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'Passage Through the Zagros' (June 2021) was evocative. Arnold Raphel (later U.S. ambassador to Pakistan) and I made the same journey in 1968, when we were serving as junior foreign [...]

Chronic sublethal hypoxia, a complication of premature birth, is associated with cognitive and motor handicaps. Responsiveness to and recovery from this hypoxic environment is dependent on induction of HIF-1 α in the cells affected. Microvascular endothelial–glial and microvascular endothelial–neuronal precursor interactions have been found to be dynamic and reciprocal, involving autocrine and paracrine signaling, with response and recovery correlated with baseline levels and levels of induction of HIF-1 α.To ascertain the roles of endothelial HIF-1 α in the responses of brain microvascular endothelial cells (EC) and neuronal precursors to hypoxia, we examined the effects of the presence and absence of endothelial HIF-1 α expression in culture and in cells comprising the subventricular zone (SVZ) and dentate gyrus under normoxic and hypoxic conditions. We used C57BL/6 WT and EC HIF-1 α -deficient mice and brain microvascular ECs isolated from these mice in western blots, immunofluorescence, and behavioral studies to examine the roles of EC HIF-1 α behaviors of endothelial and neuronal precursor cells (NPCs) in SVZ and hippocampal tissues under normoxic and hypoxic conditions and behaviors of these mice in open field activity tests. Analyses of ECs and SVZ and dentate gyrus tissues revealed effects of the absence of endothelial HIF-1 α on proliferation and apoptosis as well as open field activity, with both ECs and neuronal cells exhibiting decreased proliferation, increased apoptosis, and pups exhibiting gender-specific differences in open field activities. Our studies demonstrate the autocrine and paracrine effects of EC HIF-1 α-modulating proliferative and apoptotic behaviors of EC and NPC in neurogenic regions of the brain and gender-specific behaviors in normoxic and hypoxic settings.

Several letters to the editor are presented in response to various articles in the previous issues, including one on the cover story on Eastern Europe in the March 18, 1966 issue, one on the move of Bob Jones University to boycott the Billy Graham Greenville Crusade in the March 18, 1966 issue, and one on the Stanford Sexual Rights Forum in the March 11, 1966 issue.

Michael H. Michaud was elected president of the Maine Senate in December 2000. Michaud served in the Maine House of Representatives from 1981 until entering the Senate in 1994. He was senate chair of the Appropriations Committee from 1996-2000.

The article offers information on planting tomatoes. Topics discussed include choosing seed types, selecting heritage or heirloom tomatoes, determining habitat, and knowing fruit appearance like cherry, beefsteak and plum. Also mentioned are different types of tomatoes such as determinate and cordon or vine types.

The article offers information on growing chillies and dealing with their problems. It is said that chillies belong to the genus Capsicum, are tropical and subtropical perennials, and are a vital cooking ingredient globally. The Royal Horticultural Society (RHS) of Great Britain conducted a trial of compact-grovsang chilli cultivars in 2013.

Adhesion molecule CD44 is expressed by multiple cell types and is implicated in various cellular and immunological processes. In this study, we examined the effect of global CD44 deficiency on myelin oligodendrocyte glycoprotein peptide (MOG)-induced experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis. Compared to C57BL/6 wild-type mice, CD44-deficient mice presented with greater disease severity, increased immune cell numbers in the central nervous system, and increased anti-MOG antibody and proinflammatory cytokine production, especially those associated with T helper 17 (Th17) cells. Further, decreased numbers of peripheral CD4+CD25+FoxP3+regulatory T cells (Tregs) were observed in CD44-knockout mice throughout the disease course. CD44-knockout CD4 T cells exhibited reduced transforming growth factor-β receptor type I (TGF-β RI) expression that did not impart a defect in Treg polarization in vitro, but did correlate with enhanced Th17 polarization in vitro. Further, EAE in bone marrow–chimeric animals suggested CD44 expression on both circulating and noncirculating cells limited disease severity. Endothelial expression of CD44 limited T-cell adhesion to and transmigration through murine endothelial monolayers in vitro. Importantly, we also identified increased permeability of the blood–brain barrier in vivoin CD44-deficient mice before and following immunization. These data suggest that CD44 has multiple protective roles in EAE, with effects on cytokine production, T-cell differentiation, T-cell–endothelial cell interactions, and blood–brain barrier integrity.

The article offers information about winter squashes which are heat-loving plants native to the Americas. In Great Britain, winter squashes re grown over summer and stored for winter. The plants belong to the Cucurbita genus of the Cucurbitaceae family. Some of the features of winter squashes are sideshoots developing along a main stem, stalk and a hard skin or rind. An overview of how to cultivate winter squashes is provided.

