bluuebunny/crossref_metadata_2025 huggingface dataset:
2Animal Studies
Authors: Giraud Eva Haifa
Published: August 2022

In this year’s overview of animal studies scholarship, I examine how authors strike a difficult balancing act between making critical interventions while preserving complexity, in relation to three (overlapping) topics that have long been central to the field: domestication, consumption, and extinction. The essay begins by engaging with three texts that interrogate the dynamics of domestication, especially in relation to animal rescue: Chris Pearson’s Dogopolis, Harlan Weaver’s Bad Dog, and Elan Abrell’s Saving Animals. Next, I move on to work that offers provocations about the politics of consumption: Catherine Oliver’s Veganism, Archives, and Animals, Emelia Quinn’s Reading Veganism, and Sushmita Chatterjee and Banu Subramaniam’s edited collection Meat! The essay closes by turning to research that discusses the fraught politics of extinction and environmental catastrophe: Nayanika Mathur’s Crooked Cats and Danielle Celermajer’s Summertime. While the content of each text explores ethical concerns in relation to nonhuman animals, as I describe below, these books also offer a range of ethical provocations about the trajectory of animal studies itself, which pertain to its norms, values, and methodologies. One thing that unites many of these texts, however, is that they illustrate how staunch critique of existing relations between humans and other beings does not have to come at the expense of situatedness, conceptual nuance, and recognition of complexity.
Post‐ischemic protection of hepatocyte growth factor requires the type II transmembrane serine protease matriptase—A reciprocal regulation of the two for neuroprotection in stroke brain
Authors: Lee Sheau‐Ling , Lee Michelle Hui‐Hsin , Wu Kuo‐Jen , Chiang Chia‐Wen , Chang Yun‐Xuan , Fang Jung‐Da , Tung Hsiu‐Hui , Kuo Li‐Wei , Wang Yun
Published: August 2022

In a rat middle cerebral artery occlusion (MACo) model of ischemic stroke, intracerebroventricular administration of human recombinant hepatocyte growth factor (HGF) mitigated motor impairment and cortical infarction. Recombinant HGF reduced MCAo‐induced TNFα and IL1β expression, and alleviated perilesional reactivation of microglia and astrocyte. All of the aforementioned beneficial effects of HGF were antagonized by an inhibitor to the type II transmembrane serine protease matriptase (MTP). MCAo upregulated MTP mRNA and protein in the lesioned cortex. MTP protein, not the mRNA, was increased further by recombinant HGF but reduced when MTP inhibitor (MTPi) was added to the treatment. Changes of the endogenous active HGF by MCAo, HGF or MTPi paralleled with the changes of MTP protein under the same conditions whilst neither HGF mRNA nor the total endogenous HGF protein were altered. These data showed that the therapeutic effects of HGF in stroke brain is attributed to its proteolytic activation and that MTP is a main protease of the event. MCAo enhanced MTP mRNA and thus protein expression; the initial use of the recombinant active HGF stabilized MCAo‐induced MTP protein and subsequent activation of endogenous latent HGF which in turn stabilized further MTP protein. A reciprocal regulation between MTP and HGF appears to be present where MTP promotes HGF activation and the active HGF prevents MTP protein turnover. This study, for the first time, shows that MTP can participate in neural protection in stroke brain through activation of HGF. The cycles of HGF‐MTP regulation achieved preservation of the neurological activity.
Apelin-Induced Relaxation of Coronary Arteries Is Impaired in a Model of Second-Hand Cigarette Smoke Exposure
Authors: Anto Santo , Sathish Venkatachalem , Sun Chengwen , O'Rourke Stephen T.
Published: August 2022

Apelin, an endogenous ligand for APJ receptors, causes nitric oxide (NO)–dependent relaxation of coronary arteries. Little is known about the effects of apelin/APJ receptor signaling in the coronary circulation under pathological conditions. Here, we tested the hypothesis that the vasorelaxing effect of apelin is impaired by cigarette smoke extract (CSE), an established model for second-hand smoke exposure. Isolated rat coronary arteries were treated with 2% CSE for 4 hours. Apelin-induced relaxation of coronary arteries was abolished by CSE exposure, while relaxations to acetylcholine (ACh) (endothelium‐dependent relaxation) and to diethyl amine NONOate (NO donor) were similar in control and CSE‐treated arteries. Immunoblot analysis demonstrated that apelin increased eNOSser1177 phosphorylation under control conditions but had no effect after exposure to CSE. Moreover, GRK2 expression was increased in CSE-exposed coronary endothelial cells. Pretreatment with CMPD101, a GRK2 inhibitor, improved the relaxation response to apelin in CSE-exposed coronary arteries. CSE treatment failed to inhibit relaxations evoked by CMF‐019, an APJ receptor biased agonist that has little effect on GRK2. In arteries exposed to CSE, apelin impaired the response to ACh but not to diethyl amine NONOate. ACh‐induced relaxation was unaffected by CMF‐019 in either control or CSE‐treated coronary arteries. The results suggest that APJ receptor signaling using the GRK2 pathway contributes to both loss of relaxation to apelin itself and the ability of apelin to inhibit endothelium‐dependent relaxation to ACh in CSE-exposed coronary arteries, likely because of impaired production of NO from endothelial cells. These changes in apelin/APJ receptor signaling under pathological conditions (eg, exposure to second-hand smoke) could create an environment that favors increased vasomotor tone in coronary arteries.
Identifying Mast Cells in Gastrointestinal Biopsies in Pediatric Irritable Bowel Patients
Authors: Rizvi Syed Ahsan , Oriala Chukwuemeka , Thomas Jessina , Li Shuan , Smadi Yamen
Published: August 2022

Objectives:

Mast cells (MCs) have been proposed to be involved in the pathophysiology of irritable bowel syndrome (IBS). Nonetheless, the quantity and distribution of MCs in the gastrointestinal tract of pediatric patients with IBS are not well defined. This study aimed to compare the number of MCs in children with and without IBS and to establish histopathological reference values in pediatrics.

