas the effects of RPA on the replication of an A+T-rich, non-structure forming sequence are independent of dNTP concentration. Collectively, these results reveal complexities in lagging strand replication and provide novel insights into how flexibility regions contribute to genome instability.
An acidophilic fungus is integral to prey digestion in a carnivorous plant
Authors: Sun Pei-Feng , Lu Min R. , Liu Yu-Ching , Lin Yu-fei , Hoh Daphne Z. , Ke Huei-Mien , Wang I-Fan , Lu Mei-Yeh Jade , Kirschner Roland , Jimmy Lin Ying-Chung , Chen Ying-Lan , Tsai Isheng Jason
Published: November 2023

Carnivorous plant leaves, such as those of the spoon-leaved sundewDrosera spatulata, secrete mucilage which hosts microorganisms potentially aiding in prey digestion. We characterised the mucilage microbial communities and identified the acidophilic fungusAcrodontium crateriformeas the ecologically dominant species. The fungus grows and sporulates on sundew glands as its preferred acidic environment. We show that theA. crateriformehas a reduced genome similar to that of other symbiotic fungi. Based on the transcriptomes when encountering prey insects, we revealed a high degree of genes co-option in each species during fungus-plant coexistence and digestion. Expression patterns of the holobiont during digestion further revealed synergistic effects in several gene families including fungal aspartic and sedolisin peptidases, facilitating the digestion of sundew’s prey, as well as transporters and dose-dependent responses in plant genes involved in jasmonate signalling pathway. This study establishes that botanical carnivory is defined by multidimensional adaptations correlated with interspecies interactions.
Analysis and evaluation of blood screening testing strategies in Nagqu, Tibet: one of the highest cities in world
Authors: Zang Liang , Zhou Lei , Fan Yaxin , Liang Xiaohua , Duo Ji , Lin Hao , Bai Rui , Yang Mei , Dan Chao
Published: November 2023

The aim of this study was to evaluate the performance of blood screening strategies in Nagqu City, with a focus on serological and nucleic acid testing effectiveness. Analysis of blood donation data from 2017 to 2023 revealed a gradual increase in local blood donation rates, but the rate of unqualified donations remained higher than the national average. Serological performance verification showed good repeatability and precision, but improvements are needed in the accuracy of certain markers. Nucleic acid performance verification demonstrated excellent detection capability for low viral load HBV infections. The conclusion highlights significant progress in the screening strategies of Nagqu City, with the nucleic acid testing system showing outstanding performance. The findings provide valuable insights for blood screening in other high-altitude regions.
Comparison of gene expression in living and postmortem human brain
Authors: Collado-Torres Leonardo , Klei Lambertus , Liu Chunyu , Kleinman Joel E. , Hyde Thomas M. , Geschwind Daniel H. , Gandal Michael J. , Devlin Bernie , Weinberger Daniel R.
Published: November 2023

Molecular mechanisms of neuropsychiatric disorders are challenging to study in human brain. For decades, the preferred model has been to study postmortem human brain samples despite the limitations they entail. A recent study generated RNA sequencing data from biopsies of prefrontal cortex from living patients with Parkinson’s Disease and compared gene expression to postmortem tissue samples, from which they found vast differences between the two. This led the authors to question the utility of postmortem human brain studies. Through re-analysis of the same data, we unexpectedly found that the living brain tissue samples were of much lower quality than the postmortem samples across multiple standard metrics. We also performed simulations that illustrate the effects of ignoring RNA degradation in differential gene expression analyses, showing the effects can be substantial and of similar magnitude to what the authors find. For these reasons, we believe the authors’ conclusions are unjustified. To the contrary, while opportunities to study gene expression in the living brain are welcome, evidence that this eclipses the value of postmortem analyses is not apparent.
Operationalized releases ofwAlbBWolbachiainAedes aegyptilead to sharp decreases in dengue incidence dependent onWolbachiafrequency
Authors: Hoffmann Ary A. , Wasi Ahmad Nazni , Wan Ming Keong , Cheong Yoon Ling , Ahmad Noor Afizah , Golding Nick , Tierney Nicholas , Jelip Jenarun , Wilson Putit Perada , Mokhtar Norhayati , Singh Sandhu Sukhvinder , Lau Sai Ming , Khairuddin Khadijah , Denim Kamilan , Mohd Rosli Norazman , Shahar Hanipah , Omar Topek , Ridhuan Ghazali Muhammad Kamarul , Mohd Zabari Nur Zatil Aqmar , Abdul Karim Mohd Arif , Saidin Mohamad Irwan , Mohd Nasir Muhammad Nizam , Aris Tahir , Sinkins Steven P
Published: November 2023

