bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of peripheral VEGF signaling rapidly reduces leucocyte obstructions in brain capillaries and improves cortical blood flow in an Alzheimer’s disease mouse model
Authors: Ali Muhammad , Falkenhain Kaja , Haft‐Javaherian Mohammad , Murtaza‐Ali Muhammad , Njiru Brendah N , Nishimura Nozomi , Schaffer Chris B , Bracko Oliver
Published: December 2020

Background

We recently found that increased obstructions in capillaries caused by adhesion of leucocytes in the cortical microvascular leads to a ∼20% reduction of cerebral blood flow (CBF) in mouse models of Alzheimer’s disease. Here, we explore the contribution of peripheral Vascular Endothelial Growth Factor (VEGF) signaling at the luminal side of the brain microvasculature as a driver of capillary stalling and blood‐brain barrier (BBB) integrity in the APP/PS1 mouse model of AD.

Method

The number of stalled cortical capillaries and blood flow speeds were measured in cortical capillaries using high resolution in vivo two‐photon imaging, before and after one hour and two weeks of i.p. anti‐VEGF164 antibody injection. Capillary stalls were measured using the citizen science platform Stall Catchers. The blood‐brain barrier integrity was analyzed using immunohistochemistry.

Result

We found that inhibition of VEGF signaling in APP/PS1 mice reduces capillary stalling by ∼75% and improves average capillary speed by ∼50%. In contrast, no such effects were seen in wild‐type saline‐injected controls. The anti‐VEGF164 injection also reduced overall eNOS protein concentrations and increased the tight junction protein levels of occludin. Intriguingly, the few APP/PS1 capillaries that were still prone to obstructions after anti‐VEGF treatment had lower occludin concentrations between their endothelial cells than flowing capillaries. We further demonstrate that capillary stalling reductions and capillary speed improvements occur within an hour of intraperitoneal anti‐mouseVEGF164 injection. At the same time scale, anti‐VEGF treatment reduced Evan’s blue diffusion across the BBB.

Conclusion

This data demonstrates that peripheral inhibition of VEGF‐signaling in APP/PS1 mice restores aberrant eNOS/occludin‐associated BBB permeability, and is associated with decreased capillary stalls and increased CBF.
Chronic head injury promotes tau and amyloid‐beta pathology and accelerates cognitive decline in a humanized knock‐in model of Alzheimer's disease
Authors: Chiasseu Marius , Fesharaki Arman , Saito Takashi , Saido Takaomi C , Strittmatter Stephen M
Published: December 2020

Background

Clinical manifestation of Alzheimer's disease (AD) symptoms is known to reflect interactions between environmental and genetic factors. Unfortunately, preclinical modeling of AD has been relying primarily on transgenic overexpression of rare dominant mutations, with little considerations to the role the environment might play in triggering the disease. Hence the disappointing results towards translational progress in disease modifying therapies. Mild traumatic brain injury (mTBI) is a well‐known environmental risk factor for dementia, including Alzheimer’s, yet there has been limited mechanistic analysis of mTBI contribution to AD pathology. Here, we investigate the interplay between mTBI and Aβ precursor protein (APP) gene mutation in AD pathogenesis.

Method

We employed a knock‐in (KI) model of AD that expresses the Aß‐containing exons from human APP bearing the Swedish and Iberian (AppNL‐F/NL‐F
) mutations that we subjected to repeated mTBI (rmTBI). Injury was induced in anesthetized 4‐month‐old mice by stereotactically applying daily, a mild mechanical force on the head using a controlled cortical impactor. Impacts were applied at a speed of 5 m/s, a duration of 100 ms, and depth of 1 mm for a total of 14 days alternating between each side of the cranium. Anesthetized, uninjured genotype‐ and age‐matched mice were used as sham controls. At 3‐ and 8‐months post‐injury, cortical Aβ, phospho‐tau and Iba1 expression as well as cognitive status were assessed in the injured KI subjects.

Result

Our data reveal that relative to controls, rmTBI enhances accumulation of amyloid‐β and hyperphosphorylated tau inclusions, as well as neuroinflammation in KI mice, this in areas both proximal and distal to the injury site. Furthermore, novel object recognition and Morris water maze tests demonstrated that the AppNL‐F/NL‐F
mutations synergistically exacerbates the cognitive deficits triggered by rmTBI.

Conclusion

Therefore, this study demonstrates that combining genetic and environmental factors provides a more robust approach for modelling AD, and that chronic head injury substantially accelerates Alzheimer's pathology in a genetically susceptible situation.
Alzheimer’s pathologic change indexed by CSF B‐amyloid42 associates with longitudinal alterations in myelin content
Authors: Yang Kao Lee , Dean Douglas C , Oh Jennifer M , Koscik Rebecca L , Ma Yue , Kohli Akshay , Chin Nathaniel A , Carlsson Cynthia M , Johnson Sterling C , Asthana Sanjay , Zetterberg Henrik , Blennow Kaj , Alexander Andrew L , Bendlin Barbara B
Published: December 2020

Background

CSF Ab42 levels are associated with myelin content alterations in cognitively‐unimpaired adults (Dean et al, 2017), suggesting that myelin alterations may be an early feature of the Alzheimer’s disease (AD) pathophysiological cascade. We expand on these prior findings to examine longitudinal change in myelin content.