Methods:

Forty‐nine participants with IBS were prospectively enrolled and classified into IBS with atopy (n = 29) and IBS without atopy (n = 20). As our retrospective control group, we selected 42 individuals with a history of polyposis syndrome or gastroesophageal reflux disease with normal histopathology. Retrospective selection of the control cohort was performed in a manner similar to previously published adult and pediatric studies. MCs were prospectively stained immunohistochemically on specimens from the stomach, duodenum, terminal ileum, and descending colon of both groups.

Results:

The IBS group showed significantly more MCs per high‐power field (MCs/HPF) in the stomach, duodenum, terminal ileum, and descending colon (P < 0.001), irrespective of their atopic status. Optimal MC cutoff values for IBS are ≥20.5 MCs/HPF in the stomach (area under the curve [AUC] = 0.84); ≥23.0 MCs/HPF in the duodenum (AUC = 0.79); ≥33.5 MCs/HPF in the terminal ileum (AUC = 0.82); and ≥22.5 MCs/HPF in the descending colon (AUC = 0.86).

Conclusions:

Pediatric patients with IBS showed increased numbers of MCs in the stomach, duodenum, terminal ileum, and descending colon when compared with controls. Further trials are needed to explain the role of MCs in pediatric IBS, which might facilitate the development of targeted therapeutic interventions.
Addressing Health Equity Goals for COVID-19 Vaccination Using Integrated Data and Mapping Tools: A Collaboration Between Academia, Public Health, and Health Care Systems in Columbus and Franklin County, Ohio
Authors: Hyder Ayaz , Graffagnino Cheryl , Barbeau Rebecca , Bennett Suellen , Dent Lisa D. , French Gavin , Glover Autumn , Jones Alexandria , McAdams Jennie , Nawaz Saira , Wontumi Gold-Marie , Baryeh Nana
Published: August 2022

Context:

Data sharing between local health departments and health care systems is challenging during public health crises. In early 2021, the supply of COVID-19 vaccine was limited, vaccine appointments were difficult to schedule, and state health departments were using a phased approach to determine who was eligible to get the vaccine.

Program:

Multiple local health departments and health care systems with the capacity for mobile and pop-up vaccine clinics came together in Columbus and Franklin County, Ohio, with a common objective to coordinate where, when, and how to set up mobile/pop-up COVID-19 vaccine clinics. To support this objective, the Equity Mapping Tool, which is a set of integrated tools, workflows, and processes, was developed, implemented, and deployed in partnership with an academic institution.

Implementation:

The Equity Mapping Tool was designed after a rapid community engagement phase. Our analytical approaches were informed by community engagement activities, and we translated the Equity Mapping Tool for stakeholders, who typically do not share timely and granular data, to build capacity for data-enabled decision making.

Discussion:

We discuss our observations related to the sustainability of the Equity Mapping Tool, lessons learned for public health scientists/practitioners, and future directions for extending the Equity Mapping Tool to other jurisdictions and public health crises.
Obsessive-Compulsive Disorder and Risk of Parkinson Disease: A Nationwide Longitudinal Study
Authors: Liou Ying-Jay , Bai Ya-Mei , Chen Mu-Hong , Cheng Chih-Ming , Chen Tzeng-Ji , Tsai Shih-Jen
Published: August 2022

Objective

Several small-scale studies have suggested a biological link between obsessive-compulsive disorder (OCD) and Parkinson disease (PD). However, the temporal association of OCD and subsequent PD remained unclear.

Methods

Here, we used Taiwan National Health Insurance Research Database and included the data of 28,722 patients with OCD (International Classification of Diseases, Ninth Revision, Clinical Modification code: 300.3) and 287,220 matched controls between 2001 and 2009. They were followed until the end of 2011 to identify diagnosis of new-onset PD (International Classification of Diseases, Ninth Revision, Clinical Modification code: 332.0). The frequency of psychiatric outpatient visits for OCD per year (<5, 5–10, and >10) was identified as a proxy of OCD severity.

Results

Using the stratified Cox regression model, the hazard ratio of developing PD among patients with OCD was 2.70 (95% confidence interval = 1.74–4.18) compared with matched controls. Among patients with OCD, those with >10 psychiatric outpatient visits per year for OCD (hazard ratio = 3.18, 95% confidence interval = 2.06–4.93) were more likely to develop PD during the follow-up period compared with those with <5 psychiatric outpatient visits per years for OCD.

Conclusions

OCD was found to be an independent risk factor for PD. The mechanisms underlying the temporal association between OCD and subsequent PD require further investigation.
Sexual Minority Stress and Cellular Aging in Methamphetamine-Using Sexual Minority Men With Treated HIV
Authors: Ghanooni Delaram , Carrico Adam W. , Williams Renessa , Glynn Tiffany R. , Moskowitz Judith T. , Pahwa Savita , Pallikkuth Suresh , Roach Margaret E. , Dilworth Samantha , Aouizerat Bradley E. , Flentje Annesa
Published: August 2022

Objective

Sexual minority men (e.g., gay, bisexual, and other men who have sex with men) experience stigma and sexual minority stress, which are theorized to drive negative health outcomes. Sexual minority men with treated HIV display persistent immune dysregulation, which could be amplified by sexual minority stress responses to potentiate cellular aging.

