bluuebunny/crossref_metadata_2025 huggingface dataset:
Infection of a Nylon Foil Orbital Implant Due to Fusarium brachygibbosum and Lomentospora prolificans After Intranasal Methamphetamine Use
Authors: Zhou Paul S. , Dermarkarian Christopher R. , Andrade Rosa M. , Tao Jeremiah P.
Published: October 2023

The authors describe a case of nylon foil implant infection caused by Fusarium brachygibbosum, and Lomentospora prolificans following medial orbital wall fracture repair in the setting of postoperative nasal methamphetamine use. A 61-year-old male presented with OS pain and swelling after a physical assault on his face. A CT of maxillofacial bones without contrast showed a moderately comminuted fracture of the medial wall of the left orbit with depression of fracture fragments into the left ethmoid air cells. Six days after repair of the medial wall fracture, the patient returned with a new onset headache, OS pain, and swelling to the left medial canthal area. He reported snorting methamphetamine approximately 48 hours before his current presentation. CT imaging showed fat stranding and soft tissue density in the extraconal space adjacent to the left medial rectus muscle and chronic fracture deformity of lamina papyracea with approximately 4 mm of medial displacement of the fracture fragments. The patient showed little clinical improvement after 48 hours of intravenous antibiotics, which led to the removal of the nylon foil implant by a left orbitotomy. Intraoperative tissue cultures grew coagulase-negative Staphylococcus, F. brachygibbosum, and Lomentospora (Scedosporium) prolificans. The patient was subsequently transitioned to oral clindamycin 600 mg three times daily and voriconazole 200 mg two times daily. To the authors’ knowledge, this is the first case report to document an association between snorted methamphetamine and a fungal infection of an orbital implant.
Tendon-Sparing Extraocular Muscle Enlargement Associated With Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Authors: Dimopoulos Antonios D. , Barmettler Anne
Published: October 2023

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an inflammatory, sensorimotor polyneuropathy. It has presented with a variety of orbital and neuro-ophthalmic manifestations, including cranial nerve hypertrophy and a single case of extraocular muscle enlargement. The authors present a second case of tendon-sparing, extraocular muscle enlargement, resulting in new-onset diplopia and strabismus in a teenager with CIDP. The workup ruled out alternative causes of extraocular muscle enlargement, such as hyperthyroidism, inflammation, or malignancy. As with other cases of CIDP, management involved a combination of immunoglobulin therapy and anti-inflammatory medications. The patient experienced resolution of his symptoms, and radiologic improvement was noted in the muscle enlargement. As many CIDP patients have a favorable treatment response and long-term prognosis, awareness of this rare disease with an early and accurate diagnosis is important.
Ischemia-reperfusion injury in human AC16 cardiomyocytes is modulated by AXIN1 depending on c-Myc regulation
Authors: Li Jun , Wang Hao , Chen Li , Zhong Jialin , Wang Junsheng , Xiao Jun
Published: October 2023

Objective:

A major consequence of acute myocardial infarction is myocardial ischemia-reperfusion (I/R) injury. Collecting proof demonstrates that AXIN1 assume a basic part in different disease; however, the role of AXIN1 in I/R injury remains to a great extent obscure.

Methods:

The I/R injury model on AC16 cells was constructed. siRNA transfection was used to knockdown AXIN1. The qRT-PCR assays and western blot assays were used to detect the expression level of AXIN1 and other key proteins. CCK-8 assays and cell apoptosis assays were used to detect cell proliferation and cell apoptosis.

Results:

AXIN1 was significantly overexpressed in an in vitro model of I/R injury. Knockdown of AXIN1 significantly restored the cell proliferation inhibition caused by IR injury, while inhibiting apoptosis and inflammation. Further mechanistic studies revealed that the transcription factor c-Myc could regulate the expression of AXIN1. The effects of I/R injury on AC16 cells after overexpression of c-Myc were reversed by knockdown of AXIN1. Meanwhile, AXIN1 could regulate the SIRT1/p53/Nrf 2 pathway.

Conclusion:

Our results show an important role for AXIN1 and provide new targets for avoiding and treating I/R injury.
Worm infestation as a cause of severe anemia in a frail older adult: a case report
Authors: Shah Suveksha S. , Shah Raju , Basnet Rohan , Patel Dhruvit , Bhattarai Urza , Shah Bhupendra , Sharma Sanjib K.
Published: October 2023

Introduction:

Worm infestations are a common occurrence in low-income countries. Anemia due to iron deficiency can be brought on by human intestinal worms. The authors report a case of an 86-year-old frail older adult with upper gastrointestinal (GI) bleeding caused by a worm infestation most likely to be hookworm.

Case presentation:

An 86-year-old male, presented to the Emergency Department with complaints of bilateral lower limb swelling and shortness of breath for 4 days associated with melena for 2 months. The authors made a provisional diagnosis of heart failure precipitated by anemia. Upper GI endoscopy revealed multiple whitish exudates, which are resistant to water jets. Multiple worms were noted in the second part of the duodenum. Based on clinical evaluation and endoscopy, the diagnosis of oesophagial candidiasis and iron deficiency anemia secondary to upper GI bleeding due to Hookworm infestation was made.

