Diversity in phosphorylation of thylakoid membrane proteins in chloroplasts

Photosynthesis is the most fundamental process for life on Earth. Sunlight is highly variable and fluctuates both in intensity and duration, which induces short and longterm responses in photosynthetic organisms. Photosynthetic organisms have evolved several processes to cope with environmental stresses, including light fluctuations. Many thylakoid properties and functions are regulated by diverse protein phosphorylations, ranging from thylakoid ultrastructural changes and the optimization of excitation energy between the two photosystems via Lightharvesting complexes (LHCs) to signaling mechanisms for long-term regulation, maintaining proteostasis, and thereby ultimately regulating photosynthesis via photoprotection mechanisms. My PhD research is divided into three major projects. The first one gives evolutionary insights into the two main thylakoid kinases, STN7 and STN8 in Physcomitrium patens (previously Physcomitrella patens), and their target proteins. Physcomitrium patens differs from angiosperms in their photoprotection strategy via LHCII phosphorylations (LHCB6 and LHCBM) and in formation of a Photosystem (PS)I-supercomplex, PSI-large, depending on LHCBM phosphorylation. The second project focuses on angiosperm model species Arabidopsis thaliana and deals with protein phosphorylation-related changes in thylakoid architecture. The study reveals that the phosphorylation dynamics of LHCII and CURT1B respond co-operatively to fluctuating light intensities. The findings also suggest that CURT1B phosphorylation contributes to the fine-tuning of thylakoid membrane structure and function in response to light conditions. The third project delves into the potential association between calcium signaling and induction of photoprotective mechanisms, by providing a novel screening tool to identify calcium-dependent chloroplast proteins. Calcium-transient dependent phosphorylation of essential proteins involved in the repair of PSII, including THF1, HCF136, and FTSH protease were disclosed. Additionally, the study proposes a potential link of calcium in PSI-Fd-FNR interaction. Moreover, this study not only identifies the new phosphorylation targets but also presents opportunities for exploring the intricate interplay between calcium signaling and protein phosphorylation processes. Taken together, my PhD research helps in understanding the regulation of photosynthesis, provides new tools for photosynthesis research and will thereby contribute to engineering photosynthetically resilient organisms to cope with changing environmental conditions for improving the production of food, feed and renewable energy.---- Fotosynteesi ylläpitää elämää maapallolla muuttamalla auringon valoenergiaa kemialliseksi energiaksi. Auringonvalo vaihtelee sekä voimakkuudeltaan että kestoltaan, mikä saa aikaan lyhyt- ja pitkäaikaisia vasteita fotosynteettisissä organismeissa. Fotosynteettiset organismit ovat kehittäneet useita prosesseja selviytyäkseen ympäristönstresseistä, mukaan lukien voimakkaat valon vaihtelut. Kasvien fotosynteesi tapahtuu viherhiukkasten sisäisessä kalvosysteemissä, tylakoideissa, joiden ominaisuuksia ja toimintoja säätelevät erilaiset proteiinien fosforylaatiot. Valohaaviproteiinien (LHCII) fosforylaatio muuttaa tylakoidin hienorakennetta ja optimoi viritysenergian jakautumista kahden valoreaktion (PSII ja PSI) välillä, mutta vaikuttaa myös signaalimekanismien kautta proteostaasin ylläpitämiseen ja siten viime kädessä fotosynteesin pitkänajan säätelyyn. Tohtoritutkimukseni on jaettu kolmeen osaprojektiin. Ensimmäinen pureutuu kahdessa tärkeimmässä tylakoidikinaasissa (STN7 ja STN8) ja niiden kohdeproteiineissa evoluution aikana tapahtuneisiin muutoksiin. Tutkimus osoitti sammalen, evolutiivisesti vanhimman maakasvin, eroavan valosuojausstrategiassaan siemenkasveista, ja muokkaavan LHCB6 ja LHCBM proteiinien fosforylaatioiden ja PSI-superkompleksien muodostumisen kautta viritysenergian jakautumista PSII:n ja PSI:n välillä. Toinen osaprojekti käsittelee siemenkasvien malliorganismin, lituruohon (Arabidopsis thaliana), tylakoidiproteiinien fosforylaation aiheuttamia muutoksia tylakoidiverkoston hienorakenteessa, ja paljastaa LHCII:n ja CURT1B:n fosforylaatiodynamiikan yhteistyön vaikuttavan rakenteen ja toiminnan väliseen hienosäätöön, toimien vasteena valo-olosuhteiden muutoksille. Kolmannessa osaprojektissa tarkastellaan mahdollista kalsium-signaloinnin ja kasvin proteiinifosforylaatioon perustuvan valosuojausmekanismin välistä yhteyttä, käyttämällä hyväksi seulontaan kehitettyä uutta työkalua. Tutkimuksessa kuvattiin PSII:n korjaamiseen välttämättä tarvittavien proteiinien (THF1, HCF136 ja FTSHproteaasi) kalsiumista riippuvainen fosforylaatio. Lisäksi tutkimustulokset viittaavat kalsiumin toimintaan PSI-Fd-FNR vuorovaikutuksessa sekä erittäin monimutkaiseen vuorovaikutukseen kalsium-signaloinnin ja proteiinien fosforylaatioprosessien välillä. Yhteenvetona totean, että väitöskirjatutkimukseni auttaa ymmärtämään fotosynteesin säätelyä, tarjoaa uusia työkaluja fotosynteesin tutkimukseen ja myötävaikuttaa siten uusien, fotosynteettisesti kestävien ja tehokkaiden organismien suunnitteluun ja tuottamiseen. Tämä puolestaan edesauttaa selviytymistämme muuttuvissa ympäristöolosuhteissa ruoan, rehun ja uusiutuvan energian tuotannon parantamiseksi

