Lipid trajectories improve risk models for Alzheimer's disease and mild cognitive impairment.

In this retrospective, case-control study, we tested the hypothesis that blood-lipid concentrations during the decade prior to cognitive symptom onset can inform risk prediction for Alzheimer's disease (AD) and stable mild cognitive impairment (MCI). Clinically well-characterized cases were diagnosed using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria; MCI cases had been stable for ≥5 years; and controls were propensity matched to cases at symptom onset (MCI: 116 cases, 435 controls; AD: 215 cases, 483 controls). Participants were grouped based on (i) longitudinal trajectories and (ii) quintile of variability independent of the mean (VIM) for total cholesterol, HDL-C, low-density lipoprotein cholesterol, non-HDL-C, and ln(triglycerides).

An Integrative Migraine Polygenic Risk Score Is Associated with Age at Onset But Not Chronification.

: Genome-wide association studies (GWASs) demonstrate a complex genetic landscape for migraine risk. Migraine polygenic risk scores (PRSs) developed from GWAS data may have utility for predicting disease course. We analyzed the strength of association between an integrative migraine PRS and age at onset and chronification.

Gross morphology and adhesion-associated physical properties of Drosophila larval salivary gland glue secretion.

One of the major functions of the larval salivary glands (SGs) of many Drosophila species is to produce a massive secretion during puparium formation. This so-called proteinaceous glue is exocytosed into the centrally located lumen, and subsequently expectorated, serving as an adhesive to attach the puparial case to a solid substrate during metamorphosis. Although this was first described almost 70 years ago, a detailed description of the morphology and mechanical properties of the glue is largely missing.

Characteristics associated with response to subcutaneously administered anti-CGRP monoclonal antibody medications in a real-world community cohort of persons living with migraine: A retrospective clinical and genetic study.

Objective: To evaluate response to anti-calcitonin gene-related peptide (CGRP) migraine preventives in a real-world community cohort of persons living with migraine and to identify clinical and genetic characteristics associated with efficacious response.

Background: Erenumab-aooeb, fremanezumab-vrfm, and galcanezumab-gnlm target CGRP or its receptor; however, many patients are non-responsive.

Methods: In this retrospective clinical and genetic study, we identified 1077 adult patients who satisfied the International Classification of Headache Disorders, 3rd edition, criteria for migraine without aura, migraine with aura, or chronic migraine and who were prescribed an anti-CGRP migraine preventive between May 2018 and May 2021.

Multifactorial assessment of Parkinson's disease course and outcomes using trajectory modeling in a multiethnic, multisite cohort - extension of the LONG-PD study.

Background: The severity, progression, and outcomes of motor and non-motor symptoms in Parkinson's disease (PD) are quite variable. Following PD cohorts holds promise for identifying predictors of disease severity and progression.

Methods: PD patients ( = 871) were enrolled at five sites.

Apocrine secretion in the salivary glands of and other dipterans is evolutionarily conserved.

Apocrine secretion is a transport and secretory mechanism that remains only partially characterized, even though it is evolutionarily conserved among all metazoans, including humans. The excellent genetic model organism holds promise for elucidating the molecular mechanisms regulating this fundamental metazoan process. Two prerequisites for such investigations are to clearly define an experimental system to investigate apocrine secretion and to understand the evolutionarily and functional contexts in which apocrine secretion arose in that system.

Quantitative Electroencephalography as a Biomarker for Cognitive Dysfunction in Parkinson's Disease.

Quantitative electroencephalography (qEEG) has been suggested as a biomarker for cognitive decline in Parkinson's disease (PD). Determine if applying a wavelet-based qEEG algorithm to 21-electrode, resting-state EEG recordings obtained in a routine clinical setting has utility for predicting cognitive impairment in PD. PD subjects, evaluated by disease stage and motor score, were compared to healthy controls ( = 20 each).

An apocrine mechanism delivers a fully immunocompetent exocrine secretion.

Apocrine secretion is a recently discovered widespread non-canonical and non-vesicular secretory mechanism whose regulation and purpose is only partly defined. Here, we demonstrate that apocrine secretion in the prepupal salivary glands (SGs) of Drosophila provides the sole source of immune-competent and defense-response proteins to the exuvial fluid that lies between the metamorphosing pupae and its pupal case. Genetic ablation of its delivery from the prepupal SGs to the exuvial fluid decreases the survival of pupae to microbial challenges, and the isolated apocrine secretion has strong antimicrobial effects in "agar-plate" tests.

Variable Effects of PD-Risk Associated SNPs and Variants in Parkinsonism-Associated Genes on Disease Phenotype in a Community-Based Cohort.