Method

98 cognitively‐unimpaired (Table 1) participants from the Wisconsin Alzheimer’s Disease Research Center and Wisconsin Registry for Alzheimer’s Prevention underwent longitudinal multicomponent relaxometry (mcDESPOT) MRI, T2FLAIR MRI, and lumbar puncture (LP). All mcDESPOT MRI were normalized to MNI space using ANTs. White matter lesion volumes were extracted from T2FLAIR images using Lesion Segmentation Toolbox version 2.0.1 in SPM12. CSF was assayed for Ab42 using enzyme‐linked immunosorbent (INNOTEST) methods. 212 mcDESPOT‐derived myelin water fraction (MWF) maps, sensitive to myelin content, were generated for this analysis. MWF values were extracted from 6 white matter tracts affected in AD, and MWF values were averaged across regions to create a global index of myelin content at each timepoint. Linear mixed models were fit with longitudinal regional or global MWF as the outcome. All models included random intercepts and age‐related slopes with fixed effects of age (mean‐centered), sex, years between MRI and LP, white matter hyperintensity volume (log‐transformed) measured at first MRI, CSF Ab42 (mean‐centered) levels measured near first MRI, and Age*Ab42. All models were fitted in R (“lmer” package) version 3.6.0 and considered significant at unadjusted p < .05.

Result

We observed widespread age associations with myelin content such that older age associated with lower global myelin content (Figure 1) and lower CSF Ab42 was associated with lower global myelin content (Figure 2). There was no significant interaction of age and CSF Ab42 on global myelin content. However, an age*Ab42 effect in the cingulum and uncinate fasciculus indicated that older age and lower CSF Ab42 was associated with decreased myelin content (Figure 3).

Conclusion

We previously found that lower CSF Ab42 was associated with lower myelin content among cognitively unimpaired adults. Here, we determined that for cognitively unimpaired middle‐aged adults, amyloid‐related longitudinal changes in myelin content also occur. Future studies will test if amyloid‐related myelin alterations may account for AD cognitive decline.
The Cognitive Behavioral Score Questionnaire (Q‐CBS) in phenotyping minor and major neurocognitive disorder syndromes
Authors: Sykara Konstantina , Ramirez Jeronimo Martin , Andronas Nikolaos , Mavragani Evdoxia , Tsekou Hara , Mougias Michalis , Karageorgiou Klimentini E , Karageorgiou Elissaios
Published: December 2020

Background

The demand for specialized care in neurocognitive disorders greatly surpasses its availability. Patients have complex needs and specialists are scarce. As a result, there is a gap between the needs of patients and the capacity of health systems to address them. Expert systems help fill this gap working towards early and accurate phenotyping (description) of neurocognitive disorders to better identify and successfully allocate the limited resources. We developed the Cognitive Behavioral Score (CBS), a 51‐item structured self‐administered questionnaire and its caregiver counterpart (cCBS), conducting exploratory analyses on clinical feasibility and diagnostic utility, as well as association to neuropsychological performance.

Method

We enrolled 29 patients (age: 71.5±11.7; education: 9.6±2.8 years) with minor or major neurocognitive disorder (late age‐of‐onset Alzheimer’s disease with various degrees of vascular comorbidity; MMSE= 26.0±4.3) through the Sleep & Memory Center of the Neurological Institute of Athens. CBS and cCBS were completed by patients and/or their caregivers, covering cognitive, behavior, autonomic, and sleep symptom severity and duration. Patients underwent physical examinations, neuropsychological, biochemical and imaging testing. Statistical analyses were conducted using Pearson ρ or Kendall τ as appropriate, depending on data deviation from normality.

Results

Both CBS and cCBS were completed in‐clinic or at home within 5 minutes and provided a clinical overview of symptom progression. CBS and cCBS congruence total score was 0.36, certain domain‐specific sub scores were even better (0.46 – 0.67). Correlation to MMSE was better for cCBS (‐0.30), a feature reflective of the patient population. CBS and cCBS sub scores had varying degrees of correlation to domain‐specific neuropsychological tests, with historic symptoms of anomia having most and highest associations (≤ ‐0.76). Non‐cognitive symptoms were correlated to executive function, hinting to possible comorbid synucleinopathies or sleep deprivation.

Conclusion

The study results suggest that both CBS and cCBS have diagnostic utility for the clinician. They allow faster and more accurate description and identification of syndromic neurocognitive disorders. With better understanding, resources can be allocated in a more directed and better‐planned manner, helping low resource settings. Also these questionnaires minimize the time in history taking, allowing health professionals to dedicate more time to the patients for better and individualized care.
Perspectives surrounding brain donation among African American research participants in the Northwestern University Alzheimer’s Disease Center
Authors: Dyslin Deborah Nicole , Dunlop Sara Rose , Aldridge Brenda , Tillotson Robin , Morhardt Darby
Published: December 2020

Background

Alzheimer’s and related dementias (ADRD) disproportionately affect the African American community. Increased participation of African Americans in research is essential to further understand factors related to risk and resilience to ADRD. Brain donation remains the only mechanism to confirm a diagnosis of neurodegenerative disorders and is less common among African American research participants compared to White research participants across the US. Previous studies identified knowledge of brain donation, religious and or funeral plans, family support of decision, and distrust of medical/research community as important factors in African American participation in brain donation. However, perspectives of African American participants within the Mesulam Center ADRC are unknown.

