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Alzheimer’s disease (AD) is the most common age-associated neurodegenerative disorder, characterized by progressive cognitive decline, memory impairment, and structural brain changes, primarily involving Aβ plaques and neurofibrillary tangles of hyperphosphorylated tau protein. Recent research highlights the significance of smaller Aβ and Tau oligomeric aggregates (AβO and TauO, respectively) in synaptic dysfunction and disease progression. Calcineurin (CaN), a key calcium/calmodulin-dependent player in regulating synaptic function in the central nervous system (CNS) is implicated in mediating detrimental effects of AβO on synapses and memory function in AD. This study aims to investigate the specific impact of CaN on both exogenous and endogenous TauO through the acute and chronic inhibition of CaN. We previously demonstrated the protective effect against AD of the immunosuppressant CaN inhibitor, FK506, but its influence on TauO remains unclear. In this study, we explored the short-term effects of acute CaN inhibition on TauO phosphorylation and TauO-induced memory deficits and synaptic dysfunction. Mice received FK506 post-TauO intracerebroventricular injection and TauO levels and phosphorylation were assessed, examining their impact on CaN and GSK-3β. The study investigated FK506 preventive/reversal effects on TauO-induced clustering of CaN and GSK-3β. Memory and synaptic function in TauO-injected mice were evaluated with/without FK506. Chronic FK506 treatment in 3xTgAD mice explored its influence on CaN, Aβ, and Tau levels. This study underscores the significant influence of CaN inhibition on TauO and associated AD pathology, suggesting therapeutic potential in targeting CaN for addressing various aspects of AD onset and progression. These findings provide valuable insights for potential interventions in AD, emphasizing the need for further exploration of CaN-targeted strategies.

The article explores the aspects of the interaction between Mongolia and the USSR on the development of their bilateral relations starting from 1925 up until 1928. The author shows how the Soviet troop withdrawal issue created by Moscow influenced the settlement of disputed issues between Mongolia and China, and interfered into the normalization Mongolian-Chinese relations for many years. Soviet envoy to the MPR P.M.Nikiforov was tasked to carry out total sovietazion of all aspects of Mongolian life under the nominal cover of independent Mongolia, and to prevent any process of unification between Outer and Inner Mongolia, to urge Mongolian leaders to recognize Tannu Tuva People’s Republic without any preconditions. A.Amar, Minister for Economy, during his trip to Moscow early 1926 raised the issues of distorted Mongol-Soviet trade, industrial, transport and other bilateral economic relations and asked Moscow to make adjustments and make economic relations equal and mutually beneficial. The character of the atmosphere between Ulaanbaatar and Moscow did play a key role in solving difficult and sensitive bilateral issues and the desire of the Mongolian People’s Republic to build official relations with Moscow as equal and trustful partners was strong. Монгол-Зөвлөлтийн харилцаа (1925-1928) Хураангуй: ОК(б)Н-ын Төв Хорооны Улс төрийн товчоо 1925 оны 7 дугаар сарын 30-ны өдрийн хуралдаанаар П.М.Никифоровыг ЗСБНХУ-аас Монголд суух Бүрэн эрхт төлөөлөгч бөгөөд худалдааны төлөөлөгчөөр томилох шийдийг гаргажээ. ЗХУ-ын Гадаад хэргийн ардын комиссар Г.В.Чичерин түүнийг хүлээн авч уулзаад Монгол дахь Зөвлөлтийн зорилгыг “Бид Бүгд Найрамдах Монгол улсыг Хятадын протекторатын дор биеэ даасан автономит байдалтай байхыг ёс болгон тунхаглаж байгаа хэдий боловч бид Монголыг дотоод улс төр хийгээд эдийн засгийн байгуулалтаар зөвлөлтийн хэлбэрт ойртуулах практик ажлыг тэнд тууштай явуулах ёстой” гэжээ. Түүнчлэн Чичерин Никифоровт Дотоод Монголыг өөртөө нэгтгэх гэсэн Монголын Засгийн газрын хүсэлтийг хүлээж авахгүй, дэмжихгүй байх, Тагна Урианхайг Монголтой нэгэн адил статустай гэж үзэж байгаа тул Урианхайг Монголтой нэгтгэхийн эсрэг ажиллах заавар удирдамжийг өгч байжээ. ЗХУ, БНМАУ-ын эдийн засгийн харилцааг цаашид хөгжүүлэх үүднээс БНМАУ-д нэг сая алтан рублийн зээлийг 5 жилийн хугацаатай олгохоор 1925 оны 1 дүгээр сард шийдвэрлэсэн байна. Монгол улсын Засгийн газраас мөнгөний шинэчлэлт хийх ажлыг зохион байгуулах комиссыг 1925 онд 6 хүнтэй байгуулж, тус комисс нь мөнгөний шинэчлэлт, эргэлт хуримтлалын асуудлыг хариуцаж байв. Монгол улсын банкны анхны шинэ дүрэмд “Монголын хязгаарын дотор мөнгөний гүйлгээг журамтай болгох, үнийг тэгшитгэн бататгах, эд боловсруулах, мал үржүүлэх, худалдаа арилжааны зүйлийг бадруулах” гэжээ. Түлхүүр үгс: БНМАУ, ЗХУ, санхүү мөнгөний шинэчлэл, монгол-зөвлөлтийн худалдаа, УБХ-ын төлөөлөгчдийн айлчлал

