In Vitro Screening to Identify Anti-Toxoplasma Compounds and In Silico Modeling for Bioactivities and Toxicity.
In this study, we screened 62 compounds comprising natural products (NPs) and FDA-approved (FDA) drugs, to identify the hit compounds that suppress the growth of T. gondii. To determine the parasite inhibitory potential of the compounds, host mammalian cells were infected with a transgenic T. gondii strain, and the viability of the parasite was evaluated by luminescence. Of the 62 compounds, tubericidin, sulfuretin, peruvoside, resveratrol, narasin and diacetoxyscirpenol of the natural product isolates, as well as bortezonib, 10-Hydroxycamtothecin, mebendazole, niflumic acid, clindamycin HCl, mecamylamine, chloroquine, mit...
Source: The Yale Journal of Biology and Medicine - September 24, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

The Short N-Terminal Repeats of Transcription Termination Factor 1 Contain Semi-Redundant Nucleolar Localization Signals and P19-ARF Tumor Suppressor Binding Sites.
Authors: Boutin J, Lessard F, Tremblay MG, Moss T Abstract The p14/p19ARF (ARF) tumor suppressor provides an important link in the activation of p53 (TP53) by inhibiting its targeted degradation via the E3 ligases MDM2/HDM2. However, ARF also limits tumor growth by directly inhibiting ribosomal RNA synthesis and processing. Initial studies of the ARF tumor suppressor were compounded by overlap between the INK4A and ARF genes encoded by the CDKN2A locus, but mouse models of pure ARF-loss and its inactivation in human cancers identified it as a distinct tumor suppressor even in the absence of p53. We previously demon...
Source: The Yale Journal of Biology and Medicine - September 24, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Actin Waves and Dynamic Patterning of the Plasma Membrane.
Authors: Gerisch G, Prassler J, Butterfield N, Ecke M Abstract Plasma membrane and underlying actin network are connected to a functional unit that by non-linear interactions is capable of forming patterns. For instance, in cell motility and chemotaxis, cells polarize to form a protruding front and a retracting tail. Here we address dynamic patterns that are formed on a planar substrate surface and are therefore easily accessible to optical recording. In these patterns two distinct areas of the membrane and actin cortex are interconverted at the site of circular actin waves. The inner territory circumscribed by a w...
Source: The Yale Journal of Biology and Medicine - September 24, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Identifying Specific Subcellular Organelle Damage by Photosensitized Oxidations.
Authors: Tsubone TM, Martins WK, Baptista MS Abstract The search for conditions that maximize the outcome of Photodynamic Therapy (PDT) continues. Recent data indicate that PDT-induced cell death depends more on the specific intracellular location of the photosensitizer (PS) than on any other parameter. Indeed, knowledge of the PS intracellular location allows the establishment of clear relationships between the mechanism of cell death and the PDT efficacy. In order to determine the intracellular localization sites of a given PS, classical co-localization protocols, which are based in the comparison of the emissive...
Source: The Yale Journal of Biology and Medicine - September 24, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Divide et Impera: Drp1-mediated Mitochondrial Fission in Glioma Malignancy.
Authors: Eugenio-Pérez D, Briones-Herrera A, Martínez-Klimova E, Pedraza-Chaverri J Abstract Mitochondria are pivotal organelles involved in vital cellular functions, including energy generation, reactive oxygen species and calcium signaling, as well as intermediate biosynthesis. They are dynamic organelles that adapt their shape, size, and distribution to changes in intracellular conditions, being able to divide, fuse, or move along the cell, processes known as mitochondrial dynamics. Mitochondrial dynamics are involved in cell division and migration, as well as maintenance of pluripotency in stem (n...
Source: The Yale Journal of Biology and Medicine - September 24, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Lipid Droplets and the Management of Cellular Stress.
Authors: Jarc E, Petan T Abstract Lipid droplets are cytosolic fat storage organelles present in most eukaryotic cells. Long regarded merely as inert fat reservoirs, they are now emerging as major regulators of cellular metabolism. They act as hubs that coordinate the pathways of lipid uptake, distribution, storage, and use in the cell. Recent studies have revealed that they are also essential components of the cellular stress response. One of the hallmark characteristics of lipid droplets is their capacity to buffer excess lipids and to finely tune their subsequent release based on specific cellular requirements. ...
