Fractals and the Koch Snowflake

This paper will involve an investigation into Fractals, particularly the Koch Snowflake. The history of fractals, from Benoît Mandelbrot’s discovery in 1975 to the modern-day and future applications will be investigated. A proof will be shown for the Koch snowflake, whereby it is proved that a shape can have an infinite perimeter but a finite surface area. MATLAB will also be used in order to show visual representations of the Koch Snowflake

Role of the Visual System Homeobox gene 1 (VSX1) in keratoconus and mouse development

The main aims of this thesis were to examine the role of the Visual System Homeobox gene 1 (VSX1) in keratoconus and development using molecular biology techniques and biophysics. The opportunity existed to examine a Vsxl knockout mouse using X-ray diffraction to see whether the structure of the cornea was altered due to the removal of this gene. Upon examination with X-ray diffraction further experiments were devised in order to clarify possible interactions of other genes that may play a part in keratoconus pathogenesis. The interfibrillar and intermolecular collagen spacings and the average collagen fibril diameters between Vsxl knockout mice and background matched littermate controls were compared. There were no statistical differences found in all cases. This is a similar finding to human keratoconic corneas when compared with normal controls. It was found that the Vsxl knockout mouse had significant alterations to the preferential alignment of collagen fibrils and altered corneal collagen mass distribution. This also is similar to human keratoconic corneas, strengthening the proposition that the Vsxl knockout mouse is a model system for keratoconus. Additionally, significantly altered expression levels of the genes HSF1, Hsp47 and Aqp5 were found along with no expression of Col8a2. It was believed that the initial fault that allows keratoconus to develop occurs during development, so to explore this normal mouse development was explored using X-ray diffraction to map the collagen fibrils of the cornea as it develops in postnatal stages. This would provide a good baseline for future experiments. In addition to this, initial investigation of the expression of the Vsxl gene was undertaken to see whether it may play a role in development. It was found that the annulus of collagen fibrils that plays an important role in maintaining the structure of the cornea starts to develop at postnatal day 10 in the mouse and continues until maturity. It was also found that there is a significant alteration in expression of Vsxl which occurs in development between postnatal day 5 and day 12. Lastly a population of keratoconus patients in South Wales were screened for mutations in the Vsxl gene. Mutations in Vsxl have been observed in other studies and this investigation was undertaken in order to clarify the ongoing debate into mutations in Vsxl and their link to keratoconus. In the study presented here a number of previously identified polymorphisms were discovered in out cohort of patients but no polymorphism was deemed to be a disease causing mutation

“ Navigating the network”: localising the lesion with the advent of lesion network mapping

“Localising the lesion” is a concept well-trodden by medical students beginning their journey in neurology and is considered an important step in developing a differential diagnosis. However, as demonstrated by the first two papers discussed this month, specific symptoms may be attributable to more than one lesion location. Furthermore, lesions occupying the same anatomical location do not always result in the same symptoms, as illustrated by paper three. Lesion network mapping, the theme linking all three papers, allows us to identify common neural pathways shared when heterogeneous lesions produce the same symptom. This may not only develop our understanding of neurophysiology and neuropathology in vivo but also provide more refined and validated neural targets for neurostimulation therapy. Whilst discussing each of the papers in this month’s journal club, we encourage you to consider whether, for assessment of some neurological diseases, we should move away from “localising the lesion” and towards “navigating the network”. This approach may facilitate a better appreciation of the brain as a series of upregulating and downregulating subcortical systems under cortical influence, that together form a carefully balanced network. As a result, when these networks are affected by pathology, symptoms often occur as the sum consequence of disruption rather than lesion location. With this may come an improved understanding of the use of deep brain stimulation (DBS), why it works, and how its application can be optimised

Changes in corneal collagen architecture during mouse postnatal development

Purpose. To characterize changes in corneal collagen arrangement during mouse postnatal development. Methods. Small-angle X-ray scatter patterns were gathered from the centers of 32 excised mice corneas aged between postnatal days 10 (before eye opening) and 28 (onset of sexual maturity). These were analyzed to produce measurements of the average separation distance between corneal collagen fibrils. Changes in the predominant orientation of corneal collagen and its relative distribution during the same developmental period were determined using wide-angle X-ray scatter data collected at 0.2-mm intervals over the entire cornea and limbal region of each specimen. Results. Collagen interfibrillar spacing decreased in the days leading up to eye opening (61.3 ± 2.9 nm at day 10 to 45.5 ± 4.5 nm at day 14), after which it remained constant. However, changes in collagen orientation and distribution occurred throughout the entire developmental period. After eye opening at day 12, collagen alignment gradually increased in the peripheral cornea and limbus. By day 28, an annulus of highly aligned collagen surrounded the cornea. Conclusions. Changes in corneal thickness before and after eye opening are not caused by widespread alterations in the collagen fibrillar array but are more likely caused by expansion and contraction of regions devoid of regularly arranged collagen. The postnatal development of a corneal annulus of collagen, thought to play a role in stabilizing the curvature of the cornea, may be triggered by visual factors