The article explores the aspects of the interaction between Mongolia and Japan on the normalization of their bilateral relations starting from 1946 up until 1972. The author divided the process of normalization during that period into three periods: the first period from 1946 to 1960 as initial one, the second period of 1960-1969 during the active engagement, the third one from 1969 to 1972 as the concluding one. The author shows how the war reparation issue created by the Mongolian People’s Republic with the backing of Moscow influenced the settlement of disputed issues and interfered into the normalization Mongolian-Japanese relations for many years. The normalization of relations with Japan, a rising power in Asia, for Mongolia was the issue of national accomplishment as a sovereign nation, legitimate right in world affairs and international prestige. The character of the cold war atmosphere between Moscow and Tokyo, between Ulaanbaatar and Tokyo did play a key role in solving difficult and sensitive bilateral issues and the desire of the Mongolian People’s Republic to enter official relations with Tokyo was finally realized due to “Nixon shock” and other favorable international circumstances. Монгол ба Японы хооронд 1972 онд дипломат харилцаа тогтоосон нь: 50 жилийн өндөрлөгөөс нягтлан шинжихүй Хураангуй: БНМАУ болон Япон улсын хооронд 1972 оны 2 дугаар сард албан ёсны дипломат харилцаа тогтоосон явдал нь Өрнөдийн гүрнүүдээс зөвхөн Их Британи, Франц зэрэгтэй дипломат харилцаатай байсан Монгол улсын хувьд гадаад харилцаагаа тэлэх томоохон алхам болсон юм. Монгол-Японы хооронд дипломат харилцаа тогтоох үйл явц ийнхүү 1970-аад оны эхэн хүртэл сунжирсан явдал нь маргаантай хэд хэдэн асуудлаас үүдэлтэй байв. Дайны төлбөрийн асуудал, Японы олзны цэргүүдийн асуудал саад тотгор болж байв. Варшав, Москвагаар дамжин эхэлсэн хоёр талын албаны хүмүүсийн тандалтын шинжтэй яриа хэлэлцээ 10 орчим жил үргэлжилж, 1972 оны 2 дугаар сард Москвад хоёр орны Элчин сайд нар тодорхой шийдэлд хүрснээр төгсгөл болсон билээ. Тэр үеийн дэлхийн улс төрийн харилцаа, нэн ялангуяа Ази, Европын хүйтэн дайн, ЗХУ, БНХАУ, Тайвань, Америк зэрэг ээдрээ төвөгтэй харилцаа нөлөөлж байсан бөгөөд Япон Монголын хооронд тухайлбал, Халх голын дайн, дэлхийн II дайны үеийн 80 сая америк долларт хүрэх хэмжээний дайны нөхөн төлбөрийн асуудал, харилцан ойлголцол хангалтгүй зэрэг шалтгаан байсан юм. Нэмж хэлэхэд БНМАУ-ын гадаад бодлого ЗХУ-ын нэгдсэн бодлогод захирагдаж байсан, Япон ч гэсэн АНУ-ын “атомын шүхэрт” дулдуйдаж, АНУ-ын холбоотон Тайваньтай найрамдлын гэрээтэй, Тайваний арлын эрх баригчдад ховсдуулсан байсныг хэлэх нь зүйтэй. Түлхүүр үгс: Монгол, Япон, ЗХУ, “хүйтэн дайн”, хэвийн харилцаа, дайны төлбөр, сайн санааны айлчлал,