Clinical discussion:

In low-income countries, especially those involving the tropical area, worm infestation should be considered as an important cause of obscure acute GI bleeding and severe anemia. Usually, malignancy is suspected in an older adult with severe anemia but hookworm infestation is a treatable disease with a good prognosis and complete recovery. The most commonly used drugs for treatment are mebendazole and albendazole. In a low-income country with a high burden of worm infestations, empirical treatment of iron deficiency anemia with single dose albendazole has been recommended.

Conclusion:

Usually, severe anemia in an older adult is mostly attributed to an underlying malignancy. Our case serves as a good example of how a treatable condition can improve the quality of life in a frail older adult. Normally, there is a tendency to defer UGI endoscopy in frail elderly due to ageism. However, the diagnosis of a treatable cause of upper GI bleeding can be made by a simple upper GI endoscopy. Severe anemia due to hookworm infestation is treated effectively and quickly with albendazole and iron therapy.
Xiaoqinglong decoction suppresses childhood cough variant asthma and inhibited the body inflammatory response by regulating IL-6/STAT3 signalling pathway
Authors: Ren Yuzhe , Li Xing , Zhang Yuanjie , Yan Zilong
Published: October 2023

Xiaoqinglong decoction (XQLD) is widely used clinically in the treatment of childhood cough variant asthma (CVA). However, its potential mechanism is still unknown. In the present study, the authors investigate the biological network and signalling pathway of XQLD in treatment of childhood CVA using network pharmacology-based analysis and experimental validation. By using the Bioinformatics Analysis Tool Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) database, the authors confirmed the correlation between XQLD and asthma, and the authors screened 1338 potential target genes of Mahuang and Guizhi, the most active herbs in XQLD. By overlapping “Childhood asthma-related genes” of DisGeNET database, the authors identified 58 intersecting genes of Childhood asthma and 1338 target genes of Mahuang and Guizhi. The intersecting genes were used to construct the protein-to-protein interaction and performed Gene Ontology (GO) functional and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Gene Ontology enrichment analysis demonstrated 359 Biological Process terms, 16 Cellular Component terms, and 26 Molecular Function terms. Meantime, 75 terms of Kyoto Encyclopedia of Genes and Genomes signalling pathway were involved in enrichment analysis. These candidates showed a significant correlation with inflammatory response and positive regulation of tyrosine phosphorylation of STAT protein. In addition, XQLD treatment significantly upregulated serum interferon-γ expression, and downregulated serum interlukin-6 expression of CVA mice. XQLD treatment significantly inhibited phosphorylation of STAT3 in bronchial-lung tissues. Our data suggest that XQLD effectively alleviated bronchial-lung tissue damage in CVA mice and inhibited the body inflammatory response by regulating interlukin-6/STAT3 signalling pathway.
Antineutrophil cytoplasmic antibody-associated vasculitis with systemic sclerosis: a fatal case report
Authors: Khalayli Naram , Ibrahim Raghad , Ibrahim Rahaf , Kudsi Maysoun
Published: October 2023

Introduction and importance:

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a rare co-occurrence with systemic sclerosis, in around 2.5–9% of patients. The clinical manifestations and prognosis of vasculitis in systemic sclerosis depend on organ involvement. It presented with rapidly progressive acute renal failure without malignant hypertension, and with pitting hand and foot ulcers get along with purpuric vasculitis in some cases reports. Reports had found that survival in those with pulmonary-renal syndrome is poor. However, high-dose corticosteroids and cyclophosphamide increase the survival percent in those patients.

Case presentation:

An 81-year-old female was admitted for newly diagnosed acute renal failure and highly elevated C-reactive protein levels. She was diagnosed with systemic sclerosis 8 years previously, with a 3-year history of interstitial lung disease, and a 2-year history of pulmonary hypertension. Treatment included home oxygen on demand, prednisone 5 mg/day, and azathioprine 75 mg daily. On physical examination, she had sclerodactyly, both extremities ulcers, severe livedo reticularis, and hyperpigmented papules on her hand and feet. Laboratory findings included a markedly positive MPO (p-ANCA), and anti-Scl-70. She was treated with pulse methylprednisolone without any improvement. After a day, she developed anuria and became comatose. Then, she developed cardiac arrest, leading to death.

Clinical discussion:

The presence of ANCA in systemic sclerosis patients ranges from 2.5 to 9% of systemic sclerosis patients. It presented with rapidly progressive acute renal failure without malignant hypertension, and with pitting hand and foot ulcers. The treatment with high-dose corticosteroids and cyclophosphamide is benefit. Survival in those with pulmonary-renal syndrome is poor.

Conclusion:

The presence of ANCA-associated vasculitis is rarely reported with scleroderma. It occurs most commonly in women with limited or Calcinosis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia (CREST) variants of scleroderma, as well as those with overlap features. Severe manifestations including pulmonary-renal syndrome and death may occur.
Atypical presentation of hyperthyroidism complicated complete hydatidiform mole in a 24-year-old female: a case report
Authors: Mansour Marah , Almasri Rania , Amin Noura , Hamwi George , Attoum Rawdah , Kanbour Ilda Moafak , Jeniat Sara Mohammad Talal , AlKhrait Samar
Published: October 2023

Introduction and importance:

Molar pregnancy is the most common type of gestational trophoblastic disease. It manifests as vaginal bleeding, accompanied by high levels of β-human chorionic gonadotropin (β-HCG). This case aims to highlight the importance of considering gestational trophoblastic disease as a potential diagnosis and its serious complications.