Methods

This cross-sectional study included 52 sexual minority men living with HIV who had undetectable viral load (<40 copies/mL) and biologically confirmed recent methamphetamine use. Participants completed measures assessing sexual minority stress and openness about sexual minority status (i.e., outness). DNA methylation–derived outcomes included the following: the extrinsic epigenetic age acceleration clock, telomere length, naive CD4+ T-helper cells, and naive CD8+ T-cytotoxic/suppressor cells.

Results

After adjusting for negative affect and recent stimulant use, higher sexual minority stress was associated with a faster extrinsic epigenetic age acceleration clock (β = 0.29, p = .030), shorter telomere length (β = −0.43, p = .002), and fewer naive CD4+ (β = −0.57, p < .001) and naive CD8+ T cells (β = −0.57, p < .001). Greater outness was associated with higher naive CD4+ (β = 0.32, p = .030) and naive CD8+ T cells (β = 0.38, p = .008) as well as lower plasma interleukin 6 (β = −0.33, p = .027).

Conclusions

Sexual minority stress processes are associated with markers of cellular aging and inflammation in methamphetamine-using sexual minority men living with HIV. Longitudinal research should elucidate biobehavioral mechanisms linking sexual minority stress processes with accelerated cellular aging in those with and without HIV.
Importance of sleep for avian vocal communication
Authors: Gaviraghi Mussoi Juliane , Stanley Margaret C. , Cain Kristal E.
Published: August 2022

Sleep is one of the few truly ubiquitous animal behaviours, and though many animals spend enormous periods of time asleep, we have only begun to understand the consequences of sleep disturbances. In humans, sleep is crucial for effective communication. Birds are classic models for understanding the evolution and mechanisms of human language and speech. Bird vocalizations are remarkably diverse, critical, fitness-related behaviours, and the way sleep affects vocalizations is likely similarly varied. However, research on the effects of sleep disturbances on avian vocalizations is shockingly scarce. Consequently, there is a critical gap in our understanding of the extent to which sleep disturbances disrupt communication. Here, we argue that sleep disturbances are likely to affect all birds' vocal performance by interfering with motivation, memory consolidation and vocal maintenance. Further, we suggest that quality sleep is likely essential when learning new vocalizations and that sleep disturbances will have especially strong effects on learned vocalizations. Finally, we advocate for future research to address gaps in our understanding of how sleep influences vocal learning and performance in birds.
Wyndham John Albery. 5 April 1936—3 December 2013
Authors: Hitchman Michael L. , Bartlett Philip N.
Published: August 2022

John Albery was one of the most creative, innovative and distinguished physical chemists of his time. He was particularly noted for his pioneering work in electrochemistry and electroanalytical chemistry, proton transfer kinetics and isotope effects, and enzyme kinetics. His DPhil studies on rotating disc electrodes led to seminal papers in the 1960s on ring-disc electrodes, which laid the basis for the extensive development of a powerful tool for electrochemical diagnostics. Those doctoral studies also involved work on the mechanisms of proton transfer reactions, a subject that remained very dear to his heart, and later resulted in the application of Marcus theory to provide understanding of physical organic reactions. In a separate strand on kinetic processes, he developed the theory of enzyme catalysis, which gave important insights into reaction kinetics of biological catalysts. He was a marvellous teacher and an inspiration to generations of his students, both undergraduate and post-graduate. His legacy reached far and wide, with a scientific family that included more than a dozen professorial ‘offspring’. His talents were not only restricted to science but extended to the theatre and entertainment, with writing for the satirical programme
That was the week that was
, the production of two musicals and of numerous departmental and college cabarets and irreverent annual revues. John Albery had an irrepressible joie de vivre and was the instigator of and participant in many occasions that were full of fun and laughter and live on in the memory. But it was not all fun and games; he had a keen sense of social justice. He led the assault to admit women to the previously men-only colleges of Oxford, and in the 1970s he mounted a vigorous and successful campaign to secure permission for the great Jewish electrochemist Benjamin Levich to leave the Soviet Union.
The role of evolutionary game theory in spatial and non-spatial models of the survival of cooperation in cancer: a review
Authors: Coggan Helena , Page Karen M.
Published: August 2022

Evolutionary game theory (EGT) is a branch of mathematics which considers populations of individuals interacting with each other to receive pay-offs. An individual’s pay-off is dependent on the strategy of its opponent(s) as well as on its own, and the higher its pay-off, the higher its reproductive fitness. Its offspring generally inherit its interaction strategy, subject to random mutation. Over time, the composition of the population shifts as different strategies spread or are driven extinct. In the last 25 years there has been a flood of interest in applying EGT to cancer modelling, with the aim of explaining how cancerous mutations spread through healthy tissue and how intercellular cooperation persists in tumour-cell populations. This review traces this body of work from theoretical analyses of well-mixed infinite populations through to more realistic spatial models of the development of cooperation between epithelial cells. We also consider work in which EGT has been used to make experimental predictions about the evolution of cancer, and discuss work that remains to be done before EGT can make large-scale contributions to clinical treatment and patient outcomes.
The scope and infringement of patents claiming strains of bacteria
Authors: MacLeod Ian
Published: August 2022

