Immunotherapeutic targeting of aging-associated isoDGR motif in chronic lung inflammation.

Accumulation of damaged biomolecules in body tissues is the primary cause of aging and age-related chronic diseases. Since this damage often occurs spontaneously, it has traditionally been regarded as untreatable, with typical therapeutic strategies targeting genes or enzymes being ineffective in this domain. In this report, we demonstrate that an antibody targeting the isoDGR damage motif in lung tissue can guide immune clearance of harmful damaged proteins in vivo, effectively reducing age-linked lung inflammation.

Heat wave exposure during pregnancy and neurodevelopmental delay in young children: A birth cohort study.

Introduction: Gestation is a critical period for fetal brain development, and extreme heat exposure during this stage may have adverse impact on neurodevelopment in children. However, current evidence is scarce.

Methods: We examined the associations between maternal exposure to heat wave during pregnancy and neurodevelopmental delay in young children in a birth cohort study of 67,453 child-mother pairs from Foshan, China.

Structural insights into the membrane-bound proteolytic machinery of bacterial protein quality control.

In bacteria and eukaryotic organelles of prokaryotic origin, ATP-dependent proteases are crucial for regulating protein quality control through substrate unfolding and degradation. Understanding the mechanism and regulation of this key cellular process could prove instrumental in developing therapeutic strategies. Very recently, cryo-electron microscopy structural studies have shed light on the functioning of AAA+ proteases, including membrane-bound proteolytic complexes.

Inhibition of falcilysin from Plasmodium falciparum by interference with its closed-to-open dynamic transition.

In the absence of an efficacious vaccine, chemotherapy remains crucial to prevent and treat malaria. Given its key role in haemoglobin degradation, falcilysin constitutes an attractive target. Here, we reveal the mechanism of enzymatic inhibition of falcilysin by MK-4815, an investigational new drug with potent antimalarial activity.

Cryo-EM structure of the SPFH-NfeD family protein complex QmcA-YbbJ.

The SPFH (stomatin, prohibitin, flotillin, and HflK/C) protein family is universally present and encompasses the evolutionarily conserved SPFH domain. These proteins are predominantly localized in lipid raft and implicated in various biological processes. The NfeD (nodulation formation efficiency D) protein family is often encoded in tandem with SPFH proteins, suggesting a close functional relationship.

Identification of atypical T4SS effector proteins mediating bacterial defense.

To remain competitive, proteobacteria use various contact-dependent weapon systems to defend against microbial competitors. The bacterial-killing type IV secretion system (T4SS) is one such powerful weapon. It commonly controls the killing/competition between species by secreting the lethal T4SS effector (T4E) proteins carrying conserved XVIPCD domains into competing cells.

Gram-negative bacteria resist antimicrobial agents by a DzrR-mediated envelope stress response.

Background: Envelope stress responses (ESRs) are critical for adaptive resistance of Gram-negative bacteria to envelope-targeting antimicrobial agents. However, ESRs are poorly defined in a large number of well-known plant and human pathogens. Dickeya oryzae can withstand a high level of self-produced envelope-targeting antimicrobial agents zeamines through a zeamine-stimulated RND efflux pump DesABC.

Quantitative Proteomics of Medium-Sized Extracellular Vesicle-Enriched Plasma of Lacunar Infarction for the Discovery of Prognostic Biomarkers.

Lacunar infarction (LACI), a subtype of acute ischemic stroke, has poor mid- to long-term prognosis due to recurrent vascular events or incident dementia which is difficult to predict using existing clinical data. Herein, we aim to discover blood-based biomarkers for LACI as a complementary prognostic tool. Convalescent plasma was collected from forty-five patients following a non-disabling LACI along with seventeen matched control subjects.

Molecular basis of the key regulator WRINKLED1 in plant oil biosynthesis.

Vegetable oils are not only major components of human diet but also vital for industrial applications. WRINKLED1 (WRI1) is a pivotal transcription factor governing plant oil biosynthesis, but the underlying DNA-binding mechanism remains incompletely understood. Here, we resolved the structure of Arabidopsis WRI1 (AtWRI1) with its cognate double-stranded DNA (dsDNA), revealing two antiparallel β sheets in the tandem AP2 domains that intercalate into the adjacent major grooves of dsDNA to determine the sequence recognition specificity.

Molecular condensation and mechanoregulation of plant class I formin, an integrin-like actin nucleator.

The actin cytoskeleton (AC) undergoes rapid remodelling to coordinate cellular processes during signal transduction, including changes in actin nucleation, crosslinking, and depolymerization in a time- and space-dependent manner. Switching the initial actin nucleation often provides timely control of the entire actin network formation. Located at the cell surface, the plant class I formin family is a major class of actin nucleators that rapidly respond to exterior chemical and environmental cues.

Cryo-EM structure of the entire FtsH-HflKC AAA protease complex.

The membrane-bound AAA protease FtsH is the key player controlling protein quality in bacteria. Two single-pass membrane proteins, HflK and HflC, interact with FtsH to modulate its proteolytic activity. Here, we present structure of the entire FtsH-HflKC complex, comprising 12 copies of both HflK and HflC, all of which interact reciprocally to form a cage, as well as four FtsH hexamers with periplasmic domains and transmembrane helices enclosed inside the cage and cytoplasmic domains situated at the base of the cage.