Case presentation:

A 24-year-old female presented with vomiting, nausea, and no complaint of vaginal bleeding. Laboratory tests indicated hyperthyroidism as a complication requiring challenging preoperative prophylactic management. Initially, the patient underwent suction and curettage, but a total hysterectomy had to be performed later. The histological study concluded with the diagnosis of a complete hydatidiform mole. Post-surgery follow-up evaluations revealed high blood pressure values, and the patient was appointed for further cardiology assessment.

Discussion and conclusion:

Although uncommon, complications of a molar pregnancy include anaemia, severe cardiac distress, and hyperthyroidism. Trophoblastic Hyperthyroidism is a result of extremely high levels of β-HCG levels due to molecular cross-reactivity. History, clinical examination, and ultrasound, in addition to measuring β-HCG levels, could all help in diagnosing a molar pregnancy, but the definitive diagnosis is based on histopathology and a karyotype study. Management procedures include dilation, suction and curettage, and hysterectomy. The treatment depends on the patient’s age, desire for future pregnancies, and risk of developing gestational trophoblastic neoplasia. A follow-up with serial β-HCG measurement is recommended to monitor possible complications. Attaining and maintaining euthyroidism is a life-saving procedure before molar pregnancy surgery. Methimazole, Propranolol, Lugol’s iodine, and hydrocortisone can all be used in the prophylactic management of the thyroid storm.
Mechanical thrombectomy for AIS from large vessel occlusion – current trends and future perspectives
Authors: Parvathy Gauri , Dey Rohit C. , Kutikuppala Lakshmi Venkata Simhachalam , Maheshwari Aakansh R. , Josey Elwy , Chintala Jyothi S. , Abdullah Mohammed , Godugu Swathi
Published: October 2023

Stroke is found to be one of the global top causes of mortality and the major factor in years of life with a handicap (DALYs). Ischemic strokes contributed to nearly 70% of all strokes worldwide. For endovascular thrombectomy in acute ischemic stroke with large vessel obstruction (AIS-LVO), using stent retrievers and/or reperfusion catheters has become the gold standard of therapy. The methodology involved keyword-based search in databases like PubMed, Embase, and Google Scholar for recent publications on mechanical thrombectomy (MT), AIS, large vessel occlusion (Large Vessel Occlusion (LVO)), screening relevant articles, retrieving full texts, and synthesizing key findings on procedural advancements, patient selection, COVID-19 (coronavirus disease 2019) impact, delay effects, effectiveness, clinical outcomes, and future perspectives. Only people with substantial cerebral artery obstruction may do well from MT. This includes the distal carotid artery and the proximal middle cerebral artery (segment M1). The size of a blocked vessel and NIHSS (National Institute of Health Stroke Scale) score are directly connected. Both the 2018 and 2019 versions of the AHA/ASA (American Heart Association/American Stroke Association) Guidelines for the Early Management of Patients with Acute Ischemic Stroke contained the recommendations that cases with AIS-LVO get endovascular therapy when administered during the time frame of 0–6 h after onset (Grade IA evidence). It is questionable whether this group of patients can be managed without the need for intravenous tissue plasminogen activator at the onset. When functional independence [modified Rankin Scale (mRS) score 2] was present at long-term follow-up, the endovascular intervention was favored. Tenecteplase, which differs from alteplase in terms of genetic variation, has a greater half-life and a higher level of fibrin selectivity, enabling bolus infusion. Studies have also demonstrated its efficacy and safety, as well as its long-term cost-effectiveness.
Testicular Metastasis From Neuroendocrine Tumors
Authors: Parghane Rahul V. , Basu Sandip
Published: October 2023

Neuroendocrine tumors (NETs) are rare neoplasms arising from enterochromaffin cells, which are predominantly noted in the gastrointestinal tract and lung; metastases of NETs to the testes in NET are further uncommon. Testicular NET usually has no symptoms and/or presents with painless swelling of the scrotum. Detection of testicular lesion can be challenging and frequently missed on conventional radiological imaging. We present testicular NET missed on conventional radiological imaging, where 68Ga-DOTATATE PET/CT imaging detected the testicular lesion, and further evident on 177Lu-DOTATATE–based post–peptide receptor radionuclide therapy theranostic imaging.
A colonial-nesting seabird shows limited heart rate responses to natural variation in threats of polar bears
Authors: Geldart Erica A. , Love Oliver P. , Barnas Andrew F. , Harris Christopher M. , Gilchrist H. Grant , Semeniuk Christina A. D.
Published: October 2023

Several predator–prey systems are in flux as an indirect result of climate change. In the Arctic, earlier sea-ice loss is driving polar bears (Ursus maritimus) onto land when many colonial nesting seabirds are breeding. The result is a higher threat of nest predation for birds with potential limited ability to respond. We quantified heart rate change in a large common eider (Somateria mollissima) breeding colony in the Canadian Arctic to explore their adaptive capacity to keep pace with the increasing risk of egg predation by polar bears. Eiders displayed on average higher heart rates from baseline when polar bears were within their field of view. Moreover, eiders were insensitive to variation in the distance bears were to their nests, but exhibited mild bradycardia (lowered heart rate) the longer the eider was exposed to the bear given the hen's visibility. Results indicate that a limited ability to assess the risks posed by polar bears may result in long-term fitness consequences for eiders from the increasing frequency in interactions with this predator.
All-a-glow: spectral characteristics confirm widespread fluorescence for mammals
Authors: Travouillon Kenny J. , Cooper Christine , Bouzin Jemmy T. , Umbrello Linette S. , Lewis Simon W.
Published: October 2023

