bluuebunny/crossref_metadata_2025 huggingface dataset:
SPOTTED-LEAF7 targets the gene encoding β-galactosidase9, which functions in rice growth and stress responses
Authors: Hoang Trung Viet , Vo Kieu Thi Xuan , Rahman Md Mizanor , Zhong Ruiqin , Lee Chanhui , Ketudat Cairns James R , Ye Zheng-Hua , Jeon Jong-Seong
Published: June 2023

β-Galactosidases (Bgals) remove terminal β-D-galactosyl residues from the nonreducing ends of β-D-galactosidases and oligosaccharides. Bgals are present in bacteria, fungi, animals, and plants and have various functions. Despite the many studies on the evolution of BGALs in plants, their functions remain obscure. Here, we identified rice (Oryza sativa) β-galactosidase9 (OsBGAL9) as a direct target of the heat stress-induced transcription factor SPOTTED-LEAF7 (OsSPL7), as demonstrated by protoplast transactivation analysis and yeast 1-hybrid and electrophoretic mobility shift assays. Knockout plants for OsBGAL9 (Osbgal9) showed short stature and growth retardation. Histochemical β-glucuronidase (GUS) analysis of transgenic lines harboring an OsBGAL9pro:GUS reporter construct revealed that OsBGAL9 is mainly expressed in internodes at the mature stage. OsBGAL9 expression was barely detectable in seedlings under normal conditions but increased in response to biotic and abiotic stresses. Ectopic expression of OsBGAL9 enhanced resistance to the rice pathogens Magnaporthe oryzae and Xanthomonas oryzae pv. oryzae, as well as tolerance to cold and heat stress, while Osbgal9 mutant plants showed the opposite phenotypes. OsBGAL9 localized to the cell wall, suggesting that OsBGAL9 and its plant putative orthologs likely evolved functions distinct from those of its closely related animal enzymes. Enzyme activity assays and analysis of the cell wall composition of OsBGAL9 overexpression and mutant plants indicated that OsBGAL9 has activity toward galactose residues of arabinogalactan proteins (AGPs). Our study clearly demonstrates a role for a member of the BGAL family in AGP processing during plant development and stress responses.
A multisociety Delphi consensus statement on new fatty liver disease nomenclature
Authors: Rinella Mary E. , Lazarus Jeffrey V. , Ratziu Vlad , Francque Sven M. , Sanyal Arun J. , Kanwal Fasiha , Romero Diana , Abdelmalek Manal F. , Anstee Quentin M. , Arab Juan Pablo , Arrese Marco , Bataller Ramon , Beuers Ulrich , Boursier Jerome , Bugianesi Elisabetta , Byrne Christopher D. , Castro Narro Graciela E. , Chowdhury Abhijit , Cortez-Pinto Helena , Cryer Donna R. , Cusi Kenneth , El-Kassas Mohamed , Klein Samuel , Eskridge Wayne , Fan Jiangao , Gawrieh Samer , Guy Cynthia D. , Harrison Stephen A. , Kim Seung Up , Koot Bart G. , Korenjak Marko , Kowdley Kris V. , Lacaille Florence , Loomba Rohit , Mitchell-Thain Robert , Morgan Timothy R. , Powell Elisabeth E. , Roden Michael , Romero-Gómez Manuel , Silva Marcelo , Singh Shivaram Prasad , Sookoian Silvia C. , Spearman C. Wendy , Tiniakos Dina , Valenti Luca , Vos Miriam B. , Wong Vincent Wai-Sun , Xanthakos Stavra , Yilmaz Yusuf , Younossi Zobair , Hobbs Ansley , Villota-Rivas Marcela , Newsome Philip N. ,   on behalf of the NAFLD Nomenclature consensus group
Published: June 2023