Structural analyses of the AAA+ ATPase domain of the transcriptional regulator GtrR in the BDSF quorum-sensing system in Burkholderia cenocepacia.

Global transcriptional regulator downstream RpfR (GtrR) is a key downstream regulator for quorum-sensing signaling molecule cis-2-dodecenoic acid (BDSF). As a bacterial enhancer-binding protein (bEBP), GtrR is composed of an N-terminal receiver domain, a central ATPases associated with diverse cellular activities (AAA+) ATPase σ -interaction domain, and a C-terminal helix-turn-helix DNA-binding domain. In this work, we solved its AAA+ ATPase domain in both apo and GTP-bound forms.

Crystal structure of a chitinase (RmChiA) from the thermophilic fungus Rhizomucor miehei with a real active site tunnel.

A chitinase gene (RmChiA) encoding 445 amino acid (aa) residues from a fungus Rhizomucor miehei was cloned and overexpressed in Escherichia coli. Two kinds of RmChiA crystal forms, with space groups P3 2 1 and P1, were obtained by sitting-drop vapor diffusion and the structures were determined by X-ray diffraction. The overall structure of RmChiA monomer, which is the first structure of bacterial-type chitinases from nonpathogenic fungi, adopts a canonical triosephosphate isomerase (TIM) barrel fold with two protruding chitinase insertion domains.

Translational GTPase BipA Is Involved in the Maturation of a Large Subunit of Bacterial Ribosome at Suboptimal Temperature.

BPI-inducible protein A (BipA), a highly conserved paralog of the well-known translational GTPases LepA and EF-G, has been implicated in bacterial motility, cold shock, stress response, biofilm formation, and virulence. BipA binds to the aminoacyl-(A) site of the bacterial ribosome and establishes contacts with the functionally important regions of both subunits, implying a specific role relevant to the ribosome, such as functioning in ribosome biogenesis and/or conditional protein translation. When cultured at suboptimal temperatures, the genomic deletion strain (Δ) exhibits defects in growth, swimming motility, and ribosome assembly, which can be complemented by a plasmid-borne supplementation or suppressed by the genomic deletion.

Structural Basis and Function of the N Terminus of SARS-CoV-2 Nonstructural Protein 1.

Nonstructural protein 1 (Nsp1) of severe acute respiratory syndrome coronaviruses (SARS-CoVs) is an important pathogenic factor that inhibits host protein translation by means of its C terminus. However, its N-terminal function remains elusive. Here, we determined the crystal structure of the N terminus (amino acids [aa] 11 to 125) of SARS-CoV-2 Nsp1 at a 1.

Ribosome Protection Proteins-"New" Players in the Global Arms Race with Antibiotic-Resistant Pathogens.

Bacteria have evolved an array of mechanisms enabling them to resist the inhibitory effect of antibiotics, a significant proportion of which target the ribosome. Indeed, resistance mechanisms have been identified for nearly every antibiotic that is currently used in clinical practice. With the ever-increasing list of multi-drug-resistant pathogens and very few novel antibiotics in the pharmaceutical pipeline, treatable infections are likely to become life-threatening once again.

Emerging evidence for kindlin oligomerization and its role in regulating kindlin function.

Integrin-mediated cell-extracellular matrix (ECM) interactions play crucial roles in a broad range of physiological and pathological processes. Kindlins are important positive regulators of integrin activation. The FERM-domain-containing kindlin family comprises three members, kindlin-1, kindlin-2 and kindlin-3 (also known as FERMT1, FERMT2 and FERMT3), which share high sequence similarity (identity >50%), as well as domain organization, but exhibit diverse tissue-specific expression patterns and cellular functions.

An engineered CRISPR-Cas12a variant and DNA-RNA hybrid guides enable robust and rapid COVID-19 testing.

Extensive testing is essential to break the transmission of SARS-CoV-2, which causes the ongoing COVID-19 pandemic. Here, we present a CRISPR-based diagnostic assay that is robust to viral genome mutations and temperature, produces results fast, can be applied directly on nasopharyngeal (NP) specimens without RNA purification, and incorporates a human internal control within the same reaction. Specifically, we show that the use of an engineered AsCas12a enzyme enables detection of wildtype and mutated SARS-CoV-2 and allows us to perform the detection step with loop-mediated isothermal amplification (LAMP) at 60-65 °C.

Structure of CESA3 catalytic domain with its substrate UDP-glucose provides insight into the mechanism of cellulose synthesis.

Cellulose is synthesized by cellulose synthases (CESAs) from the glycosyltransferase GT-2 family. In plants, the CESAs form a six-lobed rosette-shaped CESA complex (CSC). Here we report crystal structures of the catalytic domain of CESA3 (AtCESA3) in both apo and uridine diphosphate (UDP)-glucose (UDP-Glc)-bound forms.

Geographical discrimination and adulteration analysis for edible oils using two-dimensional correlation spectroscopy and convolutional neural networks (CNNs).

Geographical discrimination and adulteration analysis play significant roles in edible oil analysis. A novel method for discrimination and adulteration analysis of edible oils were proposed in this study. The two-dimensional correlation spectra of edible oils were obtained by solvents perturbation and the convolutional neural networks (CNNs) were constructed to analyze the synchronous and asynchronous correlation spectra of the edible oils.