Mammalian fluorescence has been reported from numerous species of monotreme, marsupial and placental mammal. However, it is unknown how widespread this phenomenon is among mammals, it is unclear for many species if these observations of ‘glowing’ are true fluorescence and the biological function of fluorescence remains undetermined. We examined a wide range of mammal species held in a museum collection for the presence of apparent fluorescence using UV light, and then analysed a subset of preserved and non-preserved specimens by fluorescent spectroscopy at three different excitation wavelengths to assess whether the observations were fluorescence or optical scatter, and the impact of specimen preservation. We also evaluated if fluorescence was related to biological traits. We found that fluorescence is widespread in mammalian taxa; we identified examples of the phenomena among 125 species representing all 27 living mammalian orders and 79 families. For a number of model species, there was no evidence of a corresponding shift in the emission spectra when the wavelength of excitation was shifted, suggesting that observations of ‘glowing’ mammals were indeed fluorescence. Preservation method impacted the intensity of fluorescence. Fluorescence was most common and most intense among nocturnal species and those with terrestrial, arboreal and fossorial habits, with more of their body being more fluorescent. It remains unclear if fluorescence has any specific biological role for mammals. It appears to be a ubiquitous property of unpigmented fur and skin but may function to make these areas appear brighter and therefore enhance visual signalling, especially for nocturnal species.
Migratory patterns of two major influenza virus host species on tropical islands
Authors: Lebarbenchon Camille , Boucher Solenn , Feare Chris , Dietrich Muriel , Larose Christine , Humeau Laurence , Le Corre Matthieu , Jaeger Audrey
Published: October 2023

Animal migration is a major driver of infectious agent dispersal. Duck and seabird migrations, for instance, play a key role in the spatial transmission dynamics and gene flow of avian influenza viruses (AIV), worldwide. On tropical islands, brown and lesser noddies (
Anous stolidus
and
Anous tenuirostris
) may be important AIV hosts, but the lack of knowledge on their migratory behaviour limits our understanding of virus circulation in island networks. Here we show that high connectivity between islands generated by non-breeding dispersive behaviours may be a major driver in the spread and the maintenance of AIV among tropical islands of the western Indian Ocean. Tracking data highlight two types of dispersive behaviours during the non-breeding season: birds either staying in the vicinity of their breeding ground (on Bird Island, Seychelles), or moving to and roosting on other islands in the western Indian Ocean. Migrant birds used a wide range of roosting places from the Tanzanian coasts to the Maldives archipelago and Tromelin Island. Epidemiological data confirm that brown and lesser noddies are major hosts for AIV, although significant variations of seroprevalence between species suggest that other biological and ecological drivers could be involved in virus infection and transmission dynamics.
Revisiting the influence of pH on
1
J
C

α

H
and chemical shifts of glycine and alanine short oligopeptides
Authors: Shahkhatuni A. A. , Shahkhatuni A. G.
Published: October 2023

The pH dependence of several NMR parameters of glycine and alanine short oligopeptides has been reported previously in different studies. Here we have thoroughly examined, summarized and demonstrated the dependences of
1
H,
13
C and
15
N chemical shifts and protonation states of amino acids using two-dimensional NMR experiments. Nevertheless,
1
J
C

α

H
one bond spin–spin coupling constants are more informative and convenient for determination of the position and protonation state of glycine and alanine residue in the oligopeptide chain. In particular, for various oligopeptides (up to six residues), it was shown that the pH dependence of
1
J
C

α

H
of N-terminal glycine and alanine residues is larger than that of C-terminal groups, and in backbone residues, it is not influenced by pH and only slightly depends on the position of the amino acid residue in the chain.
An Insight into Genes Responsible for Fosfomycin Resistance Among Uropathogens of Asymptomatic Bacteriuria during Pregnancy: A North Indian Study
Authors: Khatoon Sajda , Sultan Asfia , Khan Fatima , Khan Tamkin , Singh Anuradha
Published: October 2023