Methods

Seven focus groups, stratified by both cognitive and decision status were conducted as part of this analysis. Focus groups ranged in attendance from 2‐8 participants, plus 2‐4 study personnel. 34 research participants and/or study partners participated in this project. Focus groups were co‐facilitated by Northwestern social workers, a Northwestern neuroscience PhD student, and a social work intern at the regional senior center. All focus group discussions were audio recorded, subsequently de‐identified, transcribed and coded for emerging themes.

Result

Qualitative analysis revealed several themes: personal connection to memory loss or dementia; altruism; personal decision making, spirituality/religion; historical and current trauma related to healthcare and research; trust; representation of African Americans in clinical and research settings, and understanding the purpose and process of brain donation. Participant identified next steps include community education initiatives centered around brain donation, building trust between the community and research institutions, and increased community engagement by Northwestern in diverse communities.

Conclusion

Overall, our findings are consistent with previous findings. Themes highlight the issue of trust, importance of increased representation of African Americans among staff in aiding participation, lack of understand of the purpose and value of brain donation, and the need for purposeful acknowledgement of past traumas by the medical research community. Next steps include both community level and institutional interventions to aid in increased participation in brain donation among African American research participants.
Lower MRI‐indexed locus coeruleus integrity in autosomal‐dominant Alzheimer's disease
Authors: Dahl Martin J , Mather Mara , Werkle‐Bergner Markus , Kennedy Brianna L , Qiao Yuchuan , Shi Yonggang , Ringman John M
Published: December 2020

Background

Tau pathology, a hallmark of Alzheimer’s disease, accumulates early in life in the locus coeruleus, the primary source of cortical norepinephrine. Dysfunctions in the noradrenergic system are hypothesized to contribute to Alzheimer’s progression; however, in‐vivo evidence has been impeded by methodological challenges in non‐invasive assessments. Advances in high‐resolution brainstem magnetic resonance imaging (MRI) hold potential to investigate the association of locus coeruleus integrity and Alzheimer’s‐related neuropathological markers in vivo.

Method

Eighteen participants (34.7±10.1 years; 9♀) with or known to be at‐risk for mutations in genes associated with autosomal‐dominant Alzheimer’s disease (ADAD) were investigated. Genotyping confirmed mutations in seven participants (PSEN1, n = 6; APP, n = 1), of which four were symptomatic. Participants underwent 3T‐MRI, flortaucipir positron emission tomography (PET), and cognitive testing. Locus coeruleus MRI intensity, a non‐invasive proxy for neuronal density, was semi‐automatically extracted from high‐resolution brainstem scans. Locus coeruleus ratios—that is, a ratio of peak locus coeruleus intensity standardized to a pontine reference—were computed across the rostrocaudal extent of the nucleus. Standard uptake value ratios (SUVR) were calculated from partial volume corrected flortaucipir PET data using cerebellar gray matter as reference. SUVR images were mapped to the cortical surface which was parcellated into 36 regions of interest. Associations between locus coeruleus ratios, clinical variables, cognitive status, and tau burden were evaluated using non‐parametric Mann‐Whitney U‐tests and bootstrapped Spearman’s correlations.

Result

Relative to healthy controls, symptomatic participants showed lower locus coeruleus ratios (Z = 2.177; p = 0.03). This effect was pronounced in rostral segments of the nucleus (Z = 3.077; p = 0.002) that project to the hippocampus. Among carriers of ADAD‐causing mutations, closer proximity to the mutation‐specific median age of dementia diagnosis was associated with lower locus coeruleus ratios (rho = ‐0.727; p = 0.048). Higher locus coeruleus ratios were observed in participants with unimpaired cognitive performance (rho = 0.527; p = 0.022). Tau burden, especially in occipito‐temporo‐parietal regions, was related to lower locus coeruleus ratios (rho = 0.54, p = 0.036).

Conclusion

Our finding of diminished locus coeruleus integrity in autosomal‐dominant Alzheimer’s disease suggest a role of the noradrenergic system in this neurodegenerative disease.
Choral singing with dementia: Examining the experience and impact of embodied and relational musical performance
Authors: Smith Andre P , Erb Tara , Kampen Ruth , MacDonald Stuart , Sheets Debra J
Published: December 2020

Background

Promising research points to the potential of singing as a novel intervention to improve cognitive function and reduce levels of stress, anxiety, loneliness, and depression in persons with dementia (PwD) (Elliott and Gardner, 2018; Unadkat et al., 2016). This study explores the impact of participation in Voices in Motion (ViM), an intergenerational community choir program designed to engage and support persons with dementia (PwD), their care partners, and students in Victoria, British Columbia, Canada. Combining narrative interviews, focus groups and observations, the study examined care partners and PwD’s experiences of ViM and their views of the benefits of choir involvement and considered the impact of ViM on social inclusion and social relationships.

Method

Over an 18‐month period, the study initiated and followed two ViM choirs—one active in research for three 3‐month sessions and the other for two sessions of the same time length. Data came from interviews with 23 dyads of PwD and care partners and focus groups with 29 high school students across the two ViM choirs. The interviews and focus groups were conducted at the end of each choir season over the course of the study.

Result

The thematic analysis revealed that PwD maintained an embodied ability to learn, experience, and perform songs in the choir despite considerable deficits in cognition, language, and memory. Results indicate that choral participation, as a type of embodied activity, effectively engages PwD and allows them to meaningfully express themselves as both singers and human beings. The ViM choirs facilitated the emergence of strong social relationships between PwD and care partners with the students who reported gaining a deeper and sympathetic understanding of PwD as individuals with rich life stories. Choral singing also served as an inspiring avenue for PwD to develop a strong sense of self and identity as choristers and performers.