Genetic risk factors for Parkinson's disease (PD) risk and progression have been identified from genome-wide association studies (GWAS), as well as studies of familial forms of PD, implicating common variants at more than 90 loci and pathogenic or likely pathogenic variants at 16 loci. With the goal of understanding whether genetic variants at these PD-risk loci/genes differentially contribute to individual clinical phenotypic characteristics of PD, we used structured clinical documentation tools within the electronic medical record in an effort to provide a standardized and detailed clinical phenotypic characterization at the point of care in a cohort of 856 PD patients. We analyzed common SNPs identified in previous GWAS studies, as well as low-frequency and rare variants at parkinsonism-associated genes in the MDSgene database for their association with individual clinical characteristics and test scores at baseline assessment in our community-based PD patient cohort: age at onset, disease duration, Unified Parkinson's Disease Rating Scale I-VI, cognitive status, initial and baseline motor and non-motor symptoms, complications of levodopa therapy, comorbidities and family history of neurological disease with one or more than one affected family members.

Olfactory Dysfunction in Familial and Sporadic Parkinson's Disease.

This minireview discusses our current understanding of the olfactory dysfunction that is frequently observed in sporadic and familial forms of Parkinson's disease and parkinsonian syndromes. We review the salient characteristics of olfactory dysfunction in these conditions, discussing its prevalence and characteristics, how neuronal processes and circuits are altered in Parkinson's disease, and what is assessed by clinically used measures of olfactory function. We highlight how studies of monogenic Parkinson's disease and investigations in ethnically diverse populations have contributed to understanding the mechanisms underlying olfactory dysfunction.

Cognitive processes that indirectly affect olfactory dysfunction in Parkinson's disease.

Introduction: Accurate early diagnosis of Parkinson's disease is hampered by its long prodromal period and the variable manifestations of its motor symptoms. While olfactory dysfunction can occur before motor-symptom onset and serve as a non-disease-specific diagnostic aid, its underlying causes are incompletely understood.

Methods: Correlation analyses, univariate density estimates, ANOVA and regression evaluated relationships between scores on the Montreal Cognitive Assessment and Hopkins Verbal Learning Test and those on the University of Pennsylvania Smell Identification Test in 1280 Parkinson's Progression Markers Initiative subjects placed into five diagnostic categories.

Two-Dimensional Correlation Spectroscopy (2D-COS) Studies of Solution Mixtures in the Low Frequency Raman Region.

Raman spectra of a series of binary solution mixtures, including chloroform (CHCl), ethanol (EtOH), and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), were analyzed using the two-dimensional correlation spectroscopic (2D-COS) technique in the low frequency region. Numerous asynchronous cross-peaks ubiquitously appeared in the concentration-dependent Raman spectra of these organic solvent mixtures. The result clearly demonstrated a deviation from ideal solution behavior, reflecting the presence of specific molecular interactions causing a subtle nonlinear spectral intensity response of Raman bands to the concentration changes.

Engineering Efficient Photon Upconversion in Semiconductor Heterostructures.

Photon upconversion is a photophysical process in which two low-energy photons are converted into one high-energy photon. Photon upconversion has broad appeal for a range of applications from biomedical imaging and targeted drug release to solar energy harvesting. Current upconversion nanosystems, including lanthanide-doped nanocrystals and triplet-triplet annihilation molecules, have achieved upconversion quantum yields on the order of 10-30%.

Unique Surface Enhanced Raman Scattering Substrate for the Study of Arsenic Speciation and Detection.

In this study, a three-dimensional surface enhanced Raman scattering (SERS) substrate comprised of silver coated gold nanorods (Ag/AuNRs) decorated on electrospun polycaprolactone (PCL) fibers has been applied,  for the first time, to quantitative analytical measurements on various arsenic species: p-arsanilic acid ( pAsA), roxarsone (Rox), and arsenate (As), with a demonstrated sensitivity below 5 ppb. As detection in a solution of common salt ions has been demonstrated, showing the tolerance of the substrate to more complex environments. pAsA adsorption behavior on the substrate surface has been investigated in detail using these unique SERS substrates.

Endosomal vacuoles of the prepupal salivary glands of Drosophila play an essential role in the metabolic reallocation of iron.

In the recent past, we demonstrated that a great deal is going on in the salivary glands of Drosophila in the interval after they release their glycoprotein-rich secretory glue during pupariation. The early-to-mid prepupal salivary glands undergo extensive endocytosis with widespread vacuolation of the cytoplasm followed by massive apocrine secretion. Here, we describe additional novel properties of these endosomes.

Two-Dimensional Raman Correlation Spectroscopy Study of Poly[(R)-3-hydroxybutyrate- co-(R)-3-hydroxyhexanoate] Copolymers.