The article explores the aspects of the interaction between the USSR and the USA on the Mongolian question within the UN during first 15 years of the Cold war. The author dwells such problems as Mongolia’s contribution to the war against Japanese militarism; the question of the involvement of Ulaanbaatar to the Korean war in 1950-1953; the arguments between Moscow and Washington concerning the package admittance of new members; the reason of the veto power exercised by the Chiang Kai-shek regime; ideological conflicts between two opposing blocs in the United Nations. The first application for Mongolia’s admission to the UN was submitted to Secretary-General Trygve Lie in a letter dated June 21, 1946, signed by Kh. Choibalsan, Prime-Minister and Minister of Foreign Affairs of the MPR. The solution of this issue, however, dragged on until 1961. During this period, the application for admission of the MPR was renewed four times - in 1948, 1955, 1956 and 1957. The Mongolian statement was considered at least 13 times in various meetings of the UN Security Council.

The article explores the aspects of the interaction between the USSR and the USA on the issue of “Outer Mongolia” as it was called within the United Nations at the first stage of the Cold War. The author divided the issue of “Outer Mongolia” at the UN during that period into three periods: the first period from 1946 to 1948, the second period from 1950 to1953, i.e. during the Korean war, the final, third one from 1955 to 1961. The author shows how the manipulation of the United Nations by the great powers in their own political interests impeded the settlement of the global issues and postponed admission of the countries such as Mongolian People’s Republic (so called Outer Mongolia) to the UN for many years. The admission to the UN for Mongolia was a matter of national pride as a sovereign nation, and gaining legitimacy in the world affairs and building a reputation in the international arena. The nature of the dialogue between Moscow and Washington played a key role in solving global and regional issues, and aspirations of small countries like the Mongolian People’s Republic had a negligible weight in international affairs. НҮБ-д Монголын асуудлыг хэлэлцсэн нь (1946-1961 он): БНМАУ-ын гишүүнчлэлийн асуудлаарх ЗХУ, АНУ-ын байр суурийн хувьсал өөрчлөлт Хураангуй: Тус өгүүлэлд “Хүйтэн дайн”-ы нөхцөлд НҮБ дахь Монголын асуудлаар ЗХУ, АНУ зэрэг их гүрнүүдийн байр суурь, тэдний зөрчил, сөргөлдөөн, эвлэрлийн уялдаа холбоог авч үзэх болно. Зохиогч НҮБ-д Монголын элссэн түүхэн үйл явцыг гурван үед буюу 1946-1948 оны эхний үе, 1950-1953 оны Солонгосын дайны үе, 1955-1961 оны НҮБ-д элссэн төгсгөлийн үе хэмээн задлан авч үзэв. “Хүйтэн дайны” үед их гүрнүүд Нэгдсэн Үндэстний байгууллагыг өөрсдийн улс төрийн зорилгод дур зоргоор ашиглаж байсан нь олон улсын маргаантай асуудлыг шийдвэрлэхэд саад болж, БНМАУ зэрэг орнуудыг НҮБ-д элсэх асуудлыг олон жилээр хойш татаж байв. БНМАУ-ын хувьд НҮБ-д элсэх нь туурга тусгаар улсын үндэсний бахархал, хууль ёсны эрхээ хүлээн зөвшөөрүүлэх, олон улсын нэр хүндээ өсгөх ач холбогдолтой байлаа. Тэр нөхцөлд Москва, Вашингтон хоорондын яриа хэлэлцээний шинж чанар нь глобаль болон бүс нутгийн асуудлыг шийдвэрлэхэд гол хүчин зүйл болж ирсэн бөгөөд жижиг орны хүсэл эрмэлзэл олон улсын хэрэгт тэр болгон үр нөлөөтэй байж чадахгүй байв. Түлхүүр үгс: НҮБ, ЗХУ, АНУ, “хүйтэн дайн”, БНМАУ-ын гишүүнчлэл, Гоминьданы Хятадын вето эрх