Conclusion

ViM facilitates the re‐humanization of dementia through well‐attended concerts and performances at public events while also challenging social narratives of decline which remain prevalent in society and stigmatize individuals living with dementia.
Racemization hypothesis of neurodegeneration (RHND)
Authors: Dyakin Victor Vasilyevich , Lajtha Abel , Dyakina‐Fagnano Nika Victorovna
Published: December 2020

Background

Biochirality, evident in the homochirality of deoxyribonucleic acid (DNA) and the prevalent chirality of amino acids (AAs) in a bilateral organism, represents a challenge for modern biochemistry and neuroscience. Attention to the spontaneous post translational racemization allow revealing the link between protein aging, cell aging, and decline of cognitive functions should be highlighted.

Method

Analytical review of current advances in the molecular biology, biophysics, and neuroscience.

Result

At the protein level, biochirality is closely associated with various post‐translational modifications (PTMs), which support the dynamic balance of the prevalent chirality of enzymes and their substrates. This review posits a racemization hypothesis of neurodegeneration (RHND) that focuses on the distinct forms of the aberrant PTMs, which critically impact enzymes‐substrate interaction named spontaneous racemization. From a thermodynamic perspective, the collapse of homochirality by racemization is the result of a conformational non‐equilibrium phase transition. At the cellular level, the concept of non‐equilibrium phase transitions (PhTs) is relevant to the biophysics of PTMs, physiology of membrane‐less organelles (MLO), and intrinsically disordered proteins (IDPs). MLOs, containing IDPs, represent coherent structures with distinct protein dynamics and biological functions. MLOs containing IDPs are implicated in protein folding and aberrant protein conformation leading to aggregation diseases. Spontaneous, non‐enzymatic PTMs within MLOs represent the internal determinants of protein aging, cell aging and age‐related diseases. Recently it has been shown that the racemization of the serine (Ser) residue occurs (preferably) in the flexible (unstructured or intrinsically disordered) regions of proteins.

Conclusion

The amyloid cascade hypothesis in Alzheimer’s disease (AD) needs to be reconciled with the failure of numerous Aβ targeting drug therapies in clinical trials. In our view, both neuroscience and thermodynamic advances are necessary for addressing the brain region, cell type, and age‐dependent racemization processes that critically influence nervous system functions. The link between protein aging, cell aging, and decline of cognitive functions should be highlighted. The chiral non‐equilibrium phase transitions (PhTs) concomitant with the protein misfolding and aggregation, evident in an increasing number of experimental results, convince as to introduce the RHND.
Social isolation, loneliness, and cognitive impairment in late life: The MYHAT study
Authors: Hughes Tiffany F , Fang Fang , Jacobsen Erin P , Snitz Beth E , Ganguli Mary
Published: December 2020

Background

Social isolation and loneliness have detrimental effects on the health of older adults. Being socially isolated and lonely are likely both predictors and consequences of cognitive impairment with aging. However, isolation and loneliness may be differentially associated with cognitive impairment and may operate through both shared and unique pathways. The present study aimed to examine the association of social isolation and loneliness with concurrent cognitive impairment, and to explore potential mechanisms of the association.

Methods

Participants (n =1,982; Mage = 77.65 years, 1,210 (61.1%) female, 1,877 (94.7%) white, 815 (41.12% > high school education) were from a population‐based study of mild cognitive impairment and dementia. Three composite measures derived from factor analysis, representing social network structure, social connectedness, and loneliness were examined in relation to clinical dementia rating (CDR normal = 0 vs. CDR impaired >= 0.5) at baseline, adjusted for demographic characteristics. The indirect effects of the composite measures were also estimated conditioned on general health and function, lifestyle factors, vascular health, depressive symptoms, and sleep.

Results

Of the participants, 569 (28.71%) were cognitively impaired at baseline. Social connectedness (OR 1.48, 95% CI=1.33‐1.64) and loneliness (OR 1.38, 95% CI=1.24‐1.54), but not social network structure, were significantly associated with greater likelihood of being cognitively impaired after adjustment for demographics. These effects remained significant after separate adjustments for general health and function, lifestyle factors, vascular health, depressive symptoms, sleep, and other composites. The effect of social connectedness was appreciably attenuated by general health status and function (OR 1.37, 95% CI=1.22‐1.54), while loneliness was appreciably attenuated by depressive symptoms (OR 1.26, 95% CI=1.12‐1.42).

Conclusions

Older adults with lower levels of social connectedness and higher perception of loneliness are more likely to be cognitively impaired, which were partially explained by health and function and depressive symptoms, respectively. Addressing these factors may reduce risk for cognitive impairment, or conversely, reduce risk for disconnectedness and loneliness among those with cognitive impairment. These results have implications for the impact that limited social contact and feelings of loneliness during the COVID‐19 pandemic may have on older adults with or at risk for cognitive impairment.
Are perceptions of self‐efficacy in preventing falls by persons with Alzheimer’s disease or related dementias considered by their family caregivers?
Authors: Panzer Victoria , Smith Veronica , Wakefield Dorothy , Fortinsky Richard H , Maher Joanne
Published: December 2020

Background

Falls are common in Persons with Alzheimer’s disease and related dementias (PwADRD) which may be affected by their self‐efficacy or that of their Family Caregivers (CGs). Our earlier studies demonstrated that older adults may be over‐confident or timid and we explored whether CG’s self‐efficacy in preventing a fall or loss of balance (FLOB) for their PwADRD considered PwADRD confidence.