FREQUENCY ANALYSIS OF RIVERFLOW IN SABAH AND SARAWAK

Design flood estimation is an important task that is required planning and design of many civil engineering projects. In this study, the flood records of 37 stations in Sabah and 5 stations in Sarawak are examined using six probability distributions mostly used in Flood Frequency Analysis which are Weibull Plotting Position, Log-Pearson III, Gumbel Type I, Log-Normal 2, Log Normal 3 and Pearson Ill. This is a continuation project of Frequency Analysis in Peninsular Malaysia made by Miss Nabila Abu Bakar, to complete the study on Frequency Analysis for Malaysia. The primary objective of frequency analysis is to relate the magnitude of occurrence, flood in this case through the use of probability distributions. To ease the process, software called DISTRIB which developed by A.P Dr Saied Saiedi (1989) is used to obtain more accurate result. A best fit distribution with the lowest error is subsequently developed for each station. The results presented herein are useful for reference for practicing engineers and will be used to predict high streamflow on any return perio

Once daily versus twice daily Linagliptin effect on glycemic levels in type 2 diabetes mellitus- an observational study

Background: DPP-4 is widely distributed in endothelial cells, pancreas, uterus, liver, salivary glands, lymph node, spleen, and thymus. DPP-4 regulates glucagon-like peptide (GLP)-1, and glucose-dependent insulin tropic peptide (GIP) which leads to glucose homeostasis via enhancing insulin secretion and suppression of glucagon, which results in control of post-prandial and fasting hyperglycemia.Methods: These 40 patients who were enrolled as per the inclusion criteria of receiving metformin dosage of 2 gram per day in established type 2 diabetes mellitus patients with no comorbidities. these patients were divided randomly into two groups comprising of 20 patients each, group A received linagliptin 5 mg per day in addition to metformin 1gm twice daily whereas group B received linagliptin 5 mg per day in a fixed dose (Linagliptin + metformin) of 2.5/1000 twice daily.Results: In the present observational study, the mean age in group A was 46.7±9.4 compared to 51.65±9.9 in group B, p >0.05, mean BMI in group A was 27.8±1.1 compared to 27.28±0.93 in group B p >0.05, Mean FBS in group A was 157.9±24.1 compared to 146.2±21.8 in group B p >0.05, Mean PPBS in group A was 245.8±32.7 compared to 246.2±39.3 in group B p >0.05 and Mean HbA1c in group A was 7.67±0.58 compared to 7.6±0.5 in group B p >0.05. Group A patients were initiated on once daily linagliptin, there was a significant reduction in FBS, PPBS and HbA1c at the end of 6 months p 100 hours), related to the saturable binding of linagliptin to DPP-4. The prolonged elimination phase does not contribute to the accumulation of the drug. Addition of linagliptin to metformin has shown a significant reduction in FBS, PPBS and HbA1c

