Increased immunogen valency improves the maturation of vaccine-elicited HIV-1 VRC01-like antibodies.

Antibodies belonging to the VRC01-class display broad and potent neutralizing activities and have been isolated from several people living with HIV (PLWH). A member of that class, monoclonal antibody VRC01, was shown to reduce HIV-acquisition in two phase 2b efficacy trials. VRC01-class antibodies are therefore expected to be one component of an effective HIV-1 vaccine elicited response.

Increased immunogen valency improves the maturation of vaccine-elicited HIV-1 VRC01-class antibodies.

Antibodies belonging to the VRC01-class display broad and potent neutralizing activities and have been isolated from several people living with HIV (PLWH). A member of that class, monoclonal antibody VRC01, was shown to reduce HIV-acquisition in two phase 2b efficacy trials. VRC01-class antibodies are therefore expected to be a key component of an effective HIV-1 vaccine.

Short CDRL1 in intermediate VRC01-like mAbs is not sufficient to overcome key glycan barriers on HIV-1 Env.

Unlabelled: VRC01-class broadly neutralizing antibodies (bnAbs) have been isolated from people with HIV-1, but they have not yet been elicited by vaccination. They are extensively somatically mutated and sometimes accumulate CDRL1 deletions. Such indels may allow VRC01-class antibodies to accommodate the glycans expressed on a conserved N276 N-linked glycosylation site in loop D of the gp120 subunit.

Priming locomotor training with transspinal stimulation in people with spinal cord injury: study protocol of a randomized clinical trial.

Background: The seemingly simple tasks of standing and walking require continuous integration of complex spinal reflex circuits between descending motor commands and ascending sensory inputs. Spinal cord injury greatly impairs standing and walking ability, but both improve with locomotor training. However, even after multiple locomotor training sessions, abnormal muscle activity and coordination persist.

Adjuvants influence the maturation of VRC01-like antibodies during immunization.

Once naive B cells expressing germline VRC01-class B cell receptors become activated by germline-targeting immunogens, they enter germinal centers and undergo affinity maturation. Booster immunizations with heterologous Envs are required for the full maturation of VRC01-class antibodies. Here, we examined whether and how three adjuvants, Poly(I:C), GLA-LSQ, or Rehydragel, that activate different pathways of the innate immune system, influence the rate and type of somatic mutations accumulated by VRC01-class BCRs that become activated by the germline-targeting 426c.

Evaluation of efficacy of subgingival administration of 1% chlorhexidine gel as an adjunct to scaling and root planing in the treatment of chronic periodontitis - A clinical and microbiological study.

Aim: The aim of the present study was to evaluate the clinical and microbiological effects of subgingival administration of 1% chlorhexidine gel (Chlorhexamed® 1% gel) in patients with chronic periodontitis.

Settings And Design: The study was done in a parallel-arm design with a total of 30 patients with 60 sites suffering from chronic periodontitis. The patients were divided into control and experimental groups.

HIV-1 VRC01 Germline-Targeting Immunogens Select Distinct Epitope-Specific B Cell Receptors.

Activating precursor B cell receptors of HIV-1 broadly neutralizing antibodies requires specifically designed immunogens. Here, we compared the abilities of three such germline-targeting immunogens against the VRC01-class receptors to activate the targeted B cells in transgenic mice expressing the germline VH of the VRC01 antibody but diverse mouse light chains. Immunogen-specific VRC01-like B cells were isolated at different time points after immunization, their VH and VL genes were sequenced, and the corresponding antibodies characterized.

Overcoming Steric Restrictions of VRC01 HIV-1 Neutralizing Antibodies through Immunization.

Broadly HIV-1 neutralizing VRC01 class antibodies target the CD4-binding site of Env. They are derived from VH1-202 antibody heavy chains paired with rare light chains expressing 5-amino acid-long CDRL3s. They have been isolated from infected subjects but have not yet been elicited by immunization.

Risk of readmission for injury in patients with epilepsy in the United States - A population-based study.

Objective: The objective of this study was to determine the 30-day injury readmission risk among persons with epilepsy vs. without epilepsy using a nationally representative US database. Secondary objectives were to examine the factors associated with injury-related readmissions among those with epilepsy and identify specific causes of readmissions within 30 days of index admission.

Stoichiometric Analyses of Soluble CD4 to Native-like HIV-1 Envelope by Single-Molecule Fluorescence Spectroscopy.

Analyses of HIV-1 envelope (Env) binding to CD4, and the conformational changes the interactions induce, inform the molecular mechanisms and factors governing HIV-1 infection. To address these questions, we used a single-molecule detection (SMD) approach to study the nature of reactions between soluble CD4 (sCD4) and soluble HIV-1 trimers. SMD of these reactions distinguished a mixture of one, two, or three CD4-bound trimer species.

