Synapse-to-synapse plasticity variability balanced to generate input-wide constancy of transmitter release.

Basal synaptic strength can vary greatly between synapses formed by an individual neuron because of diverse probabilities of action potential (AP) evoked transmitter release ( ). Optical quantal analysis on large numbers of identified larval glutamatergic synapses shows that short-term plasticity (STP) also varies greatly between synapses made by an individual type I motor neuron (MN) onto a single body wall muscle. Synapses with high and low and different forms and level of STP have a random spatial distribution in the MN nerve terminal, and ones with very different properties can be located within 200 nm of one other.

Altered Cell Clusters and Upregulated Aqp1 in Connexin 50 Knockout Lens Epithelium.

Purpose: To characterize the heterogeneity and cell clusters of postnatal lens epithelial cells (LECs) and to investigate the downstream targets of connexin 50 (Cx50) in the regulation of lens homeostasis and lens growth. To determine differentially expressed genes (DEGs) in the connexin 50 knockout (Cx50KO) lens epithelial cells that shed light on novel mechanism underlying the cataract and small size of the Cx50KO lenses.

Methods: Single-cell RNA sequencing (scRNA-seq) of lens epithelial cells isolated from one-month-old Cx50KO and wild-type (WT) mice were performed.

Deficiency in transmitter release triggers homeostatic transcriptional changes that increase presynaptic excitability.

Weakening of synaptic transmission at the Drosophila larval neuromuscular junction triggers two forms of homeostatic compensation, one that increases the probability of glutamate release per action potential (Pr) and another that increases motoneuron (MN) activity. We investigated the molecular changes in MNs that underlie the increase in MN activity. RNA-seq analysis on MNs whose glutamate release is weakened by knockdown of components of the MN transmitter release machinery reveals a reduction in expression of a group of genes that encode potassium channels and their positive modulators.

Polymyxins retain activity and efficacy against "resistant" strains when tested in physiological conditions.

The emergence of plasmid-mediated resistance threatens the efficacy of polymyxins as the last line of defense against pan-drug-resistant infections. However, we have found that using Mueller-Hinton II (MHII), the standard minimum inhibitory concentration (MIC) medium, results in MIC data that are disconnected from treatment outcomes. We found that culturing putative colistin-resistant clinical isolates, as defined by MICs of >2 mg/L in standard MHII testing conditions, in bicarbonate-containing media reduced MICs to the susceptible range by preventing colistin resistance-conferring lipopolysaccharide modifications from occurring.

Aseptic loosening around total joint replacement in humans is regulated by miR-1246 and miR-6089 via the Wnt signalling pathway.

Background: Total joint replacement for osteoarthritis is one of the most successful surgical procedures in modern medicine. However, aseptic loosening continues to be a leading cause of revision arthroplasty. The diagnosis of aseptic loosening remains a challenge as patients are often asymptomatic until the late stages.

A novel lncRNA-mediated epigenetic regulatory mechanism in periodontitis.

Periodontitis is a highly prevalent chronic inflammatory disease with an exaggerated host immune response, resulting in periodontal tissue destruction and potential tooth loss. The long non-coding RNA, LncR-ANRIL, located on human chromosome 9p21, is recognized as a genetic risk factor for various conditions, including atherosclerosis, periodontitis, diabetes, and cancer. LncR-APDC is an ortholog of ANRIL located on mouse genome chr4.

Gastroenteropancreatic neuroendocrine carcinoma tumor spheroid drug screen reveals vulnerability to tyrosyl-DNA phosphodiesterase 1 inhibitors.

Background: Gastroenteropancreatic neuroendocrine carcinomas are rare neoplasms with no effective treatments and poor prognosis. Few reliable preclinical models exist for the study of gastroenteropancreatic neuroendocrine carcinomas, limiting investigation of novel treatments. We used tumor spheroids from our recently established gastroenteropancreatic neuroendocrine carcinoma patient-derived xenograft models to systematically screen for compounds with diverse structures to identify potential new categories of therapeutic agents that can target gastroenteropancreatic neuroendocrine carcinomas.

Selective MCL-1 inhibitor ABBV-467 is efficacious in tumor models but is associated with cardiac troponin increases in patients.

Background: MCL-1 is a prosurvival B-cell lymphoma 2 family protein that plays a critical role in tumor maintenance and survival and can act as a resistance factor to multiple anticancer therapies. Herein, we describe the generation and characterization of the highly potent and selective MCL-1 inhibitor ABBV-467 and present findings from a first-in-human trial that included patients with relapsed/refractory multiple myeloma (NCT04178902).

Methods: Binding of ABBV-467 to human MCL-1 was assessed in multiple cell lines.

The cilia and flagella associated protein CFAP52 orchestrated with CFAP45 is required for sperm motility in mice.

Asthenozoospermia characterized by decreased sperm motility is a major cause of male infertility, but the majority of the etiology remains unknown. Here, we showed that the cilia and flagella associated protein 52 (Cfap52) gene was predominantly expressed in testis and its deletion in a Cfap52 knockout mouse model resulted in decreased sperm motility and male infertility. Cfap52 knockout also led to the disorganization of the midpiece-principal piece junction of the sperm tail but had no effect on the axoneme ultrastructure in spermatozoa.

Diabetes mellitus is a potential risk factor for aseptic loosening around hip and knee arthroplasty.

Background: Aseptic loosening is a leading cause of revision following total hip and knee arthroplasty which is caused by chronic inflammation around the prosthesis. Diabetes mellitus causes systemic inflammatory changes which could increase the risk of aseptic loosening. This study investigated the association between diabetes mellitus and aseptic loosening around hip and knee arthroplasty.