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defineda priorias a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms “nonalcoholic” and “fatty” were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction–associated steatotic liver disease. There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction–associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction–associated steatotic liver disease, who consume greater amounts of alcohol per week (140–350 g/wk and 210–420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and can improve awareness and patient identification.
Post-COVID-19 cavitary lung lesion due to Aspergillus flavus and Enterobacter cloacae in a patient suffering from COVID-19 pneumonia – a case report
Authors: Rajpal Kamlesh , Kumar Shailesh , Saurabh Kumar , Kumari Namrata , Kumar Rakesh , Kumar Randhir , Muni Sweta
Published: June 2023

The coronavirus disease 2019 (COVID-19) pandemic has manifested as a multifaceted paradigm but has primarily affected the respiratory system. Though a rare sequela after-COVID-19, we present a case of cavitary lung lesion in an adult patient, which manifested with common symptoms such as fever, cough and dyspnoea during the post-COVID-19 recovery period. Aspergillus flavus and

Enterobacter cloacae

were found to be the main causative organisms. Fungal and bacterial coinfection may be thought of in similar situations and appropriate treatment may be given to prevent further morbidity and mortality.
First report of a carbapenemase OXA-48-producing Hafnia alvei clinical isolate
Authors: Sevillano Laura , Herrera Cristhian , Valdes Álvaro , de la Hoz Ángela , Cardeñoso Laura , Domingo Diego , Semiglia Maria Auxiliadora
Published: June 2023

Introduction. Carbapenems are usually used in the treatment of infections caused by cephalosporin-resistant

Enterobacterales

; however, the increase in carbapenem-resistant

Enterobacterales

(CRE) has become one of the most important problems in public health.

Hafnia alvei

is associated with intestinal and extraintestinal infections, especially in patients with any chronic disease or some type of immunosupression.

H. alvei

is resistant to first-generation aminopenicillins and cephalosporins owing to the β-lactamase (Amp C) in their chromosome; the only carbapenem-resistant

Hafnia

strain described until now was due to a lack of the OmpK36 protein that plays an important role in permeability to carbapenems.

Case presentation. We present the case of a 65-year-old male diagnosed with acute lithiasic cholecystitis. Culture of the biliary prosthesis yielded a OXA-48-producing

H. alvei

that was identified by MALDI-TOF (matrix-assisted laser desorption/ionization-time of flight) MS. Carbapenemase production was detected by immunochromatography and confirmed by sequencing.

Conclusion. To our knowledge, this is the first report of OXA-48-producing

H. alvei

probably obtained by horizontal transfer from

Enterobacter cloacae

OXA-48 isolated in previous samples.
Respiratory bacterial co-infections and their antibiotic resistance pattern in COVID-19 patients at a tertiary care centre in India
Authors: Kar Mitra , Siddiqui Tasneem , Dubey Akanksha , Hashim Zia , Sahu Chinmoy , Ghoshal Ujjala
Published: June 2023

Introduction. Patients with coronavirus disease-2019 (COVID-19) are prone to develop respiratory bacterial infections irrespective of their need for mechanical ventilatory support.

Hypothesis/Gap Statement. Information about the incidence of concomitant respiratory bacterial infections in COVID- 19 patients from India is limited.

Aim. This study aimed to determine the incidence of concomitant respiratory bacterial pathogens and their drug resistance in these patients.

Methodology. A prospective study was performed by including patients who were admitted to our tertiary care centre from March 2021 to May 2021 to evaluate secondary bacterial respiratory co-infections in patients via real-time PCR (RT-PCR)-confirmed cases of COVID-19 disease caused by SARS CoV-2.

Results. Sixty-nine culture-positive respiratory samples from patients with COVID-19 were incorporated into this study. The most commonly isolated bacterial microorganisms were

Klebsiella pneumoniae

(23 samples, 33.33 %) and

Acinetobacter baumannii

(15, 21.73 %), followed by

Pseudomonas aeruginosa

(13, 18.84 %). Among the microorganisms isolated, 41 (59.4 %) were multidrug-resistant (MDR) and nine (13 %) were extensively drug-resistant (XDR). Among the Gram-negative bacteria isolated,

K. pneumoniae

showed high drug resistance. Fifty carbapenem-resistant microorganisms were isolated from the patients included in our study. Concerning the hospital stay of the patients enrolled, there was an increased length of intensive care unit stay, which was 22.25±15.42 days among patients needing mechanical ventilation in comparison to 5.39±9.57 days in patients on ambient air or low/high-flow oxygen.

