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A Longitudinal Study of Financial Difficulties and Mental Health in a National Sample of British Undergraduate Students
Previous research has shown a relationship between financial difficulties and poor mental health in students, but most research is cross-sectional. To examine longitudinal relationships over time between financial variables and mental health in students. A national sample of 454 first year British undergraduate students completed measures of mental health and financial variables at up to four time points across a year. Cross-sectional relationships were found between poorer mental health and female gender, having a disability and non-white ethnicity. Greater financial difficulties predicted greater depression and stress cross-sectionally, and also predicted poorer anxiety, global mental health and alcohol dependence over time. Depression worsened over time for those who had considered abandoning studies or not coming to university for financial reasons, and there were effects for how students viewed their student loan. Anxiety and alcohol dependence also predicted worsening financial situation suggesting a bi-directional relationship. Financial difficulties appear to lead to poor mental health in students with the possibility of a vicious cycle occurring.
Journal Article
علم الأحياء الدقيقة الطبية والعدوى : مذكرات محاضرات
يشتمل الكتاب على اثنى وأربعون فصلا مقسمة إلى أربعة أبواب. تناول الباب الأول أساسيات علم الأحياء الدقيقة من حيث تعريف وتصنيف ووصف الكائنات الدقيقة سواء كانت بكتريا أو فطريات أو فيروسات. أما الباب الثاني فقد تناول في فصوله المختلفة الأدوية المضادة لهذه الكائنات التي تم التحدث عنها في الباب الأول. أما فصول الباب الثالث فقد تناولت بالشرح المفصل موضوع العدوى بالكائنات الدقيقة المختلفة من حيث طرق العدوى والعلاج وتشخيص الأمراض الناجمة عن هذه الكائنات والتي تصيب أجهزة الجسم المختلفة. أخيرا في الباب الرابع تم سرد مجموعة من الأسئلة المتنوعة وأجوبتها عن كل فصل من فصول الكتاب المختلفة لتركيز وتبسيط ومراجعة المادة العلمية التي تناولها الكتاب.
Book
Sirtuins — novel therapeutic targets to treat age-associated diseases
Key Points
Sirtuins (SIRTs) are NAD-dependent deacetylases that have a central role in regulating the cellular proteins and their physiological pathways. Interest in therapeutically targeting this class of enzymes is gaining momentum as more data on their function is becoming available.
SIRT1 activators have the potential to mimic many aspects of calorie restriction as the levels of the protein seem to be responsive to such a regimen, and studies in lower organisms show that SIRT1 levels and activity are enhanced under conditions of calorie restriction.
Efficacy with potent small-molecule activators of SIRT1 is observed in preclinical models of metabolic, neurodegenerative and inflammatory diseases. The strategy of activation holds promise for drug discovery efforts in multiple therapeutic areas.
Evidence of therapeutic value comes from the disease area of type 2 diabetes, in which the field is currently most focused.
Currently, clinical trials are being conducted with novel small-molecule SIRT1 activators in a mitochondrial disease, MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) and in type 2 diabetes. There is a need for new type 2 diabetes treatments that are not associated with weight gain or cardiovascular risk, and SIRT1 activators are emerging as a promising alternative to existing therapeutics.
The highly conserved family of sirtuin proteins target multiple substrates, affecting a diverse range of cellular functions. Following the emergence of their potential role as regulators of mammalian lifespan, Lavu and colleagues discuss specific sirtuins that may be targeted in the treatment of diseases of ageing, including neurodegenerative and cardiovascular diseases, type 2 diabetes, and cancer.
Sirtuins post-translationally modulate the function of many cellular proteins that undergo reversible acetylation–deacetylation cycles, affecting physiological responses that have implications for treating diseases of ageing. Potent small-molecule modulators of sirtuins have shown efficacy in preclinical models of metabolic, neurodegenerative and inflammatory diseases, and so hold promise for drug discovery efforts in multiple therapeutic areas. Here, we discuss current knowledge and data that strengthens sirtuins as a druggable set of enzymes for the treatment of age-associated diseases, including activation of SIRT1 in type 2 diabetes.