Source: The Yale Journal of Biology and Medicine - September 24, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

GLUT4 Storage Vesicles: Specialized Organelles for Regulated Trafficking.
Authors: Li DT, Habtemichael EN, Julca O, Sales CI, Westergaard XO, DeVries SG, Ruiz D, Sayal B, Bogan JS Abstract Fat and muscle cells contain a specialized, intracellular organelle known as the GLUT4 storage vesicle (GSV). Insulin stimulation mobilizes GSVs, so that these vesicles fuse at the cell surface and insert GLUT4 glucose transporters into the plasma membrane. This example is likely one instance of a broader paradigm for regulated, non-secretory exocytosis, in which intracellular vesicles are translocated in response to diverse extracellular stimuli. GSVs have been studied extensively, yet these vesicles ...
Source: The Yale Journal of Biology and Medicine - September 24, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Primary Cilium, An Unsung Hero in Maintaining Functional β-cell Population.
Primary Cilium, An Unsung Hero in Maintaining Functional β-cell Population. Yale J Biol Med. 2019 Sep;92(3):471-480 Authors: Lodh S Abstract A primary challenge in type 2 diabetes (T2D) is the preservation of a functional population of β-cells, which play a central role in regulating blood glucose levels. Two congenital disorders, Bardet-Biedl syndrome (BBS) and Alström syndrome (ALMS), can serve as useful models to understand how β-cells are normally produced and regenerated. Both are characterized by obesity, loss of β-cells, and defects in primary cilia - the sensory center ...
Source: The Yale Journal of Biology and Medicine - September 24, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Inflammasomes in Colitis and Colorectal Cancer: Mechanism of Action and Therapies.
Authors: Pandey A, Shen C, Man SM Abstract Colorectal cancer is a multifactorial disease and a leading cause of cancer-related deaths worldwide. Inflammation is a driver across multiple stages in the development of colorectal cancer. The inflammasome is a cytosolic multiprotein complex of the innate immune system central to the regulation of inflammation, pyroptosis, and other cellular processes important for maintaining gut homeostasis. Studies using mouse models of colitis and colitis-associated colorectal cancer have highlighted diverse and sometimes contrasting roles of inflammasomes in maintaining a balance be...
Source: The Yale Journal of Biology and Medicine - September 24, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Sustaining Life: Maintaining Chloroplasts and Mitochondria and their Genomes in Plants.
Authors: Rose RJ Abstract Chloroplasts (members of the plastid family) and mitochondria are central to the energy cycles of ecosystems and the biosphere. They both contain DNA, organized into nucleoids, coding for critical genes for photosynthetic and respiratory energy production. This review updates the cellular and molecular biology of how chloroplasts, mitochondria, and their genomes in Angiosperms are maintained; particularly in leaf development and maternal inheritance. Maternal inheritance is the common form of transmission to the next generation. Both organelles cannot be derived de novo. Proplastids during...
Source: The Yale Journal of Biology and Medicine - September 24, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

The Leishmania Parasitophorous Vacuole Membrane at the Parasite-Host Interface.
Authors: Young J, Kima PE Abstract The Leishmania parasitophorous vacuole membrane (LPVM) sits at the interface of the parasite and its host. Evidence shows that molecules from the endocytic pathway as well as molecules from the secretory pathway are localized in the LPV and displayed on LPVM. In the review, we discuss our current understanding of the composition of the LPVM. PMID: 31543712 [PubMed - in process] (Source: The Yale Journal of Biology and Medicine)
Source: The Yale Journal of Biology and Medicine - September 24, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Phosphorylation of OXPHOS Machinery Subunits: Functional Implications in Cell Biology and Disease.