Method

Activity‐Specific Balance Confidence (ABC) is a standardized scale in which confidence in preventing a FLOB is rated (0=no confidence to 10=completely confident) in 16 specific situations. Pilot testing with standard 0‐10, 5 or 3 point Likert scales was unsuccessful with PwADRD. Therefore, CGs self‐administered the ABC, rating their confidence (0‐10) in preventing PwADRD FLOBs, while the PwADRD responded ‘Yes I Can’ or ‘No I Can’t’ prevent a FLOB to trained Interviewers for each situation. ABCtotal (CG 0‐160, PwADRD 0‐16) and Spearman correlation between CG and PwADRD ABCtotal scores were calculated. Wilcoxon two sample tests compared CG ratings between groups (PwADRD who responded Yes and those who responded No) for each situation.

Result

Thirty‐three dyads were 85% White, 3‐6% Asian, African‐American, Hispanic or Pacific‐Islander. CGs were 91% female, average age=70.3 and ABCtotalmean=105.2, SD(26.3). PwADRD were 76% male, average age=77.2, MMSE score mean=22.3, SD(6.4) and ABCtotalmean=12, SD(2.6). The correlation between CG and PwADRD ABCtotal scores (r=0.349) was significant (p=.046). We compared CG ratings between the two groups (PwADRD who responded Yes or No) for each situation. Overall, PwADRD were confident they could prevent a FLOB. In six situations, there were 3 or less who responded No, I can’t. The CG median rating for the Yes group was significantly higher than the No group in only three situations: walk in crowd (8 vs. 5, p=.008), icy sidewalks (6 vs. 2, p=.047), and bend over (8 vs. 5.5, p=.058). In all other situations, there was no significant difference in CG ratings whether the PwADRD responded Yes or No.

Conclusion

In many situations, CG's self‐efficacy for preventing FLOBs was similar irrespective of PwADRD confidence. This ‘Dual‐ABC’ approach may help to focus falls prevention interventions on situations in which the CG’s self‐efficacy does not consider the PwADRD’s confidence.
Harnessing the paradoxical phenotypes of APOE ɛ2 and APOE ɛ4 to identify genetic modifiers in Alzheimer's disease
Authors: Kim Young Won , Al‐Ramahi Ismael , Koire Amanda , Wilson Stephen J. , Konecki Daniel M. , Mota Samantha , Soleimani Shirin , Botas Juan , Lichtarge Olivier
Published: December 2020

The strongest genetic risk factor for idiopathic late‐onset Alzheimer's disease (LOAD) is apolipoprotein E (APOE) ɛ4, while the APOE ɛ2 allele is protective. However, there are paradoxical APOE ɛ4 carriers who remain disease‐free and APOE ɛ2 carriers with LOAD. We compared exomes of healthy APOE ɛ4 carriers and APOE ɛ2 Alzheimer's disease (AD) patients, prioritizing coding variants based on their predicted functional impact, and identified 216 genes with differential mutational load between these two populations. These candidate genes were significantly dysregulated in LOAD brains, and many modulated tau‐ or β42‐induced neurodegeneration in Drosophila. Variants in these genes were associated with AD risk, even in APOE ɛ3 homozygotes, showing robust predictive power for risk stratification. Network analyses revealed involvement of candidate genes in brain cell type‐specific pathways including synaptic biology, dendritic spine pruning and inflammation. These potential modifiers of LOAD may constitute novel biomarkers, provide potential therapeutic intervention avenues, and support applying this approach as larger whole exome sequencing cohorts become available.
Vascular health across young adulthood and midlife cerebral autoregulation, gait, and cognition
Authors: Mahinrad Simin , Shownkeen Meghana , Sedaghat Sanaz , Yaffe Kristine , Hausdorff Jeffrey M. , Lloyd‐Jones Donald M. , Gorelick Philip B. , Sorond Farzaneh A.
Published: December 2020

Introduction

To test the association of vascular health (VH) across young adulthood with midlife dynamic cerebral autoregulation (dCA), gait, and cognition; and to test whether dCA is a modifying factor.

Methods

We studied 196 participants from the Coronary Artery Risk Development in Young Adults cohort who were followed over 30 years. VH was assessed at each visit according to American Heart Association recommendations. At year 30, dCA was measured using transcranial Doppler ultrasound and several gait and cognitive domains were assessed.

Results

Worse VH from baseline through year 7, but not at year 30, was associated with less efficient dCA (all P < .05). Worse VH at all visits was associated with slower gait speed, and at year 7 with worse executive and global cognition (all P < .05). The association of baseline VH and midlife gait, but not cognition, was moderated by dCA (interaction P < .05).