InAedes aegyptimosquitoes, introduction of certain strains of inheritedWolbachiasymbionts results in transmission blocking of various viruses of public health importance, including dengue. This has resulted in a ‘replacement’ strategy for dengue control involving release of male and female mosquitoes, whereuponWolbachiais able to spread throughAe. aegyptipopulations to high frequency and reduces the incidence of dengue.WolbachiastrainwAlbB is an effective transmission blocker and stable at high temperatures, making it very suitable for use in hot tropical climates. Following the first trial field releases of thewAlbB strain inAe. aegyptiin Malaysia, releases ofwAlbBAe. aegyptihave for the first time become operationalized by the Malaysian health authorities. We report here on changes in dengue incidence based on a set of 20 releases sites and 76 control sites in high rise residential areas, which allows us to directly assess the impact ofWolbachiafrequency on dengue incidence. The results indicate an average reduction in dengue of 62.4% (confidence intervals 50-71%); importantly the level of suppression increased withWolbachiafrequency, with suppression of 75.8% (confidence intervals 61-87%) estimated at 100%Wolbachiafrequency. These findings emphasize the large impacts ofwAlbBWolbachiainvasions on dengue incidence in an operational setting, with the expectation that the level of dengue will further decrease as wider areas are invaded.
Cost-effective and scalable clonal hematopoiesis assay provides insight into clonal dynamics
Authors: Mack Taralynn , Vlasschaert Caitlyn , von Beck Kelly , Silver Alexander J. , Heimlich J. Brett , Poisner Hannah , Condon Henry Robert , Ulloa Jessica , Sochacki Andrew L. , Spaulding Travis P. , Kishtagari Ashwin , Bejan Cosmin A. , Xu Yaomin , Savona Michael R. , Jones Angela , Bick Alexander
Published: November 2023

Clonal hematopoiesis of indeterminate potential (CHIP) is a common age-related phenomenon that occurs when hematopoietic stem cells acquire mutations in a select set of genes commonly mutated in myeloid neoplasia which then expand clonally. Current sequencing assays to detect CHIP are not optimized for the detection of these variants and can be cost-prohibitive when applied to large cohorts or serial sequencing. Here, we present and validate a CHIP targeted sequencing assay that is affordable (∼$8/sample), accurate and highly scalable. To demonstrate the utility of this assay, we detected CHIP in a cohort of 456 individuals with DNA collected at multiple timepoints in the Vanderbilt BioVU biobank and quantified clonal expansion rates over time. A total of 101 individuals with CHIP were identified, and individual-level clonal expansion rate was calculated using the variant allele fraction (VAF) at both timepoints. Differences in clonal expansion rate by driver gene were observed, but there was also significant individual-level heterogeneity, emphasizing the multifactorial nature of clonal expansion. We further describe the mutation co-occurrence and clonal competition between multiple driver mutations.
Ophthalmic artery stenosis on three-dimensional rotational angiography: interrater agreement, prevalence, and risk factors
Authors: Diprose William K , Wang Michael T. M. , Reidy Joseph , Ma Alice , Brodie James , Steinfort Brendan
Published: November 2023

Background

There is emerging interest in ophthalmic artery stenosis angioplasty for the treatment of age-related macular degeneration. Three-dimensional rotational angiography could be used intraoperatively to determine the presence and severity of ophthalmic artery stenosis. In patients who had undergone three-dimensional rotational angiography of the internal carotid artery, we aimed to assess the interrater agreement, prevalence, and risk factors for ophthalmic artery stenosis.

Methods

Consecutive patients from two centers who had undergone diagnostic cerebral angiography with three-dimensional rotational angiography of the internal carotid arteries were enrolled in this study. Three-dimensional rotational angiograms were independently double read for the presence of ophthalmic artery stenosis, as defined as an ostial narrowing of at least 50% when compared to the more distal ‘normal’ ophthalmic artery. Interrater agreement for the evaluation of ophthalmic artery stenosis was assessed with the Cohen’s kappa coefficient. Univariate and multivariable logistic regression were used to identify potential predictors of OA stenosis.

Results

302 patients (97 men; mean±SD 57.6±13.4 years) were included in the analysis. Cohen’s kappa coefficient (95% CI) was 0.877 (0.798–0.956). Ophthalmic artery stenosis was present in 45 patients (14.9%). Multiple logistic regression demonstrated that female sex was independently associated with a higher odds of ophthalmic artery stenosis (odds ratio [OR]=2.70, 95% confidence interval [CI] 1.18-6.09, P=0.02). Smoking was a significant risk factor for ophthalmic artery stenosis (OR=2.11, 95% CI 1.10-4.06, P=0.03).

Conclusion

The evaluation of ophthalmic artery stenosis on three-dimensional rotational angiography had excellent interrater agreement. Ophthalmic artery stenosis was common and was associated with smoking and female sex.
Investigating the consumption behavior of young adults using online food delivery platforms during the COVID-19 pandemic
Authors: Leung Yi Lok , Chan Ron L.H. , Chiu Dickson K.W. , Ruwen Tian
Published: November 2023

Purpose

Online food delivery has been prevalent in recent years worldwide, especially during the COVID-19 pandemic, and people's consumption behaviors have changed significantly. This study aims to investigate the consumption behavior of young adults using online food delivery platforms during the COVID-19 pandemic and focuses on the dominant factors influencing their decision to use online food delivery platforms.

Design/methodology/approach

Semi-structured interviews including 14 young adults aged 18–25 living in Hong Kong were conducted to collect data about their perspectives on online food delivery platforms in five areas. This research adopted the stimulus-organism-response model (S-O-R model) to analyze how the factors influence young adult users' loyalty and satisfaction with online food delivery platforms.

Findings

Thematic analyses revealed that young adults were attracted to online food delivery platforms for their numerous benefits. They had a high frequency of usage and significant spending. Usability, usefulness, satisfaction and loyalty influenced young adults' behaviors on online food delivery platforms. Participants were overall satisfied with their experiences, but platforms still had room for improvement.

Originality/value

Few prior studies investigated the factors affecting the consumer experience and behavioral intention of online food delivery for young adults in Asia. This study contributes to understanding young adults' experiences and problems with online food delivery platforms. It provides practical insights for system engineers and designers to improve the current services and for the governments to enhance the existing regulatory loopholes.