Authors: Castellanos E, Lanning NJ Abstract The complexes of the electron transport chain and ATP synthase comprise the oxidative phosphorylation (OXPHOS) system. The reactions of OXPHOS generate the mitochondrial membrane potential, drive the majority of ATP production in respiring cells, and contribute significantly to cellular reactive oxygen species (ROS). Regulation of OXPHOS is therefore critical to maintain cellular homeostasis. OXPHOS machinery subunits have been found to be highly phosphorylated, implicating this post-translational modification as a means whereby OXPHOS is regulated. Multiple lines of evid...
Source: The Yale Journal of Biology and Medicine - September 24, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Role of Mitochondrial Markers in Improved Detection and Risk-Stratification in Barrett's Esophagus Patients.
Authors: Grewal US, Randhawa MS, Mehta A Abstract Barrett's esophagus (BE) is the only known precursor of esophageal adenocarcinoma (EAC) and is amenable to treatment. However, more than 90 percent of EAC patients are never diagnosed with antecedent BE. Identification of molecular markers for BE is needed to improve detection of BE through efficient non-endoscopic methods that are cost-effective, sensitive and can be used to cater to a larger group of the population at risk. Alterations in mitochondria and mitochondrial DNA have been shown to be associated with various cancers, including esophageal cancer. Mitochon...
Source: The Yale Journal of Biology and Medicine - September 24, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Chromosome Territorial Organization Drives Efficient Protein Complex Formation: A Hypothesis.
Authors: Bera M, Kalyana Sundaram RV Abstract In eukaryotes, chromosomes often form a transcriptional kissing loop during interphase. We propose that these kissing loops facilitate the formation of protein complexes. mRNA transcripts from these loops could cluster together into phase-separated nuclear granules. Their export into the ER could be ensured by guided diffusion through the inter-chromatin space followed by association with nuclear baskets and export factors. Inside the ER, these mRNAs would form a translation hub. Juxtaposed translation of these mRNAs would increase the cis/trans protein complex assembly...
Source: The Yale Journal of Biology and Medicine - September 24, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Mycobacterial Membrane Domain, or a Primordial Organelle?
Authors: Hayashi JM, Morita YS Abstract Mycobacteria, like many other prokaryotic organisms, do not appear to have membrane-bound organelles to organize the subcellular space. Nevertheless, mycobacteria and related bacteria grow their cell envelope in a spatially controlled manner, restricting cell elongation to the polar regions of the rod-shaped cell. This spatial organization demands that de novo synthesized cell envelope components must be supplied to the polar ends of the cell. Because many cell envelope components are either lipids or built as lipid-anchored precursors, the plasma membrane is the major site o...
Source: The Yale Journal of Biology and Medicine - September 24, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Uncovering the Starr of the Cell - SUN and KASH Proteins: An Interview with Daniel A. Starr, PhD.
Authors: Bacher SZ PMID: 31543717 [PubMed - in process] (Source: The Yale Journal of Biology and Medicine)
Source: The Yale Journal of Biology and Medicine - September 24, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Insights from Algae on Engineering High Efficiency Plants: An Interview with Martin Jonikas, PhD.
Authors: Bai H, Gonzalez IJ PMID: 31543718 [PubMed - in process] (Source: The Yale Journal of Biology and Medicine)
Source: The Yale Journal of Biology and Medicine - September 24, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Sorting and Trafficking in the Endo-Lysosomal System: An Interview with Chris Burd, PhD.
Authors: Qiu J PMID: 31543719 [PubMed - in process] (Source: The Yale Journal of Biology and Medicine)
Source: The Yale Journal of Biology and Medicine - September 24, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Diabetes Alters Diurnal Rhythm of Electroretinogram in db/db Mice.
In conclusion, our studies provide novel insights into the pathogenic mechanism of DR by showing an altered circadian rhythm of the ERG. PMID: 31249476 [PubMed - in process] (Source: The Yale Journal of Biology and Medicine)
Source: The Yale Journal of Biology and Medicine - July 1, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

What is Phase in Cellular Clocks?