The article discusses different ornamental and edible varieties of cucurbits in Great Britain. Recommended culinary cucurbits to grow include kiwano (Cucumis metulifer), summer squash (Cucurbita pepo) and bottle gourd (Lagenaria siceraria). Requirements for growing different cucurbits are also discussed including time of cultivation, heat requirements and the need for a polytunnel or glasshouse. INSET: GROWING UNUSUAL CUCURBITS THE WISLEY WAY.

The article provides information on cucumbers, which crop well even with little protection in Great Britain. It says that cucumber belongs to the family Cucurbitaceae together with melons, courgettes and pumpkins. According to the author, paying attention to detail and choosing the right cultivars make growing cucumbers a more productive and worthwhile experience for growers. Tips on how to sow and raise cucumbers as well as the various diseases and pests that affect them are also discussed.

Premature infants have chronic hypoxia, resulting in cognitive and motor neurodevelopmental handicaps caused by suboptimal neural stem cell (NSC) repair/recovery in neurogenic zones (including the subventricular and the subgranular zones). Understanding the variable central nervous system repair response is crucial to identifying “at risk” infants and to increasing survival and clinical improvement of affected infants. Using mouse strains found to span the range of responsiveness to chronic hypoxia, we correlated differential NSC survival and self-renewal with differences in behavior. We found that C57BL/6 (C57) pups displayed increased hyperactivity after hypoxic insult; CD-1 NSCs exhibited increased hypoxia-induced factor 1α (HIF-1α) mRNA and protein, increased HIF-1α, and decreased prolyl hydroxylase domain 2 in nuclear fractions, which denotes increased transcription/translation and decreased degradation of HIF-1α. C57 NSCs exhibited blunted stromal-derived factor 1-induced migratory responsiveness, decreased matrix metalloproteinase-9 activity, and increased neuronal differentiation. Adult C57 mice exposed to hypoxia from P3 to P11 exhibited learning impairment and increased anxiety. These findings support the concept that behavioral differences between C57 and CD-1 mice are a consequence of differential responsiveness to hypoxic insult, leading to differences in HIF-1α signaling and resulting in lower NSC proliferative/migratory and higher apoptosis rates in C57 mice. Information gained from these studies will aid in design and effective use of preventive therapies in the very low birth weight infant population.

This article discusses the characteristics and uses of the aubergine, or eggplant. Egglants come in a variety of sizes, shapes, and colors and are usually eaten when they are immature. The longer varieties are better for chopping and for use in stir frying and the larger round ones are better for slicing and layering in Italian dishes. The article also explains how to grow aubergines and how to care for them while growing.

The article provides information on cucurbits, the family of plants that the cucumber, courgette and several species of squash belong to. Details on several varieties of cucurbit and the history of how they began to be grown in the gardens of Great Britain, are included. Information on ideal growing conditions for cucurbits, and on their various processes of reproduction, is also offered. INSET: THE SEX LIVES OF CUCUMBERS.

PECAM-1 (CD31) knockout (KO) mice exhibit excessive megakaryocytopoiesis accompanied by increased numbers of megakaryocytes associated with the stromal niche rather than the vascular niche. During earlier stages of megakaryocytopoiesis in KO marrow, an expanded Lin−Sca-1+c-kit+hematopoietic stem cell (HSC) population and increased quiescent Lin−progenitor pool were identified. During the later stages of megakaryocytopoiesis, CD31KO megakaryocytes exhibited abnormal adhesion/transmigration behaviors. Lastly, KO animals exhibited excessive splenic extramedullary megakaryocytopoiesis, which likely compensates for the impaired marrow megakaryocytopoiesis, resulting in normal peripheral platelet number. Thus, PECAM-1 modulates megakaryocytopoiesis in a hierarchic manner, functioning as a thermostat to “fine-tune” megakaryocytopoiesis.

The article presents an overview of chiilies. A discussion of the origin, worldwide export and planting of the peppers is presented. The physiology of the heat in chillies, growth and maintenance of chili pepper plants, and varieties of chillies that are found worldwide is discussed. Recommendations for types of chillies which should be sampled are offered.

The article focuses on the practice of growing farm produce in allotments and gardens by the people in Great Britain. The usual crops that these people plant include runner beans, spring greens and thyme. Bottle gourd, water spinach, cucumbers and tomatoes are some of the crops grown in vegetable plots. Aside from botanical annual, biennials and perennials are also sown and harvested within the same growing season.

Features the Thai farm produce which are best suited to growing in British gardens. Tips in sowing and growing chillies and aubergines; Cultivation of kaffir limes and perennial lemon grass; Information on new ingredients in Thai cuisine, such as pak choi and choi sum. INSET: OTHER THAI VEGETABLES AND HERBS FOR GARDENERS.

Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31), an adhesion molecule expressed on hematopoietic and endothelial cells, mediates apoptosis, cell proliferation, and migration and maintains endothelial integrity in addition to its roles as a modulator of lymphocyte and platelet signaling and facilitator of neutrophil transmigration. Recent data suggest that CD31 functions as a scaffolding protein to regulate phosphorylation of the signal transducers and activators of transcription (STAT) family of signaling molecules, particularly STAT3 and STAT5. STAT3 regulates the acute phase response to innate immune stimuli such as lipopolysaccharide (LPS) and promotes recovery from LPS-induced septic shock. Here we demonstrate that CD31-deficient mice have reduced survival during endotoxic LPS-induced shock. As compared to wild-type controls, CD31-deficient mice showed enhanced vascular permeability; increased apoptotic cell death in liver, kidney, and spleen; and elevated levels of serum tumor necrosis factor α (TNF-α), interferon γ (IFNγ), MCP-1, MCP-5, sTNRF, and IL-6. In response to LPS in vivoand in vitro, splenocytes and endothelial cells from knockout mice had reduced levels of phosphorylated STAT3. These results suggest that CD31 is necessary for maintenance of endothelial integrity and prevention of apoptosis during septic shock and for STAT3-mediated acute phase responses that promote survival during septic shock.

Explores key issues associated with a joint U.S.-Soviet mission. Major focus of NASA's exploration studies; Considerations when planning for a possible future mission; U.S.-Soviet model; Basic models of how the project will be managed; Other nations which are emerging space powers.

Spaceflight and the ever-increasing knowledge of the astronomical universe raise again the age-old questions if our existence as a species has any meaning, if the universe itself is a blind deterministic working-out of physical laws, or is the meaning of existence simply hidden from us? Here the emergence of an extraterrestrial paradigm is postulated, a new pattern, far transcending the limits of our planet, leading through the philosophy and psychology of expansion, to exploration and then colonization of space. That intelligence must expand its influence on the universe and thus assure its survival, is the author's final conclusion. The views expressed here are personal.

Several letters to the editor are presented in response to articles in previous issues including one on the election in Greece, the American Federation of Labor and Congress of Industrial Organizations (AFL-CIO) lobbying in the November 25, 1974 issue, and one on U.S. President Gerald Ford's press handling.

Several letters to the editor are presented, including one on the victory of U.S. President-elect Richard Nixon in the November 1968 election, one on the essay "The Difficult Art of Losing" in the November 15, 1968 issue, and the story of Bishop James Pike concerning the survival of personality after death.

The article offers several opportunities to evaluate the functions of the Foreign Service of the U.S. including the Foreign Service is recruiting among a generation of young people; basic change of philosophy in the Foreign Service; and focusing on the essential and discarding the unimportant.

The article presents the author's perspectives on the potential roadmap for reforming how to deliver benefits and care to veterans in the U.S. He mentions that veterans need to have the means to minimize the economic, mental or physical disadvantages of service. He states that the Veterans Affairs need to realign its operations into fewer regions, the same to how the Department of Health & Human Services and Social Security Administration operate.

In the article, the author discusses the importance of taking care of the military veterans as a cost of war. He claims that the U.S. federal government fails to ensure that veterans will not get homeless. He cites the efforts by the Department of Veterans Affairs (VA) to reduce the number of homeless veterans in the country. He presents his move as lawmaker to increase the funding for the Department of Housing and Urban Development-Veterans Affairs Supportive Housing (HUD-VASH) program.

Apoptotic cells have long been considered as intrinsically tolerogenic or unable to elicit immune responses specific for dead cell-associated antigens. However, multiple stimuli can trigger a functionally peculiar type of apoptotic demise that does not go unnoticed by the adaptive arm of the immune system, which we named “immunogenic cell death” (ICD). ICD is preceded or accompanied by the emission of a series of immunostimulatory damage-associated molecular patterns (DAMPs) in a precise spatiotemporal configuration. Several anticancer agents that have been successfully employed in the clinic for decades, including various chemotherapeutics and radiotherapy, can elicit ICD. Moreover, defects in the components that underlie the capacity of the immune system to perceive cell death as immunogenic negatively influence disease outcome among cancer patients treated with ICD inducers. Thus, ICD has profound clinical and therapeutic implications. Unfortunately, the gold-standard approach to detect ICD relies on vaccination experiments involving immunocompetent murine models and syngeneic cancer cells, an approach that is incompatible with large screening campaigns. Here, we outline strategies conceived to detect surrogate markers of ICD in vitroand to screen large chemical libraries for putative ICD inducers, based on a high-content, high-throughput platform that we recently developed. Such a platform allows for the detection of multiple DAMPs, like cell surface-exposed calreticulin, extracellular ATP and high mobility group box 1 (HMGB1), and/or the processes that underlie their emission, such as endoplasmic reticulum stress, autophagy and necrotic plasma membrane permeabilization. We surmise that this technology will facilitate the development of next-generation anticancer regimens, which kill malignant cells and simultaneously convert them into a cancer-specific therapeutic vaccine.

Presents a letter to the editor on adjusting the loan limits for student aid programs in the U.S.