Conclusion. COVID-19 patients need increased length of hospitalization and have a high incidence of secondary respiratory bacterial infections and high antimicrobial drug resistance.
Igniting children’s enthusiasm for microbes with an origami paper microscope
Authors: Gardner Joshua , Perry Cynthia , Cervantes Jorge
Published: June 2023

The COVID-19 pandemic has highlighted the urgent need for microbiology literacy in society. Microbiology knowledge, and its dissemination, can help inform and increase the objectivity of important decisions, such as treatment or vaccination.
A microbiology learning experience, titled “What you can’t see can hurt you” was delivered as part of a larger outreach event (Medventure) where children were exposed to various aspects of medicine and health care fields. The activity involved an introduction to and a discussion of bacteria of clinical importance, and the use of a smartphone-attachable paper-based foldable microscope.
To explore the impact of this activity on participants’ interest in science and microbiology, a pre- and post-activity survey of 5 questions in an emoji-based Likert scale was completed by the participants.
A statistically significant increase in their interest in microbes and where to find them, as well as in microscopy, was observed after the event.
Making microbes visible to children and allowing them to capture images of microbes exposes them directly and personally to microscopy and microbiology. An affordable low-cost paper-based microscope can become an alternative approach to teaching and learning to deliver clinical microbiology information to a wide audience range.
Acquiring Bifidobacteria species from formula-fed and breast-fed newborns, identifying, quantifying, and creating an antibiogram.
Authors: kammara Rajagopal , Nellikka Anagha
Published: June 2023

After examining the Bifidobacterium spp. population in faeces samples from breastfed and formula-fed infants, an antibiogram was created. The prevalence of Bifidobacterium spp. in faeces was determined using common bacterial growth media, including Man Rogos Sharpe (MRS), Brain Heart Infusion (BHI), Luria Bertani (LB) broth, and Bifidobacteria agar. According to the findings, infants who are breastfed have a high population of Bifidobacterium spp. in their faeces, whereas newborns who are fed formula have a low population. Through using phylogenetic analysis of the 16S rRNA, (Xylose/Fructose-6-phosphate phosphoketolase) xfp, and RFLP mapping of Bifidobacterium isolates, it was possible to identify new and unique Bifidobacterium species. The intensity of the reddish brown colour produced during the F6PPK (Fructose-6-phosphate phosphoketolase) assay is an accurate indicator of the proportion of various Bifidobacteria present. Bifidobacteria agar media produced the greatest amounts of Bifidobacteria diversity and recovery. Small (SCV) and large colony variations (BCV) were formed during growth on different mediums. We are aware that the varied antibiotic minimum inhibitory concentration (MIC) values can change depending on the use of different media, growth circumstances, bile salt treatment, and low pH. The findings of this study demonstrate that test conditions also impact the diversity of microbiological conditions that distinguish between resistant and susceptible bacteria.
Multiple interspecies recombination events documented by whole genome sequencing in multidrug resistant Haemophilus influenzae clinical isolates.
Authors: Michel Charlotte , Argudín Maria A. , Wautier Magali , Echahidi F. , Prevost Benoit , Vandenberg Olivier , Martiny Delphine , Hallin Marie
Published: June 2023