Increasing numbers of patents directed to bacteria and bacterial products are being filed and granted, many of which claim specific deposited strains of bacteria. However, there remains significant uncertainty regarding exactly what scope patent claims limited to deposited strains might have. A claim limited to a specific deposited strain could be interpreted extremely narrowly, extending only to descendants of that deposit. However, a review of the available guidance from courts across the globe suggests that in practice such claims are likely to be infringed by competitor products. The commercial value of patent claims to bacteria depends on the regulatory and competitive landscape, and can be strengthened by appropriate details in patent applications.
Huaxiibacter chinensis gen. nov., sp. nov., recovered from human sputum
Authors: He Yanling , Wu Shikai , Feng Yu , Zong Zhiyong
Published: August 2022

Strain 155047T was recovered from human sputum in China in 2021. Preliminary species identification based on limited phenotypic tests assigned the strain to the genus

Enterobacter

of the family

Enterobacteriaceae

. The genome sequence of the strain was obtained and had ≤84.43 % average nucleotide identity (ANI) and ≤26.3 % in silico DNA–DNA hybridization (isDDH) values with the genomes of type strains of known

Enterobacteriaceae

species. The highest ANI and isDDH matches were with

Lelliottia nimipressuralis

and

Enterobacter asburiae

, respectively. The ANI and isDDH values support that the strain belongs to a novel species of the family

Enterobacteriaceae

. Phylogenomic analysis based on core genes revealed that strain 155047T was located in the Enterobacter–Leclercia–Lelliottia–Pseudenterobacter lineage. The highest ANI and average amino acid identity values between 155047T and any species of the Enterobacter–Leclercia–Lelliottia–Pseudenterobacter lineage were 84.43 % and 90.21 %, respectively, lower than the maximum inter-genus pairwise values. This indicates that 155047T belongs to a novel species of a novel genus in the lineage. Strain 155047T could be differentiated from

Enterobacter

,

Lelliottia

,

Leclercia

and

Pseudenterobacter

species by a negative reaction for β-galactosidase and the ability to produce acid from l-fucose but not from sucrose. The names Huaxiibacter gen. nov. and Huaxiibacter chinensis sp. nov. are proposed for the novel genus and species, respectively. The type strain is 155047T (= GDMCC 1.2980T=JCM 35262T).
Reliable energy-based antibody humanization and stabilization
Authors: Tennenhouse Ariel , Khmelnitsky Lev , Khalaila Razi , Yeshaya Noa , Noronha Ashish , Lindzen Moshit , Makowski Emily , Zaretsky Ira , Sirkis Yael Fridmann , Galon-Wolfenson Yael , Tessier Peter M. , Abramson Jakub , Yarden Yosef , Fass Deborah , Fleishman Sarel J.
Published: August 2022

Humanization is an essential step in developing animal-derived antibodies into therapeutics, and approximately one third of approved antibodies have been humanized. Conventional humanization approaches graft the complementarity-determining regions (CDRs) of the animal antibody onto several homologous human frameworks. This process, however, often drastically lowers stability and antigen binding, demanding iterative mutational fine-tuning to recover the original antibody properties. Here, we present Computational hUMan AntiBody design (CUMAb), a web-accessible method that starts from an experimental or model antibody structure, systematically grafts the animal CDRs on thousands of human frameworks, and uses Rosetta atomistic simulations to rank the designs by energy and structural integrity (http://CUMAb.weizmann.ac.il). CUMAb designs of five independent antibodies exhibit similar affinities to the parental animal antibody, and some designs show marked improvement in stability. Surprisingly, nonhomologous frameworks are often preferred to the highest-homology ones, and several CUMAb designs that use different human frameworks and differ by dozens of mutations are functionally equivalent. Thus, CUMAb presents a general and streamlined approach to optimizing antibody stability and expressibility while increasing humanness.
Rapid waning of protection induced by prior BA.1/BA.2 infection against BA.5 infection
Authors: Malato João , Ribeiro Ruy M. , Fernandes Eugénia , Leite Pedro Pinto , Casaca Pedro , Antunes Carlos , Fonseca Válter R. , Gomes Manuel Carmo , Graca Luis
Published: August 2022

SARS-CoV-2 omicron subvariants BA.1 and BA.2 became dominant in many countries in early 2022. These subvariants are now being displaced by BA.4 and BA.5. While natural infection with BA.1/BA.2 provides some protection against BA.4/BA.5 infection, the duration of this protection remains unknown.

We used the national Portuguese COVID-19 registry to investigate the waning of protective immunity conferred by prior BA.1/BA.2 infection towards BA.5. We divided the individuals infected during the period of BA.1/BA.2 dominance (>90% of sample isolates) in successive 15-day intervals and determined the risk of subsequent infection with BA.5 over a fixed period.

Compared with uninfected people, one previous infection conferred substantial protection against BA.5 re-infection at 3 months (RR=0.12; 95% CI: 0.11-0.12). However, although still significant, the protection was reduced by two-fold at 5 months post-infection (RR=0.24; 0.23-0.24).

These results should be interpreted in the context of vaccine breakthrough infections, as the vaccination coverage in the individuals included in the analyses is >98% since the end of 2021.