Afro-Asian countries liberated from colonialism by the end of the WWII became a new factor in international relations. Most of them sought to establish a peaceful co-existence with other countries. Pancha-Shila five principles have been first proclaimed by India and China in 1954. These five principles proclaimed respect for sovereignty and territorial integrity, mutual non-aggression, equal and mutual usefulness, peaceful coexistence. The Bandung Conference of 29 Asian and African countries held in Indonesia in April 1955 was a significant event in international relations. It proclaimed famous 10 Bandung principles which were embraced by the Mongolian People’s Republic enthusiastically. Бандунгийн бага хурал ба БНМАУ Ази, Африкийн орнуудтай харилцах цонх нээсэн нь (1955-1961) Хураангуй: Дэлхийн II дайны дараа колончлолоос чөлөөлөгдөж биеэ даасан улс байгуулсан Ази, Африкийн орнууд олон улсын харилцааны шинэ хүчин зүйл болсон билээ. Тэдгээр улс орнуудын дийлэнх нь бусад улс оронтой энх тайвнаар зэрэгцэн орших үндсэн дээр харилцахыг эрмэлзэж байлаа. Энэ эрмэлзэл нь 1954 онд БНХАУ, БНЭУ-ын хоорондын харилцаанд тунхагласан Панча-Шила хэмээх таван зарчимд тусгалаа олов. Энэхүү таван зарчим нь нутаг дэвсгэрийн бүрэн бүтэн байдал ба суверенитетийг хүндэтгэх, харилцан үл довтлолцох, эрх тэгш харилцан ашигтай байх, энх тайвнаар зэрэгцэн орших зэрэг болно. 1955 оны 4 дүгээр сард Индонезийн Бандунг хотод хуралдсан Ази, Африкийн 29 орны Бага хурал олон улсын харилцааны түүхэнд онцгой байр суурийг эзэлдэг. Дэлхийн хүн амын талаас илүү нь оршин суудаг Ази, Африк хоёр тивийн Төр засгийн тэргүүн, Гадаад хэргийн сайд нар анх удаа хуран цугларч, дэлхийн улс төрд хоёр тивийн орнуудын гүйцэтгэх үүрэг, шинэ колоничлолын эсрэг, эдийн засаг, соёлын хамтын ажиллагааг бэхжүүлэх, хүний эрх ба өөрөө засан тохинох эрхийг хэрэгжүүлэх, улс хоорондын харилцаанд баримтлах Бандунгийн 10 зарчим зэргийг хэлэлцэн тохирч чадсан нь дэлхийн геополитикт тун содон сонин үйл явдал болсон билээ. Панча-Шила ба Бандунгийн 10 зарчмыг дэлхийн олон улс орон, түүн дотор БНМАУ ч талархалтай хүлээн авсан юм. Түлхүүр үгс: Бандунгийн бага хурал, Ази, Африкийн орнууд, энх тайвнаар зэрэгцэн орших 5 зарчим, 10 зарчим, БНМАУ-ын энх тайванч бодлого.

Abstract Background Adult hippocampal neurogenesis plays an important role in synaptic plasticity and cogntive function. We reported that higher numbers of neural stem cells (NSC) in the hippocampus of cognitively-intact individuals with high Alzheimer’s disease (AD) pathology (plaques and tangles) is associated with decreased synaptic amyloid beta oligomers (Aβο), an event linked to onset of dementia in AD. While these findings suggest a link between NSC and synaptic resistance to Aβο, the involved mechanism remains to be determined. With this goal in mind, here we investigated the ability of exosomes secreted from hippocampal NSC to promote synaptic resilience to Aβo. Methods Exosomes isolated from media of hippocampus NSC (NSC-exo) or mature hippocampal neuronal (MN-exo) cultures were delivered intracerebroventricularly (ICV) to mice before assessment of Aβο-induced suppression of hippocampal long-term potentiation (LTP) and memory deficits. Aβο binding to synapses was assessed in cultured hippocampal neurons and on synaptosomes isolated from hippocampal slices from wild type mice and from an inducible mouse model of NSC ablation (Nestin-δ-HSV-TK mice) treated with exosomes. Expression of CaMKII and of AMPA and NMDA glutamate receptor subunits in synaptosomes was measured by western blot. Small RNA Deep sequencing was performed to identify microRNAs enriched in NSC-exo as compared to MN-exo. Mimics of select miRNAs were injected ICV. Results NSC-exo, but not MN-exo, abolished Aβo-induced suppression of LTP and subsequent memory deficits. Furthermore, in hippocampal slices and cultured neurons, NSC-exo significantly decreased Aβo binding to the synapse. Similarly, transgenic ablation of endogenous NSC increased synaptic Aβo binding, which was reversed by exogenous NSC-exo. Phosphorylation of synaptic CaMKII was increased by NSC-exo, while AMPA and NMDA receptors were not affected. Lastly, we identified a set of miRNAs enriched in NSC-exo that, when injected ICV, protected the synapses from Aβo-binding and Aβo-induced LTP inhibition. Conclusions These results identify a novel mechanism linking NSC-exo and synaptic susceptibility to Aβo that may underscore cognitive resilience of certain individuals with increased neurogenesis in spite of AD neuropathology and unmask a novel target for the development of a new treatment concept for AD centered on promoting synaptic resilience to toxic amyloid proteins.