PRIMARY GASTROINTESTINAL STROMAL TUMOUR OF THE PROSTATE: A CASE REPORT OF A RARE TUMOUR

A 70-year-old gentleman underwent prostatectomy for bladder outlet obstruction due to enlarged prostate and was found to have primary extragastrointestinal stromal tumour (EGIST). He has been started on imatinib therapy and is presently on follow-up. Prostatic EGIST should be one of the differential diagnoses in patients with enlarged prostate with normal prostate-specific antigen levels.Key words: Prostate, gastrointestinal stromal tumour, PSA 

FREQUENCY ANALYSIS OF RIVERFLOW IN SABAH AND SARAWAK

Design flood estimation is an important task that is required planning and design of many civil engineering projects. In this study, the flood records of 37 stations in Sabah and 5 stations in Sarawak are examined using six probability distributions mostly used in Flood Frequency Analysis which are Weibull Plotting Position, Log-Pearson III, Gumbel Type I, Log-Normal 2, Log Normal 3 and Pearson Ill. This is a continuation project of Frequency Analysis in Peninsular Malaysia made by Miss Nabila Abu Bakar, to complete the study on Frequency Analysis for Malaysia. The primary objective of frequency analysis is to relate the magnitude of occurrence, flood in this case through the use of probability distributions. To ease the process, software called DISTRIB which developed by A.P Dr Saied Saiedi (1989) is used to obtain more accurate result. A best fit distribution with the lowest error is subsequently developed for each station. The results presented herein are useful for reference for practicing engineers and will be used to predict high streamflow on any return perio

Stretching the boundaries of medical education: A case of medical college embracing humanities and social sciences in medical education

Objective: Aga Khan University, a private medical college, had a vision of producing physicians who are not only scientifically competent, but also socially sensitive, the latter by exposure of medical students to a broad-based curriculum. The objective of this study was to identify the genesis of broad-based education and its integration into the undergraduate medical education program as the Humanities and Social Sciences (HASS) course. Methods: A qualitative methodology was used for this study. Sources of data included document review and in-depth key informant interviews. Nvivo software was utilized to extract themes. Results: The study revealed the process of operationalization of the institutional vision to produce competent and culturally sensitive physicians. The delay in the establishment of the Faculty of Arts and Sciences, which was expected to take a lead role in the delivery of a broad-based education, led to the development of an innovative HASS course in the medical curriculum. The study also identified availability of faculty and resistance from students as challenges faced in the implementation and evolution of HASS. Conclusions: The description of the journey and viability of integration of HASS into the medical curriculum offers a model to medical colleges seeking ways to produce socially sensitive physicians

Impact of humanities and social sciences curriculum in an undergraduate medical education programme