Authors: Caranica C, Cheong JH, Qiu X, Krach EK, Deng Z, Mao L, Schüttler HB, Arnold J Abstract Four inter-related measures of phase are described to study the phase synchronization of cellular oscillators, and computation of these measures is described and illustrated on single cell fluorescence data from the model filamentous fungus, Neurospora crassa. One of these four measures is the phase shift ϕ in a sinusoid of the form x(t) = A(cos(ωt + ϕ), where t is time. The other measures arise by creating a replica of the periodic process x(t) called the Hilbert transform x̃(t), which is 90 degrees out of...
Source: The Yale Journal of Biology and Medicine - July 1, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Chronotype Variability and Patterns of Light Exposure of a Large Cohort of United States Residents.
Authors: Refinetti R Abstract Chronotype (i.e., disposition for activity early or late in the day) has traditionally been measured with questionnaires. A few studies with small sample sizes have also been conducted using actigraphy devices. In the present study, analysis was conducted of the daily pattern of activity of 1887 United States residents who wore actigraphy devices for a whole week. The devices also recorded the participants' exposure to light. As determined by cosinor analysis, the mean pattern of ambulatory activity exhibited robust 24-hour oscillation with a peak at 14:48. On average, participants wen...
Source: The Yale Journal of Biology and Medicine - July 1, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Exceptional Entrainment of Circadian Activity Rhythms With Manipulations of Rhythm Waveform in Male Syrian Hamsters.
Authors: Gorman MR, Elliott JA Abstract The activity/rest rhythm of mammals reflects the output of an endogenous circadian oscillator entrained to the solar day by light. Despite detailed understanding of the neural and molecular bases of mammalian rhythms, we still lack practical tools for achieving rapid and flexible adjustment of clocks to accommodate shift-work, trans-meridian jet travel, or space exploration. Efforts to adapt clocks have focused on resetting the phase of an otherwise unaltered circadian clock. Departing from this tradition, recent work has demonstrated that bifurcation of circadian waveform in...
Source: The Yale Journal of Biology and Medicine - July 1, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Refractory Insomnia in an Adolescent with Total Blindness.
We present a totally blind adolescent with refractory insomnia due to a combination of Non-24 hour sleep-wake disorder and restless leg syndrome that was successfully treated with tasimelteon, iron replacement, and gabapentin. To our knowledge, this is the first published report of treatment of N24 with tasimelteon in an adolescent. In addition, this case highlights the importance of recognizing and treating multifactorial causes of insomnia. PMID: 31249480 [PubMed - in process] (Source: The Yale Journal of Biology and Medicine)
Source: The Yale Journal of Biology and Medicine - July 1, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Actigraphy-based Sleep Parameters and Rest-activity Circadian Rhythm in a Young Scoliotic Patient Treated with Rigid Bracing: A Case Study.
Authors: Vitale JA, Negrini F, Rebagliati G, Giacomelli L, Donzelli S, Banfi G Abstract The correct expression of circadian rhythmicity, together with a good sleep behavior, are key factors for the body homeostasis. Rest-activity circadian rhythms (RARs) are involved in the control of the sleep-wake cycle and altered RARs could lead to a compromised health status. Therefore, we aimed to investigate the existence of RAR and to study actigraphy-based sleep behavior in a 14-year-old male patient affected by severe idiopathic scoliosis and treated with a rigid brace 23 hours per day. RAR and sleep parameters were studi...
Source: The Yale Journal of Biology and Medicine - July 1, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

A Rhythmic Gene Entrained to Midnight May Regulate Photoperiod-Controlled Flowering in Arabidopsis.
Authors: Yeang HY Abstract The widely held explanation for photoperiod-controlled flowering in long-day plants is largely embodied in the External Coincidence Hypothesis which posits that flowering is induced when activity of a rhythmic gene that regulates it (a putative "flowering gene") occurs in the presence of light. Nevertheless, re-examination of the Arabidopsis flowering data from non 24-hour cycles of Roden et al. suggests that External Coincidence is not tenable if the circadian rhythm of the "flowering gene" were entrained to sunrise as commonly accepted. On the other hand, the hypothe...
Source: The Yale Journal of Biology and Medicine - July 1, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Time is on the Immune System's Side, Yes it is.