Instability of the forearm is a complex problem that leads to pain and limited motions. Up to this time, no universal consensus has yet been reached as regards the optimal treatment for forearm instability. In some cases, conservative treatments are recommended for forearm instability injuries. However, quantitative studies on the conservative treatment of forearm instability are lacking. The present study developed a finite element model of the forearm to investigate the contribution of the distal radioulnar joint stabilizer on forearm stability. The stabilizer was designed to provide stability between the radius and ulna. The forearm model with and without the stabilizer was tested using the pure transverse separation and radial pull test for the different ligament sectioned models. The percentage contribution of the stabilizer and ligament structures resisting the load on the forearm was estimated. For the transverse stability of the forearm, the central band resisted approximately 50% of the total transverse load. In the longitudinal instability, the interosseous membrane resisted approximately 70% of the axial load. With the stabilizer, models showed that the stabilizer provided the transverse stability and resisted almost 1/4 of the total transverse load in the ligament sectioned models. The stabilizer provided transverse stability and reduced the loading on the ligaments. We suggested that a stabilizer can be applied in the conservative management of patients who do not have the gross longitudinal instability with the interosseous membrane and the triangular fibrocartilage complex disruption.

The purpose of this study was to evaluate the variability of subcutaneous abdominal adipose tissue (AT) dynamics in obese subjects with a wide range of insulin sensitivity (IS) and the correlation between these two metabolic measures. Ten obese (BMI 30-40 kg/m²) nondiabetic subjects with (n = 6) and without (n = 4) the metabolic syndrome were studied following a 12-wk ²H₂O labeling period. Subcutaneous abdominal AT biopsies were collected. Deuterium incorporation into triglyceride (TG)-glycerol and TG-palmitate were measured by gas chromatography-mass spectrometry for the calculation of fractional TG synthesis (fTG) and fractional de novo lipogenesis (fDNL). Muscle IS and insulin-mediated nonesterified fatty acid (NEFA) suppression (a measure for adipose IS) indexes were derived from the oral glucose tolerance test (OGTT). The ability of subcutaneous abdominal AT to synthesize lipids varied significantly in obese subjects (fTG range 7-28%, fDNL range 1.1-4.6%) with significantly lower values (>35% reduction) for both parameters in obese with the metabolic syndrome. fTG correlated positively with muscle IS (r = 0.64, P = 0.04) and inversely with NEFA suppression during the OGTT (r = -0.69, P = 0.03). These results demonstrate a large variability in subcutaneous abdominal AT lipid turnover in obesity. Moreover, a reduced capacity for subcutaneous abdominal AT fat storage is associated with muscle and adipose tissue insulin resistance as well as with the metabolic syndrome, thus identifying a form of obesity at heightened risk for type 2 diabetes and cardiovascular disease.

Decorin was isolated from 7 M urea extract of bovine placental cotyledons by ion-exchange and hydrophobic chromatography. Decorin and its core protein showed a broad band at about 115 kDa and a single band at 47 kDa, respectively by SDS-PAGE. Anti-decorin core protein antiserum from pig skin was reacted with placental decorin and its core protein in western blotting. The NH2-terminal amino acid sequence of core protein from placental cotyledons was not different from that of core protein from skin and bone. Glycosaminoglycan of decorin was identified as dermatan sulfate by electrophoresis on a cellulose-acetate membrane and chondroitinase digestivity. Decorin bound to collagen in the order for type III, I, and V.