Mechanoenzymatic reactions for the hydrolysis of PET

Recent advances in the enzymatic degradation of poly(ethylene terphthalate) (PET) have led to a number of PET hydrolytic enzymes and mutants being developed. With the amount of PET building up in the natural world, there is a pressing need to develop scalable methods of breaking down the polymer into its monomers for recycling or other uses. Mechanoenzymatic reactions have gained traction recently as a green and efficient alternative to traditional biocatalytic reactions. For the first time we report increased yields of PET degradation by whole cell PETase enzymes by up to 27-fold by utilising ball milling cycles of reactive aging, when compared with typical solution-based reactions. This methodology leads to up to a 2600-fold decrease in the solvent required when compared with other leading degradation reactions in the field and a 30-fold decrease in comparison to reported industrial scale PET hydrolysis reactions

You Look Familiar: How Malaysian Chinese Recognize Faces

East Asian and white Western observers employ different eye movement strategies for a variety of visual processing tasks, including face processing. Recent eye tracking studies on face recognition found that East Asians tend to integrate information holistically by focusing on the nose while white Westerners perceive faces featurally by moving between the eyes and mouth. The current study examines the eye movement strategy that Malaysian Chinese participants employ when recognizing East Asian, white Western, and African faces. Rather than adopting the Eastern or Western fixation pattern, Malaysian Chinese participants use a mixed strategy by focusing on the eyes and nose more than the mouth. The combination of Eastern and Western strategies proved advantageous in participants' ability to recognize East Asian and white Western faces, suggesting that individuals learn to use fixation patterns that are optimized for recognizing the faces with which they are more familiar

Novel Cell- and Tissue-Based Assays for Detecting Misfolded and Aggregated Protein Accumulation Within Aggresomes and Inclusion Bodies

Aggresomes and related inclusion bodies appear to serve as storage depots for misfolded and aggregated proteins within cells, which can potentially be degraded by the autophagy pathway. A homogenous fluorescence-based assay was devised to detect aggregated proteins inside aggresomes and inclusion bodies within an authentic cellular context. The assay employs a novel red fluorescent molecular rotor dye, which is essentially nonfluorescent until it binds to structural features associated with the aggregated protein cargo. Aggresomes and related structures were generated within cultured cells using various potent, cell permeable, proteasome inhibitors: MG-132, lactacystin, epoxomicin and bortezomib, and then selectively detected with the fluorescent probe. Employing the probe in combination with various fluorescein-labeled primary antibodies facilitated co-localization of key components of the autophagy system (ubiquitin, p62, and LC3) with aggregated protein cargo by fluorescence microscopy. Furthermore, cytoplasmic aggregates were highlighted in SK-N-SH human neuroblastoma cells incubated with exogenously supplied amyloid beta peptide 1–42. SMER28, a small molecule modulator of autophagy acting via an mTOR-independent mechanism, prevented the accumulation of amyloid beta peptide within these cells. The described assay allows assessment of the effects of protein aggregation directly in cells, without resorting to the use of non-physiological protein mutations or genetically engineered cell lines. With minor modification, the assay was also adapted to the analysis of frozen or formalin-fixed, paraffin-embedded tissue sections, with demonstration of co-localization of aggregated cargo with β-amyloid and tau proteins in brain tissue sections from Alzheimer’s disease patients

In the zone: an exploration of personal characteristics underlying affective responses to heavy exercise

Positive affective responses to exercise have been linked with longer term adherence. The Dual-Mode Model indicates that affective responses during heavy exercise (between the ventilatory threshold and the respiratory compensation point) are subject to interindividual variability (zone of response variability). Participants (N = 48) completed measures to assess personal characteristics prior to a graded exercise test (GXT). Responses to the Feeling Scale were recorded during the GXT and subsequently used to group participants as either Negative Responders or Neutral/Positive Responders to heavy exercise. Discriminant Function Analysis was applied and a significant weighted linear composite predicted affective response. Preference for exercise intensity and sex were significant predictors (p = .003). Negative Responders had lower Preference scores and were more likely to be men. The combination of these two variables successfully predicted group membership 71% of the time. Individual differences appear relevant when examining affective responses to heavy exercise