Introduction:  Haemophilus influenzae (Hi) was long known as an easy-to-treat bacterium but the rise of resistance against beta-lactams and other critically important antibiotics is now an increasing concern. We describe here the whole genome sequencing (WGS) analysis of three non-typeable Hi isolates received in 2018 – 2019 by the Belgian National Reference Centre (NRC) for Hi as they presented an unusual multi-resistant profile.
The three isolates were resistant to ampicillin, cefuroxime, cefotaxime, ceftriaxone, ciprofloxacin, macrolides and trimethoprim-sulfamethoxazole. Two of them were also resistant to amoxicilline-clavulanic acid and showed a reduced susceptibility to meropenem. All three isolates belonged to the MLST Clonal Complex (CC) 422, and WGS revealed that the three were very similar. Their Antimicrobial Resistance (AMR) genotype was studied. They harbored mobile genetic elements (plasmids and transposons carrying blaTEM-1B, mefA and msrD genes associated with resistance), mutations in gyrA and parC linked to fluoroquinolone resistance as well as remodeling events in ompP2 that might be related to lower penems susceptibility or heteroresistance profile. The isolates also harbored interspecies recombination patterns in the murF-murE-ftsI region involved in cell wall synthesis. 
Conclusion: The Hi evolution towards AMR is a complex and poorly understood phenomenon. To better understand the respective roles of clonal expansion, horizontal gene transfers, spontaneous mutations and interspecies genetic rearrangements in shaping AMR in Hi, both analysis of Hi communities over time within individuals and worldwide monitoring of non-typeable Hi causing infections should be conducted.
Nocardiopsis suaedae sp. nov. and Nocardiopsis endophytica sp. nov., two novel halophilic actinobacteria isolated from halophytes
Authors: Chantavorakit Tanatorn , Suriyachadkun Chanwit , Hong Kui , Duangmal Kannika
Published: June 2023

A polyphasic approach was used to describe two halophilic actinobacterial strains, designated LSu2-4T and RSe5-2T, which were isolated from halophytes [Suaeda maritima (L.) Dum. and Sesuvium portulacastrum (L.) L.] collected from Prachuap Khiri Khan province, Thailand. Comparative analysis of 16S rRNA gene sequences showed that strains LSu2-4T and RSe5-2T were assigned to the genus

Nocardiopsis

, with

Nocardiopsis chromatogenes

YIM 90109T(99.2 and 99.2 % similarities, respectively) and

Nocardiopsis halophila

DSM 44494T(99.0 and 98.8 % similarities, respectively) being their closely related strains. Whereas the 16S rRNA gene sequence similarity between LSu2-4T and RSe5-2T was 99.4 %. Phylogenetic and phylogenomic analyses based on 16S rRNA gene and whole-genome sequences revealed that both strains clustered with

N. chromatogenes

YIM 90109T and

N. halophila

DSM 44494T. The average nucleotide identity (ANI) based on blast, ANI based on MUMmer and digital DNA–DNA hybridization (dDDH) relatedness values between the two strains and their closest type strains were below the threshold values for identifying a novel species. Morphological characteristics and chemotaxonomic features of both strains were typical for the genus

Nocardiopsis

by formed well-developed substrate mycelia and aerial mycelia which fragmented into rod-shaped spores. Whole-cell hydrolysates contained meso-diaminopimelic acid as the diagnostic diamino acid. The predominant menaquinones were variously hydrogenated with 10 isoprene units and contained phosphatidylcholine in their polar lipid profiles. Major fatty acids were iso-C16:0 and 10-methyl C18:0. In silico analysis predicted that the genomes of LSu2-4T and RSe5-2T contained genes associated with stress responses and biosynthetic gene clusters encoding diverse bioactive metabolites. Characterization based on chemotaxonomic, phenotypic, genotypic and phylogenetic evidence demonstrated that strains LSu2-4T and RSe5-2T represents two novel species of the genus

Nocardiopsis

, for which the names Nocardiopsis suaedae sp. nov. (type strain LSu2-4T=TBRC 16415T=NBRC 115855T) and Nocardiopsis endophytica sp. nov. (type strain RSe5-2T=TBRC 16416T=NBRC 115856T) are proposed.
Development and evaluation of Microbe Finder (MiFi)®: a novel in silico diagnostic platform for pathogen detection from metagenomic data
Authors: Narayanan Sai , Espindola Andres S. , Malayer Jerry , Cardwell Kitty , Ramachandran Akhilesh
Published: June 2023

Introduction. With expanding demand for diagnostics, newer methodologies are needed for faster, user-friendly and multiplexed pathogen detection. Metagenome-based diagnostics offer potential solutions to address these needs as sequencing technologies have become affordable. However, the diagnostic utility of sequencing technologies is currently limited since analysis of the large amounts of data generated, are either computationally expensive or carry lower sensitivity and specificity for pathogen detection.