Authors: Abele SH, Meadows KE, Medeiros D, Silver AC Abstract From bacteria to mammals, nearly all organisms have adapted their physiology and behavior to a daily rhythm. These circadian (daily) rhythms influence virtually all aspects of physiological architecture (i.e., from gene expression to organismal behavior). Therefore, it is not surprising that several features of the immune response are regulated in a time-of-day dependent manner. The field of chrono-immunology has expanded tremendously over the past decade. In this abridged review, we present studies from the past five years that have revealed new paramet...
Source: The Yale Journal of Biology and Medicine - July 1, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Retinal Circadian Clocks are Major Players in the Modulation of Retinal Functions and Photoreceptor Viability.
Authors: DeVera C, Baba K, Tosini G Abstract Circadian rhythms control many biochemical and physiological functions within the body of an organism. These circadian rhythms are generated by a molecular clock that is located in almost every cell of the body. Accumulating data indicate that dysfunction of the circadian clock negatively affects the health status of the tissue in which the circadian clock has been disabled. The eye also contains a complex circadian system that regulates many important functions such as the processing of light information, the release of neurotransmitters, and phagocytic activity by the ...
Source: The Yale Journal of Biology and Medicine - July 1, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Protein Kinases in the Photic Signaling of the Mammalian Circadian Clock.
Authors: Alessandro MS, Golombek DA, Chiesa JJ Abstract Circadian clocks drive biological rhythms in physiology and behavior, providing a selective advantage by enabling organisms to synchronize to the 24 h environmental day. This process depends on light-dark transitions as the main signal that shifts the phase of the clock. In mammals, the light input reaches the master circadian clock in the hypothalamic suprachiasmatic nucleus through glutamatergic afferents from the retina, resulting in phase-shifts of the overt rhythms which depend on the time of the day at which light is applied, leading to changes in the ac...
Source: The Yale Journal of Biology and Medicine - July 1, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Effects of BMAL1 Manipulation on the Brain's Master Circadian Clock and Behavior.
Authors: Haque SN, Booreddy SR, Welsh DK Abstract Bmal1 is the only single circadian clock gene that is essential for rhythmic gene expression in the mammalian circadian timing system. Genetic approaches targeting Bmal1 expression have been used to further assess its role in the circadian clock and to test for behavioral effects of clock disruption. In particular, disruptions in circadian clock function have been implicated in human mood disorders, and clock gene manipulation in mice may provide valuable models for studying depression-like behavior. In this review, we explore various approaches to manipulating Bmal...
Source: The Yale Journal of Biology and Medicine - July 1, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Evidence for Internal Desynchrony Caused by Circadian Clock Resetting.
Authors: Nicholls SK, Casiraghi LP, Wang W, Weber ET, Harrington ME Abstract Circadian disruption has been linked to markers for poor health outcomes in humans and animal models. What is it about circadian disruption that is problematic? One hypothesis is that phase resetting of the circadian system, which occurs in response to changes in environmental timing cues, leads to internal desynchrony within the organism. Internal desynchrony is understood as acute changes in phase relationships between biological rhythms from different cell groups, tissues, or organs within the body. Do we have strong evidence for intern...
Source: The Yale Journal of Biology and Medicine - July 1, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Dopamine Signaling in Circadian Photoentrainment: Consequences of Desynchrony.
Authors: Grippo RM, Güler AD Abstract Circadian rhythms, or biological oscillations of approximately 24 hours, impact almost all aspects of our lives by regulating the sleep-wake cycle, hormone release, body temperature fluctuation, and timing of food consumption. The molecular machinery governing these rhythms is similar across organisms ranging from unicellular fungi to insects, rodents, and humans. Circadian entrainment, or temporal synchrony with one's environment, is essential for survival. In mammals, the central circadian pacemaker is located in the suprachiasmatic nucleus (SCN) of the hypothalamus and ...
Source: The Yale Journal of Biology and Medicine - July 1, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Old and New Roles and Evolving Complexities of Cardiovascular Clocks.