This waning of protection following BA.1/BA.2 infection highlights the need to assess the stability and durability of immune protection induced with the adapted vaccines (based on BA.1) over time.
Neighbourhood deprivation across eight decades and late-life cognitive function in the Lothian Birth Cohort 1936: A life-course study
Authors: Baranyi Gergő , Conte Federica , Deary Ian J. , Shortt Niamh , Thompson Catharine Ward , Cox Simon R. , Pearce Jamie
Published: August 2022

Introduction

Although neighbourhood may predict late-life cognitive function, studies mostly relies on measurements at a single time point, with few investigations applying a life-course approach. Further, it is unclear whether the associations between neighbourhood and cognitive tests scores relate to specific cognitive domains or general ability. This study explored how neighbourhood deprivation across eight decades contributes to late-life cognitive function.

Methods

Data were drawn from the Lothian Birth Cohort 1936 (n=1091) with cognitive function measured through 10 tests at ages 70, 73, 76, 79 and 82. Participants’ residential history was gathered with ‘lifegrid’ questionnaires and linked to neighbourhood deprivation in childhood, young adulthood, and mid-to-late adulthood. Associations were tested with latent growth curve models for levels and slopes of general (g) and domain-specific abilities (visuospatial ability, memory, and processing speed), life-course associations were explored with path analysis.

Results

Higher mid-to-late adulthood neighbourhood deprivation was associated with lower age 70 levels (β=-0.113, 95%CI: −0.205, −0.021) and faster decline of g over 12 years (β=-0.160, 95%CI: −0.290, −0.031). Initially-apparent findings with domain-specific cognitive functions (e.g. processing speed) were due to their shared variance with g. Path analyses suggested that childhood neighbourhood disadvantage is indirectly linked to late-life cognitive function through education and selective residential mobility.

Conclusions

To our knowledge, we provide the most comprehensive assessment of the relationship between life-course neighbourhood deprivation and cognitive ageing. Living in advantaged areas in mid-to-late adulthood may contribute to better cognitive function and slower decline, whereas advantaged childhood neighbourhood environment likely affects functioning through cognitive reserves.
Aerodigestoscopy (ADS): A retrospective examination of the feasibility, safety, and comfort of a new procedure for the evaluation of physiological disorders of the aerodigestive tract
Authors: Arnold Robert J. , Bausek Nina , Gaskill Christopher S. , Johnson Lawrence F. , Aldarondo Sigfredo , Aull Cody , Midani Malik , Midani Tarek , Midani Ramiz , Brown Ashton S. , Wallace Alana
Published: August 2022

Limited access to comprehensive assessment of physiological disorders of the upper aerodigestive tract by different specialties represents a barrier to care in rural healthcare settings, which may lead to misdiagnosis, underdiagnosis, and increased associated mortality. No single differential diagnostic exam for the comprehensive assessment of all functions of the upper aerodigestive tract is available to bridge this gap. We present a single procedure for assessment of physiological functions of the upper aerodigestive tract including swallow, voice, respiration, and cough while also screening for gastric retention and obstructive sleep apnea which might contribute to these disorders. Our procedure, called Aerodigestoscopy (ADS), represents a procedure incorporating other established exams as integral components to evaluate patients with aerodigestive disorders. Patients who might particularly benefit from our ADS diagnostic algorithm are those in a rural community referred by other health professionals due to complaints of aerodigestive symptoms and signs. We present a brief overview of how the procedure was developed, what it includes, and retrospective safety data from over 18,000 ADS procedures performed over the last 10 years, demonstrating safety and feasibility of this procedure.
Convergent evolution of skim feeding in baleen whales
Authors: Dutoit Ludovic , Mitchell Kieren J. , Dussex Nicolas , Kemper Catherine M. , Larsson Petter , Dalén Love , Rawlence Nicolas J. , Marx Felix G.
Published: August 2022

The origin of pygmy right whales (Caperea marginata), the smallest and most enigmatic of the living baleen whales, remains contentious. Morphological analyses largely continue to ally Caperea with right whales (balaenids) based on shared cranial features like a tall braincase and a narrow, highly arched rostrum. By contrast, molecular data and some anatomical evidence suggest a closer relationship with rorquals (balaenopterids), but fail to explain “the substantial issue of convergence posed by the many balaenid features of Caperea” (Berta & Demere, 2017). To resolve this question, we sequenced the nuclear genome of C. marginata (812,269,251 paired reads; 47X average depth of coverage, with 89.33% of the genome covered at ≥10X) and subjected it to a multispecies coalescent analysis including representatives of all baleen whale families. Our results confirm Caperea as sister to rorquals and, thus, the convergent origin of its right whale-like anatomy. Considering this overwhelming molecular evidence, we propose that the traditional taxonomic grouping of Caperea with right whales be abandoned.
An atlas of thyroid hormone receptors target genes in mouse tissues
Authors: Zekri Yanis , Guyot Romain , Flamant Frédéric
Published: August 2022

We gathered in a single database available RNA-seq and ChIP-seq data to better characterize the target genes of the thyroid hormone receptors in several cell types. This database can serve as a resource to analyze the mode of action of the hormone. Also, it is an easy-handling convenient tool to obtain information on specific genes in regards to T3 regulation, or extract larger list of genes of interest based on the users’ criteria. Overall, this atlas is a unique compilation of recent sequencing data focusing on thyroid hormones, their receptors, mode of action, targets and roles which may profit researchers within the field. A preliminary analysis indicates extensive variations in the repertoire of target genes which transcription is upregulated by chromatin-bound nuclear receptor. Although it has a major influence, chromatin accessibility is not the only parameter that determines the cellular selectivity of hormonal response.
Loss of protein stability and function caused by P228L variation in NADPH-cytochrome P450 reductase linked to lower testosterone levels
Authors: Velazquez Maria Natalia Rojas , Noebauer Mathias , Pandey Amit V.
Published: August 2022