Therapeutic, Humanized Monoclonal Antibody Exhibits Broad Binding and Protective Efficacy against Acinetobacter baumannii.

Acinetobacter baumannii is an extremely drug-resistant pathogen necessitating the development of new therapies. We seek to generate a cocktail of monoclonal antibodies (MAbs) that can target the full diversity of A. baumannii isolates.

Phase I study of anti-epidermal growth factor receptor antibody-drug conjugate serclutamab talirine: Safety, pharmacokinetics, and antitumor activity in advanced glioblastoma.

Background: Serclutamab talirine (Ser-T, formerly ABBV-321) is an antibody-drug conjugate consisting of an antibody (AM-1-ABT-806) directed against activated epidermal growth factor receptor (EGFR) and a pyrrolobenzodiazepine dimer. We investigated Ser-T monotherapy in a phase I, first-in-human, dose-escalation, and dose-expansion study in patients with advanced solid tumors associated with EGFR overexpression.

Methods: Eligible patients (≥18 years) had advanced, histologically confirmed solid tumors associated with EGFR overexpression (centralized testing).

Development of a Bispecific Antibody Targeting Clinical Isolates of Acinetobacter baumannii.

Background: We previously reported developing 2 anticapsular monoclonal antibodies (mAbs) as a novel therapy for Acinetobacter baumannii infections. We sought to determine whether a bispecific mAb (bsAb) could improve avidity and efficacy while maximizing strain coverage in one molecule.

Methods: Humanized mAb 65 was cloned into a single-chain variable fragment and attached to humanized mAb C8, combining their paratopes into a single bsAb (C73).

Comparison of 2 open-sourced 3-dimensional modeling techniques for orthopaedic application.

Although 3-dimensional (3D) printing is becoming more widely adopted for clinical applications, it is yet to be accepted as part of standard practice. One of the key applications of this technology is orthopaedic surgical planning for urgent trauma cases. Anatomically accurate replicas of patients' fracture models can be produced to guide intervention.

Acacia Fiber Protects the Gut from Extended-Spectrum Beta-Lactamase (ESBL)-Producing Escherichia coli Colonization Enabled by Antibiotics.

Novel approaches to combating antibiotic resistance are needed given the ever-continuing rise of antibiotic resistance and the scarce discovery of new antibiotics. Little is known about the colonization dynamics and the role of intrinsic plant-food characteristics in this process. We sought to determine whether plant fiber could alter colonization dynamics by antibiotic-resistant bacteria in the gut.

Gallium-Strontium Phosphate Conversion Coatings for Promoting Infection Prevention and Biocompatibility of Magnesium for Orthopedic Applications.

Device-associated infections remain a clinical challenge. The common strategies to prevent bacterial infection are either toxic to healthy mammalian cells and tissue or involve high doses of antibiotics that can prompt long-term negative consequences. An antibiotic-free coating strategy to suppress bacterial growth is presented herein, which concurrently promotes bone cell growth and moderates the dissolution kinetics of resorbable magnesium (Mg) biomaterials.

Establishment of Novel Neuroendocrine Carcinoma Patient-Derived Xenograft Models for Receptor Peptide-Targeted Therapy.

Gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) are rare cancers consisting of neuroendocrine carcinomas (NECs) and neuroendocrine tumors (NETs), which have been increasing in incidence in recent years. Few cell lines and pre-clinical models exist for studying GEP NECs and NETs, limiting the ability to discover novel imaging and treatment modalities. To address this gap, we isolated tumor cells from cryopreserved patient GEP NECs and NETs and injected them into the flanks of immunocompromised mice to establish patient-derived xenograft (PDX) models.

The High Association of Ophthalmic Manifestations in Individuals With Mucolipidosis Type IV.

Purpose: To present a case report of mucolipidosis type IV (ML4) and review the literature for all of the ophthalmic abnormalities associated with this disease.

Methods: A systematic review of the literature using PubMed/Medline was conducted, and with the addition of the current case report, the eye and ocular adnexa findings of 93 patients with ML4 are summarized.

Results: The most common ophthalmic findings reported among the 93 patients included corneal clouding (90.

Ophthalmic abnormalities in Wieacker-Wolff syndrome.

Wieacker-Wolff syndrome is an X-linked condition caused by variants of the ZC4H2 gene that results in in utero muscular weakness that manifests clinically as arthrogryposis congenita as well as facial and bulbar weakness. We report the case of a young girl with a de novo pathogenic deletion in the ZC4H2 gene and clinical features consistent with Wieacker-Wolff syndrome. Common eye manifestations of the syndrome reported in the literature include ptosis, strabismus, and oculomotor apraxia.

Pharmacological prevention of renal ischemia-reperfusion injury in a rat model.

Introduction: Renal ischemia-reperfusion injury (IRI) can lead to significant morbidity and mortality. It remains a leading cause of acute kidney injury and is therefore an important issue in trauma and renal transplant surgery. Various pharmaceutical agents have been used in an attempt to dampen the harmful effects of IRI but few have been shown to be useful clinically.

Eye and ocular adnexa manifestations of -related disorders.

Background: -related disorders are a rare group of intellectual disability syndromes with a broad range of phenotypic characteristics. The phenotypic spectrum of -related disorders currently includes X-Linked Ohdo Syndrome, Lujan-Fryns Syndrome (LS), and FG syndrome type 1 (FG), also known as Opitz-Kaveggia Syndrome. The gene encodes the largest component of the mediator complex of RNA polymerase II, which is critical for recruiting activators and repressors to regulate the transcription of genes critical to growth, development, and differentiation.

Corrigendum #2 to "Eye Manifestations of Shprintzen-Goldberg Craniosynostosis Syndrome: A Case Report and Systematic Review".

[This corrects the article DOI: 10.1155/2020/7353452.].