Authors: Xu Y, Pi W, Rudic RD Abstract The cardiovascular (CV) system has been established to be significantly influenced by the molecular components of circadian rhythm. Oscillations of circadian rhythm occur within the circulation to affect thrombosis and blood pressure and within CV tissues including arteries, heart, and kidney to control function. Physiologic and molecular oscillations of circadian rhythm have been well connected via global, tissue-specific, and transgenic reporter mouse models of key core clock signals such as Bmal1, Period, and Clock, which can produce both pathology and protection with their...
Source: The Yale Journal of Biology and Medicine - July 1, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Do Disruptions in the Circadian Timing System Contribute to Autonomic Dysfunction in Huntington's Disease?
Authors: Park S, Colwell CS Abstract Huntington's disease (HD) patients suffer from a progressive neurodegenerative disorder that inflicts both motor and non-motor symptoms. HD is caused by a CAG repeat expansion within the first exon of the huntingtin (HTT) gene that produces a polyglutamine repeat that leads to protein misfolding, soluble aggregates, and inclusion bodies detected throughout the body. Both clinical and preclinical research indicate that cardiovascular dysfunction should be considered a core symptom in at least a subset of HD patients. There is strong evidence for dysautonomia (dysfunctional autono...
Source: The Yale Journal of Biology and Medicine - July 1, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

It's About Time: Advances in Understanding the Circadian Regulation of DNA Damage and Repair in Carcinogenesis and Cancer Treatment Outcomes.
Authors: Ashok Kumar PV, Dakup PP, Sarkar S, Modasia JB, Motzner MS, Gaddameedhi S Abstract The circadian rhythm is established by a coordinated network of peripheral clocks interlocked and regulated by a central pacemaker. This network is maintained by the rhythmic expression of core clock genes, which in turn generate oscillatory expression patterns of different sets of target proteins in a tissue-specific manner. Precise regulation of biological processes driven by the body's circadian network in response to periodic changes in the environment determines healthy life. The delicate balance in the cycling of enzym...
Source: The Yale Journal of Biology and Medicine - July 1, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Chronodisruption, Metabolic Homeostasis, and the Regulation of Inflammation in Adipose Tissues.
Authors: Kolbe I, Oster H Abstract Molecular circadian clocks align daily behavioral and metabolic rhythms with the external day-night cycle. Priming energy metabolism for recurring changes on a 24-hour basis, these clocks are deeply interlinked with metabolic homeostasis and health. Circadian rhythm disruptions, as occurring in shift work or sleep disorders, are often accompanied by metabolic disturbances - from the promotion of overweight and type-2 diabetes to the development of the metabolic syndrome. An important indicator of the adverse outcomes of overweight seems to be a systemic low-grade inflammation whic...
Source: The Yale Journal of Biology and Medicine - July 1, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Peripheral Circadian Oscillators.
Authors: Brown AJ, Pendergast JS, Yamazaki S Abstract Circadian rhythms are ~24-hour cycles of physiology and behavior that are synchronized to environmental cycles, such as the light-dark cycle. During the 20th century, most research focused on establishing the fundamental properties of circadian rhythms and discovering circadian pacemakers that were believed to reside in the nervous system of animals. During this time, studies that suggested the existence of circadian oscillators in peripheral organs in mammals were largely dismissed. The discovery of a single-locus circadian pacemaker in the nervous system of se...
Source: The Yale Journal of Biology and Medicine - July 1, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Circadian Responses to Fragmented Light: Research Synopsis in Humans.
Authors: Fernandez F Abstract Light is the chief signal used by the human circadian pacemaker to maintain precise biological timekeeping. Though it has been historically assumed that light resets the pacemaker's rhythm in a dose-dependent fashion, a number of studies report enhanced circadian photosensitivity to the initial moments of light exposure, such that there are quickly diminishing returns on phase-shifting the longer the light is shown. In the current review, we summarize findings from a family of experiments conducted over two decades in the research wing of the Brigham and Women's Hospital that examined ...
Source: The Yale Journal of Biology and Medicine - July 1, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Time to Target Stroke: Examining the Circadian System in Stroke.