Cytochrome P450 oxidoreductase (POR) is the redox partner of steroid and drug-metabolizing cytochromes P450 located in the endoplasmic reticulum. Mutations in POR cause a broad range of metabolic disorders. The POR variant rs17853284 (P228L) identified by genome sequencing has been linked to lower testosterone levels and reduced P450 activities. We expressed POR wild type and the P228L variant in bacteria, purified the proteins, and performed protein stability and catalytic functional studies. Variant P228L affected the stability of the protein as evidenced by lower unfolding temperatures and higher sensitivity to urea denaturation. A significant reduction of model electron acceptors was observed with POR P228L while activities of CYP3A4 were reduced by 25%, and activities of CYP3A5, and CYP2C9 were reduced by more than 40% compared to WT POR. The 17,20 lyase activity of CYP17A1 responsible for production of main androgen precursor dehydroepiandrosterone, was reduced to 27% of WT in presence of P228L variant of POR. Based on in silico and in vitro studies we predict that the change of proline to leucine may change the rigidity of the protein, causing conformational changes in POR, leading to altered electron transfer to redox partners. A single amino acid change can affect protein stability and cause a severe reduction in POR activity. Molecular characterization of individual POR mutations is crucial for a better understanding of the impact on different redox partners of POR.
Elucidating the unknown transcriptional responses and PHR1 mediated biotic and abiotic stress tolerance during phosphorus-limitation
Authors: Scheible Wolf-Rűdiger , Pandey-Pant Pooja , Pant Bikram D. , Krom Nick , Allen Randy D. , Mysore Kirankumar S.
Published: August 2022

Phosphorus (P) limitation in the majority of world soils is a major constraint for plant growth and crop productivity. RNA sequencing was used to discover novel P-responsive gene transcripts (PRGT) in leaves and roots of Arabidopsis. Hisat StringTie and Cufflinks TopHat transcript assembler were used to analyze reads and identify 1,074 PRGTs with a >5-fold altered abundance during P-limitation. Interestingly, 60% of these transcripts were not previously reported. Among the novel PRGT, 106 were from unannotated genes, and some were among the most P-responsive, includingAt2g36727which encodes a novel microRNA. Annotated novel PRGTs encode for transcription factors, microRNAs, small signaling peptides, long non-coding RNAs, defense-related proteins, and transporters, along with proteins involved in many biological processes. We identified several genes that undergo alternative splicing during P-limitation, including a novelmiR399resistant splice variant ofPHOSPHATE2(PHO2.2). Several novel P-responsive genes were regulated byPHOSPHATE STARVATION RESPONSE1(PHR1),PHR1-LIKE 1(PHL1) andPHO2. We discovered that P-limited plants show increased resistance to pathogens and drought stress mediated by PHR1-PHL1. Identification of novel P-responsive transcripts and the discovery of the influence of P-limitation on biotic and abiotic stress adds a significant component to our understanding of plant P-signaling.

Highlight

Phosphorus limitation elicits the expression of several novel genes including many previously unannotated genes, noncoding RNAs, small peptides and alternatively spliced RNAs, and leads to enhanced disease and drought tolerance.
Deep learning for satellite image forecasting of vegetation greenness
Authors: Kladny Klaus-Rudolf , Milanta Marco , Mraz Oto , Hufkens Koen , Stocker Benjamin D.
Published: August 2022

The advent of abundant Earth observation data enables the development of novel predictive methods for forecasting climate impacts on the state and health of terrestrial ecosystems. Here, we target the spatial and temporal variations of land surface reflectance and vegetation greenness, measuring the density of green vegetation and active foliage area, conditioned on current and past climate and the local topography. We train two alternative recurrent deep learning models that rely on convolutional layers for forecasting the spatially resolved deviation of surface reflectance across a heterogeneous landscape from a specified initial state (Baseline Framework). We demonstrate efficiency of the Baseline Framework with respect to training convergence speed. Using data from diverse ecosystems and land cover types across Europe and following a standardized model evaluation framework (EarthNet2021 Challenge), results indicate increased performance in predicting surface greenness during drought events of the models presented here, compared to currently published benchmarks. Our results demonstrate how deep learning methods enable early-warning of vegetation responses to the impacts of climatic extreme events, such as the drought-related loss of green foliage.
Non-invasive fecal DNA yields whole genome and metagenomic data for species conservation
Authors: de Flamingh A. , Ishida Y. , Pečnerová P. , Vilchis S. , Siegismund H.R. , van Aarde R.J. , Malhi R.S. , Roca A.L.
Published: August 2022