Conclusions

VH as early as young adulthood may influence midlife brain health, and dCA may modify this relationship.
Two‐Dimensional (2D) or Quasi‐2D Superstructures from DNA‐Coated Colloidal Particles
Authors: Liu Mingzhu , Zheng Xiaolong , Grebe Veronica , He Mingxin , Pine David J. , Weck Marcus
Published: December 2020

This contribution describes the synthesis of colloidal di‐patch particles functionalized with DNA on the patches and their assembly into colloidal superstructures via cooperative depletion and DNA‐mediated interactions. The assembly into flower‐like Kagome, brick‐wall like monolayer, orthogonal packed single or double layers, wrinkled monolayer, and colloidal honeycomb superstructures can be controlled by tuning the particles’ patch sizes and assembly conditions. Based on these experimental results, we generate an empirical phase diagram. The principles revealed by the phase diagram provide guidance in the design of two‐dimensional (2D) materials with desired superstructures. Our strategy might be translatable to the assembly of three‐dimensional (3D) colloidal structures.
Thiazolo[5,4‐d]thiazole‐Based Donor–Acceptor Covalent Organic Framework for Sunlight‐Driven Hydrogen Evolution
Authors: Li Wenqian , Huang Xiaofeng , Zeng Tengwu , Liu Yahu A. , Hu Weibo , Yang Hui , Zhang Yue‐Biao , Wen Ke
Published: December 2020

2D covalent organic frameworks (COFs) could have well‐defined arrangements of photo‐ and electro‐active units that serve as electron or hole transport channels for solar energy harvesting and conversion, but their insufficient charge transfer and rapid charge recombination impede the sunlight‐driven photocatalytic performance. We report a new donor–acceptor (D–A) system, PyTz‐COF that was constructed from the electron‐rich pyrene (Py) and electron‐deficient thiazolo[5,4‐d]thiazole (Tz). With its bicontinuous heterojunction, PyTz‐COF demonstrated exceptional optoelectronic properties, photocatalytic ability in superoxide anion radical‐mediated coupling of (arylmethyl)amines and photoelectrochemical activity in sunlight‐driven hydrogen evolution. Remarkably, PyTz‐COF exhibited a photocurrent up to 100 μA cm−2 at 0.2 V vs. RHE and could reach a hydrogen evolution rate of 2072.4 μmol g−1 h−1. This work is paving the way for reticular design of highly efficient and highly active D–A systems for solar energy harvesting and conversion.
On‐POM Ring‐Opening Polymerisation of N‐Carboxyanhydrides
Authors: Soria‐Carrera Héctor , Franco‐Castillo Isabel , Romero Pilar , Martín Santiago , de la Fuente Jesús M. , Mitchell Scott G. , Martín‐Rapún Rafael
Published: December 2020

The ring‐opening polymerisation of α‐amino acid N‐carboxyanhydrides (NCAs) offers a simple and scalable route to polypeptides with predicted and narrow molecular weight distributions. Here we show how polyoxometalates (POMs)—redox‐active molecular metal‐oxide anions—can serve as inorganic scaffold initiators for such NCA polymerisations. This “On‐POM polymerisation” strategy serves as an innovative platform to design hybrid materials with additive or synergistic properties stemming from the inorganic and polypeptide component parts. We have used this synthetic approach to synthesise a library of bactericidal poly(lysine)–POM hybrid derivatives that can be used to prevent biofilm formation. This versatile “On‐POM polymerisation” method provides a flexible synthetic approach for combining inorganic scaffolds with amino acids, and the potential to tailor and improve the specificity and performance of hybrid antimicrobial materials.
Non‐Equilibrium Large‐Scale Membrane Transformations Driven by MinDE Biochemical Reaction Cycles
Authors: Fu Meifang , Franquelim Henri G. , Kretschmer Simon , Schwille Petra
Published: December 2020

The MinDE proteins from E. coli have received great attention as a paradigmatic biological pattern‐forming system. Recently, it has surfaced that these proteins do not only generate oscillating concentration gradients driven by ATP hydrolysis, but that they can reversibly deform giant vesicles. In order to explore the potential of Min proteins to actually perform mechanical work, we introduce a new model membrane system, flat vesicle stacks on top of a supported lipid bilayer. MinDE oscillations can repeatedly deform these flat vesicles into tubules and promote progressive membrane spreading through membrane adhesion. Dependent on membrane and buffer compositions, Min oscillations further induce robust bud formation. Altogether, we demonstrate that under specific conditions, MinDE self‐organization can result in work performed on biomimetic systems and achieve a straightforward mechanochemical coupling between the MinDE biochemical reaction cycle and membrane transformation.
Using a conductive sphere as a probe to characterize the sensitivity of soft piezoresistive films
Authors: Green Christopher , Rogers Jeremy , Kovenburg Robert , Aksak Burak
Published: December 2020

Flexible piezoresistive films, such as, carbon black/polydimethylsiloxane (C‐PDMS) composites, are often used as skin analogs and integrated into complex array sensors for tactile sensing. The uniformity of the sensor characteristics heavily depends on the homogeneity of the composite. Therefore, the ability to locally characterize a film that will be integrated into a complex force sensor could be critical. Here, a method to characterize the local sensitivity of flexible piezoresistive films is presented. Using a conductive sphere, which was chosen over a flat probe to eliminate misalignment issues, the surface of a thin film composite is indented to characterize the change in resistivity in terms of average strain. Experiments were performed with 15 and 18 wt% carbon black C‐PDMS films of varying thickness. The contact radius of the probe with the piezoresistive film was estimated using the Johnson‐Roberts‐Kendall contact theory. Theoretical contact area estimates were found to agree with contact radius measurements carried out using optically transparent PDMS films observed through an optical microscope. Results show that C‐PDMS with 15 wt% carbon black exhibit a higher rate if change of resistivity and gauge factor than films of same thickness with 18 wt% carbon black. On the other hand, thicker films exhibit higher gauge factors for the two tested carbon black contents. Tests carried out at multiple locations yielded consistent sensitivity values, making these types of composites suitable for array type force sensors.
Potential antibacterial and antifungal activities of novel sulfamidophosphonate derivatives bearing the quinoline or quinolone moiety
Authors: Bazine Ismahene , Bendjedid Samira , Boukhari Abbes
Published: December 2020