Hypothesis/Gap Statement. There is a need for novel, user friendly, and computationally inexpensive platforms for metagenome sequence analysis for diagnostic applications.

Methods. In this study, we report the use of MiFi® (Microbe Finder), a computationally inexpensive algorithm with a user-friendly online interface, for accurate, rapid and multiplexed pathogen detection from metagenome sequence data. Detection is accomplished based on identification of signature genomic sequence segments of the target pathogen in metagenome sequence data. In this study we used bovine respiratory disease (BRD) complex as a model.

Results and Conclusions. Using MiFi®, multiple target bacteria and a DNA virus were successfully detected in a multiplex format from metagenome sequences acquired from bovine lung tissue. Overall, 51 clinical samples were assessed and MiFi® showed 100 % analytical specificity and varying levels of analytical sensitivity (62.5 %–100 %) when compared with other traditional pathogen detection techniques, such as PCR. Consistent detection of bacteria was possible from lung samples artificially spiked with 109–104 c.f.u. of

Mannheimia haemolytica

.
Distinguished biological adaptation architecture aggravated population differentiation of Tibeto-Burman-speaking people inferred from 500 whole-genome data from 39 populations
Authors: Sun Yuntao , Wang Mengge , Sun Qiuxia , Liu Yan , Duan Shuhan , Wang Zhiyong , Zhou Yunyu , Zhong Jun , Huang Yuguo , Huang Xinyu , Li Xiangping , Su Haoran , Cai Yan , Jiang Xiucheng , Chen Jing , Yan Jiangwei , Nie Shengjie , Hu Liping , Yang Junbao , Tang Renkuan , Wang Chuan-Chao , Liu Chao , Deng Xiaohui , He Guanglin , Yun Libing
Published: June 2023

Tibeto-Burman (TB) people have tried to adapt to the hypoxic, cold and high-UV high-altitude Tibetan Plateau and complex disease exposure in the lowland wet and hot rainforest since the late Paleolithic period. However, the full landscape of genetic history and biological adaptation of geographically diverse TB people and their interaction mechanism remained unknown. We generated a whole-genome-based meta-database of 500 individuals from 39 TB populations from East Asia and Southeast Asia and presented a comprehensive landscape of genetic diversity, admixture history and differentiated adaptative features of geographically different TB people. We identified geography/language-related genetic differentiation among Tibetan Plateau, Tibetan-Yi-Corridor (TYC) and Southeast Asian TB people, consistent with their differentiated admixture process with incoming or indigenous ancestral source populations. A robust genetic connection between TYC people and ancient YR people supported the Northern origin hypothesis of TB people. We reported population substructure-related differentiated biological adaptative signatures between highland Tibetans and lowland TB people and between geographically different Lolo speakers. Highland adaptativeEPAS1andEGLNvariants riched in Tibetans but lacked in TYC people whose adaptation is associated with the physical features and skin pigmentation (EDARandSLC24A5), hepatic alcohol metabolism (ALDH9A1), regulation of cell-cell adhesion of muscle cells (CTNNA3)and immune/fat metabolism-related adaptative signature. TB-related genomic resources provided new insights into the genetic basis of phenotype differences and better reference for the anthropologically-informed sampling design in biomedical and genomic cohort research.
(Micro)saccade-related potentials during face recognition: A study combining EEG, eye-tracking, and deconvolution modeling
Authors: Spiering Lisa , Dimigen Olaf
Published: June 2023