Non-invasive biological samples benefit studies that investigate rare, elusive, endangered, and/or dangerous species. Integrating genomic techniques that use non-invasive biological samples with advances in computational approaches can benefit and inform wildlife conservation and management. Here we present a molecular pipeline that uses non-invasive fecal DNA samples to generate low- to medium-coverage genomes (e.g., >90% of the complete nuclear genome at 6X coverage) and metagenomic sequences, combining in a novel fashion widely available and accessible DNA collection cards with commonly used DNA extraction and library building approaches. DNA preservation cards are easy to transport and can be stored non-refrigerated, avoiding cumbersome and/or costly sample methods. The genomic library construction and shotgun sequencing approach did not require enrichment or targeted DNA amplification. The utility and potential of the data generated by this pipeline was demonstrated by the application of genome-scale analysis and metagenomics to zoo and free-ranging African savanna elephants (Loxodonta africana). Fecal samples collected from free-ranging individuals contained an average of 12.41% (5.54-21.65%) endogenous elephant DNA. Clustering of these elephants with others from the same geographic region was demonstrated by a principal component analysis of genetic variation using nuclear genome-wide SNPs. Metagenomic analyses generated compositional taxon classifications that included Loxodonta, green plants, fungi, arthropods, bacteria, viruses and archaea, showcasing the utility of our approach for addressing complementary questions based on host-associated DNA, e.g., pathogen and parasite identification. The molecular pipeline presented here extends applications beyond what has previously been shown for target-enriched datasets and contributes towards the expansion and application of genomic techniques to conservation science and practice.
The Hydroxyproline O-arabinosyltransferase FIN4 is required for tomato pollen intine development
Authors: Jaffri Syeda Roop Fatima , Scheer Holly , MacAlister Cora A.
Published: August 2022

The pollen grain cell wall is a highly specialized structure composed of distinct layers formed through complex developmental pathways. The production of the innermost intine layer, composed of cellulose, pectin and other polymers, is particularly poorly understood. Here we demonstrate an important and specific role for the hydroxyproline O-arabinosyltransferase (HPAT) FIN4 in tomato intine development. HPATs are plant-specific enzymes which initiate glycosylation of certain cell wall structural proteins and signaling peptides. FIN4 was expressed throughout pollen development in both the developing pollen and surrounding tapetal cells. A fin4 mutant with a partial deletion of the catalytic domain displayed significantly reduced male fertility in vivo and compromised pollen hydration and germination in vitro. However, fin4 pollen that successfully germinated formed morphologically normal pollen tubes with the same growth rate as the wild-type pollen. When we examined mature fin4 pollen, we found they were cytologically normal, and formed morphologically normal exine, but produced significantly thinner intine. During intine deposition at the late stages of pollen development we found fin4 pollen had altered polymer deposition, including reduced cellulose and increased detection of pectin, specifically homogalacturonan with both low and high degrees of methylesterification. Therefore, FIN4 plays an important role in intine formation and, in turn pollen hydration and germination and the process of intine formation involves dynamic changes in the developing pollen cell wall.
High-dimensional profiling of pediatric immune responses to solid organ transplantation
Authors: Rao Mahil , Amouzgar Meelad , Harden James T. , Lapasaran M. Gay , Trickey Amber , Armstrong Brian , Odim Jonah , Debnam Tracia , Esquivel Carlos O. , Bendall Sean C. , Martinez Olivia M. , Krams Sheri M.
Published: August 2022

Solid organ transplant remains a life-saving therapy for children with end-stage heart, lung, liver, or kidney disease; however, ∼25% of allograft recipients experience acute rejection within the first 12 months after transplant. Our ability to detect rejection early and to develop less toxic immunosuppressive agents is hampered by an incomplete understanding of the immune changes associated with rejection, particularly in the pediatric population. Here we used high-dimensional single-cell proteomic technologies (CyTOF) to generate the first detailed, multi-lineage analysis of the peripheral blood immune composition of pediatric solid organ transplant recipients. We report that the organ transplanted impacts the immune composition post-transplant. When taking these allograft-specific differences into account, we further observed that differences in the proportion of subsets of CD8 and CD4 T cells were significantly associated with allograft health. Together, these data form the basis for mechanistic studies into the pathobiology of rejection to develop less invasive tools to identify early rejection and new immunosuppressive agents with greater specificity and less toxicity.
Epigenetic-focused CRISPR/Cas9 screen identifies ASH2L as a regulator of glioblastoma cell survival
Authors: Ozyerli-Goknar Ezgi , Kala Ezgi Yagmur , Aksu Ali Cenk , Bulut Ipek , Cingöz Ahmet , Nizamuddin Sheikh , Biniossek Martin , Seker-Polat Fidan , Morova Tunc , Aztekin Can , Kung Sonia H.A. , Syed Hamzah , Tuncbag Nurcan , Gonen Mehmet , Philpott Martin , Cribbs Adam P. , Acilan Ceyda , Lack Nathan A. , Onder Tamer T. , Timmers H.T. Marc , Bagci-Onder Tugba
Published: August 2022

Glioblastoma is the most common and aggressive primary brain tumor with poor prognosis, highlighting an urgent need for novel treatment strategies. In this study, we investigated epigenetic regulators of glioblastoma cell survival through CRISPR/Cas9 based genetic ablation screens using a customized sgRNA library EpiDoKOL, which targets critical functional domains of chromatin modifiers. Screens conducted in multiple cell lines revealed ASH2L, a histone lysine methyltransferase complex subunit, as a major regulator of glioblastoma cell viability. ASH2L depletion led to cell cycle arrest and apoptosis. RNA sequencing and greenCUT&RUN together identified a set of cell cycle regulatory genes, such as TRA2B, BARD1, KIF20B, ARID4A and SMARCC1 that were downregulated upon ASH2L depletion. Mass spectrometry analysis revealed the interaction partners of ASH2L in glioblastoma cell lines as SET1/MLL family members including SETD1A, SETD1B, MLL1 and MLL2. We further showed that glioblastoma cells had a differential dependency on expression of SET1/MLL family members for survival. The growth of ASH2L-depleted glioblastoma cells was markedly slower than controls in orthotopic in vivo models. TCGA analysis showed high ASH2L expression in glioblastoma compared to low grade gliomas and immunohistochemical analysis revealed significant ASH2L expression in glioblastoma tissues, attesting to its clinical relevance. Therefore, high throughput, robust and affordable screens with focused libraries, such as EpiDoKOL, holds great promise to enable rapid discovery of novel epigenetic regulators of cancer cell survival, such as ASH2L. Together, we suggest that targeting ASH2L could serve as a new therapeutic opportunity for glioblastoma.
Oxygen kinetics during CXL using symmetrically and asymmetrically pulsed UV-irradiation
Authors: Komninou Maria A. , Nambiar Malavika H. , Frueh Beatrice E. , Enzmann Volker , Büchler Philippe , Seiler Theo G.
Published: August 2022