Journal Article
Optical inter-site spin transfer probed by energy and spin-resolved transient absorption spectroscopy
Optically driven spin transport is the fastest and most efficient process to manipulate macroscopic magnetization as it does not rely on secondary mechanisms to dissipate angular momentum. In the present work, we show that such an optical inter-site spin transfer (OISTR) from Pt to Co emerges as a dominant mechanism governing the ultrafast magnetization dynamics of a CoPt alloy. To demonstrate this, we perform a joint theoretical and experimental investigation to determine the transient changes of the helicity dependent absorption in the extreme ultraviolet spectral range. We show that the helicity dependent absorption is directly related to changes of the transient spin-split density of states, allowing us to link the origin of OISTR to the available minority states above the Fermi level. This makes OISTR a general phenomenon in optical manipulation of multi-component magnetic systems.
Optically driven spin transfer is the fastest process to manipulate magnetism. Here, the authors show that this process emerges as the dominant mechanism in femtosecond spin dynamics enabling to the engineering of functional magnetic systems for future all optical technologies.
Journal Article
AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity
Energy metabolism
AMP-activated protein kinase (AMPK) is a cellular energy sensor that helps coordinate glucose and lipid metabolism. Here, AMPK is shown to transcriptionally regulate genes involved in controlling energy metabolism in skeletal muscle by acting together with the NAD
+
-dependent deacetylase SIRT1. AMPK enhances SIRT1 activity by increasing cellular NAD
+
levels. This results in the deacetylation and activation of the SIRT1 downstream target PGC-1α.
AMP-activated protein kinase (AMPK) is shown to transcriptionally regulate genes involved in controlling energy metabolism in skeletal muscle by acting together with the NAD
+
-dependent deacetylase SIRT1. AMPK enhances SIRT1 activity by increasing cellular NAD
+
levels, resulting in the deacetylation and activation of the SIRT1 downstream target PGC-1α.
AMP-activated protein kinase (AMPK) is a metabolic fuel gauge conserved along the evolutionary scale in eukaryotes that senses changes in the intracellular AMP/ATP ratio
1
. Recent evidence indicated an important role for AMPK in the therapeutic benefits of metformin
2
,
3
, thiazolidinediones
4
and exercise
5
, which form the cornerstones of the clinical management of type 2 diabetes and associated metabolic disorders. In general, activation of AMPK acts to maintain cellular energy stores, switching on catabolic pathways that produce ATP, mostly by enhancing oxidative metabolism and mitochondrial biogenesis, while switching off anabolic pathways that consume ATP
1
. This regulation can take place acutely, through the regulation of fast post-translational events, but also by transcriptionally reprogramming the cell to meet energetic needs. Here we demonstrate that AMPK controls the expression of genes involved in energy metabolism in mouse skeletal muscle by acting in coordination with another metabolic sensor, the NAD
+
-dependent type III deacetylase SIRT1. AMPK enhances SIRT1 activity by increasing cellular NAD
+
levels, resulting in the deacetylation and modulation of the activity of downstream SIRT1 targets that include the peroxisome proliferator-activated receptor-γ coactivator 1α and the forkhead box O1 (FOXO1) and O3 (FOXO3a) transcription factors. The AMPK-induced SIRT1-mediated deacetylation of these targets explains many of the convergent biological effects of AMPK and SIRT1 on energy metabolism.
Journal Article
Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes
SIRT1 activators in diabetes
SIRT1, an NAD
+
-dependent deacetylase that acts on proteins involved in cellular regulation, has been implicated in longevity and as a mediator of the beneficial effects of calorie restriction. A new screening programme has identified a series of small-molecule SIRT1 activators that are structurally unlike, and 1,000-fold more potent than, resveratrol, the well-known SIRT1 activator found in red wine. These new compounds improve metabolic function in animal models of diabetes and obesity, suggesting that they may have therapeutic potential in type 2 diabetes and insulin resistance.
This work describes the identification and characterization of novel small molecule activators of SIRT1, an NAD
+
-dependent deacetylase that mediates the beneficial effects of caloric restriction. These small molecules are structurally unrelated to, and much more potent than, resveratrol, and improve metabolic function in animal models of diabetes and obesity.