Purpose: Asymptomatic bacteriuria (ASB) is a common finding during pregnancy. Effective antibiotic treatment could reduce its adverse effects on both mother and fetus. However, emerging antimicrobial resistance limits the treatment options. Fosfomycin might be a promising drug in this regard, as its resistance is still low. The aim of the study was to determine the antimicrobial susceptibility pattern of fosfomycin in isolates causing ASB by disc diffusion and agar dilution (in selected isolates), determine minimum inhibitory concentration (MIC) by agar dilution in isolates resistant by disc diffusion and detect the genes responsible for fosfomycin resistance.
Material and Methods: This was a 2-year study carried in the Department of Microbiology, Jawaharlal Nehru Medical College and Hospital (JNMCH), Aligarh Muslim University (AMU), Aligarh. Total 10252 urine samples from asymptomatic pregnant females (18-45 years) attending the antenatal care (ANC) outpatient department (OPD) were submitted. Identification of pathogen and antimicrobial susceptibility testing (AST) done as per standard methods of CLSI. There was phenotypic detection of methicillin resistant Staphylococcus aureus (MRSA) and Other Staphylococcus species (MRSS), high level aminoglycoside resistance (HLAR), vancomycin resistant Enterococci (VRE) and S. aureus (VRSA), extended spectrum β-lactamase (ESBL) and carbapenem resistant Enterobacterales (CRE). All the fosfomycin resistant isolates (by disk diffusion) were tested by agar dilution. Conventional PCR was performed for murA, fosA, uhpT and glpT genes on all resistant isolates.
Result: In this study, the prevalence of ASB among pregnant females was 1173(11.4%), in which Escherichia coli 495(42%) being the predominant organism. The overall sensitivity of fosfomycin among Gram-positive cocci (GPC) and Gram-negative bacilli (GNB) was 99% and 97.6% respectively. MRSA and MRSS accounted for 50 (66.6%) and 71 (76%) respectively. Highest rate of MIC >2048 µg/ml were shown by most isolates (mainly E. coli) on agar dilution. PCR studies revealed four E. coli strains possessed both murA (also present in 1 K. pneumoniae strain) and glpT genes. While only one isolate (E. faecalis) was positive for fosA gene. But none of the strain possessed uhpT gene.
Conclusion: According to this study, murA and glpT genes were more frequent than fosA. We cannot comment on the prevalence and regional distribution of fosfomycin resistant genes based on this preliminary study. Therefore, more Indian studies should be carried out to create awareness about the presence of genes in a particular area.
Epidemiology and characterization of Providencia stuartii isolated from hospitalized patients in southern Brazil: A possible emerging pathogen
Authors: Guidone Gustavo Henrique Migliorini , Cardozo Jennifer Germiniani , Silva Luana Carvalho , Sanches Matheus Silva , Galhardi Ligia Carla Faccin , Kobayashi Renata Katsuko Takayama , Vespero Eliana Carolina , Rocha Sergio Paulo Dejato
Published: October 2023

This study aimed to characterize the virulence factors and antimicrobial resistance of Providencia stuartii, an opportunistic pathogen that causes human infections. We examined 45 isolates of P. stuartii both genotypically and phenotypically by studying their adherence to HeLa cells, biofilm formation, cytotoxicity, and antimicrobial resistance, and analyzed their genomes for putative virulence and resistance genes. This study found that most isolates possessed multiple virulence genes, including fimA, mrkA, fptA, iutA, ireA, and hlyA, and were cytotoxic to Vero cells. All the isolates were resistant to amoxicillin plus clavulanic acid, levofloxacin, and sulfamethoxazole plus trimethoprim, and most were resistant to ceftriaxone and cefepime. All isolates harbored extended-spectrum beta-lactamase coding genes such as blaCTX-M-2 and 23/45 (51.11 %) of them also harbored blaCTX-M-9. The gene KPC-2 (carbapenemase) was detected in 8/45 (17.77 %) isolates. This study also found clonality among the isolates, indicating the possible spread of the pathogen among patients at the hospital. These results have significant clinical and epidemiological implications and emphasize the importance of a continued understanding of the virulence and antimicrobial resistance of this pathogen for the prevention and treatment of future infections.
Genomic investigation of the emergence of vanD vancomycin resistant Enterococcus faecium
Authors: Baines Sarah Louise , Guérillot Romain , Ballard Susan , Johnson Paul D R , Stinear Timothy P , Roberts Sally , Howden Benjamin P
Published: October 2023

Vancomycin-resistant Enterococcus (VRE) is an increasingly identified cause of human disease with most infections resulting from the vanA and vanB genotypes; less is known about other clinically relevant genotypes. Here we report a genomic exploration of a vanD VRE faecium (VREfm), which arose de novo during a single infectious episode. The genomes of the vancomycin-susceptible E. faecium (VSEfm) recipient and resulting VREfm were subjected to long-read sequencing and closed, with whole genome alignments and cross-mapping used to identified genomic variation. Three key differences were identified. (i) The VREfm chromosome gained a 142.6kb integrative conjugative element (ICE) harbouring the vanD locus. (ii) The native ligase (ddl) was disrupted by an ISEfm1 insertion. (iii) A large 1.74Mb chromosomal inversion of unknown consequence occurred. Alignment and phylogenetic-based comparisons of the VREfm with a global collection of vanD-harbouring genomes identified strong similarities in the 120-160kb genomic region surrounding vanD, suggestive of a common mobile element and integration site, irrespective of the diverse taxonomic, geographic, and host origins of the isolates. This isolate diversity revealed that this putative ICE (and its source) is globally disseminated and is capable of being acquired by different genera. Although the incidence of vanD VREfm is low, understanding its emergence and potential for spread is crucial for the ongoing efforts to reduce antimicrobial resistance.
Evolution and diversity of nucleotide and dinucleotide composition in poxviruses
Authors: Molteni Cristian , Forni Diego , Cagliani Rachele , Bravo Ignacio G. , Sironi Manuela
Published: October 2023