Under natural viewing conditions, complex stimuli such as human faces are typically looked at several times in succession, implying that their recognition may unfold across multiple eye fixations. Although electrophysiological (EEG) experiments on face recognition typically prohibit eye movements, participants still execute frequent (micro)saccades on the face, each of which generates its own visuocortical response. This finding raises the question of whether the fixation-related potentials (FRPs) evoked by these tiny gaze shifts also contain psychologically valuable information about face processing. Here we investigated this question by co-recording EEG and eye movements in an experiment with emotional faces (happy, angry, neutral). Deconvolution modeling was used to separate the stimulus-ERPs to face onset from the FRPs generated by subsequent microsaccades-induced refixations on the face. As expected, stimulus-ERPs exhibited typical emotion effects, with a larger early posterior negativity (EPN) for happy/angry compared to neutral faces. Eye-tracking confirmed that participants made small saccades within the face in 98% of the trials. However, while each saccade produced a strong response over visual areas, this response was unaffected by the face’s emotional expression, both for the first and for subsequent (micro)saccades. This finding suggests that the face’s affective content is rapidly evaluated after stimulus onset, leading to only a short-lived sensory enhancement by arousing stimuli that does not repeat itself during immediate refixations. Methodologically, our work demonstrates how eye-tracking and deconvolution modeling can be used to extract several brain responses from each EEG trial, providing insights into neural processing at different latencies after stimulus onset.
Task-evoked pulse wave amplitude tracks cognitive load
Authors: Pavlov Yuri G. , Gashkova Anastasia S. , Kasanov Dauren , Kosachenko Alexandra I. , Kotyusov Alexander I. , Kotchoubey Boris
Published: June 2023

Cognitive load is a crucial factor in mentally demanding activities and holds significance across various research fields. This study aimed to investigate the effectiveness of pulse wave amplitude (PWA) as a measure for tracking cognitive load and associated mental effort in comparison to heart rate (HR) during a digit span task. The data from 78 participants were included in the analyses. Participants performed a memory task in which they were asked to memorize sequences of 5, 9, or 13 digits, and a control task where they passively listened to the sequences. PWA and HR were quantified from photoplethysmography (PPG) and electrocardiography (ECG), respectively. Pupil dilation was also assessed as a measure of cognitive load. We found that PWA showed a strong suppression with increasing memory load, indicating sensitivity to cognitive load. In contrast, HR did not show significant changes with task difficulty. Moreover, when memory load exceeded the capacity of working memory, a reversal of the PWA pattern was observed, indicating cognitive overload. In this respect, changes in PWA in response to cognitive load correlated with the dynamics of pupil dilation, suggesting a potential shared underlying mechanism. Additionally, both HR and PWA demonstrated a relationship with behavioral performance, with higher task-evoked HR and lower PWA associated with better memory performance. Our findings suggest that PWA is a more sensitive measure than HR for tracking cognitive load and overload. PWA, measured through PPG, holds significant potential for practical applications in assessing cognitive load due to its ease of use and sensitivity to cognitive overload. The findings contribute to the understanding of psychophysiological indicators of cognitive load and offer insights into the use of PWA as a non-invasive measure in various contexts.
Unexpectedly high coral heat tolerance at thermal refugia
Authors: Lachs Liam , Humanes Adriana , Mumby Peter J , Donner Simon D. , Bythell John , Beauchamp Elizabeth , Bukurou Leah , Buzzoni Daisy , de la Torre Cerro Ruben , East Holly K. , Edwards Alasdair J. , Golbuu Yimnang , Martinez Helios M. , van der Steeg Eveline , Ward Alex , Guest James R.
Published: June 2023

Marine heatwaves and mass bleaching have led to global declines in coral reefs. Corals can adapt, yet, to what extent local variations in thermal stress regimes influence heat tolerance and adaptive potential remains uncertain. Here we identify persistent local-scale thermal refugia and hotspots among the reefs of a remote Pacific archipelago, based on 36 years of satellite-sensed temperatures. Theory suggests that hotspots should promote coral heat tolerance through acclimatisation and directional selection. While historic patterns of mass bleaching and marine heatwaves align with this expectation, we find a contrasting pattern for a single species,Acropora digitifera, exposed to a marine heatwave experiment. Higher heat tolerance at thermal refugia (+0.7 °C-weeks) and correlations with other traits suggest that non-thermal selective pressures may also influence heat tolerance. We also uncover widespread heat tolerance variability, indicating climate adaptation potential. Compared to the least-tolerant 10% of theA. digitiferapopulation, the most-tolerant 10% could withstand an additional heat stress of 5.2 and 4.1 °C-weeks for thermal refugia and hotspots, respectively. Despite expectations, local-scale thermal refugia can harbour higher heat tolerance, and mass bleaching patterns do not necessarily predict species responses. This has important implications for designing climate-smart initiatives to tackle global-scale adaptive management problems.
New distance measure for comparing protein using cellular automata image
Authors: Souza Luryane F. , de B. Pereira Hernane B. , da Rocha Filho Tarcisio M. , Machado Bruna A. S. , Moret Marcelo A.
Published: June 2023