Two-dimensional correlation analysis was applied to the time-dependent evolution of Raman spectra during the isothermal crystallization of bioplastic, poly[(R)-3-hydroxybutyrate- co-(R)-3-hydroxyhexanoate] or PHBHx copolymer. Simultaneous Raman measurement of both carbonyl stretching and low-frequency crystalline lattice mode regions made it possible to carry out the highly informative hetero-mode correlation analysis. The crystallization process of PHBHx involves: (1) the early nucleation stage; (2) the primary growth of well-ordered crystals of PHBHx; and (3) the secondary crystal growth phase.

Observation of Intermolecular Hydrogen Bonding Interactions in Biosynthesized and Biodegradable Poly [(R)-3-hydroxybutyrate- co-(R)-3-hydroxyhexanoate] in Chloroform and 1,1,1,3,3,3-Hexafluoro-2-propanol (HFIP).

In this work, we describe polymer-solvent interactions in biosynthesized and biodegradable poly[(R)-3-hydroxybutyrate- co-(R)-3-hydroxyhexanoate] (PHBHx) and the atactic homopolymer, poly(3-hydroxybutyrate) (a-PHB), which were studied both as neat polymers and in solutions of chloroform and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP). Specifically, infrared frequency shifts of the carbonyl band were observed in semi-crystalline PHBHx, but not in a-PHB, because it cannot form the helical conformation required for crystallization. The carbonyl band of PHBHx exhibited the high frequency associated with amorphous structure in chloroform and the lower frequency traditionally attributed to the helical crystalline structure in HFIP.

Artifact Correction in Temperature-Dependent Attenuated Total Reflection Infrared (ATR-IR) Spectra.

A spectral processing method was developed and tested for analyzing temperature-dependent attenuated total reflection infrared (ATR-IR) spectra of aliphatic polyesters. Spectra of a bio-based, biodegradable polymer, 3.9 mol% 3HHx poly[(R)-3-hydroxybutyrate- co-(R)-3-hydroxyhexanoate] (PHBHx), were analyzed and corrected prior to analysis using two-dimensional correlation spectroscopy (2D-COS).

Assessment of Olfactory Function in MAPT-Associated Neurodegenerative Disease Reveals Odor-Identification Irreproducibility as a Non-Disease-Specific, General Characteristic of Olfactory Dysfunction.

Olfactory dysfunction is associated with normal aging, multiple neurodegenerative disorders, including Parkinson's disease, Lewy body disease and Alzheimer's disease, and other diseases such as diabetes, sleep apnea and the autoimmune disease myasthenia gravis. The wide spectrum of neurodegenerative disorders associated with olfactory dysfunction suggests different, potentially overlapping, underlying pathophysiologies. Studying olfactory dysfunction in presymptomatic carriers of mutations known to cause familial parkinsonism provides unique opportunities to understand the role of genetic factors, delineate the salient characteristics of the onset of olfactory dysfunction, and understand when it starts relative to motor and cognitive symptoms.

Massive excretion of calcium oxalate from late prepupal salivary glands of Drosophila melanogaster demonstrates active nephridial-like anion transport.

The Drosophila salivary glands (SGs) were well known for the puffing patterns of their polytene chromosomes and so became a tissue of choice to study sequential gene activation by the steroid hormone ecdysone. One well-documented function of these glands is to produce a secretory glue, which is released during pupariation to fix the freshly formed puparia to the substrate. Over the past two decades SGs have been used to address specific aspects of developmentally-regulated programmed cell death (PCD) as it was thought that they are doomed for histolysis and after pupariation are just awaiting their fate.

Selective and Quantitative Detection of Trace Amounts of Mercury(II) Ion (Hg²⁺) and Copper(II) Ion (Cu²⁺) Using Surface-Enhanced Raman Scattering (SERS).

We report the development of a surface-enhanced Raman scattering (SERS)-based heavy metal ion sensor targeting the detection of mercury(II) ion (Hg(2+)) and copper(II) ion (Cu(2+)) with high sensitivity and selectivity. To achieve the detection of vibrational-spectroscopically silent heavy metal ions, the SERS substrate composed of gold nanorod (AuNR)-polycaprolactone (PCL) nanocomposite fibers was first functionalized using metal ion-binding ligands. Specifically, 2,5-dimercapto-1,3,4-thiadiazole dimer (di-DMT) and trimercaptotriazine (TMT) were attached to the SERS substrates serving as bridging molecules to capture Hg(2+) and Cu(2+), respectively, from solution.

Vacuole dynamics in the salivary glands of Drosophila melanogaster during prepupal development.

A central function of the Drosophila salivary glands (SGs), historically known for their polytene chromosomes, is to produce and then release during pupariation the secretory glue used to affix a newly formed puparium to a substrate. This essential event in the life history of Drosophila is regulated by the steroid hormone ecdysone in the late-larval period. Ecdysone triggers a cascade of sequential gene activation that leads to glue secretion and initiates the developmentally-regulated programmed cell death (PCD) of the larval salivary glands, which culminates 16 h after puparium formation (APF).