Poxviruses (family Poxviridae) have long dsDNA genomes and infect a wide range of hosts, including insects, birds, reptiles and mammals. These viruses have substantial incidence, prevalence and disease burden in humans and in other animals. Nucleotide and dinucleotide composition, mostly CpG and TpA, have been largely studied in viral genomes because of their evolutionary and functional implications. We analysed here the nucleotide and dinucleotide composition, as well as codon usage bias, of a set of representative poxvirus genomes, with a very diverse host spectrum. After correcting for overall nucleotide composition, entomopoxviruses displayed low overall GC content, no enrichment in TpA and large variation in CpG enrichment, while chordopoxviruses showed large variation in nucleotide composition, no obvious depletion in CpG and a weak trend for TpA depletion in GC-rich genomes. Overall, intergenome variation in dinucleotide composition in poxviruses is largely accounted for by variation in overall genomic GC levels. Nonetheless, using vaccinia virus as a model, we found that genes expressed at the earliest times in infection are more CpG-depleted than genes expressed at later stages. This observation has parallels in betahepesviruses (also large dsDNA viruses) and suggests an antiviral role for the innate immune system (e.g. via the zinc-finger antiviral protein ZAP) in the early phases of poxvirus infection. We also analysed codon usage bias in poxviruses and we observed that it is mostly determined by genomic GC content, and that stratification after host taxonomy does not contribute to explaining codon usage bias diversity. By analysis of within-species diversity, we show that genomic GC content is the result of mutational biases. Poxvirus genomes that encode a DNA ligase are significantly AT-richer than those that do not, suggesting that DNA repair systems shape mutation biases. Our data shed light on the evolution of poxviruses and inform strategies for their genetic manipulation for therapeutic purposes.
Break-induced replication underlies formation of inverted triplications and generates unexpected diversity in haplotype structures
Authors: Grochowski Christopher M. , Bengtsson Jesse D. , Du Haowei , Gandhi Mira , Lun Ming Yin , Mehaffey Michele G. , Park KyungHee , Höps Wolfram , Benito-Garagorri Eva , Hasenfeld Patrick , Korbel Jan O. , Mahmoud Medhat , Paulin Luis F. , Jhangiani Shalini N. , Muzny Donna M. , Fatih Jawid M. , Gibbs Richard A. , Pendleton Matthew , Harrington Eoghan , Juul Sissel , Lindstrand Anna , Sedlazeck Fritz J. , Pehlivan Davut , Lupski James R. , Carvalho Claudia M.B.
Published: October 2023

Background

The duplication-triplication/inverted-duplication (DUP-TRP/INV-DUP) structure is a type of complex genomic rearrangement (CGR) hypothesized to result from replicative repair of DNA due to replication fork collapse. It is often mediated by a pair of inverted low-copy repeats (LCR) followed by iterative template switches resulting in at least two breakpoint junctionsin cis. Although it has been identified as an important mutation signature of pathogenicity for genomic disorders and cancer genomes, its architecture remains unresolved and is predicted to display at least four structural variation (SV) haplotypes.

Results

Here we studied the genomic architecture of DUP-TRP/INV-DUP by investigating the genomic DNA of 24 patients with neurodevelopmental disorders identified by array comparative genomic hybridization (aCGH) on whom we found evidence for the existence of 4 out of 4 predicted SV haplotypes. Using a combination of short-read genome sequencing (GS), long- read GS, optical genome mapping and StrandSeq the haplotype structure was resolved in 18 samples. This approach refined the point of template switching between inverted LCRs in 4 samples revealing a DNA segment of ∼2.2-5.5 kb of 100% nucleotide similarity. A prediction model was developed to infer the LCR used to mediate the non-allelic homology repair.

Conclusions

These data provide experimental evidence supporting the hypothesis that inverted LCRs act as a recombinant substrate in replication-based repair mechanisms. Such inverted repeats are particularly relevant for formation of copy-number associated inversions, including the DUP-TRP/INV-DUP structures. Moreover, this type of CGR can result in multiple conformers which contributes to generate diverse SV haplotypes in susceptibleloci.
Spiral NeuroString: High-Density Soft Bioelectronic Fibers for Multimodal Sensing and Stimulation
Authors: Khatib Muhammad , Zhao Eric Tianjiao , Wei Shiyuan , Abramson Alex , Bishop Estelle Spear , Chen Chih-Hsin , Thomas Anne-Laure , Xu Chengyi , Park Jaeho , Lee Yeongjun , Hamnett Ryan , Yu Weilai , Root Samuel E. , Yuan Lei , Chakhtoura Dorine , Kim Kyun Kyu , Zhong Donglai , Nishio Yuya , Zhao Chuanzhen , Wu Can , Jiang Yuanwen , Zhang Anqi , Li Jinxing , Wang Weichen , Salimi-Jazi Fereshteh , Rafeeqi Talha A. , Hemed Nofar Mintz , Tok Jeffrey B.-H. , Chen Xiaoke , Kaltschmidt Julia A. , Dunn James C.Y. , Bao Zhenan
Published: October 2023

Bioelectronic fibers hold promise for both research and clinical applications due to their compactness, ease of implantation, and ability to incorporate various functionalities such as sensing and stimulation. However, existing devices suffer from bulkiness, rigidity, limited functionality, and low density of active components. These limitations stem from the difficulty to incorporate many components on one-dimensional (1D) fiber devices due to the incompatibility of conventional microfabrication methods (e.g., photolithography) with curved, thin and long fiber structures. Herein, we introduce a fabrication approach, “spiral transformation″, to convert two-dimensional (2D) films containing microfabricated devices into 1D soft fibers. This approach allows for the creation of high density multimodal soft bioelectronic fibers, termed Spiral NeuroString (S-NeuroString), while enabling precise control over the longitudinal, angular, and radial positioning and distribution of the functional components. We show the utility of S-NeuroString for motility mapping, serotonin sensing, and tissue stimulation within the dynamic and soft gastrointestinal (GI) system, as well as for single-unit recordings in the brain. The described bioelectronic fibers hold great promises for next-generation multifunctional implantable electronics.
A tale of two springs: contrasting forest soundscapes during the COVID-19 lockdown (2020) and after the record snowstorm Filomena (2021) from Central Spain
Authors: Ortiz-Álvarez Rüdiger , Leiva-Dueñas Carmen
Published: October 2023