One of the first steps in protein sequence analysis is comparing sequences to look for similarities. We propose an information theoretical distance to compare cellular automata representing protein sequences, and determine similarities. Our approach relies in a stationary Hamming distance for the evolution of the automata according to a properly chosen rule, and to build a pairwise similarity matrix and determine common ancestors among different species in a simpler and less computationally demanding computer codes when compared to other methods.
Does the seed fall far from the tree? Weak fine-scale genetic structure in a continuous Scots pine population
Authors: Niskanen Alina K. , Kujala Sonja T. , Kärkkäinen Katri , Savolainen Outi , Pyhäjärvi Tanja
Published: June 2023

Knowledge of fine-scale spatial genetic structure,i.e., the distribution of genetic diversity at short distances, is important in evolutionary research and in practical applications such as conservation and breeding programs. In trees, related individuals often grow close to each other due to limited seed and/or pollen dispersal. The extent of seed dispersal also limits the speed at which a tree species can spread to new areas.

We studied the fine-scale spatial genetic structure of Scots pine (Pinus sylvestris) in two naturally regenerated sites located 20 km from each other in continuous south-eastern Finnish forest. We genotyped almost 500 adult trees for 150k SNPs using a custom made Affymetrix array. We detected some pairwise relatedness at short distances, but the average relatedness was low and decreased with increasing distance, as expected.

Despite the clustering of related individuals, the sampling sites were not differentiated (FST= 0.0005). According to our results, Scots pine has a large neighborhood size (Nb= 1680– 3210), but a relatively short gene dispersal distance (σg= 36.5–71.3 m). Knowledge of Scots pine fine-scale spatial genetic structure can be used to define suitable sampling distances for evolutionary studies and practical applications. Detailed empirical estimates of dispersal are necessary both in studying post-glacial recolonization and predicting the response of forest trees to climate change.
Scanning ultrasound-mediated memory and functional improvements do not require amyloid-β reduction
Authors: Leinenga Gerhard , To Xuan Vinh , Bodea Liviu-Gabriel , Yousef Jumana , Richter-Stretton Gina , Palliyaguru Tishila , Chicoteau Antony , Dagley Laura , Nasrallah Fatima , Götz Jürgen
Published: June 2023

A prevalent view in treating age-dependent disorders including Alzheimer’s disease (AD) is that the underlying amyloid plaque pathology must be targeted for cognitive improvements. In contrast, we report here that repeated scanning ultrasound (SUS) treatment at 1 MHz frequency can ameliorate memory deficits in the APP23 mouse model of AD without reducing amyloid-β (Aβ) burden. Different from previous studies that had shown Aβ clearance as a consequence of blood-brain barrier (BBB) opening, here, the BBB was not opened as no microbubbles were used. Quantitative proteomics and functional magnetic resonance imaging revealed that ultrasound induced long-lasting functional changes that correlate with the improvement in memory. Intriguingly, the treatment was more effective at a higher frequency (1MHz) than at a frequency within the range currently explored in clinical trials in AD patients (286 kHz). Together, our data suggest frequency-dependent bio-effects of ultrasound and a dissociation of cognitive improvement and Aβ clearance, with important implications for the design of trials for AD therapies.