Authors: Stubblefield JJ, Lechleiter JD Abstract Stroke is the 5th leading cause of death in the United States and a leading cause of long-term disability. Ischemic strokes account for 87 percent of total stroke cases, yet the only FDA-approved treatments involve disruption of the blood clot to restore blood flow. New treatments aimed at saving or protecting neural tissue have largely failed in clinical trials and so new methodology or targets must be found. The occurrence of strokes significantly increases between 6 AM and 12 PM, implicating the circadian system in the onset of this debilitating brain injury. But ...
Source: The Yale Journal of Biology and Medicine - July 1, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

An Interdisciplinary Perspective on the Association Between Chronotype and Well-being.
Authors: Bullock B Abstract Individuals with a circadian preference for mental and physical activity later in the day ("Evening types") are consistently found to fare worse on most facets of well-being than individuals with a circadian preference for mental and physical activity earlier in the day ("Morning types"). Several explanatory hypotheses of this association between chronotype and well-being have been proposed, including shared genetic, biological, developmental, and psychosocial mechanisms. This paper presents a critical summary of these explanatory mechanisms and offers suggestions for...
Source: The Yale Journal of Biology and Medicine - July 1, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Infant Attention and Age 3 Executive Function.
Authors: Kraybill JH, Kim-Spoon J, Bell MA Abstract Executive function (EF) abilities refer to higher order cognitive processes necessary to consciously and deliberately persist in a task and are associated with a variety of important developmental outcomes. Attention is believed to support the development and deployment of EF. Although preschool EF and attentional abilities are concurrently linked, much less is known about the longitudinal association between infant attentional abilities and preschool EF. The current study investigated the impact of infant attention orienting behavior on preschool EF. Maternal rep...
Source: The Yale Journal of Biology and Medicine - March 31, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Sequential Information Processing: The "Elevated First Response Effect" Can Contribute to Exaggerated Intra-Individual Variability in Older Adults.
In this study we examined attention-related reaction time (RT) and intra-individual variability (IIV) in younger and older adults using an iPad-based visual search test, in which, for each trial, participants were required to sequentially press a series of on-screen stimuli numbered from 1 to 8. Although overall performance RT was significantly slower, with greater IIV for the older compared to the younger adult group, there was also a disproportionately slowed RT and greater IIV for the first item in the series compared to all other responses within the trial. When the response to the first stimulus was removed from stati...
Source: The Yale Journal of Biology and Medicine - March 31, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

The Role of Attention in Learning in the Digital Age.
Authors: Lodge JM, Harrison WJ Abstract New and evolving technologies provide great opportunities for learning. With these opportunities, though, come questions about the impact of new ways of acquiring information on our brain and mind. Many commentators argue that access to the Internet is having a persistent detrimental impact on the brain. In particular, attention has been implicated as a cognitive function that has been negatively impacted by use of digital technologies for learning. In this paper, we critique this claim by analyzing the current understanding of the cognitive neuroscience of attention and rese...
Source: The Yale Journal of Biology and Medicine - March 31, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Social Functioning in Youth with Attention-Deficit/Hyperactivity Disorder and Sluggish Cognitive Tempo.
Authors: Ferretti NM, King SL, Hilton DC, Rondon AT, Jarrett MA Abstract The current review summarizes the research to date on social functioning for youth with attention-deficit/hyperactivity disorder (ADHD) with a focus on three key domains: peer rejection, friendship, and social information processing. The review extends past reviews by examining the research to date on how the presence of sluggish cognitive tempo (SCT) symptoms, a common correlate of ADHD, affects the social presentation of youth with ADHD. Overall, youth with ADHD show significant difficulty with peer rejection, forming and maintaining friends...
Source: The Yale Journal of Biology and Medicine - March 31, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

A Review on the Trajectory of Attentional Mechanisms in Aging and the Alzheimer's Disease Continuum through the Attention Network Test.