During the COVID-19 pandemic, humanity temporarily retired from the outdoors. The strict lockdown measures in Spain coincided with the onset of the nesting season of birds, thriving in an unusually quiet environment. Here, we have recorded in forests near San Lorenzo de El Escorial (Central Spain) during the lockdown period in 2020, and the closer to normal spring in 2021. We found strong differences in soundscapes by recording year and location, regardless of the effects of meteorology and human mobility. Species altered their behaviour by increasing their calling intensity during 2021 to cope with higher noise levels, however, acoustic activity was generally less diverse and complex. The difference between years was particularly detrimental for the highest-pitched biophony in 2021. We interpret that an extreme snowfall, Filomena, may have caused a mortality event with lasting effects in the community during the 2021 spring. Since extreme climatic events are likely going to keep happening in the area due to climate change, our data is a useful baseline to guide future conservation efforts, and examine how our activity and climate change are changing the soundscapes of Spanish Mediterranean forests.
ID transcription factors regulate the ability of Müller glia to become proliferating neurogenic progenitor-like cells
Authors: Taylor Olivia B. , Patel Snehal P. , Hawthorn Evan C. , El-Hodiri Heithem M. , Fischer Andy J.
Published: October 2023

The purpose of this study was to investigate how ID transcription factors (TFs) regulate the ability of Müller glia (MG) to reprogram into proliferating MG-derived progenitor cells (MGPCs) in the chick retina. We found thatID1is transiently expressed by maturing MG, whereasID4is upregulated and maintained in maturing MG in embryonic retinas. In mature retinas,ID4was prominently expressed by resting MG, but in response to retinal damageID4was rapidly upregulated and then downregulated in MGPCs. By contrast,ID1, ID2andID3were low in resting MG and then upregulated by MGPCs. Inhibition of ID TFs following retinal damage decreased numbers of proliferating MGPCs. Inhibition of IDs after the proliferation of MGPCs significantly increased numbers of progeny that differentiate as neurons. In damaged or undamaged retinas inhibition of IDs increased levels of p21Cip1in MG. In response to damage or insulin+FGF2 levels ofCDKN1Amessage and p21Cip1protein were decreased, absent in proliferating MGPCs, and elevated in MG returning to a resting phenotype. Inhibition of Notch- or gp130/Jak/Stat-signaling in damaged retinas increased levels of ID4 but not p21Cip1in MG. AlthoughID4is the predominant isoform expressed by MG in the chick retina,id1andid2aare predominantly expressed by resting MG and downregulated in activated MG and MGPCs in zebrafish retinas. We conclude that ID TFs have a significant impact on regulating the responses of MG to retinal damage, controlling the ability of MG to proliferate by regulating levels of p21Cip1, and suppressing the neurogenic potential of MGPCs.
Streptococcus agalactiaeandEscherichia coliInduce Distinct Effector γδ T Cell Responses During Neonatal Sepsis
Authors: Witt Lila T. , Greenfield Kara G. , Knoop Kathryn A.
Published: October 2023

Neonates born prematurely are highly vulnerable to life-threatening conditions such as bacterial sepsis.Streptococcus agalactiae, also known as group BStreptococcus(GBS) andEscherichia coliare frequent causative pathogens of neonatal sepsis, however, it remains unclear if distinct sepsis pathogens induce differential adaptive immune responses. In the present study, we find that γδ T cells in neonatal mice rapidly respond to single-organism GBS andE. colibloodstream infections and that these pathogens induce distinct activation and cytokine production from IFN-γ and IL-17 producing γδ T cells, respectively. We also report differential reliance on γδTCR signaling to elicit effector cytokine responses during neonatal sepsis, with IL-17 production duringE. coliinfection being driven by γδTCR signaling, and IFN-γ production during GBS infection occurring independently of γδTCR signaling. Furthermore, we report that the divergent effector responses of γδ T cells during GBS andE. coliinfections impart distinctive neuroinflammatory phenotypes on the neonatal brain. The present study reveals that the neonatal adaptive immune system differentially responds to distinct bacterial stimuli, resulting in unique neuroinflammatory phenotypes.
BNT162b2 mRNA vaccine-induced sex differences in the single-cell transcriptome of peripheral blood mononuclear cells in healthy adults
Authors: Knapp Johannes D , Bhargava Aditi
Published: October 2023

Introduction

Men reportedly experience more severe disease and adverse outcomes from COVID-19, including death. Women report more adverse events (AEs) after vaccination in general. While few studies have addressed sex-specific risk factors or molecular mechanisms behind COVID-19, none have examined sex differences in the response to COVID-19 vaccination.

Methods

We searched AE reporting databases to find sex differences specific to COVID-19 vaccines. We analyzed public datasets to identify baseline sex differences in gene expression across cell types and time points, and sex differences in the response to the second BNT162b2 mRNA vaccine dose.