A series of new α‐sulfamidophosphonate/sulfonamidophosphonate (4a–n) and cyclosulfamidophosphonate (5a–d) derivatives containing the quinoline or quinolone moiety was designed and synthesized via Kabachnik–Fields reaction in the presence of ionic liquid under ultrasound irradiation. This efficient methodology provides new 1,2,5‐thiadiazolidine‐1,1‐dioxide derivatives 5a–d in one step and optimal conditions. The molecular structures of the novel compounds 4a–n and 5a–d were confirmed using various spectroscopic methods. All these compounds were evaluated for their in vitro antibacterial activity against Gram‐negative (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853) and Gram‐positive (Staphylococcus aureus ATCC 27923) bacteria, in addition to three clinical strains (E. coli 1, P. aeruginosa 1, and S. aureus 1). Most of the tested compounds showed more potent inhibitory activities against both Gram‐positive and ‐negative bacteria compared with the sulfamethoxazole reference. The following compounds, 4n, 4f, 4g, 4m, 4l, 4d, and 4e, are the most active sulfamidophosphonate derivatives. Furthermore, these molecules gave interesting zones of inhibition varying between 28 and 49 mm, against all tested bacterial strains, with a low minimum inhibitory concentration (MIC) value ranging from 0.125 to 8 μg/ml. All the synthesized derivatives were also evaluated for their in vitro antifungal activity against Fusarium oxyporum f. sp. lycopersici and Alternaria sp. The results revealed that all the synthesized compounds exhibited excellent antifungal inhibition and the compounds 4f, 4g, 4m, and 4i were the most potent derivatives with MIC values ranging from 0.25 to 1 µg/ml against the two tested fungal strains. The strongest inhibition of bacteria and fungi strains was detected by the effect of quinolone and sulfamide moieties.
Network architecture and sex chromosome turnovers
Authors: Tao Wenjing , Conte Matthew A. , Wang Deshou , Kocher Thomas D.
Published: December 2020

Recent studies have revealed an astonishing diversity of sex chromosomes in many vertebrate lineages, prompting questions about the mechanisms of sex chromosome turnover. While there is considerable population genetic theory about the evolutionary forces promoting sex chromosome replacement, this theory has not yet been integrated with our understanding of the molecular and developmental genetics of sex determination. Here, we review recent data to examine four questions about how the structure of gene networks influences the evolution of sex determination. We argue that patterns of epistasis, arising from the structure of genetic networks, may play an important role in regulating the rates and patterns of sex chromosome replacement.
Patterning of protein‐based materials
Authors: Humenik Martin , Winkler Anika , Scheibel Thomas
Published: December 2020

Micro‐ and nanopatterning of proteins on surfaces allows to develop for example high‐throughput biosensors in biomedical diagnostics and in general advances the understanding of cell‐material interactions in tissue engineering. Today, many techniques are available to generate protein pattern, ranging from technically simple ones, such as micro‐contact printing, to highly tunable optical lithography or even technically sophisticated scanning probe lithography. Here, one focus is on the progress made in the development of protein‐based materials as positive or negative photoresists allowing micro‐ to nanostructured scaffolds for biocompatible photonic, electronic and tissue engineering applications. The second one is on approaches, which allow a controlled spatiotemporal positioning of a single protein on surfaces, enabled by the recent developments in immobilization techniques coherent with the sensitive nature of proteins, defined protein orientation and maintenance of the protein activity at interfaces. The third one is on progress in photolithography‐based methods, which allow to control the formation of protein‐repellant/adhesive polymer brushes.
Das Xperium in St. Englmar: Naturgesetze zum Anfassen
Authors: Eitner Pascal
Published: December 2020

Mitten im bayerischen Wald in St. Englmar befindet sich ein Ort, der Groß und Klein zum Experimentieren einlädt. Das Bayerwald Xperium ist ein Mitmach‐Museum, das über 100 Versuche zur Physik, Sinnesphysiologie und Mathematik bietet.
The minimalist process: An interpretivist study
Authors: Oliveira de Mendonça Gabrielle , Coelho Rocha Ana Raquel , Bogéa da Costa Tayt‐son Débora
Published: December 2020

Lifestyle politics express the politicization of everyday life and have emerged in opposition to the discourse, generally reproduced by the media, that consumption is essential to achieve a happy and satisfactory life. This paper investigates one of these lifestyles: minimalism. The adopters of this lifestyle believe that by avoiding overconsumption, they are adhering to conscious consumption and challenging the so‐called consumer society. Nevertheless, the development path for minimalists remains unclear. Through this multi‐method study, we seek to discover how a consumer becomes a minimalist. We targeted self‐proclaimed minimalists and members of Facebook communities related to this lifestyle politics. The findings led us to propose a visual representation of a non‐linear minimalist process, composed by overlapped stages, in which consumers choose to engage. By showing the component parts of minimalism, we indicate a new way to approach the topic. We also contributed to outline how consumers forge their identities through de‐growth in consumption practices and unveiled tensions behind minimalism lifestyle. We concluded by proposing venues for future research.
Percutaneous coronary intervention in octogenarians: A risk scoring system to predict 30‐day outcomes in the elderly
Authors: Cockburn James , Kemp Tiffany , Ludman Peter , Kinnaird Tim , Johnson Tom , Curzen Nick , Robinson Derek , Mamas Mamas , de Belder Adam , Hildick‐Smith David ,   The British Cardiovascular Intervention Society (BCIS)
Published: December 2020