Purpose

To investigate oxygen kinetics during symmetrically pulsed and asymmetrically pulsed crosslinking (p-CXL) with and without supplementary oxygen at different irradiances and corneal depths.

Design

Experimental, laboratory study

Methods

In de-epithelialized porcine eyes, a femtosecond-laser generated tunnel was used to place a fibre-probe in corneal depths of 200 and 300 µm to measure the local oxygen concentration. After riboflavin imbibition, the corneas were irradiated at 9, 18 and 30 mW/cm2 for 10 seconds On and 10 seconds Off; while the oxygen concentration was continuously measured until oxygen levels depleted below the oxygen sensor’s threshold (1%) or until stabilized. All experiments were performed under normoxic (21%) and hyperoxic (>95%) conditions and the obtained data were used to identify parameters of a numerical algorithm for oxygen consumption and diffusion. Following the algorithm’s development, the suggested asymmetrical pulsing values were experimentally tested. For 9, 18 and 30 mW/cm2 the suggested tested pulsing schemes were 3 seconds On : 9 seconds Off, 2 seconds On : 9 seconds Off and 1 second On : 9 seconds Off respectively.

Results

The minimum, available stromal oxygen for p-CXL in normoxic environment was decreasing <1% for 9, 18 and 30 mW/cm2 in 200 and 300 μm. Using optimized p-CXL, the minimum available oxygen increased to 3.8, 1.8 and 2.8 % at 200 μm, for irradiances of 9, 18 and 30 mW/cm2, respectively, where the periods exhibited an equilibrium state. At 300 μm, 1.1 % of oxygen was available for 30 mW/cm2. Using a hyperoxic environment, the oxygen concentration was 19.2% using 9 mW/cm2 in 200 μm, dropping to 17.0% in 300 μm. At 18 mW/cm2, the concentrations were 3.9% and 1% in 200 and 300 μm, respectively. Using 30 mW/cm2, all oxygen was depleted below the threshold limit (1% O2) for both depths. Using optimized pulsing in combination with hyperoxic environment, the oxygen concentration was 42.0% using 9 mW/cm2 in 200 μm and 43.3% in 300 μm. At 18 mW/cm2, the concentrations were 24.7% and 16.1% in 200 and 300 μm, respectively. Using 30 mW/cm2, the minimum oxygen availability was 25.7% and 13.7% in 200 and 300 μm, respectively.

Conclusion

Supplementary oxygen during symmetrical and asymmetrical p-CXL increased the oxygen availability during corneal cross-linking. The pulsed irradiance and the hyperoxic environment potentially increased the efficacy of corneal cross-linking in deeper corneal layers and higher irradiances. The numerical algorithm for asymmetrical pulsing led to the quantification of “On” and “Off” times related to different scenarios such as irradiances.
The nanomechanical fingerprint of colorectal cancer -derived peritoneal metastasis
Authors: Lorenc Ewelina , Varinelli Luca , Chighizola Matteo , Brich Silvia , Pisati Federica , Guaglio Marcello , Baratti Dario , Deraco Marcello , Gariboldi Manuela , Podesta Alessandro
Published: August 2022

Peritoneal metastases (PM) are one of the most common routes of dissemination for colorectal cancer (CRC) and remain a lethal disease with a poor prognosis. The compositional, mechanical and structural properties of the extracellular matrix (ECM) play an important role in cancer development; studying how these properties change during the progression of the disease is crucial to understand CRC-PM development.

The elastic properties of ECMs derived from human samples of normal and neoplastic PM in different pathological conditions were studied by atomic force microscopy (AFM); results were correlated to patients’ clinical data and to the expression of ECM components related to metastatic spread.

Our results show that PM progression is accompanied by stiffening of ECM as a common feature; spatially resolved mechanical analysis highlighted significant spatial heterogeneity of the elastic properties of both normal and neoplastic ECMs, which show significant overlap in the two conditions. On the micrometre scale, ECMs that are considered normal according to the pathological classification possess stiffer spatial domains, which are typically associated with cancer associated fibroblasts (CAF) activity and tumour development in neoplastic matrices; on the other hand, softer regions are found in neoplastic ECMs on the same scales. Our results support the hypothesis that local changes (stiffening) in the normal ECM can create the ground for growth and spread from the tumour of invading metastatic cells.

Mechanical changes correlate well with the presence of CAF and an increase in collagen deposition, which are well known markers of cancer progression. Furthermore, we have found correlations between the mechanical properties of the ECM and patients’ clinical data like age, sex, presence of mutations inBRAFandKRASgenes and tumour grade.

Overall, our findings suggest that the mechanical phenotyping of the PM-ECM has the potential for predicting tumour development.