Calorie restriction extends lifespan and produces a metabolic profile desirable for treating diseases of ageing such as type 2 diabetes
1
,
2
. SIRT1, an NAD
+
-dependent deacetylase, is a principal modulator of pathways downstream of calorie restriction that produce beneficial effects on glucose homeostasis and insulin sensitivity
3
,
4
,
5
,
6
,
7
,
8
,
9
. Resveratrol, a polyphenolic SIRT1 activator, mimics the anti-ageing effects of calorie restriction in lower organisms and in mice fed a high-fat diet ameliorates insulin resistance, increases mitochondrial content, and prolongs survival
10
,
11
,
12
,
13
,
14
. Here we describe the identification and characterization of small molecule activators of SIRT1 that are structurally unrelated to, and 1,000-fold more potent than, resveratrol. These compounds bind to the SIRT1 enzyme–peptide substrate complex at an allosteric site amino-terminal to the catalytic domain and lower the Michaelis constant for acetylated substrates. In diet-induced obese and genetically obese mice, these compounds improve insulin sensitivity, lower plasma glucose, and increase mitochondrial capacity. In Zucker
fa/fa
rats, hyperinsulinaemic-euglycaemic clamp studies demonstrate that SIRT1 activators improve whole-body glucose homeostasis and insulin sensitivity in adipose tissue, skeletal muscle and liver. Thus, SIRT1 activation is a promising new therapeutic approach for treating diseases of ageing such as type 2 diabetes.
Journal Article
Valley polarization of graphene via the saddle point
Graphene, and other members of the monolayer Xene family, represent an ideal materials platform for “valleytronics”, the control of valley localized charge excitations. The absence of a gap in these semi-metals, however, precludes valley excitation by circularly polarized light pulses, sharply circumscribing the possibility of a lightwave valleytronics in these materials. Here we show that combining a deep ultraviolet linearly polarized light pulse with a THz envelope can induce highly valley polarized states in graphene. This dual frequency lightform operates by (i) the deep ultraviolet pulse activating a selection rule at the M saddle points and (ii) the THz pulse displacing the M point excitation to one of the low-energy K valleys. Employing both tight-binding and state-of-the-art time dependent density functional theory, we show that such a pulse results in a near perfect valley polarized excitation in graphene, thus providing a route via the saddle point to a lightwave valleytronics in the gapless Xene family.
Journal Article
SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass
Summary Increased expression of SIRT1 extends the lifespan of lower organisms and delays the onset of age‐related diseases in mammals. Here, we show that SRT2104, a synthetic small molecule activator of SIRT1, extends both mean and maximal lifespan of mice fed a standard diet. This is accompanied by improvements in health, including enhanced motor coordination, performance, bone mineral density, and insulin sensitivity associated with higher mitochondrial content and decreased inflammation. Short‐term SRT2104 treatment preserves bone and muscle mass in an experimental model of atrophy. These results demonstrate it is possible to design a small molecule that can slow aging and delay multiple age‐related diseases in mammals, supporting the therapeutic potential of SIRT1 activators in humans.
Journal Article
Systematic Discovery of Multicomponent Therapeutics
Multicomponent therapies, originating through deliberate mixing of drugs in a clinical setting, through happenstance, and through rational design, have a successful history in a number of areas of medicine, including cancer, infectious diseases, and CNS disorders. We have developed a high-throughput screening method for identifying effective combinations of therapeutic compounds. We report here that systematic screening of combinations of small molecules reveals unexpected interactions between compounds, presumably due to interactions between the pathways on which they act. Through systematic screening of ≈120,000 different two-component combinations of reference-listed drugs, we identified potential multicomponent therapeutics, including (i) fungistatic and analgesic agents that together generate fungicidal activity in drug-resistant Candida albicans, yet do not significantly affect human cells, (ii) glucocorticoid and antiplatelet agents that together suppress the production of tumor necrosis factor-α in human primary peripheral blood mononuclear cells, and (iii) antipsychotic and antiprotozoal agents that do not exhibit significant antitumor activity alone, yet together prevent the growth of tumors in mice. Systematic combination screening may ultimately be useful for exploring the connectivity of biological pathways and, when performed with reference-listed drugs, may result in the discovery of new combination drug regimens.
Journal Article