Objective

Octogenarians are a high‐risk group presenting for percutaneous coronary intervention (PCI). We aimed to create a 30‐day mortality risk model for octogenarians presenting with both acute coronary syndrome (ACS) and chronic stable angina (CSA), using comprehensive mandatory UK data submissions to the UK National database.

Background

Octogenarians are a high‐risk group presenting for percutaneous coronary intervention, and decisions on whether or not to undertake intervention in this cohort can be challenging. The increasing number of octogenarians in the general population means they represent an important high‐risk subgroup of patients.

Methods

The data group consisted of 425,897 PCI procedures undertaken in the UK between 2008 and 2012 during which time there was comprehensive data linkage to mortality via the Office of National Statistics. Of these procedures, 44,221 (10.4%) were in patients aged ≥80. These comprised the model group. Logistic regression was used to create a predictive score which ultimately consisted of the following weightings: age 80–89 (n = 1); age > 90 (n = 2); unstable angina/non‐ST‐elevation myocardial infraction (NSTEMI) (n = 1); STEMI (n = 2); creatinine >200 mmol/L (n = 1); preprocedural ventilation (n = 1); left ventricular ejection fraction <30% (n = 1); cardiogenic shock (n = 2). Multiple imputation was used to account for missing data.

Results

The patient cohort was divided into a derivation (n = 22,072) and a validation dataset (n = 22,071). Receiver operating characteristic analyses were used to derive the area‐under‐the‐curve to assess properties of the score. The scoring system generated an AUC 0.83, (95% CI 0.80–0.85) suggesting high sensitivity and specificity. Scores of 1–4 were associated with good survival but scores ≥5 were associated with an estimated likelihood of death within 30 days of ≥40%.

Conclusions

This octogenarian risk score maybe a useful tool to determine the chance of a successful outcome in elderly patients presenting for PCI.
Moderators of Career Calling and Job‐Search Behaviors Among Unemployed Individuals
Authors: Dalla Rosa Anna , Vianello Michelangelo , Galliani Elisa Maria , Duffy Ryan D.
Published: December 2020

We examined the relationship between calling, job‐search clarity, and job‐search intensity in a cross‐sectional study of Italian unemployed job seekers (N = 315). Structural equation modeling with observed variables and latent moderated structural equation models were adopted to test whether optimism, self‐esteem, and perseverance moderate the relation between calling, job‐search clarity, and job‐search intensity. Perceiving a calling was positively related with job‐search clarity and intensity, and these relations were stronger in individuals with lower levels of optimism, self‐esteem, and perseverance. This study suggests that perceiving a calling is an important personal resource that is related to a clearer job‐search goal and to more intense job‐search activities and can support job seekers in personal adverse conditions. These results suggest integrating job‐search behaviors in the work‐as‐calling theory and that incorporating the construct of calling into career counselors' practices may increase the efficacy of job‐search activities.
Experiences of Counselor Education Doctoral Student Mothers With Young Children
Authors: Lundquist Brooke , Rubel Deborah , Ng Kok‐Mun
Published: December 2020

We explored the mothering experiences of 11 counselor education doctoral student mothers who have at least one young child under the age of 5. Six themes emerged from the study, including ambivalence, increased use of coping mechanisms, striving for balance, “superwoman syndrome,” indistinguishable roles, and leading by example.
Interaction of Imposter Phenomenon and Research Self‐Efficacy on Scholarly Productivity
Authors: Wester Kelly L. , Vaishnav Shreya , Morris Carrie Wachter , Austin Jordan L. , Haugen Jaimie Stickl , Delgado Heather , Umstead Lindsey K.
Published: December 2020

Research self‐efficacy, imposter phenomenon, and scholarly productivity were explored among a sample of 247 counselor educators. In most cases, feeling like an imposter hindered scholarly productivity; however, the interaction of a moderate to frequent amount of imposter feelings with high research self‐efficacy increased scholarly productivity.
Evaluation of Tensile Adhesion Strength in Simulated Dust Cakes on Fabric Filters
Authors: Zhang Qian , Horst David , Schmidt Eberhard
Published: December 2020

Based on the results of a 3D simulation of cake formation on characteristic filter models for fabric filters with different surface structure, the tensile adhesion strengths in simulated dust cakes are evaluated on the basis of the resulting inhomogeneous local porosity distribution of the particle packing by calculating fracture points at a balance between adhesion and detaching strengths. Both the evaluation method itself and the evaluation results for a computation example are presented and discussed. A significant proportion of fracture points are found in deeper levels in the filter medium, and the distribution of tensile adhesion strengths there differs strongly from the distributions in top levels of the filter medium. The fracture points in the top layer of the filter medium, where a special surface texture is generated, can contribute a considerable part of the tensile adhesion strengths over the whole filter area.