The therapeutic effect of ultrasound on memory in AD mice leads to altered protein expression and improved functional connectivity in the absence of amyloid-β removal. Of two frequencies explored, the higher ultrasound frequency (1 MHz) is more effective.
Aryl hydrocarbon receptor (AHR) and IL-13 signaling crosstalk in human keratinocytes and atopic dermatitis
Authors: Proper Steven P. , Dwyer Alexander T. , Appiagyei Andrews , Felton Jennifer M. , Morgenstern Netali Ben-Baruch , Marlman Justin M. , Kotliar Michael , Barski Artem , Troutman Ty D. , Rothenberg Marc E. , Mersha Tesfaye B. , Azouz Nurit P.
Published: June 2023

Atopic dermatitis (AD) is an allergic skin disease mediated by skin barrier impairment and IL-13-driven immune response. Activation of the aryl hydrocarbon receptor (AHR) has shown promise in early clinical trials for AD, however, the mechanism by which AHR mediates this function is unknown. Herein, AHR signaling is shown to be dysregulated in AD patients using publicly available gene expression data from biopsies of patients with AD compared with controls. AHR target genes,CYP1A1,CYP1A2andNFE2L2were decreased in lesional skin compared with healthy control skin (p=0.001, p<1.0*10-10and p=6.1*10-6respectively). Single cell RNA sequencing studies demonstrated increased expression ofAHR(p<1.0*10-4and p=0.049) and decreased expression ofCYP1A1in lesional AD keratinocytes compared with healthy control keratinocytes (p=5.0*10-4and p=0.21). AHR activation reversed IL-13-dependent gene expression of several key genes in AD pathogenesis, most notably the eosinophil chemoattractant,CCL26(Eotaxin-3). There was substantial overlap between differentially expressed genes in keratinocytes of patients with atopic dermatitis and AHR-regulated genes. Mechanistically, there was evidence for direct transcriptional effects of AHR as its binding motifs were identified in the differentially expressed genes from lesional AD keratinocytes compared to control keratinocytes and AHR activation did not modify IL-13-dependent signal transducer and activator of transcription 6 (STAT6) translocation to the nucleus. Together these data imply that AHR modulates IL-13 downstream signaling in keratinocytes through genome-wide direct transcriptional regulatory effects.
Deep intravital brain tumor imaging enabled by tailored three-photon microscopy and analysis
Authors: Schubert Marc Cicero , Soyka Stella Judith , Tamimi Amr , Maus Emanuel , Denninger Robert , Wissmann Niklas , Reyhan Ekin , Tetzlaff Svenja Kristin , Beretta Carlo , Drumm Michael , Schroers Julian , Steffens Alicia , Walshon Jordain , McCortney Kathleen , Heiland Sabine , Golebiewska Anna , Kurz Felix Tobias , Wick Wolfgang , Winkler Frank , Kreshuk Anna , Kuner Thomas , Horbinski Craig , Prevedel Robert , Venkataramani Varun
Published: June 2023

Intravital two-photon microscopy has emerged as a powerful technology to study brain tumor biology and its temporal dynamics, including invasion, proliferation and therapeutic resistance in the superficial layers of the mouse cortex. However, intravital microscopy of deeper cortical layers and especially the subcortical white matter, an important route of glioblastoma invasion and recurrence, has not yet been feasible due to low signal-to-noise ratios, missing spatiotemporal resolution and the inability to delineate myelinated axonal tracts. Here, we present a tailored intravital microscopy and artificial intelligence-based analysis methodology and workflow that enables routine deep imaging of glioblastoma over extended time periods, named Deep3P. We show that three-photon microscopy, adaptive optics, as well as customized deep learning-based denoising and machine learning segmentation together allow for deep brain intravital investigation of tumor biology up to 1.2 mm depth. Leveraging this approach, we find that perivascular invasion is a preferred invasion route into the corpus callosum as compared to intracortical glioblastoma invasion and uncover two vascular mechanisms of glioblastoma migration in the white matter. Furthermore, we can define an imaging biomarker of white matter disruption during early glioblastoma colonization. Taken together, Deep3P allows for an efficient and non-invasive investigation of brain tumor biology and its tumor microenvironment in unprecedented deep white and gray matter of the living mouse, opening up novel opportunities for studying the neuroscience of brain tumors and other model systems.