Authors: McDonough IM, Wood MM, Miller WS Abstract Multiple domains of cognition are known to decline in both normal aging and in the trajectory towards Alzheimer's disease (AD). While declines in episodic memory are most well-known in both normal aging and AD, some of these memory differences might stem from early deteriorations in attention that have consequences for later memory. Further complicating the matter is that attention is a multifaceted construct that might be differentially affected in normal aging and AD. According to cognitive neuroscience models of attention, three types of attention networks exist...
Source: The Yale Journal of Biology and Medicine - March 31, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Sleep and Attention in Alzheimer's Disease.
Authors: Hennawy M, Sabovich S, Liu CS, Herrmann N, Lanctôt KL Abstract Individuals with Alzheimer's disease (AD) present with a wide variety of symptoms, including sleep disruption and sleep disorders. Conversely, disordered sleep has been associated with an increased risk of developing AD. Both conditions individually have adverse effects on attention, which can be further divided into selective, sustained, divided, and alternating attention. The neural mechanisms underpinning sleep problems in AD involve the disruption of the circadian system. This review comprehensively discusses the types of attention im...
Source: The Yale Journal of Biology and Medicine - March 31, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Can Slow-Wave Sleep Enhancement Improve Memory? A Review of Current Approaches and Cognitive Outcomes.
The objective of this review was to synthesize the results of recent experimental studies that have used auditory stimulation, electrical, and pharmacological methods to boost both SWS and cognitive performance. A systematic review was done to identify and consolidate all currently existing empirical studies in this area. We found that each stimulation method could enhance slow-wave power and/or SWS duration in human subjects. Closed-loop, in-phase auditory stimulation enhanced verbal declarative memory in healthy adults. Electrical stimulation using so-tDCS showed some efficacy in promoting verbal declarative memory, pict...
Source: The Yale Journal of Biology and Medicine - March 31, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Circadian Rhythms in Attention.
Authors: Valdez P Abstract Attention is a cognitive process crucial for human performance. It has four components: tonic alertness, phasic alertness, selective attention, and sustained attention. All the components of attention show homeostatic (time awake, sleep deprivation) and circadian (time of day) variations. The time course of the circadian rhythms in attention is important to program work and school-related activities. The components of attention reach their lowest levels during nighttime and early hours in the morning, better levels occur around noon, and even higher levels can be observed during afternoon...
Source: The Yale Journal of Biology and Medicine - March 31, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Homer1a and mGluR1/5 Signaling in Homeostatic Sleep Drive and Output.
Authors: Martin SC, Monroe SK, Diering GH Abstract Sleep is an essential physiological behavior that promotes cognitive development and function. Although the switch between sleep/wake cycles is controlled by specific neural circuits, sleep need and the restorative benefits of sleep are likely controlled by cellular mechanisms localized in critical areas of the brain involved in learning and memory including the cortex and hippocampus. However, the molecular basis for the restorative function(s) of sleep that support cognition, or for the homeostatic build-up of sleep need are poorly understood. Synapses undergo lo...
Source: The Yale Journal of Biology and Medicine - March 31, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Flexibility in Attentional Control: Multiple Sources and Suppression.
Authors: Carlisle NB Abstract In daily life, it is critical that we are able to direct our visual attention to information that is important for our tasks while avoiding distracting information. To control our attention, we engage "attentional templates" that reconfigure how incoming visual signals are processed in our brains. But what are these attentional templates and how do they work? Much of our understanding of the nature of attentional templates has been driven by the proposed mechanism linking attentional templates and working memory from the biased competition model [1] (Desimone and Duncan, 1995...
Source: The Yale Journal of Biology and Medicine - March 31, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research

Attention in Urban and Natural Environments.
Authors: White H, Shah P Abstract With advances in technology and increases in global urbanization, the complexity of our sensory environment has increased dramatically in the last few hundred years. However, our brains have remained essentially unchanged. The cognitive resources that support complex goal-directed behaviors operate differently in urban versus natural environments. In this short perspective, we consider how the attention system, designed for interacting with nature, is taxed by urban environments and discuss how exposure to nature may support its rejuvenation. PMID: 30923478 [PubMed - in process...
Source: The Yale Journal of Biology and Medicine - March 31, 2019 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research