Drosophila CRY Entrains Clocks in Body Tissues to Light and Maintains Passive Membrane Properties in a Non-clock Body Tissue Independent of Light.

Circadian (∼24 hr) clocks regulate daily rhythms in physiology, metabolism, and behavior via cell-autonomous transcriptional feedback loops. In Drosophila, the blue-light photoreceptor CRYPTOCHROME (CRY) synchronizes these feedback loops to light:dark cycles by binding to and degrading TIMELESS (TIM) protein. CRY also acts independently of TIM in Drosophila to alter potassium channel conductance in arousal neurons after light exposure, and in many animals CRY acts independently of light to repress rhythmic transcription.

An RNAi Screen To Identify Protein Phosphatases That Function Within the Drosophila Circadian Clock.

Circadian clocks in eukaryotes keep time via cell-autonomous transcriptional feedback loops. A well-characterized example of such a transcriptional feedback loop is in Drosophila, where CLOCK-CYCLE (CLK-CYC) complexes activate transcription of period (per) and timeless (tim) genes, rising levels of PER-TIM complexes feed-back to repress CLK-CYC activity, and degradation of PER and TIM permits the next cycle of CLK-CYC transcription. The timing of CLK-CYC activation and PER-TIM repression is regulated posttranslationally, in part through rhythmic phosphorylation of CLK, PER, and TIM.

The Drosophila Receptor Protein Tyrosine Phosphatase LAR Is Required for Development of Circadian Pacemaker Neuron Processes That Support Rhythmic Activity in Constant Darkness But Not during Light/Dark Cycles.

Unlabelled: InDrosophila, a transcriptional feedback loop that is activated by CLOCK-CYCLE (CLK-CYC) complexes and repressed by PERIOD-TIMELESS (PER-TIM) complexes keeps circadian time. The timing of CLK-CYC activation and PER-TIM repression is regulated post-translationally, in part through rhythmic phosphorylation of CLK, PER, and TIM. Although kinases that control PER, TIM, and CLK levels, activity, and/or subcellular localization have been identified, less is known about phosphatases that control clock protein dephosphorylation.

Comparative clinical evaluation of glycosylated haemoglobin level in healthy and chronic periodontitis patients: A chairside diagnostic method.

Objective And Background: Glycosylated haemoglobin (HbA1c) level can consequently be interpreted as an average of the blood glucose present over the past 3-4 months. Periodontitis is associated with glycemic control in patients with diabetes. The purpose of this study was to determine the level of HbA1c in healthy and periodontitis patients who were previously not diagnosed with diabetes mellitus.

The clinical efficacy of laser assisted modified Widman flap: A randomized split mouth clinical trial.

Objective: The objective of the study was to compare the clinical efficacy of use of a diode laser (DL) (810 nm) as an adjunct to modified Widman flap (MWF) surgery to that of MWF alone.

Materials And Methods: Twenty-five patients between the ages of 20 and 50 years with generalized chronic periodontitis were selected for the study. Control sites (Group A) were randomly selected to receive an MWF, and the contralateral test sites (Group B) received MWF in conjunction with low-level laser therapy.

Closure of chronic non healing ankle ulcer with low level laser therapy in a patient presenting with thalassemia intermedia: Case report.

In this single case study, the possible effect of low-level laser therapy (LLLT) was explored in the form of light emitting diodes on a chronic non-healing wound of 6 months duration in an 18-year-old male patient suffering from thalassemia intermedia. After irradiation, with LLLT dosage of 17.3 J/cm(2) for 8 min for 2 weeks duration followed by proliferative dosage of 8.

Novel restriction enzyme SSiI for the detection of mutation in GyrA gene of Salmonella enterica serovar Typhi.

Aim: Enteric fever is an ongoing problem in the developing nations. Resistance and reduced susceptibility to ciprofloxacin narrows the therapeutic options in enteric fever. The present study was carried out with the objective of determining molecular basis of resistance to fluoroquinolone among the clinical isolates of Salmonella enterica serovar Typhi from different parts of India.

Prevalence of extended-spectrum beta-lactamases among Escherichia coli and Klebsiella pneumoniae isolates in a tertiary care hospital.

Extended-spectrum beta-lactamases (ESBLs) continue to be a major problem in clinical setups the world over, conferring resistance to the expanded-spectrum cephalosporins. Knowledge about their prevalence is essential to guide towards appropriate antibiotic treatment. The aim of the present study is to determine the prevalence of ESBL producers among Escherichia coli and Klebsiella pneumoniae isolates at a tertiary care institution.