Results

Sex differences in AE rates for mRNA vaccines equaled those for other non-mRNA vaccines. T cells and monocytes showed the greatest number of sexually dimorphic genes. Platelet counts in the study population differed significantly before vaccination (3.6% in females vs 1.8% in males) but not after the second BNT162b2 dose (7.2% vs 7.3%). There were no notable sex differences in the expression of key genes induced by the second dose after exclusion of platelets. BNT162b2 dose 2-specific APOBEC3Ahighmonocytes and the dose 2-induced gene signature persisted for longer in women. Glucocorticoid-responsiveTSC22D3, CEBPB/DandDDIT4were specifically induced in females; the voltage-gated potassium channel regulatory subunitKCNE3was specifically induced in males.

Conclusions

This sexual dimorphism in both X-linked and autosomal gene transcriptome in PBMCs after mRNA COVID-19 vaccination might explain fatigue, autoimmune, and neurological AEs reported after vaccination at different rates in women and men.
mitoBKCais functionally expressed in murine and human breast cancer cells and potentially contributes to metabolic reprogramming
Authors: Bischof Helmut , Maier Selina , Koprowski Piotr , Kulawiak Bogusz , Burgstaller Sandra , Jasińska Joanna , Serafimov Kristian , Zochowska Monika , Gross Dominic , Schroth Werner , Matt Lucas , Juarez Lopez David Arturo , Zhang Ying , Bonzheim Irina , Büttner Florian A. , Fend Falko , Schwab Matthias , Birkenfeld Andreas L. , Malli Roland , Lämmerhofer Michael , Bednarczyk Piotr , Szewczyk Adam , Lukowski Robert
Published: October 2023

Alterations in the function of K+channels such as the voltage- and Ca2+activated K+channel of large conductance (BKCa) reportedly promote breast cancer (BC) development and progression. Underlying molecular mechanisms remain, however, elusive. Here, we provide electrophysiological evidence for a BKCasplice variant localized to the inner mitochondrial membrane of murine and human BC cells (mitoBKCa). Through a combination of genetic knockdown and knockout along with cell permeable BKCachannel blocker, we show that mitoBKCamodulates overall cellular and mitochondrial energy production and mediates the metabolic rewiring referred to as the “Warburg effect”, thereby promoting BC cell proliferation in the presence and absence of oxygen. Additionally, we detect mitoBKCaand BKCatranscripts in low or high abundance, respectively, in clinical BC specimens. Together, our results emphasize, that targeting mitoBKCacould represent a treatment strategy for selected BC patients in future.
Accurate cryo-EM protein particle picking by integrating the foundational AI image segmentation model and specialized U-Net
Authors: Gyawali Rajan , Dhakal Ashwin , Wang Liguo , Cheng Jianlin
Published: October 2023

Picking protein particles in cryo-electron microscopy (cryo-EM) micrographs is a crucial step in the cryo-EM-based structure determination. However, existing methods trained on a limited amount of cryo-EM data still cannot accurately pick protein particles from noisy cryo-EM images. The general foundational artificial intelligence (AI)-based image segmentation model such as Meta’s Segment Anything Model (SAM) cannot segment protein particles well because their training data do not include cryo-EM images. Here, we present a novel approach (CryoSegNet) of integrating an attention-gated U-shape network (U-Net) specially designed and trained for cryo-EM particle picking and the SAM. The U-Net is first trained on a large cryo-EM image dataset and then used to generate input from original cryo-EM images for SAM to make particle pickings. CryoSegNet shows both high precision and recall in segmenting protein particles from cryo-EM micrographs, irrespective of protein type, shape, and size. On several independent datasets of various protein types, CryoSegNet outperforms two top machine learning particle pickers crYOLO and Topaz as well as SAM itself. The average resolution of density maps reconstructed from the particles picked by CryoSegNet is 3.32 Å, 7% better than 3.57 Å of Topaz and 14% better than 3.85 Å of crYOLO.
Parrot politics: social decision-making in wild parrots relies on both individual recognition and intrinsic markers
Authors: Penndorf J. , Farine D. R. , Martin J. M. , Aplin L. M.
Published: October 2023

Dominance hierarchies are generally thought to form over time via memory of repeated interactions. However, dominance hierarchies are also occasionally reported in species with fission-fusion social dynamics, where individuals may encounter large numbers of individuals, leading to incomplete social information. It it has been alternatively proposed that the complex decision-making required in these circumstances may lead to increased selection for social cognition and memory, or to the evolution of mixed strategies that rely on memory for interaction with familiars and status signals for strangers.

Here, test these competing hypotheses by recording social associations and aggressive interactions in a highly social, large-brained parrot, the sulphur-crested cockatoo(Cacatua galerita). We followed 411 individuals across three neighbouring roost sites, where individuals exhibit stable dominance hierarchies within roosts, alongside a high degree of fission-fusion dynamics within roosts and regular between-roost movements.

We found evidence that sulphur-crested cockatoos use a two-fold social strategy when initiating or reacting to an aggression. For familiar individuals, aggressions were initiated or escalated based on rank difference. When facing less familiar individuals, decisions to interact — or escalate — were based on the relative weight, with interactions directed towards, and more likely to escalate between, individuals of similar weight.

Our results suggest that social knowledge remains an important determinant of aggressive interactions in highly fission-fusion systems, but that individuals can dynamically incorporate other potential cues of competitive ability when knowledge is lacking.