Objective: To evaluate the impact of humanities and social sciences curriculum in an undergraduate medical education programme.Methods: The qualitative study was conducted from May 2016 to May 2017 at a private medical college in Karachi where humanities and social sciences subject is an art of the undergraduate curriculum as a 6-week module at the start of Year 1 of the five-year programme. Focus group discussions were held with students from all the five years as well as with faculty related to humanities and social sciences, basic sciences and their clinical counterparts. The views of alumni of the undergraduate programme who are now members of the faculty at the institution were also explored and semi-structured interviews were conducted with institutional academic leaders. MAXQDA software was used to identify the themes for analysis.Results: Of the 50 participants, 27(54%) were students, 21(42%) were faculty members and 2(4%) were academic leaders. From the 11 sub-themes, 5 themes were identified: Expectations, Strengths, Challenges, Way forward, and Institutional role and responsibility. Faculty members perceived humanities and social sciences as encouraging creative and critical thinking, boosting students\u27 confidence and positively impacting their behaviour. Student perception seemed to change as they progressed through the years and they appreciated its impact at different stages.Conclusions: The existing humanities and social sciences curriculum can be further strengthened by integrating contents throughout the five-year programme and continuing it as a longitudinal theme rather than limiting it to a one-time exposure at the start of the programme

Development and validation of scale for self evaluation of soft skills in postgraduate dental students

Objective: To develop and validate a soft skills questionnaire, and to use it for self-evaluation by postgraduate dentistry students.Methods: The cross-sectional descriptive study was conducted at University College of Dentistry, , University of Lahore, Lahore, Pakistan, from February 2020 to April 2020 and comprised of residents from first to final year of training for either Masters in Dental Surgery or Fellowship of the College of Physicians and Surgeons Pakistan programmes. A soft skills questionnaire was generated and was validated through exploratory factor analysis of the elements and items of the questionnaire using SPSS 23.Results: Of the 60 subjects, 37(61.7%) were MDS residents and 23(38.3%) were Fellowship residents. The mean age of the sample was 29.650±2.815 years, and 26(43.3%) subjects were males. The questionnaire was validated (p\u3c0.001). Three domains measured the attitude of dentists, with 7 scenarios having 5 items per scenario. Both categories of trainees had high agreement in understanding and application of non-technical skills, with the exception of leadership skills. However, the difference between the groups was non-significant (p\u3e0.05).Conclusions: A self-generated questionnaire was successfully validated

DOES PATHOLOGICAL T3A UPSTAGING OF CLINICAL T1 STAGE HAS ANY DIFFERENCE ON LONG-TERM SURVIVAL WHEN COMPARED TO PATHOLOGICAL AND CLINICAL T1 STAGE RENAL CELL CARCINOMA

Background: A high number of clinical T1 (cT1) stage renal cell carcinoma (RCC) is upstaged to pathological T3a (pT3a) stage on histopathological findings. Several study results show that there is no survival difference among those cT1 stage who are upstaged on histopathological findings to those who remain pT1 stage RCC.Objectives: The objectives of this study were to assess any survival difference for cT1 stage renal cell carcinoma (RCC) which is upstaged to pT3a stage as compared to those which remain pT1 stage RCC on histopathological findings.Materials and Methods: It was a retrospective cohort study looking at patient aged ≥18 years with cT1 RCC who underwent nephrectomy between January 2006 and December 2016. Patients were divided into two groups based on histopathological findings (pT1 vs. pT3a). Survival was analysed for the  two groups using Kaplan–Meier method, and the difference in survival was calculated using log-rank model.Results: The study included 187 patients. The mean age at presentation was 52.56 years, with 58.3% of the patients being male while 41.7% were female. The most common presentation was incidental diagnosis (50.3%). Overall5-year survival for cT1a and pT1a RCC was 68% while that for cT1a and pT3a RCC was 100%. There was no significant survival difference among the two groups (P = 0.316). The overall 5-year survival for cT1b and pT1b RCC was 81% while that for cT1b and pT3a was 65%. There was no significant survival difference among the two groups (P = 0.136).Conclusion: We found no survival difference in cT1 RCC who were upstaged to pT3a on histopathology as compared to cT1 RCC-staged pT1 on histopathology.Key words: Clinical T1 stage, pathological T3a stage, radical nephrectomy, renal cell carcinoma, surviva